Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis.
Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91-1.29; p = 0.4) and 1.01 (95% CI, 0.78-1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.


Laryngeal effects of nasal allergen provocation in singers with allergic rhinitis.
In spite of our recent insight into nasobronchial interaction mechanisms in allergic airway disease, the association between allergic rhinitis and voice complaints remains obscure. To evaluate the effects of nasal allergen provocation and seasonal grass pollen exposure on subjective and objective laryngeal parameters in singers with and without allergic rhinitis, an observational case control study was conducted. Prior to the pollen season, six grass pollen allergic and six non-allergic semiprofessional singers were exposed to nebulized sham solution and grass pollen extract (HAL°) in rising concentrations. After 3 min, 60 min and 24 h, nasal and laryngeal complaints were evaluated by the use of a visual analog scale (VAS). Laryngeal parameters like voice appearance (video stroboscopic images), voice range profile and subjective (GRBAS) and objective (jitter, shimmer, H/N, DSI) voice quality were evaluated before provocation, after 60 min and 24 h. During the pollen season, the allergic singers were re-evaluated. Results showed that in allergic singers both nasal (TNS of 4.0 ± 2.4 vs. 0.0 ± 0.0, p < 0.05) and laryngeal complaints (TLS of 1.4 ± 1.1 vs. 0.0 ± 0.2, p < 0.05) were induced at 3 min after the provocation. The induced laryngeal complaints were the feeling of laryngeal irritation, secretions and globus. No change in voice quality or stroboscopy score was measured. During the pollen season, laryngeal complaints were present (TLS of 2.4 ± 2.4) in allergic singers, without evidence for objective voice and laryngeal changes. In conclusion, we here demonstrate the rapid induction of laryngeal complaints in allergic singers by nasal allergen provocation and during the pollen season. There was no subject reported or investigator measured change in voice quality. No change in stroboscopy score was measured.


[Effects of exposure time using preliminary concentrations on the mutagenic effect of the basic action of one-center and dual-center mutagens].
The effect of exposition with pretreatment for thiophosphamide and dipin of human lymphocytes at Go phase was investigated. There were used 5 low concentrations of mutagens: 2, 0, 2; 2.10(-2); 2.10(-3), 2.10(-4) mcg/ml with different exposure: 1/4 hr, 1/2 hr, 1 hr and 4 hr and high concentration of 20 mcg/ml by which cell have been treated. There was discovered the dependence of the "protective" concentration on the exposition: the increase of exposition of pretreatment induced the decrease of "protective" concentration and vice versa.


Elevated expression temperature in a mesophilic host results in increased secretion of a hyperthermophilic enzyme and decreased cell stress.
Efficient protein folding and trafficking are essential for high-level production of secretory proteins. Slow folding or misfolding of proteins can lead to secretory bottlenecks that reduce productivity. We previously examined the expression of a hyperthermophilic tetramer Pyrococcus furiosus beta-glucosidase in the yeast Saccharomyces cerevisiae. A secretory bottleneck was found in the endoplasmic reticulum, presumably due to beta-glucosidase misfolding. By increasing expression temperature from 30 degrees C up to 40 degrees C, secretion yields increased by as much as 440% per cell to greater than 100 mg/L at 37 degrees C. We examined the effect of temperature on beta-glucosidase folding and secretion and determined that increased expression temperature decreased intracellularly retained, insoluble beta-glucosidase. Likewise, stress on the cell caused by beta-glucosidase expression was found to be greatly reduced at 37 degrees C compared to 30 degrees C. Levels of the abundant endoplasmic reticulum chaperone, BiP, were relatively unchanged at these temperatures during heterologous expression. Using cycloheximide to inhibit new protein synthesis, we determined that the increase in secretion is likely due to the effect of temperature on the beta-glucosidase itself rather than the cell's response to elevated temperatures. We believe that this is the first evidence of in vivo effects of temperature on the secretion of hyperthermophilic proteins.


What counts when heartbeats are counted.
Schandry's mental heartbeat tracking task is a widely used measure of interoception, assessing heartbeat perception. We classify the factors that contribute to performance on the task as (i) trait-like characteristics, (ii) expectation-related factors, and (iii) factors showing participants' task set. We recommend conducting further research to better understand what exactly the task measures.


The link between mind wandering and learning in children.
Mind wandering is a common everyday experience during which attention shifts from the here and now; in adults and adolescents, it is associated with poorer performance in educationally significant tasks. This study is the first to directly assess the impact of mind wandering on memory retention in children before the adolescent period. A sample of 97 children aged 6-11 years engaged in a listening activity, and the frequency of mind wandering was measured using intermittent thought probes. Participants then completed a memory retention test. Children reported mind wandering on ∼25% of the thought probes, and frequency did not increase with age. When controlling for the impact of age and vocabulary skills, mind wandering frequency accounted for a large and significant portion of variance in memory scores. Mind wandering frequency also mediated the relation between children's ratings of topic interest and memory scores. The results indicate that mind wandering can be reliably measured in children and is of educational significance.


Quantification of non-alcoholic fatty liver disease progression in 3D liver microtissues using impedance spectroscopy.
Non-alcoholic fatty liver disease (NAFLD) has become a global pandemic. However, a pharmacological cure has not been approved for NAFLD treatment. The greatest barriers to the development of new treatments are the ambiguous criteria among the NAFLD stages and the lack of quantitative methodologies for its disease assessment in a translatable preclinical model. In this study, we developed impedance assessment systems to quantify NAFLD progression in three-dimensional (3D) liver microtissue (hMT). The hMT model undergoing NAFLD represents clinical-like characteristics for a range of stages, such as lipid accumulation, cell ballooning, and stiffening. Each stage can be quantitatively assessed by an impedance system with microchannels under constant or dynamic pressure, depending on the relevant mechanical and morphological changes used in the clinical assessment of NAFLD. We determined a correlation between the impedance parameters and pathophysiological characteristics, such as gap widening and cytoplasmic deformation associated with NAFLD progression using bioimpedance simulation, showing hMTs struggling to return to normal states. In addition, we identified the relative stiffness to assess fibrogenesis from the correlation of resistance change and elongation length into the smaller channel of hMTs. We hope this methodology will have a significant impact on drug development by facilitating improved NAFLD assessment.


The equilibrium of phosphatidylcholine-amino acid system in monolayer at the air/water interface.
Monolayers of phosphatidylcholine, tyrosine, and phenylalanine and binary mixtures phosphatidylcholine-tyrosine or phosphatidylcholine-phenylalanine were investigated at the air/water interface. Phosphatidylcholine (lecithin, PC), tyrosine (Tyr), and phenylalanine (Phe) were used in the experiment. The surface tension values of pure and mixed monolayers were used to calculate π-A isotherms. The surface tension measurements were carried out at 22°C using an improved Teflon trough and a Nima 9000 tensiometer. The Teflon trough was filled with a subphase of triple-distilled water. Known amounts of lipid dissolved in 1-chloropropane were placed at the surface using a syringe. The interactions between lecithin and amino acid result in significant deviations from the additivity rule. An equilibrium theory to describe the behavior of monolayer components at the air/water interface was developed in order to obtain the stability constants of PC-Tyr as well as PC-Phe complexes. We considered the equilibrium between the individual components and the complex and established that lecithin and amino acid formed highly stable 1:1 complex.


Bone mineral losses in alcoholics.
Bone mineral measurements were performed at five skeletal sites in seven alcoholics. The mean annual loss of bone mineral in alcoholics was about 2 per cent higher than that of controls.


