Prospective associations between social vulnerabilities and children's weight status. Results from the IDEFICS study.
In high-income countries, childhood obesity follows a clear socioeconomic gradient with greater prevalence in children with lower socioeconomic status (SES). The extent to which the trend of other social vulnerabilities over time and the accumulation of these vulnerabilities can affect children's weight is still unknown. In the IDEFICS study, 8624 children aged 2.0-9.9 years from eight European countries were examined at baseline and after 2 years. Sociodemographic variables, maternal body mass index (BMI), and lifestyle were reported by parents. Children were measured and classified as thin, normal weight, and overweight/obese using the extended IOTF criteria. Four vulnerable groups were defined: children whose parents were migrants, children whose parents lack a social network, children from non-traditional families (children not living with both biological parents), and children with unemployed parents. Logistic mixed-effects models were used to study the association between vulnerabilities and children's weight at baseline and follow-up, temporal trends in vulnerabilities and children's weight and accumulation of vulnerabilities and children's weight. Models were adjusted for lifestyle, maternal BMI, parental education, and income. Children whose parents lost their social support at follow-up were more likely to be thin than non-vulnerable children (OR = 1.69, 99% CI = 1.03-2.78). Children whose parents had a migrant background (OR = 1.30, 99% CI 1.04-1.62), children from non-traditional families at both time points (OR = 1.40, 99% CI 1.03-1.90) and whose parents were unemployed at baseline and follow-up (OR = 2.03, 99% CI 1.03-3.99) were more likely to be overweight/obese compared to non-vulnerable children. Cross-sectionally, we did not find an association between parental lack of network, non-traditional family structure, or employment and children's weight status. Policy actions are required to tackle inadequate weight loss and gain among vulnerable children (especially those exposed over the long term) since they are at a higher risk of thinness and overweight.


Effects of optineurin mutants on SH-SY5Y cell survival.
Mutations in the optineurin gene (OPTN) have been found to be associated with glaucoma and amyotrophic lateral sclerosis (ALS). However, the mechanism by which this single gene mutation leads to neurodegeneration in those two diseases remains unrevealed. To study the roles of wild-type (WT) OPTN and its pathogenic mutants in neuronal survival, here we overexpressed SH-SY5Y cells with WT OPTN or its four mutants (E50K, M98K, Q398X and E478G), and detected their effects on neuronal viability under normal or oxidative stress conditions. We found that overexpression of WT OPTN or its glaucoma-linked mutants (E50K and M98K) causes little harm in SH-SY5Y cells, while ALS-associated OPTN mutants (Q398X and E478G) leads to remarkably increased oxidative status and decreased antioxidase activity, which might result in severe mitochondrial dysfunction and neuronal injury. Further investigation suggests that overexpression of WT OPTN promotes endogenous antioxidase activation in the SH-SY5Y cells under oxidative stress and increases neuronal survival. Nevertheless, this neuroprotective effect of WT OPTN is abolished by its four mutants. Our results indicate that oxidative stress may play a central role in the pathogenesis of glaucoma and ALS caused by OPTN mutation.


Corrigendum: Interpreting flow cytometry with caution: a case report of follicular lymphoma in leukemic phase misdiagnosed as chronic lymphocytic leukemia.
[This corrects the article DOI: 10.3389/fonc.2023.1170598.].


Prevalence of Post-Glucose Challenge Hypoglycemia in Adult Patients With Cystic Fibrosis and Relevance to the Risk of Cystic Fibrosis-Related Diabetes.
The clinical relevance of fasting and postprandial hypoglycemia in patients with cystic fibrosis (CF) is poorly characterized. Our aim in this study was to characterize the prevalence of hypoglycemia in adult patients during oral glucose tolerance test (OGTT) screening and determine its impact on the risk of developing CF-related diabetes (CFRD). We analyzed 2 cohorts of pancreatic insufficient patients with CF exposed to comparable treatment recommendations in France (Lyon CF cohort [DIAMUCO]) and Canada (Montréal CF cohort [MCFC]). Patients were classified into 3 groups based on hypoglycemia absence or presence as well as its severity at baseline. We defined the groups as follows: level 2 hypoglycemia (L2H; plasma glucose [PG]<3.0 mmol/L), level 1 hypoglycemia (L1H; PG 3.0 to <4.0 mmol/L) and no hypoglycemia (NH) during an OGTT. A total of 153 MCFC and 114 DIAMUCO subjects were included in the study. In total, 22% of the patients experienced hypoglycemia, with 5% having it on 2 or more OGTTs. The L1H and L2H groups tended to have a lower 2-hour glucose and higher early-phase insulin secretion (insulin area under the curve at 0 to 30 minutes) compared with NH patients. In both cohorts, a greater proportion of men and patients with normal glucose tolerance had hypoglycemia. Over a 5-year period, there were no cases of CFRD in the L2H group, whereas 4 subjects in the L1H group and 36 in the NH group developed CFRD. Patients with hypoglycemia were at lower risk of developing CFRD, but at higher risk of early-phase insulin secretion and unsuppressed insulin secretion. This could potentially lead to further hypoglycemia after the 2-hour OGTT, suggesting high clinical relevance.


Evidence-based guideline recommendations on the use of positron emission tomography imaging in oesophageal cancer.
To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of oesophageal cancer. A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts. The results from the Facey et al. review for oesophageal cancer included four other systematic reviews and six primary studies. The 2005 to 2010 updated search included two additional systematic reviews and 29 primary studies. Recommendations were developed based on this evidence and accepted by consensus. PET is recommended to improve the accuracy of M staging for the staging work-up of patients with oesophageal cancer who are potential candidates for curative therapy. Due to insufficient evidence, no recommendation was made for or against the use of PET for the assessment of treatment response and the evaluation of suspected recurrence.


Myelin membrane from adrenoleukodystrophy brain white matter--biochemical properties.
Adrenoleukodystrophy (ALD) is an X-linked progressive neurological disorder characterized by the accumulation of saturated very-long-chain fatty acids (C24 to C30) in lipids, especially cholesterol esters of the brain white matter and adrenal cortex. In the present study we have investigated the localization of accumulated cholesterol esters in brain white matter. During isolation of purified myelin membrane from regions of active demyelination, significant enrichment in cholesterol ester was found in two fractions, mainly in a low-density floating fraction and to a lesser degree in the purified myelin preparation. The fatty acid composition of cholesterol esters from both the ALD floating and myelin fractions was enriched approximately 10-fold in saturated very-long-chain fatty acids (greater than or equal to C24) compared with control preparations.


Above cuff vocalisation (ACV): A scoping review.
Patients in intensive care frequently suffer from not being able to communicate verbally. The aim of this scoping review was to study the safety and effectiveness of the above cuff vocalisation (ACV) on speech and quality of life (QOL) in patients dependent on a cuffed tracheostomy. A scoping review was conducted. The databases Ovid Medline, Cochrane Library, and Embase were systematically searched in May 2020. We included clinical studies with patients exposed to ACV where speech, QOL or safety issues were assessed. Overall, 17 studies were included, of which 15 were observational and 2 were randomised controlled trials. Totally, 231 patients were included. ACV enabled most of the included patients (115/131; 88%) to speak with an audible voice or whisper (moderate quality of evidence). Voice related QOL (V-RQOL) and QOL in mechanically ventilated patients (QOL-MV) improved from pre- to post- ACV compared to a control group not tolerating a one-way speaking valve (P = .01 and P = .04, respectively) (very low quality of evidence). Several minor complications or problems were reported in 20/75 (27%) cases in addition to two serious adverse events: subcutaneous emphysema in one patient where the tracheostomy was dislodged and a distended trachea in another due to the misconnection of continuous gas to the cuff (low/ very low quality of evidence). ACV facilitated communication in patients dependent on a cuffed tracheostomy and attempting to communicate. Quality of evidence in improved V-RQOL and QOL-MV was very low. Several minor complications and two serious adverse events were reported.


Absence of "cheese effect" during deprenyl therapy: some recent studies.
Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.


Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.
The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility.


Identification of differentially expressed genes in early-postmortem Semimembranosus muscle of Italian Large White heavy pigs divergent for glycolytic potential.
Glycolytic potential (GP) is one of the postmortem traits used to predict the quality of the final meat products. Despite that, the knowledge of the molecular and metabolic pathways controlling this trait is still not complete. To add some information on this field we used two pools of Italian Large White heavy pigs divergent for GP to investigate through a microarray approach the differences of gene expressions between the two pools. On the whole, 32 genes were differentially expressed, and among them 31 were overexpressed in low GP pool. These genes were involved in mitochondrial functions and adenosine triphosphate (ATP) biosynthetic processes, in calcium homeostasis, and in lipid metabolism, with Peroxisome proliferator-activated receptor (PPAR) signaling being a possible master regulator of the molecular differences observed between the two pools. The different GP levels between the two pools could have determined in low GP muscles a more rapid occurrence of the molecular cascade related to the events triggering cell death.


How are we 'doing' cultural diversity? A look across English Canadian undergraduate medical school programmes.
Cultural diversity education is a required curriculum component at all accredited North American medical schools. Each medical school determines its own content and pedagogical approaches. This preliminary study maps the approaches to cultural diversity education in English Canadian medical schools. A review of 14 English Canadian medical school websites was undertaken to identify the theoretical approaches to cultural diversity education. A PubMed search was also completed to identify the recent literature on cultural diversity medical education in Canada. Data were analysed using 10 criteria that distinguish pedagogical approaches, curricular structure, course content and theoretical understandings of cultural diversity. Based on the information posted on English Canadian medical school websites, all schools offer cultural diversity education although how each 'does' cultural diversity differs widely. Two medical schools have adopted the cultural competency model; five have adopted a critical cultural approach to diversity; and the remaining seven have incorporated some aspects of both approaches. More comprehensive research is needed to map the theoretical approaches to cultural diversity at Canadian medical schools and to evaluate the long-term effectiveness of these approaches on improving physician-patient relationships, reducing health disparities, improving health outcomes and producing positive learning outcomes in physicians.


