Functional differences between aggregated and dispersed insulin-producing cells.
Beta cells situated in the islet of Langerhans respond more vigorously to glucose than do dissociated beta cells. Mechanisms for this discrepancy were studied by comparing insulin-producing MIN6 cells aggregated into pseudoislets with MIN6 monolayer cells and mouse and human islets. MIN6 monolayers, pseudoislets and mouse and human islets were exposed to glucose, α-ketoisocaproic acid (KIC), pyruvate, KIC plus glutamine and the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin. Insulin secretion (ELISA), cytoplasmic Ca(2+) concentration ([Ca(2+)]c; microfluorometry), glucose oxidation (radiolabelling), the expression of genes involved in mitochondrial metabolism (PCR) and the phosphorylation of insulin receptor signalling proteins (western blotting) were measured. Insulin secretory responses to glucose, pyruvate, KIC and glutamine were higher in pseudoislets than monolayers and comparable to those of human islets. Glucose oxidation and genes for mitochondrial metabolism were upregulated in pseudoislets compared with single cells and monolayers, respectively. Phosphorylation at the inhibitory S636/639 site of IRS-1 was significantly higher in monolayers and dispersed human and mouse cells than pseudoislets and intact human and mouse islets. PI3K inhibition only slightly attenuated glucose-stimulated insulin secretion from monolayers, but substantially reduced that from pseudoislets and human and mouse islets without suppressing the glucose-induced [Ca(2+)]c response. We propose that islet architecture is critical for proper beta cell mitochondrial metabolism and IRS-1 signalling, and that PI3K regulates insulin secretion at a step distal to the elevation of [Ca(2+)]c.


AHSG, a Gene Promoting Tumour Proliferation, Migration and Invasion, is an Independent Prognostic Factor for Poor Overall Survival in Lung Adenocarcinoma.
Recent studies have shown that the metabolic process-related gene AHSG is involved in multiple pathological processes of tumours. This study will explore the relationship between AHSG and lung adenocarcinoma. Expression analysis, survival analysis and co-expression analysis of AHSG were performed using a public database, and cytological and molecular biology assays were performed to explore the role of AHSG in lung adenocarcinoma. Compared with normal tissues, AHSG expression was significantly higher in cancer tissues in the TCGA-LUAD database, and pan-cancer analysis revealed abnormal AHSG expression in different kinds of tumours. Survival analysis revealed that compared with the low expression group, the patients in the high expression group had a significantly worse overall survival duration in the TCGA-LUAD database, and a subsequent study confirmed that AHSG expression could be an independent prognostic factor of overall survival in lung adenocarcinoma. AHSG-related genes are involved in multiple physiological and pathophysiological pathways. In subsequent cytological and molecular biology experiments, inhibition of AHSG expression suppressed proliferation, migration and invasion in lung adenocarcinoma cell lines, and the EMT process was blocked after knockdown of AHSG. AHSG could be used as a prognostic factor for OS in patients with lung adenocarcinoma. It can promote the biological behaviour of lung adenocarcinoma and may become a potential target for treatment, which is worthy of further study.


Similar effects of pulsatile and constant intravenous insulin delivery.
Effects of constant and pulsatile i.v. insulin delivery were examined in seven healthy subjects by means of euglycemic clamp technique. Each subject received constant insulin infusion (0.175 mU/kg.min) or insulin pulses at 12-min intervals (2.1 mU/kg) in randomized order for 8-h periods (08.00-16.00 h). Endogenous secretion of insulin was inhibited by concomitant administration of somatostatin (300 micrograms/h). Serum insulin concentrations during constant infusion (12 +/- 1 microU/ml) did not differ from basal values (11 +/- 1 microU/ml). Pulsatile insulin delivery resulted in oscillations of mean concentrations between values of about 10 and 20 microU/ml. Mean blood glucose concentrations during experiments were kept at 80 +/- 1 mg/dl, irrespective of the mode of insulin administration. Moreover, dextrose requirements for maintenance of these glucose concentrations did not differ over the hole periods of examination. We conclude that effects of constant and pulsatile delivery of basal amounts of insulin are not different. This at least applies to peripheral, short-term insulin administration in somatostatin-treated normal man, during an euglycemic clamp.


Different Leishmania Species Drive Distinct Neutrophil Functions.
Leishmaniases are vector-borne diseases of serious public health importance. During a sand fly blood meal, Leishmania parasites are deposited in the host dermis where neutrophils are rapidly recruited. Neutrophils are the first line of defense and can kill pathogens by an array of mechanisms. They can also form web-like structures called neutrophil extracellular traps (NETs) that can trap and/or kill microbes. The function of neutrophils in leishmaniasis was reported to be either beneficial by contributing to parasite killing or detrimental by impairing immune response development and control of parasite load. Here we review recent data showing that different Leishmania species elicit distinct neutrophil functions thereby influencing disease outcomes. Emerging evidence suggests that neutrophils should be considered important modulators of leishmaniasis.


Airway smooth muscle: a modulator of airway remodeling in asthma.
Asthma is a disease characterized, in part, by airway hyperresponsiveness and inflammation. Although asthma typically induces reversible airway obstruction, in some patients with asthma, airflow obstruction can become irreversible. Such obstruction might be a consequence of persistent structural changes in the airway wall caused by the frequent stimulation of airway smooth muscle (ASM) by contractile agonists, inflammatory mediators, and growth factors. Traditional concepts concerning airway inflammation have focused on trafficking leukocytes and on the effects of inflammatory mediators, cytokines, and chemokines secreted by these cells. Recent studies suggest that ASM cells might modulate airway remodeling by secreting cytokines, growth factors, or matrix proteins and by expressing cell adhesion molecules and other potential costimulatory molecules. These ASM cell functions might directly or indirectly modulate submucosal airway inflammation and promote airway remodeling.


Versatility of peroxisomes: An evolving concept.
Research spanning almost 50 years has highlighted unique characteristics and irreplaceable list of diverse functions performed by peroxisomes in various model systems. Peroxisomes are single membrane bound highly dynamic organelles ubiquitous to most eukaryotic cells. Proliferation by division of pre-existing organelles and the role of endoplasmic reticulum in the biogenesis of these organelles is now well established. The earliest identified conserved functions of peroxisomes are β-oxidation of fatty acids and reactive oxygen species metabolism. Several studies over the last few decades have reported the importance of this organelle and its numerous cell type, tissue and environment-dependent functions. Their role in several aspects of human health and disease is now under investigation. Studies related to peroxisome biology and functions are now also extended to diverse model systems like Drosophila melanogaster, trypanosomatids, etc. Peroxisomes also intricately collaborate and carry out these functions together with several other organelles in a cell. In this review, we aim to present an overview of our current knowledge of the repertoire of functions of peroxisomes in various model systems.


Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma.
Rab25, an epithelial-specific member of the Rab family of small GTPases, was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the mRNA and protein level. Quantitative PCR analysis of 112 Müllerian serous carcinomas (84 effusions, 28 primary ovarian carcinomas) and 22 malignant mesotheliomas (19 effusions, 3 solid specimens) showed significantly higher RAB25 mRNA expression in the former tumor (p < 0.001). Immunohistochemical analysis of Rab25 protein expression in 245 effusions showed significantly higher expression of this protein in Müllerian serous carcinoma compared to malignant mesothelioma (189/209 vs. 12/36 positive tumors, respectively; p < 0.001). Immunostaining of 101 patient-matched solid Müllerian carcinoma specimens (34 primary carcinomas, 67 metastases) showed expression levels comparable to effusions (94/101 positive specimens; p > 0.05). Rab25 mRNA and protein expression levels in Müllerian carcinoma effusions did not correlate with overall or progression-free survival. Our data confirm that Rab25 effectively differentiates Müllerian carcinomas from malignant mesothelioma at the mRNA and protein level, suggesting a role in the diagnostic work-up of serosal cancers.


Assignment of the structural gene for subunit M1 of human ribonucleotide reductase to the short arm of chromosome 11.
By using a species-specific monoclonal antibody that recognizes subunit M1 of ribonucleotide reductase from human but not hamster origin, we have been able to assign the structural gene for the human protein M1 to the short arm of chromosome 11. Protein extracts from a panel of human-Chinese hamster somatic cell hybrids were subjected to electrophoresis in sodium dodecyl sulfate (SDS) denaturating polyacrylamide gels, and then transferred and coupled covalently to diazobenzyloxymethyl paper. These were screened for human protein M1 by incubation with the mouse monoclonal anti-M1 antibody AD 203, followed by rabbit anti-mouse IgG, 125I-labelled Staphylococcus protein A and finally autoradiography. In all tested hybrids the detection of human protein M1 was correlated with the presence of chromosome 11, specifically with the short arm of this chromosome. This region also contains the human genes for insulin, insulin-like growth factor II, and the c-Harvey-ras 1 oncogene.


A Naphthalimide-Based Fluorescent Probe for the Detection and Imaging of Mercury Ions in Living Cells.
The selective and efficient monitoring of mercury (Hg2+ ) contamination found in the environment and ecosystem has been carried out. Thus, a new 1,8-naphthalimide-based fluorescent probe NADP for the detection of Hg2+ based on a fluorescence enhancement strategy has been designed and synthesized. The NADP probe can detect Hg2+ with high selectivity and sensitivity and a low detection limit of 13 nm. The detection mechanism was based on a Hg2+ -triggered deprotection reaction, resulting in a dramatic change in fluorescence from colorless to green at physiological pH. Most importantly, biological investigation has shown that the NADP probe can be successfully applied to the monitoring of Hg2+ in living cells and zebrafish with low cytotoxicity.