Using ambulatory assessment to measure dynamic risk processes in affective disorders.
Rapid advances in the capability and affordability of digital technology have begun to allow for the intensive monitoring of psychological and physiological processes associated with affective disorders in daily life. This technology may enable researchers to overcome some limitations of traditional methods for studying risk in affective disorders, which often (implicitly) assume that risk factors are distal and static - that they do not change over time. In contrast, ambulatory assessment (AA) is particularly suited to measure dynamic "real-world" processes and to detect fluctuations in proximal risk for outcomes of interest. We highlight key questions about proximal and distal risk for affective disorders that AA methods (with multilevel modeling, or fully-idiographic methods) allow researchers to evaluate. Key questions include between-subject questions to understand who is at risk (e.g., are people with more affective instability at greater risk than others?) and within-subject questions to understand when risk is most acute among those who are at risk (e.g., does suicidal ideation increase when people show more sympathetic activation than usual?). We discuss practical study design and analytic strategy considerations for evaluating questions of risk in context, and the benefits and limitations of self-reported vs. passively-collected AA. Measurements may only be as accurate as the observation period is representative of individuals' usual life contexts. Active measurement techniques are limited by the ability and willingness to self-report. We conclude by discussing how monitoring proximal risk with AA may be leveraged for translation into personalized, real-time interventions to reduce risk.


A novel multi-objective metaheuristic algorithm for protein-peptide docking and benchmarking on the LEADS-PEP dataset.
Protein-peptide interactions have attracted the attention of many drug discovery scientists due to their possible druggability features on most key biological activities such as regulating disease-related signaling pathways and enhancing the immune system's responses. Different studies have utilized some protein-peptide-specific docking algorithms/methods to predict protein-peptide interactions. However, the existing algorithms/methods suffer from two serious limitations which make them unsuitable for protein-peptide docking problems. First, it seems that the prevalent approaches require to be modified and remodeled for weighting the unbounded forces between a protein and a peptide. Second, they do not employ state-of-the-art search algorithms for detecting the 3D pose of a peptide relative to a protein. To address these restrictions, the present study aims to introduce a novel multi-objective algorithm, which first generates some potential 3D poses of a peptide, and then, improves them through its operators. The candidate solutions are further evaluated using Multi-Objective Pareto Front (MOPF) optimization concepts. To this end, van der Waals, electrostatic, solvation, and hydrogen bond energies between the atoms of a protein and designated peptide are computed. To evaluate the algorithm, it is first applied to the LEADS-PEP dataset containing 53 protein-peptide complexes with up to 53 rotatable branches/bonds and then compared with three popular/efficient algorithms. The obtained results indicate that the MOPF-based approaches which reduce the backbone RMSD between the original and predicted states, achieve significantly better results in terms of the success rate in predicting the near-native conditions. Besides, a comparison between the different types of search algorithms reveals that efficient ones like the multi-objective Trader/differential evolution algorithm can predict protein-peptide interactions better than the popular algorithms such as the multi-objective genetic/particle swarm optimization algorithms.


A quick measure to guide allocation of chaplains' time with hospitalized veterans.
Assessing veterans' desire to see a chaplain can be difficult. Due to alleged personal weakness associated with seeing a chaplain while on active duty, veterans may still be reluctant to admit a need. Additionally chaplains may be challenged with multiple time demands. We devised and correlated with known instruments a single item containing four graded responses. One correlation was strong, suggesting the question's potential for serving as a useful tool for allocation of chaplains' time.


Correlation of in vitro anti-proliferative potential with in vivo teratogenicity in a series of valproate analogues.
The prediction that an anti-proliferative effect coupled with a pro-differentiative action will detect a neural tube teratogen has been validated by comparison of these in vitro endpoints with in vivo teratogenicity in a series of closely allied valproate structural analogues. The majority of the compounds significantly inhibited C6 glioma proliferation, the most potent compounds being ranked as octanoic acid > 2-propylhexanoic acid > or = 2-ethylhexanoic acid > or = valproic acid. The anti-proliferative potency of these compounds did not correlate strictly to their relative in vivo teratogenic potential. Valproic acid exhibited an anti-proliferative IC50 of 1.45 mM, whereas 2-propyl-2-pentenoic acid and 2-propyl-4-pentenoic acid were virtually indistinguishable, exhibiting significantly lower IC50 values of 2.5 and 2.55 mM, respectively. The concanavalin A lectin affinity assay was employed to establish whether an anti-proliferative action was coupled with an increased state of cell differentiation. In this lectin affinity assay, the most potent analogues to significantly attenuate the affinity of exposed C6 glioma cells for concanavalin A lectin-coated plastic included 2-butylhexanoic acid, 2-propyl-4-pentenoic acid, 2-propylhexanoic acid and 2-ethylhexanoic acid in a manner which can be related to their relative teratogenic potencies in vivo. All compounds screened positive in both the anti-proliferative and pro-differentiative assays exhibited in vivo exencephalic rates of 5-44%. These included valproic acid, 2-ethylhexanoic acid, 2-propylhexanoic acid and 2-butylhexanoic acid. It would appear that combined anti-proliferative and pro-differentiative screens provide a promising detection system for teratogenic status in a series of valproate analogues.


Maturity-onset diabetes of the young secondary to HNF1B variants (HNF1B-MODY): a series of 10 patients from a single diabetes center.
Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant condition and represents 1-5% of all cases of diabetes mellitus. MODY is often misdiagnosed as type 1 or type 2 diabetes. The rare subtype 5 (HNF1B-MODY) is due to hepatocyte nuclear factor 1β (HNF1B) molecular alteration and is remarkable for its multisystemic phenotypes characterized by a broad spectrum of pancreatic and extra-pancreatic clinical manifestations. Retrospective study of patients with HNF1B-MODY diagnosis followed in the Centro Hospitalar Universitário Lisboa Central (Lisbon, Portugal). Demographic data, medical history, clinical and laboratory data, follow-up and treatment procedures were obtained from electronic medical records. We found 10 patients with HNF1B variants (7 index cases). The median age at diabetes diagnosis was 28 (IQR 24) years and the median age at HNF1B-MODY diagnosis was 40.5 (IQR 23) years. Six patients were initially misclassified as type 1 and 4 as type 2 diabetes. The average time between diabetes diagnosis and the diagnosis of HNF1B-MODY was 16.5 years. Diabetes was the first manifestation in half of the cases. The other half presented with kidney malformations and chronic kidney disease at pediatric age as the first manifestation. All these patients were submitted to kidney transplantation. Long-term diabetes complications included retinopathy (4/10), peripheral neuropathy (2/10) and ischemic cardiomyopathy (1/10). Other extra-pancreatic manifestations included liver test alterations (4/10) and congenital malformation of the female reproductive tract (1/6). History of a first-degree relative with diabetes and/or nephropathy diagnosed at a young age was present in 5 of the 7 index cases. Despite being a rare disease, HNF1B-MODY is underdiagnosed and often misclassified. It should be suspected in patients with diabetes and CKD, especially when diabetes appears at a young age, a family history is present, and nephropathy appears before/shortly after the diagnosis of diabetes. Presence of unexplained liver disease increases the degree of suspicion for HNF1B-MODY. Early diagnosis is important to minimize complications and to allow familial screening and pre-conception genetic counseling. Trial registration not applicable due to the retrospective nature of the study, non-interventional.


Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis.
Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma and the vascular walls of patients with cardiovascular diseases, especially in atherosclerotic lesions. Consequently, their role in lipid disorders is widely suspected, but they may also contribute to the development of important degenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, osteoporosis, age-related macular degeneration, and cataract. Since these pathologies can be associated with the presence of apoptotic cells, oxidative and inflammatory processes, and lipid disorders, the ability of oxysterols to trigger cell death, activate oxidation and inflammation, and modulate lipid homeostasis is being extensively studied. There are several important considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols. It is therefore important to determine their biological activities and identify their signaling pathways, when they are used either in isolation or as mixtures. In these conditions, oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or no effects whatsoever. Moreover, with cytotoxic oxysterols, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures was observed, demonstrating that cytotoxic oxysterols were phospholipidosis inducers. This basic knowledge on oxysterols contributes to a better understanding of the associated pathologies, so that new treatments and drugs can be designed.