ChIRP-MS: RNA-Directed Proteomic Discovery.
Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-ms) is a novel technique for studying endogenous ribonucleoprotein complexes. ChIRP-ms is robust across a wide range of expression level, from abundant housekeeping RNAs (e.g., spliceosomal U RNAs) to relatively lowly expressed RNAs (e.g., Xist). In vivo RNA-protein interactions are chemically cross-linked, and purified using biotinylated antisense oligonucleotides against RNA of interest. Coprecipitated proteins are gently eluted, and identified by mass-spectrometry (for discovery) or by western blotting (for validation).


Comparative analysis of gene expression between articular cartilage-derived cells to assess suitability of fibronectin adhesion assay to enrich chondroprogenitors.
Enhanced chondrogenesis and reduction in hypertrophy are essential pre-requisites for cell-based therapy in regenerative research for cartilage loss. Chondroprogenitors, isolated by fibronectin adhesion assay (FAA), have shown promising results in various preclinical studies due to their inherent characteristics. However, the need for monolayer culture and the effect of expansion on cell phenotype render differentiation between chondroprogenitors and chondrocytes (native cartilage cells) difficult. This is further complicated due to reported de-differentiation of chondrocytes in culture. Thus, the aim of our study was to harvest cells from articular cartilage and compare their gene expression to cells demonstrating adherence and non-adherence to fibronectin. Fresh-cells (FC) were isolated from human osteoarthritic knee joints(n = 3) and subjected to FAA. Cells unbound to fibronectin (20 min after plating) were termed as FAA-ve. Attached cells were further cultured for five population doublings and designated FAA+ve. RNA from all three cell groups was assessed for SOX-9, ACAN, COL2A1, COL1A1, RUNX2 and COL10A1. All three groups exhibited moderate to high expression of markers of chondrogenesis and marker of chondrocyte hypertrophy. FAA+ve group exhibited significantly lower levels of hypertrophy markers: RUNX2 (vs FC and FAA-ve, P = 0.018) and COL10A1(vs FAA-ve, P = 0.005). Our results demonstrated that fibronectin effectively isolated cells distinct from mature chondrocytes in terms of reduced hypertrophic tendency. This is noteworthy as cells isolated by FAA, retaining their inherent progenitor phenotype, with upregulation of chondrogenic markers may be used successfully for cartilage repair in future translational work.


Evaluation of natural killer cell activity in patients with persistent generalized lymphadenopathy and acquired immunodeficiency syndrome.
Natural killer (NK) cell activity was quantitated using 51Cr release from the human erythroleukemia cell line K562 in 39 heterosexual males, 60 asymptomatic homosexuals, 39 patients with persistent generalized lymphadenopathy (PGL), and 16 patients with acquired immunodeficiency syndrome (AIDS). PGL and AIDS patients showed a slight decrease in NK cell activity compared to control groups. Absolute numbers of Leu 11a-positive cells were decreased in PGL and AIDS patients, and this decrease correlated with a decrease in absolute number of both the T4+ and T8+ cell subsets. Autologous plasma inhibited NK cell activity in 48% of asymptomatic homosexuals, 63% of PGL patients, and 63% of AIDS patients, but in none of the heterosexual controls. NK cell responses in fetal calf serum, normal human plasma, or autologous plasma showed no correlation with absolute numbers of T4+ cells, or with T4/T8 ratio. We conclude that NK cell responses are not of prime importance in the pathogenesis of PGL and AIDS.


Technicolour transgenics: imaging tools for functional genomics in the mouse.
Over the past decade, a battery of powerful tools that encompass forward and reverse genetic approaches have been developed to dissect the molecular and cellular processes that regulate development and disease. The advent of genetically-encoded fluorescent proteins that are expressed in wild type and mutant mice, together with advances in imaging technology, make it possible to study these biological processes in many dimensions. Importantly, these technologies allow direct visual access to complex events as they happen in their native environment, which provides greater insights into mammalian biology than ever before.


Hairy root culture: bioreactor design and process intensification.
The cultivation of hairy roots for the production of secondary metabolites offers numerous advantages; hairy roots have a fast growth rate, are genetically stable, and are relatively simple to maintain in phytohormone free media. Hairy roots provide a continuous source of secondary metabolites, and are useful for the production of chemicals for pharmaceuticals, cosmetics, and food additives. In order for hairy roots to be utilized on a commercial scale, it is necessary to scale-up their production. Over the last several decades, significant research has been conducted on the cultivation of hairy roots in various types of bioreactor systems. In this review, we discuss the advantages and disadvantages of various bioreactor systems, the major factors related to large-scale bioreactor cultures, process intensification technologies and overview the mathematical models and computer-aided methods that have been utilized for bioreactor design and development.


Aptamer-functionalized magnetic nanoparticles conjugated organic framework for immobilization of acetylcholinesterase and its application in inhibitors screening.
Construction of new enzyme reactor based on aptamer functionalized magnetic nanoparticles conjugated organic framework (COF) for acetylcholinesterase immobilization has been an enabling endeavor in this work. The aptamer against acetylcholinesterase was selected through a method based on capillary electrophoresis in one round. A new magnetic COF material rich of carboxyl groups was firstly synthesized, and its surface was then modified with the selected aptamer through covalently linking. Acetylcholinesterase was immobilized to fabricate the enzyme reactor Fe3O4@COF-Apt-AChE through the high affinity and specificity with its binding aptamer. The as constructed enzyme reactor was comprehensively characterized and the key factors that affected its catalysis efficiency were investigated in detail. Owing to the surface modification of the magnetic COF materials by aptamer for acetylcholinesterase immobilization, the immobilized enzyme exhibited improved substrates affinity. What's more, good reusability (more than 8 times) and prolonged stability (enzyme activity still kept at 90% after 42 days) were also achieved. Finally, the enzyme reactor could be applied in AChE inhibitors screening, which expanded its application capability. The proposed protocol not only paves a new way for fabrication of novel aptamer functionalized magnetic COF materials as enzyme reactors, but also indicates a broadened application of the integration of aptamer and its enzyme.


Comparative analysis of two navigation techniques based on augmented reality technology for the orthodontic mini-implants placement.
To analyze and compare the accuracy and root contact prevalence, comparing a conventional freehand technique and two navigation techniques based on augmented reality technology for the orthodontic self-drilling mini-implants placement. Methods Two hundred and seven orthodontic self-drilling mini-implants were placed using either a conventional freehand technique (FHT) and two navigation techniques based on augmented reality technology (AR TOOTH and AR SCREWS). Accuracy across different dental sectors was also analyzed. CBCT and intraoral scans were taken both prior to and following orthodontic self-drilling mini-implants placement. The deviation angle and horizontal were then analyzed; these measurements were taken at the coronal entry point and apical endpoint between the planned and performed orthodontic self-drilling mini-implants. In addition, any complications resulting from mini-implant placement, such as spot perforations, were also analyzed across all dental sectors.Results The statistical analysis showed significant differences between study groups with regard to the coronal entry-point (p < 0.001), apical end-point(p < 0.001) and angular deviations (p < 0.001). Furthermore, statistically significant differences were shown between the orthodontic self-drilling mini-implants placement site at the coronal entry-point (p < 0.0001) and apical end-point (p < 0.001). Additionally, eight root perforations were observed in the FHT group, while there were no root perforations in the two navigation techniques based on augmented reality technology.Conclusions The navigation techniques based on augmented reality technology has an effect on the accuracy of orthodontic self-drilling mini-implants placement and results in fewer intraoperative complications, comparing to the conventional free-hand technique. The AR TOOTH augmented reality technique showed more accurate results between planned and placed orthodontic self-drilling mini-implants, comparing to the AR SCREWS and conventional free-hand techniques. The navigation techniques based on augmented reality technology showed fewer intraoperative complications, comparing to the conventional free-hand technique.


Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis.
The aim of this meta-analysis was to evaluate the effects of additional trimetazidine (TMZ) treatment on patients with chronic heart failure (CHF). Conflicting results currently exist on the clinical use of TMZ in CHF patients. PubMed, MEDLINE, EMBASE, and EBM Reviews databases were searched through November 2010 for randomized controlled trials (RCTs) assessing TMZ treatment in CHF patients. Data concerning the study design, patient characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models. Sixteen RCTs involving 884 CHF patients were included. Hospitalization for cardiac causes (RR: 0.43, p = 0.03), but not all-cause mortality (RR: 0.47, p = 0.27), was reduced by TMZ treatment. Moreover, TMZ therapy was associated not only with the increase of left ventricular ejection fraction (WMD: 6.46%, p < 0.0001) and total exercise time (WMD: 63.75 seconds, p < 0.0001), but also with the decrease of New York Heart Association functional class (WMD: -0.57, p = 0.0003), left ventricular end-systolic diameter (WMD: -6.67 mm, p < 0.0001), left ventricular end-diastolic diameter (WMD: -6.05 mm, p < 0.0001), and B-type natriuretic peptide (WMD: -203.40 pg/ml, p = 0.0002). Additional use of TMZ in CHF patients may decrease hospitalization for cardiac causes, improve clinical symptoms and cardiac function, and simultaneously ameliorate left ventricular remodeling.


