Impacts of Neonatal Hospitalization on Families during the 2019 Coronavirus Pandemic.
Limited data are available regarding family and financial well-being among parents whose infants were hospitalized during the 2019 coronavirus (COVID-19) pandemic. The study objective was to evaluate the family and financial well-being of parents whose infants were hospitalized in the neonatal intensive care unit (NICU) during COVID-19. Parents were recruited for this online, cross-sectional survey via support groups on social media. Data collection was completed between May 18, 2020 and July 31, 2020. The final sample consisted of 178 parents, who had an infant hospitalized in an NICU between February 1, 2020 and July 31, 2020. The primary outcomes were impact on family life and financial stability, as measured by the Impact on Family scale, an instrument that evaluates changes to family life as a result of infant or childhood illness. Of the 178 parent respondents, 173 (97%) were mothers, 107 (59.4%) were non-Hispanic White, and 127 (69.5%) of the infants were born prematurely. Parents reported significant family impact and greater financial difficulty. Extremely premature infants, lower household income, parent mental health, and lower parental confidence were predictive of greater impacts on family life. Parents reported significant family and financial impacts during their infant's hospitalization amid COVID-19. Further studies are needed to guide clinical practice and inform family-supportive resources that can mitigate consequences to family well-being. · Impact of infant hospitalization in the context of COVID-19 is largely unknown.. · In a cohort of NICU parents during COVID-19, they reported changes to family life and finances.. · Greater impacts were reported by parents with lower income, confidence, and very premature infants..


Promoting oligodendrogenesis and myelin repair using the multiple sclerosis medication glatiramer acetate.
The formation of oligodendrocytes (oligodendrogenesis) and myelin is regulated by several neurotrophic factors. Strategies to increase the level of these trophic molecules may facilitate repair in demyelinating conditions, such as multiple sclerosis (MS). Because leukocytes are a source of neurotrophic factors, and as glatiramer acetate (GA) generates T helper 2 (Th2) lymphocytes that are not known to be harmful, we tested the hypothesis that GA regulates oligodendrogenesis and myelin formation. First, we generated GA-reactive Th2 cells and determined that they produced transcripts for neurotrophic factors, including insulin-like growth factor-1 (IGF-1). The conditioned medium from GA-reactive T cells elevated IGF-1 protein and promoted the formation of oligodendrocyte precursor cells (OPCs) from embryonic brain-derived forebrain cells in culture. We next subjected mice to lysolecithin-induced demyelination of the spinal cord. At 7 days after the insult, the number of OPCs in the demyelinated dorsal column was higher than that in uninjured controls, and was further increased by the daily s.c. injection with GA. Increased OPC generation by GA was associated temporally with the elevation of IGF-1 and brain-derived neurotrophic factor (BDNF) in the spinal cord. Finally, the resultant remyelination at 28 days was higher in mice treated with GA during the first 7 days of injury compared with vehicle controls. These results indicate that GA promotes oligodendrogenesis and remyelination through mechanisms that involve the elevation of growth factors conducive for repair.


The Roles of Cholesterol and Its Metabolites in Normal and Malignant Hematopoiesis.
Hematopoiesis is sustained throughout life by hematopoietic stem cells (HSCs) that are capable of self-renewal and differentiation into hematopoietic progenitor cells (HPCs). There is accumulating evidence that cholesterol homeostasis is an important factor in the regulation of hematopoiesis. Increased cholesterol levels are known to promote proliferation and mobilization of HSCs, while hypercholesterolemia is associated with expansion of myeloid cells in the peripheral blood and links hematopoiesis with cardiovascular disease. Cholesterol is a precursor to steroid hormones, oxysterols, and bile acids. Among steroid hormones, 17β-estradiol (E2) induces HSC division and E2-estrogen receptor α (ERα) signaling causes sexual dimorphism of HSC division rate. Oxysterols are oxygenated derivatives of cholesterol and key substrates for bile acid synthesis and are considered to be bioactive lipids, and recent studies have begun to reveal their important roles in the hematopoietic and immune systems. 27-Hydroxycholesterol (27HC) acts as an endogenous selective estrogen receptor modulator and induces ERα-dependent HSC mobilization and extramedullary hematopoiesis. 7α,25-dihydroxycholesterol (7α,25HC) acts as a ligand for Epstein-Barr virus-induced gene 2 (EBI2) and directs migration of B cells in the spleen during the adaptive immune response. Bile acids serve as chemical chaperones and alleviate endoplasmic reticulum stress in HSCs. Cholesterol metabolism is dysregulated in hematologic malignancies, and statins, which inhibit de novo cholesterol synthesis, have cytotoxic effects in malignant hematopoietic cells. In this review, recent advances in our understanding of the roles of cholesterol and its metabolites as signaling molecules in the regulation of hematopoiesis and hematologic malignancies are summarized.


The timeline development of female canine germ cells.
During the sex differentiation, the primordial germ cells (PGCs) pass through a differentiation, becoming spermatogonial cells in males and oocytes in females. In this phase, there is difference in gene expression and differentiation potency between males and females. Specific cell markers have been essential in the PGC meiosis beginning and become oocyte cells. However, there are few studies about germline in domestic animals. The domestic dog (Canis lupus familiaris) is an interesting animal model to be used in the investigation about the mammal development because it has several biochemical and physiological similarities to humans. In addition, some additional investigations about dogs may contribute to a better understanding of the biology and genetic components, improving clinical veterinary and zoological sciences. Here, we elucidated by immunofluorescence and quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), the dynamics of the expression of pluripotent (POU5F1 and NANOG) and germline (DDX4, DAZL and DPPA3) markers that are very important in the development of female canine germ cells during 35-50 days post-fertilization (dpf). The female canine germ cells were positive for pluripotent markers during middle developmental period. The number of DDX4, DAZL and DPPA3 cells increased along the germ cell maturation from 45 to 50 dpf. We provided an expression analysis of the pluripotent and germline markers in paraffin sections using the middle and later periods in female canine germ cells. The results can contribute the understanding about the timeline of each marker along the maturation of female canine germ cells. These results have a great significance to demonstrate the germ cell profile changes because it may allow the development of protocols about in vitro germ cell derivation.


The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model.
Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors. However, mechanisms underlying LID occurrence are still unclear. Regulator of G-protein signaling RGS9, a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, has been reported participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we compared the rotational responses and AIMs in 6-OHDA lesioned rats with L-DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days whereas control animals received injections of saline. Furthermore, whether sub-chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion rats were also evaluated. As results shown, rotational behavior was not increased significantly, while an obvious AIMs were observed in rats with L-DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition, expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR with striatal extracts increased significantly after L-DOPA/benserazide. These data demonstrate that RGS9 expression can be modulated by sub-chronic L-DOPA/benserazide administration and increased RGS9 expression in striatum may be one of the reasons for the side effects such as dyskinesia induced by L-DOPA therapy.


A Dwarf Mutant of Arabidopsis Generated by T-DNA Insertion Mutagenesis.
Most plant genes that control complex traits of tissues, organs, and whole plants are uncharacterized. Plant height, structure of reproductive organs, seed development and germination, for example, are traits of great agronomic importance. However, in the absence of knowledge of the gene products, current molecular approaches to isolate these important genes are limited. Infection of germinatng seeds of Arabidopsis thaliana with Agrobacterium results in transformed lines in which the integrated T-DNA from Agrobacterium and its associated kanamycin-resistance trait cosegregate with stable, phenotypic alterations. A survey of 136 transformed lines produced plants segregating in a manner consistent with Mendelian predictions for phenotypes altered in height, flower structure, trichomes, gametogenesis, embryogenesis, and seedling development. This report is the characterization of a dwarf mutant in which the phenotype is inherited as a single recessive nuclear mutation that cosegregates with both the kanamycin-resistance trait and the T-DNA insert.


A study of the effects of column porosity on gradient separations of proteins.
The type of the stationary phase for reversed-phase liquid chromatography significantly affects the sample elution. Hydrodynamic properties, efficiency and gradient elution of proteins were investigated on five commercial C18 columns with wide-pore totally porous particles, with superficially porous layer particles, non-porous particles and a silica-based monolithic bed. The efficiency in the terms of reduced plate height is higher for low-molecular ethylbenzene than for proteins, but depends on the character of the pores in the individual columns tested. The superficially porous Poroshell and the non-porous Micra columns provide the best efficiency for proteins at high mobile phase flow rates, probably because of similar pore architecture in the stationary phase. The Zorbax column with similar pore architecture as the Poroshell active layer, i.e. narrow pore distribution of wider pores shows better efficiency than the packed column with narrow pores and broad pore distribution. The monolithic column shows lower efficiency for proteins at high flow rates, but it performs better than the broad-pore distribution totally porous particulate columns. Different pore architecture affects also the retention and selectivity for proteins on the individual columns. The retention times on all columns can be predicted using the model for reversed-phase gradient elution developed originally for low-molecular compounds. Consideration of the limited pore volume accessible to the biopolymers has negligible effect on the prediction of retention on the columns packed with non-porous or superficially porous particles, but improves the accuracy of the predicted data for the totally porous columns with broad pore distribution.


News in Nanocrystals Seminar: Self-Assembly of Early Career Researchers toward Globally Accessible Nanoscience.
In 2020, many in-person scientific events were canceled due to the COVID-19 pandemic, creating a vacuum in networking and knowledge exchange between scientists. To fill this void in scientific communication, a group of early career nanocrystal enthusiasts launched the virtual seminar series, News in Nanocrystals, in the summer of 2020. By the end of the year, the series had attracted over 850 participants from 46 countries. In this Nano Focus, we describe the process of organizing the News in Nanocrystals seminar series; discuss its growth, emphasizing what the organizers have learned in terms of diversity and accessibility; and provide an outlook for the next steps and future opportunities. This summary and analysis of experiences and learned lessons are intended to inform the broader scientific community, especially those who are looking for avenues to continue fostering discussion and scientific engagement virtually, both during the pandemic and after.


