Non-Cirrhotic Portal Hypertension in a Patient With Colonic Carcinoma Treated With Oxaliplatin.
Oxaliplatin is a chemotherapeutic agent with direct toxic action on deoxyribonucleic acid (DNA), which is known to cause an arrest in its synthesis and inducing cell death. It is a crucial medication for colorectal carcinoma, and in combination with other medications has demonstrated to exhibit synergism, managing to increase patients' survival, especially when compared to monotherapy with 5-fluoracil. Neurotoxicity is its most well-known adverse effect. However, other less frequent secondary effects have been described in case reports, among them liver injury, which is usually secondary to liver sinusoid injury. Despite the wide frequency of the use of this drug, the relationship of oxaliplatin with the development of portal non-cirrhotic hypertension is largely unknown, which translates into a sub-diagnosis, representing an additional risk to patients who develop this complication. We present the case of an adult patient, who during treatment with the FOLFOX scheme for colorectal carcinoma, presents signs suggestive of portal hypertension, without other risk factors besides the administration of oxaliplatin.


Cannabis use: signal of increasing risk of serious cardiovascular disorders.
Cannabis is known to be associated with neuropsychiatric problems, but less is known about complications affecting other specified body systems. We report and analyze 35 recent remarkable cardiovascular complications following cannabis use. In France, serious cases of abuse and dependence in response to the use of psychoactive substances must be reported to the national system of the French Addictovigilance Network. We identified all spontaneous reports of cardiovascular complications related to cannabis use collected by the French Addictovigilance Network from 2006 to 2010. We described the clinical characteristics of these cases and their evolution: 1.8% of all cannabis-related reports (35/1979) were cardiovascular complications, with patients being mostly men (85.7%) and of an average age of 34.3 years. There were 22 cardiac complications (20 acute coronary syndromes), 10 peripheral complications (lower limb or juvenile arteriopathies and Buerger-like diseases), and 3 cerebral complications (acute cerebral angiopathy, transient cortical blindness, and spasm of cerebral artery). In 9 cases, the event led to patient death. Increased reporting of cardiovascular complications related to cannabis and their extreme seriousness (with a death rate of 25.6%) indicate cannabis as a possible risk factor for cardiovascular disease in young adults, in line with previous findings. Given that cannabis is perceived to be harmless by the general public and that legalization of its use is debated, data concerning its danger must be widely disseminated. Practitioners should be aware that cannabis may be a potential triggering factor for cardiovascular complications in young people.


Hsp25-induced radioresistance is associated with reduction of death by apoptosis: involvement of Bcl2 and the cell cycle.
We previously demonstrated the protective effect of the small heat-shock protein against oxidative damage induced by tumor necrosis factor alpha. Here we have extended our studies of the possible role of Hsp25 in ionizing radiation-induced damage. For these studies, we transfected murine fibroblast L929 cells with the Hsp25 gene and selected three stably transfected clones. Hsp25 overexpression conferred radioresistance as detected by clonogenic survival and induction of apoptosis. Interestingly, the Hsp25-transfected cells showed an increase in the level of the anti-apoptosis molecule Bcl2. We also observed alterations of cell growth in the Hsp25-transfected cells. The cell cycle time of Hsp25-transfected cells was 3-4 h slower than that of vector-transfected control cells. Flow cytometry analysis of synchronized cells at late G(1) phase by mimosine treatment also showed the growth delay in Hsp25-overexpressing cells. In addition, reduced cyclin D1, cyclin A and Cdc2 levels and increased levels of Cdkn1a (also known as p21(Waf)) were observed in Hsp25-transfected cells, which probably caused the reduction in cell growth. In addition, synchronization by mimosine treatment only partially altered radioresistance in the Hsp25-transfected cells. Taken together, these data suggest that Hsp25-induced radioresistance is associated with growth delay as well as induction of Bcl2.


Deep-learning projector for optical diffraction tomography.
Optical diffraction tomography is an effective tool to estimate the refractive indices of unknown objects. It proceeds by solving an ill-posed inverse problem for which the wave equation governs the scattering events. The solution has traditionally been derived by the minimization of an objective function in which the data-fidelity term encourages measurement consistency while the regularization term enforces prior constraints. In this work, we propose to train a convolutional neural network (CNN) as the projector in a projected-gradient-descent method. We iteratively produce high-quality estimates and ensure measurement consistency, thus keeping the best of CNN-based and regularization-based worlds. Our experiments on two-dimensional-simulated and real data show an improvement over other conventional or deep-learning-based methods. Furthermore, our trained CNN projector is general enough to accommodate various forward models for the handling of multiple-scattering events.


Declining mortality from hypertension and stroke.
Recorded mortality from hypertension and stroke has decreased dramatically in most countries during the last 50 to 75 years. The reported reduction in mortality may be due to changes in diagnostic fashions or coding procedures. However, the magnitude and consistency of the decline suggests the occurrence of a true decrease. The possibility that better treatment of hypertension is responsible for the reduction in mortality is attractive. However, based on temporal relationships, it seems more likely that much of the fall has resulted from an alteration in the determinants of blood pressure. Increasing use of antihypertensive drug therapy may account for an acceleration in the decline of stroke mortality during the last decade. If so, this represents one of the first tangible benefits of the massive public health efforts to detect and treat hypertension in the community.


Preparation and evaluation of oral soft chewable jelly containing flurbiprofen.
Oral jelly is a semisolid preparation that could resolve problem associated with dosage form's swallowing, especially in pediatric and elderly ones. This work aimed to prepare oral flurbiprofen (FBP) jelly to improve patient compliance. Heating and congealing method was used to prepare FBP jelly using three different polymers (pectin, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose). The effect of different concentrations of pectin and sucrose on jelly properties was studied. The results revealed that both pectin and sodium carboxymethyl cellulose polymers gave acceptable jelly appearance and consistency. It was also observed that the increase of pectin or sucrose concentration had a significant impact on jelly viscosity. All pectin jellies except formula containing 5.5% pectin and 50% weight by volume (w/v) sucrose exhibited more than 50% and 85% of FBP releasing within 15 and 30 min, respectively. The formula (FP2) consisting of 4.5% pectin and 40% w/v sucrose was selected as optimum formula which had a high percent dissolution efficiency (78.95%) and better consistency during handling. This work succeeded in the preparation of new FBP oral jelly, which can be considered a promising dosage form for enhancement of patient compliance and drug solubility.


Evidence of commonality between canine and human extraintestinal pathogenic Escherichia coli strains that express papG allele III.
Although dogs have been proposed as carriers of extraintestinal pathogenic Escherichia coli (ExPEC) with infectious potential for humans, presumed host species-specific differences between canine and human ExPEC strains have cast doubt on this hypothesis. The recent discovery that allele III of papG (the P fimbrial adhesin gene) predominates among human cystitis isolates and confers an adherence phenotype resembling that of canine ExPEC prompted the present reevaluation of the canine-human ExPEC connection. Sixteen paired pap-positive urine and rectal E. coli isolates from dogs with urinary tract infection were studied. papG (adhesin) and papA (pilin) allele type, agglutination phenotypes, virulence factor genotypes, and randomly amplified polymorphic DNA and pulsed-field gel electrophoresis fingerprints were analyzed and compared with those of human ExPEC controls. The 16 canine strains contained predominantly papG allele III. Agglutination phenotypes segregated strictly according to papG allele status and were homogeneous among strains with the same papG allele profile irrespective of their human versus canine origin. Canine and human PapG variant III peptide sequences were highly homologous, without host species-specific differences. The most prevalent canine papA allele was F48, a novel variant recently identified among human urosepsis isolates. In addition to pap, human ExPEC-associated virulence genes detected among the canine strains included sfa/focDE, sfaS, fyuA, hlyA, cnf1, cdtB, kpsMT-II and -III, rfc, traT, ompT, and a marker for a pathogenicity-associated island from archetypal human ExPEC strain CFT073. Molecular fingerprinting confirmed the fecal origin of all but one canine urine isolate and showed one pair of O6 canine urine and fecal isolates to be extremely similar to an O6 human urosepsis isolate with which they shared all other genotypic and phenotypic characteristics analyzed. These data demonstrate that canine ExPEC strains are similar to, and in some instances essentially indistinguishable from, human ExPEC strains, which implicates dogs and their feces as potential reservoirs of E. coli with infectious potential for humans.


Linking brain stroke risk factors to human movement features for the development of preventive tools.
This paper uses human movement analyses to assess the susceptibility of brain stroke, one of the most important causes of disability in elders. To that end, a computerized battery of nine neuromuscular tests has been designed and evaluated with a sample of 120 subjects with or without stoke risk factors. The kinematics of the movements produced was analyzed using a computational neuromuscular model and predictive characteristics were extracted. Logistic regression and linear discriminant analysis with leave-one-out cross-validation was used to infer the probability of presence of brain stroke risk factors. The clinical potential value of movement information for stroke prevention was assessed by computing area under the receiver operating characteristic curve (AUC) for the diagnostic of risk factors based on motion analysis. AUC mostly varying between 0.6 and 0.9 were obtained, depending on the neuromuscular test and the risk factor investigated (obesity, diabetes, hypertension, hypercholesterolemia, cigarette smoking, and cardiac disease). Our results support the feasibility of the proposed methodology and its potential application for the development of brain stroke prevention tools. Although further research is needed to improve this methodology and its outcome, results are promising and the proposed approach should be of great interest for many experimenters open to novel approaches in preventive medicine and in gerontology. It should also be valuable for engineers, psychologists, and researchers using human movements for the development of diagnostic and neuromuscular assessment tools.