Prevalence and Definition of Multilevel Lumbar Developmental Spinal Stenosis.
Cross-sectional study. To define multilevel lumbar developmental spinal stenosis (DSS) using a composite score model and to determine its prevalence. This was a cohort study of 2385 openly recruited subjects with lumbosacral (L1-S1) MRIs. All subjects with previous spinal surgery or spinal deformities were excluded. The anteroposterior (AP) vertebral canal diameter was measured by two independent observers. Any associations between level-specific vertebral canal diameter and subject body habitus were analysed with non-parametric tests. Three or more stenotic levels, equivalent to a composite score of 3 or more, were considered as multilevel DSS. The median values of these subjects' AP canal diameters were used to construct the multilevel DSS values. Receiver operating characteristic analysis was utilized to determine the ability of these cut-off values to screen for DSS by presenting their area under curve, sensitivity and specificity. Subject body habitus was poorly correlated with AP vertebral canal diameter. Multilevel DSS was identified as L1<19 mm, L2<19 mm, L3<18 mm, L4<18 mm, L5<18 mm, S1<16 mm with 81%-96% sensitivity and 72%-91% specificity. The prevalence of multilevel DSS in this cohort was 7.3%. Utilizing a large homogeneous cohort, the prevalence of multilevel DSS is determined. Our cut-offs provide high diagnostic accuracy. Patients with multiple levels that fulfil these criteria may be at-risk of spinal canal compressions at multiple sites. III.


Diagnosis and treatment of xerosis cutis - a position paper.
Xerosis cutis (also referred to as xeroderma, dry skin, asteatosis) affects more than 10 million individuals in Germany. It is among the most common dermatological diagnoses and a cardinal symptom of many dermatological, internal and neurological diseases. Even though it has been established that basic skin care plays a significant role in the management of patients with xerosis cutis, there are as yet no evidence-based algorithms for diagnosis and treatment. The present position paper provides physicians across all specialties with a practical, symptom-based approach to the prevention, diagnosis and treatment of xerosis cutis. Within a structured decision-making process, a panel of experienced dermatologists first defined questions relevant to everyday clinical practice, which were then addressed by a systematic review of the literature. Based on the evidence available as well as expert consensus, diagnostic and treatment algorithms were subsequently developed and agreed upon. Xerosis cutis is generally diagnosed on clinical grounds. Possible trigger factors must be avoided, and comorbidities should be adequately and specifically treated. Suitable skin care products should be chosen with a view to improving skin hydration and restoring its barrier function. They should therefore contain both rehydrating and lipid-replenishing components. The "drier" the skin appears, the greater the lipid content should be (preferably using water-in-oil formulations). The choice of ingredients is based on a patient's individual symptoms, such as scaling (e.g., urea), fissures/rhagades (e.g., urea or dexpanthenol), erythema (e.g., licochalcone A) and pruritus (e.g., polidocanol). Other factors to be considered include the site affected and patient age. Ingredients or rather combinations thereof for which there is good clinical evidence should be preferentially used. The best evidence by far is available for urea, whose efficacy in the treatment of xerosis is further enhanced by combining it with other natural moisturizing components and ceramides. The "xerosimeter" is a tool developed in an effort to facilitate patient management and for training purposes. It not only includes practical tools for diagnosis and follow-up but also a classification of ingredients and a structured treatment algorithm. The structured symptom- and evidence-based approach proposed herein contains a road map for diagnosis and treatment of xerosis cutis. It aims to raise awareness in terms of prevention and early treatment of this condition and may thus improve quality of life and prevent potential sequelae.


Update on the approach of urinary tract infection in childhood.
Urinary tract infection (UTI) is the most common bacterial infection in childhood. UTI may be the sentinel event for underlying renal abnormality. There are still many controversies regarding proper management of UTI. In this review article, the authors discuss recent recommendations for the diagnosis, treatment, prophylaxis, and imaging of UTI in childhood based on evidence, and when this is lacking, based on expert consensus. Data were obtained after a review of the literature and a search of Pubmed, Embase, Scopus, and Scielo. In the first year of life, UTIs are more common in boys (3.7%) than in girls (2%). Signs and symptoms of UTI are very nonspecific, especially in neonates and during childhood; in many cases, fever is the only symptom. Clinical history and physical examination may suggest UTI, but confirmation should be made by urine culture, which must be performed before any antimicrobial agent is given. During childhood, the proper collection of urine is essential to avoid false-positive results. Prompt diagnosis and initiation of treatment is important to prevent long-term renal scarring. Febrile infants with UTIs should undergo renal and bladder ultrasonography. Intravenous antibacterial agents are recommended for neonates and young infants. The authors also advise exclusion of obstructive uropathies as soon as possible and later vesicoureteral reflux, if indicated. Prophylaxis should be considered for cases of high susceptibility to UTI and high risk of renal damage.


Molecular plasticity and functional enhancements of leg muscles in response to hypergravity in the fruit fly Drosophila melanogaster.
Studies of organismal and tissue biomechanics have clearly demonstrated that musculoskeletal design is strongly dependent on experienced loads, which can vary in the short term, as a result of growth during life history and during the evolution of animal body size. However, how animals actually perceive and make adjustments to their load-bearing musculoskeletal elements that accommodate variation in their body weight is poorly understood. We developed an experimental model system that can be used to start addressing these open questions, and uses hypergravity centrifugation to experimentally manipulate the loads experienced by Drosophila melanogaster We examined effects of this manipulation on leg muscle alternative splicing of the sarcomere gene troponin T (Dmel\up; Fbgn0004169, herein referred to by its synonym TnT), a process that was previously demonstrated to precisely correlate with quantitative variation in body weight in Lepidoptera and rat. In a similar fashion, hypergravity centrifugation caused fast (i.e. within 24 h) changes to fly leg muscle TnT alternative splicing that correlated with body weight variation across eight D. melanogaster lines. Hypergravity treatment also appeared to enhance leg muscle function, as centrifuged flies showed an increased negative geotaxis response and jump ability. Although the identity and location of the sensors and effectors involved remains unknown, our results provide further support for the existence of an evolutionarily conserved mechanism that translates signals that encode body weight into appropriate skeletal muscle molecular and functional responses.


In vitro human phase I metabolism of xenobiotics I: pesticides and related chemicals used in agriculture and public health, September 2001.
Human phase I enzymes and their isoforms that metabolize pesticides are listed in a database that will be updated periodically. This initial version includes enzymes and isoforms that metabolize organophosphorus insecticides, chloroacetamide herbicides and triazine herbicides.


Mitochondria-associated satellite I RNA binds to hnRNP K protein.
hnRNP K protein, which localizes to the nucleus, cytoplasm and mitochondria, is involved in the various cellular processes that compose gene expression. We used a SAGE-based assay to profile RNAs associated with hnRNP K protein in rat mitochondria. RNA was isolated from mitoplasts obtained from highly purified and RNase-treated mitochondria. Total RNA and RNA associated with hnRNP K protein were then used as input material for generating two SAGE libraries. Mitochondrion-derived tags isolated from the total mitoplast RNA library represented 86.3%, while those isolated from the library constructed from RNA associated with hnRNP K protein represented only 28.2% of selected tags. Thus, an unexpected number of nuclear-encoded RNAs were purified from mitochondria. Many of these transcripts were co-purified with hnRNP K protein, and high levels of nuclear-encoded RNAs co-immunoprecipitating with K protein corresponded to elevated hnRNP K protein levels of the organelle. The most abundant RNAs that were co-purified with hnRNP K protein represented transcripts originating from satellite I DNA. While satellite I RNA levels were higher in the nucleus and cytoplasm than in mitochondria, the most abundant binding of satellite I transcripts to hnRNP K protein was found in mitochondria. The role of satellite I RNA in mitochondria remains to be elucidated.


Congruency effects on the basis of instructed response-effect contingencies.
Previous research indicated that stimulus-response congruency effects can be obtained in one task (the diagnostic task) on the basis of the instructed stimulus-response mappings of another task (the inducer task) and this without having executed the instructions of the inducer task once. A common interpretation of such finding is that instructed stimulus-response mappings are implemented into functional associations, which automatically trigger responses when being irrelevant and this without any practice. The present study investigated whether instruction-based congruency effects are also observed for a different type of instructions than instructed S-R mappings, namely instructed response-effect contingencies. In three experiments, instruction-based congruency effects were observed in the diagnostic task when the instructions of the inducer task specified response-effect contingencies. On the one hand, our results indicate that instruction-based congruency effects are not restricted to instructed S-R mappings. On the other hand, our results suggest that the representations that mediate these effects do not specify the nature of the relation between response and effect even though this relation was explicitly specified by the instructions.


A new immunoblotting assay for thymidylate synthetase and its application to the regulation of enzyme activity in regenerating rat liver.
A highly sensitive and specific immunoblot assay has been developed to quantitate the content of rat liver thymidylate synthetase (EC 220.127.116.11). Applying the method, it is demonstrated that the increase of the activity of thymidylate synthetase in liver regeneration after partial hepatectomy is due to the de novo synthesis of the enzyme protein. Administration of cycloheximide, phenoxybenzamine, phorbol 12-myristate 13-acetate, nifedipine, dexamethasone or indomethacin to partially hepatectomized rats prevented the synthesis of thymidylate synthetase in regenerating liver. Thyroparathyroidectomy also inhibited the increase of the enzyme in liver regeneration. These observations are discussed in relation to the signal transduction concerning the alpha 1-receptor, which was shown to regulate liver regeneration in our previous papers.


