Eating behaviour, quality of life and cardiovascular risk in obese and overweight children and adolescents: a cross-sectional study.
Childhood obesity is a major cardiovascular risk factor because it predisposes individuals to comorbidities that are implicated in an increased risk of cardiovascular events. Its origin may be related to poor eating habits, such as the intake of foods of low nutritional value or inadequate eating behaviours related to emotional factors. This work aims to evaluate the relationship between the total body mass of children and adolescents and its association with eating habits, quality of life (QoL), and possible changes in early markers of cardiovascular risk. This was a cross-sectional observational study that evaluated anthropometric and cardiovascular parameters, QoL, and eating behaviour in 181 children and adolescents aged between 5 and 13 years. Participants were stratified according to BMI/age into three groups (Adequate Weight, Overweight, and Obesity). Anthropometry included weight, height, waist and hip circumferences, waist-hip ratio, and waist-height ratio. QoL was assessed using the Peds-QL 4.0 questionnaire, and eating behaviour was assessed using the Children's Eating Behaviour Questionnaire (CEBQ). Cardiovascular parameters were assessed using the Mobil-O-Graph® device, which measures the pulse wave velocity (PWV) and augmentation index (AIx@75) to estimate arterial stiffness (AS), which is considered an early marker of cardiovascular disease. In addition to the increase in anthropometric measurements (p < 0.001), the Obesity group exhibited behaviour related to food intake (p < 0.05). When analysing QoL, a worsening in the social domain was also observed in the Obesity group (p < 0.05). However, PWV and AIx@75 did not differ between groups. Eating behaviour is related to the development of childhood obesity. However, early markers of cardiovascular risk related to AS did not change as a function of total body mass in the children evaluated.


Prenatal diagnosis and antenatal history of persistent truncus arteriosus: A case report.
We report the prenatal diagnosis and the natural history of a fetus with truncus arteriosus. A 31-year-old woman, gravida 3, was referred for detailed examination for suspected cardiac anomaly during her 33rd week of gestation. Fetal echocardiography demonstrated a large truncal vessel overriding a ventricular septal defect, a right-side aortic arch, and a dilated ascending aortic arch. Pulsed-wave and color-flow Doppler imaging showed truncal valvular stenosis without insufficiency. No sign of congestive heart failure was detected during the prenatal period. A fetus weighing 2860 grams was delivered during the 38th week of gestation. Cyanosis was noted the day after delivery, however, and a Rastelli procedure was carried out 9 days after delivery. The baby died 7 days after the operation.


Clinical trial search: Using biomedical language understanding models for re-ranking.
Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art effectiveness in some of the biomedical information processing applications. We investigate the effectiveness of these techniques for clinical trial search systems. In precision medicine, matching patients to relevant experimental evidence or prospective treatments is a complex task which requires both clinical and biological knowledge. To assist in this complex decision making, we investigate the effectiveness of different ranking models based on the BERT models under the same retrieval platform to ensure fair comparisons. An evaluation on the TREC Precision Medicine benchmarks indicates that our approach using the BERT model pre-trained on scientific abstracts and clinical notes achieves state-of-the-art results, on par with highly specialised, manually optimised heuristic models. We also report the best results to date on the TREC Precision Medicine 2017 ad hoc retrieval task for clinical trial search.


The effect of hyperglycemia on brain capillary permeability in the lizard, Anolis carolinensis. A freeze-fracture analysis of blood-brain barrier pathology.
The anatomical basis of the blood-brain barrier in the American chameleon, Anolis carolinensis, is the system of tight intercellular junctions that occurs between apposed endothelial cells of brain capillaries. Under normal physiological conditions, capillaries in the brain cortex of these animals remain sealed by interendothelial zonulae occludentes and, consequently, escape of exogenous tracer proteins such as horseradish peroxidase (HRP) into the extracellular compartment of the central nervous system is prevented. Systemic injection of 2.7 mg of D-glucose into chameleons results in increased brain capillary permeability, as evidenced by escape of HRP or Trypan blue into the intercellular spaces of central neuropil. Freeze-fracture analysis of brain capillary endothelia of glucose-hyperglycemic lizards revealed no alteration of the ridge and groove construction of endothelial tight junctions, indicating that although the blood-brain interface becomes leaky during severe hyperglycemia, the capillary zonulae occludentes are not affected. Evidence obtained in this study strongly supports the notion that the increased capillary permeability is the result of amplified transendothelial transport. The effect is manifest as and facilitated by the formation of chains of pinocytotic vesicles derived from the luminal surface of the endothelial cells, which fuse to create open trans-endothelial conduits. It is likely that formation of open channels that traverse brain capillary endothelial cells, as a response to hyperglycemia, could allow temporarily unrestricted passage of a wide range of molecules, some potentially toxic, into the CNS extracellular milieu. This is the first report to unequivocally document with freeze-cleave techniques, that abnormally elevated levels of blood sugar can affect blood-brain interface permeability. This finding suggests that similar consequences may be expected to result from diabetic hyperglycemia in humans.


Functional analysis of GnRH receptor ligand binding using biotinylated GnRH derivatives.
The objective of this study was to determine whether the gonadotrophin-releasing hormone (GnRH) ligand binds to the GnRH receptor (GnRH-R) with either the N- and C-termini or the beta-II turn pointing towards the cell. The functionality of GnRH and two biotinylated GnRH derivatives, biotin [D-Lys6]GnRH and biotin [Gln1]GnRH biotinylated at positions 6 and 1, respectively was assessed. Streptavidin was also used in combination with these peptides to investigate the effects of the steric hindrance caused by this molecule on ligand binding when bound to the biotin molecules at the two positions. GnRH bound to the receptor with high affinity, which was not affected by the addition of streptavidin. Both the biotinylated derivatives bound to the receptor though with lower affinities than GnRH. The biotin [D-Lys6]GnRH-streptavidin complex bound to the receptor albeit with lower affinity compared to biotin [D-Lys6]GnRH only, although it maintained its ability to cause receptor internalisation. The ability of the biotin [Gln1]GnRH to bind to the receptor was abolished in the presence of excess streptavidin. Both GnRH and biotin [D-Lys6]GnRH stimulated total inositol phosphate production whereas biotin [Gln1]GnRH exhibited GnRH antagonist activity. It appears that the small biotin molecule can be accommodated within the binding pore when attached to position 1 of the ligand but not when complexed to streptavidin. The fact that biotin [D-Lys6]GnRH maintains functionality when complexed to streptavidin while biotin [Gln1]GnRH does not, suggests that the N- and possibly the C-termini are required for receptor binding. Thus the most likely binding orientation for the ligand is with the N- and C-termini pointing inwards with the residue at position 6 pointing away from the binding site.


Inhibition by swainsonine of the degradation of endocytosed glycoproteins in isolated rat liver parenchymal cells.
Swainsonine, an alpha-mannosidase inhibitor found in the Australian plant Swainsona canescens and in spotted locoweed, was tested for its effect on the degradation of endocytosed proteins in rat liver cells. The compound inhibited the release of proteolytically derived breakdown products from endocytosed glycoproteins but not from nonglycoproteins. Fifty per cent inhibition of the degradation of 125I-asialofetuin occurred at a concentration of swainsonine in the medium of 6 X 10(-7) M. In the presence of the inhibitor, there was an increased cellular accumulation of the glycoproteins corresponding quantitatively to the decreased degradation, so that total uptake was the same in the presence or absence of the inhibitor. The excess 125I-labeled material which accumulated within cells under these conditions was found entirely in the lysosomal peak on Percoll density gradient centrifugation and migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a mobility indistinguishable from that of the original material. Thus, the inhibition of breakdown occurs prior to any conversion of the protein to intermediates of detectably smaller size. In contrast to the results with swainsonine, degradation of both glycoproteins and nonglycoproteins was inhibited by chloroquine and by 3-methyladenine. The findings with 3-methyladenine are in conflict with earlier reports in the literature on the effect of this compound on degradation of endocytosed proteins.


Visual evaluation of binding to mucosal cells of a medical device against the common cold.
The objective of this study was to investigate the possibility of visualizing the ability of hydroxypropylmethylcellulose (HPMC) and a nasal spray (First Defense), in which the bioadhesive is HPMC, to bind to human mucosal cells using inorganic (black carbon particles and Congo red dye) and organic markers (Escherichia coli). A significant reduction in the bacterial adhesiveness has been observed. Our findings indicate the possibility of counteracting the lock-and-key mechanism of microorganism adhesion using the bioadhesive properties of polymers, such as HPMC, in First Defense to prevent a possible contact between adhesins and complementary receptors.


Evidence that apomorphine induces penile erection and yawning by releasing oxytocin in the central nervous system.
Oxytocin (10 and 30 ng) injected into a lateral ventricle (i.c.v.) or the dopamine agonist apomorphine (40 and 80 micrograms/kg) injected subcutaneously induced repeated episodes of penile erection and yawning in male rats. The concomitant administration of the two substances did not produce any further increase in the number of penile erection and yawning episodes. Penile erection and yawning induced by either oxytocin or apomorphine were antagonized in a dose-dependent manner by i.c.v. pretreatment with the oxytocin antagonists [d(CH2)5Tyr(Me)-Orn8]vasotocin, [Pen1,Phe(Me)2,Thr4,Orn8]oxytocin and [d(CH2)5Tyr(Me)-Arg8]vasopressin, with a rank order of potency that follows their antioxytocic activity. (i.e. [d(CH2)5Tyr(Me)-Orn8]vasotocin congruent to [Pen1,Phe(Me)2,Thr4,Orn8]-oxytocin greater than [d(CH2)5Tyr(Me)-Arg8]vasopressin). The results suggest that apomorphine induces penile erection and yawning by releasing oxytocin in the central nervous system.


Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data.
RTS,S is the most advanced candidate malaria vaccine but it is only partially protective and the causes of inter-individual variation in efficacy are poorly understood. Here, we investigated whether peripheral blood monocyte-to-lymphocyte ratios (ML ratio), previously shown to correlate with clinical malaria risk, could account for differences in RTS,S efficacy among phase II trial participants in Africa. Of 11 geographical sites where RTS,S has been evaluated, pre-vaccination ML ratios were only available for trial participants in Kilifi, Kenya (N = 421) and Lambarene, Gabon (N = 189). Using time to first clinical malaria episode as the primary endpoint we evaluated the effect of accounting for ML ratio on RTS,S vaccine efficacy against clinical malaria by Cox regression modeling. The unadjusted efficacy of RTS,S in this combined dataset was 47% (95% confidence interval (CI) 26% to 62%, P <0.001). However, RTS,S efficacy decreased with increasing ML ratio, ranging from 67% (95% CI 64% to 70%) at an ML ratio of 0.1 to 5% (95% CI -3% to 13%) at an ML ratio of 0.6. The statistical interaction between RTS,S vaccination and ML ratio was still evident after adjustment for covariates associated with clinical malaria risk in this dataset. The results suggest that stratification of study participants by ML ratio, easily measured from full differential blood counts before vaccination, might help identify children who are highly protected and those that are refractory to protection with the RTS,S vaccine. Identifying causes of low vaccine efficacy among individuals with high ML ratio could inform strategies to improve overall RTS,S vaccine efficacy. ClinicalTrials.Gov numbers NCT00380393 and NCT00436007.


Radiological, clinical and functional evaluation using the Quick Disabilities of the Arm, Shoulder and Hand questionnaire of children with medial epicondyle fractures treated surgically.
The main goal of this study was to retrospectively evaluate the clinical, functional and radiographic outcomes of displaced medial epicondyle fractures with or without associated elbow dislocation in children undergoing surgical treatment and to evaluate upper-extremity function with the Quick Disbilities of the Arm, Shoulder and Hand (Quick DASH) questionnaire. The hypothesis was that patients with associated elbow dislocation would have similar functional outcome to patients with displaced fractures with or without intra-articular entrapment of the medial epicondyle. A review of medical charts was performed to identify all children and adolescents who underwent surgical treatment for displaced medial epicondyle humeral fractures managed at a single institution. Patients with a closed fracture on plain radiographs, presence of growth cartilages and managed surgically were included in the study. Fractures were radiologically assessed on anteroposterior and lateral radiographs and rated according to Papavasiliou and Crawford classification. Functional outcome was measured with the Quick DASH questionnaire. Sixty-six patients met inclusion criteria, and 38 children presented with isolated displaced medial epicondyle fracture (Group A: type II and type III) and 28 with medial epicondyle fractures associated with elbow dislocation (Group B: type IV). The Papavasiliou and Crawford system classified 36 fractures as type II (54.6%), two (3%) as type III and 28 as type IV (42.4%). All patients underwent open reduction. Fracture fixation was performed with K-wires in 26 (35%) children and a with single screw in 40 (65%). Mean follow-up was 37.5 months (range, 12-68). Overall complication rate was 18%. In particular, three adverse events (3/38, 8%) were recorded in Group -A and nine (9/28, 32%) in Group B (p = 0.003). Mean Quick DASH score at final follow-up was 4.6 ± 3.8 (range, 0-15.9) and was not significantly different between Groups A (5.4 ± 4.3; range, 0-15.9) and B (4.1 ± 3.5; range, 0-15.9) (p > 0.05). Children with type II, III and IV medial epicondyle fractures undergoing surgical treatment have good radiological, clinical and functional outcome but warrant special attention to detect intra-articular entrapment of the broken epicondyle. In these cases, both patient and family should be warned of the potential risk of loss of elbow range of motion and possibly poor functional outcome, especially if treatment is delayed.


The release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha.
Plasma level of the protein VAP-1/SSAO (Vascular Adhesion Protein-1/Semicarbazide-Sensitive Amine Oxidase) is increased in diabetes and/or obesity and may be related to vascular complications associated to these pathologies. The aim of this work was to complete a preceding study where we described the role played by some hormones or metabolites, implicated in diabetes and/or obesity, in the regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes. Here we focused on the previously observed effect produced by TNFalpha in the release of VAP-1/SSAO and studied the effect of a beta-adrenergic compound, isoproterenol. Both compounds stimulated the release of VAP-1/SSAO to the culture medium but had a different effect on the VAP-1/SSAO membrane form. While TNFalpha produced a decrease on VAP-1/SSAO membrane form content, isoproterenol did not modify it. We thus observed two different ways of regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes by metabolites implicated in diabetes and adipose tissue physiopathology. Our work permits a better understanding of this increased plasma VAP-1/SSAO levels observed in diabetes.


A Novel Method of Adrenal Venous Sampling via an Antecubital Approach.
Currently, almost all adrenal venous sampling (AVS) procedures are performed by femoral vein access. The purpose of this study was to establish the technique of AVS via an antecubital approach and evaluate its safety and feasibility. From January 2012 to June 2015, 194 consecutive patients diagnosed as primary aldosteronism underwent AVS via an antecubital approach without ACTH simulation. Catheters used for bilateral adrenal cannulations were recorded. The success rate of bilateral adrenal sampling, operation time, fluoroscopy time, dosage of contrast, and incidence of complications were calculated. A 5F MPA1 catheter was first used to attempt right adrenal cannulation in all patients. Cannulation of the right adrenal vein was successfully performed in 164 (84.5%) patients. The 5F JR5, Cobra2, and TIG catheters were the ultimate catheters for right adrenal cannulation in 16 (8.2%), 5 (2.6%), and 9 (4.6%) patients, respectively. For left adrenal cannulation, JR5 and Cobra2 catheters were used in 19 (9.8%) and 10 (5.2%) patients, respectively, while only TIG catheters were used in the remaining 165 (85.1%) patients. The rate of successful adrenal sampling on the right, left, and bilateral sides was 91.8%, 93.3%, and 87.6%, respectively. The mean time of operation was (16.3 ± 4.3) minutes, mean fluoroscopy time was (4.7 ± 1.3) minutes, and the mean use of contrast was (14.3 ± 4.7) ml. The incidence of adrenal hematoma was 1.0%. This study showed that AVS via an antecubital approach was safe and feasible, with a high rate of successful sampling.


Detection of Group II Intron-Generated Chimeric mRNAs in Bacterial Cells.
Chimeric RNAs are the transcripts composed of exons from two separate genes or transcripts. Although the presence of these joined RNA molecules have mainly been documented in a variety of eukaryotes, we recently demonstrated that the Ll.LtrB group II intron, from the gram-positive bacterium Lactococcus lactis, can generate chimeric mRNAs through a novel intergenic trans-splicing pathway. Here we describe the detailed experimental procedures to detect group II intron-generated mRNA-mRNA chimeras from total RNA extracts using stringent reverse transcription conditions along with a reverse splicing-deficient group II intron as a negative control.


Influence of high lead and cadmium soil content on human reproductive outcome.
The influence of lead and cadmium on human reproductive outcome was studied in areas of Eastern Poland with high specific soil contamination with these heavy metals. By personal interviews, information on socioeconomic background factors as well as obstetrical and gynecological histories were obtained from 136 women living in villages with high amounts of lead and cadmium and from 269 women of nearby villages with no increased content of these metals. Physical examination and estimations of blood concentrations of lead and cadmium were also performed in 89 and 175 women from these areas, respectively. In the contaminated areas, there were significantly fewer women with three or more pregnancies (39 vs. 52%) and deliveries at full term (35 vs. 44%) than in nearby villages with normal concentrations of these heavy metals, and the weight of preterm newborns was lower (1930 vs. 2225 g). Furthermore, hypertension was more common (15 vs. 22%) and of higher magnitude (mean blood pressure 140 vs. 129 mmHg) in the study group than in the control women. The mean blood concentrations of lead in the two groups. 675 and 621 micrograms/dl did not differ statistically, whereas the concentrations of cadmium of 29 and 25 micrograms/dl were significantly higher in the study than in the control group. There was a significant correlation between cadmium levels and number of preterm deliveries. These results suggest that cadmium and lead could be factors of importance in reproductive outcome.


Profile of Published Cochrane Systematic Reviews in Child Health From Low- and Middle-Income Countries.
Setting priorities in health research is a challenge at the global and national levels. Use of evidence-based approach is uncommon and needs to be promoted in low-and middle-income countries (LMIC). We describe profile of Cochrane systematic reviews focussing on participation from LMIC. We searched six Cochrane review groups producing reviews relevant to child health in low- and middle-income countries for published Cochrane systematic reviews from 1 March, 2009 till 18 March, 2015 in the Cochrane Library. A total of 669 Cochrane systematic reviews from six review groups were found. Low proportion of lead authors from low- and middle-income countries was found in 4 out of 6 review groups. About 50% of the reviews showed inconclusive evidence. 101/669 (15%) empty reviews were found needing more primary studies. The proportion of Cochrane authors from low- and middle-income countries is low. Capacity-building in systematic reviews and good quality primary research in these countries is warranted.


Age-related occurrence of simple renal cysts studied by ultrasonography.
Three hundred forty-eight outpatients without evidence of renal disease were examined by ultrasound. Their ages ranged from 18 to 83 years. Unexpected renal cysts of more than 1 cm were found in 47 patients (13.5%). No cysts were demonstrated in patients less than 23 years old; thereafter the number of patients with cysts increased significantly with age. The cyst diameter also tended to increase with age, but the correlation with age was not significant. There was no statistical difference of cyst occurrence between the right and left kidney, or between males and females. The upper portion of the kidney was most often affected in the equally divided three portions along the long axis. These results confirm that the development of simple renal cysts is age-related.