A rare-male advantage in the housefly induced by wing clipping and some general considerations for Drosophila.
Multiple-choice crosses among five geographic strains of the housefly, Musca domestica L., were carried out in equal (10:10) and low-frequency (4:16) ratios. Initially, a low-frequency-male mating advantage was apparent, but further analyses related this minority advantage to a reduction of male mating success during marking by wing clipping. When there are fluctuating differences in the level of sexual vigor between competing male types over replicate trials of a cross, a mating advantage will accrue to the minority type. Even if males from the two competing strains are equally vigorous, such fluctuating differences will occur during sampling of flies. Harming the flies during marking will serve to enhance this effect and make significant departures toward greater mating success of rare males highly likely. This statistical bias in favor of minority males was substantiated in simulations of the KENCE-BRYANT model of mating success and compared with our results of a minority advantage in the housefly and with published results of a minority advantage in Drosophila. Our evidence, though circumstantial, that an advantage to minority males could have been induced by such an experimental bias suggests that a re-examination of existing data, as well as new experimentation, is necessary to discern whether or not a real rare-male advantage exists.


IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin.
Autism spectrum disorder (ASD) does not have a distinct pathogenesis or effective treatment. Increasing evidence supports the presence of immune dysfunction and inflammation in the brains of children with ASD. In this report, we present data that gene expression of the antiinflammatory cytokine IL-37, as well as of the proinflammatory cytokines IL-18 and TNF, is increased in the amygdala and dorsolateral prefrontal cortex of children with ASD as compared to non-ASD controls. Gene expression of IL-18R, which is a receptor for both IL-18 and IL-37, is also increased in the same brain areas of children with ASD. Interestingly, gene expression of the NTR3/sortilin receptor is reduced in the amygdala and dorsolateral prefrontal cortex. Pretreatment of cultured human microglia from normal adult brains with human recombinant IL-37 (1 to 100 ng/mL) inhibits neurotensin (NT)-stimulated secretion and gene expression of IL-1β and CXCL8. Another key finding is that NT, as well as the proinflammatory cytokines IL-1β and TNF increase IL-37 gene expression in cultured human microglia. The data presented here highlight the connection between inflammation and ASD, supporting the development of IL-37 as a potential therapeutic agent of ASD.


White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics.
Late-life depression has been associated with white matter changes in studies using the regions of interest approach. To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics. The sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression. Individuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up. Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.


Signaling mechanisms in the establishment of plant and fucoid algal polarity.
The establishment of polarity is a fundamental property of most cells. In tip-growing plant and in fucoid algal cells, polarization specifies a growth pole, the center of localized secretion of new plasma membrane and cell wall material, generating a protrusion with a dome-shaped apex. Although much progress has been made concerning the cellular machinery required to execute tip growth, less is known regarding the signaling mechanisms involved in selecting the growth site and regulating vectorial cell division and expansion. Fucoid algal zygotes use extrinsic cues to orient their growth axes and are thus well-suited for studies of de novo selection of an axis. This process has been investigated largely by both pharmacological and immuno-localization studies. In tip growing plant cells, polarity is often predetermined, as in the formation of root hairs or moss protonema branches. More focus has been on genomic and genetic studies to reveal the molecules involved in expressing a growth axis. Here we review the common roles of the cytoskeleton and signal transduction pathways in the formation of a developmental axis in fucoid algal cells and the control of tip growth in higher plant cells.


Designed aromatic homo-dipeptides: formation of ordered nanostructures and potential nanotechnological applications.
Molecular self-assembly offers new routes for the fabrication of novel materials at the nano-scale. Peptide-based nanostructures represent nano-objects of particular interest, as they are biocompatible, can be easily synthesized in large amounts, can be decorated with functional elements and can be used in various biological and non-biological applications. We had previously revealed the formation of highly ordered tubular structures by the diphenylalanine peptide, the core recognition motif of Alzheimer's beta-amyloid polypeptide, due to specific aromatic interactions. We further confirmed this model and demonstrated that a non-charged peptide analogue, Ac-Phe-Phe-NH2, self-assembled into similar tubular structures. We later explored other amine and carboxyl modified diphenylalanine peptide analogues and revealed that these dipeptides can form ordered tubular structures at the nanometric scale. Moreover, a very similar peptide, the diphenylglycine, self-assembled into ordered nano-spherical assemblies. Here we extend our research and explore the self-assembly of other homo-aromatic dipeptides in which their phenyl side-chains are modified with halogen atoms (di-para-fluoro-Phe, di-pentafluoro-Phe, di-para-iodo-Phe), additional phenyl groups (di-4-phenyl-Phe), or with nitro substitutions (di-para-nitro-Phe). We also probed the effect of the alteration of the phenyl groups with naphtyl groups (di-D-1-Nal and di-D-2-Nal). In all cases, well-ordered nanostructures were obtained and studied by scanning electron microscopy, transmission electron microscopy and vibrational spectroscopy. Taken together, the current work and previous ones define the homo-aromatic dipeptide as a central motif for the formation of ordered self-assembled tubular, spherical and two-dimensional structures at the nano-scale.


Phylogenomic conflict analyses of the plastid and mitochondrial genomes via deep genome skimming highlight their independent evolutionary histories: A case study in the cinquefoil genus Potentilla sensu lato (Potentilleae, Rosaceae).
Phylogenomic conflicts are widespread among genomic data, with most previous studies primarily focusing on nuclear datasets instead of organellar genomes. In this study, we investigate phylogenetic conflict analyses within and between plastid and mitochondrial genomes using Potentilla as a case study. We generated three plastid datasets (coding, noncoding, and all-region) and one mitochondrial dataset (coding regions) to infer phylogenies based on concatenated and multispecies coalescent (MSC) methods. Conflict analyses were then performed using PhyParts and Quartet Sampling (QS). Both plastid and mitochondrial genomes divided the Potentilla into eight highly supported clades, two of which were newly identified in this study. While most organellar loci were uninformative for the majority of nodes (bootstrap value < 70%), PhyParts and QS detected conflicting signals within the two organellar genomes. Regression analyses revealed that conflict signals mainly occurred among shorter loci, whereas longer loci tended to be more concordant with the species tree. In addition, two significant disagreements between the two organellar genomes were detected, likely attributed to hybridization and/or incomplete lineage sorting. Our results demonstrate that mitochondrial genes can fully resolve the phylogenetic relationships among eight major clades of Potentilla and are not always linked with plastome in evolutionary history. Stochastic inferences appear to be the primary source of observed conflicts among the gene trees. We recommend that the loci with short sequence length or containing limited informative sites should be used cautiously in MSC analysis, and suggest the joint application of concatenated and MSC methods for phylogenetic inference using organellar genomes.


Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death in hypertrophic cardiomyopathy.
Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence of the five traditional SCA-associated risk factors was assessed, as well as the HCM risk-SCD score. 16 (30%) patients experienced aborted cardiac arrest over 8.5±4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On univariate analysis, T-wave amplitude was associated with appropriate ICD therapy (HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per 0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead V2 to the traditional risk factors resulted in significant improvement in risk stratification (C-statistic from 0.65 to 0.75) but did not improve the performance of the HCM SCD-risk score. T-wave amplitude is a novel marker of SCA in this high risk HCM population and may provide incremental predictive value to established risk factors. Further work is needed to define the role of repolarisation abnormalities in predicting SCA in HCM.


Cronkhite-Canada syndrome associated with serrated adenoma and malignant polyp: a case report and a literature review of 13 cronkhite-Canada syndrome cases in Korea.
Cronkhite-Canada syndrome (CCS) is a rare nonfamilial polyposis syndrome characterized by epithelial disturbances both in the gastrointestinal tract and in the epidermis. The pathologic finding of the polyp is usually a hamartomatous polyp of the juvenile type; however, the possibility of serrated adenoma associated malignant neoplasm was reported in some Japanese cases. Up till now in South Korea, 13 CCS cases have been reported, but there was no case accompanied by the colon cancer. We report the first case of CCS associated with malignant colon polyp and serrated adenoma in Korea. A 72-year-old male patient who complained of diarrhea and weight loss was presented with both hands and feet nail dystrophy, hyperpigmentation, and alopecia. Endoscopic examination showed numerous hamartomatous polyps from the stomach to the colon. The pathologic results confirmed colon cancer and serrated adenoma. Helicobacter pylori eradication and prednisolone was used. Thus, the authors report this case along with a literature review.


[Specific and nonspecific cortical-subcortical mechanisms of behavior].
The paper presents data on comparative morphological study of afferent connections between the cat, dog, monkey brain basal ganglia with structures of the "motor" and "limbic" systems, neurophysiological data on specifics of involvement of the pre-frontal cortex, amygdala, caudate nucleus and thalamus in the processes of learning, perception and assessment of the stimuli significance, formation of short- and long-term memory's programs, decision making, programming the actions and assessment of the actions being performed, experimental data on the role of glutamatergic, dopaminergic, cholinergic, GABA-ergic systems of the cortex and a number of subcortical structures in the mechanisms of formation and implementation of the food and defence reflexes.