A genetic variant c.553G > T in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and altered triglyceride levels in a Chinese population.
Elevation in plasma triglycerides (TG) has been widely accepted as a coronary artery disease (CAD) risk predictor. Recently, a new apolipoprotein playing an important role in TG metabolism named apolipoprotein AV (apoAV) was discovered, which is encoded by the APOA5 gene. Several single nucleotide polymorphisms (SNPs) of APOA5 associated with increased TG concentrations have been identified. We here report that a recently identified genetic variant, c.553G>T in the APOA5 gene which causes a substitution of a cysteine for a glycine residue at amino acid residue 185(G185C) is also associated with increased TG levels. To investigate the association between this genetic variation and the risk of CAD, a case-control study comprising 232 patients with CAD and 302 controls from the same area of China was performed. The minor allele frequencies of c.553G > T for the CAD and control groups were 7.76 and 3.97%, respectively (P = 0.008). In both the CAD and control groups, the T allele carriers had higher serum TG levels than homozygous carriers of the major G allele (CAD group: 2.67 +/- 1.48 mmol/l versus 1.95 +/- 1.02 mmol/l, P = 0.021; controls: 2.31 +/- 1.20 mmol/l versus 1.68 +/- 0.95 mmol/l, P = 0.002). After adjustment for age, gender, body mass index, smoking status, glucose and presence of hypertension, the odds ratio (OR) for CAD in the T allele carriers was 2.089 (95% CI = 1.140-3.830, P = 0.017), in comparison to the individuals without the T allele. These results suggest that the APOA5 c.553G > T polymorphism is an important predictor for hypertriglyceridemia and CAD.


Coronal plane femoral bowing in Far East Asians: implications for the strategy of distal femoral resection in total knee arthroplasty.
The accuracy of distal femoral resection in intramedullary (IM) guided total knee arthroplasty (TKA) depends on femoral morphology and varies according to individual anatomy. This study aimed to characterise coronal plane femoral bowing in Far East Asians according to age, sex, and severity of varus deformity to identify optimal strategies for distal femoral resection in TKA. Femoral anatomical parameters in 656 patients (M/F = 232:424) were assessed using standing long-leg anteroposterior radiography which was fulfilling strict standard. The femur was divided into three longitudinal segments to measure the segmental anatomical axial deviation from the mechanical axis and intersegmental bowing. Coronal plane femoral bowing pattern was categorised based on combined gross bowing and distal bowing. Mean hip-knee-ankle angle; neck-shaft angle; proximal, middle, and distal segmental axial differences; mechanical lateral distal femoral angle; and femur length were 6.7 ± 6.8°, 125.0 ± 5.5°, 5.9 ± 1.7°, 6.1 ± 1.1°, 5.3 ± 1.6°, 88.4 ± 2.6°, and 432.3 ± 23.9 mm in male and 8.4 ± 5.5°, 126.4 ± 5.6°, 5.4 ± 1.5°, 6.6 ± 0.9°, 5.6 ± 1.6°, 89.3 ± 2.6°, and 410.6 ± 23.3 mm in female, respectively. Mean proximal, distal, and gross femoral bowing was 0.3 ± 1.8°, - 0.8 ± 1.8°, and - 0.5 ± 2.9° in male and 1.2 ± 1.6°, - 1.0 ± 1.6°, and 0.2 ± 2.7° in female, respectively. Grossly straight femur with a straight distal part was the most common femoral bowing pattern in Far East Asians. Distal bowing was proved to be a key factor to choose method for distal femoral resection in TKA. Using IM-guide to achieve accurate distal femoral resection in the femora with distal segmental axial deviation between 4-8° and distal bowing less than ± 1° is considered feasible.


Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations.
Electron microscopic and morphometric investigations on undescended testicles show a decreased volume density of the spermatogonia up to the age of 5 (approximately 60%, p smaller than 0.005), corresponding to investigations by light microscopy. There are no ultrastructural differences in the seminiferous tubules between normal and undescended testicles up to the age of 1 yr. There are ultrastructural changes of Leydig cells within the first year of life. Based on these investigations, we conclude that the optimal time for surgical intervention in case of undescended testes is in the second year.


Functional analysis of the MATB mating-type idiomorph of the dimorphic fungus Yarrowia lipolytica.
The whole MATA cassette from Yarrowia lipolytica, a dimorphic fungus, was replaced by the URA3 gene through a double homologous recombination. This MAT-less strain lost its mate capacity with A or B Y. lipolytica strains. Introduction of polymerase chain reaction-synthesized idiomorph MATB in a null strain of A locus by double homologous recombination gave rise to a "transsexual" B strain. Mating capacity of this engineered mutant was assayed using Y. lipolytica strains of either A or B mating type. Mating took place only with an A strain, demonstrating the MATB idiomorph functionality in a MATA phenotype. Our data suggest that specific downstream genes are responsible for the final A or B phenotypes present in all Y. lipolytica cells, independent of their MAT idiomorph phenotype.


Application of the Microtox test and pollution indices to the study of water toxicity in the Albufera Natural Park (Valencia, Spain).
The toxic effects of waters collected from irrigation channels in a Mediterranean wetland (Albufera Natural Park, Valencia, Spain) were tested with the Microtox assay and compared with six pollution indices (PIs) defined from analytical parameters. Chemical oxygen demand (COD), biological oxygen demand (BOD), nutrients, heavy metals and pesticides were measured. The bioassay result (concentrations of the water sample (% V/V) that reduced light emission to 10%, 20% and 50%, EC10, EC20 and EC50, respectively (ECs)) was compared with the PIs. This comparison has demonstrated a general agreement between ECs and PIs, except in the case of irrigation channels affected by herbicides used in rice farming (molinate and thiobencarb). No pronounced inhibition was detected in the bioluminescence in relation to the eutrophic parameters in the irrigation waters for EC50 values, indicating that this parameter does not suffice to detect eutrophic waters. Data derived from irrigation water pollution and bioassay were assembled by multivariate statistical techniques (principal component analysis). These components were associated with various contamination sources.


Quantification of ultrastructural variations in enriched blood basophils: correlation of morphological changes and antigen-induced histamine release.
Highly purified preparations of human basophils have been studied ultrastructurally to delineate quantifiably those alterations associated with immunologically-induced histamine release. Of six characteristic variations of basophil morphology, totally degranulated cells, those with some exteriorized granules and those with some extracellular vesicles were almost exclusively associated with antigen challenge. Of these, total degranulation without extracellular granules or vesicles was most frequent. A correlation was found between percentage histamine released and percentage totally degranulated cells present in the samples incubated with antigen. In addition, increased plasma membrane folding and irregularity were more prevalent in stimulated samples than in controls and their mean frequency was related quantifiably to the percentage of histamine released in each group. Cells with empty vesicles or electronlucent intracellular granules or both occurred to the same extent in experimental and control aliquots. The possible of histamine release is discussed.


[Occult stromal tumour of the small intestine: a cause of chronic intestinal blood loss in a 70 year-old woman].
The case of a 70 year-old woman with a chronic gastrointestinal blood loss due to a stromal tumor located in the middle third of the small intestine is reported. The peculiarities of the case are the characteristic immunohistochemistry of the neoplasm and, particularly, the mimetic clinical presentation, a kind of ''phantom tumor'' confirmed only with celiotomy and surgical excision.


Generation of carboxy-terminally deleted forms of STAT5 during preparation of cell extracts.
Carboxy-terminally deleted forms of STAT5 have been described to be generated in vivo either by proteolytic processing or by differential splicing mechanisms. By comparing two different cell extraction procedures, we can show that in the mammary gland carboxy-terminally deleted forms are produced in vitro and are not detectable in extracts prepared by SDS lysis.


Highly porous terpolymer-ZIF8@BA MOF composite for identification of mono- and multi-glycosylated peptides/proteins using MS-based bottom-up approach.
A hydrophilic terpolymer MOF composite is designed with high surface area and porosity to enrich mono- and multi-glycosylated peptides facilitating a bottom-up approach. Terpolymer@ZIF-8 is synthesized using free radical polymerization followed by layer by layer ZIF-8 fabrication. Subsequent surface modification was made by aminophenylboronic acid (AMBA). The enrichment ability of terpolymer@ZIF-8@BA is evaluated by using tryptic digest of IgG and HRP to exemplify mono- and multi-glycosylated protein samples. Improved selectivity of 1:200 for spiked HRP in BSA digest and sensitivity down to 1 fmol μL-1 is achieved. Batch to batch reproducibility is better 1% RSD which favors the adoption of the developed method for routine N-linked glycopeptide/protein determination. Cost-effective nature of given approach is given by regeneration of the material up to four cycles. Total 318 N-linked glycopeptides have been identified from 1 μL human serum digest after subjecting the enriched and PNGase-treated deglycosylated peptides to LC-MS. Thus, terpolymer@ZIF-8@BA holds the potential both for mono- and multi-glycosylated peptides from complex biological sample. Graphical abstract.


Confirmation that Plasmodium falciparum has aperiodic infectivity to Anopheles gambiae.
In preparation for field studies of transmission-blocking malaria vaccines, a study was carried out to determine whether P. falciparum infections obtained in An. gambiae blood-fed at 16.00 hours were quantitatively similar to infections obtained at 23.00 hours. Using a group of children aged 5-12 years from villages at Ahero, near Kisumu in Kenya, 71/74 (96%) of whom were found to be positive for P.falciparum parasitaemia, one batch of fifty colony-bred An.gambiae females were fed on volunteers at 16.00 hours and another batch at 23.00 hours. No statistically significant differences were found in the proportions of mosquitoes becoming infected, the numbers of children infecting mosquitoes or the mean numbers of malaria oocysts developing in mosquitoes blood-fed at the different times. Because mosquito infections obtained by day (16.00 hours) are equivalent in quantity to those obtained at night (23.00 hours), experimental infections can be carried out in the afternoon, when it is most convenient, rather than during the night.