Internal fixation of fractures of the proximal end of the radius in adults.
Eight cases of internal fixation for fractures of the proximal end of the radius in adults are discussed. The reasons for this procedure, after considering the patient's age and activity and the type of fracture, was to avoid the sequelae of resection of the radial head. By following an appropriate technique, and provided that there are no compications, the results obtained have been excellent.


Mutations in the PIGW gene associated with hyperphosphatasia and mental retardation syndrome: a case report.
Mutations in the PIGV, PIGO, PIGL, PIGY, PGAP2, PGAP3, and PIGW genes have recently been reported to cause hyperphosphatasia accompanied by mental retardation syndrome (HPMRS); the latter is an autosomal-recessive neurological disorder typically characterised by recurrent seizures, intellectual disability, and distinct facial features. Here, we report an extremely rare case of a Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations, confirmed by Sanger sequencing. Mutations in the PIGW gene in infants can cause various symptoms and multiple anomalies. Next-generation sequencing efficiently detects such mutations. The compound PIGW mutations that we describe expand the genotype/phenotype spectrum of HPMRS and may aid in clinical treatment.


Self-help group attendance and participation among cocaine dependent patients.
The authors examined frequency and patterns of self-help group attendance and active participation over a 6-month period among 411 patients receiving treatment in the NIDA Collaborative Cocaine Treatment Study. Nearly two-thirds of patients attended at least one self-help group, and nearly all of these actively participated. Alcoholics Anonymous and Narcotics Anonymous meetings were attended most frequently. Statistical analyses included chi square, one-way analyses of variance, and cluster techniques. While patterns of attendance were relatively consistent over time, findings suggest that a treatment emphasizing the importance of self-help groups is likely to encourage more self-help group attendance and participation over time.


Incidence of bilateral discoid lateral meniscus in an Asian population: an arthroscopic assessment of contralateral knees.
To investigate the incidence of bilateral discoid lateral meniscus (DLM) and to evaluate the arthroscopic features of lateral meniscus in asymptomatic contralateral knees in an Asian population who presented with symptomatic DLMs. This study prospectively enrolled 52 consecutive patients who underwent arthroscopic procedures for symptomatic DLMs (31 complete and 21 incomplete) and who consented to the examination of the contralateral knee at the time of arthroscopy. Types of DLMs and of meniscus tears were assessed by use of arthroscopic findings. Preoperative and postoperative functional outcomes were evaluated with Lysholm and Tegner activity scores. Arthroscopic examinations showed 21 complete DLMs, 19 incomplete DLMs, 11 normal lateral menisci, and 1 ring-shaped lateral meniscus in contralateral knees. The incidence of bilateral DLM in our study population was 79% (41 of 52 contralateral knees). Furthermore, 65% of patients (34 pairs of knees) had the same DLM types. In addition, 3 pairs of knees with complete DLMs had menisci of different thicknesses. DLM tears were observed in 2 contralateral knees (1 radial and 1 longitudinal) and were treated by partial central meniscectomy. This study provides evidence of the high prevalence of bilateral DLM in an Asian population.


Drying characteristics and equilibrium moisture content of steam-treated Douglas fir (Pseudotsuga menziesii L.).
Douglas fir (Pseudotsuga menziesii L.) particles were exposed to high pressure saturated steam (200 and 220 °C for 5 and 10 min) to improve the durability and hydrophobicity of pellets produced from them. Depending on treatment severity, the moisture content of the particles increased from 10% to 36% (wet basis). Douglas fir particles steam-treated at 220 °C for 10 min had the fastest drying rate of 0.014 min(-1). The equilibrium moisture content (EMC) of steam-treated samples decreased with increasing steam temperature and treatment time. The Giggnheim-Anderson-deBoer (GAB) equilibrium model gave a good fit with the equilibrium data with R(2) = 0.99. The adsorption rate of untreated pellets exposed to humid air (30 °C, 90% RH) for 72 h was 0.0152 min(-1) while that of steam-treated pellets ranged from 0.0125 to 0.0135 min(-1) without a clear trend with steam treatment severity. These findings are critical to develop durable and less hygroscopic pellets.


Development and validation of a behavioural video coding scheme for detecting mental workload in manual assembly.
Manual assembly in the future Industry 4.0 workplace will put high demands on operators' cognitive processing. The development of mental workload (MWL) measures therefore looms large. Physiological gauges such as electroencephalography (EEG) show promising possibilities, but still lack sufficient reliability when applied in the field. This study presents an alternative measure with a substantial ecological validity. First, we developed a behavioural video coding scheme identifying 11 assembly behaviours potentially revealing MWL being too high. Subsequently, we explored its validity by analysing videos of 24 participants performing a high and a low complexity assembly. Results showed that five of the behaviours identified, such as freezing and the amount of part rotations, significantly differed in occurrence and/or duration between the two conditions. The study hereby proposes a novel and naturalistic method that could help practitioners to map and redesign critical assembly phases, and researchers to enrich validation of MWL-measures through measurement triangulation. Practitioner summary: Current physiological mental workload (MWL) measures still lack sufficient reliability when applied in the field. Therefore, we identified several observable assembly behaviours that could reveal MWL being too high. The results propose a method to map MWL by observing specific assembly behaviours such as freezing and rotating parts. Abbreviations: MWL: mental workload; EEG: electroencephalography; fNIRS: functional near infrared spectroscopy; AOI: area of interest; SMI: SensoMotoric Instruments, ETG: Eye-Tracking Glasses; FPS: frames per second; BORIS: Behavioral Observation Research Interactive Software; IRR: inter-rater reliability; SWAT: Subjective Workload Assessment Technique; NASA-TLX: National Aeronautics and Space Administration Task Load Index; EL: emotional load; DSSQ: Dundee Stress State Questionnaire; PHL: physical load; SBO: Strategisch Basis Onderzoek.


Determinants of vitamin D levels in men receiving androgen deprivation therapy for prostate cancer.
Studies found an association between decreased 25-OH vitamin D blood level and prostate cancer progression. Vitamin D supplementation is controversial and dosage recommendations inconsistent. This study identified factors associated with 25-OH vitamin D levels and whether vitamin D supplementation with 800 IU/day raised vitamin D levels in prostate cancer patients receiving androgen deprivation therapy (ADT). We recruited 108 men treated with ADT for ≥9 months from eight cancer and urology practices. Sections of the NHANES 2005-2006 questionnaire and Canadian Fitness Survey were completed identifying age, ethnicity, length of ADT use, calcium supplementation ≥1000 IU mg/day, body mass index, exercise, alcohol and tobacco use, and vitamin D supplementation ≥800 IU/daily. Blood was collected for 25-OH vitamin D analysis. The majority of men (66%) had blood levels of 25-OH vitamin D <32 ng/mL. Regression analysis showed vitamin D supplementation (β = 6.556, CI 1.463, 11.650; p = .012) and African American ethnicity (β = -7.816, CI -12.996, -2.635; p = .003) is associated with 25-OH vitamin D level after controlling age and tobacco use. Findings support current recommendations for supplementation with ≥800 IU vitamin D/day for men receiving ADT. Nurse practitioners caring for prostate cancer patients receiving ADT should include vitamin D monitoring and supplementation.


Mechanisms of colchicine neurotoxicity in the dentate gyrus: dissociation of seizures and cell death.
Extracellular field potentials and the EEG were studied in the dentate gyrus of the rat after intrahippocampal injections of colchicine, which is a relatively selective neurotoxin for dentate granule cells. Injection of colchicine (0.5 microliters of a 5-mg/ml solution of colchicine in deionized water) resulted in granule cell hyperexcitability manifested by multispike field potentials in response to stimulation of the excitatory projections from the entorhinal cortex. In anesthetized rats, this state of granule cell hyperexcitability was occasionally accompanied by interictal epileptic spiking or brief electrographic seizures, but granule cell death was observed even in the absence of epileptic activity. Injection of colchicine into the CA1 area of the hippocampus also resulted in multispike field potentials in response to stimulation of the CA3 commissural pathway, but CA1 pyramidal cells were not destroyed by colchicine. Colchicine has been reported to act as a convulsant agent in the dentate gyrus, but it is a relatively selective neurotoxin for dentate granule cells even in the absence of epileptic activity.


Low-density lipoprotein receptor-related protein-1: a serial clearance homeostatic mechanism controlling Alzheimer's amyloid β-peptide elimination from the brain.
Low-density lipoprotein receptor-related protein-1 (LRP1), a member of the low-density lipoprotein receptor family, has major roles in the cellular transport of cholesterol, endocytosis of 40 structurally diverse ligands, transcytosis of ligands across the blood-brain barrier, and transmembrane and nuclear signaling. Recent evidence indicates that LRP1 regulates brain and systemic clearance of Alzheimer's disease (AD) amyloid β-peptide (Aβ). According to the two-hit vascular hypothesis for AD, vascular damage precedes cerebrovascular and brain Aβ accumulation (hit 1) which then further amplifies neurovascular dysfunction (hit 2) preceding neurodegeneration. In this study, we discuss the roles of LRP1 during the hit 1 and hit 2 stage of AD pathogenesis and describe a three-level serial LRP1-dependent homeostatic control of Aβ clearance including (i) cell-surface LRP1 at the blood-brain barrier and cerebrovascular cells mediating brain-to-blood Aβ clearance (ii) circulating LRP1 providing a key endogenous peripheral 'sink' activity for plasma Aβ which prevents free Aβ access to the brain, and (iii) LRP1 in the liver mediating systemic Aβ clearance. Pitfalls in experimental Aβ brain clearance measurements with the concurrent use of peptides/proteins such as receptor-associated protein and aprotinin are also discussed. We suggest that LRP1 has a critical role in AD pathogenesis and is an important therapeutic target in AD.