Physical Operations of a Self-Powered IZTO/β-Ga2O3 Schottky Barrier Diode Photodetector.
In this work, a self-powered, solar-blind photodetector, based on InZnSnO (IZTO) as a Schottky contact, was deposited on the top of Si-doped β-Ga2O3 by the sputtering of two-faced targets with InSnO (ITO) as an ohmic contact. A detailed numerical simulation was performed by using the measured J-V characteristics of IZTO/β-Ga2O3 Schottky barrier diodes (SBDs) in the dark. Good agreement between the simulation and the measurement was achieved by studying the effect of the IZTO workfunction, β-Ga2O3 interfacial layer (IL) electron affinity, and the concentrations of interfacial traps. The IZTO/β-Ga2O3 (SBDs) was tested at a wavelength of 255 nm with the photo power density of 1 mW/cm2. A high photo-to-dark current ratio of 3.70×105 and a photoresponsivity of 0.64 mA/W were obtained at 0 V as self-powered operation. Finally, with increasing power density the photocurrent increased, and a 17.80 mA/W responsivity under 10 mW/cm2 was obtained.


Hypothesis testing in animal social networks.
Behavioural ecologists are increasingly using social network analysis to describe the social organisation of animal populations and to test hypotheses. However, the statistical analysis of network data presents a number of challenges. In particular the non-independent nature of the data violates the assumptions of many common statistical approaches. In our opinion there is currently confusion and uncertainty amongst behavioural ecologists concerning the potential pitfalls when hypotheses testing using social network data. Here we review what we consider to be key considerations associated with the analysis of animal social networks and provide a practical guide to the use of null models based on randomisation to control for structure and non-independence in the data.


Highly Stable and Antibacterial Two-Dimensional Tungsten Disulfide Lamellar Membrane for Water Filtration.
Two-dimensional (2D) lamellar membranes consisting of restacked WS2 nanosheets have shown excellent separation properties for water filtration. The stability, antifouling properties, and antibacterial activities of the WS2 laminar membranes were investigated for practical application. We discovered that the separation properties of the WS2 laminar membranes changed slightly after soaking in water for 28 days as well as that of a 45 h-cross-flow filtration, demonstrating an extraordinary operational stability of the WS2 laminar membranes. The remarkable stability is related to the dominant van der Waals interactions between WS2 nanosheets. In addition, the WS2 laminar membranes exhibited excellent antibacterial properties against S. aureus and E. coli with antibacterial rates of 91.3 % and 89.7 %, respectively. These properties of the WS2 laminar membranes make them promising candidates for application in water filtration.


Adherence as a Predictor of Glycemic Control Among Adolescents With Type 1 Diabetes: A Retrospective Study Using Real-world Evidence.
Metabolic control among adolescents with type 1 diabetes mellitus (T1DM) is generally poor. Nonadherence is a contributor to this poor glycemic control, leading to adverse outcomes. The findings of studies reporting the association between adherence and glycemic control are conflicting. This study aimed to assess the level of adherence among adolescents with T1DM and its relationship with glycemic control. This was a retrospective, cross-sectional study that was conducted at Sidra Medicine, a state-of-the-art tertiary health care facility for women and children in Qatar. Mean blood or interstitial glucose monitoring frequency (BGMF) was used to assess adherence level among adolescents with T1DM, whereas glycemic control was assessed via documented glycated hemoglobin A1c (HbA1c). Adolescents who had a mean BGMF of ≥4 checks per day were considered adherent, and those who had an HbA1c level of <7% were considered as having controlled diabetes. Correlational and logistic regression analyses were performed to assess the relationship between adherence and glycemic control, incorporating other covariates into the model. The rate of adherence among adolescents with T1DM in Qatar was 40.9%. Adherent adolescents had significantly lower median HbA1c levels compared with nonadherent adolescents (9.0% vs. 9.7%; P = 0.002). A significant negative correlation was found between BGMF and HbA1c level (correlation coefficient rs = -0.325; P < .001). Approximately 97% of nonadherent adolescents compared with 87% of adherent adolescents had suboptimal diabetes control (HbA1c ≥7%) (P = .016). Furthermore, nonadherent adolescents were 78% less likely to have controlled diabetes compared with adherent adolescents (adjusted odds ratio = 0.221; 95% CI, 0.063-0.778; P = 0.019). The combined effect of the determinants of glycemic control among adolescents with T1DM that were included in the multiple regression model was able to explain approximately 9% of the variances in glycemic control (Cox and Snell R2 = 0.092). The current findings suggest that nonadherence was highly prevalent among adolescents with T1DM and was a significant independent predictor of glycemic control, explaining 9% of the variability. This finding warrants further exploration of other possible predictors of poor glycemic control among the adolescent population. Comprehensive interventions, including educational, technological, and health service delivery aspects, aimed at improving adherence and ultimately optimizing glycemic control are warranted in adolescents with T1DM.


Association between Hippocampal Volume and Working Memory in 10,000+ 9-10-Year-Old Children: Sex Differences.
This study tested sex differences in the association between hippocampal volume and working memory of a national sample of 9-10-year-old children in the US. As the hippocampus is functionally lateralized (especially in task-related activities), we explored the results for the right and the left hippocampus. This is a cross-sectional study using the Adolescent Brain Cognitive Development (ABCD) Study data. This analysis included baseline ABCD data (n = 10,093) of children between ages 9 and 10 years. The predictor variable was right and left hippocampal volume measured by structural magnetic resonance imaging (sMRI). The primary outcome, list sorting working memory, was measured using the NIH toolbox measure. Sex was the moderator. Age, race, ethnicity, household income, parental education, and family structure were the covariates. In the overall sample, larger right (b = 0.0013; p < 0.001) and left (b = 0.0013; p < 0.001) hippocampal volumes were associated with higher children's working memory. Sex had statistically significant interactions with the right (b = -0.0018; p = 0.001) and left (b = -0.0012; p = 0.022) hippocampal volumes on children's working memory. These interactions indicated stronger positive associations between right and left hippocampal volume and working memory for females compared to males. While right and left hippocampal volumes are determinants of children's list sorting working memory, these effects seem to be more salient for female than male children. Research is needed on the role of socialization, sex hormones, and brain functional connectivity as potential mechanisms that may explain the observed sex differences in the role of hippocampal volume as a correlate of working memory.


Use of a portable glucose meter in a Nigerian diabetic clinic.
We assessed the performance of a portable glucose meter in a tropical environment. This was undertaken in an effort to reduce the costs of regular blood glucose measurements for our diabetic patients, many of whom were finding regular laboratory tests financially burdensome. The glucose meter was as accurate as the laboratory up to glucose concentrations of 250 mg/dl (14 mmol/l) but slightly overestimated results above that level. Nevertheless, it gave results comparable to those obtained with similar instruments in temperate countries, with a correlation coefficient of 0.91. Its cheapness, alternative power source from dry battery, use of finger prick capillary rather than venous blood, ease of operation, and quick production of results make it almost ideal for use in developing countries.


Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis.
Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown. In this work, CAD was investigated for its effect on AS using low-density lipoprotein receptor knockout mice and tumor necrosis factor-alpha (TNF-α)-stimulated endothelial cells (ECs). After a 12-week intervention, CAD was found to significantly prevent AS formation in the aortic root and aortic tree, reduce the necrotic core area, and inhibit aortic inflammation and oxidative stress. Moreover, CAD quenched TNF-α-provoked inflammation and oxidative stress in ECs. RNA-sequencing identified nuclear factor erythroid-2 related factor 2 (NFE2L2, NRF2)/heme oxidase 1 (HO1) signaling to be drastically activated by CAD. CAD is a known activator of the aryl hydrocarbon receptor (AHR) which is a transcription factor of the NFE2L2 gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.


Arf GAPs and membrane traffic.
The selective transfer of material between membrane-delimited organelles is mediated by protein-coated vesicles. In many instances, formation of membrane trafficking intermediates is regulated by the GTP-binding protein Arf. Binding and hydrolysis of GTP by Arf was originally linked to the assembly and disassembly of vesicle coats. Arf GTPase-activating proteins (GAPs), a family of proteins that induce hydrolysis of GTP bound to Arf, were therefore proposed to regulate the disassembly and dissociation of vesicle coats. Following the molecular identification of Arf GAPs, the roles for GAPs and GTP hydrolysis have been directly examined. GAPs have been found to bind cargo and known coat proteins as well as directly contribute to vesicle formation, which is consistent with the idea that GAPs function as subunits of coat proteins rather than simply Arf inactivators. In addition, GTP hydrolysis induced by GAPs occurs largely before vesicle formation and is required for sorting. These results are the primary basis for modifications to the classical model for the function of Arf in transport vesicle formation, including a recent proposal that Arf has a proofreading, rather than a structural, role.


Antibacterial activity of Cichorium intybus.
Antibacterial activity of the water, ethanol and ethyl acetate extracts of Cichorium intybus was investigated. All the tested extracts showed antibacterial activity, the ethyl acetate extract being the most active. Water extract inhibits Agrobacterium radiobacter sp. tumefaciens, Erwinia carotovora, Pseudomonas fluorescens and P. aeruginosa.


Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.
To compare preterm delivery rates (before 34 weeks of gestation) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone. Cervical length was measured in patients with risk factors or symptoms of cervical incompetence. Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence, previous preterm premature rupture of membranes before 32 weeks of gestation, history of cold knife conization, diethylstilbestrol exposure, and uterine anomaly. When a cervical length of <25 mm was measured before a gestational age of 27 weeks, a randomization for therapeutic cerclage and bed rest (cerclage group) or bed rest alone (bed rest group) was performed. The analysis is based on intention to treat. Of the 35 women who met the inclusion criteria, 19 were allocated randomly to the cerclage group and 16 to the bed rest group. Both groups were comparable for mean cervical length and mean gestational age at time of randomization, mean overall 20 mm and 21 weeks. Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group (7 of 16 vs none, respectively; P =.002). There was no statistically significant difference in neonatal survival between the groups (13 neonates survived in the bed rest group vs all in the cerclage group). The compound neonatal morbidity, defined as admission to the neonatal intensive care unit or neonatal death, was significantly higher in the bed rest group than in the cerclage group (8 of 16 vs 1 of 19, respectively; P =.005; RR = 9.5, 95% CI, 1.3-68.1). Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and/or symptoms of cervical incompetence and a cervical length of <25 mm before 27 weeks of gestation.


Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.
To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. International, multicenter, retrospective study. Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.


Fetal and maternal manifestations of tuberous sclerosis complex: Value of fetal MRI.
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign hamartomas in various organ systems of the body. Prenatal screening of fetuses of mothers affected with TSC using ultrasonography (US) may detect cardiac lesions. Fetal US is not sensitive for evaluation of the brain. We describe brain MRI findings in a fetus with cardiac rhabdomyomas identified on prenatal screening US. Postnatal brain MRI at 5 days of age demonstrated fetal MRI findings without significant added information. Fetal MRI is the imaging modality of choice for evaluation of cerebral manifestations of TSC. Maternal manifestations of TSC in the abdomen or pelvis may also be demonstrated on fetal MRI.


Secure attachments predict prosocial behaviors: A moderated mediation study.
Previous research has shown that secure attachment promotes prosocial behavior. However, the mechanism underlying the link between attachment and prosocial behavior has received relatively little attention. The current study examined the mechanism underlying the link between attachment and prosocial behavior by specifically focusing on the potential mediating role of moral disengagement and whether this mediation effect is moderated by moral identity. Self-report questionnaires designed to measure attachment, moral identity, moral disengagement, and prosocial behavior were administered to Chinese students (n = 395; 250 females; Mage = 23.38 years). Results showed that secure attachment (maternal attachment, paternal attachment, and peer attachment) was associated with prosocial behavior. In addition, moral disengagement was found to mediate the association between secure attachment and prosocial behavior. Moreover, the mediation effect was moderated by moral identity; specifically, the mediation effect was stronger for individuals with a high level of moral identity than their low-level moral identity counterparts. The present results suggest that morality could explain the association between attachment and prosocial behaviors.


A UK nationwide prospective study of treatment change in MODY: genetic subtype and clinical characteristics predict optimal glycaemic control after discontinuing insulin and metformin.
Treatment change following a genetic diagnosis of MODY is frequently indicated, but little is known about the factors predicting future treatment success. We therefore conducted the first prospective study to determine the impact of a genetic diagnosis on individuals with GCK-, HNF1A- or HNF4A-MODY in the UK, and to identify clinical characteristics predicting treatment success (i.e. HbA1c ≤58 mmol/mol [≤7.5%]) with the recommended treatment at 2 years. This was an observational, prospective, non-selective study of individuals referred to the Exeter Molecular Genetic Laboratory for genetic testing from December 2010 to December 2012. Individuals from the UK with GCK- or HNF1A/HNF4A-MODY who were not on recommended treatment at the time of genetic diagnosis, and who were diagnosed below the age of 30 years and were currently aged less than 50 years, were eligible to participate. A total of 44 of 58 individuals (75.9%) changed treatment following their genetic diagnosis. Eight individuals diagnosed with GCK-MODY stopped all diabetes medication without experiencing any change in HbA1c (49.5 mmol/mol [6.6%] both before the genetic diagnosis and at a median of 1.25 years' follow-up without treatment, p = 0.88). A total of 36 of 49 individuals (73.5%) diagnosed with HNF1A/HNF4A-MODY changed treatment; however, of the 21 of these individuals who were being managed with diet or sulfonylurea alone at 2 years, only 13 (36.1% of the population that changed treatment) had an HbA1c ≤58 mmol/mol (≤7.5%). These individuals had a shorter diabetes duration (median 4.6 vs 18.1 years), lower HbA1c (58 vs 73 mmol/mol [7.5% vs 8.8%]) and lower BMI (median 24.2 vs 26.0 kg/m2) at the time of genetic diagnosis, compared with individuals (n = 23/36) with an HbA1c >58 mmol/mol (>7.5%) (or <58 mmol/mol [<7.5%] on additional treatment) at the 2 year follow-up. Overall, 64% (7/11) individuals with a diabetes duration of ≤11 years and an HbA1c of ≤69 mmol/mol (≤8.5%) at time of the genetic test achieved good glycaemic control (HbA1c ≤58 mmol/mol [≤7.5%]) with diet or sulfonylurea alone at 2 years, compared with no participants with a diabetes duration of >11 years and an HbA1c of >69 mmol/mol (>8.5%) at the time of genetic diagnosis. In participants with GCK-MODY, treatment cessation was universally successful, with no change in HbA1c at follow-up. In those with HNF1A/HNF4A-MODY, a shorter diabetes duration, lower HbA1c and lower BMI at genetic diagnosis predicted successful treatment with sulfonylurea/diet alone, supporting the need for early genetic diagnosis and treatment change. Our study suggests that, in individuals with HNF1A/HNF4A-MODY with a longer duration of diabetes (>11 years) at time of genetic test, rather than ceasing current treatment, a sulfonylurea should be added to existing therapy, particularly in those who are overweight or obese and have a high HbA1c.


Adaptive variation in fall cold hardiness of aspen from northwestern Ontario.
We investigated adaptive variation in fall cold hardiness development based on the electrical conductivity of tissue diffusates (EC) among 20 aspen provenances from northwestern Ontario. Provenance accounted for over 40% of the total variation in cold injury for seven dates from September through November in three provenance trials. Principal component analysis was performed to summarize the combinations of results for all sampling sites, dates and temperatures (traits). Principal component (PC)-1 represented fully developed cold hardiness differences among provenances; PC-2 represented differences in the timing of the onset of cold hardiness development; and PC-3 represented a site-related difference in cold hardiness development. Heat sum in early summer and late summer precipitation together were the best predictors of absolute degree of cold hardiness (PC-1), whereas temperatures for mid- to late summer were best for predicting onset of cold hardiness development (PC-2). In a second study, we assessed the efficacy of chlorophyll fluorescence (CF) as a simpler technique for determining the cold hardiness of aspen stem samples. Fall cold hardiness of stem samples of 12 of the original 20 provenances was estimated by CF, and the results were evaluated by a visual scoring (VS) method. Correlations between EC and CF measurements from the two studies were moderately strong based on the extent of cold hardiness in October of each year, but were negative for September dates because of a later onset of cold hardiness in the EC study year. Although the EC and CF methods gave similar cold hardiness values for stem samples from 12 provenances, the CF method may be preferred to the EC or VS method for species with chlorophyllous stems because of its greater ease of use.


Real-time demonstration of a low-complexity PS scheme for 16QAM-DMT signals in an IM-DD system.
We experimentally demonstrated a low-complexity probabilistic shaping (PS) 16-ary quadrature amplitude modulation (16QAM) scheme based on intra-symbol bit-weighted distribution matching (Intra-SBWDM) for discrete multi-tone (DMT) symbols with field-programmable gate array implementation in an intensity modulation and direct detection (IM-DD) system. Different from the traditional PS scheme such as Gallager many-to-one mapping, hierarchical distribution matching and constant composition distribution matching, the Intra-SBWDM scheme with lower computation and hardware complexity does not need to continuously refine the interval to find the target symbol probability, nor does it need a look-up table, so it does not introduce a large number of extra redundant bits. In our experiment, four PS parameter values (k = 4, 5, 6, and 7) are investigated in a real-time short-reach IM-DD system. 31.87-Gbit/s net bit PS-16QAM-DMT (k = 4) signal transmission is achieved. The results show that the receiver sensitivity in terms of the received optical power of the real-time PS scheme based on Intra-SBWDM (k = 4) over OBTB/20 km standard single-mode fiber can be improved by about 1.8/2.2 dB at the bit error rate (BER) of 3.8 × 10-3, compared to the uniformly-distributed DMT. In addition, the BER is steadily lower than 3.8 × 10-3 during a one-hour measurement for PS-DMT transmission system.


Demosaicking Using a Spatial Reference Image for an Anti-Aliasing Multispectral Filter Array.
Multispectral imaging with a multispectral filter array (MSFA) facilitates snapshot imaging; however, a demosaicking process is required to estimate a fully defined multispectral image based on undersampled sensor data. Undersampling induces aliasing and adverse artifacts in the reconstructed image. To solve this problem, Jia et al. proposed the Fourier spectral filter array (FSFA), which can reduce aliasing. In this paper, we analyze the FSFA and a more generalized anti-aliasing MSFA, and we identify the property that makes MSFAs anti-aliasing. Furthermore, we propose a novel demosaicking method that is a hybrid of frequency-decomposition-based and compressive-sensing-based demosaicking. Anti-aliasing MSFAs enable demosaicking to comprehend the precise spatial structures of an image. The image assists our proposed method in precisely reconstructing images using compressive sensing. Our experimental results demonstrated that the proposed method performs better than the existing demosaicking methods, especially in terms of spatial reconstruction.