Association between preterm births and socioeconomic development: analysis of national data.
The increasing prevalence of preterm birth, which is a global phenomenon, is attributable to the increased medical indications, artificial gestations, and some socioeconomic factors. This study was conducted to identify whether development and equality indices are associated with the incidence of preterm birth, specifically, spontaneous and elective preterm births. This retrospective observational study comprised an analysis of data on live births from 2019 in Brazil and on socioeconomic indices that were derived from census information in 2017. Data were summarised using absolute and relative frequencies. Spearman's correlation was used to determine the correlation between socioeconomic factors and the preterm birth rate. Multiple beta regression analysis was performed to determine the best model of socioeconomic covariates and preterm birth rate. The significance level was set at 5%. In 2019 in Brazil, the preterm birth rate was 11.03%, of which 58% and 42% were spontaneous and elective deliveries, respectively. For all preterm births, Spearman's correlation varied from ρ = 0.4 for the Gini Index and ρ = - 0.24 for illiteracy. The best fit modelled the spontaneous preterm birth fraction as a negative function of the Human Development Index (HDI). The best-fit model considered the expected elective preterm birth fraction as a positive function of the HDI and as a negative function of the Gini Index, which was used as a precision parameter. We observed a reduction in the fraction of spontaneous preterm births; however, the distribution was not uniform in the territory: higher rates of spontaneous preterm birth were noticed in the north, northeast, and mid-west regions. Thus, areas with lower education levels and inequal income distribution have a higher proportion of spontaneous preterm birth. The fraction of elective preterm birth was positively associated with more advantaged indices of socioeconomic status.


Chronic nicotine and withdrawal affect glutamatergic but not nicotinic receptor expression in the mesocorticolimbic pathway in a region-specific manner.
Tobacco addiction is a complex form of dependence process that leads high relapse rates in people seeking to stop smoking. Nicotine elicits its primary effects on neuronal nicotinic cholinergic receptors (nAChRs), alters brain reward systems, and induces long-term changes during chronic nicotine use and withdrawal. We analysed the effects of chronic nicotine treatment and withdrawal on the mesocorticolimbic pathway (a brain reward circuit in which addictive drugs induce widespread adaptations) by analysing the expression of nAChRs in the midbrain, striatum and prefrontal cortex (PFC) of mice receiving intravenous infusions of nicotine (4mg/kg/h) or saline (control) for 14 days and mice sacrified two hours, and one, four and 14 days after treatment withdrawal. We biochemically fractionated whole tissue homogenates in order to obtain crude synaptosomal membranes. Western blotting analyses of these membrane fractions, ligand binding and immunoprecipitation studies, showed that chronic nicotine up-regulates heteromeric β2* nAChRs in all three mesocorticolimbic areas, and that these receptors are rapidly removed from synapses upon the cessation of nicotine treatment. The extent of nicotine-induced nAChR up-regulation, and the time course of its reversal were comparable in all three areas. We also analysed the expression of glutamate receptor subunits (GluRs) and scaffold proteins, and found that it was altered in an area-specific manner during nicotine exposure and withdrawal. As the functional properties of GluRs are determined by their subunit composition, the observed changes in subunit expression may indicate alterations in the excitability of mesocorticolimbic circuitry, and this may underlie the long-term biochemical and behavioural effects of nicotine dependence.


A modest but significant effect of CGB5 gene promoter polymorphisms in modulating the risk of recurrent miscarriage.
To confirm the effect of single nucleotide polymorphisms (SNPs) in chorionic gonadotropin beta (CGB) genes in modulating the susceptibility to recurrent miscarriage (RM) in Danes and in a meta-analysis across Danes and the discovery samples from Estonia and Finland. Case-control association study, restriction fragment length polymorphism genotyping, resequencing. Fertility clinics at the Rigshospitalet, Copenhagen, and Aalborg Hospital, Aalborg, Denmark. Four hundred fifty Danish women and men from couples with RM and 119 women with children and no miscarriages in new study. A total of 634 women and men from RM couples and 314 female controls in a combined study of Estonians, Finns, and Danes. None. Distribution of CGB5 and CGB8 allele and haplotype frequencies in patients and controls. For the majority of studied SNPs, the allelic and haplotypic distribution differed statistically between the Danish and the previous Estonian-Finnish sample. In Danes, two CGB5 promoter SNPs (c5-155; c5-142) exhibited a nonsignificant trend for higher allele frequency in fertile women compared with RM patients. The meta-analysis of results from three populations confirmed a modest but significant effect on carriage of c5-155C (odds ratio = 0.64; 95% confidence interval [CI] 0.44-0.94) and c5-142A (odds ratio = 0.66; 95% CI, 0.45-0.94) variants in reducing the risk of RM. None of the investigated genetic variants in the CGB8 gene was associated with RM. Carriage of particular variants in the promoter of the CGB5 gene seems to protect against RM. No common genetic variants in CGB5 and CGB8 were associated with increased RM susceptibility in the studied North European populations.


[Anxiety and depression in craniomandibular disorders; the use of the Symptom Checklist 90].
Anxiety and depression of CMD-patients in a Clinic for Special Dental Care were assessed with the Symptom Checklist-90. The results of the female patients did not differ from the general population; the men showed significantly higher scores. Approximately one third of the patients scored 'high' or 'very high' on anxiety or depression and may need special attention for psychological problems. The SCL-90 may be a useful instrument to assess the presence of clinically significant anxiety or depression. Psychological data should be interpreted with great care and always in combination with data from the dental examination.


Contemporary assessment of laryngotracheal trauma.
Laryngotracheal trauma is a rare and potentially deadly spectrum of injuries. We sought to characterize the contemporary mechanisms, diagnostic modalities, and outcomes common in laryngotracheal trauma today. We performed a retrospective analysis of all laryngotracheal trauma cases at 2 major metropolitan hospitals between 1996 and 2004, detailing mechanisms, associated injuries, diagnostic modalities, and outcomes of laryngotracheal trauma. We identified 71 patients with a mean age of 32.8 +/- 13.3 years (range, 15-71 years). In our series penetrating trauma was the cause in 73.2% of patients; however, blunt trauma had a significantly higher mortality (63.2% vs 13.5%, respectively; P < .0001). Blunt mechanisms involved older patients (38.5 +/- 15.2 years vs 30.1 +/- 11.9 years, P = .017), and these patients were more likely to require emergency airways than those with penetrating trauma (78.9% vs 46.2%, P = .017). The requirement of an emergency airway was an independent predictor of mortality (P = .0066). Laryngotracheal trauma is a deadly spectrum of injuries with a mortality of 26.8%. Blunt mechanisms are decreasing in frequency. This might reflect improvements in automobile safety. Additionally, violent crime is on the increase, producing penetrating injuries with increasing frequency. The most fundamental intervention for patients with laryngotracheal injury is airway control. Either routine intubation or a tracheostomy can secure the airway. Blunt trauma and the requirement of an emergency airway are independent predictors of mortality. Laryngotracheal trauma requires prompt recognition, airway protection, and skillful management to lessen the mortality of this deadly spectrum of injuries.


Regulatory requirements for providing adequate veterinary care to research animals.
Provision of adequate veterinary care is a required component of animal care and use programs in the United States. Program participants other than veterinarians, including non-medically trained research personnel and technicians, also provide veterinary care to animals, and administrators are responsible for assuring compliance with federal mandates regarding adequate veterinary care. All program participants therefore should understand the regulatory requirements for providing such care. The author provides a training primer on the US regulatory requirements for the provision of veterinary care to research animals. Understanding the legal basis and conditions of a program of veterinary care will help program participants to meet the requirements advanced in the laws and policies.


Phytochrome photosensory signalling networks.
Light is life for plants. To continuously assess and adapt to fluctuations in the quality and quantity of this essential commodity, plants deploy sensory photoreceptors, including the phytochromes. Having captured an incoming photon, the activated phytochrome molecule must relay this information to nuclear genes that are poised to respond by directing appropriate adjustments in growth and development. Defining the intricate intracellular signalling networks through which this sensory information is transduced is an area of intense research activity.


Development of social functioning in preadolescent children at familial high-risk of schizophrenia or bipolar disorder - a 4-year follow-up study from age 7 to 11.
Social functioning is a major indicator of psychosis risk and evidence is lacking regarding social functioning development during preadolescence in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). We aimed to investigate development of social functioning from age 7 to 11 in children at FHR-SZ or FHR-BP compared with population-based controls. At 4-year follow-up, 179 children at FHR-SZ (mean age 12.0 y, SD 0.3), 105 children at FHR-BP (mean age 11.9 y, SD 0.2), and 181 controls (mean age 11.9 y, SD 0.2) participated. We used the Vineland-II to measure social functioning. Development of social functioning was non-significantly different across groups on the Socialization Composite score as well as the subscales Interpersonal Relations, Play and Leisure, and Coping Skills. At 4-year follow-up, children at FHR-SZ demonstrated impaired social functioning, whereas children at FHR-BP displayed social functioning comparable to controls except from impaired coping skills. From age 7 to 11, the maturational pace of social functioning in children at FHR-SZ and FHR-BP is parallel to that of controls. Children at FHR-SZ show stable social functioning deficits, whereas children at FHR-BP show normal social functioning except from emergence of discretely impaired coping skills at age 11.


Development of biosimilars.
To provide an overview of the underlying scientific principles and standards for developing a biosimilar product. An Internet-based literature search through June 2015 was performed for information related to biosimilar manufacturing and development, including a review of regulatory guidelines and requirements. Biologics, both biosimilars and their corresponding reference products, are complex molecules produced by biotechnology in living systems. The development of biologics involves multiple levels of intricate, highly controlled manufacturing processes, combined with pre-clinical structural, functional, and biological assessments, as well as clinical efficacy and safety, including immunogenicity, analyses. In addition, to ensure a high degree of similarity, a biosimilar must undergo a comparability exercise at every step of its development, as outlined by regulatory agencies, to demonstrate that potential differences from the reference product are not clinically meaningful with regard to quality, safety, and efficacy [European Medicines Agency (EMA)] or safety, purity, and potency [US Food and Drug Administration (FDA)]. At the foundation of the biosimilar development process lays the establishment of a high degree of structural similarity with its reference product. State-of-the-art technologies must be employed to demonstrate a high degree of structural and functional similarity. Finally, clinical pharmacokinetic and pharmacodynamic as well as clinical efficacy and safety similarity must be confirmed between biosimilar and originator. Regulators, including the FDA and the EMA consider the totality of the evidence from this comprehensive step-wise comparative similarity exercise in its determination of biosimilarity for licensing. The rigorous and highly regulated processes required to develop a biosimilar have been designed as such to establish a high degree of biosimilarity with a reference product in terms of the structural, functional, biological, and clinical attributes.