Clinical pharmacokinetics of carboplatin.
The pharmacokinetics of carboplatin were investigated in cancer patients after single, IV infusion doses of 75, 150, 247.5, 300, 375, and 450 mg/m2. Total plasma and urine platinum and plasma ultrafilterable platinum concentrations were determined by atomic absorption spectrometry. Carboplatin was analyzed in plasma by a specific high-performance liquid chromatography (HPLC) procedure. Total plasma platinum, which represented free carboplatin, protein-bound platinum and metabolites, declined triexponentially; plasma half-lives (t1/2 lambda 1, 0.2 to 0.4 hr; t1/2 lambda 2, 1.3 to 1.7 hr; t1/2 lambda 3, 22 to 40 hr) and total body clearance (CLTB 2.8 +/- 0.5 L/m2/hr) were dose independent. Maximum plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) increased proportionally with dose. Plasma ultrafilterable platinum and carboplatin concentrations at doses of 375 and 450 mg/m2 declined in a biphasic manner. Plasma carboplatin elimination (t1/2 lambda 1, 0.50 hr; t1/2 lambda 2, 2.2 hr) and CLTB (4.4 to 5.6 L/m2/hr) were also independent of dose; AUC and Cmax increased proportionally to dose. Plasma free platinum was essentially all carboplatin for 8 or 12 hours after administration. Carboplatin did not bind to plasma protein in vitro but did degrade (t1/2-26 hours) to yield a reactive intermediate that bound rapidly and irreversibly to protein. The long terminal elimination half-life of plasma platinum was associated with irreversible binding of a platinum metabonate to plasma protein. The urinary excretion of platinum (0 to 24 hours) accounted for 58 to 72% of doses in 12 to 24 hours. The remainder of the dose is slowly excreted. The pharmacokinetics, in vivo stability, protein binding, and elimination of carboplatin are distinct from the first-generation analog cisplatin.


M-protein gene-type distribution and hyaluronic acid capsule in group A Streptococcus clinical isolates in Chile: association of emm gene markers with csrR alleles.
Streptococcus pyogenes causes a variety of infections because of virulence factors such as capsular hyaluronic acid and M protein. The aim of this study was to determine emm types and capsule phenotype in 110 isolates of S. pyogenes from patients with invasive (sterile sites) and non-invasive (mainly pharyngitis) infections in Chile, and the relationship between both virulence factors. The most abundant types found were emm12, emm1, emm4 and emm28 and their distribution was similar to that seen in Latin America and developed countries, but very different from that in Asia and Pacific Island countries. Ten of 16 emm types identified in pharyngeal isolates were found in sterile-site isolates, and three of nine emm types of sterile-site isolates occurred in pharyngeal isolates; three emm subtypes were novel. The amount of hyaluronic acid was significantly higher in sterile-site isolates but did not differ substantially among emm types. Only three isolates were markedly capsulate and two of them had mutations in the csrR gene that codes for a repressor of capsule synthesis genes. We found a non-random association between emm types and csrR gene alleles suggesting that horizontal gene transfer is not freely occurring in the population.


LncRNA EPIC1 promotes tumor angiogenesis via activating the Ang2/Tie2 axis in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is considered a highly fatal tumor. Importantly, angiogenesis is critical for tumor progression. Long non-coding RNAs (lncRNAs), which are untranslatable, control cell functions through different pathways. lncRNA EPIC1 has been reported to promote cell viability, cell cycle progression, and invasion. However, the relationship between EPIC1 and tumor angiogenesis remains an enigma. We explored the role of EPIC1 in tumor angiogenesis in NSCLC. First, EPIC1 expression was analyzed using the GEPIA database and was further verified using qPCR in tumor tissues from patients with NSCLC and NSCLC cell lines. Next, EPIC1 function was detected using loss-of-function and gain-of-function assays. Moreover, EdU staining, flow cytometry, and channel formation assays were performed to assess HUVEC proliferation and channel the formation in the NSCLC-HUVEC transwell co-culture system. EPIC1 expression was significantly upregulated in NSCLC tissues and cell lines. Furthermore, the overexpression of EPIC1 in NSCLC cells stimulated HUVEC channel formation and proliferation by activating Ang2/Tie2 signaling, and the opposite results were obtained when EPIC1 was silenced in NSCLC cells. The density of new blood vessels was simultaneously increased by EPIC1 overexpression in vivo, using CAM angiogenesis model and a nude mouse tumor model. Finally, all these experimental findings could be established in the samples from patients with NSCLC. We postulate that EPIC1 promotes tumor angiogenesis by activating the Ang2/Tie2 axis in NSCLC. Elucidating the molecular and cellular mechanisms of EPIC1 in tumor angiogenesis provides a novel perspective on NSCLC clinical therapy.


Further applications of Archimedes' principle in the correction of asymmetrical breasts.
Archimedes' law of buoyancy has been extended to the preoperative bedside assessment of volume differences between breasts, whatever their cause. The simple method described has proved to be a helpful aid in surgical procedures for the correction of breast asymmetry.


Seasonal changes in the densities of alpha(2) noradrenergic receptors are inversely related to changes in testosterone and the volumes of song control nuclei in male European starlings.
The functions of song and the contextual cues that elicit song change seasonally in parallel with testosterone (T) concentrations in male European starlings. T is high in spring when at least one function of male song is that of immediate mate attraction, and low outside the context of breeding, when starlings primarily use song for dominance or flock maintenance. Several brain nuclei that control song contain high densities of alpha(2)adrenergic receptors. T can regulate the density of alpha(2)adrenergic receptors in the avian brain, indicating that the density of alpha(2) adrenergic receptors within the song system might change seasonally. Although the function of seasonal brain variation is not entirely clear, in many songbirds the volumes of song nuclei are largest when T is high and males sing most. Male starlings, however, sing both when T is high and when T is low. Therefore, exploring seasonal changes in T and the volumes of song nuclei could provide insight into the function of these changes. The present study was performed to explore the relationships among T, the volumes of song nuclei, and the densities of alpha(2) adrenergic receptors within the song system of male starlings. Song nuclei (the high vocal center [HVc], robust nucleus of the archistriatum [RA], and Area X) were largest, T was highest, and the density of alpha(2) adrenergic receptors (within HVc and RA) was lowest during the breeding season. The reverse pattern was observed outside of the breeding season. These results suggest that changes in T, volumes of song nuclei, and alpha(2) receptor densities might regulate seasonal changes in song behavior or the context that will elicit song in male starlings.


Proteome profiling of interleukin-12 treated human T helper cells.
Selective activation of T helper subsets 1 (Th1) and 2 (Th2) plays a crucial role in different pathological conditions. Th1 cell response is involved in pathogenesis of autoimmune diseases, such as type II diabetes and multiple sclerosis, and Th2 cell response in pathogenesis of allergy and asthma. Cytokine interleukin-12 (IL-12) is one of the key factors in the differentiation of naïve CD4(+) T cells into Th1 cells. In this study we used 2-DE and MS to find and identify IL-12 regulated proteins in human CD4(+) T cells. In total, 42 protein spots were found to be differentially expressed following IL-12 stimulation, of which 22 were up- and 20 down-regulated. Among the upregulated proteins there are a multifunctional cytokine macrophage migration inhibitory factor and a known IL-12 target gene Programmed cell death 4. Downregulated proteins include p21-activated kinase 2 and its upstream GTPase Cdc42. Compared to previous reports our analysis provides a new view on the IL-12 induced changes on CD4(+) T cells underscoring the importance of creating and combining the data generated at various levels to build a comprehensive view of a given biological process of the cell.


Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer.
Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC. MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival. BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4(+) and CD8(+)) and macrophages. Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.


Duct, exocrine, and endocrine components of cultured fetal mouse pancreas.
Twenty to twenty-two days postcoitum mouse fetal pancreas organ bits were cultured on the dermal surface of irradiated pigskin as a substrate. The medium used for long term culture consisted of Eagle's Minimum Essential Medium with the addition of 10% bovine serum, 0.02 U/ml insulin, 0.025 microgram/ml glucagon, 3.63 microgram/ml hydrocortisone, 100 microgram/ml soybean trypsin inhibitor or 10(-8) M atropine. When the medium lacked trypsin inhibitor or atropine but contained the three hormones, the pigskin support began to be destroyed after 2 to 4 wk in culture. Thereafter, the cultured cells could not grow and survive on the digested pigskin. When 10(-6) M atropine was added to the medium, amylase secretion from cultured cells and destruction of pigskin were inhibited completely but pancreas cells could not grow or survive. In contrast, 100 microgram/ml soybean trypsin inhibitor or 10(-8) M atropine permitted cell growth, permitted amylase secretion from the cultured acinar cells, and prevented the destruction of pigskin. Under these conditions pancreas cells migrated or grew or both from the organ bits onto the surface of the pigskin dermis and organoid aggregations formed. Hydrocortisone was needed to permit growth for more than 2 wk. Glucagon and insulin had additive effects. Light and electron microscopic observations indicated the culture of at least five kinds of cells, i.e., duct, acinar, centroacinar, endocrine, and mesenchymal. The majority of cultured cells were duct cells and acinar cells. There were few mesenchymal cells. Mouse pancreas cells were cultured for at least 12 wk by this method.


Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer.
Acquired metastasis and invasion of cancer cells during radiotherapy are in part due to induction of epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, which are mediated by TGF-β signaling. Here we evaluated the anti-metastatic therapeutic potential of vactosertib, an orally bioavailable TGF-β type I receptor (activin receptor-like kinase 5, ALK5) inhibitor, via suppression of radiation-induced EMT and CSC properties, oxidative stress generation, and breast to lung metastasis in a breast cancer mouse model and breast cancer cell lines. Co-treatment of vactosertib with radiation was investigated in the 4T1-Luc allografted BALB/c syngeneic mouse model and in 4T1-Luc and MDA-MB-231 cells. The anti-metastatic therapeutic potential of vactosertib in breast cancer was investigated using fluorescence immunohistochemistry, real-time quantitative reverse transcription-polymerase chain reaction, western blotting, wound healing assay, mammosphere formation assay, and lung metastasis analysis in vitro and in vivo. Radiation induced TGF-β signaling, EMT markers (Vimentin, Fibronectin, Snail, Slug, Twist, and N-cadherin), CSC properties (expression of pluripotent stem cell regulators, mammosphere forming ability), reactive oxygen species markers (NOX4, 4-HNE), and motility of breast cancer cells in vitro and in vivo. Vactosertib attenuated the radiation-induced EMT and CSC properties by inhibiting ROS stress in breast cancer. Moreover, vactosertib combined with radiation showed a significant anti-metastatic effect with suppression of breast to lung metastasis in vivo. These results indicate that inhibition of TGF-β signaling with vactosertib in breast cancer patients undergoing radiotherapy would be an attractive strategy for the prevention of cancer metastasis and recurrence.


Remembering stories as a function of the medium of presentation.
Participants (50 women, 35 men) either watched, listened to, or read a piece of fiction for television. An immediate cued recall test showed, as predicted, that the group who read the piece remembered more than either of the other two groups. This confirms previous findings on adults that recall of material presented in the print medium is superior to that from audio-only and audio-visual presentation.


Neuroimaging of Patients in the Intensive Care Unit: Pearls and Pitfalls.
A brief introduction is provided of the different imaging modalities encountered in the intensive care unit (ICU). The spectrum of intracranial pathology as well as potential postsurgical complications is reviewed, with a focus on pearls and pitfalls. A brief overview also is provided of imaging of the spine in an ICU patient.


Genome-wide identification and immune response analysis of mitogen-activated protein kinase cascades in tea geometrid, Ectropis grisescens Warren (Geometridae, Lepidoptera).
Tea geometrid Ectropis grisescens (Geometridae: Lepidoptera), is one of the most destructive defoliators in tea plantations in China. The MAPK cascade is known to be an evolutionarily conserved signaling module, acting as pivotal cores of host-pathogen interactions. Although the chromosome-level reference genome of E. grisescens was published, the whole MAPK cascade gene family has not been fully identified yet, especially the expression patterns of MAPK cascade gene family members upon an ecological biopesticide, Metarhizium anisopliae, remains to be understood. In this study, we have identified 19 MAPK cascade gene family members in E. grisescens, including 5 MAPKs, 4 MAP2Ks, 8 MAP3Ks, and 2 MAP4Ks. The molecular evolution characteristics of the whole Eg-MAPK cascade gene family, including gene structures, protein structural organization, chromosomal localization, orthologs construction and gene duplication, were systematically investigated. Our results showed that the members of Eg-MAPK cascade gene family were unevenly distributed in 13 chromosomes, and the clustered members in each group shared similar structures of the genes and proteins. Gene expression data revealed that MAPK cascade genes were expressed in all four developmental stages of E. grisescens and were fairly and evenly distributed in four different larva tissues. Importantly, most of the MAPK cascade genes were induced or constitutively expressed upon M. anisopliae infection. In summary, the present study was one of few studies on MAPK cascade gene in E. grisescens. The characterization and expression profiles of Eg-MAPK cascades genes might help develop new ecofriendly biological insecticides to protect tea trees.


Chemotaxonomic profiling of Penicillium setosum using high-resolution mass spectrometry (LC-Q-ToF-MS).
In the present study, secondary metabolites produced by an endophytic fungus Penicillium setosum were extracted using colony agar plug and culture broth extraction methods. High resolution LC-MS was used to explore the chemical nature of the secondary metabolites, as well, compare the reliability of the methods. P. setosum was chemotaxonomically distinguished from other members of section Lanata-divaricata, by its ability to produce mycotoxin, patulin and also by the presence of certain phenol-derived compounds, like quercetin, dihydroflavonols (dihydroquercetin and dihydromyricetin), kaempferol, luteolin, while some Penicillium specific compounds such as, citromycetin and andrastin D reveal its similarity towards section Lanata-Divaricata members. For the first time, the presence of dihydroquercetin is remarkably and spectrometrically confirmed from a microbial source. In addition, a few polyketides, anthroquinone compounds, hydrocarbons, and fatty acids were also detected in the culture extract. Being the first report on the production of polyphenolic compounds by an endophytic fungus of Penicillium species, the current research is crucial, and moreover the starin itself is a novel species.


Does menstrual hygiene management and water, sanitation, and hygiene predict reproductive tract infections among reproductive women in urban areas in Ethiopia?
Reproductive tract infections (RTIs) are a public health concern in Ethiopia. However, the relationship between menstrual hygiene management (MHM) and water, sanitation, and hygiene (WASH) factors to RTIs have not been well addressed. A community-based cross-sectional study was conducted from January to March 2019 among 602 systematically selected reproductive-age women aged 15-49 years in Dessie City. Data were collected using a questionnaire and a direct observation checklist. RTIs were identified by the presence during one year before data collection of one or more signs of vaginal discharge, itching/irritation or ulcers/lesions around the vulva, pain during urination and sexual intercourse, and lower abdominal pain and lower back pain. Data were analyzed using multivariable logistic regression analysis with 95%CI (confidence interval). The self-reported prevalence of RTIs was 11.0%(95%CI:8.5-13.7%) during one year prior to the survey. The most commonly reported symptoms of RTI were burning micturition (9.1%) and vaginal discharge (6.1%). Three-fourths 443(75.0%) of households used traditional pit latrines and the majority of the study participants 527(89.2%) did not meet the basic access requirement of 20 liters of water per capita per day. The majority 562(95.1%) of the study participants did not have multiple sexual partners during the last year and 97.8% did not practiced sexual intercourse during menstruation. The most common type of blood-absorbent material used was a sanitary pad 497(84.8%) followed by cloth 89(15.2%). Factors significantly associated with RTIs were using unclean latrines (AOR: 4.20; 95%CI:2.00-8.80), not washing hands with soap before touching the genital area (AOR: 3.94; 95%CI:1.49-10.45), history of symptoms of RTIs in the past year (AOR: 5.88; 95%CI:2.30-14.98), having multiple sexual partners in the past year (AOR: 4.46; 95%CI:1.59-12.53), changing absorbent material only once per day (AOR: 8.99; 95%CI:4.51-17.92), and washing the genital area only once per day during menstruation (AOR: 5.76; 95%CI:2.07-16.05). The self-reported prevalence of RTI showed that one women experienced RTI among ten reproductive-age women. Designing a women's health policy that focuses on ensuring availability of WASH facilities and improving MHM at the community level is key for sustainably preventing RTIs.


SecReT6 update: a comprehensive resource of bacterial Type VI Secretion Systems.
Type VI Secretion System (T6SS) plays significant roles in microbial activities via injecting effectors into adjacent cells or environments. T6SS increasingly gained attention due to its important influence on pathogenesis, microbial competition, etc. T6SS-associated research is explosively expanding on numerous grounds that call for an efficient resource. The SecReT6 version 3 provides comprehensive information on T6SS and the interactions between T6SS and T6SS-related proteins such as T6SS regulators and T6SS effectors. To assist T6SS researches like microbial competition and regulatory mechanisms, SecReT6 v3 developed online tools for detection and analysis of T6SS and T6SS-related proteins and estimation of T6SS-dependent killing risk. We have identified a novel T6SS regulator and T6SS-dependent killing capacity in Acinetobacter baumannii clinical isolates with the aid of SecReT6 v3. 17,212 T6SSs and plentiful T6SS-related proteins in 26,573 bacterial complete genomes were also detected, analyzed and incorporated into the database. The database is freely available at https://bioinfo-mml.sjtu.edu.cn/SecReT6/ .


Multiscale combined techniques for evaluating emulsion stability: A critical review.
Emulsions are multiscale and thermodynamically unstable systems which will undergo various unstable processes over time. The behavior of emulsifier molecules at the oil-water interface and the properties of the interfacial film are very important to the stability of the emulsion. In this paper, we mainly discussed the instability phenomena and mechanisms of emulsions, the effects of interfacial films on the long-term stability of emulsions and summarized a set of systematic multiscale combined methods for studying emulsion stability, including droplet size and distribution, zeta-potential, the continuous phase viscosity, adsorption mass and thickness of the interfacial film, interfacial dilatational rheology, interfacial shear rheology, particle tracking microrheology, visualization technologies of the interfacial film, molecular dynamics simulation and the quantitative evaluation methods of emulsion stability. This review provides the latest research progress and a set of systematic multiscale combined techniques and methods for researchers who are committed to the study of oil-water interface and emulsion stability. In addition, this review has important guiding significances for designing and customizing interfacial films with different properties, so as to obtain emulsion-based delivery systems with varying stability, oil digestibility and bioactive substance utilization.


Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study.
In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects. Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups. This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.