A rationale for universal tranexamic acid in major joint arthroplasty: overall efficacy and impact of risk factors for transfusion.
Tranexamic acid (TXA) therapy is effective in reducing postoperative red blood cell (RBC) transfusion in total joint arthroplasty (TJA), yet uncertainty persists regarding comparative efficacy and safety among specific patient subgroups. We assessed the impact of a universal TXA protocol on RBC transfusion, postoperative hemoglobin (Hb), and adverse outcomes to determine whether TXA is safe and effective in TJA, both overall and in clinically relevant subgroups. A retrospective observational study was performed on patients undergoing TJA at our institution spanning 1 year before and after the implementation of a universal protocol to administer intravenous (IV) TXA. The primary outcome was percentage of patients transfused, and secondary outcomes were perioperative Hb and occurrence of adverse events (death, myocardial infarction, stroke, seizure, pulmonary embolism, deep vein thrombosis, and acute kidney injury ). Outcomes were compared in pre- and post-protocol groups with χ2 analysis. Logistic regression compared risk of transfusion in pre- and post-protocol subgroups of patients with differing risk for transfusion (anemia, body mass index [BMI], and sex). No differences were found in baseline patient characteristics across pre- and post-protocol groups (n = 1084 and 912, respectively). TXA use increased from 32.3% to 92.2% while transfusion rates decreased from 10.3% to 4.8% (p < 0.001). Postoperative Day 3 Hb increased from 95.8 to 101.4 g/L (p < 0.001). Logistic regression demonstrated reduced transfusion in post-protocol subgroups regardless of sex, anemia, or BMI (p < 0.001). No increase in adverse events was observed (p = 0.8451). Universal TXA was associated with a reduction of RBC transfusion, overall and in clinically relevant subgroups, strengthening the rationale for universal therapy.


Genome-Wide Reinforcement of DNA Methylation Occurs during Somatic Embryogenesis in Soybean.
Somatic embryogenesis is an important tissue culture technique that sometimes leads to phenotypic variation via genetic and/or epigenetic changes. To understand the genomic and epigenomic impacts of somatic embryogenesis, we characterized soybean (Glycine max) epigenomes sampled from embryos at 10 different stages ranging from 6 weeks to 13 years of continuous culture. We identified genome-wide increases in DNA methylation from cultured samples, especially at CHH sites. The hypermethylation almost exclusively occurred in regions previously possessing non-CG methylation and was accompanied by increases in the expression of genes encoding the RNA-directed DNA methylation (RdDM) machinery. The epigenomic changes were similar between somatic and zygotic embryogenesis. Following the initial global wave of hypermethylation, rare decay events of maintenance methylation were observed, and the extent of the decay increased with time in culture. These losses in DNA methylation were accompanied by downregulation of genes encoding the RdDM machinery and transcriptome reprogramming reminiscent of transcriptomes during late-stage seed development. These results reveal a process for reinforcing already silenced regions to maintain genome integrity during somatic embryogenesis over the short term, which eventually decays at certain loci over longer time scales.


[Cystic degeneration of the popliteal artery: Report of one case].
Cystic degeneration of the popliteal artery is an uncommon cause of intermittent claudication. We report a 52 years old male consulting for intermittent claudication referred to the calf. The angiography showed a 93% stenosis in segment of 45 mm length of the left popliteal artery with a smooth surface, suggesting an extrinsic compression. A CT angiography of the lower limb suggested the presence of a cystic degeneration. The patient was operated and the middle third of the popliteal artery was excised. The pathological study of the surgical piece was informed as artery media cystic degeneration.


Guardians of cell death: the Bcl-2 family proteins.
Apoptosis is mediated through at least three major pathways that are regulated by (i) the death receptors, (ii) the mitochondria and (iii) the ER (endoplasmic reticulum). In most cells, these pathways are controlled by the Bcl-2 family of proteins that can be divided into anti-apoptotic and pro-apoptotic members. Although the overall amino acid sequence homology between the family members is relatively low, they contain highly conserved domains, referred to as BH (Bcl-2 homology) domains (BH1-4), that are essential for homo- and hetero-complex formation, as well as for their cell-death-inducing capacity. Structural and functional analyses revealed that the pro-apoptotic homologues can be subdivided into the Bax subfamily and the growing BH3-only subfamily. Recent data indicate that BH3-only proteins act as mediators that link various upstream signals, including death receptors and DNA damage signalling, to the mitochondrial and the ER pathway. This review discusses recent structural and functional insights into how these subfamilies promote or inhibit cell-death signals, and how these properties may be utilized for development of apoptosis-promoting small molecules, e.g. in cancer therapy.


A comparison of the clinical features of hospital out-patients with rheumatoid disease and osteoarthritis in Pakistan and England.
Several studies have demonstrated differences between ethnic groups in the severity and pattern of rheumatoid arthritis (RA) and osteoarthritis (OA). The current investigation compared RA and OA in Pakistani and British White Caucasian out-patients in two teaching hospitals. There were 88 RA patients in each setting, matched for age, gender and disease duration. The pattern of OA was sought by recording the details of 44 consecutive new referrals to each clinic. Amongst the RA patients, joint deformity and tenderness were similar, but disability was more severe, ESR higher, anaemia more pronounced and RA latex more often positive amongst the Pakistani patients. X-ray damage was more pronounced amongst the British patients, especially in the feet. The British were also more likely to have rheumatoid nodules and to have undergone disease-modifying treatment or joint surgery. The paradox of more severe indices of disease activity and disability with less X-ray erosion in hands and feet might be explained by the impact of treatment on joint inflammation and the beneficial influence of surgery on disability in the British. The worse X-ray scores in the White Caucasians might indicate a genetic predisposition to radiologically more severe disease. The age of the British OA patients was significantly higher, but this is unlikely to have influenced the striking disparity in the frequency of isolated knee OA, which was significantly greater in the Pakistani patients. Comparison with age- and sex-matched healthy Pakistani subjects suggested that susceptibility to knee OA was strongly associated with body weight, but not with knee bending at prayer or with joint laxity. Amongst the Pakistanis, Heberden nodes, hip involvement and evidence of generalized OA were significantly less, but these observations may have been due to their younger age. The study confirmed differences in the clinical presentation of both RA and OA amongst patients in Pakistan compared with White Caucasians in Britain. Several confounding factors, such as patient recruitment, culture, treatment and age, may have influenced the results, but it remains likely that genetic factors are important.


Solution NMR analyses of the C-type carbohydrate recognition domain of DC-SIGNR protein reveal different binding modes for HIV-derived oligosaccharides and smaller glycan fragments.
The C-type lectin DC-SIGNR (dendritic cell-specific ICAM-3-grabbing non-integrin-related; also known as L-SIGN or CD299) is a promising drug target due to its ability to promote infection and/or within-host survival of several dangerous pathogens (e.g. HIV and severe acute respiratory syndrome coronavirus (SARS)) via interactions with their surface glycans. Crystallography has provided excellent insight into the mechanism by which DC-SIGNR interacts with small glycans, such as (GlcNAc)2Man3; however, direct observation of complexes with larger, physiological oligosaccharides, such as Man9GlcNAc2, remains elusive. We have utilized solution-state nuclear magnetic resonance spectroscopy to investigate DC-SIGNR binding and herein report the first backbone assignment of its active, calcium-bound carbohydrate recognition domain. Direct interactions with the small sugar fragments Man3, Man5, and (GlcNAc)2Man3 were investigated alongside Man9GlcNAc derived from recombinant gp120 (present on the HIV viral envelope), providing the first structural data for DC-SIGNR in complex with a virus-associated ligand, and unique binding modes were observed for each glycan. In particular, our data show that DC-SIGNR has a different binding mode for glycans on the HIV viral envelope compared with the smaller glycans previously observed in the crystalline state. This suggests that using the binding mode of Man9GlcNAc, instead of those of small glycans, may provide a platform for the design of DC-SIGNR inhibitors selective for high mannose glycans (like those on HIV). (15)N relaxation measurements provided the first information on the dynamics of the carbohydrate recognition domain, demonstrating that it is a highly flexible domain that undergoes ligand-induced conformational and dynamic changes that may explain the ability of DC-SIGNR to accommodate a range of glycans on viral surfaces.


Pentobarbital quantification in the presence of phenobarbital by fluorescence polarization immunoassay.
We developed a method for measuring pentobarbital in samples that also contain phenobarbital. The phenobarbital is destroyed by adding sodium hydroxide and then heating at 95 degrees C for 60 min. Pentobarbital is not affected by this pretreatment and can then be measured with an Abbott TDx barbiturates kit. Using this method, we obtained an average analytical recovery of 98% of added pentobarbital and a correlation of y = 0.953x + 3.4 vs HPLC. The intra-assay CV was 3.7% at 25.8 mg/L; the interassay CV was 6.2% at 16.1 mg/L. Other long-acting barbiturates, e.g., hexobarbital, are also effectively destroyed by this alkali pretreatment. Other short-acting barbiturates, e.g., secobarbital, are not removed and would produce an interference.