Twice-weekly intravenous treatment of pancreatic cancer with atrial natriuretic peptide and vessel dilator.
Atrial natriuretic peptide (ANP) and vessel dilator eliminate 80% and 33% of human pancreatic adenocarcinomas growing in athymic mice when given subcutaneously for 28 days via osmotic pumps. To determine if similar beneficial effects can be obtained by ANP and vessel dilator on a bi-weekly basis, bolus infusion via vascular ports bi-weekly for 4 weeks was given to athymic mice bearing human pancreatic adenocarcinomas. Vessel dilator and ANP (each at 100 microM) (n=6 for each) resulted in a 33% (p<0.01) and 17% (p<0.05) elimination of human pancreatic adenocarcinomas, respectively, while the tumor volume increased 64-fold (p<0.001) in the placebo-treated mice (n=12). During the 4 weeks of treatment, the growth velocity decreased 92% and 68% with vessel dilator and ANP, respectively, compared to untreated mice. Biweekly vessel dilator and ANP both eliminate some human pancreatic adenocarcinomas in athymic mice.


Synthesis of recyclable carbon/lignin biocomposite sorbent for in-situ uptake of BTX contaminants from wastewater.
In this work, both palm-date pits and pulping black liquor industrial wastes were recycled as low-cost starting materials for the production of three series of granule activated carbon (gAC)/Kraft lignin (KL) (gAC/KLx, x = 33, 50 and 67%) biocomposites using a one-pot solid-state method. The gAC/KLx biocomposites with defined characteristics were examined towards batch adsorption of BTX (Benzene, Toluene, and Xylene) in multi-solute salty wastewaters. Optimization of adsorption performances under different experimental conditions were carried out using high performance liquid chromatography (HPLC). Adsorption modeling versus contact time (0-12 h) and BTX concentrations (150-2250 mg/L) were examined using non-linear forms of nine kinetic and five isotherm equations to best understand gAC/KL0.5 suitability for BTX sorption/recovery processing. Accordingly, the gAC/KLx at KL blended ratio of 50% was found to be the topmost to achieve the highest BTX capacity even at broad ranges of water salinity (0-100 g/L) and pH (3-9) values. The adsorption mechanism found to best described by physico-sorption (E ≈ 0.12-1.38 kJ/mol) via the hydrophobic interaction and diffusion mechanisms. In respect to gAC/KL0.5 affinities, the sorption capacity followed the descending sequence of X ≥ T > B. Particularly, the maximum theoretical BTX capacity using the best fitted Langmuir-Freundlich model (L-FM) for gAC/KL0.5 was found to be slightly higher than obtained by gAC (363.9 and 360.1 mg/g, respectively), along with higher initial sorption (h) rate (≈742.47 mg/g.h) than of gAC (≈559.85 mg/g.h) and KL (≈22.22 mg/g.h). Batch BTX sorption/recovery processes and estimated cost suggested the effective utilization of gAC/KL0.5 as a promising in-expensive sorbent (0.31 ± 0.05 US$/kg) for commercial decontamination of petroleum hazardous (BTX) pollutants from wastewaters up to five reuse cycles.


Human axillary secretions influence women's menstrual cycles: the role of donor extract of females.
Menstrual synchrony in human females has previously been demonstrated among women attending a predominantly female university as well as among women attending coeducational universities. In each of these studies, women who spent the most time together were most likely to show the menstrual synchrony. In this experiment, the possibility that substances in axillary secretions might mediate this effect was tested using a prospective, double-blind research design and a combined axillary extract from a group of female donors. Female subjects who reported themselves to have normal (29.5 +/- 3 day) cycles were exposed to the axillary extracts or blank/ethanol for 10 to 13 weeks. Recipients of the axillary extracts showed a significant reduction in "days' difference in menses onset" relative to the donor cycle, no change was evident for recipients of blank/ethanol. These results demonstrate that constituents from the axillary region of donor females can shift the time of menstrual onset of another group to conform with the donors' cycle and that this effect can occur even in the absence of social contact.


Hyperbetalipoproteinemia with small low-density lipoprotein, a characteristic disorder of lipoprotein in essential hypertension.
The purpose of the present study was to elucidate the characteristic lipoprotein disorder in essential hypertension. Twenty-six patients with essential hypertension (HT) but without diabetes mellitus or obesity and 24 healthy subjects (control) were recruited into this study. Lipoproteins of HT and controls were separated by ultracentrifugation to very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density liproprotein (LDL), and (HDL) fractions. Cholesterol and triglycerides were determined with enzyme assay, and apoB were determined by highly sensitive latex agglutination (Kyowa-hakko Co. LD). There was no difference in age (mean +/- SE; HT, 63 +/- 2 versus control, 60 +/- 2 years) or body-mass index (22.7 +/- 0.4 versus 21.7 +/- 0.5 kg/m2) between HT and controls. Blood pressure in HT and controls was 158 +/- 2/87 +/- 12 mm Hg and 123 +/- 3/72 +/- 2 mm Hg, respectively. Cholesterol did not change significantly in plasma (192.1 +/- 7.0 versus 176.4 +/- 4.2 mg/dL), VLDL (15.2 +/- 2.4 versus 11.8 +/- 1.7 mg/dL), IDL (14.8 +/- 2.4 versus 10.7 +/- 1.6 mg/dL), LDL (93.7 +/- 4.6 versus 83.1 +/- 3.9 mg/dL), nor in HDL (51.9 +/- 2.7 versus 58.1 +/- 3.2 mg/dL). Triglycerides (TG) increased in plasma (120.0 +/- 10.0 versus 87.5 +/- 9.3 mg/dL, p < 0.05), although TG did not change in all subfractions. ApoB increased in plasma (105.5 +/- 5.1 versus 85.6 +/- 3.6 mg/dL, p < 0.01), IDL (9.0 +/- 1.3 versus 5.4 +/- 0.6 mg/dL, p < 0.05), and LDL (76.3 +/- 4.3 versus 59.4 +/- 3.7 mg/dL, p < 0.01) in HT compared with controls. The ratio of cholesterol to apoB in LDL decreased (1.27 +/- 0.06 versus 1.48 +/- 0.08, p < 0.05). In essential HT, number of apoB containing lipoproteins (IDL, LDL) increased. Low ratio of cholesterol to apoB was noted in LDL, indicating the presence of small, dense LDL. As cholesterol in LDL was normal, hyperbetalipoproteinemia is also a characteristic disorder of essential HT.


Effects of imidazenil, a new benzodiazepine receptor partial agonist, in the treatment of convulsions in organophosphate intoxications.
Anticonvulsant and antilethal effects of imidazenil, a new imidazobenzodiazepine derivative, in fluostigmine (DFP; diisopropyl phosphorofluoridate) intoxications were studied and compared with the effects of diazepam on mice and rats. Special attention was payed to the myorelaxant effects of both drugs. It was stated that imidazenil (i) significantly decreased convulsion intensity in mice, (ii) quickly inhibited seizure patterns in bioelectrical activity in the rat's brain, (iii) significantly increased antilethal effectiveness of the standard therapy in mice intoxicated with DFP. These effects are comparable to those of diazepam. However, effects of imidazenil in the rota-rod test of the mouse were noted in doses 5-10 times higher than therapeutic ones, when effects of diazepam on motor co-ordination were seen in therapeutic dosage.


Topically applied thiabendazole in the treatment of scabies.
Forty patients were treated for scabies with a 10% suspension of thiabendazole applied externally. Thirty-two patients (80%) had a satisfactory response to one course of therapy, while a second course was necessary in six (15%). Two patients (5%) required intralesional injections of triamcinolone diacetate because of persistent scabious nodules.


Detection of chicken anaemia agent DNA sequences by the polymerase chain reaction.
A polymerase chain reaction (PCR) assay was developed for detection of chicken anaemia agent (CAA) DNA. The assay used a single set of 20-base primers complementary to sequences located in the coding regions of the CAA replicative form (RF) DNA genome at positions 485 to 504 and 1048 to 1067. The observed amplification product had the expected size of 583 bp and was confirmed to derive from CAA RF DNA by a unique Hind III restriction enzyme cleavage pattern. The amplified fragment was shown to be specific for CAA RF DNA after chemiluminescence dot blot hybridisation with a digoxigenin-labelled 25-base internal probe. The optimised PCR assay was specific for CAA and highly sensitive, being able to detect a single CAA-infected MDCC-MSB1 cell and at least 100 fg of CAA RF DNA. Preliminary results also showed that the PCR assay can detect CAA DNA in clinical specimens from chicks experimentally infected with CAA.