[Gefitinib enhances the radiosensitivity of nasopharyngeal carcinoma cell line CNE2 in vitro].
To study the radiosensitizing effect of gefitinib on nasopharyngeal carcinoma cell line CNE2 in vitro. Nasopharyngeal carcinoma cell line CNE2 was cultured in RP2MI 1640. MTT assay was performed to evaluate the cell proliferation changes in response to gefitinib treatment and the radiosensitizing effect of gefitinib. The cell survival curves and sensitive enhancement ratio (SERs) were obtained with a clonogenic assay. Flow cytometry analysis was applied to detect the cell cycle changes and cell apoptosis. MTT assay showed that cells exposed to gefitinib and radiation had a significantly lower survival ratio compared to the cells with radiation exposure only (0.582∓0.012 vs 0.398∓0.016, P=0.002), with a SER of 1.535∓0.134. The S phase cell percentage was significantly decreased and G(2)-M phase cells increased in gefitinib plus radiation group (P=0.000), suggesting a synergistic effect of gefitinib and radiation. Gefitinib can enhance the radiosensitivity of nasopharyngeal carcinoma CNE2 cells in vitro possibly by inhibiting cell proliferation, inducing cell apoptosis, and causing changes in the cell cycle distribution.


Electrically triggered all-or-none Ca(2)+-liberation during action potential in the giant alga Chara.
Electrically triggered action potentials in the giant alga Chara corallina are associated with a transient rise in the concentration of free Ca(2)+ in the cytoplasm (Ca(2)+(cyt)). The present measurements of Ca(2)+(cyt) during membrane excitation show that stimulating pulses of low magnitude (subthreshold pulse) had no perceivable effect on Ca(2)+(cyt). When the strength of a pulse exceeded a narrow threshold (suprathreshold pulse) it evoked the full extent of the Ca(2)+(cyt) elevation. This suggests an all-or-none mechanism for Ca(2)+ mobilization. A transient calcium rise could also be induced by one subthreshold pulse if it was after another subthreshold pulse of the same kind after a suitable interval, i.e., not closer than a few 100 ms and not longer than a few seconds. This dependency of Ca(2)+ mobilization on single and double pulses can be simulated by a model in which a second messenger is produced in a voltage-dependent manner. This second messenger liberates Ca(2)+ from internal stores in an all-or-none manner once a critical concentration (threshold) of the second messenger is exceeded in the cytoplasm. The positive effect of a single suprathreshold pulse and two optimally spaced subthreshold pulses on Ca(2)+ mobilization can be explained on the basis of relative velocity for second messenger production and decomposition as well as the availability of the precursor for the second messenger production. Assuming that inositol-1,4,5,-trisphosphate (IP(3)) is the second messenger in question, the present data provide the major rate constants for IP(3) metabolism.


A reasoned approach to hospital planning in an uncertain world.
The historical approach to planning community hospitals fails to recognize the substantial impact of finance on program decisions. A fundamentally different approach, an approach that involves the chief financial officer in the planning effort, is proposed here. By integrating financial planning within the overall planning effort, a hospital can develop a truly strategic plan based on the best information from everyone on the hospital management team.


Tetrodotoxins (TTXs) and Vibrio alginolyticus in Mussels from Central Adriatic Sea (Italy): Are They Closely Related?
Tetrodotoxins (TTXs), potent neurotoxins, have become an increasing concern in Europe in recent decades, especially because of their presence in mollusks. The European Food Safety Authority published a Scientific Opinion setting a recommended threshold for TTX in mollusks of 44 µg equivalent kg-1 and calling all member states to contribute to an effort to gather data in order to produce a more exhaustive risk assessment. The objective of this work was to assess TTX levels in wild and farmed mussels (Mytilus galloprovincialis) harvested in 2018-2019 along the coastal area of the Marche region in the Central Adriatic Sea (Italy). The presence of Vibrio spp. carrying the non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes, which are suspected to be involved in TTX biosynthesis, was also investigated. Out of 158 mussel samples analyzed by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry (HILIC-MS/MS), 11 (7%) contained the toxins at detectable levels (8-26 µg kg-1) and 3 (2%) contained levels above the EFSA safety threshold (61-76 µg kg-1). Contaminated mussels were all harvested from natural beds in spring or summer. Of the 2019 samples, 70% of them contained V. alginolyticus strains with the NRPS and/or PKS genes. None of the strains containing NRPS and/or PKS genes showed detectable levels of TTXs. TTXs in mussels are not yet a threat in the Marche region nor in Europe, but further investigations are surely needed.


Collector Size or Range Independence of SNR in Fixed-Focus Remote Raman Spectrometry.
When sensitivity allows, remote Raman spectrometers can be operated at a fixed focus with purely electronic (easily multiplexable) range gating. To keep the background small, the system etendue must be minimized. For a maximum range larger than the hyperfocal one, this is done by focusing the system at roughly twice the minimum range at which etendue matching is still required. Under these conditions the etendue varies as the fourth power of the collector diameter, causing the background shot noise to vary as its square. As the signal also varies with the same power, and background noise is usually limiting in this type instrument, the SNR becomes independent of the collector size. Below this minimum etendue-matched range, the transmission at the limiting aperture grows with the square of the range, canceling the inverse square loss of signal with range. The SNR is thus range independent below the minimum etendue matched range and collector size independent above it, with the location of transition being determined by the system etendue and collector diameter. The range of validity of these outrageousstatements is discussed.


[Case of goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS) in a patient with rheumatoid arthritis (RA)].
In early June 2004, a 50-year-old female was admitted to the hospital for slight fever, general fatigue, hemoptysis, dyspnea, and renal dysfunction (serum creatinine[Cr] : 6.05 mg/dL). She had been treated with prednisolone (PSL : 10-20 mg/day) for RA. She was diagnosed with Goodpasture syndrome based on a high titer of anti-glomerular basement membrane antibody (87 EU), and pulmonary hemorrhage. The renal and pulmonary impairments were markedly improved by the pulse therapy, plasma exchange and temporary hemodialysis. However, the Cr level remained at 2.0 mg/dL, indicating nephrotic syndrome. Light microscopy with Periodic acid-Shiff(PAS) staining demonstrated global sclerosis in three of ten glomeruli. Five glomeruli showed the formation of cellular, and fibrocellular crescents, and the formation of fibrous crescents. Tubular damage and interstitial fibrosis were severe. Immunofluorescence microscopy disclosed major depositions of IgG in a linear pattern along the glomerular basement membrane(GBM). Electron microscopy revealed foot process effacement (>50%)and no electron-dense deposits. Therefore, we diagnosed Goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS). Some reports have dealt with the association of RA and Goodpasture syndrome with D-penicillamine, and of RA and antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis with pulmonary hemorrhage, but none has dealt with cases complicated with RA and Goodpasture syndrome associated with MCNS. Accordingly, whether or not there is a causal relationship between RA and Goodpasture syndrome remains obscure, but since the number of reported cases is small, experience with more cases is necessary to clarify this matter.


Ventilator-Associated Pneumonia and Events in Pediatric Intensive Care: A Single Center Study.
Ventilator-associated pneumonia is the second most common nosocomial infection in pediatric intensive care. The Centers for Disease Control and Prevention recently issued diagnosis criteria for pediatric ventilator-associated pneumonia and for ventilator-associated events in adults. The objectives of this pediatric study were to determine the prevalence of ventilator-associated pneumonia using these new Centers for Disease Control and Prevention criteria, to describe the risk factors and management of ventilator-associated pneumonia, and to assess a simpler method to detect ventilator-associated pneumonia with ventilator-associated event in critically ill children. Retrospective, observational, single-center. PICU in a tertiary-care university hospital. Consecutive critically ill children mechanically ventilated for greater than or equal to 48 hours between November 2013 and November 2015. None. Of 304 patients mechanically ventilated for greater than or equal to 48 hours, 284 were included. Among them, 30 (10.6%) met clinical and radiologic Centers for Disease Control and Prevention criteria for ventilator-associated pneumonia, yielding an prevalence of 7/1,000 mechanical ventilation days. Median time from mechanical ventilation onset to ventilator-associated pneumonia diagnosis was 4 days. Semiquantitative culture of tracheal aspirates was the most common microbiological technique. Gram-negative bacteria were found in 60% of patients, with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Antibiotic therapy complied with adult guidelines. Compared with patients without ventilator-associated pneumonia, those with ventilator-associated pneumonia had significantly longer median durations of mechanical ventilation (15 vs 6 d; p < 0.001) and PICU stay (19 vs 9 d; p < 0.001). By univariate analysis, risk factors for ventilator-associated pneumonia were younger age, reintubation, acute respiratory distress syndrome, and continuous enteral feeding. Among the 30 patients with ventilator-associated pneumonia, 17 met adult ventilator-associated event's criteria (sensitivity, 56%). Ventilator-associated pneumonia is associated with longer times on mechanical ventilation and in the PICU. Using the ventilator-associated event criteria is of interest to rapidly screen for ventilator-associated pneumonia in children. However, sensitivity must be improved by adapting these criteria to children.


Epidemiology and control of schistosomiasis in Southeast Asia.
Schistosomiasis in Southeast Asia, caused by Schistosoma japonicum, Schistosoma mekongi and Schistosoma japonicum-like, have been reported from six different countries. The S. japonicum infections are highly prevalent in the Philippines with Oncomelania hupensis quadrasi as the vector snail, and in localized areas in Indonesia with O.h. lindoensis as the snail vector. The S. mekongi infections are recent discovery in the Lower Mekong Basin in Laos and Kampuchea, with Tricula aperta as the vector snail. The S. japonicum-like infections are found as isolated cases diagnosed by the finding of S. japonicum-like eggs in the faeces, rectal biopsy, tissue biopsy or at necropsy in Thailand and Malaysia. The control measures of schistosomiasis have been implemented in the Philippines and Indonesia, while further research studies are being conducted in Thailand and Malaysia.