Pediatric issues in disaster preparedness: meeting the educational needs of nurses-are we there yet?
Children have unique physical, emotional, and developmental needs making them particularly vulnerable during disasters. Most existing disaster preparedness courses lack a pediatric perspective. This article describes a pediatric disaster preparedness program presented to pediatric nurses in an urban, Level 1 trauma center. Survey results from the participants prior to the program revealed a lack of awareness of pediatric issues. Although the program resulted in an immediate improvement in awareness, retention fell back to precourse levels 2 years later. We conclude that pediatric disaster preparedness training should be integrated into hospital nursing curriculum on a regular basis.


Hypothalamic neuropeptides and the regulation of appetite.
Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding, acting both within the hypothalamus, and at other appetite regulating centres throughout the brain. Where classical neurotransmitters signal only within synapses, neuropeptides diffuse over greater distances affecting both nearby and distant neurons expressing the relevant receptors, which are often extrasynaptic. As well as triggering a behavioural output, neuropeptides also act as neuromodulators: altering the response of neurons to both neurotransmitters and circulating signals of nutrient status. The mechanisms of action of hypothalamic neuropeptides with established roles in feeding, including melanin-concentrating hormone (MCH), the orexins, α-melanocyte stimulating hormone (α-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin, are reviewed in this article, with emphasis laid on both their effects on appetite regulating centres throughout the brain, and on examining the evidence for their physiological roles. In addition, evidence for the involvement of several putative appetite regulating hypothalamic neuropeptides is assessed including, ghrelin, cocaine and amphetamine-regulated transcript (CART), neuropeptide W and the galanin-like peptides. This article is part of a Special Issue entitled 'Central control of Food Intake'.


Effect of a recent injection of purified protein derivative on diagnostic tests for tuberculosis in cattle infected with Mycobacterium bovis.
The intradermal injection of avian and bovine purified protein derivative into 15 Mycobacterium bovis-infected cattle reduced the capacity of a second single intradermal comparative tuberculin test carried out seven days later to predict accurately the animals' infection status (P < 0.001). In vitro lymphyocyte blastogenesis was also reduced (P < 0.05) but the in vitro production of interferon-gamma was unaffected.


Interactions of hydrology, geochemistry, and biodiversity in woodland ponds located in riverine floodplains: case study from Scotland.
The Gore Glen pond is located in the forested floodplain of the Gore River, in the Mid-Lothian region near Edinburgh, Scotland. This work has considered in detail the hydrology, hydrochemistry, and biodiversity of the pond together with all their interactions and in addition interactions with the adjacent Gore River. It is important as it is one of few studies considering all these issues for a pond located in a riverine floodplain. This work shows the pond is connected to the Gore River for discharge events in the river larger than a 1 in 5-year return period. For these events, the pond acts as an online storage feature and will attenuate the flow, thus contributing towards the mitigation of downstream flooding. These large events are also a potential source of the large amount of sediments, as well as adsorbed chemicals, accumulated in the pond. The open water surface of the pond is covered by duckweed, Lemna minor, for most of the year, and that has profound implications for the hydrobiological community and biogeochemical cycling. The system is characterised by nutrient release from sediments due to the extensive hypolimnion anoxia in the summer/autumn period caused by the decomposition of organic matter. Algae are mostly represented by epiphytic diatoms and the cyanobacterium Microcystis, but their development appears to be constrained by light penetration. The eutrophic conditions are also conducive for the population of Difflugia (Protozoa, Rhizopoda). This work improves our understanding of the ecological relations of testate amoebae-an important group which has recently been used as biological indicators for the analysis of paleoecological relationships and paleogeographical reconstructions.


Magnetic resonance imaging (MRI) helps differentiate renal cell carcinoma with sarcomatoid differentiation from renal cell carcinoma without sarcomatoid differentiation.
The aim of the present study is to identify predictive imaging findings and construct a diagnostic model for differentiating renal cell carcinoma (RCC) with and without sarcomatoid dedifferentiation (sRCC and non-sRCC). This study is a single-center retrospective study. All patients had magnetic resonance imaging (MRI) with gradient-echo T1-weighted images, single-shot T2-weighted images (T2WI), and enhanced nephrographic phase images. Forty pathologically confirmed sRCCs and 80 non-sRCCs were included in this study. Control cases were selected by matching the tumor diameter and the year of MRI. Two radiologists independently evaluated the following findings: growth pattern, presence of low-intensity area on T2WI in the tumor (T2LIA), presence of non-enhancing area, local tumor stage, and presence of regional lymphadenopathy. Two radiologists measured the diameter of the tumor, T2LIA, and the non-enhancing area. Multivariable logistic regression analysis was used to identify independent predictive factors for differentiating sRCC from non-sRCC. Selected variables were entered in the logistic regression model, and the area under the curve (AUC) was calculated for each reader with 95% confidence intervals (CIs). Larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 were associated with sRCC, and selected for the subsequent construction of a logistic regression model. With this model, the AUCs were 0.76 (95% CI, 0.66-0.85) and 0.70 (95% CI, 0.59-0.81) for prediction of sRCC. In conclusion, larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 are predictive findings of sRCC. As a result, the model constructed using these findings demonstrated a moderate degree of diagnostic accuracy.


Cognitive loss in dementia with Lewy bodies and Alzheimer disease.
Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.


Synthesis and spectroscopic properties of a new class of strongly fluorescent dipyrrinones.
A new, highly fluorescent (Phi(F) > or = 0.8) chromophore has been synthesized in one step from dipyrrinones by reaction with N,N-carbonyldiimidazole to form the 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidine-3,5-dione nucleus.


Efficacy of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline in Twin Families (VIPP-Twins): Study protocol for a randomized controlled trial.
Intervention programs with the aim of enhancing parenting quality have been found to be differentially effective in decreasing negative child outcomes such as externalizing behavioral problems, resulting in modest overall effect sizes. Here we present the protocol for a randomized controlled trial to examine the efficacy of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline for Twin Families (VIPP-Twins) on parenting quality and children's behavioral control and social competence. In addition, we aim to test the differential susceptibility theory; we examine differential efficacy of the intervention based on genetic make-up or temperament for both parents and children. Lastly, we explore neurobiological mechanisms underlying intervention effects on children's developmental outcomes. The original VIPP-SD was adapted for use in families with twins. The VIPP-Twins consists of five biweekly sessions in which the families are visited at home, parent-child interactions are videotaped and parents receive positive feedback on selected video fragments. Families (N = 225) with a same sex twin (mean age = 3.6 years) were recruited to participate in the study. The study consists of four assessments. After two baseline assessments in year 1 and year 2, a random 40 % of the sample will receive the VIPP-Twins program. The first post-test assessment will be carried out one month after the intervention and there will be a long term follow-up assessment two years after the intervention. Measures include observational assessments of parenting and children's social competence and behavioral control, and neurobiological assessments (i.e., hormonal functioning and neural (re-)activity). Results of the study will provide insights in the efficacy of the VIPP-Twins and reveal moderators and mediators of program efficacy. Overall the randomized controlled trial is an experimental test of the differential susceptibility theory. Dutch Trial Register: NTR5312 ; Date registered: July 20, 2015.


Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases.
First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day. With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.


Immunomodulatory effect of vitamin D on the STATs and transcription factors of CD4+ T cell subsets in pregnant women with preeclampsia.
This study evaluated the in vitro modulatory effect of vitamin D (VD) on T cells, by determining the expression of STATs and the transcription factors of each CD4+ T cell subsets. Twenty women with preeclampsia (PE) and 20 normotensive pregnant women were studied. Peripheral blood mononuclear cells were cultured with or without VD to analyse the STATs and transcription factors by flow cytometry, and cytokines production by ELISA. The plasma levels of VD were lower in the PE group. Treatment of cells with VD decreased STAT1/STAT4/T-bet, STAT3/RORγt, and increased STAT6/GATA-3 and STAT5/FoxP3 in preeclamptic women. Treatment with VD also decreased the levels of inflammatory cytokines and increased IL-10 and TGF-β. This hormone exerts immunomodulatory effects on the STAT signalling pathway, shifting the inflammatory profiles, Th1/Th17 cells to Th2/Treg profiles, and it can be suggested as a promising strategy to regulate the systemic inflammatory response in PE.


Disparities in alcohol use and heavy episodic drinking among bisexual people: A systematic review, meta-analysis, and meta-regression.
Alcohol consumption is more prevalent among sexual minorities than among heterosexuals; however, differences between minority sexual orientation groups are understudied. This systematic review and meta-analysis aimed to summarize existing evidence on the prevalence of alcohol use among bisexual people compared to their lesbian/gay and heterosexual counterparts. A systematic review of literature from 1995 to May 2020 was performed using Medline, PsycInfo, and Embase (OVID), Scopus, CINHAL and LGBT Life (EBSCO), combining keywords for bisexuality and alcohol use. Peer-reviewed publications that reported quantitative data on alcohol use among bisexual people were included. A random-effects model was used to pool the prevalence of two outcomes: any alcohol use and heavy episodic drinking (HED). Subgroup analysis and random-effects meta-regression were used to explore heterogeneity. Of 105 studies eligible for data extraction, the overall prevalence of alcohol use was higher among bisexuals compared to lesbian/gay and heterosexual people. For example, the prevalence of past-month HED was 30.0% (28.2, 31.8) among bisexual people versus 25.5% (23.8, 27.2) among lesbian/gay and 21.3% (19.6, 23.0) among heterosexual individuals. Pooled odds ratio estimates showed that bisexual people were more likely to report alcohol use and HED compared to their counterparts. Gender was a significant effect modifier in meta-regression analysis, with greater disparities among women than among men. These results highlight the need for additional research to understand factors underlying bisexual people's greater risk, and particularly bisexual women, as well as alcohol use interventions that are targeted towards the specific needs of bisexual people.