Identification of a functional variant of estrogen receptor beta in an African population.
In this study, we identified five novel polymorphisms in the estrogen receptor beta (ERbeta) gene in an African population. Interestingly, two of these variants are expected to change the amino acid sequence of the ERbeta protein. These changes correspond to an isoleucine to valine substitution at amino acid position 3 (I3V) and a valine to glycine substitution at position 320 (V320G), respectively. The functional consequences of these amino acid substitutions were determined in different in vitro assays. The I3V mutation displayed no differences with regard to transcriptional activity in a reporter assay, as compared with the wild-type receptor. The V320G mutation, however, showed significantly decreased maximal transcriptional activity in a reporter assay, although its binding affinity for 17beta-estradiol was not affected. A pull-down assay indicated that the interaction of full-length TIF2 with hERbetaV320G was weaker than with hERbetawt. Moreover, surface plasmon resonance analysis revealed reduced interaction of the V320G ERbeta variant with the NR box I and II modules of TIF2. To our knowledge, this represents the first identification of a functional polymorphism in the ERbeta gene. This novel polymorphism provides a tool for human genetic studies of diseases in the African population.


Five-year follow-up results of thermal ablation for benign thyroid nodules: Systematic review and meta-analysis.
Confidence in long-term treatment results of thermal ablation for benign thyroid nodules (BTNs) is required in comparison with surgery. The objective of this meta-analysis is to report 5-year follow-up results of thermal ablation for BTNs. Ovid PUBMED, COCHRANE, and EMBASE databases were searched through Feb 30, 2023, for studies reporting outcomes in patients with BTNs treated with thermal ablation and followed up for about 5 years. Pooled volume reduction rates (VRRs) at 6, 12, 24, 36, 48, and 60 months after thermal ablation were assessed. Data were extracted and methodological quality was assessed independently by two radiologists according to the PRISMA guidelines. Five studies, involving 939 patients, met the inclusion criteria through database searches. 137 patients experienced local nodules recurrence during a mean pooled 59.25-month follow-up. Seventeen of them proved to be non-benign. Fifty of all patients with nodules regrowth had a secondary surgery, while 35 had a secondary thermal ablation. The pooled mean major complication rate was 7.70 %, with no patient experiencing life-threatening or delayed complications. Thermal ablation is an excellent local nodules control method in patients with BTNs, and results in a clinically significant and long-lasting volume reduction of BTNs. The risk of regrowth and needing retreatment was lower after thermal ablation.


Rates of susceptibility of carbapenems, ceftobiprole, and colistin against clinically important bacteria collected from intensive care units in 2007: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).
Data on susceptibility to ceftobiprole and colistin, and the complete evolutionary trends of minimum inhibitory concentrations (MICs) of important carbapenem agents among important pathogens collected in intensive care units (ICUs) in Taiwan are lacking. We surveyed the MIC distribution patterns of ceftobiprole and colistin and susceptibility profiles of some important pathogens collected from patients hospitalized in intensive care units (ICUs) of major teaching hospitals throughout Taiwan in 2007. We also investigated the rates of nonsusceptibility to powerful carbapenems (imipenem, meropenem) among four important species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis) collected during the same period. MIC breakpoints recommended by the Clinical and Laboratory Standards Institute in 2014 were applied. Colistin showed excellent in vitro activity (susceptibility rate, 96%) against Acinetobacter baumannii isolates but moderate (73-77% susceptibility rate) activity against isolates of Pseudomonas aeruginosa and E. cloacae. The ceftobiprole MIC90 value was 4 μg/mL for methicillin-resistant Staphylococcus aureus and 16 μg/mL for P. aeruginosa. The phenotype of methicillin resistance did not markedly increase the MIC value of ceftobiprole among S. aureus isolates. Interestingly, the proportion of isolates that displayed nonsusceptibility to imipenem was significantly higher among P. mirabilis isolates than among isolates of the other three Enterobacteriaceae species, regardless of the production of extended-spectrum β-lactamase. Continuous monitoring of susceptibility profiles of ICU pathogens to important antibiotics is warranted to provide appropriate antimicrobial regimens against infections in the ICU.


Gut ischemia/reperfusion induced acute lung injury is an alveolar macrophage dependent event.
Although the role of the lung alveolar macrophage (AM) as a mediator of acute lung injury (ALI) after lung ischemia/reperfusion (I/R) has been suggested by animal experiments, it has not been determined whether AMs mediate ALI after intestinal I/R. The objective of this study was to determine the effect of AM elimination on ALI after intestinal I/R in rats. Male Wistar rats (n = 90) were randomly divided into three groups: the clodronate-liposomes (CLOD-LIP) group received intratracheal treatment with CLOD-LIP; the liposomes (LIP) group received intratracheal treatment with LIP; and the nontreated (UNTREAT) group received no treatment. Twenty-four hours later each group was randomly divided into three subgroups: the intestinal I/R subgroup was subjected to 45-minute intestinal ischemia and 2-hour reperfusion; the laparotomy (LAP) subgroup was subjected to LAP and sham procedures; the control (CTR) subgroup received no treatment. At the end of reperfusion, ALI was quantitated in all the animals by the Evans blue dye (EBD) method. ALI values are expressed as EBD lung leakage (microg EBD/g dry lung weight). EBD lung leakage values in the CLOD-LIP group were 32.59 +/- 12.74 for I/R, 27.74 +/- 7.99 for LAP, and 33.52 +/- 10.17 for CTR. In the LIP group, lung leakage values were 58.02 +/- 18.04 for I/R, 31.90 +/- 8.72 for LAP, and 27.17 +/- 11.48 for CTR. In the UNTREAT group, lung leakage values were 55.60 +/- 10.96 for I/R, 35.99 +/- 6.89 for LAP, and 30.83 +/- 8.41 for CTR. Within each group, LAP values did not differ from CTR values. However, in the LIP and UNTREAT groups, values for both the LAP and CTR subgroups were lower than values for the I/R subgroup (p < 0.001). The CLOD-LIP I/R subgroup value was less (p < 0.001) than the I/R subgroup values in the LIP and UNTREAT groups. These results indicated that I/R provokes ALI that can be prevented by CLOD-LIP treatment, and further suggested that AMs are essential for ALI occurrence induced by intestinal I/R in rats.


A genetic map of cucumber composed of RAPDs, RFLPs, AFLPs, and loci conditioning resistance to papaya ringspot and zucchini yellow mosaic viruses.
The watermelon strain of papaya ringspot virus (PRSV-W) and zucchini yellow mosaic virus (ZYMV) are potyviruses that cause significant disease losses in cucumber. Resistances have been identified primarily in exotic germplasm that require transfer to elite cultivated backgrounds. To select more efficiently for virus resistances, we identified molecular markers tightly linked to PRSV-W and ZYMV resistances in cucumber. We generated F6 recombinant inbred lines (RILs) from a cross between Cucumis sativus L. 'Straight 8' and a line from 'Taichung Mou Gua', TMG1 (susceptible and resistant, respectively, to both viruses), and studied the segregations of amplified fragment length polymorphism (AFLP) markers, randomly amplified polymorphic DNAs (RAPDs), restriction fragment length polymorphisms (RFLPs), and resistances to PRSV-W and ZYMV. A 353-point map of cucumber was generated, delineating 12 linkage groups at LOD 3.5. Linkage arrangements among RFLPs were consistent with previously published maps; however linkages among RAPDs in our map did not agree with a previously published map. Resistances to PRSV-W and ZYMV were tightly linked (2.2 cM) and mapped to the end of one linkage group. One AFLP cosegregated with resistance to ZYMV.


[HEMAN, a nutritional screening method for patients newly admitted hospital].
Given the high prevalence of the hospitable malnutrition (from 30 % to 50%) there is imposed to determine to the admission the nutritional status of the patients. With it one would manage to identify those individuals in condition of malnutrition and to treat them, which would allow to shorten his/her hospitable stay and to reduce the sanitary bill. For it, we must elaborate a nutritional screening tool of high sensibility and specificity, related in addition to a low cost and rapidity. To validate a screening nutritional program, called HEMAN, which allows us to discriminate against the undernourished patients to the hospitable admission, comparing it with a method already standardized as the NRS 2002. Patients evaluated to the admission of the services of Internal Medicine and Oncology of the General Universitary Hospital of Valencia with the method HEMAN and the NRS 2002 simultaneously. There were examined 112 different patients, 63 men and 49 women. The method HEMAN obtained 8 more patients in nutritional risk that the NRS 2002, with a percentage of patients in risk of 74% and 67%, respectively. The sensibility of the method HEMAN was 100 % and the specificity was 80% compared to the NRS 2002. Due to the fact that HEMAN evaluates separately IMC, weight loss and variation of the ingestion we can classify the undernourished patients with major precision and discriminate between them to know which needs a major nutritional attention, on the basis of the criteria of the phase III of the HEMAN´s method.


Antiproliferative effects of NO and ANP in cultured human airway smooth muscle.
Airway smooth muscle (ASM) hypertrophy and hyperplasia are important determinants of bronchial responsiveness in asthma, and agents that interfere with these processes may prevent airway remodeling. We tested the hypothesis that activators of soluble and particulate guanylyl cyclases would inhibit human ASM cell (HASMC) proliferation. We report that the nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP; 10(-6) to 10(-4) M) and sodium nitroprusside (10(-5) to 10(-3) M) and human atrial natriuretic peptide [ANP-(1-28); 10(-8) to 10(-6) M], which activate soluble and particulate guanylyl cyclases, respectively, inhibited serum- and thrombin-induced proliferation of cultured HASMCs. The antimitogenic effect of SNAP was reversed by hemoglobin (10(-5) M), an NO scavenger, suggesting that NO donation was involved. The antiproliferative effects of SNAP and ANP-(1-28) were potentiated by the cGMP-specific phosphodiesterase zaprinast and mimicked by 8-bromo-cGMP (10(-6) to 10(-3) M), suggesting that cGMP-dependent mechanisms were involved. However, first, ANP-(1-28) produced a smaller antiproliferative effect than SNAP in contrast to their abilities to elevate cGMP, and second, rat ANP-(104-126), which binds selectively to ANP clearance receptors without elevating cGMP, had a small antiproliferative effect, suggesting that cGMP-independent mechanisms were also involved. These results provide evidence for a novel antiproliferative effect of NO and ANP in HASMCs mediated through cGMP-dependent and cGMP-independent mechanisms.