Right hemicolectomy plus pancreaticoduodenectomy vs partial duodenectomy in treatment of locally advanced right colon cancer invading pancreas and/or only duodenum.
Pancreatic or duodenal invasion by locally advanced right colon cancer is an unusual event whose management still represents a surgical challenge. This review aims to compare results of limited vs. extended resection in case of primary right colon cancer invading pancreas and/or duodenum. A systematic search in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. All trials describing the surgical treatment of right colon cancer invading pancreas and/or duodenum were considered. A data extraction sheet was developed, based on the Cochrane Consumers and Communication Review Group's data extraction template. 5-years overall survival was 52% after en bloc pancreaticoduodenectomy plus right hemicolectomy vs. 0 and 25% in case of duodenal resection with correction by direct suture or pedicled ileal flap, respectively. 30-day postoperative morbidity rate was slightly higher after en block resections (12.8%) with respect to duodenal local resection and direct suture or pedicled ileal flap repair (0 and 12.2%, respectively). After extended resection the rate of pancreatico-jejunal anastomotic leakage was 7.7%. In patients with right colon cancer extended to the pancreas and/or duodenum surgical multivisceral resection is suggested when complete tumour removal (R0) is achievable. Even though no significant differences in postoperative morbidity and mortality have been shown, 5 y OS has improved in extended resections as compared to duodenal local resection with defect repair either by direct suture or by a pedicled ileal flap.


Genetic ablation of epidermal EGFR reveals the dynamic origin of adverse effects of anti-EGFR therapy.
Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients' plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils. As the skin phenotype evolved, changes in blood counts and circulating chemokines reproduced those seen in the gefitinib-treated patients. Crossing the mutant mice with mice deficient for tumor necrosis factor-α (TNF-α) receptors, MyD88, NOS2, CCR2, T cells, or B cells failed to reverse the skin phenotype. However, local depletion of macrophages provided partial resolution, suggesting that this model can identify targets that may be effective in preventing the troublesome and dose-limiting skin response to anti-EGFR drugs. These results highlight the importance of EGFR signaling in maintaining skin immune homeostasis and identify a macrophage contribution to a serious adverse consequence of cancer chemotherapy.


[Antiviral chemotherapeutic agents. XVIII. Adamantane derivatives of amphetamine. Their potential interest as autonomic and antiparkinson agents].
Adamantane isologs of amphetamine, methamphetamine and pheniprazine and several derivatives were synthesized in order to study the influence of their more pronounced lipophilic characteristics on their biological properties. A preliminary examination of their toxicity, antiviral, CNS stimulant and antiparkinson activity is described. The adamantyl amphetamine, which proved active, will be further studied.


Western blot analysis of a limited number of cells: a valuable adjunct to proteome analysis of paraffin wax-embedded, alcohol-fixed tissue after laser capture microdissection.
In recent years, laser capture microdissection (LCM) has been used successfully to obtain distinct populations of cells for subsequent molecular analysis. Because of the limited sample availability and the absence of in vitro amplification steps for proteins, the use of LCM for proteome analysis largely depends on highly sensitive protein detection methods. In this study, a western blot protocol was developed and validated for the detection of beta-actin and the moderately expressed cell death protein caspase-3 in small numbers of cells. Initially, cultured human U937 monocytes and whole sections of paraffin wax-embedded, alcohol-fixed human tonsils were used to optimize protein electrophoresis and western blotting conditions. High-performance NuPAGE Bis-Tris gels in combination with high-quality transfer membranes, optimized antibody concentrations, and a sensitive chemiluminescent substrate provided a strong signal for beta-actin with approximately 500 U937 cells. In the same way, procaspase-3 could be identified with approximately 1000 cells. Similar results were obtained with germinal centre cells that were procured from paraffin wax-embedded, alcohol-fixed human tonsils by LCM. Treatment of U937 cells with etoposide rapidly induced cell death and allowed the detection of active caspase-3 with approximately 2500 cells (0.8 pg of protein). The findings of this study suggest that western blotting is a valuable adjunct to proteome analysis of LCM procured cells.


Physiological activity of some organophosphorous compounds and their influence on mechanical properties of erythrocytes.
Hemolysis and fluidization of erythrocytes (RBC) membranes by some newly synthesized aminophosphonates as well as their potency to induce electrolyte efflux from cucumber (Cucumis sativus cv "Wisconsin") cotyledons were studied. Also, the chlorophyll content in aminophosphonate-treated cotyledons was affected. The compounds studied differed mainly in hydrophobicity of their substituents at the carbon, nitrogen and phosphorus atoms. It was found that aminophosphonate potency to fluidize RBC membranes depended on the combination of its overall lipophilicity and/or the kind of substituent at the P atom. Especially, iso-propyl groups enhanced that potency. The sequence of aminophosphonates that exhibited the strongest fluidization activity was paralelled by their physiological and hemolytic activities; in the latter case for these compounds that hemolyzed RBC under used concentrations. A general conclusion is that both the stereochemistry and lipophilicity determine the efficiency of the aminophosphonates studied. This efficiency is most probably related to the interaction of aminophosphonates with the lipid phase of biological objects.


Gastric Stenosis After Laparoscopic Sleeve Gastrectomy: Diagnosis and Management.
The use of laparoscopic sleeve gastrectomy (LSG) is increasing worldwide. Although post-LSG gastric stenosis (GS) is less frequent, it has not been well defined and lacks standardized management procedures. The objective of the present study was to describe a series of patients with GS symptoms after LSG and to develop a standardized management procedure for this complication. We performed a retrospective analysis of a prospective database of patients presenting with GS after LSG procedures performed between January 2008 and March 2014. The primary efficacy criterion was the frequency of post-LSG GS. GS was classified as functional (i.e. a gastric twist) or organic. The secondary efficacy criteria included the time interval between LSG and diagnosis of GS, the type of stenosis, the type of management, and the follow-up data. During the study period, 1210 patients underwent primary or secondary LSG. Seventeen patients had post-operative symptoms of GS (1.4%); one patient had achalasia that had not been diagnosed preoperatively and thus was excluded from our analysis. The median time interval between LSG and diagnosis of GS was 47.2 days (1-114). Eleven patients had organic GS and six had functional GS. Seven patients required nutritional support. Endoscopic treatment was successful in 15 patients (88.2%) after balloon dilatation (n = 13) or insertion of a covered stent (n = 2). Two of the 15 patients required conversion to Roux-en-Y gastric bypass (11.8%). GS after LSG is a rare complication but requires standardized management. Most cases can be treated successfully with endoscopic balloon dilatation.


Silibinin pretreatment protects against ochratoxin A-mediated apoptosis in primary rat hepatocytes.
The inhibitory effect of silibinin on ochratoxin A (OTA)-mediated apoptosis on primary rat hepatocytes was investigated. Rat hepatocytes were prepared by two different methods: the classical enzymatic digestion method by collagenase perfusion and a new EDTA-perfusion method. The EDTA-perfusion method yielded hepatocytes, which were stably cultivated without DNA fragmentation for up to 96 h, whereas the collagenase-prepared hepatocytes showed apoptosis events as early as from the start of preparation even in the absence of OTA. Treatment with 12.5 μmol/l OTA of cultured hepatocytes prepared under ETDA perfusion developed DNA-laddering after 24-36 h. Lipopolysaccharide (LPS) of 0.1 up to 12.5 μg/ml showed no apoptotic DNA-effects under these conditions. A low concentration of 26 μmol/l silibinin given prior to OTA slightly prevented OTA-mediated DNA-laddering, whereas a five times higher concentration of silibinin (130 μmol/l) completely inhibited OTA-mediated apoptosis. Under the same conditions, caspase-3 activity in hepatocytes increased in a time-dependent manner under OTA exposure within 12-24 h but was blocked by 130 μmol/l silibinin. In contrast, LPS incubation for 12 and 24 h did not alter caspase-3 activity. To measure viability of OTA-/LPS-treated hepatocytes, the MTT-test and Live/Dead kit were applied. The results demonstrated that the used OTA concentration of 12.5 μmol/l only moderately decreased viability for up to 24 h but showed cytotoxic effects depending on longer incubation times (≥36 h). In contrast, LPS up to 12.5 μg/ml exhibited no cytotoxic effects up to 48 h. In summary, our results showed contrasting effects on apoptosis in primary rat hepatocytes by OTA (produces apoptosis) versus LPS (produces no apoptosis), also depending on the method of hepatocyte preparation. Silibinin at 130 μmol/l showed significant hepatoprotective and antiapoptotic effects against OTA-mediated cell damage on cultured rat hepatocytes.


Sleep in athletes undertaking protocols of exposure to nocturnal simulated altitude at 2650 m.
A popular method to attempt to enhance performance is for athletes to sleep at natural or simulated moderate altitude (SMA) when training daily near sea level. Based on our previous observation of periodic breathing in athletes sleeping at SMA, we hypothesised that athletes' sleep quality would also suffer with hypoxia. Using two typical protocols of nocturnal SMA (2650 m), we examined the effect on the sleep physiology of 14 male endurance-trained athletes. The selected protocols were Consecutive (15 successive exposure nights) and Intermittent (3x 5 successive exposure nights, interspersed with 2 normoxic nights) and athletes were randomly assigned to follow either one. We monitored sleep for two successive nights under baseline conditions (B; normoxia, 600 m) and then at weekly intervals (nights 1, 8 and 15 (N1, N8 and N15, respectively)) of the protocols. Since there was no significant difference in response between the protocols being followed (based on n=7, for each group) we are unable to support a preference for either one, although the likelihood of a Type II error must be acknowledged. For all athletes (n=14), respiratory disturbance and arousal responses between B and N1, although large in magnitude, were highly individual and not statistically significant. However, SpO2 decreased at N1 versus B (p<0.001) and remained lower on N8 (p<0.001) and N15 (p<0.001), not returning to baseline level. Compared to B, arousals were more frequent on N8 (p=0.02) and N15 (p=0.01). The percent of rapid eye movement sleep (REM) increased from N1 to N8 (p=0.03) and N15 (p=0.01). Overall, sleeping at 2650 m causes sleep disturbance in susceptible athletes, yet there was some improvement in REM sleep over the study duration.