Elevated interleukin-1 expression in human neonatal neutrophils.
Newborn infants have an increased morbidity and mortality from infection caused in part by diminished polymorphonuclear leukocyte (PMN) function and impaired recruitment of PMN to sites of inflammation. Recent studies in our laboratory and others have demonstrated the in vitro expression of several cytokines, including IL-1-beta, in adult human peripheral blood PMN. Because newborn infants have an impaired inflammatory response, we sought to compare the synthetic capability and regulation of cytokine expression in neonatal and adult PMN. In our present studies, we found that tumor necrosis factor-alpha and lipopolysaccharide could induce IL-1-beta expression in both neonatal and adult PMN and that neonatal PMN produced significantly more IL-1-beta when compared with adult PMN. The PMN chemotactic peptide fMet-Leu-Phe did not induce IL-1-beta expression in either adult or neonatal PMN. Elevated cytokine expression by neonatal PMN may play an important role in the regulation of the immune and inflammatory systems at sites of injury and infection in neonates.


Neural correlates of the behavioral-autonomic interaction response to potentially threatening stimuli.
Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as "harmless" or "threatening." Individuals' stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, "threatening," compared with "harmless" behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl's gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual's propensity to assess stimuli as "threatening." SCRs may modulate cognitive assessments on a "harmless-threatening" dimension, thereby modulating affective tone and hence behavior.


Predicting the success of defibrillation by electrocardiographic analysis.
We investigated an electrocardiographic signal analysis technique for predicting whether an electrical shock would reverse ventricular fibrillation (VF) in an effort to minimize the damaging effects of repetitive shocks during CPR. An established model of CPR was utilized. VF was electrically induced in anesthetized 40 kg domestic pigs. Defibrillation was attempted after either 4 or 7 min of untreated VF. Failing to reverse VF, a 1 min interval of precordial compression and mechanical ventilation preceded each subsequent defibrillation attempt. The amplitude frequency spectrum of digitally filtered VF wavelets was computed with Fourier analysis during uninterrupted precordial compression from conventional right infraclavicular and left apical electrodes. Of a total of 34 electrical defibrillation attempts, 24 animals were restored to spontaneous circulation (ROSC). An amplitude spectrum analysis (AMSA) value of 21 mV Hz had a negative predictive value of 0.96 and a positive predictive value of 0.78. AMSA predicted when an electrical shock failed to restore spontaneous circulation during CPR with a high negative predictive value. This method potentially fulfills the need for minimizing ineffective defibrillation attempts and their attendant adverse effects on the myocardium.


Decompensated ureteropelvic junction obstruction in renal allograft.
We report a case of complete obstruction at the ureteropelvic junction in a renal allograft 6 months after related kidney transplantation. Surgical treatment consisted of a Foley nondismembered Y-V pyeloplasty. Although the donor harbored undetected bilateral, mild, ureteropelvic junction stenosis, as established by review of the excretory urogram that was performed before nephrectomy, the remaining kidney functioned well, as confirmed by renal function and morphological appearance on a repeat excretory urogram. The possible mechanisms of ureteropelvic junction decompensation, the most crucial of which appears to be autonomic denervation of the allograft, are discussed.


Effect of salinity and humidity on δ13C value of halophytes-Evidence for diffusional isotope fractionation determined by the ratio of intercellular/atmospheric partial pressure of CO2 under different environmental conditions.
Seedlings of two mangrove species, Avicennia marina and Aegiceras corniculatum, were grown in a range of salinities and humidities in controlled environment chambers, and Phaseolus vulgaris plants were grown in the glasshouse. The fractionation of carbon isotopes in the three species was correlated with the ratio of intercellular and ambient partial pressures of CO2. The results are consistent with fractionation being due both to diffusion in air and to carboxylation in the leaf. It was concluded that the latter process discriminates against 13CO2 relative to 12CO2 by about 27‰.


Changes in densities and kinetics of delayed rectifier potassium channels during neuronal differentiation.
Single-channel K+ currents were recorded from young and mature spinal neurons cultured from Xenopus embryos to examine the bases of the developmental increases in density and in rate of activation of the macroscopic voltage-dependent delayed rectifier K+ current (IKv). K+ channels of three conductance classes (integral of 80, 30, and 15 pS) are present at both ages, but only the intermediate and small conductance classes are voltage-dependent and thus underlie IKv. The increase in the density of IKv is due to increases in the numbers of intermediate and small channels per cell, but not to changes in their open probabilities. The increase in rate of activation of IKv results from a change in the activation kinetics of the intermediate channel class alone.


Consuming fructose-sweetened beverages increases body adiposity in mice.
The marked increase in the prevalence of obesity in the United States has recently been attributed to the increased fructose consumption. To determine if and how fructose might promote obesity in an animal model, we measured body composition, energy intake, energy expenditure, substrate oxidation, and several endocrine parameters related to energy homeostasis in mice consuming fructose. We compared the effects of ad libitum access to fructose (15% solution in water), sucrose (10%, popular soft drink), and artificial sweetener (0% calories, popular diet soft drink) on adipogenesis and energy metabolism in mice. Exposure to fructose water increased adiposity, whereas increased fat mass after consumption of soft drinks or diet soft drinks did not reach statistical significance (n = 9 each group). Total intake of energy was unaltered, because mice proportionally reduced their caloric intake from chow. There was a trend toward reduced energy expenditure and increased respiratory quotient, albeit not significant, in the fructose group. Furthermore, fructose produced a hepatic lipid accumulation with a characteristic pericentral pattern. These data are compatible with the conclusion that a high intake of fructose selectively enhances adipogenesis, possibly through a shift of substrate use to lipogenesis.


Within-trial contrast: when you see it and when you don't.
Within-trial contrast occurs when a discriminative stimulus that is preceded by a relatively aversive event is preferred over another that is preceded by a less aversive event. Recent failures to replicate (Arantes & Grace, 2008; Vasconcelos, Urcuioli, & Lionello-DeNolf, 2007) may allow us to identify factors that may be responsible. In the case of Vasconcelos et al., it is likely that insufficient training was provided (often 35-65 sessions are required). In the case of Arantes and Grace (Experiment 2), these pigeons had been involved in prior experiments involving lean schedules of reinforcement, and we find that prior experience its occurrence. with lean (relatively aversive) schedules appears to reduce the presumed aversiveness of the many-peck requirement, thus obviating the contrast effect. Finally, in the case of Vasconcelos and Urcuioli (2008), although the contrast effect with a simultaneous discrimination was not reliable, it was not reliably smaller than with a successive discrimination that did show a reliable effect, and the contrast effect was also similar in magnitude to a reliable effect reported by Kacelnik and Marsh (2002). Thus, although there have been several failures to replicate the original effects reported by Clement, Feltus, Kaiser and Zentall (2000), insufficient training, prior history with lean schedules of reinforcement, and low statistical power may have been responsible for those failures.


Maternal Depression and Early Intervention: A Call for an Integration of Services.
Depression is a serious disorder with severe and far-reaching consequences. Two decades of observational research have shown robust associations between maternal depression and adverse consequences on offspring (Campbell et al., 2004; Campbell, Matestic, von Stauffenberg, Mohan, & Kirchner, 2007; Campbell, Morgan-Lopez, Cox, & McLoyd, 2009; National Research Council & Institute of Medicine, 2009). Depressive symptoms may pose particular risk to infants and toddlers with neurodevelopmental disabilities, whose long-term outcomes depend heavily on the provision of Early Intervention (EI). EI is most effective with active parental engagement. Maternal depressive symptoms may reduce parental engagement, thereby limiting EI benefits to the child (Gaynes, Gavin & Meltzer -Brody, 2005; O'Hara & Swain, 1996). At present, maternal mental health is not directly addressed in EI. The purpose of this paper is to discuss the literature and significance of maternal depression and apply that evidence to mothers of children with developmental delays and disabilities. We conclude that maternal mental health and well-being is currently insufficiently addressed in the EI population. An increased integration of mental health and EI services is needed to serve the unique needs of families who face an increased risk of stress and depression while coping with their child's special needs.


Investigating pain in heart failure patients: rationale and design of the Pain Assessment, Incidence & Nature in Heart Failure (PAIN-HF) study.
Heart failure is a major cause of morbidity and mortality and is increasing in prevalence. Treatments for heart failure permit a growing number of persons to live with the illness for many years. The burden of symptoms in persons with advanced heart failure is high. Fatigue, limited exertion, dyspnea, and depression are commonly associated with heart failure, but pain is common as well. Although it is known that underlying comorbidities modify the response to and experience of pain, the interaction between pain and the clinical syndrome of heart failure has not been studied to date. The Pain Assessment, Incidence & Nature in Heart Failure (PAIN-HF) study will evaluate pain in patients with advanced heart failure. Specifically, PAIN-HF will examine the anatomical location of pain, prevalence of pain, its association with aspects of patients' heart failure and comorbid conditions, and its relation to interventions and medications to treat pain. This study to identify the nature, incidence, and character of pain is an important step in relieving distress and discomfort in persons with heart failure.


Usability and Acceptance of the Librarian Infobutton Tailoring Environment: An Open Access Online Knowledge Capture, Management, and Configuration Tool for OpenInfobutton.
The Librarian Infobutton Tailoring Environment (LITE) is a Web-based knowledge capture, management, and configuration tool with which users can build profiles used by OpenInfobutton, an open source infobutton manager, to provide electronic health record users with context-relevant links to online knowledge resources. We conducted a multipart evaluation study to explore users' attitudes and acceptance of LITE and to guide future development. The evaluation consisted of an initial online survey to all LITE users, followed by an observational study of a subset of users in which evaluators' sessions were recorded while they conducted assigned tasks. The observational study was followed by administration of a modified System Usability Scale (SUS) survey. Fourteen users responded to the survey and indicated good acceptance of LITE with feedback that was mostly positive. Six users participated in the observational study, demonstrating average task completion time of less than 6 minutes and an average SUS score of 72, which is considered good compared with other SUS scores. LITE can be used to fulfill its designated tasks quickly and successfully. Evaluators proposed suggestions for improvements in LITE functionality and user interface.