Silica nanoparticles containing nano-silver and chlorhexidine respond to pH to suppress biofilm acids and modulate biofilms toward a non-cariogenic composition.
Dental caries is caused by acids from biofilms. pH-sensitive nanoparticle carriers could achieve improved targeted effectiveness. The objectives of this study were to develop novel mesoporous silica nanoparticles carrying nanosilver and chlorhexidine (nMS-nAg-Chx), and investigate the inhibition of biofilms as well as the modulation of biofilm to suppress acidogenic and promote benign species for the first time. nMS-nAg was synthesized via a modified sol-gel method. Carboxylate group functionalized nMS-nAg (COOH-nMS-nAg) was prepared and Chx was added via electrostatic interaction. Minimal inhibitory concentration (MIC), inhibition zone, and growth curves were evaluated. Streptococcus mutans (S. mutans), Streptococcus gordonii (S. gordonii), and Streptococcus sanguinis (S. sanguinis) formed multispecies biofilms. Metabolic activity, biofilm lactic acid, exopolysaccharides (EPS), and TaqMan real-time polymerase chain reaction (RT-PCR) were tested. Biofilm structures and biomass were observed by scanning electron microscopy (SEM) and live/dead bacteria staining. nMS-nAg-Chx possessed pH-responsive properties, where Chx release increased at lower pH. nMS-nAg-Chx showed good biocompatibility. nMS-nAg-Chx exhibited a strong antibacterial function, reducing biofilm metabolic activity and lactic acid as compared to control (p < 0.05, n = 6). Moreso, biofilm biomass was dramatically suppressed in nMS-nAg-Chx groups. In control group, there was an increasing trend of S. mutans proportion in the multispecies biofilm, with S. mutans reaching 89.1% at 72 h. In sharp contrast, in nMS-nAg-Chx group of 25 μg/mL, the ratio of S. mutans dropped to 43.7% and the proportion of S. gordonii and S. sanguinis increased from 19.8% and 10.9 to 69.8% and 56.3%, correspondingly. pH-sensitive nMS-nAg-Chx had potent antibacterial effects and modulated biofilm toward a non-cariogenic tendency, decreasing the cariogenic species nearly halved and increasing the benign species approximately twofold. nMS-nAg-Chx is promising for applications in mouth rinse and endodontic irrigants, and as fillers in resins to prevent caries.


Heat Stress Effects on Physiological and Blood Parameters, and Behavior in Early Fattening Stage of Beef Steers.
This study was conducted to investigate the effect of heat stress (HS) on physiological, blood, and behavioral parameters, according to the temperature-humidity index (THI), in beef steers. Twelve Korean native beef steers (342.7 ± 13.81 days old, body weight (BW) of 333.0 ± 18.53 kg) were used in this experiment. Beef steers were randomly distributed into three homogenized groups (four beef steers each) for 14 days, namely, threshold (THI = 64-71), mild-moderate (THI = 72-79), and severe (THI = 80-87). Feed and water intake were recorded daily. Physiological parameters, including heart rate and rectal temperature, and behavioral patterns (standing and lying down) were measured weekly. Blood was sampled every week to analyze hormones, heat shock protein (HSP) levels, metabolites, and hematological parameters. All data were analyzed using repeated-measures analysis. Beef steers exposed to severe THI had significantly increased (p < 0.001) water intake, heart rate, and rectal temperature compared to the threshold and mild-moderate THI beef steers. Additionally, increased blood cortisol (p < 0.001), HSP70 (p < 0.001), blood urea nitrogen (BUN) (p = 0.014), and time spent standing (p < 0.001) were observed in beef steers after exposure to severe THI compared to beef steers in the threshold and mild-moderate THI groups. However, dry matter intake, blood glucose, and non-esterified fatty acids were not different among the THI groups. In conclusion, heart rate, rectal temperature, blood cortisol, HSP70, BUN, and time spent standing were closely associated with severe HS conditions in beef steers. These phenomena indicated that beef steers exposed to HS modulated their behavior and blood parameters, as well as their physiological response, to maintain homeostasis.


A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme.
A new patient affected by Guanidinoacetate methyltransferase (GAMT) deficiency was reported. This 13-year-old girl presented with mental retardation, as main symptom, associated with a typical pattern of biochemical and neurochemical (brain magnetic resonance spectroscopy) alterations. Molecular study detected a L197P transition on exon 6 of the GAMT gene. Since this mutation leaves the isoform B of the GAMT enzyme unaffected, the occurrence of biochemical alterations and disease in this subject testifies against the possibility that isoform b had GAMT activity.


A statistical view of protein chemical synthesis using NCL and extended methodologies.
Native chemical ligation and extended methodologies are the most popular chemoselective reactions for protein chemical synthesis. Their combination with desulfurization techniques can give access to small or challenging proteins that are exploited in a large variety of research areas. In this report, we have conducted a statistical review of their use for protein chemical synthesis in order to provide a flavor of the recent trends and identify the most popular chemical tools used by protein chemists. To this end, a protein chemical synthesis (PCS) database (http://pcs-db.fr) was created by collecting a set of relevant data from more than 450 publications covering the period 1994-2017. A preliminary account of what this database tells us is presented in this report.


Modulation of in vitro erythropoiesis: enhancement of erythroid colony growth by cyclic nucleotides.
Mammalian erythropoiesis, as assayed by erythroid colony formation in vitro, is enhanced by cyclic adenosine nucleotides and agents which are capable of raising intracellular cyclic AMP (cAMP) levels. With canine marrow cells as target, this enhancement was shown to be specific for cAMP and its mono- and dibutyryl derivatives. Adenosine and its derivatives, such as AMP, ADP and ATP, and other cyclic nucleotides, such as cGMP, dibutyryl-cGMP, cCMP and cIMP and sodium butyrate were inactive. The phosphodiesterase inhibitor, RO-20-1724, and the adenyl cyclase stimulator, cholera enterotoxin, both markedly increased colony numbers. Studies with tritiated thymidine showed that about 50% of the cells responding to either erythropoietin (ESF) or dibutyryl cAMP (db-cAMP) were in DNA synthesis. However, by unit gravity sedimentation velocity analysis, the peak of ESF-responsive colony forming cells sedimented more rapidly (8-7 +/- 0-2 mm/hr) than the peak of db-cAMP-responsive cells (7-5 +/- 0 mm/hr). These results demonstrate that adenyl cyclase-linked mechanisms influence in vitro erythropoietic proliferation and suggest that other hormones and simple molecules might interact with surface receptors and thus modulate the action of ESF at the cellular level.


Assessment of left ventricular systolic function by echocardiography.
Echocardiography serves an extremely important role in the diagnosis and management of patients with heart failure. The various stages of structural and functional changes that constitute progressive left ventricle remodeling have all been characterized by two-dimensional echocardiography. In addition, echocardiography has defined the transition from compensated hypertrophy to left ventricle dilatation and progression to end-stage heart failure. Echocardiography has also played an important role in clinical heart failure trials of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and demonstrated their efficacy in heart failure.