Effect of body mass on exercise-induced bronchospasm and atopy in African children.
Sensitization to allergen is common in rural populations in less affluent countries, but atopic disease is less frequent than in richer countries. Variables explaining this dichotomy may provide insight into underlying mechanisms of atopic diseases like asthma. To test whether risk of exercise-induced bronchospasm (EIB) in urbanized African populations is increased in association with greater skin sensitivity or increased body mass. A total of 3322 children were enrolled in a prevalence survey of EIB in urban and rural South Africa. Children responding positively to an exercise challenge and a random sample of children responding negatively were recruited into a case-control study (393 controls, 380 cases). Subjects were investigated by using allergen skin prick testing, anthropometry, and assay of IgE. Stools were analyzed for parasite infestation. The prevalence of EIB was higher in urban (14.9%) than rural (8.9%) areas (P < .0001). The difference in risk of EIB between urban and rural subjects was associated with atopy (odds ratio [OR] for upper tertile of skin wheal diameter, 2.65; 95% CI, 1.43-4.89; P < .0001), increasing weight (OR for upper tertile of body mass index [BMI], 2.17; 95% CI, 1.45-3.26; P = .001), and affluence. Increasing BMI was also associated with a greater strength of association between specific IgE and the corresponding skin test (Dermatophagoides pteronyssinus, OR for a positive skin test result in presence of specific IgE: heavier subjects, OR, 34.6; 95% CI, 0.9-109.3; P < .0001; lighter subjects, OR, 8.05; 95% CI, 2.74-23.6; P < .001). Increases in BMI of rural children in subsistence economies may lead to an increased prevalence of atopic disease. This observation merits further investigation in prospective studies.


Bile Acid Regulates the Colonization and Dissemination of Candida albicans from the Gastrointestinal Tract by Controlling Host Defense System and Microbiota.
Candida albicans (CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of taurocholic acid (TCA), a major bile acid in antibiotic-treated mice susceptible to CA infection. In vivo findings indicate that administration of TCA through drinking water is sufficient to induce colonization and dissemination of CA in wild-type and immunosuppressed mice. Treatment with TCA significantly reduced mRNA expression of immune genes ang4 and Cxcr3 in the colon. In addition, TCA significantly decreased the relative abundance of three culturable species of commensal bacteria, Turicibacter sanguinis, Lactobacillus johnsonii, and Clostridium celatum, in both cecal contents and mucosal scrapings from the colon. Taken together, our results indicate that TCA promotes fungal colonization and dissemination of CA from the GI tract by controlling the host defense system and intestinal microbiota that play a critical role in regulating CA in the intestine.


Torsades de pointes related to transient marked QT prolongation following successful emergent percutaneous coronary intervention for acute coronary syndrome.
We report 2 patients in whom transient marked QT prolongation occurred after successful emergent percutaneous coronary intervention (PCI) for acute coronary syndrome. One patient developed torsades de pointes. In both cases, the QT interval became markedly prolonged within 24 hours after PCI, and this prolongation persisted for 4 days. The T waves had a giant and bizarre negative shape with a prolonged T-wave peak to T-wave end interval. No new-onset ischemia or congenital long QT syndrome was related to the episodes. The patients had not taken any drugs that could have prolonged the QT interval, and their serum potassium levels were within normal limits. Torsades de pointes following successful PCI for acute coronary syndrome is uncommon, but acquired long QT syndrome should be considered and treated in patients in whom giant and bizarre negative T waves and QT prolongation develop after PCI.


The structure and development of osteogenetic repair tissue according to Ilizarov Technique in man. Characterization of extracellular matrix.
Distraction osteogenesis by the method of Ilizarov has permitted the study of bone formation. This is an analysis of 64 human biopsies in patients who were undergoing tibial lengthening by the method of Ilizarov. After analysis by conventional and polarized light microscopy, four stages of bone formation were identified. Bone formation is of the direct type with no cartilaginous phase.


Dentin Matrix Protein 1 Compensates for Lack of Osteopontin in Regulating Odontoblastlike Cell Differentiation after Tooth Injury in Mice.
Although dentin matrix protein 1 (DMP1) and osteopontin (OPN) act as substrates and signaling molecules for odontoblastlike cell differentiation after tooth injury, the mutual interaction between these proteins in the mechanism of odontoblastlike cell differentiation remains to be clarified. This study aimed to elucidate the role of DMP1 and OPN in regulating odontoblastlike cell differentiation after tooth injury. A groove-shaped cavity was prepared on the mesial surface of the upper first molars in wild-type and Opn knockout (KO) mice. The demineralized paraffin sections were processed for immunohistochemistry for nestin and DMP1 and in situ hybridization for Dmp1. For the in vitro assay, the experiments of organ culture for evaluating dentin-pulp complex regeneration using small interfering RNA treatment were performed. Once preexisting odontoblasts died, nestin-positive newly differentiated odontoblastlike cells were arranged along the pulp-dentin border and began to express DMP1/Dmp1. In Opn KO mice, the expression of DMP1/Dmp1 was up-regulated compared with that of wild-type mice. The in vitro assay showed that the gene suppression of Dmp1 by small interfering RNA showed a tendency to decrease the differentiation rate of odontoblastlike cells from 70.1% to 52.2% in wild-type teeth. In addition, the suppression of Dmp1 in Opn KO teeth tended to lead to the inhibition of odontoblastlike cell differentiation. These results suggest that the expression of Dmp1 is up-regulated in Opn KO mice both in vivo and in vitro, and DMP1 compensates for the lack of OPN in regulating odontoblastlike cell differentiation after tooth injury.


Characterization of amorphous ursodeoxycholic acid prepared by spray-drying.
The objectives of this study were to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples prepared by spray-drying, and to demonstrate the applicability of thermal and water-vapour-adsorption techniques for studying the material. Amorphous UDCA was prepared by spray-drying a solution of the compound in a mixture of ethanol and dichloromethane. The amorphous material was characterized by powder X-ray diffraction, infrared (IR) spectroscopy, isothermal microcalorimetry, differential scanning calorimetry (DSC) and water-vapour adsorption. When the inlet-air temperature of the spray drier was increased beyond 140 degrees C, the intensity of X-ray diffraction peaks from crystalline UDCA decreased and the IR bands in the hydroxyl-stretching and carboxyl-stretching regions changed. Dissolution of intact and spray-dried samples of UDCA prepared at 60 and 100 degrees C was an endothermic process but the dissolution became exothermic with increasing inlet-air temperature. UDCA samples differing in crystallinity were obtained, depending on the inlet-air temperature. A good correlation was obtained between the heat of solution and the heat of crystallization determined from DSC peak area. A good correlation was also obtained between the heat of solution and the crystallinity determined by Ruland's method from X-ray diffraction patterns. The amount of water vapour adsorbed on UDCA samples increased with increasing inlet-air temperature, indicating hydrogen bonding between water molecules and the hydroxyl groups or the carboxyl groups of amorphous UDCA. These results indicate that measurement of adsorption of water vapour and thermal analysis can both be used to evaluate the crystallinity of solid substances.


Metals in the tissues of two fish species from the rare and endemic fish nature reserve in the upper reaches of the Yangtze River, China.
Concentrations of copper, zinc, mercury, and arsenic were measured in the muscle, gill and liver tissues of Coreius heterodon and Pelteobagrus vachelli collected from the rare and endemic fish nature reserve in the upper reaches of the Yangtze River. The concentrations of copper and zinc in the tissues of these two fish species were higher than those of mercury and arsenic. Highest metal concentrations were generally found in fish samples from Yibin. The concentrations of copper, zinc, mercury, and arsenic in C. heterodon were higher than that in P. vachelli. The fish from this study area were not safe for human consumption.


Cardiac complications in preterm infants with percutaneous long lines: the importance of early diagnosis.
Percutaneous long lines, routinely used in preterm infants, can be associated with several cardiac complications such as pericardial effusion and consequent cardiac tamponade. We report three patients with pericardial effusion highlighting the importance of cardiac ultrasound monitoring to both early diagnosis and treatment.


Non-exposed endoscopic wall-inversion surgery as a novel partial gastrectomy technique.
In gastric full-thickness resection employing both endoscopy and laparoscopy, intraabdominal contamination or even possibly tumor seeding is unavoidable as a result of iatrogenic perforation and the resultant spread of gastric juice. To minimize contamination and resected tissue volume, we developed a new technique without perforation termed non-exposed endoscopic wall-inversion surgery (NEWS), and present here the preliminary results. In a clinical observation cohort study, NEWS was attempted in six patients with gastric SMT to investigate the procedure, mortality, and morbidity. NEWS consists of several steps: marking around a tumor on the mucosal as well as the serosal surface, submucosal injection of sodium hyaluronate with indigo carmine dye, circumferential seromuscular dissection with suture closure under laparoscopy, and circumferential mucosubmucosal incision under gastric endoscopy. The resected specimen is then retrieved perorally. Perforation occurred as a result of misidentification and technical inadequacy in the first three patients. After modification of the devices, the entire procedure was successfully achieved in the latter three. There were no complications in any of our six cases. NEWS allows en bloc full-thickness resection, theoretically avoiding contamination and tumor dissemination into the peritoneal cavity.


Medical therapy in patients with endogenous hypoglycaemia: Is euglycaemia achievable?
While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalize plasma glucose levels can be useful. The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions. All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording. Twenty-seven patients (inappropriate insulin secretion n = 25 and IGF2 secretion n = 2), treated with diazoxide (n = 16), somatostatin analogues (n = 7), glucocorticoids (n = 3) or a combination of these treatments (n = 1) were enroled. Twenty-five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in seven patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in five patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%). Despite the disappearance of hypoglycaemia-related clinical symptoms and normalization of blood glucose self-monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo- and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo- or hyperglycaemic excursions.