[Modeling the process of excitatory transmission from the mechanical portion of the auditory system to the nerve endings of the auditory nerve].
Sharpening of frequency selectivity of the mechanical part of the hearing system due to the transformation of the signals in the receptor system is investigated. It is proposed that excitation of neuron endings is proportional to the amplitude of the current which was produced by the difference of microphonic potentials in the neighbouring hair cells. It is shown that possible degree of the selectivity sharpening of the cochlea which can be explained by this model is in a good agreement with the known experimental results.


USA Vs Europe: Who Is Leading the Diabetes Tech Race?
To highlight global advancements in diabetes technology and compare available technologies and device approval processes in the USA and Europe and their impact on safety and innovation. The last two decades have seen a rapid growth in diabetes technology driven by the impetus to improve glycemic control, avoid complications of insulin therapy, improve quality of life, and hand more autonomy to individuals with diabetes. Meanwhile, changes to regulatory processes in the USA and Europe aim to facilitate entry of new devices into the marketplace. Major strides have been made in digitization of insulin pens, continuous glucose monitors and their integration with insulin pumps, automated insulin delivery systems, and closed-loop insulin pump systems. The centralized regulatory body in the USA and more decentralized approval bodies in Europe have led to differences in the rate of market availability of diabetes devices. While both US and Europe systems have different advantages and disadvantages in device approval, they continue to struggle with balancing accelerated device access with adequate clinical evidence and monitoring to ensure safety of such devices.


The impact of non-thermal plasma on the adhesion of polyetherketoneketone (PEKK) to a veneering composite system.
The PEKK material can be used in prosthodontics for framework manufacturing and is commonly laminated with veneering composites to achieve a better esthetics. Various surface treatment methods including sandblasting, etching, laser and cold plasma treatments were reported to enhance the adhesive properties of dental polymers. Both tensile and shear bond test were employed to quantify the bond strength between PEKK and veneering composites. The present in vitro study aims to evaluate the influence of acetylene, argon, air, nitrogen and oxygen plasma on the shear bond strength between PEKK and one veneering composite. Firstly, to determine which bond test type should be applied, n = 40 PEKK specimens were treated with argon plasma. Both shear and tensile bond tests were performed and compared to the control group (n = 40). In shear bond testing, values were 8.14 ± 1.70 MPa for Argon plasma while 5.83 ± 1.42 MPa for control group. In tensile bond testing, Argon plasma 1.50 ± 0.51 MPa while control group 0.58 ± 0.50 MPa. Afterwards n = 160 PEKK specimens were treated with rocatec sandblasting (n = 20), adhesive (n = 20), acetylene (n = 20), argon (n = 20), air (n = 20), nitrogen (n = 20), oxygen (n = 20) plasma types and compared to the untreated control group (n = 20) using shear bond strength test (SBS). Additionally surface roughness and scanning electron microscopy analyses were performed. The following SBS values were revealed: 10.22 ± 1.06 MPa for rocatec; 9.89 ± 3.08 MPa for acetylene, 9.16 ± 1.48 MPa for adhesive, 7.54 ± 1.52 MPa for argon, 7.09 ± 1.99 MPa for air, 7.03 ± 1.48 MPa for nitrogen, 5.69 ± 1.59 MPa for oxygen plasma types and 4.71 ± 1.54 MPa for the control group. All groups, except control group, showed SBS over 5 MPa, which means that they are suitable for the clinical application, according to ISO 10477. Acetylene showed the highest SBS among all plasma types (p < 0.0001), which was on a level of rocatec sandblasting group. Rocatec and acetylene groups demonstrated Ra values significantly different to the reference group (p < 0.0001). Plasma treatment especially with acetylene gas can be an effective more convenient surface treatment method for strengthening the bond strength between PEKK and veneering composites than traditional sandblasting/adhesive treatment.


Cryptococcus laurentii fungaemia in a cervical cancer patient.
Infections caused by emerging Cryptococcus non-neoformans species are being reported with increasingly frequency. Here, we present a case of fungaemia by Cryptococcus laurentii in a woman receiving aggressive immunosuppressive therapy for cervical neoplasia. Three venous blood samples were aseptically collected on consecutive days and C. laurentii was isolated and identified through phenotypic and molecular methods. After central venous catheter removal and appropriate antifungal therapy, the patient showed significant improvement and blood culture became negative. Thus, patients following immunosuppressive therapies and using invasive medical devices are at risk of C. laurentii blood infections.


Pulmonary sequestration.
A review of 41 patients over a 15-year period with a diagnosis of pulmonary sequestration was undertaken. The most common presenting complaint was repeated infections of the sequestrated segment. Two of our patients were symptomatic since the neonatal period. On an average, each patient was admitted three times to the hospital before undergoing surgery. All our patients had abnormal chest x-rays. Two patients had severe purulent infection needing emergency resection of the sequestrated lobe. In our experience, almost all cases of pulmonary sequestration require surgery in the long-term.


CT-guided transbronchial biopsy using an ultrathin bronchoscope with virtual bronchoscopic navigation.
We evaluated the feasibility, safety, and efficacy of CT-guided transbronchial biopsy (TBB) using an ultrathin bronchoscope with navigation by virtual bronchoscopy (VB) for small peripheral pulmonary lesions of < 20 mm in diameter. A pilot study. A national university hospital. We performed CT-guided TBB after VB navigation for 25 patients with 26 small peripheral pulmonary lesions (average diameter, 13.2 mm) between June 1, 2001, and October 31, 2002. Of the 26 lesions, 10 were in the right upper lobe, 2 were in the right middle lobe, 6 were in the right lower lobe, and 8 were in the left upper lobe. Nineteen lesions were not detected on chest radiographs. VB images were reconstructed from helical CT scans. CT-guided TBB was performed using an ultrathin bronchoscope after studying the VB image. CT-guided TBB was performed safely without any complications for all patients. The bronchi seen under VB imaging were highly consistent with the actual bronchi confirmed using an ultrathin bronchoscope. The ultrathin bronchoscope was inserted between the fifth and eighth generation bronchi. The average durations of the initial scan, the first biopsy, and the total examination were 5.46, 12.96, and 29.27 min, respectively. Seventeen lesions (65.4%) were diagnosed from pathology examinations (primary lung cancers, 13; atypical adenomatous hyperplasia, 1; metastatic cancer, 1; sarcoidosis, 1; and nontuberculous mycobacteriosis, 1). Diagnoses were not obtained for the remaining lesions due to an insufficient number of specimens (six specimens) or to the inability to reach the lesions even using the ultrathin bronchoscope (three specimens). In summary, CT-guided TBB using an ultrathin bronchoscope with VB navigation was safely performed and was effective for diagnosing small peripheral pulmonary lesions.


Analysis of in vivo occupancy of Aebp1, a transcription factor, using high resolution tiling array.
Aebp1 is a transcription factor that negatively regulates adipogenesis and also is upregulated in primary GBM as against secondary GBM. Here we describe a systematic approach to map the in vivo occupancy sites of Aebp1 by using a combination of chromatin immune-precipitation technique and hybridization to Agilent high resolution human promoter tiling array (2×224) containing 474393 probes. We also describe the use of various bioinformatics tools for analysis of the hybridization data and identification of Aebp1 occupancy sites in U87MG glioma cell line.


Recombination between Vaccine and Field Strains of Porcine Reproductive and Respiratory Syndrome Virus.
We isolated and plaque purified IA76950-WT and IA70388-R, 2 porcine reproductive and respiratory syndrome viruses from pigs in the same herd in Iowa, USA, that exhibited coughing and had interstitial pneumonia. Phylogenetic and molecular evolutionary analysis indicated that IA70388-R is a natural recombinant from Fostera PRRSV vaccine and field strain IA76950-WT.


Identification and in vitro anti-inflammatory activity of different forms of phenolic compounds in Camellia oleifera oil.
Camellia oleifera (C. oleifera) oil is known as "oriental olive oil". We previously reported the anti-inflammatory activity of C. oleifera oil was mainly attributed to the phenolic compounds, but the specific compounds remain uncovered. In this study, phenolic compounds in the form of free (11.92 μg GAE/g), esterified (37.57 μg GAE/g), glycosylated (128.71 μg GAE/g), and insoluble (47.53 μg GAE/g) were prepared from C. oleifera oil. Their anti-inflammatory activities were evaluated by lipopolysaccharide induced RAW 264.7 macrophage. Glycosylated fraction showed the highest anti-inflammatory activity as indicated by the low production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Subsequently, 13 different glycosylated polyphenols were identified by UPLC-Q-TOF/MS, and the major compounds were purified for anti-inflammatory re-evaluation. Lower anti-inflammatory activities of compound 3 and compound 6 were observed when compared to kaempferol. Overall, these results would promote the utilization of phenolic compounds in C. oleifera oil.


Psoralen photoallergy caused by plant contact.
A case of acquired photocontact allergy to furocumarins in plants is reported. Photopatch testing was performed with four psoralens [8-methoxypsoralen (8-MOP), 5-methoxypsoralens (5-MOP), trimethylpsoralen (TMP) and imperatorin (IMP)[. The use of serial dilutions of the test compounds made it possible to differentiate between photoallergic and phototoxic reactions. 8-MOP gave a positive eczematous test reaction down to a concentration of 0.0001%. The reactions to 5-MOP and imp also were positive, while that to TMP awas negative. Histopathological examination of a biopsy specimen from a positive test site showed changes consistent with photoallergic contact dermatitis. The multiple reactions could be explained on the basis of multiple sensitization but cross reactions cannot be ruled out.