Insulin resistance in adipocytes after downregulation of Gi subtypes.
To determine whether downregulation of Gi proteins is associated with insulin resistance, we incubated isolated adipocytes with N6-(2-phenylisopropyl)adenosine (PIA; an A1-adenosine receptor agonist; 300 nM), prostaglandin E1 (PGE1; 3 microM), or nicotinic acid (1 mM) for 4 days in primary culture. The cells were washed, and the rate of glucose transport (2-deoxy-[3H]glucose uptake) was measured after incubation with various concentrations of insulin for 45 min. Both PIA and PGE1 (which downregulate Gi) decreased the maximal responsiveness of the cells to insulin by approximately 30% and caused a rightward shift in the dose-response curve. By contrast, nicotinic acid (which does not downregulate Gi) did not alter the insulin sensitivity of the cells. Prolonged treatment of adipocytes with either PIA or PGE1 (but not nicotinic acid) rendered the cells completely resistant to the antilipolytic effect of insulin. The ability of insulin to stimulate autophosphorylation of the beta-subunit of the insulin receptor was decreased by approximately 30% in PIA-treated cells, and the dose-response curve was shifted to the right. Similarly, the ability of the receptor to phosphorylate poly(Glu4-Tyr1) was decreased by approximately 35%. This decrease in tyrosine kinase activity of the receptor may account for the decrease in insulin sensitivity of glucose transport but cannot account for the complete loss of antilipolysis. The findings suggest both a direct and indirect involvement of Gi proteins in insulin action.


Loss of Slc35a2 alters development of the mouse cerebral cortex.
Brain somatic variants in SLC35A2 are associated with clinically drug-resistant epilepsy and developmental brain malformations, including mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). SLC35A2 encodes a uridine diphosphate galactose translocator that is essential for protein glycosylation; however, the neurodevelopmental mechanisms by which SLC35A2 disruption leads to clinical and histopathological features remain unspecified. We hypothesized that focal knockout (KO) or knockdown (KD) of Slc35a2 in the developing mouse cortex would disrupt cerebral cortical development through altered neuronal migration and cause changes in network excitability. We used in utero electroporation (IUE) to introduce CRISPR/Cas9 and targeted guide RNAs or short-hairpin RNAs to achieve Slc35a2 KO or KD, respectively, during early corticogenesis. Following Slc35a2 KO or KD, we observed disrupted radial migration of transfected neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter. Slc35a2 KO in neurons did not induce changes in oligodendrocyte number, suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects. Spontaneous seizures were not observed, but intracranial EEG recordings after focal KO showed a reduced seizure threshold following pentylenetetrazol injection. These results demonstrate that Slc35a2 KO or KD in vivo disrupts corticogenesis through altered neuronal migration.


World Rabies Day: focusing attention on a neglected disease.
Rabies kills 55,000 people every year mainly in Africa and Asia, despite being entirely preventable through vaccination and prompt medical treatment. Spurred on by this statistic, the first ever World Rabies Day will be held on September 8 in order to raise global awareness of rabies prevention and control. The driving force behind the initiative is the Alliance for Rabies Control, a charity formed in 2006 by a group of researchers and professionals committed to eradicating rabies. To mark the event, The Veterinary Record has commissioned experts in the field of rabies control to discuss what veterinary surgeons have done and can do to tackle this devastating disease. The message that emerges is that veterinary surgeons, in close collaboration with the medical profession, have a vital role to play. In the first article, Deborah Briggs from Kansas State University and Cathleen Hanlon from the Centers for Disease Control and Prevention in the USA describe the impetus behind the day, who is supporting it and what it hopes to achieve. Articles on the following pages describe other veterinary contributions to this field.


The Top End Sleepiness Scale (TESS): A New Tool to Assess Subjective Daytime Sleepiness Among Indigenous Australian Adults.
To illustrate the utility of a newly developed culturally safe and clinically relevant subjective daytime sleepiness assessment tool "Top End Sleepiness Scale" (TESS) for use among Indigenous Australians. The TESS questionnaire consists of pictorial representations of 6 items representing daily activities that would induce daytime sleepiness specific for Indigenous Australians living in the regional and remote Australia. Consecutive adult Indigenous patients who consented to pilot the TESS questionnaire prior to undergoing a diagnostic polysomnography (PSG) at the Top End Health Service region, Northern Territory of Australia were assessed. The TESS questionnaire was evaluated for its correlation in predicting obstructive sleep apnea (OSA) according to apnea-hypopnea index. Eighty-two patients were included. The majority (70%) had moderate to severe OSA (AHI ≥15). Patients were aged in their mid-40's (45.47 95% CI (42.9, 48.05)) with a tendency to obesity (median BMI 33.67 IQR 30.86, 38.95) and a high prevalence of chronic conditions (72%) (hypertension, diabetes or heart disease). The TESS showed high internal consistency (Split half Spearman correlation=0.71, Cronbach's α =0.81), and a cut-off value ≥3 resulted in sensitivity 84%, specificity 38%. Comparison of area under the curve for TESS to Epworth Sleepiness Scale (ESS) in this sample showed the TESS to have greater sensitivity and specificity overall, which approached significance (p=0.072) when cut-off values of ≥3 and ≥8 (TESS & ESS respectively) were used. The sensitivity and specificity for TESS was also comparable to the other currently used questionnaires, such as the Berlin Questionnaire, STOP-BANG and OSA 50. Currently, there are no subjective daytime sleepiness assessment toll available specifically for Indigenous population. The proposed TESS sleepiness screening tool represented in this study can potentially complement or adopted alongside other existing questionnaire, which may offer greater utility in the assessment of sleep disorders among Indigenous people.


Inflammation, stress, and diabetes.
Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity. It is now clear that obesity is associated with a state of chronic low-level inflammation. In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes. We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity. We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease.


Comprehensive Bird Preservation at Wind Farms.
Wind as a clean and renewable energy source has been used by humans for centuries. However, in recent years with the increase in the number and size of wind turbines, their impact on avifauna has become worrisome. Researchers estimated that in the U.S. up to 500,000 birds die annually due to collisions with wind turbines. This article proposes a system for mitigating bird mortality around wind farms. The solution is based on a stereo-vision system embedded in distributed computing and IoT paradigms. After a bird's detection in a defined zone, the decision-making system activates a collision avoidance routine composed of light and sound deterrents and the turbine stopping procedure. The development process applies a User-Driven Design approach along with the process of component selection and heuristic adjustment. This proposal includes a bird detection method and localization procedure. The bird identification is carried out using artificial intelligence algorithms. Validation tests with a fixed-wing drone and verifying observations by ornithologists proved the system's desired reliability of detecting a bird with wingspan over 1.5 m from at least 300 m. Moreover, the suitability of the system to classify the size of the detected bird into one of three wingspan categories, small, medium and large, was confirmed.


Feasibility of using the Multinational Association of Supportive Care in Cancer Antiemesis Tool for assessment of chemotherapy-induced nausea and vomiting at the Tom Baker Cancer Centre.
Chemotherapy-induced nausea and vomiting (CINV) has been shown to adversely impact patient anxiety, quality of life, treatment adherence, and use of health care resources. CINV control still remains a challenge, and lack of effective communication between the patient and clinician has been highlighted in the literature as the main barrier to optimal control. The Multinational Association of Supportive Care in Cancer (MASCC) has developed a tool (MASCC Antiemesis Tool (MAT)) to improve assessment and subsequent management of CINV by enhancing communication between patients and their clinicians. This study assessed the feasibility of using the MAT in patients at the Tom Baker Cancer Centre. The secondary objective was to describe the incidence of CINV as identified by the tool. This study involved a prospective survey using the MAT in patients receiving intravenous chemotherapy. Subjects completed the MAT twice post-chemotherapy regarding CINV symptoms and returned it at their next clinic appointment. Participants were also surveyed to evaluate feasibility with regard to using the MAT. Of the 50 patients recruited, 56% returned surveys. The majority of patients reported that the MAT facilitated communication with their clinician, particularly those who had experienced CINV. Fifty-four percent of patients who returned the MAT reported CINV; however, less than half of them had received American Society of Clinical Oncology-recommended antiemetic regimens. Only four patients with CINV had antiemetic changes made for subsequent cycles. The MAT is a feasible tool which can improve communication of CINV symptoms between patients and clinicians, a foundational step toward improving CINV management.


Sarcoma classification by DNA methylation profiling.
Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.


Upregulation of long non-coding RNA LOC284454 may serve as a new serum diagnostic biomarker for head and neck cancers.
Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear. We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs. LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively. LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.