Intracellular transport and processing of lysosomal cathepsin B.
Intracellular transport and processing of lysosomal cathepsin B was investigated in the subcellular fractions of rat liver by pulse-labeling experiments with [35S]methionine in vivo. A newly synthesized procathepsin B with a molecular weight of 39 kDa firstly appeared in the rough microsomal fraction at 10 min postinjection of label. This procathepsin B moved from the microsomal fractions to the Golgi subfractions at 30 min postinjection, and then a processed mature enzyme appeared in the lysosomal fraction at 60 min. These results suggest that the propeptide-processing of procathepsin B takes place in lysosomes in the course of intracellular transport from endoplasmic reticulum through Golgi complex to lysosomes.


Learning by doing: action performance facilitates affordance perception.
We investigated the effect of action performance on perceptual judgments by evaluating accuracy in judging whether doorways allowed passage. Participants made judgments either before or after walking through doorways of varying widths. Participants in the action-first group benefited from action feedback and made more accurate judgments compared to a perception-first group that judged doorways before walking through them. Action feedback aided perceptual judgments by facilitating scaling to body dimensions: Judgments in the action-first group were strongly related to height, weight, and torso size, whereas judgments in the perception-first group were not.


Remote pharmacological preconditioning on median nerve territory increases Hsp32 expression and attenuates ischemia-reperfusion injury in rat heart.
The aim of this study was to test the hypothesis that remote pharmacological preconditioning (RPP) induced myocardial heat shock protein (Hsp) 32 expression and attenuated the ischemia-reperfusion (I/R) injury of the heart in rats. Animals were injected at the left median nerve territory with chloralose and urethane mixture. At different time intervals, myocardial Hsp32 gene expression was analyzed. Primary heart cultures were used to investigate the direct effect of drug mixture on Hsp32 expression. The results showed that Hsp32 was time- and dose-dependently increased by in vivo drug mixture treatment, but not in primary cultures. RPP significantly decreased the duration of arrhythmia and incidence of stony heart in rats with subsequent I/R injury. We conclude that RPP on the left median nerve territory induced Hsp32 gene expression in the heart and attenuates myocardial damage functionally after subsequent I/R injury.


Scaling of morphogenetic patterns in reaction-diffusion systems.
Development of multicellular organisms is commonly associated with the response of individual cells to concentrations of chemical substances called morphogens. Concentration fields of morphogens form a basis for biological patterning and ensure its properties including ability to scale with the size of the organism. While mechanisms underlying the formation of morphogen gradients are reasonably well understood, little is known about processes responsible for their scaling. Here, we perform a formal analysis of scaling for chemical patterns forming in continuous systems. We introduce a quantity representing the sensitivity of systems to changes in their size and use it to analyse scaling properties of patterns forming in a few different systems. Particularly, we consider how scaling properties of morphogen gradients forming in diffusion-decay systems depend on boundary conditions and how the scaling can be improved by passive modulation of morphogens or active transport in the system. We also analyse scaling of morphogenetic signal caused by two opposing gradients and consider scaling properties of patterns forming in activator-inhibitor systems. We conclude with a few possible mechanisms which allow scaling of morphogenetic patterns.


Disassembly of F-actin filaments in human endothelial cells cultured on type V collagen.
We examined the inhibitory activity of type V collagen on cell attachment and cell growth and the role of stress fibers and beta 1 integrin in cultured human endothelial cells. Human endothelial cells cultured on type V collagen attached temporarily to the substrate and formed stress fibers. However, the cells failed to proliferate and gradually detached from the substrate. After 24 h, the cells on type V collagen lacked discernible stress fibers (F-actin filaments) and exhibited dots in small aggregates of F-actin. In addition, the cells expressed little or no proteins as focal adhesions, including vinculin and beta 1 integrin. In contrast, the cells on fibronectin and type I collagen formed complete F-actin filaments, exhibited sufficient vinculin and beta 1 integrin, and grew logarithmically from 2 days. On the other hand, human smooth muscle cells formed complete F-actin filaments, revealed typical focal adhesions, and started to proliferate rapidly after 24 h on type V collagen as well as on fibronectin and type I collagen. Thus, the disassembly of F-actin filaments was observed as a specific phenomenon in human endothelial cells cultured on type V collagen. Moreover, the F-actin filaments disappeared from endothelial cells treated with cytochalasin D after 24 h and the cells detached from fibronectin and type I collagen with time, a result consistent with the observations on type V collagen. Accordingly, the disassembly of F-actin filaments in focal adhesions may result in the detachment of endothelial cells from type V collagen.


The Effect of Leg Dominance and Group Difference in Star Excursion Balance Test between Individuals with Chronic Ankle Instability, Ankle Sprain Copers and Healthy Controls.
To evaluate patients with chronic ankle instability (CAI), copers who had a sprain without instability, and healthy controls using the Star Excursion Balance Test (SEBT). In addition, the reach distance was assessed between the both legs in terms of dominant and non-dominant in all groups. A total of 75 subjects (25 healthy, 25 CAI, and 25 Coper) participated. The maximum reach distance in SEBT was assessed in anterior (ANT), postero-medial (PM), and postero-lateral (PL) directions in both legs for each subject. All data were analyzed by SPSS version 21. Tukey post hoc test was used to compare all groups. Paired T-test was used to compare dominant and non-dominant legs in each group. In 75 subjects have participated in the data collection, no significant differences were reported among all groups for age and BMI measurements. Significant lower reach distance in scores of ANT in the dominant leg of the CAI was demonstrated when compared with the control and the coper groups (P=0.008). No statistical significant difference was determined between the dominant and non-dominant legs in each group (P>0.05). It seems that relevant strategies for postural control should be taken into account in the rehabilitation setup of individuals with CAI.


Erratum.
Cheek, J., Lipschitz, D. L., Abrams, E. M., Vago, D. R., & Nakamura, Y. (2015). Dynamic reflexivity in action: An armchair walkthrough of a qualitatively driven mixed-method and multiple methods study of mindfulness training in schoolchildren. Qualitative Health Research, 25(6), 751-762. (Original DOI: 10.1177/1049732315582022).


Removal of trace organic contaminants from wastewater by superfine powdered activated carbon (SPAC) is neither affected by SPAC dispersal nor coagulation.
Powdered activated carbon (PAC) is increasingly used as tertiary treatment for the removal of trace organic contaminants (TrOCs) from wastewater (WW). To enhance the sorption kinetics and capacity, the PAC particles can be milled down to superfine powdered activated carbon (SPAC). However, the small-grained SPAC particles are prone to aggregation, which may impact their treatment performance. In this study we examined the effect of SPAC dispersion and aggregation on TrOC removal kinetics and sorption capacity. Specifically, we assessed how two interventions that modulate the apparent size of SPAC - ultrasonication and coagulation - affect the uptake of TrOCs in secondary WW effluent. We quantified the removal of fourteen TrOCs, of which twelve are indicator substances for micropollutant removal in WWTPs as designated by the Swiss Water Protection Ordinance. We determined that at high SPAC doses (> 1.6 mgSPAC/mg Dissolved Organic Carbon [DOC]), the TrOC removal kinetics were fast even for aggregated SPAC, such that SPAC dispersal by ultrasonication yielded no benefit. At low SPAC doses (< 1.6 mgSPAC/mgDOC) and contact times (< 2 minutes) ultrasonication was beneficial, in particular if the SPAC particles reached complete dispersion prior to exposure to TrOCs. However, the energy consumption of such an ultrasonication step should be carefully weighed against the additional energy requirement associated with using a higher SPAC dose. Finally, a coagulant to mitigate membrane fouling can be added simultaneously with the SPAC without compromising the TrOC removal efficiency. We conclude that under realistic SPAC application scenarios in WWTPs, interventions that disperse SPAC during TrOC sorption are not necessary, and processes that aggregate SPAC are acceptable.


Recurrent aphasia with subclinical bioelectric status epilepticus during sleep.
We present a six years follow up of a 6 1/2 year-old boy with recurrent aphasia, sporadic emotional regression and a convulsive disorder. The electroencephalogram reading during sleep showed continuous, generalized, hypersynchronous activity without clinical evidence of seizure ("subclinical bioelectric status epilepticus"). Clinical, laboratory and instrumental data revealed no evidence of a morphological lesion of the brain, either space-occupying, inflammatory, degenerative, or autoimmune. Remissions occured with and without anticonvulsant and steroid therapy. The hypothetical location, type, and etiology of the process are discussed. The syndrome appears to represent a functional disorganisation of speech-controlling areas of the brain.


The role of physical exercise in prevention and management of osteoporosis.
The effect of exercises on vertebral trabecular bone mineral content (BMC) was investigated in 24 women with osteoporosis (OP) diagnosed by Quantitative Computed Tomography (QCT). Two groups were formed: an exercise and a control group with no exercise. Subjects in the exercise group exercised for one hour, twice weekly for a period of 6 months under the supervision of a physical therapist. A home exercise program which included the same exercises used in the hospital plus walking for half an hour every day was also assigned. Initial lumbar X-ray films, values obtained from laboratory investigations, physical activity scores and spinal BMC measurements were compared with those obtained after 6 months. The increase in the level of physical activity in the exercise group after exercise therapy was found statistically significant (p less than 0.001). After the exercise period, BMC values showed a 4.76% increase whereas in the control group, a decrease of 2.7% was found. The results demonstrated the beneficial effect of exercise in the prevention and management of OP.


Rat hepatic mitochondria are more sensitive to allyl alcohol than are those of mice.
The hepatotoxic effects of allyl alcohol with particular reference to mitochondrial morphology and function were compared in male CD1 mice and male CD rats 24 h after 0.05 ml/kg i.p. in corn oil. As already noted by others, allyl alcohol-treated rats usually showed histologic evidence of tissue necrosis when hematoxylin-eosin-stained tissue sections were examined whereas mouse tissue sections did not. The serum glutamic pyruvic transaminase (SGPT) activities were significantly elevated in both mice and rats but to a much greater extent in the latter. Pentobarbital sleeping time was significantly increased over that of corn oil control groups in rats but decreased in mice. In rats electron microscopy showed mitochondria which contained flocculent densities. State 4 respiration was not altered by allyl alcohol in rats, but state 3 respiration was significantly depressed indicating an absence of respiratory control and an inability to perform energy coupling. In allyl alcohol-treated mice the isolated mitochondria were found to be primarily in a condensed form. Except for the effect on pentobarbital sleeping time and SGPT, no other findings were different from those in control groups given only corn oil. When the dose of allyl alcohol in mice was increased to 0.15 ml/kg in an attempt to elicit more severe signs of hepatotoxicity, there was a high mortality in the first 24 h period without histologic evidence of liver necrosis. Thus, we confirm that at equivalent doses, male rats are more sensitive to the hepatotoxic effects of allyl alcohol than are male mice, and extend the generalization to the liver mitochondria of the 2 species.