Publisher Correction: Development of an efficient cytosolic isobutanol production pathway in Saccharomyces cerevisiae by optimizing copy numbers and expression of the pathway genes based on the toxic effect of α-acetolactate.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Personal Protection Equipment Kit Tracker.
The primary efficient review on the status of individual defensive gear for medical services workers in India has uncovered that practically all parts of PPE were discovered to be either deficiently accessible or inaccessible in many clinics. PPEs are a significant clinical asset for cutting edge laborers during the pandemic that incorporate body coveralls, N-95 covers, goggles, face shields among others. The public authority has been guaranteeing that after the underlying long stretches of the pandemic, PPE were just imported and there is no deficiency since the most recent couple of months as several homegrown makers are delivering almost 4.5 lakh PPE units every day now. Nonetheless, the most recent review by a gathering of free wellbeing analysts has affirmed that cutting edge workers are as yet not getting these units. The study depended on reactions from specialists, inhabitants and understudies, attendants and network wellbeing workers. Almost 33% of respondents revealed that covers were not accessible at all. (According to an article by The New Indian Express). There are claims that demonstrate no deficiencies of PPE units the nation over, yet as per ongoing overviews, the undeniable realities are not replicated. These realities get significantly more heart-breaking when we move from green zones (one out of five) to red zones (one out of three). At present, India does not have an appropriate framework for the board of the PPE packs, guaranteeing legitimate unit purchasing and selling or permitting taking an interest element to chip away at the regular stage to fix bargains with respect to PPE parts, as indicated by their prerequisites.


Uptake of adenosine into cultured cerebral endothelium.
Adenosine uptake by cultured cerebral endothelium is a carrier-mediated process. The Km value for adenosine uptake is 5.0 microM and the vmax is 1.15 nmol/min/mg cell protein. The uptake system is inhibited by the adenosine analog 2-chloroadenosine at low adenosine concentrations. The results prove the existence of a nucleoside transport system associated with cerebral capillary endothelium.


Development of a near infrared multi-wavelength, multi-channel, time-resolved spectrometer for measuring brain tissue haemodynamics and metabolism.
We present a novel time domain functional near infrared spectroscopy system using a supercontinuum laser allowing us to measure the coefficient of absorption and scattering of up to 16 multiplexed wavelengths in the near infrared region. This is a four detector system that generates up to 3 mW of light for each wavelength with a narrow 2-3 nm FWHM bandwidth between 650 and 890 nm; each measurement of 16 wavelengths per channel can be performed up to a rate of 1 Hz. We can therefore quantify absolute haemoglobin changes in tissue and are currently investigating which and how many wavelengths are needed to resolve additional chromophores in tissue, such as water and the oxidation state of cytochrome-c-oxidase.


Noninvasive assessment of pulmonary vascular resistance and pressure in patients with congenital heart disease: a new method using M-mode echocardiography.
The accurate evaluation of pulmonary vascular resistance (PVR) and mean pulmonary artery pressure is important to determine the optimal management and therapeutic strategy for patients with congenital heart disease (CHD). We evaluated the PVR and mean pulmonary artery pressure in 46 patients with several CHD types using the interventricular septum (IVS) motion determined by M-mode echocardiography. We divided the patients into 2 groups according to the different IVS motions. We measured the maximum anterior displacement from the baseline during early systole (a) and the maximum posterior displacement from the baseline during early diastole (b). We defined type A to be a/b greater than or equal to 1.0, and type B to be a/b less than 1.0. The PVR and mean pulmonary artery pressure in type A patients were significantly higher than those in type B patients (p < 0.05). Type A IVS motion predicted patients with high PVR (>2.5 unit/m(2)) and high mean pulmonary artery pressure (>25 mmHg) (sensitivity 89%, specificity 89% and sensitivity 70%, specificity 91%, respectively). Our method can noninvasively separate high and low PVR among patients with CHD. This noninvasive method is therefore considered to be useful in the management of patients with CHD in a clinical setting.


Young Friesian horses show familial aggregation in fitness response to a 7-week performance test.
The aim of this study was to monitor the fitness level of young Friesian horses and to assess whether fitness data are predictive for final performance score and whether familial aggregation of response to training could be detected. Sixty-six young Friesian horses, the offspring of six different stallions (A, B, C, D, E and F), underwent a 7-week performance test. The horses were given a performance score for their ability for dressage (in weeks 5 and 7; 0-110 points) and were evaluated for fitness using standardised exercise tests (SETs) at the beginning (week 2, SET-I) and the end (week 6, SET-II) of the period. Heart rate (HR, beats/min) was measured in both SETs, and plasma lactate concentration (LA, mmol/L) was measured only in SET-II. Fitness of the horses improved moderately but significantly between SET-I and SET-II (P=0.015). There was a large heterogeneity in responsiveness to training; some horses were high responders, whereas others were non- or low responders. There was a familial aggregation of HR canter-1 response to training (P=0.039), while the HR of stallion C's offspring decreased significantly more than those of stallions A (P=0.09), D (P=0.013) and F (P=0.009). Horses that were reluctant to exercise did not differ in HR or LA concentrations compared to those that completed the SET, which may have been a sign of overreaching. HR had no predictive value for the performance score, but horses that did not reach the anaerobic threshold in SET-II scored significantly better (73.8 ± 5.6 points) than horses that did not (69.9 ± 5.9 points, P=0.025). The findings demonstrate for the first time in the horse a familial aggregation of HR response to training, as has been reported previously in humans. Familial aggregation suggests a genetic influence on the effect of training on fitness in horses. HR could not predict final performance score, but LA concentrations during SET-II were predictive.


[Anatomical hepatic resection using radiofrequency thermoablation in the treatment of primary or secondary liver tumors].
Radiofrequency thermoablation (RFA) in performing parenchymal liver section has been tested. Eleven patients with primary cancer or colorectal cancer metastasis underwent anatomical major liver resection after vascular control. Parenchymal section was performed by knife after coagulative necrosis. No deaths, clinical or technical complications or blood losses occurred. Such technique is feasible and effective.


The analysis of 100 genes supports the grouping of three highly divergent amoebae: Dictyostelium, Entamoeba, and Mastigamoeba.
The phylogenetic relationships of amoebae are poorly resolved. To address this difficult question, we have sequenced 1,280 expressed sequence tags from Mastigamoeba balamuthi and assembled a large data set containing 123 genes for representatives of three phenotypically highly divergent major amoeboid lineages: Pelobionta, Entamoebidae, and Mycetozoa. Phylogenetic reconstruction was performed on approximately 25,000 aa positions for 30 species by using maximum-likelihood approaches. All well-established eukaryotic groups were recovered with high statistical support, validating our approach. Interestingly, the three amoeboid lineages strongly clustered together in agreement with the Conosa hypothesis [as defined by T. Cavalier-Smith (1998) Biol. Rev. Cambridge Philos. Soc. 73, 203-266]. Two amitochondriate amoebae, the free-living Mastigamoeba and the human parasite Entamoeba, formed a significant sister group to the exclusion of the mycetozoan Dictyostelium. This result suggested that a part of the reductive process in the evolution of Entamoeba (e.g., loss of typical mitochondria) occurred in its free-living ancestors. Applying this inexpensive expressed sequence tag approach to many other lineages will surely improve our understanding of eukaryotic evolution.


Mixed protein-templated luminescent metal clusters (Au and Pt) for H2O2 sensing.
A simple and cost-effective method to synthesize the luminescent noble metal clusters (Au and Pt) in chicken egg white aqueous solution at room temperature is reported. The red-emitting Au cluster is used as fluorescent probe for sensitive detection of H2O2.


Body composition of New Zealand-born term babies differs by ethnicity, gestational age and sex.
Body composition provides important information on nutrition and future metabolic risk. New Zealand has a diverse ethnic population for which there are no newborn body composition data. To determine body composition in a cohort of New Zealand-born term babies. Observational study. Healthy, term infants between 37+0 and 41+6 weeks' gestation in two hospitals in Auckland, New Zealand. Body composition by air displacement plethysmography and anthropometry measured within 5 days of birth. Parent-identified ethnicity was prioritised according to Ministry of Health criteria. Data were analysed using t-test, ANOVA with Tukey post-hoc tests, quantile regression and are mean(SD). 440 babies (54% male) were included. Pacific Island/Māori (PI/M) were heavier at birth than Asian/Middle Eastern/Latin American/African (Asian+) babies (3403(506) vs 3181(485) g, p < .05). PI/M and European (E) babies were longer with larger head and waist circumferences than Asian+ babies (all p < .05). Absolute fat mass (FM) was not different amongst ethnicities (E, 365(156), PI/M, 347(183), Asian+, 357(188) g) but PI/M babies had significantly lower FM% than Asian+ (9.8(4.3) vs 10.9(4.5) %, p < .05). Fat-free mass (FFM) was greater in PI/M (3056(400) g) than E (2952(345) g (p < .05) and both PI/M and E had greater FFM than Asian+ (2824(363) g, p < .05). Early term babies had less FFM than term and late-term babies (2732(370), 3012(352), 3173(302)g, p < .001) respectively. Asian+ babies were the smallest babies with the least FFM yet had similar FM and the highest FM%, indicative of a thin, fat phenotype from birth.


Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki.
The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 μM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.


Heavy metal concentrations in surface sediments and Manila clams (Ruditapes philippinarum) from the Dalian coast, China after the Dalian port oil spill.
We conducted an investigation of heavy metal concentrations in Manila clams (Ruditapes philippinarum) and surface sediments after the Dalian Port oil spill. Samples were collected from three mariculture zones (Jinshitan, Dalijia, and Pikou) along the Dalian coast. Heavy metal concentrations in R. philippinarum were consistent and ranked in decreasing order of Zn > Cu > As > Cr > Pb > Cd > Hg, while concentrations in surface sediments were ranked as Zn > Cr > Cu > Pb > As > Cd > Hg, respectively. Bioaccumulation of Zn, Cd, and Hg had obviously occurred in R. philippinarum. Statistically significant correlations (p < 0.05) between concentrations of Pb, Cd, and Hg in R. philippinarum and in surface sediments were observed. Except for Cr and As, heavy metal concentrations in R. philippinarum were well within the legal limits for human consumption.