Pseudomonas haemolytica sp. nov., isolated from raw milk and skimmed milk concentrate.
Two strains, WS 5063T and WS 5067, isolated from raw cow's milk and skimmed milk concentrate, could be affiliated as members of the same, hitherto unknown, Pseudomonas species by 16S rRNA and rpoD gene sequences. Multilocus sequence and average nucleotide identity (ANIm) analyses based on draft genome sequences confirmed the discovery of a novel Pseudomonas species. It was most closely related to Pseudomonas synxantha DSM 18928T with an ANIm of 91.4 %. The DNA G+C content of WS 5063T was 60.0 mol %. Phenotypic characterizations showed that the isolates are rod-shaped, motile, catalase- and oxidase-positive, and aerobic. Growth occurred at 4-34 °C and at pH values of pH 5.5-8.0. Both strains showed strong β-haemolysis on blood agar. The major cellular polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The dominant quinone was Q-9 (90 %), but noticeable amounts of Q-8 (9 %) and traces of Q-7 were also detected. Fatty acid profiles were typical for Pseudomonas species and exhibited C16 : 0 as a major component. Based on these results, we conclude that both strains belong to a novel species, for which the name Pseudomonas haemolytica sp. nov. is proposed. The type strain is WS 5063T (=DSM 108987T=LMG 31232T) and an additional strain is WS 5067 (=DSM 108988=LMG 31233).


GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation.
This study aims to explore the differences of the ovarian stimulation (OS) characteristics, laboratory, and clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol during controlled ovarian hyperstimulation (COH). About 1883 consecutive IVF/ICSI fresh cycles of normal ovarian responders were retrospectively analyzed, with 1229 in the single-dose GnRH agonist protocol group and 654 in the GnRH antagonist protocol group at Reproductive Medical Center of Tongji Hospital from 1 January 2014 to 31 December 2017. The follicular-phase single-dose GnRH agonist group showed significantly more oocytes obtained, higher implantation rate and pregnancy rate, as well as lower luteinizing hormone (LH) level and estradiol (E2)/oocyte ratio on the day of human chorionic gonadotropin (hCG) administration. However, differences were not significant in meiosis II (MII) oocyte rate, two pronuclear zygote (2PN) embryo rate, viable embryo rate or high-quality embryo rate, compared with the GnRH antagonist group. Further comparison of clinical outcomes in the first frozen-thawed cycles did not show significant difference in either implantation or clinical pregnancy rate between the two protocol groups. Follicular-phase single-dose GnRH agonist protocol may achieve better clinical outcomes in normal ovarian responders, which could be explained more by positive effect on endometrial receptivity rather than embryo quality.


Analysis of a Length-Structured Density-Dependent Model for Fish.
We present a length-structured matrix model for fish populations in which the probability that a fish grows into the next length class is a decreasing nonlinear function of the total biomass of the population. We present mathematical results classifying the dynamics that this density-dependent model predicts. We illustrate these results with numerical simulations for an invasive white perch population and show how the mathematical results can be used to predict the persistence and/or boundedness of the population as well as an equilibrium structure that is dominated by small fish. We illustrate the results with management recommendations for an invasive white perch population.


Organization and expression of the mouse spot35/calbindin-D28k gene: identification of the vitamin D-responsive promoter region.
Spot35/calbindin-D28k is transcriptionally induced by 1,25-dihydroxyvitamin D3 in the intestine and kidney but not the brain. The structural organization of the mouse calbindin-D28k gene has now been determined and its transcriptional activation examined. Two direct repeat motifs homologous to other vitamin D-responsive elements were identified at positions -2295 to -2281 and -1160 to -1146. Undirectional deletion analyses of the 5' flanking region indicated that the sequence between -1339 and -1038 conferred vitamin D sensitivity on a reporter construct. Furthermore, the proximal (AGGTGAtgaAAGTCA), but not the distal (AGGTGAacaGGTTCA), direct repeat enhanced 1,25(OH)2D3-stimulated transcription in an orientation-dependent manner when placed upstream of the heterologous SV40 promoter. In conclusion, the proximal direct repeat plays a critical role in mediating the vitamin D-induced expression of calbindin-D28k in the kidney.


[The study of the ultrastructure of the female reproductive system in a parasite of bats Allassogonoporus amphoraeformis (Digenea: Allassogonoporidae)].
The morphology and fine structure of the female reproductive system of allassogonoporid trematode Allassogonoporus amphoraeformis have been described for the first time. The ovary consists of the germ cells being at various developmental stages and supporting cells of two types. The oviduct, seminal receptacle with its short duct and the proximal portion of Laurer's canal are lined by flattened cellular epithelium with lamellae and cilia on its luminal surface and well-developed basal infoldings. The distal part of Laurer's canal and metraterm are tegumental in structure and are characterized by sparse secretory inclusions and lacking of spines. Mehlis' glands of two types open into ootype. The uterus wall is composed of highly flattened epithelial cells surrounded by basal lamina and sparse muscle bundles. Vitelline lobules consist only of the vitelline cells at various developmental stages. The mature vitelline cells contain two types of inclusions: vitelline droplets and rarely scattered lipids. Vitelline ducts are lined by cellular epithelium with highly folded luminal surface and devoid of cilia. Presented results are compared with earlier obtained data on other lecithodendrioiden trematode Prosthodendrium ascidia ([symbol: see text], 1990).


Virus shedding and potential for interspecies waterborne transmission of highly pathogenic H5N1 influenza virus in sparrows and chickens.
To elucidate the role of sparrows as intermediate hosts of highly pathogenic avian influenza H5N1 viruses, we assessed shedding and interspecies waterborne transmission of A/duck/Laos/25/06 in sparrows and chickens. Inoculated birds shed virus at high titers from the oropharynx and cloaca, and infection was fatal. Waterborne transmission from inoculated sparrows to contact chickens was absent, while 25% of sparrows were infected via waterborne transmission from chickens. The viral shedding and susceptibility to infection we observed in sparrows, coupled with their presence in poultry houses, could facilitate virus spread among poultry and wild birds in the face of an H5N1 influenza virus outbreak.


CBX3 promotes colon cancer cell proliferation by CDK6 kinase-independent function during cell cycle.
Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6. Our results demonstrate a key role of CBX3 in colon carcinogenesis via suppressing the expression of CDK6/p21, which may disrupt the role of CDK6 in transcriptionally regulating p21, as part of a negative feedback loop to limit CDK6 excessive activation.


Effect of P-450scc inhibitors on corticosterone production by rat adrenal cells.
Suspensions of rat adrenocortical cells produce corticosterone as the major glucocorticoid. Cholesterol side-chain cleavage, the initial and rate-limiting step in the glucocorticoid biosynthetic pathway, is catalyzed by P-450scc. We have examined the effect of a variety of P-450scc inhibitors on corticosterone production by isolated rat adrenocortical cells. These inhibitors include reversible, noncovalently interacting inhibitors as well as mechanism-based inhibitors which irreversibly inactivate P-450scc in vitro. (20S)-22-nor-22-thiacholesterol and (22R)-22-aminocholesterol cause 50% inhibition of corticosterone production at 4 microM and 30 nM, respectively. Inhibition by these compounds was essentially not time-dependent. (20R)-20-(1-hexynyl)-pregn-5-en-3 beta, 20-diol and (20R)-20-(1,5-hexdiynyl)-pregn-5-en-3 beta, 20-diol at 10 microM inhibited corticosterone production in a time-dependent manner, resulting in 30% inhibition of corticosterone production during a 100-min incubation. (20S)-20-(2-trimethylsilyl ethyl)-pregn-5-en-3 beta, 20-diol inhibited in a strongly time-dependent manner. At 10 microM this compound irreversibly inhibited more than 90% of the side-chain cleavage capacity of the cell during a 40-min incubation. Cells treated with this steroid did not regain their capacity for side-chain cleavage after removal of free steroid. None of the inhibitors described above inhibited production of corticosterone by cells supplied with pregnenolone, the product of the P-450scc reaction. We suggest that the only significant effect of these compounds under these conditions is inhibition of the side-chain cleavage enzyme.


Korean nursing students' ethical problems and ethical decision making.
This Korean study replicated a previously published American study. The conceptual framework and method combined ethical enquiry and phenomenology. The research questions were: (1) What is nursing students' experience of ethical problems involving nursing practice? and, (2) What is nursing students' experience of using an ethical decision-making model? The participants were 97 senior baccalaureate nursing students, each of whom described one ethical problem and chose to use one of five ethical decision-making models. From 97 ethical problems, five content categories emerged, the largest being health professionals (69%). The basic nature of the ethical problems was the students' experience of conflict, resolution and rationale. Using an ethical decision-making model helped 94% of the students. A comparison of the Korean and American results yields important implications for nursing ethics education, practice and research.


Mapping oncology services in regional and rural Australia.
To map clinical oncology services in regional and rural Australia. A self-administered survey was sent to 161 regional hospitals administering chemotherapy (RHAC) in Australia. RHAC were categorised by state, Hospital Peer Group and the Australian Standard Geographical Classification (ASGC) Remoteness Areas classification. Survey data provided percentage and aggregate figures about availability of medical, radiation and surgical oncologists, chemotherapy nurses, breast cancer nurses, palliative care physicians and allied health professionals according to remoteness and state. Chemotherapy prescribing practices, adherence to occupational health and safety guidelines and availability of multidisciplinary clinics were also explored. A 98% survey completion rate was achieved. Significant deficiencies in service provision were identified in RHAC. Only 21% of RHAC reported a resident medical oncology service, 7% had a radiation oncology unit, and 6% had a resident surgical oncologist. Only 24% of RHAC reported a dedicated palliative care specialist and 39% identified a dedicated oncology counselling service. Other issues included administration of chemotherapy by nurses outside a recognised facility or by nurses without recognised oncology training, limited availability of funded breast care nurses and lack of multidisciplinary clinics. Survey data highlight marked cancer service deficiencies in rural and regional Australia. It is not unreasonable to conclude that these deficiencies might contribute to poorer outcomes for cancer patients living in these areas. The results suggest the need for short- and long-term measures to improve access to best-practice cancer services for patients living in regional, rural and remote areas of Australia.