Clinical and radiographic characteristics of increased signal intensity of the spinal cord at the vertebral body level in patients with cervical myelopathy.
Increased signal intensity (ISI) is usually recognized at the disc level of the responsible lesion in the patients with cervical myelopathy. However, it is occasionally seen at the vertebral body level, below the level of compression. We aimed to investigate the clinical significance and the radiographic characteristics of ISI at the vertebral body level. This retrospective study included 135 patients with cervical spondylotic myelopathy who underwent surgery and with local ISI. We measured the local and C2-7 angle at flexion, neutral, and extension. We also evaluated the local range of motion (ROM) and C2-7 ROM. The patients were classified into group D (ISI at disc level) and group B (ISI at vertebral body level). The prevalence was 80.7% (109/135) and 19.3% (26/135) for groups D and B, respectively. Local angle at flexion and neutral were more kyphotic in group B than in group D. The local ROM was larger in group B than in group D. Moreover, C2-7 angle at flexion, neutral and extension were more kyphotic in group B than in group D. Two years later, local angle at flexion, neutral, and extension were also kyphotic in group B than group D; however, local and C2-7 ROM was not significantly different between the two groups. There was no significant difference of clinical outcomes 2 years postoperatively between both groups. Group B was associated with the kyphotic alignment and local greater ROM, compared to group D. As the spinal cord is withdrawn in flexion, the ISI lesion at vertebral body might be displaced towards the disc level, which impacted by the anterior components of the vertebrae. ISI at the vertebral body level might be related to cord compression or stretching at flexion position. This should be different from the conventionally held pincer-mechanism concept.


Early type III endoleak with an Endurant endograft.
We report the case of an 81-year-old man who presented with an intraoperative type III endoleak after treatment with an Endurant endograft for a 60-mm abdominal aortic aneurysm. To our knowledge, this is the first case of a type III endoleak reported with this new device. It was most likely due to a tear in the polyester graft, the cause of which remains speculative. The tear was demonstrated by postoperative angiography, which was more informative than computed tomography. The endoleak was successfully treated by relining with an aorto-uni-iliac device.


Do changes in land use, water bodies, and grazing pastures have a detrimental influence on environmental quality? Opportunities and threats to long-term growth.
Land use activities mainly for economic and agricultural purposes have converted one third to one half of our planet's land surface into urban expansion and agricultural practice, which has had significant impacts on natural ecosystems, food production, and environmental quality, attracting the attention of researchers and policymakers. Consequently, land use is emerging as a fundamental issue in global environmental change and sustainable development. This study represents an addition to the prevailing literature by investigating the asymmetric impacts of land-use and land-cover changes on environmental quality in Pakistan using time series data from 1961 to 2016. Carbon dioxide (CO2) emissions were deemed a dependent variable (a proxy for environmental quality), whereas built-up land, cropland, water bodies, and grazing land were considered independent. A nonlinear ARDL bound testing technique (NARDL) was used to investigate dynamic cointegration among the study variables. Moreover, this study used the BDS test and structural break unit root test to confirm nonlinearity and stationarity of the data set. The results confirm that the variables exhibit asymmetrical co-integration. There is a symmetric unidirectional causation, running from built-up land and grazing land towards CO2 emissions with coefficients of 10.570 and 17.045, respectively. Furthermore, asymmetric causality shows that any positive shocks to built-up land (6.134) and water bodies (20.335) significantly cause CO2 emissions. Similarly, a negative shock to grazing land (16.470) also causes CO2 emissions. By contrast, a neutral effect was found between cropland and CO2 emissions.


Cost-effectiveness analysis of antiepileptic drugs in the treatment of Lennox-Gastaut syndrome.
An economic model evaluated the costs and outcomes of adjunctive clobazam therapy for Lennox-Gastaut syndrome (LGS) compared with adjunctive lamotrigine, rufinamide, and topiramate. Clinical data were used to estimate baseline frequency and the percentage of drop-seizure reductions over 3 months (all comparators) and 2 years (rufinamide). Claims data from a large US health care plan were employed to estimate costs. After 3 months, 21.5% of those receiving clobazam were drop-seizure-free. Over a 3-month horizon, clobazam was more effective and less expensive than comparators, with the assumption that >0.77% of drop seizures required medical care. Below this threshold, topiramate was less costly than clobazam. With the base-case assumption that 2.3% of drop seizures were medically attended, costs for patients receiving clobazam totaled $30,147 versus $34,223-$35,378 for comparators. Clobazam was more efficacious and less costly than rufinamide over a 2-year horizon. The percentage of medically attended drop seizures was a driver of results. Clobazam treatment may be cost-saving.


Lingual projections to the dorsal pons of the rat, studied by the field potential analysis.
Electrical stimulation of the chorda tympani (CT) of a rat produced a negative field potential with a peak latency of 8 msec localized in the parabrachial nucleus (PB) which may correspond to the pontine taste area. In contrast, stimulation of the glossopharyngeal nerve (GL) gave rise to no detectable negative field potential around the brachium conjunctivum. Stimulation of the lingual nerve (L) produced a large negative field potential with a similar latency, whose focus was found located just lateral to the focus of the negative potentials produced by CT stimulation.


Rapid virus subunit visualization by direct sedimentation of samples on electron microscope grids.
Airfuge direct ultracentrifugation of viral samples on electron microscope grids offers a rapid way for concentrating viral particles or subunits to facilitate their detection and study. Using the A-100 fixed angle rotor (30 degrees) with a K factor of 19 at maximum speed (95,000 rpm), samples up to 240 microliters can be prepared for electron microscopy observation in a few minutes: observation time is decreased and structural details are highlighted. Using latex spheres to calculate the increase in sensitivity compared to the inverted drop procedure, we obtained a 10- to 40-fold increase in sensitivity depending on the size of particles. Application of this technique to rubella virus permitted better visualization of viral membrane subunits on the particles. Rubella hemagglutinin immuno-stimulating complexes preparations were also better visualized and their morphology conserved after direct ultracentrifugation on the specimen grids. Similar observations are reported for respiratory syncytial virus associated subunits.


Selection of a halophytic plant for assessing the phytotoxicity of dredged seaport sediment stored on land.
The filling of dry quarries in coastal areas with sediments dredged in seaports represents a potentially interesting method of recycling of these materials. However, this recycling requires the prior carrying out of an Environmental Risk Assessment of the scenario concerned. For this, the question arose as to the type of plants capable of developing on the surface of such a deposit and the method to implement for assessing the possible phytotoxicity of dredged sediments. To answer this question, we chose to work with halophytic plants to be free from the salt-related effect and to assess only the effect related to the toxic compounds present. Based on the objectives set, these works led to the use of common plants of the French coast, with direct seeding, and with pollution-sensitive plants. Three species of angiosperms, Armeria maritima, Anthemis maritima and Plantago coronopus, were finally tested. As a result of this work, Armeria maritima was retained as the most suitable plant for testing the possible phytotoxic effect of dredged marine sediments stored on land. The results obtained with this plant are as follows: germination of 40 % of the seeds in 31 days, produced biomass of 493 mg FW in 6 months and a capacity to bioaccumulate metal pollutants in roots with 350 and 720 mg/kg DW for Zn and Cu, respectively.


Transcriptional activity and nucleolar ultrastructure of embryonic rabbit nuclei after transplantation to enucleated oocytes.
Changes in the level of transcriptional activity in 32-cell stage morula nuclei were studied after blastomere electrofusion to enucleated oocytes. Nuclear transplant recipients were pulse labelled with 3H-uridine during cultivation in vitro, embryos were then fixed and processed for autoradiography and electron microscopy. Transcriptional activity substantially decreased after 4.5 hr and was completely inhibited at last 15 hr after fusion. Transcription resumed thereafter in two-cell stage embryos and could be detected in both nuclei from 70% of the embryos analyzed. Transcription activity rapidly increased at the eight 16-cell stages, reaching the level typical for 32-cell stage nuclei used for the transfer. Changes in nucleolar ultrastructure after the nuclear transfer reflected the inhibition and subsequent reactivation of rRNA transcription. Nucleoli of 32-cell embryos had a typical structure of active nucleoli; many fibrillar centers surrounded and interconnected by threads of the dense fibrillar component and embedded in the granular component. Six hours following nuclear transplantation, these nucleoli underwent drastic changes including loss of granular material, collapse of nucleolar structure, and segregation of nucleolar components. Following the first cleavage, segregated fibrillar components of nucleoli manifested a complete inhibition of nucleolar transcription. Ribosomal RNA transcription was restored at the eight-cell stage and the sequence of ultrastructural changes was similar to that of the normal development. However, at the 32-cell stage, excessive extrusion of pre-ribosomal particles in the cytoplasm occurred, suggesting a possible alteration in regulating mechanisms of ribosome delivery. These results show that after fusion with enucleated metaphase II cytoplasm and subsequent activation, transcription is inhibited in donor embryonic nuclei and progressively increases again during cleavage; almost as in normal embryos. Migration of ribosomes into cytoplasm appears more intense in 32-cell stage reconstituted embryos but this does not seem to inhibit blastocyst building.