Gastroenterology: the first 40 years.
Functional gastroenterological disorders were diagnosed in over 50 per cent of patients aged 40 years and under, referred to a district general hospital combined gastroenterology clinic. Peptic ulceration, gastro-oesophageal reflux, biliary tract disease and inflammatory bowel disease accounted for almost 70 per cent of the organic disorders encountered. Malignant disease was rare. The implications for diagnostic investigation in this age group are discussed.


Resource translocation drives δ(13) C fractionation during recovery from disturbance in giant kelp, Macrocystis pyrifera.
Resource allocation and translocation are fundamental physiological functions for autotrophs. The mobilization and use of resources drive population dynamics by regulating growth and recovery of individuals, but also influences ecosystem-level processes such as primary productivity and carbon cycling. This study provides the first observation of translocation-driven gradients of δ(13) C in macroalgae, a critically important phenomenon recognized in vascular plants for decades. A ~10‰ δ(13) C increase in new giant kelp (Macrocystis pyrifera) fronds relative to mature canopy blades was produced after 5 weeks following a biomass removal experiment, more than twice the variation typical for macroalgae. The observed δ(13) C patterns are consistent with tissue enrichment following resource translocation in vascular plants. The analogous source-sink relationships and consistent translocation patterns in Macrocystis and vascular plants suggest that translocation of stored resources is critical for structuring productivity and recovery from disturbance in important, habitat-forming macroalgae such as kelps and fucoids.


Structure and kinetics of chemically cross-linked protein gels from small-angle X-ray scattering.
Glutaraldehyde (GA) reacts with amino groups in proteins, forming intermolecular cross-links that, at sufficiently high protein concentration, can transform a protein solution into a gel. Although GA has been used as a cross-linking reagent for decades, neither the cross-linking chemistry nor the microstructure of the resulting protein gel have been clearly established. Here we use small-angle X-ray scattering (SAXS) to characterise the microstructure and structural kinetics of gels formed by cross-linking of pancreatic trypsin inhibitor, myoglobin or intestinal fatty acid-binding protein. By comparing the scattering from gels and dilute solutions, we extract the structure factor and the pair correlation function of the gels. The protein gels are spatially heterogeneous, with dense clusters linked by sparse networks. Within the clusters, adjacent protein molecules are almost in contact, but the protein concentration in the cluster is much lower than in a crystal. At the ∼1 nm SAXS resolution, the native protein structure is unaffected by cross-linking. The cluster radius is in the range 10-50 nm, with the cluster size determined mainly by the availability of lysine amino groups on the protein surface. The development of structure in the gel, on time scales from minutes to hours, appears to obey first-order kinetics. Cross-linking is slower at acidic pH, where the population of amino groups in the reactive deprotonated form is low. These results support the use of cross-linked protein gels in NMR studies of protein dynamics and for modeling NMR relaxation in biological tissue.


Meta-analysis: the detection of pancreatic malignancy with positron emission tomography.
Several factors contribute to the high mortality of pancreatic cancer, including limitations of diagnostic imaging. To perform a meta-analysis to assess the diagnostic accuracy of Fluro-deoxy-glucose positron emission tomography with computed tomography compared with computed tomography alone. Articles were identified through a MEDLINE search and bibliography review. Summary estimates and receiver operating curves were calculated using Meta-Test 0.6. Publication bias and heterogeneity were assessed with a funnel plot and chi-squared test. The summary estimate and 95% confidence interval for sensitivity and specificity were as follows: computed tomography 81% (72-88%) and 66% (53-77%), PET after a positive computed tomography 92% (87-95%) and 68% (51-81%), PET after a negative computed tomography 73% (50-88%) and 86% (75-93%) and PET after an indeterminate computed tomography 100 and 68%. The area under the summary receiver operating curve was 0.82 for computed tomography and 0.94 for PET. There was no heterogeneity or publication bias. Our results suggest that although adding Fluro-deoxy-glucose positron emission tomography to the diagnostic work-up may enhance the diagnosis of pancreatic malignancy, its usefulness will vary depending upon the pretest probability of the patient, the results of computed tomography and the provider's testing thresholds. Further evaluation using a well-designed prospective study with a cost-effectiveness analysis is needed to clarify the appropriate role of Fluro-deoxy-glucose positron emission tomography.


Submaximal Exercise Capacity in Juvenile Dermatomyositis after Longterm Disease: The Contribution of Muscle, Lung, and Heart Involvement.
To compare submaximal exercise capacity in patients with juvenile dermatomyositis (JDM) with controls, and analyze contributions of muscle, heart, and lung impairment in patients. Fifty-nine patients with JDM, with a mean 16.9 years after symptom onset, and 59 sex- and age-matched controls completed a 6-min walk test (6MWT) and a timed up and go (TUG) test. Muscle function, disease activity/damage, and health-related quality of life (HRQOL) were assessed by validated tools; heart function by echocardiography and electrocardiography; and lung function by spirometry, DLCO, and body plethysmography. A thoracic high-resolution computed tomography (HRCT) scan and magnetic resonance imaging of the thighs were completed in patients. The 6MWT distance (6MWD) was 592 ± 81 m in patients versus 649 ± 79 m in controls (p < 0.001), and 563 ± 75 m in active versus 622 ± 76 m in inactive JDM (p = 0.004). The TUG time was 13.1 ± 2.1 s in patients versus 12.3 ± 2.0 s in controls (p = 0.034), and 13.7 ± 2.2 s in active versus 12.5 ± 1.8 s in inactive JDM (p = 0.028). No statistically significant difference was found between inactive JDM and controls in either test. In patients, the Childhood Myositis Assessment Score influenced the 6MWD and TUG time the most, followed by a low DLCO and HRCT pathology in the 6MWT and forced vital capacity in the TUG test. Medical Outcomes Study Short Form-36 physical component summary correlated strongly with both tests. Submaximal exercise capacity was reduced in patients with JDM, particularly those with active disease. This reduction was associated with muscle and lung dysfunction and poorer HRQOL.


Siderophore-mediated iron acquisition from transferrin by Pseudomonas aeruginosa.
Pseudomonas aeruginosa placed across a dialysis membrane from [55Fe]transferrin caused the mobilization of the iron from the transferrin side to the bacterial or dialysate side of the membrane. Although the bacteria were capable of obtaining iron from transferrin for growth, the siderophores of P. aeruginosa failed to convert iron bound to transferrin into dialyzable, low-molecular-weight chelates. The crucial factor produced by the bacteria which was not present when the siderophores were added alone was the acid produced from the glucose minimal medium. The siderophores mobilized considerable iron from transferrin when used in the dialysis assay at pH values between 5.0 and 6.0, values which were commonly found during incubation of bacteria in the assays. When the siderophores were tested individually, pyoverdin was more effective than pyochelin in mobilizing iron across dialysis membranes at pH values of 5.0 and 6.0, but neither had appreciable activity at pH 7.4. The amounts of iron mobilized from conalbumin were comparable to the amounts from transferrin, but there was negligible release from lactoferrin at the three pH values. When the two siderophores were combined, the level of iron mobilization was identical to that demonstrated by pyoverdin alone. When the dialysis membrane was removed and the bacteria were mixed with the siderophores and transferrin, pyoverdin was again more active than pyochelin in mediating iron transport. Although no pyochelin-mediated iron mobilization could be detected at pH 7.4, there was transport. Therefore, the bacteria appeared to be aiding the siderophores in iron mobilization from transferrin.


Single-unit activity in the medial prefrontal cortex during immediate and delayed extinction of fear in rats.
Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit.


On the consequences of the stereochemical activity of the Bi(iii) 6s2 lone pair in cyclen-based complexes. The [Bi(DO3A)] case.
We report a detailed study of the structure of the [Bi(DO3A)] complex both in the solid state and in solution. The X-ray crystal structure of [Bi(DO3A)] evidences the octa-coordination of the Bi(iii) ion, which is directly coordinated to the four nitrogen atoms of the cyclen unit and three oxygen atoms of the carboxylate groups. The octa-coordination is completed by an oxygen atom of a neighboring carboxylate group, which bridges Bi(iii) ions thanks to μ2-η1:η1 coordination, resulting in the formation of a coordination polymer. The Bi(iii) ion presents a twisted-square antiprismatic (TSAP) coordination geometry associated with the Δ(δδδδ)/Λ(λλλλ) enantiomeric pair. A computational DFT study indicates that the 6s2 lone pair of Bi(iii) is stereochemically active in [Bi(DO3A)] and most of the cyclen-based complexes reported in the literature. Depending on the spatial arrangement of the donor atoms of the ligand the lone pair points in different directions, so that Bi(iii) can easily accommodate different coordination environments. In solution the [Bi(DO3A)] complex exists as a monomeric complex, as demonstrated by DOSY measurements. The stability constant of the [Bi(DO3A)] complex, determined by using batch spectrophotometric titrations, was found to be rather high (log K = 26.85(5)). The complex presents characteristic absorption in the UV spectrum at 299 nm (ε = 8770 M-1 cm-1) that was attributed to the Bi(iii)-centered 6p ← 6s band on the basis of TDDFT calculations. Spectrophotometric titrations reveal weak binding of different anions to the [Bi(DO3A)] complex, with association constants of K11 = 3.55(8), 3.09(7), 6.2(1) and 2.19(5) for Cl-, Br-, I- and N3-, respectively.