Prevalence and correlation of C-shaped root canals of mandibular premolars and molars in Eastern Chinese individuals.
The aim of this study was to investigate the prevalence, correlation, and differences of C-shaped root canals (CSRCs) morphology in permanent mandibular premolars and molars in Eastern Chinese individuals using cone-beam computed tomography (CBCT). A total of 8000 mandibular first premolars (MFPs), mandibular second premolars (MSPs), mandibular first molars (MFMs), and mandibular second molars (MSMs) CBCT images from 1000 patients (692 females and 308 males) were collected. The prevalence, correlation, bilateral/unilateral presence, the morphology of CSRCs, level of canal bifurcation, gender differences, and location of radicular grooves (RGs) were evaluated. The prevalence of CSRCs in MFPs, MSPs, MFMs and MSMs were 10.25%, 0.25%, 0.55% and 47.05%, respectively. The prevalence of CSRCs in MFPs of males was higher than that in females, while the prevalence of CSRCs in MSMs of females was higher than that in males (P < 0.05). The bilateral symmetry presence of CSRCs in MSMs was significant but not in MFPs, MSPs, and MFMs. RGs were predominantly found on the mesiolingual (ML) surface of premolars and the lingual surface of molars. There was a high prevalence of CSRCs in MFPs and MSMs in the Eastern Chinese population, but there was no correlation. The prevalence of CSRCs in MFPs and MSMs differ significantly by gender (P < 0.05).


Design and evaluation of a multimodal balance training system.
Current balance training systems are designed exclusively for one particular type of training and assessment. Additionally, they comprise monotonous training programs. Therefore, patients in different stages of rehabilitation must use different balance training models from different manufacturers, resulting in high treatment cost. Furthermore, large spaces are required to accommodate the balance training machines, and doctors and physiotherapists have to learn to operate multiple machines. We aimed to design a multimodal balance training and assessment system that can accommodate the assessment and training of static, dynamic, reactive and proactive balance to satisfy individual needs. The difficulty associated with combining static, dynamic, reactive and proactive balance training in a single system was to use radial and circumferential driving mechanisms together with a clutch mechanism, whereby circumferential and radial drivers were installed in the base of the system to drive a compound foot plate system with interchangeable springs, in order to adjust stiffness using the clutch. Based on the kinematic equation, the influence of system parameters on the change of the body's center of gravity were evaluated. The parameters included the radial offset of the driving mechanism (r), circumferential angle of rotation (θ), height of the base of the balance training system (h), horizontal distance between the body's standing center of gravity and the center of the foot plate (R), thickness of the padding mat (ΔH) and inclination angle (α). The difficulties associated with combining static, dynamic, reactive and proactive balance training models in a single system were solved using radial and circumferential driving mechanisms together with a clutch mechanism. The foot plate can swing back and forth within ±20° around the X-axis, swing left and right within ±20° around the Y-axis, swing diagonally within ±20°, swing 360° around the Z-axis, and adjust the height along the Z-axis. Furthermore, the inclination angle α, circumferential angle of rotation θ, and speed (dα/dt and dθ/dt) of the system can be controlled in real time. The developed balance training system is suitable for patients in different stages of rehabilitation. By providing multiple functionalities, this system can ensure high use rates, reduce costs and save space.


Array comparative genomic hybridization of keratoacanthomas and squamous cell carcinomas: different patterns of genetic aberrations suggest two distinct entities.
Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether KA is a variant of SCC (Hodak et al., 1993). To date, no reported criteria are sensitive enough to discriminate reliably between KA and SCC, and consequently there is a clinical need for discriminating markers. Our previous study analyzed 132 KAs and 29 SCCs and revealed significantly different regions of genomic aberrations using chromosomal comparative genomic hybridization (CGH). In the present study, we applied array CGH to investigate 98 KAs and 22 SCCs from the above samples. The result shows that all KAs and SCCs have some degree of genetic aberrations. The distribution of numbers of aberrant clones per sample differed significantly between KAs and SCCs (P<0.02), which also demonstrated recurrent aberrations that differed significantly (P<0.001), as illustrated by unsupervised cluster analysis. Classifiers for clinicopathological parameters of KAs were established based on t-test statistics and permutation tests. Tumor size, fibrosis, and inflammation, which are related to the developmental stages of KAs, showed significant (t-test, permutation test) associations with aberrations of selected genomic regions. This suggests chromosomal instability during the whole life cycle of KAs.


[Study of the total nucleic acid content of lymphoid tissue plasma cells for assessing the immunodepressive action of various antirheumatic agents].
The influence of antirheumatic drugs, acetylsalicylic acid, diacetoxibenzoic acid, imurane and D-penicillamine, on the status of immunocompetent cells in experimental infectious-allergic carditis was studied morphologically in 70 rabbits. The immunosuppressive effect of all 4 drugs was established which was manifested by a decrease in the number of plasma cells in the lymphoid tissue and a decrease in the content of nucleic acids in their cytoplasm. D-penicillamine was the exception as after its use the content of nucleic acids in the cell cytoplasm was found to be increased which was considered to be due to clasmatosis of plasma cells, marginal karyolysis, damage of the nuclear membrane and release of nucleic acids from the nucleus into the cytoplasm. Acetylsalicylic acid and diacetooxybenzoic acid decrease RNA content in the cytoplasm of plasma cells less than imurane and do not cause cell degeneration with contamination of the extracellular environment with products of cells degeneration.


'Breaking out of the asylum': developments in the geography of mental ill-health--the influence of the informal sector.
This paper focuses on the changing role of the voluntary sector in the provision of care and support to community-based individuals with mental ill-health (MIH) in contemporary Scotland. In doing so, it reflects on the ways in which deinstitutionalisation is contributing to changing interrelationships between the formal and informal sector, the influence of the voluntary sector in the development of the locational geographies of individuals with MIH, and factors contributing to geographical variations in access and availability of voluntary sector supports. These developments are considered within the framework of the shadow state.


Clinical outcomes of EUS-guided transluminal drainage with a novel lumen-apposing metal stent for postoperative pancreatic fluid collection after pancreatic surgery.
EUS-guided transluminal drainage (EUS-TD) is increasingly used for the treatment of postoperative pancreatic fluid collections (POPFCs). A novel lumen-apposing metal stent (LAMS) was recently developed and used for the drainage of POPFCs. This study aimed to evaluate the efficacy and safety of a novel LAMS in patients with POPFCs. Forty-seven patients with symptomatic POPFCs who underwent EUS-TD with a novel LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea) between April 2019 and July 2020 were included in this study. Clinical outcomes, including technical success, clinical success, and adverse events, were retrospectively evaluated. EUS-TD was technically successful in 41 of 47 patients (87.2%). Clinical success was achieved in 37 of 41 patients (90.2%). The mean procedure time was 13.7 ± 3.5 minutes. The mean POPFC size was 59 ± 18.9 mm. The mean time interval from surgery to EUS-TD was 24.2 ± 37.6 days. Five patients experienced 6 procedural adverse events (12.8%): 4 (8.5%) POPFC infections and 2 (4.3%) distal stent migrations. The 4 patients with POPFC infection underwent additional endoscopic interventions. Of the 2 patients with stent migration, 1 underwent laparoscopic exploration and surgical extraction of the stent and 1 (2.1%) experienced POPFC recurrence, which was managed with percutaneous drainage. EUS-TD for symptomatic POPFCs with a novel LAMS is technically feasible and effective, with an acceptable adverse event rate. Further larger-scale prospective studies are required to confirm the findings of this study.


Infectivity of Paranosema locustae (Microsporidia) against gregarious-phase South American locust (Orthoptera) when treated en masse.
En masse inoculations with Paranosema locustae, an intracellular parasite of adipose tissue of grasshoppers and locusts and the only microsporidium registered as a biocontrol agent, were conducted against crowded fourth-instar nymphs of the South American locust Schistocerca cancellata and the grasshoppers Dichroplus schulzi and Ronderosia bergii. Infection did not develop in the locust, but was highly prevalent in the two grasshopper species. We hypothesize that absolute absence of infection in S. cancellata may constitute a case of density-dependent prophylactic resistance, an elevation of the baseline immunity of an organism in order to cope with disease that is prevalent in species exhibiting phase polyphenism.


Sociodemographic factors and social media use in 9-year-old children: the Generation R Study.
We aimed to investigate the associations between sociodemographic factors and instant messaging and social network site exposure among 9-year-old children. Data of 4568 children from the Generation R study, a population-based cohort study performed in Rotterdam, the Netherlands, were analyzed. Instant messaging exposure was defined as using online chat applications such as MSN, chat boxes, WhatsApp, and Ping. Social network site exposure was defined as using Hyves or Facebook. A series of multiple logistic regression analyses were performed, adjusting for covariates. Children of low educated mothers had a higher odds ratio (OR) for instant messaging (OR: 1.44, 95% CI: 1.12, 1.86) and social network site exposure (OR: 1.73, 95% CI: 1.13, 2.66) than their counterparts. Being a child from a single-parent family was associated with instant messaging (OR: 1.48, 95% CI: 1.16, 1.88) and social network site exposure (OR: 1.34, 95% CI: 1.01, 1.78) more often than their counterparts. Children of low educated fathers (OR: 1.48, 95% CI: 1.12, 1.95) or from families with financial difficulties (OR: 1.28, 95% CI: 1.04, 1.59) were associated with a higher OR of social network site exposure than their counterparts. The findings suggest that several indicators of lower social position are associated with higher social network site and instant messaging exposure among 9-year-old children. More research is needed in younger children to understand the determinants and impact of social media use.