Benefits of haemoglobin in the cladoceran crustacean Daphnia magna.
To determine the contribution of haemoglobin (Hb) to the hypoxia-tolerance of Daphnia magna, we exposed Hb-poor and Hb-rich individuals (2.4-2.8 mm long) to a stepwise decrease in ambient oxygen partial pressure (P(O(2)amb)) over a period of 51 min from normoxia (20.56 kPa) to anoxia (<0.27 kPa) and looked for differences in their physiological performance. The haem-based concentrations of Hb in the haemolymph were 49 micromol l(-1) in Hb-poor and 337 micromol l(-1) in Hb-rich animals, respectively. The experimental apparatus made simultaneous measurement of appendage beating rate (fA), NADH fluorescence intensity (I(NADH)) of the appendage muscles, heart rate (fH) and in vivo Hb oxygen-saturation possible. In response to progressive, moderate hypoxia, both groups showed pronounced tachycardia and a slight decrease in fA. The fA and fH of Hb-rich animals were generally 4-6 % lower than those of Hb-poor animals. In addition, Hb-rich animals showed a significant decrease in the P(O(2)amb) at which the Hb in the heart region was half-saturated and a striking reduction in the critical P(O(2)amb) of appendage-related variables. In Hb-poor animals, the I(NADH) signal indicated that the oxygen supply to the limb muscle tissue started to become impeded at a critical P(O(2)amb) of 4.75 kPa, although the high level of fA was largely maintained until 1.77 kPa. The obvious discrepancy between these two critical P(O(2)amb) values suggested an anaerobic supplementation of energy provision in the range 4.75-1.77 kPa. The fact that I(NADH) of Hb-rich animals did not rise until P(O(2)amb) fell below 1.32 kPa strongly suggests that the extra Hb available to Hb-rich animals ensured an adequate oxygen supply to the limb muscle tissue in the P(O(2)amb) range 4.75-1.32 kPa. This finding illustrates the physiological benefit of Hb in enabling the animal to sustain its aerobic metabolism as the energetically most efficient mode of fuel utilization under conditions of reduced oxygen availability.


Choke or thrive? The relation between salivary cortisol and math performance depends on individual differences in working memory and math-anxiety.
In the current study, we explored how a person's physiological arousal relates to their performance in a challenging math situation as a function of individual differences in working memory (WM) capacity and math-anxiety. Participants completed demanding math problems before and after which salivary cortisol, an index of arousal, was measured. The performance of lower WM individuals did not depend on cortisol concentration or math-anxiety. For higher WM individuals high in math-anxiety, the higher their concentration of salivary cortisol following the math task, the worse their performance. In contrast, for higher WM individuals lower in math-anxiety, the higher their salivary cortisol concentrations, the better their performance. For individuals who have the capacity to perform at a high-level (higher WMs), whether physiological arousal will lead an individual to choke or thrive depends on math-anxiety.


Precision of incidence predictions based on Poisson distributed observations.
Disease incidence predictions are useful for a number of administrative and scientific purposes. The simplest ones are made using trend extrapolation, on either an arithmetic or a logarithmic scale. This paper shows how approximate confidence prediction intervals can be calculated for such predictions, both for the total number of cases and for the age-adjusted incidence rates, by assuming Poisson distribution of the age and period specific numbers of incident cases. Generalizations for prediction models, for example, using power families and extra-Poisson variation, are also presented. Cancer incidence predictions for the Stockholm-Gotland Oncological Region in Sweden are used as an example.


High-efficiency peroxidase mimics for fluorescence detection of H2O2 and L-cysteine.
Enzyme-based sensing platforms have undergone rapid development in the field of diagnosis and bioanalysis. Here we present a novel fluorescent artificial enzyme-based detection strategy for L-cysteine (Cys) and H2O2 by fabricating a series of Au-Ag bimetallic nanoparticles with peroxidase-like activity. Taking advantage of the enhanced performance of catalysts by optimizing the surface structure, the sensitive detection of Cys with an ultralow detection limit of 0.035 μM and accurate quantification in the range of 0.075-2 μM were achieved. It was revealed that the mechanism of the catalytic process on the Au-Ag surface follows the electron transfer mechanism rather than active species, that is the peroxidase-like catalysts work as electron transfer intermediates and the electron transfer efficiency will increase with the larger electron cloud density of active sites derived from the electronic synergistic effect between Au and Ag, contributing to the enhanced catalytic activity of peroxidase mimics. This finding could provide guidance for the structural design of high-activity peroxidase mimics.


Functional pectoralis minor muscle flap transplantation for reconstruction of thumb opposition: an anatomic study and clinical applications.
In this report, we present the results of an anatomic study on the dimensions of the pectoralis minor muscle and its neurovascular supply in 10 adult human cadavers, in attempt to evaluate the feasibility of microsurgical transplantation of a part of the muscle for thumb opposition reconstruction. A series of five patients consequently underwent thenar reconstruction with the pectoralis minor muscle flap from December 2004 to October 2006. The transferred muscle was reinnervated with the third lumbrical branch of the ulnar nerve. Follow-up assessment showed that the patients recovered functional opposition of carpometacarpal joint with 24 degrees of pronation, and a muscle power with M4 to M5. All patients were satisfied with the appearance of reconstructed thenar eminence. We recommend this new technique for thenar and opposition reconstruction in patients who have severe loss of thenar muscles, injury to the median nerve, and wish to improve the appearance of thenar eminence.


Velocity synchronized fourier transform hologram camera system.
Methods for recording holograms of hypervelocity particles were studied. It was assumed that the particle would move an appreciable distance during the exposure time. The problem was to find a method of maintaining stationary hologram interference fringes as the object moved within the field of view. A Fourier transform method employing an interferometer and using a reference beam produced by back reflection from the object was found to be conceptually correct. The stationarity of the approach was demonstrated experimentally. It was also proven possible to change arbitrarily the position of the reconstructed image relative to the hologram axis.


Economics of autonomous equipment for arable farms.
By collecting more data at a higher resolution and by creating the capacity to implement detailed crop management, autonomous crop equipment has the potential to revolutionise precision agriculture (PA), but unless farmers find autonomous equipment profitable it is unlikely to be widely adopted. The objective of this study was to identify the potential economic implications of autonomous crop equipment for arable agriculture using a grain-oilseed farm in the United Kingdom as an example. The study is possible because the Hands Free Hectare (HFH) demonstration project at Harper Adams University has produced grain with autonomous equipment since 2017. That practical experience showed the technical feasibility of autonomous grain production and provides parameters for farm-level linear programming (LP) to estimate farm management opportunities when autonomous equipment is available. The study shows that arable crop production with autonomous equipment is technically and economically feasible, allowing medium size farms to approach minimum per unit production cost levels. The ability to achieve minimum production costs at relatively modest farm size means that the pressure to "get big or get out" will diminish. Costs of production that are internationally competitive will mean reduced need for government subsidies and greater independence for farmers. The ability of autonomous equipment to achieve minimum production costs even on small, irregularly shaped fields will improve environmental performance of crop agriculture by reducing pressure to remove hedges, fell infield trees and enlarge fields. The online version contains supplementary material available at 10.1007/s11119-021-09822-x.


In vitro evaluation on the antioxidant capacity of triethylchebulate, an aglycone from Terminalia chebula Retz fruit.
To evaluate the antioxidant and free-radical scavenging activities of triethylchebulate (TCL), an aglycone isolated from the fruit of Terminalia chebula Retz. Microsomes, mitochondria and red blood cells (RBCs) were isolated from rat liver. The antioxidant capacities were evaluated by determining the inhibitory effects of TCL on lipid peroxidation, hydrogen peroxide (H(2)O(2))-induced RBCs hemolysis and RBCs autoxidative hemolysis. The free-radical scavenging activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and 2´,7´-dichlorodihydrofluorescin diacetate (DCFH(2)-DA) assay. TCL significantly inhibited FeSO(4)/Cys-induced microsomes lipid peroxidation and protected both H(2)O(2-)-induced RBCs hemolysis and RBCs auto-hemolysis in a dose-dependent manner. Furthermore, TCL demonstrated potent DPPH free-radical scavenging ability with IC(50) at 2.4×10(-5) M. In addition, TCL also moderately suppressed azide-induced mitochondria ROS formation. These results demonstrated that TCL was a strong antioxidant and free-radical scavenger, which might contribute to the anti-oxidative ability of Terminalia chebula Retz.