Contribution of soluble and particulate-matter fractions to the total glyphosate and AMPA load in water bodies associated with horticulture.
Glyphosate-based herbicides are used in horticulture to prepare the soil for planting and to remove weeds surrounding greenhouses. Superficial runoff from production units can lead to glyphosate reaching nearby water bodies. Previous publications reported glyphosate's high affinity for suspended solids. The aim of the present work was to investigate the occurrence and concentrations of glyphosate and aminomethylphosphonic acid (AMPA) in soluble and suspended-particulate-matter fractions within the basin of the Carnaval-Stream, a water body traversing a horticultural greenbelt. Glyphosate and AMPA were detected in 67% and 83% of the samples, occurring in both fractions simultaneously at respective maximum concentrations of 17.0 and 4.5 μg.L1 in the soluble fraction and 35,620 and 19,586 μg.kg1 in the particulates. Although the calculated partition coefficients Kd confirmed that these compounds had tended to be associated with the particulate matter, the soluble glyphosate and AMPA contributed, on the average, to more than 90% of the total water volume. Although the analysis of suspended particulates is considered a more sensitive strategy for glyphosate and AMPA detection in surface water, these results demonstrate the need to analyze the soluble phase. The continual occurrence throughout a 3-year sampling was sufficient evidence demonstrating the use of glyphosate in horticulture.


Associations between mixed urinary phenols and parabens metabolites and bone mineral density: Four statistical models.
Phenols and parabens widely exist in personal care and consumer products and have been proved to be endocrine disrupting chemicals that could disturb bone metabolism. The current studies focusing on the associations between phenols and parabens with bone mineral density (BMD) drew contradictory conclusions. Considering the bias might be due to not considering the effects of mixed exposure, we conducted the first cross-sectional study to investigate the associations of both single and mixed metabolites of phenols and parabens with BMD in three populations by setting up four models: generalized linear regression model (GLM), weighted quantile sum (WQS) regression model, quantile g-computation (qgcomp) model and Bayesian kernel machine regression (BKMR) model, based on the US National Health and Nutrition Examination Survey (NHANES) database. We found that the association between the mixtures and total femur BMD in men was significantly negative. Bisphenol A (BPA) was shown to play the most important role in this negative association in the BKMR model, and this negative association was also confirmed in the GLM model with β coefficient (95% CI) being -0.02 (-0.04, -0.01). The relationships between the mixtures and femoral neck and trochanter BMD in postmenopausal women were significantly positive. Benzophenone-3 (BP-3) played the most significant role in the positive association with trochanter BMD, as confirmed by the WQS, qgcomp and BKMR models, and this positive association was also verified by the GLM model with β coefficient (95% CI) being 0.01 (0.00, 0.02). In conclusion, the association between the mixed phenols and parabens and BMD was negative in men while was positive in postmenopausal women, which was gender-specific. This study might provide new ideas for the prevention and treatment of osteoporosis and the control of personal care and consumer products containing phenols and parabens in the future.


Sugar consumption and behavioural inhibition in the rat.
The metabolic effects of sugary drinks have been extensively studied, whereas the effects on psychological processes have received relatively limited attention. Several studies have found that high-sugar diets can produce impaired performance by rats on tests assessing spatial learning and memory. In contrast, despite claims that weakened inhibitory control underlies many sugar-induced deficits, evidence supporting this proposal has been limited. The aim of the present study was to assess the impact of high-sugar diets on response inhibition, as measured by rats' performance on a differential reinforcement of low rates schedule (DRL) in Experiments 1 and 2 and on a Pavlovian discrimination reversal task in Experiment 3. In all three experiments a 30-day diet stage, in which Sugar groups were given unrestricted access to 10% sucrose solution and Control groups had access to water only, was followed by behavioural tests. In Experiment 1 the Sugar group performed poorly on a spatial memory task, but no difference was detected between the performances of the two groups in the DRL test. In Experiment 2 longer DRL training was given and post-diet performance was assessed both before and after access to sugar was withdrawn. Null results were obtained under both conditions. In Experiment 3 rats' performance on a discrimination learned prior to the diet intervention was not affected by the high-sugar diet, but neither was performance once the discrimination was reversed. The implications of these results for understanding of sugar-induced psychological deficits are discussed.


Eating disorders and social maladjustment in female medical students.
A survey of eating disorders in female medical students showed that 15% had a lifetime history of bulimia or anorexia nervosa. On the work, social/leisure, and overall subscales of the Social Adjustment Scale Self-Report, those medical students who had current or previous eating disorders reported greater social maladjustment then medical students who did not have eating disorders.


The role of glutamic acid 73 in adrenomedullin interactions with rodent AM2 receptors.
Adrenomedullin (AM) is a peptide, which is important for vascular development. There is much interest in the clinical potential of its receptors. The mode of AM binding to its receptors is poorly understood. Previous studies have identified amino acid Glu74, which is found in the receptor activity-modifying protein (RAMP3) subunit of the AM(2) receptor as important for high affinity AM interactions with this receptor. Its reciprocal residue in RAMP1 (Trp) impedes AM interactions in the closely related human calcitonin gene-related peptide (CGRP) receptor. The Glu is conserved in RAMP3 across species, supporting its role in contributing to AM binding. We mutated this residue in rat and mouse RAMP3 to Ala, Lys and Trp to determine its function in rodent AM(2) receptors. Only the Trp substitution in mouse RAMP3 produced a substantial reduction in AM potency. However, mutation of the Lys found in rat RAMP1 to Glu enhanced AM potency. Although Glu is highly conserved in RAMP3, this work suggests that it may only make a small or indirect contribution to AM interactions. Nevertheless, the equivalent amino acid in RAMP1 may serve to impair high affinity AM interactions.


Disappearance of sleep apnea by tracheal intubation in Creutzfeldt-Jakob disease.
We have described a patient with Creutzfeldt-Jakob disease who showed disappearance of sleep apnea by tracheal intubation. All night polygraphic study revealed a clear correlation between the cyclic EEG change and sleep apnea. The periodic synchronous discharge (PSD) phase in EEG corresponded to the breathing phase in respiration and non-PSD phase corresponded to the apneic phase. Intratracheal intubation has completely stopped both the apnea and the cyclic EEG change. Therefore, we assumed that the PSD-non-PSD cycle in EEG might causally relate with the peripheral obstruction of the airway during sleep.


Acceleration time ratio for the assessment of extracranial internal carotid artery stenosis.
To apply the acceleration time (AcT) ratio as an additional marker for diagnosing internal carotid artery (ICA) stenosis. Carotid artery sonography was performed in 140 patients, and the AcT ratio was calculated as the AcT of the ICA divided by the AcT of the ipsilateral common carotid artery, and compared with diameter stenosis. There was a significant correlation between diameter stenosis and the AcT ratio. The receiver operating characteristic curve revealed a cutoff level of 1.5, with 90.0 % sensitivity and 93.5 % specificity for stenosis >65 %. Our results indicate that applying the AcT ratio can help in the diagnosis of ICA stenosis.


HIV associated dementia: role for neurosteroids.
HIV associated dementia (HAD), is a neuronal complication of HIV infection and causes cognitive and motor impairment. The cognitive decline in HAD is due to widespread synaptic loss than neuronal loss. The neurotoxicity in HAD is caused by activation of NMDA receptors by HIV-proteins but the exact mechanism of the synaptic loss is yet to be determined. This article explores a novel pathomechanism for the observed synaptic loss. The HIV-proteins augment NMDA mediated increase of intracellular Ca(2+) in neurons which activates nNOs for Nitric Oxide (NO) synthesis. The NO activates MAPK and phosphorylates Microtubule-associated protein-2(MAP2) at specific sites causing conformational changes, microtubular disassembly and promote MAP2 degradation by the ubiquitin-proteosome pathway. Under physiological conditions Ca(2+) signaling increases cholesterol transport into mitochondria for steroidogenesis by the CYP11A1. The neurosteroid pregnenolone binds to MAP2 and causes inhibition of phosphorylation, increase in microtubule assembly and decrease MAP2 degradation. The NO can inhibits CYP11A1 in a concentration dependent manner and reduces steroidogeneisis. There is a upregulation of NO production in HAD from HIV infected microglia and astrocytes which cross neuronal membrane and increase intracellular NO. This can cause profound inhibition of steroidogenesis in the brain, increase MAP2 degradation and synaptic loss in presence of HIV-proteins.


Association between number of abnormal glucose values and severity of fasting plasma glucose in IADPSG criteria and maternal outcomes in women with gestational diabetes mellitus.
The International Association for Diabetes in Pregnancy Study Group (IADPSG) criteria recommend a single-step diagnostic oral glucose tolerance test (OGTT) for diagnosis of gestational diabetes mellitus (GDM). The aim of this study was to examine the association between the number of abnormal glucose values and levels of FPG with pregnancy outcomes. Pregnant women (n=1,044) were screened for GDM at maternity centers in South India using IADPSG criteria. OGTTs were classified based on the number of abnormal glucose values (any one value or more than one value high) and fasting plasma glucose (FPG) values (<92mg/dl,92-100mg/dl,>100mg/dl) and correlated with pregnancy outcomes. Odds ratio were adjusted for age, BMI, gestational week at diagnosis, family history of diabetes, previous history of GDM, gestational week at delivery and birth weight. For macrosomia and large for gestation age, birth weight was excluded from the model. Risk of caesarean section was significantly higher in women with any one abnormal glucose value (OR: 1.49; 95%CI: 1.07-2.09). This further increased in those with >1 value (OR: 1.35; 95%CI: 0.87-2.10), when compared to women with all values normal. Risk of large for gestation age (LGA) was higher in women with FPG 92-100mg/dl (OR: 1.37; 95%CI: 0.80-2.35) and in those with FPG >100mg/dl (OR: 1.87; 95%CI: 1.04-3.35), compared to those with FPG <92mg/dl. The risk for poor pregnancy outcomes starts in those with one abnormal value in the OGTT or with FPG >92mg/dl but becomes significantly higher in those with higher abnormal values.