Catch me if you can: capturing microbial community transformation by extracellular DNA using Hi-C sequencing.
The transformation of environmental microorganisms by extracellular DNA is an overlooked mechanism of horizontal gene transfer and evolution. It initiates the acquisition of exogenous genes and propagates antimicrobial resistance alongside vertical and conjugative transfers. We combined mixed-culture biotechnology and Hi-C sequencing to elucidate the transformation of wastewater microorganisms with a synthetic plasmid encoding GFP and kanamycin resistance genes, in the mixed culture of chemostats exposed to kanamycin at concentrations representing wastewater, gut and polluted environments (0.01-2.5-50-100 mg L-1). We found that the phylogenetically distant Gram-negative Runella (102 Hi-C links), Bosea (35), Gemmobacter (33) and Zoogloea (24) spp., and Gram-positive Microbacterium sp. (90) were transformed by the foreign plasmid, under high antibiotic exposure (50 mg L-1). In addition, the antibiotic pressure shifted the origin of aminoglycoside resistance genes from genomic DNA to mobile genetic elements on plasmids accumulating in microorganisms. These results reveal the power of Hi-C sequencing to catch and surveil the transfer of xenogenetic elements inside microbiomes.


Predictors of Skin, Hair, and Nail Supplement Use: Analysis of National Health and Nutrition Examination Survey (NHANES) Cross-Sectional Data.
Approximately half of US adults use dietary supplements, often for dermatologic purposes. When survey respondents in a nationally representative population were asked the reasons for their use of a specific supplement, 87% chose "for healthy skin, hair, and nails." Despite widespread use, supplements have potential risks and lack regulatory safeguards. Because most supplement users choose to use them without the advice of a healthcare professional, it is important to identify factors predicting use. This study examined demographic predictors of skin, hair, and nail supplement use among 2015-2016 US National Health and Nutrition Examination Survey respondents, a nationally representative sample. Weighted descriptive analysis using χ2 tests examined group differences among respondents who took skin, hair, and nail supplements and those who did not take supplements in the past 30 days. Multivariable logistic regression models were performed to identify predictors of skin supplement use. Statistically significant differences in sex, education, income, and insurance status were observed between dermatologic supplement users and nonsupplement users (P < 0.0001). Factors significantly increasing the likelihood of skin supplement use included age between 30 and 60 years (odds ratio [OR] 1.788, 95% confidence interval [CI] 1.439-2.222), age older than 60 years (OR 4.983, 95% CI 3.838-6.469), having a college degree or above (OR 2.696, 95% CI 1.952-3.724), attending some college or above (OR 1.844, 95% CI 1.364-2.494), having an annual income of >$75,000 (OR 1.285, 95% CI 1.029-1.605), and having health insurance (OR 1.559, 95% CI 1.236-1.967). Male respondents were half as likely to use supplements, compared with females (OR 0.579, 95% CI 0.488-0.687). Factors such as age, education, income, and sex predict supplement use. Knowledge of such trends may help practitioners counsel patients on potential supplement risks and the many unknowns related to their use. Any patient could be using skin, hair, and nail supplements over the counter, including pregnant and older adult populations, as well as generally healthy patients. This would help protect patients from the possible dangers of supplements, including laboratory test interference and teratogenicity.


Recent Advances in Molecular Mechanisms of Taste Signaling and Modifying.
The sense of taste conveys crucial information about the quality and nutritional value of foods before it is ingested. Taste signaling begins with taste cells via taste receptors in oral cavity. Activation of these receptors drives the transduction systems in taste receptor cells. Then particular transmitters are released from the taste cells and activate corresponding afferent gustatory nerve fibers. Recent studies have revealed that taste sensitivities are defined by distinct taste receptors and modulated by endogenous humoral factors in a specific group of taste cells. Such peripheral taste generations and modifications would directly influence intake of nutritive substances. This review will highlight current understanding of molecular mechanisms for taste reception, signal transduction in taste bud cells, transmission between taste cells and nerves, regeneration from taste stem cells, and modification by humoral factors at peripheral taste organs.


Movement patterns of Cetonia beetles (Scarabaeidae) among flowering Viburnum opulus (Caprifoliaceae) : Option for long-distance pollen dispersal in a temperate shrub.
The movement patterns of flower-visiting Cetonia (Coleoptera, Scarabaeidae) were studied in central Sweden over 4 years, providing the first quantitative study of beetle pollination behaviour conducted in a temperate zone. The beetles were marked individually and tracked throughout their visits to Viburnum opulus L. (Caprifoliaceae), a partly beetle-pollinated shrub displaying large umbel-like, creamy-white blossoms. Beetle abundance differed greatly between study years. Of marked beetles observed on V. opulus flowers, an average of 26% returned each year. The beetles performed frequent inter-plant flights, and showed fidelity to particular V. opulus individuals at the study site. Furthermore, they preferred V. opulus to other plants flowering concomitantly and showed considerable constancy in this habit. Movements were mostly between individuals from unshaded locations with high inflorescence and flower number. Normally, the beetles flew on average about 4 times the horizontal nearest-neighbour distance between flowering V. opulus (c. 18 m). From these observations it is concluded that Cetonia beetles are powerful long-distance dispersal agents for V. opulus pollen, perhaps leading to an enhanced gene flow not possible with the plant's other pollinators.


A multicenter study on molecular epidemiology of rhinovirus isolated from children with community acquired pneumonia in China during 2017-2019.
Rhinoviruses (RVs) are a major pathogen of community acquired pneumonia in children. To investigate the prevalence and genetic characteristics of RVs in China, we performed a molecular epidemiological study during 2017-2019 in community acquired pneumonia (CAP) in pediatric patients. In this multicenter study, 109 RV-A, 20 RV-B and 80 RV-C were identified. Among them, RV-A12, RV-A101, RV-A78, RV-A49, RV-A22, RV-B52, RV-C2, RV-C53 and RV-C5 were the common genotypes in the study. A total of 23 complete genome of RVs including 4 RV-A, 1 RV-B and 18 RV-C were obtained. Furthermore, in the RV-C isolates, one RV-C5 and five RV-C53 genotypes were found, which have a limited number in the GenBank. Phylogenetic analysis of the complete genome showed that most of the RVs isolated in the study have high nucleotide sequence identities (>95%) compared with the corresponding reference sequence in the GenBank. In RV-A9, RV-A28, RV-A61 and RV-B52, amino acid mutations were found in the potential neutralizing immunogenic (Nim) sites (Nim-1a and Nim-1b) of the VP1. In RV-B52, one of RV-C2 and RV-C5 isolates, amino acid mutations were found in the P1a peptide of the VP1. However, no recombination events were found in the study. In conclusion, RV-A was the predominant specie of RVs followed by RV-C in the study. The complete genomes of one RV-C5 and five RV-C53 genotypes were obtained which have a limited number sequence in the GenBank. High nucleotide sequence identities (>95%) were found among the complete genome obtained in the study and the corresponding reference sequence in the GenBank. Amino acid mutations were found in the potential Nim-1a, Nim-1b sites and P1a peptide region of the VP1 in parts of RVs.


Semi-supervised interactive fusion network for MR image segmentation.
Medical image segmentation is an important task in the diagnosis and treatment of cancers. The low contrast and highly flexible anatomical structure make it challenging to accurately segment the organs or lesions. To improve the segmentation accuracy of the organs or lesions in magnetic resonance (MR) images, which can be useful in clinical diagnosis and treatment of cancers. First, a selective feature interaction (SFI) module is designed to selectively extract the similar features of the sequence images based on the similarity interaction. Second, a multi-scale guided feature reconstruction (MGFR) module is designed to reconstruct low-level semantic features and focus on small targets and the edges of the pancreas. Third, to reduce manual annotation of large amounts of data, a semi-supervised training method is also proposed. Uncertainty estimation is used to further improve the segmentation accuracy. Three hundred ninety-five 3D MR images from 395 patients with pancreatic cancer, 259 3D MR images from 259 patients with brain tumors, and four-fold cross-validation strategy are used to evaluate the proposed method. Compared to state-of-the-art deep learning segmentation networks, the proposed method can achieve better segmentation of pancreas or tumors in MR images. SFI-Net can fuse dual sequence MR images for abnormal pancreas or tumor segmentation. The proposed semi-supervised strategy can further improve the performance of SFI-Net.


Ultrastructural and cytochemical characterization of T1 and T2 secretory bodies from the tegument of Echinostoma paraensei.
Trematodes are lined by a syncytial layer that is named the tegument and contains small mitochondria and two different kinds of secretory inclusions. The structure and size of these bodies differs among genera and species. In a previous study, we observed many secretory bodies in the tegument of Echinostoma paraensei and named these bodies the T1 and T2 secretory bodies. No previous studies analyzed the secretory bodies of trematodes from the genus Echinostoma. Thus, the aim of this work was to use electron microscopy and cytochemistry to characterize these secretory bodies and to provide a detailed ultrastructural and morphological picture of these bodies, which are found in the tegument of E. paraensei. After ultrastructural cytochemistry analysis, we showed that both the T1 and T2 secretory bodies of E. paraensei were formed by glycoconjugates. 3D reconstruction confirmed the ovoid form of T1 secretory bodies and the biconcave and thin form of T2 secretory bodies.


Enhancement of solar inactivation of Escherichia coli by titanium dioxide photocatalytic oxidation.
To improve solar water disinfection using a photocatalysing semi-conductor and to study the mechanisms involved in this process. Cells of Escherichia coli were used as the microbiological indicator to study the possibility of improving the efficiency of solar water disinfection using titanium dioxide (TiO2) as a photooxidizing semi-conductor. TiO2 was used either as a suspended powder or in an immobilized form. Both applications improved the efficiency of solar disinfection. TiO2 in suspension was more effective than the immobilized form, producing enhancement factors of 1.62 and 1.34, respectively. The concentration of TiO2 greatly affected efficiency, with a maximum effect at 1 mg ml(-1). Higher TiO2 concentrations reduced the efficiency. Dimethyl sulphoxide (DMSO) and cysteamine (Cys), hydroxyl radical (OH.) scavengers, were used to elucidate the mechanisms involved in the presence of TiO2. Both DMSO and Cys totally abolished the enhancing effect produced by the presence of TiO2. Sunlight has a potential water disinfecting capacity. The use of TiO2 greatly improved this efficiency. The effect of TiO2 was mainly concentration-dependent, giving maximum efficiency at 1 mg ml(-1). The presence of DMSO and Cys removed the TiO2-induced enhancement, indicating that OH. may be involved in the process of cell killing. The efficiency of solar disinfection is limited and time-consuming and needs to be improved. The use of a semi-conductor is promising as it reduces the time of exposure and therefore increases the efficiency of solar disinfection. This would allow for the availability of good quality water, and hence would improve the quality of life.