The Use of the ICF Classification Sheet to Assess Cognitive-Behavioral Disorders and Verbal Communication in Patients after Ischemic and Hemorrhagic Stroke during Rehabilitation.
Background: In patients after experiencing stroke, the cognitive-behavioral deficits and disorders of verbal communication limit the effectiveness of rehabilitation. The key is to diagnose them at an early stage of rehabilitation and to implement appropriate psychological and speech therapy. Objective: Identify differences in the frequency and effectiveness of cognitive-behavioral disorder therapy depending on the clinical type of stroke, assessed before and after rehabilitation treatment, and their presentation using the ICF (International Classification of Functioning, Disability, and Health) classification. Materials and Methods: The study was prospective and included the analysis of cognitive-behavioral and verbal communication disorders. The study consisted of 47 patients after intracerebral hemorrhage (ICH) and 47 patients after an ischemic stroke (IS) before the implementation of rehabilitation and after completing a 4-week rehabilitation. Results: In the group after ICH, psychological therapy significantly reduced the disturbances of consciousness and orientation (p < 0.001) and improved the speed of performing tasks in tests (p < 0.001). In patients after IS and ICH, memory and attention function improved significantly (p < 0.001). Moreover, in patients after ICH, language function deficits decreased significantly (p = 0.018). Mood disturbances were maintained in 17% of patients after ICH and 40% of patients after IS (p = 0.007). Speech therapy reduced speech articulation disorders and aphasia in 85% of patients after ICH (p = 0.001) and in 68% of patients after IS (p = 0.033). Conclusions: The frequency and type of cognitive-behavioral and verbal communication disorders vary depending on the history of ICH or IS. The ICF classification may be useful in assessing and analyzing cognitive-behavioral and verbal communication disorders, which may lead to the implementation of appropriate psychological and speech therapy at an early stage of rehabilitation and increase the effectiveness of the therapy.


Kawasaki Disease: Unusual Presentation with Retropharyngeal Involvement.
Kawasaki disease is an acute febrile generalized vasculitic syndrome of childhood of unknown ethology. The most severe complication may involve the hearth and include acute myocarditis with hearth failure, arrythmia, and coronary artery aneurism. The typical clinical symptoms are fever, conjunctivitis, rash, cervical lymphadenopathy, and mucocutaneous changes, and the diagnosis is made by the clinical criteria. Early use of aspirin and immunoglobuline improves symptoms and prevent heart complications. Case Presentation. A 4-year-old male presented to our attention for multiple unilateral laterocervical lymphadenopathies, odynophagia, and neck stiffness, initially treated with IV antibiotic therapy with partial resolution of symptoms. After four months he made a new ER access for cervicalgia, tonsils asymmetry, trismus, stiff neck, lameness, and phalanx hyperaemia and increase in the size of cervical lymph nodes. Radiology showed increase of lymphnodes dimension and retropharyngeal space asymmetry. The same day heart murmur appeared, so the patient underwent cardiological evaluation that documented dilation of the coronary arteries. This sign made it possible to place the diagnostic suspicion of Kawasaki disease and to start IV immunoglobulins and acetylsalicylic acid administration with prompt response. Kawasaki disease presents with a range of symptoms which, taken individually, are very common in childhood. One of these symptoms is represented by the swollen of neck lymph nodes. It is only clinical reasoning that leads to the correct diagnosis, and therefore, to the correct setting of the therapy, reducing the risk of complications.


A lattice model of vitrification and gelation.
In this work we introduce a simple lattice model with T-shaped molecules in two dimensions that exhibits a rich range of morphological behaviors. Depending on the volume fraction and quench path, this system can adopt uniform liquid, solution, and phase-separated states, as well as inhomogeneous glass or gel-like states, as revealed by dynamic mean-field simulations. An important characteristic of this system is the existence of a large number of degenerate low-energy states with small barriers that leads to a broad, kinetically explored landscape. The mean-field stability and phase diagram of this model is constructed and provides a useful guide for understanding the complex behaviors of the system. One striking feature is that there is a cascade of instabilities that converge to mark the onset of what we identify as the glass transition. Both dynamic mean-field and Monte Carlo simulations reveal glass-like relaxation dynamics. Our results lead to a picture of gelation as a continuation of the glass transition into the two-phase region, or equivalently, as an incomplete phase separation arrested by the onset of the glass transition.


Determining a detectable threshold of signal intensity in cDNA microarray based on accumulated distribution.
In microarray data mining, one of the key problems is how to handle weak signals. Based on a bent piecewise linear accumulated distribution generally found in the microarray data, a new detectable threshold finding method is proposed to filter genes with unreliable information in this paper. More reliable and reproducible data is produced for the subsequent data mining.


Clinicopathological Significance, Related Molecular Changes and Tumor Immune Response Analysis of the Abnormal SWI/SNF Complex Subunit PBRM1 in Gastric Adenocarcinoma.
Background: PBRM1 gene abnormalities were recently found to play a role in tumor development and tumor immune activity. This article will explore the clinicopathological and molecular changes and tumor immune activity of the abnormal SWI/SNF complex subunit PBRM1 in gastric adenocarcinoma (GAC) and its significance. Methods: The cBioPortal, LinkedOmics and TISIDB datasets were used to analyze the abnormality of the PBRM1 gene in GAC and its relationship with prognosis, related molecular changes and tumor-infiltrating lymphocytes (TILs). In addition, 198 GAC cases were collected to further study the relationship between the loss/attenuation of PBRM1 expression and clinicopathology, prognosis, microsatellite stability, PD-L1 expression and TIL in GAC. DNA whole-exome sequencing was performed on 7 cases of gastric cancer with loss of PBRM1 expression. Results: The cBioPortal data showed that PBRM1 deletion/mutation accounted for 7.32% of GAC and was significantly associated with several molecular changes, such as molecular subtypes of GAC. The LinkedOmics dataset showed that PBRM1 mutation and its promoter DNA methylation showed lower PBRM1 mRNA expression, and PBRM1 mutation cases showed significantly higher mRNA expression of PD-L1 (CD274). TISIDB data showed that PBRM1 abnormalities were significantly positively associated with multiple TILs. In our group of 198 cases, the loss/attenuation of PBRM1 expression was significantly positively correlated with intra-tumoral tumor infiltrating lymphocytes (iTILs) and deficient MMR and PD-L1 expression. Kaplan-Meier survival analysis showed that the overall survival of GAC patients with loss/attenuation of PBRM1 expression was significantly better (p = 0.023). iTIL was an independent prognostic factor of GAC. Loss of PBRM1 expression often co-occurs with mutations in other SWI/SNF complex subunit genes, and there are some repetitive KEGG signaling changes. Conclusion: Abnormality of the PBRM1 gene may be related to the occurrence of some GACs and can affect tumor immune activity, thereby affecting clinicopathology and prognosis. It may be a potentially effective predictive marker for immunotherapy and a novel therapeutic approach associated with synthetic lethality.


Visible Light Photoelectrochemical Sensor for Dopamine: Determination Using Iron Vanadate Modified Electrode.
This study reports a facile approach for constructing low-cost and remarkable electroactivity iron vanadate (Fe-V-O) semiconductor material to be used as a photoelectrochemical sensor for dopamine detection. The structure and morphology of the iron vanadate obtained by the Successive Ionic Adsorption and Reaction process were critically characterized, and the photoelectrochemical characterization showed a high photoelectroactivity of the photoanode in visible light irradiation. Under best conditions, dopamine was detected by chronoamperometry at +0.35 V vs. Ag/AgCl, achieving two linear response ranges (between 1.21 and 30.32 μmol L-1, and between 30.32 and 72.77 μmol L-1). The limits of detection and quantification were 0.34 and 1.12 μmol L-1, respectively. Besides, the accuracy of the proposed electrode was assessed by determining dopamine in artificial cerebrospinal fluid, obtaining recovery values ranging from 98.7 to 102.4%. The selectivity was also evaluated by dopamine detection against several interferent species, demonstrating good precision and promising application for the proposed method. Furthermore, DFT-based electronic structure calculations were also conducted to help the interpretation. The dominant dopamine species were determined according to the experimental conditions, and their interaction with the iron vanadate photoanode was proposed. The improved light-induced DOP detection was likewise evaluated regarding the charge transfer process.


Characterization and role of lentivirus-associated host proteins.
Enveloped viruses obtain their envelopes during the process of budding from infected cells. During this process, however, these viruses acquire parts of the host cell membranes and host cell-derived proteins as integral parts of their mature envelopes. These host-derived components of viral envelopes may subsequently exhibit various effects on the life cycle of the virus; virus cell interactions, especially host response to virus-incorporated self-proteins; and the pathogenesis of the disease induced by these viruses. Although it was known for some time that various viruses incorporate host cell-derived proteins, the issue of the role of these proteins has received increased attention, specifically in connection with human immunodeficiency virus (HIV) infection and development of acquired immunodeficiency syndrome (AIDS) in humans. The aim of this review is to summarize our current knowledge of the analysis and role of host-derived proteins associated with enveloped viruses, with emphasis on the potential role of these proteins in the pathogenesis of AIDS. Clearly, differences in the clinical outcome of those nonhuman primates infected with simian immunodeficiency virus (SIV) that are disease resistant compared with SIV-infected species that are disease susceptible provide a unique opportunity to determine whether differences in the incorporation of distinct sets of host proteins play a role with distinct clinical outcomes.


Health-Related Quality of Life and Experiences of Brazilian Celiac Individuals over the Course of the Sars-Cov-2 Pandemic.
Since the end of 2019, the world has been facing an unpredicted COVID-19 pandemic with consequences for the economy, environment, society, and health. The COVID-19 pandemic has increased the risk of death, bringing unbearable psychological pressure upon people worldwide. For celiac patients, the pandemic may represent an additional burden concerning the inherent aspects of celiac disease (CD) that compromise these individuals' quality of life (QoL). Therefore, the objective of this study was to evaluate Brazilian celiac patients' QoL during the course of the COVID-19 pandemic caused by its outbreak and rapid spread and subsequent restrictive measures in addition to the dietary restrictions and other burdens caused by CD. This country-wide cross-sectional study was conducted using a self-administered instrument previously validated in Brazilian-Portuguese to investigate the QoL of individuals with CD. Data collected through the online self-administration of the Brazilian version of the celiac disease quality of life questionnaire (CDQ) comprised 674 CD individuals' responses. Although pandemics have historically posed a challenge for Brazilian population, this period was not associated with a negative impact on Brazilian CD individuals' QoL. During the pandemic, the QoL of Brazilian's with CD was more affected by gastrointestinal aspects than emotions and social aspects and worries. Gender, age, marital status, having (or not) children, occupation, and a positive test for COVID-19 did not affect CD individuals' QoL. However, the study revealed a larger burden and diminished QoL for individuals not following a gluten-free diet and those using antidepressants. Additional research is necessary to verify how the length of the pandemic will affect celiac individuals and then compare those outcomes compare to the COVID-19 period and after.


Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.
To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.


Fetal and uteroplacental flow velocity waveforms and placental grading.
Doppler studies were performed on umbilical, fetal internal carotid, and arcuate arteries within 36 to 40 weeks of gestation in 85 women (66 with healthy pregnancies and 18 complicated by growth retardation, and results were analyzed by calculating the pulsatility index. In each case the placenta was examined and graded sonographically. No significant correlation was found between pulsatility index in fetal and uteroplacental vessels and placental grading in normal pregnancies. This suggests that tissue changes responsible for the echogenicity of maturing placenta are not directly related to vascular impedance of the placental vascular bed.


Simulation of hip operations and design of custom-made endoprostheses using virtual reality techniques.
In this paper a system for the virtual planning of hip operations with endoprosthetic reconstruction and its application in bone tumor surgery is described. The system enables the simulation of the operation and the construction of a custom-made implant depending on the chosen resection planes and the patient's anatomy. During the planning process integrated virtual reality techniques facilitate the interaction with the three-dimensional (3D) medical objects. Stereo viewing improves the perception of the 3D nature of bone structures and tumors. In comparison to conventional planning procedures, different operation strategies and their influence on the geometry of the custom-made endoprosthesis can be easily compared. Furthermore, the combination of multi-modal image information (CT and MR) enables an accurate 3D visualization of the bone tumor within the bone.


Enhanced MET Translation and Signaling Sustains K-Ras-Driven Proliferation under Anchorage-Independent Growth Conditions.
Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to chemotherapeutic drugs as well as molecular targeting agents. Although numerous approaches are ongoing to find effective ways to treat these tumors, there are still no effective therapies for K-Ras mutant cancer patients. Here we report that K-Ras mutant cancers are more dependent on K-Ras in anchorage-independent culture conditions than in monolayer culture conditions. In seeking to determine mechanisms that contribute to the K-Ras dependency in anchorage-independent culture conditions, we discovered the involvement of Met in K-Ras-dependent, anchorage-independent cell growth. The Met signaling pathway is enhanced and plays an indispensable role in anchorage-independent growth even in cells in which Met is not amplified. Indeed, Met expression is elevated under anchorage-independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, in spite of a global downregulation of mRNA translation during anchorage-independent growth, we find that Met mRNA translation is specifically enhanced under these conditions. Importantly, ectopic expression of an active Met mutant rescues K-Ras ablation-derived growth suppression, indicating that K-Ras-mediated Met expression drives "K-Ras addiction" in anchorage-independent conditions. Our results indicate that enhanced Met expression and signaling is essential for anchorage-independent growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors of Met could be effective for K-Ras mutant tumor patients.


ADP-dependent platelet function prior to and in the early course of pediatric liver transplantation and persisting thrombocytopenia are positively correlated with ischemia/reperfusion injury.
Little is known about the role of platelets in relation to ischemia/reperfusion injury (IRI) of the liver graft especially in children. Thrombocyte function was prospectively analysed in 21 consecutive pediatric liver transplantation (pLT) patients by platelet aggregometry secondary to adenosine diphosphate (ADP), collagen, and the von Willebrand factor activator ristocetin (VWF:rco). Post-OP serum levels of ALT were used to divide patients into groups with high (highHD, n = 8) and low (lowHD, n = 13) hepatocellular damage. Clinically, highHD-patients showed impaired plasmatic coagulation and elevated serum bilirubin levels early after pLT when compared with lowHD-patients. Further, platelet counts markedly decreased between pre-OP and postreperfusion (postrep.) in the highHD group (P = 0.003) and did not recuperate by POD6. In lowHD individuals thrombocytopenia improved from both pre-OP (P < 0.05) and postrep. (P < 0.001) respectively towards POD6. Experimental thrombocyte testing revealed that before graft reperfusion only ADP-dependent platelet aggregation correlated with reperfusion injury, thrombocytopenia and early graft function. During the first 48 h after graft reperfusion, all inducers tested demonstrated elevated platelet aggregation levels in the highHD group. Our data suggest a possible role of platelets and their aggregative status in liver IRI subsequent to clinical pLT. Reperfusion-independent ADP-triggered platelet function may be a determinant for IRI in the pediatric hepatic graft recipient.


Electrokinetic Size-Based Spatial Separation of Micro/Nanospheres Using Paper-Based 3D Origami Preconcentrator.
Sample preparation steps (e.g., preconcentration and separation) are key to enhancing sensitivity and reliability in biomedical and analytical chemistry. However, conventional methods (e.g., ultracentrifugation) cause significant loss of sample as well as their contamination. In this study, we developed a paper-based three-dimensional (3D) origami ion concentration polarization preconcentrator (POP) for highly efficient and facile sample preparation. The unique design of POP enables simultaneous preconcentration and spatial separation of target analytes rapidly and economically. The POP comprises accordion-like multifolded layers with convergent wicking areas that can separate analytes based on their sizes in different layers, which can then be easily isolated by unfolding the POP. We first demonstrated 100-fold preconcentration of albumin and its isolation on the specific layers. Then, we demonstrated the simultaneous preconcentration and spatial separation of microspheres of three different sizes (with diameters of 0.02, 0.2, and 2 μm) on the different layers.


A traction control strategy with an efficiency model in a distributed driving electric vehicle.
Both active safety and fuel economy are important issues for vehicles. This paper focuses on a traction control strategy with an efficiency model in a distributed driving electric vehicle. In emergency situation, a sliding mode control algorithm was employed to achieve antislip control through keeping the wheels' slip ratios below 20%. For general longitudinal driving cases, an efficiency model aiming at improving the fuel economy was built through an offline optimization stream within the two-dimensional design space composed of the acceleration pedal signal and the vehicle speed. The sliding mode control strategy for the joint roads and the efficiency model for the typical drive cycles were simulated. Simulation results show that the proposed driving control approach has the potential to apply to different road surfaces. It keeps the wheels' slip ratios within the stable zone and improves the fuel economy on the premise of tracking the driver's intention.


Gender-Oriented Mental Health Prevention: A Reappraisal.
Many studies have investigated the impact of gender on mental health, but only a few have addressed gender differences in mental health risk and prevention. We conducted a narrative review to assess the current state of knowledge on gender-specific mental health preventive interventions, along with an analysis of gender-based risk factors and available screening strategies. Out of 1598 articles screened using a comprehensive electronic search of the PubMed, Web-of-Science, Scopus, and Cochrane databases, 53 were included for review. Among risk factors for mental health problems, there are individual, familiar, social, and healthcare factors. Individual factors include childhood adversities, which show gender differences in distribution rates. However, current childhood abuse prevention programs are not gender-specific. Familiar factors for mental health problems include maternity issues and intimate partner violence, and for both, some gender-specific preventive interventions are available. Social risk factors for mental health problems are related to education, employment, discrimination, and relationships. They all display gender differences, but these differences are rarely taken into account in mental health prevention programs. Lastly, despite gender differences in mental health service use being widely known, mental health services appear to be slow in developing strategies that guarantee equal access to care for all individuals.


Comparison of cord blood and 6-month-old vitamin D levels of healthy term infants supplemented with 400 IU/day dose of vitamin D.
To determine the prevalence and risk factors of vitamin D deficiency in pregnant women and their infants at birth (cord blood) and at six months of age in Turkey, as well as to assess the compliance rates of families with vitamin D supplementation. Serum 25-hydroxyvitamin D [25(OH)D] level was measured of the mothers before delivery and of the infants both at birth (cord blood) and at six months of age. Infants who received and did not take regular vitamin D supplements were compared in terms of 25(OH) levels. Independent risk factors were determined by multiple logistic regression analysis. The study included a total of 140 pregnant women and their infants. Vitamin D deficiency was found in 95.7% of the mothers. The prevalence of vitamin D deficiency was 87.1% in infants at birth but decreased to 5.8% at sixth month. 65.7% of infants received vitamin D supplements regularly. Despite regular vitamin D use, it was determined that 2.2% of the infants in the supplementation compliant group had vitamin D deficiency. Maternal age, maternal education level, and the number of siblings were determined to be determining factors on infants' 25(OH)D levels at six months (p < 0.05). In Turkey, vitamin D deficiency still exists in both pregnant women and infants. Healthcare professionals and the public need to be more educated about the importance of regular supplementation. Serum 25(OH)D levels of infants should be tested periodically and personalized vitamin D supplementation planning is required based on test results.


Minimally Invasive Fetal Surgery and the Next Frontier.
Most patients with congenital anomalies do not require prenatal intervention. Furthermore, many congenital anomalies requiring surgical intervention are treated adequately after birth. However, there is a subset of patients with congenital anomalies who will die before birth, shortly after birth, or experience severe postnatal complications without fetal surgery. Fetal surgery is unique in that an operation is performed on the fetus as well as the pregnant woman who does not receive any direct benefit from the surgery but rather lends herself to risks, such as hemorrhage, abruption, and preterm labor. The maternal risks involved with fetal surgery have limited the extent to which fetal interventions may be performed but have, in turn, led to technical innovations that have significantly advanced the field. This review will examine congenital abnormalities that can be treated with minimally invasive fetal surgery and introduce the next frontier of prenatal management of fetal surgical pathology.