Review of Pharmacologic Considerations in the Use of Azole Antifungals in Lung Transplant Recipients.
Mold-active azole antifungals are commonly prescribed for the prevention of invasive fungal infections in lung transplant recipients. Each agent exhibits a unique pharmacologic profile, an understanding of which is crucial for therapy selection and optimization. This article reviews pharmacologic considerations for three frequently-used azole antifungals in lung transplant recipients: voriconazole, posaconazole, and isavuconazole. Focus is drawn to analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population.


The efficacy of 0.12% chlorhexidine versus 0.12% chlorhexidine plus hyaluronic acid mouthwash on healing of submerged single implant insertion areas: a short-term randomized controlled clinical trial.
The study was performed to evaluate the incidence of post-surgical adverse events at submerged implant sites as well as the antiplaque, antigingivitis and antistaining effects in the entire dentition of patients treated with two mouthwashes. The present randomized controlled clinical study considered 40 patients subjected to dental implant treatment. Two 0.12% chlorhexidine mouthwashes were compared for 15 days: one with 0.1% hyaluronic acid (CHX⊗HYL group) and one without it (CHX group). Surgical outcome variables, and plaque, gingival, and staining indexes were recorded. Significant differences were found between the two rinses regarding the presence of oedema within 2 days after surgery (20% for the CHX⊗HYL group and 78% for the CHX group). No other significant differences were recorded between the two mouthwashes. No intergroup differences in plaque, staining and gingivitis indexes were registered. The intragroup analysis revealed that for the plaque and gingival indexes, the differences between the baseline values (before surgery) and those at 15 days were all found to be significant just for CHX⊗HYL rinse, with final values ranging from 0.18 to 0.23 for the plaque index and from 0.06 to 0.07 for the gingival index. The staining index increased for both mouthwash types with significant results (with final value of 0.19 and 0.31 for CHX⊗HYL and CHX groups, respectively). In the sites of patients subjected to dental implant placement, an additional anti-oedematigenous effect in early healing seemed to be disclosed for 0.12% CHX⊗HYL mouthwash. Regarding antiplaque and antigingivitis activities, HYL seemed to be ineffective.


Association of low-grade inflammation and platelet activation in patients with hypertension with microalbuminuria.
Increased levels of sCD40L (soluble CD40 ligand) have been associated with enhanced in vivo platelet activation, and may represent a molecular link between inflammation and a prothrombotic state. The aim of the present study was to analyse the relationship between platelet activation, endothelial dysfunction, low-grade inflammation and sCD40L in patients with hypertension with or without MA (microalbuminuria). A cross-sectional comparison of sCD40L levels was performed in 25 patients with MH (essential hypertension with MA) pair-matched for gender and age with 25 patients with EH (essential hypertension) and 25 HS (healthy subjects with normotension). Circulating levels of CRP (C-reactive protein), a marker of inflammation, sP-selectin (soluble P-selectin), a marker of in vivo platelet activation, and ADMA (asymmetric dimethylarginine) and vWF (von Willebrand factor), markers of endothelial dysfunction, were analysed in each subject. sCD40L levels were increased in patients with MH compared with either patients with EH (P<0.001) or HS (P<0.0001). A highly significant correlation between plasma sCD40L and sP-selectin (P<0.0001), vWF (P<0.001) or CRP levels (P<0.05) was observed in patients with MH. Multivariate regression analysis showed that sP-selectin was the strongest independent predictor of sCD40L levels (P<0.0001) in patients with MH. Patients with hypertension with both vWF and CRP levels above the median had the highest sCD40L levels (P<0.0001). Factorial ANOVA of all of the patients with hypertension confirmed that only patients with MH with low-grade inflammation had elevated levels of sCD40L. In conclusion, sCD40L levels appear to discriminate a subset of patients characterized by MA and low-grade inflammation, suggesting that inhibition of the CD40/CD40L system may represent a potential therapeutic target in subjects with hypertension at a high risk of cardiovascular events.


Est-ce que c'est vous même dans la glace?--the phenomenology of Rorschach expressive constraint.
From the Rorschach Construct Scales, a sixth factor has been separated--termed Emotional and Expressive Constriction--in addition to the five established (Big Five) components of personality. Taking into account recent warnings that statistical techniques have the power to take away from the individual's interaction with the clinician, it is concluded that this Constriction factor in Rorschach-based data sets is a measure of the phenomenology of the Rorschach process, representing not only the client's disposition, but also reflecting the clinician.


Fluoroquinolones: A micro-species equilibrium in the protonation of amphoteric compounds.
The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports a number of contrasting evaluations on the existence of tautomeric forms of mono-protonated species, described by a set of protonation micro-constants. Here the protonation sequence and the related protonation constants of four representative molecules are evaluated by a combined potentiometric-spectrophotometric method. The experimental observations necessary to differentiate between a protonation scheme represented by macro-constants alone, and the one that requires the introduction of a micro-protonation scheme, are clearly delineated based on a careful analysis of experimental data and of simulated models. The role of the medium was investigated and UV-vis spectra in water- methanol solution were analyzed. The existence of the zwitterionic species alone at physiological pH in water, and an increase of the relative amount of the neutral species with the lipophilicity of the medium were remarked. This surely affects the bioavailability of FQs, with the increase of the neutral species when the molecules approach the local lipophilic environment close to the cellular membranes. NMR studies allowed the attribution of the protonation sites of the different forms. Quantum chemical evaluation of all the possible existent forms with different protonation degrees and in different sites strongly substantiates the experimental results. The study of the relevant frontier molecular orbitals completed the detailed theoretical characterization of the species.


[Ultrastructural organization of Mycobacterium tuberculosis processed by cryogenic ultratomy].
The ultrastructural organization of M. tuberculosis has been studied by the method of cryo-ultratomy. The cell-wall structures and the connective formations localized in the cytoplasm between parallel intracellular membranes have been revealed. Ethylene glycol and polyvinyl alcohol have been shown to be the most suitable cryoprotecting agents.


Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages.
Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.


[Waist circumference measured before the 12th week of pregnancy: correlation with serum leptin levels].
To evaluate the correlation between maternal waist circumference measured before the 12th week of gestation and serum leptin levels during pregnancy, as well as to compare the leptin levels of women with and without abdominal obesity diagnosed in early pregnancy. Prospective study including 40 pregnant women receiving low-risk prenatal care, older than 20 years, nonsmokers, with singleton pregnancies and without chronic disease. Waist circumference was measured before the 12th week and serum leptin levels were measured between the 9th and 12th, 25th and 28th and 34th and 37th weeks of gestation. According to waist circumference measurement, the cohort was divided into two groups: with and without abdominal obesity. The Mann-Whitney and χ(2) tests were used to assess the differences between groups. The Pearson correlation coeffient was used to assess the association between waist circumference and serum leptin levels during pregnancy. The level of significance was set at p<0.05. The mean weight and body mass index of patients with abdominal obesity (74.4±11.0 kg/28.9±4.1) was higher than that of patients without abdominal obesity (55.6±5.9 kg/21.1±2.4) (p=0.001). The mean leptin levels in pregnant patients with abdominal obesity (41.9±3.5 ng/mL) was higher than in patients without abdominal obesity (23.6±2.7 ng/mL) (p<0.0002). A positive correlation was obtained between the waist circumference measured during the same period and the mean serum leptin levels (r=0.7; p<0.0001). Waist circumference measured before the 12th week of pregnancy is a valid and simple method to predict the serum leptin levels throughout pregnancy. Pregnant women with abdominal obesity diagnosed before 12th week have higher mean serum leptin levels during pregnancy than those without abdominal obesity.


Reliable detection, sequencing, and transfection of foot-and-mouth disease virus RNA from badly preserved vesicular epithelium.
Epithelium or fluid from vesicular lesions are the preferred samples to confirm foot-and-mouth disease virus (FMDV) infection in livestock. A pH-neutral buffered transport medium is recommended for optimal preservation of epithelial samples, but may not be necessary for all circumstances based on the results of our study. Pieces of epithelium were collected from FMDV-infected cattle (isolates O/FRA/1/2001 and A/IRN/22/2015) and stored at room temperature in sealed tubes without any liquid or preservatives. Using RNA extracted from the severely decayed epithelium up to 3 wk after collection, FMDV was successfully detected by RT-rtPCR, and the viral strain was identified by sequencing of capsid protein VP1. Direct isolation of the virus in cell culture was only possible for vesicular material stored for up to 2-5 d, depending on the serotype, but, for both serotypes, infectious virus was recovered by transfection of RNA extracted from epithelium after 3 wk of storage at room temperature. Specialized transport medium will give optimal results, particularly for low-titer samples, but is not required for the reliable detection and characterization of FMDV in highly positive vesicular epithelium by molecular methods.