Glucocorticoid-sensitive ventral hippocampal-orbitofrontal cortical connections support goal-directed action - Curt Richter Award Paper 2019.
In an ever-changing and often ambiguous environment, organisms must use previously learned associations between antecedents and outcomes to predict future associations and make optimal choices. Chronic stress can impair one's ability to flexibly adjust behaviors when environmental contingencies change, particularly in cases of early-life stress. In mice, exposure to elevated levels of the primary stress hormone, corticosterone (CORT), during early adolescence is sufficient to impair response-outcome decision making later in life, biasing response strategies towards inflexible habits. Nevertheless, neurobiological mechanisms are still being defined. Here, we report that exposure to excess CORT in adolescence causes a loss of dendritic spines on excitatory pyramidal neurons in the lateral, but not medial, orbital prefrontal cortex (loPFC) of mice, and spine loss correlates with the severity of habit biases in adulthood. Excess CORT also reduces the presence of ventral hippocampal (vHC) axon terminals in the loPFC. To identify functional consequences, we inactivated vHC→loPFC projections in typical healthy mice during a period when mice must update response-outcome expectations to optimally acquire food reinforcers. Inactivation impaired the animals' subsequent ability to sustainably choose actions based on likely outcomes, causing them to defer to habit-based response strategies. Thus, vHC→loPFC projections are necessary for response-outcome expectancy updating and a target of excess glucocorticoids during early-life development. Their degradation is likely involved in long-term biases towards habit-based behaviors following glucocorticoid excess in adolescence.


Laser hair removal.
Laser hair removal is a rapidly growing aesthetic procedure requested predominantly by women. At a time of falling reimbursement by payers, gynecologists have an opportunity to improve the fiscal health of their practices while delivering a service valued by their patients. As a result, practicing gynecologists should become acquainted with aesthetic lasers and should know how to incorporate them into their practices. This article introduces the practicing gynecologist to aesthetic lasers and the procedure of laser hair removal.


Outcomes of diverting loop ileostomy reversal in the elderly: a case-control study.
Although diverting loop ileostomy (DLI) reversal is considered to be a relatively simple procedure, it is not immune from major morbidity. We aimed to compare outcomes of DLI reversal between elderly and non-elderly patients. Retrospective review of all patients who underwent DLI reversal at a single tertiary medical centre between 2010 and 2020. The elderly group consisted of patients 70 or older compared to a control group of those younger than 70 years. During the study period, 307 patients underwent DLI reversal. Of these, 76 patients were in the elderly group (mean age 75.6) and 231 in the control group (mean age 55.3). The groups were comparable in terms of mean time interval between the creation of the ileostomy and reversal (242 versus 255 days, respectively, P = 0.5), choice between stapled and hand-sewn anastomoses (97.4% stapled anastomosis versus 93.1%, P = 0.086), median post-operative length of stay (5 days in both, P = 0.086), rates of post-operative complications (26.3% versus 26.8%, P = 0.99), severe complications (5.3% versus 6.9%, P = 0.81) and 30-day readmission rates (13.2% versus 10.8%, P = 0.58). Multivariate analysis found the time interval between the creation of the stoma and its reversal to be the only significant risk factor for major post-operative morbidity. Age was not found to be correlated with post-operative morbidity. The outcomes of loop ileostomy reversal in elderly patients are similar to non-elderly patients. Efforts should be made to decrease the time interval between the creation of the stoma and its reversal as this is a significant risk factor for major post-operative morbidity.


Innovative curriculum is needed to address residents' attitudes toward older adults: the case of geriatric trauma.
Medical trainees' negative perceptions towards older adult care have been widely reported, catalyzing targeted curricula in geriatric medicine. Little is known about surgical residents' attitudes toward and perceptions of the educational value of caring for injured older adults. This information is needed to ensure the surgical workforce is adequately trained to care for this growing patient population. In this study, we assessed surgical trainees' attitudes towards geriatric trauma care to inform a curriculum in geriatric trauma. We surveyed North American general surgery trainees' beliefs and attitudes toward caring for older trauma patients, and the educational value they ascribed to learning about older trauma patient care. Descriptive statistics were used to report participant characteristics and responses. Three hundred general surgery trainees from 94 post-graduate programs responded. Respondents reported too much time co-ordinating care (56%), managing non-operative patients (56%), and discharge planning (65%), all activities important to the care of older trauma patients. They recognized the importance of geriatric trauma care for their future careers (52%) but were least interested in reading about managing geriatric trauma patients (28%). When asked to rank clinical vignettes by educational value, respondents ranked the case of an older adult as least interesting (74%). As respondents progressed through their training, they reported less interest in geriatric trauma care. Our survey results demonstrate the generally negative attitudes and beliefs held by postgraduate surgical trainees towards the care of older adult trauma patients. Future work should focus on identifying specific changes to the postgraduate surgical curriculum which can effectively alter these attitudes and beliefs and improve the care for injured older adults.


Role of adrenal hormones (adrenaline and DOCA) in experimental hypertension. A histopathological study.
The effect of prolonged treatment with adrenaline and sodium chloride combined with desoxycorticosterone acetate (DOCA), on the blood pressure of unilaterally nephrectomized (UN) rats and the histology of circulatory organs was studied. Hypertension developed in this experimental hypertension model in all of the test groups. Adrenaline alone raised the blood pressure as much as the adrenaline + NaCl + DOCA treatment. Organic changes in the renal blood vessels developed only in the Adrenaline + DOCA + NaCl group, where the highest increases in cardiac and renal organ weights were also found. These findings indicate that adrenal stress hormones may play an important sensitizating role in the multifactoral genesis of vascular changes associated with hypertension.


Homocysteine up-regulates endothelin type A receptor in vascular smooth muscle cells through Sirt1/ERK1/2 signaling pathway.
Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ETA) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ETA receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ETA receptor through the Sirt1/ERK1/2 signaling pathway. In vitro experiments were performed in the rat superior mesenteric artery. The rat superior mesenteric artery was cultured with or without homocysteine (Hcy) in the presence and absence of Resveratrol (Res, a Sirt1 agonist), SRT1720 (a specific Sirt1 agonist) or U0126 (an ERK1/2 signaling pathway inhibitor) in serum-free medium for 24h. In vivo, the rats received subcutaneous injections of Hcy in the presence of or absence of Res or U0126 for 3weeks. The contractile response to ET-1 was studied using a sensitive myograph. In addition, the level of protein expression was determined using western blotting. Hcy significantly increased the expression of ETA receptor and also increased the ETA receptor-mediated contractile response induced by ET-1 in vitro. These effects were inhibited by Res, SRT1720 and U0126 treatment. In addition, Hcy down-regulated the level of Sirt1, and up-regulated the level of phosphorylated ERK1/2, which was reversed upon Res or SRT1720 treatment. In vivo results showed that HHcy results in the up-regulation of ETA receptor expression, and elevated blood pressure in rats. However, Res and U0126 could block these effects, respectively. In conclusion, these results suggest that Hcy regulates ETA receptor expression via the Sirt1/ERK1/2 signaling pathway in VSMCs.


Decreased enrollment in breast cancer trials by histologic subtype: does invasive lobular carcinoma resist RECIST?
Enrollment in metastatic breast cancer trials usually requires measurable lesions, but patients with invasive lobular carcinoma (ILC) tend to form diffuse disease. We found that the proportion of patients with metastatic ILC enrolled in clinical trials at our institution was significantly lower than that of patients with invasive ductal carcinoma (IDC). Possible links between requiring measurable disease and decreased enrollment of ILC patients require further study to ensure equitable trial access.


Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study.
Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21-30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.


The effect of nystatin on the morphology of Candida albicans.
The effect of nystatin on Candida albicans was observed by light and scanning electron microscopy; it caused abnormal growth. Some cells had deep depressions in the cell walls; budding and germ tube formation were reduced.


Neuroprotective effects of Buyang Huanwu decoction against hydrogen peroxide induced oxidative injury in Schwann cells.
Buyang Huanwu decoction (BYHWD) is a traditional Chinese medicine and can be used to promote peripheral nerve regeneration. However the regenerative mechanism of BYHWD remains unclear. The objective of this study was to investigate the protective mechanisms of BYHWD in Schwann cells damaged by hydrogen peroxide (H(2)O(2)). Schwann cells which were derived from neonatal sciatic nerves of rats were used in subsequent experiments. Schwann cells were injured by various concentrations of H(2)O(2) (0.25, 0.5 and 1mM final concentration). BYHWD (600 μg/ml final concentration) was added to the medium either simultaneously or 1h later after the addition of H(2)O(2). Subsequently, methyl thiazolyl tetrazolium (MTT) assay was performed. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were also examined after 12h. The expression of Caspase 3 and the concentration of intercellular Ca(2+) ([Ca(2+)]i) were also determined. Among three concentrations of H(2)O(2), 0.5mM H(2)O(2) induced Schwann cells swelled and neuritis disappeared after 12h. In the presence of BYHWD, MTT assay showed that more cells were viable in comparison with the H(2)O(2) injury group. Moreover, the addition of BYHWD has also increased the SOD activity with decreased in MDA level. Furthermore, the concentration of [Ca(2+)]i and expression of Caspase 3 were decreased with the addition of BYHWD in culture. Our results revealed that BYHWD protected Schwann cells from oxidative injury. The mechanism of BYHWD promoting neural regeneration possibly associated with its anti-oxidative activity.