Production of Ficoll, Percoll, and albumin gradients by the freeze-thaw method.
Ficoll, sucrose, albumin, and Percoll, a modified colloidal silica centrifugation medium, all form density gradients upon freezing and thawing. The data suggest that any density gradient material will form gradients upon freezing and thawing, provided the material is stable to freezing.


Complete sequence of a novel alphaendornavirus from the phytopathogenic fungus Arthrocladiella mougeotii.
A novel double-stranded RNA (dsRNA) virus, which was provisionally named Arthrocladiella mougeotii endornavirus (AmEV), was isolated from Arthrocladiella mougeotii, the phytopathogenic fungus infecting Lycium chinense in Beijing, China. The genome of AmEV is 11,683 nucleotides in length with a 5' and 3' non-coding region of 16 and 50 nt, respectively, as well as a single 11,617-nt long open reading frame potentially encoding a putative protein of 3,871 amino acids with conserved Helicase and RNA-dependent RNA polymerase (RdRp) domains. Phylogenetic analysis based on the the amino acid sequence of the RdRp showed that AmEV is most closely related to Erysiphe cichoracearum endornavirus (EcEV).


Incorporating water-release and lateral protein interactions in modeling equilibrium adsorption for ion-exchange chromatography.
The equilibrium adsorption of two albumin proteins on a commercial ion exchanger has been studied using a colloidal model. The model accounts for electrostatic and van der Waals forces between proteins and the ion exchanger surface, the energy of interaction between adsorbed proteins, and the contribution of entropy from water-release accompanying protein adsorption. Protein-surface interactions were calculated using methods previously reported in the literature. Lateral interactions between adsorbed proteins were experimentally measured with microcalorimetry. Water-release was estimated by applying the preferential interaction approach to chromatographic retention data. The adsorption of ovalbumin and bovine serum albumin on an anion exchanger at solution pH>pI of protein was measured. The experimental isotherms have been modeled from the linear region to saturation, and the influence of three modulating alkali chlorides on capacity has been evaluated. The heat of adsorption is endothermic for all cases studied, despite the fact that the net charge on the protein is opposite that of the adsorbing surface. Strong repulsive forces between adsorbed proteins underlie the endothermic heat of adsorption, and these forces intensify with protein loading. It was found that the driving force for adsorption is the entropy increase due to the release of water from the protein and adsorbent surfaces. It is shown that the colloidal model predicts protein adsorption capacity in both the linear and non-linear isotherm regions, and can account for the effects of modulating salt.


Chromosome-Length Haplotypes with StrandPhaseR and Strand-seq.
Dense local haplotypes can now readily be extracted from long-read or droplet-based sequence data. However, these methods struggle to combine subchromosomal haplotype blocks into global chromosome-length haplotypes. Strand-seq is a single cell sequencing technique that uses read orientation to capture sparse global phase information by sequencing only one of two DNA strands for each parental homolog. In combination with dense local haplotypes from other technologies, Strand-seq data can be used to obtain complete chromosome-length phase information. In this chapter, we run the R package StrandPhaseR to phase SNVs using publicly available sequence data for sample HG005 of the Genome in a Bottle project.


Biological stress responses to multitasking and work interruptions: A randomized controlled trial.
In the course of digitalization, new stressors are emerging. In modern working and living environments, two ubiquitous, technology-mediated stressors are multitasking demands and work interruptions. However, biological stress response patterns to multitasking and work interruptions have been sparsely investigated so far. We thus aimed to comprehensively assess biological stress response patterns to both stressors and, additionally, test whether responses differ between digital and partially non-digital settings. A controlled experimental set-up was established and humans' biological markers of the Sympathetic Nervous System (SNS), the hypothalamic-pituitary adrenal (HPA) axis, and the immune system were assessed. N = 186 healthy participants (mean age: 23.2 ± 4.3 years, 74.7% female, body mass-index: 22.3 ± 3.1 kg/m2) took part in this pre-registered study. Each participant was randomly assigned to one of 6 experimental conditions (1 digital single-task, 3 dual-tasks [2 parallel tasks and 1 interruption], 1 multitasking, and 1 passive, control condition). Each one of the dual-tasking as well as the multitasking conditions included a non-digital sub-task, i.e., performing a task in presence of an examiner. All other conditions involved digital tasks only. Salivary alpha-amylase (sAA) levels as a marker for SNS reactivity significantly changed in work interruptions, parallel dual-tasking, and multitasking conditions. No changes were found for control conditions. Furthermore, no significant changes over time and no differences between the conditions were identified for three biological markers: cortisol as marker for HPA axis activity as well as for two immune system markers (secretory Immunoglobulin-A, C-reactive protein). A time course similar to sAA was found for perceived stress: with increases during task execution and decreases afterwards in multitasking and parallel dual-tasking. Yet, it did not change for the work interruption, passive control, and single-tasking condition. Overall, our findings show that dual- and multitasking are perceived as stressful and are associated with an activation of the SNS, but not with responses of HPA axis or immune system. This was consistent for digital as well as partially digital task demands. Our findings will also inform future research into the differential stress effects of digital and non-digital tasks to advance our understanding of biological stress response-patterns to multitasking and work interruptions. Therefore, our findings are highly relevant for understanding the long-term biological health effects of stress in modern (digitalized) environments.


Prediction of Salmonella carcass contamination by a comparative quantitative analysis of E. coli and Salmonella during pig slaughter.
Faecal contamination of carcasses in the slaughterhouse is generally considered to be the source of Salmonella on pork. In this study the hygiene indicator Escherichia coli is used to quantify faecal contamination of carcasses and it is hypothesized that it can be used to predict the quantitative carcass contamination with Salmonella, when the distribution of Salmonella concentrations in faeces is known. Paired pig sample data (faecal samples and carcass swabs) were obtained from five slaughterhouses and analysed for prevalence and concentrations of E. coli and Salmonella. A simple model was developed to describe the faecal contamination of carcasses using the E. coli data. The E. coli results suggested different hygiene performances in different slaughterhouses, and showed that a model assuming that carcasses are predominantly contaminated by their own faeces was not appropriate. Observed Salmonella prevalences were low (on average 1.9% on carcasses) and between slaughterhouses the prevalences ranked differently than the hygiene performance based on the E. coli data suggested. Also, the Salmonella concentrations predicted using E. coli as a faecal indicator were lower than the observed Salmonella concentrations. It is concluded that the faecal carriage of Salmonella together with the faecal contamination of carcasses, as predicted from E. coli data in the animal faeces and hygiene performance of the slaughterhouse, is not sufficient to explain carcass contamination with Salmonella. Our extensive data set showed that other factors than the observed faecal carriage of Salmonella by the individual animals brought to slaughter, play a more important role in the Salmonella carcass contamination of pork.


New Insights into Mechanisms and Functions of Nuclear Size Regulation.
Nuclear size is generally maintained within a defined range in a given cell type. Changes in cell size that occur during cell growth, development, and differentiation are accompanied by dynamic nuclear size adjustments in order to establish appropriate nuclear-to-cytoplasmic volume relationships. It has long been recognized that aberrations in nuclear size are associated with certain disease states, most notably cancer. Nuclear size and morphology must impact nuclear and cellular functions. Understanding these functional implications requires an understanding of the mechanisms that control nuclear size. In this review, we first provide a general overview of the diverse cellular structures and activities that contribute to nuclear size control, including structural components of the nucleus, effects of DNA amount and chromatin compaction, signaling, and transport pathways that impinge on the nucleus, extranuclear structures, and cell cycle state. We then detail some of the key mechanistic findings about nuclear size regulation that have been gleaned from a variety of model organisms. Lastly, we review studies that have implicated nuclear size in the regulation of cell and nuclear function and speculate on the potential functional significance of nuclear size in chromatin organization, gene expression, nuclear mechanics, and disease. With many fundamental cell biological questions remaining to be answered, the field of nuclear size regulation is still wide open.


Development and validation of a reversed-phase ion-pair liquid chromatography method for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams.
A reversed-phase ion-pair high-performance liquid chromatographic method was developed and validated for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams. The determination was performed on a BDS C 18 analytical column (250 x 4.6 mm i.d., 5 microm particle size); the mobile phase consisted of 0.020 M tetrabutylammonium hydroxide and 0.025 M potassium dihydrogen phosphate (pH 6.8) mixed with acetonitrile in a ratio (77:23, v/v) and pumped at a flow rate 1.00 ml min(-1). The UV detector was operated at 260 nm. The retention times of the magnesium ascorbyl phosphate, melatonin and chlorthalidone that was used as internal standard, were 6.55, 9.18 and 11.07 min, respectively. Calibration graphs are linear (r better than 0.9990, n=6), in concentration range 1.00-10.00 microg ml(-1) for magnesium ascorbyl phosphate and 0.63-6.25 microg ml(-1) for melatonin. The intra- and inter-day R.S.D. values were less than 6.0%, while the relative percentage error E(r) was less than 3.5% (n=5). The quantitation limits were 0.69 and 0.47 microg ml(-1), for magnesium ascorbyl phosphate and melatonin, respectively. The method was applied to the analysis of a cosmetic cream and proved to be suitable for rapid and reliable quality control.