Investigation of hyperelastic models for nonlinear elastic behavior of demineralized and deproteinized bovine cortical femur bone.
In this study, the hyperelastic models of demineralized and deproteinized bovine cortical femur bone were investigated and appropriate models were developed. Using uniaxial compression test data, the strain energy versus stretch was calculated and the appropriate hyperelastic strain energy functions were fitted on data in order to calculate the material parameters. To obtain the mechanical behavior in other loading conditions, the hyperelastic strain energy equations were investigated for pure shear and equi-biaxial tension loadings. The results showed the Mooney-Rivlin and Ogden models cannot predict the mechanical response of demineralized and deproteinized bovine cortical femur bone accurately, while the general exponential-exponential and general exponential-power law models have a good agreement with the experimental results. To investigate the sensitivity of the hyperelastic models, a variation of 10% in material parameters was performed and the results indicated an acceptable stability for the general exponential-exponential and general exponential-power law models. Finally, the uniaxial tension and compression of cortical femur bone were studied using the finite element method in VUMAT user subroutine of ABAQUS software and the computed stress-stretch curves were shown a good agreement with the experimental data.


Repurposing sodium diclofenac as a radiation countermeasure agent: A cytogenetic study in human peripheral blood lymphocytes.
We assessed the radioprotective and mitigative actions of sodium diclofenac, a non-steroidal anti-inflammatory drug using cultured human peripheral blood as a model. Both pre- and post-irradiation treatments with the drug reduced gamma radiation-induced formation of dicentric chromosome, cytochalasin-blocked micronuclei and γ-H2AX foci in human peripheral blood lymphocytes. This work supports the concept that sodium diclofenac may be a useful radiation countermeasure agent.


Increased Internet Searches for Insomnia as an Indicator of Global Mental Health During the COVID-19 Pandemic: Multinational Longitudinal Study.
Real-time global mental health surveillance is urgently needed for tracking the long-term impact of the COVID-19 pandemic. This study aimed to use Google Trends data to investigate the impact of the pandemic on global mental health by analyzing three keywords indicative of mental distress: "insomnia," "depression," and "suicide." We examined increases in search queries for 19 countries. Significant increases were defined as the actual daily search value (from March 20 to April 19, 2020) being higher than the 95% CIs of the forecast from the 3-month baseline via ARIMA (autoregressive integrated moving average) modeling. We examined the correlation between increases in COVID-19-related deaths and the number of days with significant increases in search volumes for insomnia, depression, and suicide across multiple nations. The countries with the greatest increases in searches for insomnia were Iran, Spain, the United States, and Italy; these countries exhibited a significant increase in insomnia searches on more than 10 of the 31 days observed. The number of COVID-19-related deaths was positively correlated to the number of days with an increase in searches for insomnia in the 19 countries (ρ=0.64, P=.003). By contrast, there was no significant correlation between the number of deaths and increases in searches for depression (ρ=-0.12, P=.63) or suicide (ρ=-0.07, P=.79). Our analysis suggests that insomnia could be a part of routine mental health screening during the COVID-19 pandemic.


O-GlyThr: Prediction of human O-linked threonine glycosites using multi-feature fusion.
O-linked glycosylation is one of the most complex post-translational modifications (PTM) of human proteins modulating various cellular metabolic and signaling pathways. Unlike N-glycosylation, the O-glycosylation has non-specific sequence features and unstable glycan core structure, which makes identification of O-glycosites more challenging either by experimental or computational methods. Biochemical experiments to identify O-glycosites in batches are technically and economically demanding. Therefore, development of computation-based methods is greatly warranted. This study constructed a prediction model based on feature fusion for O-glycosites linked to the threonine residues in Homo sapiens. In the training model, we collected and sorted out high-quality human protein data with O-linked threonine glycosites. Seven feature coding methods were fused to represent the sample sequence. By comparison of different algorithms, random forest was selected as the final classifier to construct the classification model. Through 5-fold cross-validation, the proposed model, namely O-GlyThr, performed satisfactorily on both training set (AUC: 0.9308) and independent validation dataset (AUC: 0.9323). Compared with previously published predictors, O-GlyThr achieved the highest ACC of 0.8475 on the independent test dataset. These results demonstrated the high competency of our predictor in identifying O-glycosites on threonine residues. Furthermore, a user-friendly webserver named O-GlyThr (http://cbcb.cdutcm.edu.cn/O-GlyThr/) was developed to assist glycobiologists in the research associated with glycosylation structure and function.


Long-term assessment of negative arthroscopies.
A study of 75 patients was performed to assess the accuracy of arthroscopy carried out for clinical diagnosis of meniscal tear. In these patients, arthroscopy did not detect any intraarticular pathology that could explain the preoperative symptoms. Of the 75 patients, seven were subsequently reoperated on, but in 68 the typical symptoms of meniscal tear improved after the diagnostic arthroscopy.


Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.
Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.


Fourier light-field imaging of human organoids with a hybrid point-spread function.
Volumetric interrogation of the cellular morphology and dynamic processes of organoid systems with a high spatiotemporal resolution provides critical insights for understanding organogenesis, tissue homeostasis, and organ function. Fluorescence microscopy has emerged as one of the most vital and informative driving forces for probing the cellular complexity in organoid research. However, the underlying scanning mechanism of conventional imaging methods inevitably compromises the time resolution of volumetric acquisition, leading to increased photodamage and inability to capture fast cellular and tissue dynamic processes. Here, we report Fourier light-field microscopy using a hybrid point-spread function (hPSF-FLFM) for fast, volumetric, and high-resolution imaging of entire organoids. hPSF-FLFM transforms conventional 3D microscopy and enables exploration of less accessible spatiotemporally-challenging regimes for organoid research. To validate hPSF-FLFM, we demonstrate 3D imaging of rapid responses to extracellular physical cues such as osmotic and mechanical stresses on human induced pluripotent stem cells-derived colon organoids (hCOs). The system offers cellular (2-3 μm and 5-6 μm in x-y and z, respectively) and millisecond-scale spatiotemporal characterization of whole-organoid dynamic changes that span large imaging volumes (>900 μm × 900 μm × 200 μm in x, y, z, respectively). The hPSF-FLFM method provides a promising avenue to explore spatiotemporal-challenging cellular responses in a wide variety of organoid research.


Genetics and genomics to the clinic: a long road ahead.
Advances in genomic technology have produced an explosion of new information about the genetic basis for human disease, fueling extraordinarily high expectations for improved treatments. This perspective will take brief stock of what genetics/genomics have brought to clinical practice to date and what we might expect for the future.


Substance flow analysis on the leachate DOM molecules along five typical membrane advanced treatment processes.
The processes combining biological treatment with membrane separation technologies have been widely adopted for leachate treatment. However, dissolved organic matter (DOM) of leachate membrane concentrates generated from various membrane separation technologies has not been systematically investigated in field scale. Therefore, substance flow analysis based on DOM molecular information of leachate membrane concentrates from primary membrane systems (i.e. nanofiltration (NF) and reverse osmosis (RO)) and secondary membrane systems (i.e. disk-tube reverse osmosis (DTRO) and humic substance filtration system (HSF)) in five engineering-scale leachate treatment facilities, obtained via ultra-performance liquid chromatography coupled with hybrid quadrupole Orbitrap mass spectrometry, was given and simultaneously compared. In NF concentrates (NFC), 45.1-98.5% of DOM originated from raw leachate (L-DOM) was concentrated, showing poor biodegradability. The L-DOM interception characteristics of NFC-fed HSF were mainly based on volume reduction but concentration effect. L-DOM in RO concentrates (ROC) showed a higher proportion of peak intensity reduced components, accounting for 50.3-96.8%, and organic composition changes were more dependent on water quality characteristics than membrane types. ROC-fed DTRO intercepted 49.3-72.6% of L-DOM, but DTRO may be less effective at intercepting DOM molecules in landfill leachate with higher oxidation levels. Considering risks from feasible treatment technologies, the difficulty for the treatment of leachate membrane concentrates followed the order of DTRO concentrates > ROC > NFC. This study suggests that ROC-fed DTRO need to be controlled to avoid amplifying the treatment difficulty. Besides, treatment technologies for RO and DTRO concentrates with low-concentrated but refractory DOM and high salts should be explored.


The airway microbiome mediates the interaction between environmental exposure and respiratory health in humans.
Exposure to environmental pollution influences respiratory health. The role of the airway microbial ecosystem underlying the interaction of exposure and respiratory health remains unclear. Here, through a province-wide chronic obstructive pulmonary disease surveillance program, we conducted a population-based survey of bacterial (n = 1,651) and fungal (n = 719) taxa and metagenomes (n = 1,128) from induced sputum of 1,651 household members in Guangdong, China. We found that cigarette smoking and higher PM2.5 concentration were associated with lung function impairment through the mediation of bacterial and fungal communities, respectively, and that exposure was associated with an enhanced inter-kingdom microbial interaction resembling the pattern seen in chronic obstructive pulmonary disease. Enrichment of Neisseria was associated with a 2.25-fold increased risk of high respiratory symptom burden, coupled with an elevation in Aspergillus, in association with occupational pollution. We developed an individualized microbiome-based health index, which covaried with exposure, respiratory symptoms and diseases, with potential generalizability to global datasets. Our results may inform environmental risk prevention and guide interventions that harness airway microbiome.