Predictive estimation of ovine hip joint centers: A regression approach.
Estimation of the hip joint center in ovine biomechanical analysis is often overlooked or estimated using a marker on the greater trochanter which can result in large errors that propagate through subsequent analyses. The purpose of this study was to develop a novel method of estimating the hip joint centers in sheep to facilitate more accurate analysis of ovine biomechanics. CT scans from 16 sheep of varying ages, weight, sex, and phenotypes were acquired and the data was used to calculate the known hip joint center by sphere fitting the femoral head. Anatomical measurements and additional subject information were used to create a variety of regression models to estimate the hip joint centers in absence of CT data. The best regression equation created utilized markers placed on the tuber coxae and tuber ischii of the pelvis and resulted in a mean 3D Euclidean distance error of 6.43 ± 2.22 mm (mean ± standard deviation) between the known and estimated hip joint center. The regression models produced allow for more detailed, accurate and robust analysis of sheep biomechanics.


[Simulation in anesthesia].
Simulation in anesthesia is reviewed. Its aim includes education/training, analysis of phenomena, explanation or interpretation of phenomena and instrument checks. It deals with pharmacokinetics/pharmacodynamics of inhalational and intravenous agents, respiration and circulation, action and behavior of anesthesiologists and income analysis. Simulations are accomplished mainly by using computers, yet few use physical models or a physical model combined with computers. For writing this review, CD-ROM's of Medline data were used. Problems in searching literatures through this route are discussed. Finally, the problem of the distribution of softwares is also discussed.


Relevance of urocortins to cardiovascular disease.
Acquired cardiovascular diseases such as coronary heart disease, peripheral artery disease and related vascular problems contribute to more than one-third of worldwide morbidity and mortality. In many instances, particularly in the under developed world, cardiovascular diseases are diagnosed at a late stage limiting the scope for improving outcomes. A range of therapies already exist for established cardiovascular disease, although there is significant interest in further understanding disease pathogenesis in order to improve diagnosis and achieve primary and secondary therapeutic goals. The urocortins are a group of recently defined peptide members of the corticotrophin-releasing factor family. Previous pre-clinical work and human association studies suggest that urocortins have potential to exert some beneficial and other detrimental effects on the heart and major blood vessels. More current evidence however favours beneficial effects of urocortins, for example these peptides have been shown to inhibit production of reactive oxygen species and vascular cell apoptosis, and thus may have potential to antagonise the progression of cardiovascular disease. This review summarises published data on the potential role of urocortins in cardiovascular disease.


Selenium increases photosynthetic capacity, daidzein biosynthesis, nodulation and yield of peanuts plants (Arachis hypogaea L.).
This study aimed to investigate the roles of selenium (Se) application on the profile of photosynthetic pigments, oxidant metabolism, flavonoids biosynthesis, nodulation, and its relation to agronomic traits of peanut plants. Two independent experiments were carried out: one conducted in soil and the other in a nutrient solution. When the plants reached the V2 growth stage, five Se doses (0, 7.5, 15, 30, and 45 μg kg-1) and four Se concentrations (0, 5, 10, and 15 μmol L-1) were supplied as sodium selenate. The concentration of photosynthetic pigments, activity of antioxidant enzymes and the concentration of total sugars in peanut leaves increased in response to Se fertilization. In addition, Se improves nitrogen assimilation efficiency by increasing nitrate reductase activity which results in a higher concentration of ureides, amino acids and proteins. Se increases the synthesis of daidzein and genistein in the root, resulting in a greater number of nodules and concentration and transport of ureides to the leaves. Se-treated plants showed greater growth, biomass accumulation in shoots and roots, yield and Se concentration in leaves and grains. Our results contribute to food security and also to increase knowledge about the effects of Se on physiology, biochemistry and biological nitrogen fixation in legume plants.


Induction of physical dependence upon alcohol in nonhuman primates.
Following the description of the alcohol withdrawal syndrome in man, efforts have been made to use the nonhuman primate as an animal model for studying the development of physical dependence upon alcohol. There is now general agreement regarding the qualitative description of the withdrawal reaction in the rhesus monkey, and various approaches, including intravenous infusion, intragastric intubation, and nonvolitional oral intake of ethanol have been successful in producing withdrawal in these animals. There still remain the major problems of developing objective procedures for quantitatively assessing the severity of the withdrawal syndrome and establishing the dose dependent and time dependent relationships between ethanol intake and the development of physical dependence. Until these basic issues are empirically resolved, little progress can be expected in our understanding of the critical determinants of the addictive process.


Molecular mechanisms involved in endothelial cell aging: role of telomerase reverse transcriptase.
Aging is one major risk factor for the incidence of coronary artery disease and the development of atherosclerosis. The functional integrity of the endothelial cell monolayer is essential to prevent lesion formation. Endothelial cells show profound changes with age. However, the molecular mechanisms are not well understood. Important players in the process of endothelial cell aging are reactive oxygen species, nitric oxide bioavailability, mitochondrial integrity and the activity of telomerase reverse transcriptase. This review will demonstrate the evidence that these processes are involved in endothelial cell aging and linked to each other. The future goal of understanding endothelial cell aging would allow for an anti-aging therapy to reduce the influence of aging in the development of atherosclerosis and coronary artery disease.


Electron-precise/deficient La(5-x)Ca(x)Ge4 (3.4 < or = x < or = 3.8) and Ce(5-x)Ca(x)Ge4 (3.0 < or = x < or = 3.3): probing low-valence electron concentrations in metal-rich Gd5Si4-type germanides.
We report for the first time the syntheses of electron-precise/deficient alloys, Ln5-xCaxGe4 (Ln = La, Ce; x = 3.37, 3.66, 3.82 for La; x = 3.00, 3.20, 3.26 for Ce), in the metal-rich R5Tt4 Zintl system (R = rare earth metal; Tt = Si, Ge). The new alloys extend the phase width from electron-rich to open-shell electron-deficient region in the metal-rich Zintl system and demonstrate possible occurrence of varied electron deficiencies in Zintl phases without structural changes, as a result of other existing structure-forming factors.


Computed tomography angiography for aerodigestive injuries in penetrating neck trauma: A systematic review.
Management of hemodynamically stable patients with penetrating neck trauma (PNT) has evolved in recent years with improvements in imaging technology. Computed tomography angiography (CTA) encompassing all zones of the neck has become part of the standard diagnostic algorithm for PNT patients who do not require immediate surgical intervention for vascular or aerodigestive injuries (ADI). Several studies have demonstrated favorable operating characteristics for CTA at excluding arterial injuries; however, consensus as to CTA's ability to detect ADI is lacking. We conducted a systematic review (PROSPERO registration number CRD42019133509) to answer the question Is CTA sufficient to rule out ADI in hemodynamically stable PNT patients without hard signs? Investigators independently searched PubMed, EMBASE, and Web of Science from their inception to August 2020 for the search terms "penetrating neck injuries" and "CT scan." To be included, studies required sufficient data to construct a 2×2 table of CTA for ADI. The operating characteristics of CTA for detecting ADIs are reported as sensitivity, specificity, and likelihood ratios (LRs), with 95% confidence intervals (95% CIs). Bias in our studies was quantified by QUADAS-2. Our search identified 1,242 citations with seven studies with moderate to high risk of bias meeting our inclusion/exclusion criteria and encompassing 877 subjects with an ADI prevalence of 13.4%. CTA for ADI had sensitivity of 92% (95% CI = 85% to 97%), specificity of 88% (95% CI = 85% to 90%), positive likelihood ratio of 12.2 (95% CI = 4.6 to 32), and negative LR of 0.14 (95% CI = 0.05 to 0.37). Of the 26 identified esophageal injuries across our studies that were diagnosed by either swallow studies or surgical exploration, five (19%, 95% CI = 8.1% to 38.3%) were initially missed by CTA. CTA alone is not sufficient to exclude esophageal injuries in PNT. Because delayed diagnosis is associated with increased morbidity, additional diagnostic interventions should be undertaken if there is remaining concern for esophageal injury.