Allosteric regulation of kinase activity in living cells.
The dysregulation of protein kinases is associated with multiple diseases due to the kinases' involvement in a variety of cell signaling pathways. Manipulating protein kinase function, by controlling the active site, is a promising therapeutic and investigative strategy to mitigate and study diseases. Kinase active sites share structural similarities making it difficult to specifically target one kinase, allosteric control allows specific regulation and study of kinase function without directly targeting the active site. Allosteric sites are distal to the active site but coupled via a dynamic network of inter-atomic interactions between residues in the protein. Establishing an allosteric control over a kinase requires understanding the allosteric wiring of the protein. Computational techniques offer effective and inexpensive mapping of the allosteric sites on a protein. Here, we discuss methods to map and regulate allosteric communications in proteins, and strategies to establish control over kinase functions in live cells and organisms. Protein molecules, or "sensors" are engineered to function as tools to control allosteric activity of the protein as these sensors have high spatiotemporal resolution and help in understanding cell phenotypes after immediate activation or inactivation of a kinase. Traditional methods used to study protein functions, such as knockout, knockdown, or mutation, cannot offer a sufficiently high spatiotemporal resolution. We discuss the modern repertoire of tools to regulate protein kinases as we enter a new era in deciphering cellular signaling and developing novel approaches to treat diseases associated with signal dysregulation.


Cross-cultural comparison of depressive symptoms in Europe does not support stereotypes of ageing.
Stereotypes of older people suggest that they are depressed. To examine depression symptoms among people aged > or = 65 in the general population and to ask the following questions. Are there high proportions of depressive symptoms among otherwise well people? Do these levels reflect the prevalence of depression? Do key symptoms vary with age and do they confirm stereotypes? Nine centres contributed data from community-based random samples, using standardised methods (GMS-AGECAT package). Proportions of depressive symptoms varied between centres. Some often associated with ageing were rare. Many were more common in women. Low-prevalence centres tended to have fewer symptoms among 'well' people, but there were inconsistencies. Low levels of symptoms among the well population of a centre did not necessarily predict lower levels in the depressed. Variations in the prevalence of depressive symptoms occurred between centres, not always related to levels of illness. There was no consistent relationship between proportions of symptoms in well persons and cases for all centres. Few symptoms were present in > 60% of the older population--stereotypes of old age were not upheld.


A hybrid of CdS/HCa2Nb3O10 ultrathin nanosheets for promoting photocatalytic hydrogen evolution.
A hybrid of CdS/HCa2Nb3O10 ultrathin nanosheets was synthesized successfully through a multistep approach. The structures, constitutions, morphologies and specific surface areas of the obtained CdS/HCa2Nb3O10 were characterized well by XRD, XPS, TEM/HRTEM and BET, respectively. The TEM and BET results demonstrated that the unique structural features of CdS/HCa2Nb3O10 restrained the aggregation of CdS nanoparticles as well as the restacking of nanosheets effectively. HRTEM showed that CdS nanocrystals of about 25-30 nm were firmly anchored on HCa2Nb3O10 nanosheets and a tough heterointerface between CdS and the nanosheets was formed. Efficient interfacial charge transfer from CdS to HCa2Nb3O10 nanosheets was also confirmed by EPR and photocurrent responses. The photocatalytic activity tests (λ > 400 nm) showed that the optimal hydrogen evolution activity of CdS/HCa2Nb3O10 was about 4 times that of the bare CdS, because of the efficient separation of photo-generated carriers.


Directory of members, Genetics Society of America.
In Drosophila melanogaster, individuals heterozygous for translocations between chromosomes Y and 3 can generate, by means of mitotic recombination, somatic cells bearing duplications and deletions. Using translocations with different breakpoints, I have studied the behavior of clones of cells with increasing degrees of aneuploidy in the abdominal cuticle. Both hyper- and hypoploid cells can survive being duplicated or deficient even for large chromosome 3 fragments. While hyperploidy does not severely affect cell viability, the recovery of hypoploid clones decreases linearly as a function of the size of the deleted fragment. In this report, the quantitative and qualitative aspects of this effect are discussed.


Role of sulfotransferases in resveratrol metabolism in human adipocytes.
Polyphenols such as resveratrol received interest for their wide-ranging biological benefits, including anti-obesity potential, mimicking effects of caloric restriction with reduced body fat and increased energy expenditure. However, resveratrol is rapidly metabolized, and it is not completely understood which form of resveratrol is responsible for the effects observed within target cells such as adipocytes. Also the role of metabolizing enzymes has not been investigated before. Resveratrol metabolism was evaluated in human adipocytes by UHPLC-MS at low physiological doses. Resveratrol was found to rapidly metabolize into its sulfated form, while resveratrol glucuronides were undetectable. Only resveratrol, but not its sulfated nor glucuronidated forms had an antilipolytic effect on adipocytes. The metabolizing enzyme responsible for sulfation of polyphenols is SULT1A1, and was found to be upregulated upon adipocyte differentiation. Knocking down SULT1A1 in adipocytes led to decreased resveratrol sulfate and increased resveratrol intra- and extracellularly. This lower SULT1A1 activity resulted in an increased antilipolytic effect of resveratrol on adipocytes, as demonstrated by lower glycerol accumulation, which could be attributed to lower activity of the lipolytic protein, perilipin. Sulfotransferase activity modulates metabolism of resveratrol in adipocytes with potential consequences on bioavailability and thus metabolic action of this polyphenol.


Potato (Solanum tuberosum L.) tuber ageing induces changes in the proteome and antioxidants associated with the sprouting pattern.
During post-harvest storage, potato tubers age as they undergo an evolution of their physiological state influencing their sprouting pattern. In the present study, physiological and biochemical approaches were combined to provide new insights on potato (Solanum tuberosum L. cv. Désirée) tuber ageing. An increase in the physiological age index (PAI) value from 0.14 to 0.83 occurred during storage at 4 degrees C over 270 d. Using this reference frame, a proteomic approach was followed based on two-dimensional electrophoresis. In the experimental conditions of this study, a marked proteolysis of patatin occurred after the PAI reached a value of 0.6. In parallel, several glycolytic enzymes were up-regulated and cellular components influencing protein conformation and the response to stress were altered. The equilibrium between the 20S and 26S forms of the proteasome was modified, the 20S form that recycles oxidized proteins being up-regulated. Two proteins belonging to the cytoskeleton were also differentially expressed during ageing. As most of these changes are also observed in an oxidative stress context, an approach focused on antioxidant compounds and enzymes as well as oxidative damage on polyunsaturated fatty acids and proteins was conducted. All the changes observed during ageing seemed to allow the potato tubers to maintain their radical scavenging activity until the end of the storage period as no accumulation of oxidative damage was observed. These data are interpreted considering the impact of reactive oxygen species on the development and the behaviour of other plant systems undergoing ageing or senescence processes.


High total antioxidant activity and uric acid in tracheobronchial aspirate fluid of preterm infants during oxidative stress: an adaptive response to hyperoxia?
The effect of O2 exposure, expressed by mean daily fractional inspired oxygen concentration (FiO2), was evaluated during the first 6 d of life in the tracheobronchial aspirate fluid of 16 mechanically ventilated preterm infants in terms of both antioxidant response and oxidative damage, by measuring total antioxidant activity, uric acid concentrations and protein carbonyl content. Each day linear regression analysis was performed and a positive correlation was found between total antioxidant activity and FiO2 during the study period, especially on day 2 of life (r = 0.91, p < 0.0001), but uric acid correlated only in the first 3 d, especially on the 2nd day (r = 0.83, p < 0.0001). No correlation was found between carbonyl content and FiO2. The highest values of total antioxidant activity (416 and 790 micromol l(-1)) were found in 2 babies ventilated with highest FiO2: 1 and 0.80, respectively. Total antioxidant activity was not detectable or was very low in the babies not requiring O2 therapy. The highest value of uric acid (270 micromol l(-1)) was found in the baby ventilated with 100% oxygen. Uric acid concentrations obtained in these babies were much higher then those reported in the bronchoalveolar lavage fluid of adults. Preterm babies seem to have an antioxidant response in the tracheobronchial aspirate fluid following an oxidative stress and uric acid may be physiologically important as an antioxidant of the respiratory tract, especially during the first days of life.


FXYD-3 expression in relation to local recurrence of rectal cancer.
In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.


The role of toxoplasmosis in congenital disease in Malaysia.
Toxoplasmosis was found not to be an important cause of intrauterine infection in Malaysia as the rate of toxoplasma-specific IgM in 1,060 congenitally defective Malaysian children, 0 to 4 months old (0.4%) was lower than that in 405 normal children of the same age group (2.0%). A total of 8.2 intra-uterine toxoplasmic infections per 1,000 live births was detected of which one-third (2.7 per 1,000 live births) was overt, manifesting symptoms more of liver damage, than eye or brain damage. A comparison was made with the rates in U.S.A. and Europe. The role of toxoplasmosis in abortion needs to be studied.


'It is a Big Thing': Exploring the Impact of Osteoarthritis from the Perspective of Adults Caring for Parents - The Sandwich Generation.
The aim of the present study was to explore the experiences and impact of caring for an individual with severe osteoarthritis (OA) from the perspective of adult children, looking at the relationship between adult children caring for parents with this condition and the tensions of the 'sandwich generation'. A mixed qualitative approach, combining focus groups and individual semi-structured interviews was used. In total, 36 participants were purposively sampled and discussed the impact of caring for a parent with OA. Data analysis was based upon interpretative phenomenological analysis. Findings reported the impact and complexity of caring for a parent with OA. We present three themes related to the work of caring for a relative with this condition: (i) the physical and emotional work of caring; (ii) changes in reciprocal family roles; (iii) the imbalance in caring roles within the family. Participants described the significant and extensive impact on their lives of caring for a parent with long-term OA, particularly when faced with the pressures of caring for their own children as well. Copyright © 2016 The Authors Musculoskeletal Care Published by John Wiley & Sons Ltd.