[The topography and cytoarchitectonic of the diencephalon of the cow (Bos taurus var. domesticus L.) I. The topography of the diencephalon of the cow. (Bos taurus var. domesticus L.) (author's transl)].
The study contains a comprehensive review of the literature on the brain of the cattle, followed by notes on form and location of the brain in the skull of the cow and of the diencephalon. In addition we point to some possibilities for locating the brain by stereotaxic manipulations. Several structural particularities are discussed, where to a limited extent references to structures of the brains of other domestic artiodactyla are made.


Development and application of a triplex real-time PCR assay for the detection of H3, H4, and H5 subtypes of avian influenza virus.
Avian influenza virus (AIV) poses a significant threat to the poultry industry and public health. Among the diverse AIV subtypes, H3, H4, and H5 are frequently detected in waterfowl and live poultry markets (LPM). The expeditious and precise identification of these subtypes is imperative in impeding the dissemination of the disease. In this study, we have developed a triplex real-time PCR assay endowed with the capacity to simultaneously discriminate AIV subtypes H3, H4, and H5. This method showcases remarkable specificity, selectively amplifying H3, H4, and H5 AIV subtypes sans any cross-reactivity with other subtypes or common avian pathogens. Furthermore, this method exhibits high sensitivity, with a detection threshold of 2.1 × 102 copies/μL for H3, H4, and H5 AIV subtypes. Additionally, the assay demonstrates reproducibility, as evidenced by intra- and interassay variability, with a coefficient of variation below 1.5%. A total of 338 cloacal swabs were collected from LPM to evaluate the performance of our assay. The obtained results evinced a high level of concordance with the sequencing data. In summary, our study has developed a triplex real-time PCR method that can be employed in laboratory-based testing and surveillance of AIV. This assay holds promise in augmenting our ability to detect and monitor AIV subtypes, thereby facilitating timely interventions and safeguarding both the poultry industry and public health.


Comparative performance and reusability studies of lipases on syntheses of octyl esters with an economic approach.
A suitable immobilized lipase for esters syntheses should be selected considering not only its cost. We evaluated five biocatalysts in syntheses of octyl caprylate, octyl caprate, and octyl laurate, in which conversions higher than 90% were achieved. Novozym® 435 and non-commercial preparations (including a dry fermented solid) were selected for short-term octyl laurate syntheses using different biocatalysts loadings. By increasing the biocatalyst's loading the lipase's reusability also raised, but without strict proportionality, which resulted in a convergence between the lowest biocatalyst loading and the lowest cost per batch. The use of a dry fermented solid was cost-effective, even using loadings as high as 20.0% wt/wt due to its low obtaining cost, although exhibiting low productiveness. The combination of biocatalyst's cost, esterification activity, stability, and reusability represents proper criteria for the choice. This kind of assessment may help to establish quantitative goals to improve or to develop new biocatalysts.


Synergistic Degradation of a Hyperuricemia-Causing Metabolite Using One-Pot Enzyme-Nanozyme Cascade Reactions.
Multi-enzyme cascade reactions are frequently found in living organisms, in particular when an intermediate should be eliminated. Recently, enzyme-mimic nanomaterials (nanozymes) received much attention for various applications, because they are usually more stable and cost-effective than enzymes. However, enzyme-nanozyme cascade reations have not been yet extensively exploited. Therefore, in this study, we investigated one-pot enzyme-nanozyme cascade reactions using urate oxidase (UOX) and catalase-mimic gold nanoparticle nanozyme (AuNP) with the ultimate goal of treatment of hyperuricemia. UOX degrades hyperuricemia-causing uric acid, but also generates hydrogen peroxide raising several health concerns. We successfully demonstrated that one-pot UOX-AuNP cascade systems degrade uric acid more than five times faster than UOX alone, by eliminating potentially cytotoxic hydrogen peroxide, similar to enzyme-enzyme reactions.


Genome maintenance during embryogenesis.
Genome maintenance during embryogenesis is critical, because defects during this period can be perpetuated and thus have a long-term impact on individual's health and longevity. Nevertheless, genome instability is normal during certain aspects of embryonic development, indicating that there is a balance between the exigencies of timely cell proliferation and mutation prevention. In particular, early embryos possess unique cellular and molecular features that underscore the challenge of having an appropriate balance. Here, we discuss genome instability during embryonic development, the mechanisms used in various cell compartments to manage genomic stress and address outstanding questions regarding the balance between genome maintenance mechanisms in key cell types that are important for adulthood and progeny.


A lifelong preoccupation with the sociality of moral obligation.
Tomasello provides compelling evidence that children understand that people are morally obligated toward members of their social group. We call for expanding the scope of inquiry to encompass the full developmental trajectory of humans' understanding of the relation between moral obligation, sociality, and stancetaking in interaction. We suggest that humans display a lifelong preoccupation with the sociality of moral obligation.


Multifocal contact lens design, not addition power, affects accommodation responses in young adult myopes.
Prolonged nearwork has been implicated in myopia progression. Accommodation responses of young-adult myopes wearing different multifocal contact lenses were compared. Twenty adults, 18-25 years, with myopia (spherical equivalent refraction -0.50 to -5.50 D, mean -2.1 ± 1.6 D) wore five lens types in random order: Proclear single vision distance (SV), MiSight concentric dual-focus +2.00 D Add (MS), Biofinity aspheric centre distance +1.50 D Add (CD1) and +2.50 D Add (CD2) (all Coopervision), and NaturalVue aspheric (Visioneering Technologies) (NVue). Using a Grand-Seiko WAN-5500 autorefractor with binocular correction and viewing right eye accommodative responses were measured after a 10 min adaptation period at 4.0, 1.0, 0.5, 0.33 and 0.25 m distances. Dynamic measurements were taken for 4 s at 6 Hz. Accommodative stimuli and responses were referenced to 4 m (i.e., refraction differences between 4 m and nearer distances). Accommodation lags and refraction instabilities (standard deviations of dynamic responses) were determined. For comparison, results were obtained for an absolute presbyopic eye, where trial lenses counteracted the accommodation stimulus. For SV and MS, accommodation responses were similar to the stimulus values. For aspheric lenses CD1, CD2 and NVue, accommodation responses were approximately 1.0 D lower across the stimulus range than with SV and MS, and rates of change were approximately 0.84 D per 1 D stimulus change. MS produced greater refraction instabilities than other lenses. For the presbyope, changes in refraction matched the trial lenses, indicating that corrections due to measurement through the different lenses were not needed. Reductions in accommodation response occurred in young myopes wearing aspheric multifocal contact lenses independent of the labelled 'add' power. The concentric dual-focus MS lens produced minimal lags but had greater instability than the other lenses. The results indicate that the mechanism of multifocal contact lenses slowing myopia progression is unlikely to be through relaxing accommodation, at least in young adults.


[Nocardiosis as a Differential Diagnosis of Pulmonary Epitheloid Cell Granulomas].
A 47-year-old man presented with fever, weight loss and pulmonary consolidations and cavitation in the x-ray of the thorax. The comprehensive diagnostics resulted pulmonary epitholoid cell granulomas, therefore an immunosuppressive therapy was applied on suspicion of sarcoidosis. Progressivly the pulmonary infiltration increased and cerebral and abdominal abscesses were determined with microbiological detection of Nocardia farcinica. Despite antibiotic therapy, the patient died in a septic shock with multiple organ failure.Nocardiosis is a rare granulomatous bacterial infectious disease. Risk factors include immunosuppression and structural lung diseases. Characteristic is an abscess formation that can occur in any organ, while pulmonary onset is common.The case demonstrates the importance of considering rare differential diagnoses in the detection of pulmonary epithelioid granulomas.


The use of positive behaviour support plans in mental health inpatient care: A mixed methods study.
WHAT IS KNOWN ON THE SUBJECT?: There is a drive to use positive and proactive approaches to mental health care to reduce the use of restrictive practices such as seclusion and restraint. Positive behaviour support plans have been used successfully to do this in learning disability services, and in England, it is now a regulatory requirement that anyone with challenging behaviour should have an individualized behaviour support plan. However, positive behaviour support plans specifically have not been evaluated as part of routine mental health care and mental health nurses' and relatives' attitudes towards them are unknown. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This evaluation of positive behaviour support plans in routine mental health inpatient care found that they had not been widely implemented or completed as intended. Barriers to the use of the plans included confusion among nurses and relatives around the principles of positive behaviour support, including how, when and for whom the plans should be used, difficulties in being able to describe the function of a patient's behaviour and lack of engagement with relatives and patients. Nevertheless, nurses and relatives valued the plans, in particular for their potential to facilitate holistic care. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: To use the plans successfully, mental health nurses will need training to understand fully the rationale behind the positive behaviour support approach and will need to engage more with relatives and patients. Commitment to the approach from the whole care team and organization will be needed to implement the plans consistently for all patients. Abstract Introduction An international drive is to minimize restrictive practices in mental health care. Positive behaviour support plans (PBSPs) help staff prevent behaviour which would require restrictive intervention. Originating in learning disability services, data within mental health care are limited. Aims To evaluate PBSPs within a mental health inpatient service; understand mental health nurses' and relatives' attitudes to them; and understand the barriers and facilitators for their use in routine mental health care. Methods Mixed methods-quality ratings and interviews with relatives and nurses. Results Positive behaviour support plans were poorly implemented. Relatives and nurses valued the potential of PBSPs to facilitate holistic care, though no relative had contributed to one and not every eligible patient had one. Barriers to their use included confusion around positive behaviour support, including how, when and for whom PBSPs should be used, and difficulties describing the function of a behaviour. Discussion The potential of PBSPs to improve mental health care is recognized. However, there are barriers to their use which should be addressed to ensure that PBSPs have been properly implemented before their impact on patient care can be assessed. Implications for practice Mental health professionals implementing PBSPs should engage with relatives and patients, gain organizational commitment and ensure that those involved understand fully the positive behaviour support approach.


Membrane-protein interaction and the molten globule state: interaction of alpha-lactalbumin with membranes.
The insertion of soluble proteins into membranes has been a topic of considerable interest. We have studied the insertion of bovine alpha-lactalbumin into single-bilayer vesicles prepared from egg phosphatidylcholine (PC). Fluorescence studies indicated rapid and tight binding of apo-alpha-lactalbumin (apo-alpha-LA) to PC vesicles as a function of pH. The binding was maximal at pH values which favor the formation of the molten globule state. As an increase of hydrophobic surface is observed in the molten globule state, this conformational state can provide a molecular basis for insertion of soluble proteins into membranes. The membrane-bound complex formed at low pH (3.0) could be isolated and was found to be stable at neutral pH. The structural characterization of the apo-alpha-LA-PC complex was studied by fluorescence quenching using iodide, acrylamide, and 9,10-dibromostearic acid. The results obtained indicated that some of the tryptophans of apo-alpha-LA were buried in the membrane interior and some were exposed on the outer side. Fluorescence quenching and CD studies indicated the membrane-bound conformation of apo-alpha-LA was some conformational state that is between the soluble, fully folded conformation and the molten globule state.


Comparison of 12-cm versus 6-cm long peripheral catheters in patients with difficult intravenous access (DIVA).
Long peripheral catheter is 6-15 cm long vascular device. The aim of the study was to compare the frequency of complications of two types of long peripheral catheters with different length inserted in DIVA patients. Under ultrasound navigation 2.7F 6.4 cm or 4Fr 12 cm long peripheral catheter was inserted. Complications of both long peripheral catheters were prospectively observed and their relationship to the patient's age, gender, selected vein, number of punctures and Barthel score system was evaluated. Ninety-three 12 cm and fifty-five 6.4 cm long peripheral catheters were inserted. Median of dwelling time was 8 days for 6.4 cm and 9 days for 12 cm long peripheral catheter. There were 17 (26%) complications in 6.4 cm (38/1000 catheter days) and 15 (16%) in 12 cm catheter (17/1000 catheter days), p = 0.04. The complications of both peripheral catheters were not associated with the age of patients, gender, number of punctures and selected vein for insertion. Unlike 12 cm catheter, the complications of 6.4 cm long peripheral catheter were significantly associated with the result of Barthel scoring system (p = 0.003). The frequency of complications was more common with 6,4 cm than with 12 cm catheter.


Both endogenous and exogenous ACh plays antinociceptive role in the hippocampus CA1 of rats.
The present study examines the effect of acetylcholine (ACh), muscarinic acetylcholine receptors (mAChRs) agonist pilocarpine and mAChRs antagonist atropine on the pain-evoked response of pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the hippocampal CA1 of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN and PIN in the hippocampal CA1 were recorded by glass microelectrode. The results showed that intrahippocampal microinjection of ACh (2 microg/1 microl) or pilocarpine (2 microg/1 microl) decreased the frequency of discharge of PEN, and increased the frequency of discharge of PIN evoked by the noxious stimulation in the hippocampal CA1, while intrahippocampal administration of atropine (0.5 microg/1 microl) produced opposite response. On the basis of the above findings, we can deduce that ACh and mAChRs are involved in the modulation of nociceptive information transmission in the hippocampal CA1.


Benign proliferative myositis of the sternohyoid muscle: review and case report.
We report a case of a 51-year-old woman who presented with a rapidly enlarging, painful, midline neck mass that developed over a three day period. A CT scan of the neck showed a solid circumscribed mass in the sternohyoid muscle. The initial differential diagnosis included inflammation of thyroglossal duct remnant, an abnormal lymph node, and thyroid carcinoma. The patient underwent operative excision with final pathology revealing proliferative myositis. Proliferative myositis is an uncommon benign proliferation of skeletal muscle and has only been reported a limited number of times in the head and neck region.


Effects of dexamethasone on bovine circulating T lymphocyte populations.
In cattle, gamma delta T cells represent a higher proportion of circulating T cells than in humans. Bovine gamma delta T cells can be recognized by expression of gamma delta cell receptor (gamma delta TCR) determinants or by a 215/230-kDa surface antigen (WC1). WC1 is expressed on 90% or more of circulating bovine gamma delta T cells. The effects of dexamethasone on this and other subsets (CD3, CD2, CD4, CD8) of peripheral blood T lymphocytes were determined by flow cytometric analysis. Twelve 15-month old bulls were injected with dexamethasone (0.04 mg/kg/day) for 3 consecutive days and four bulls were untreated controls. Blood samples were collected daily for 3 days before dexamethasone injections and for an additional 7 days starting on the third day. Data were recorded as percent positive cells and as mean fluorescent intensity (MFI) of positive cells. Initially, CD3+ cells represented 65-73% of all peripheral blood clear cells (PBMC). Dexamethasone reduced CD3+/- cells (PBMC). Dexamethasone reduced CD3+ cells to 30% and these recovered to 50% positive cells by 9 days after the last dexamethasone injection. Loss of CD3+ cells was not due to reductions in alpha beta T cells because dexamethasone did not influence the percent CD2+, CD4+, or CD8+ cells. However, percent WC1+ cells rapidly declined from a baseline of 26.4% of PBMC to < 6% by the final injection. During injections, the MFI of WC1 increased. The MFI of WC1 returned to control values 7 days after the last injection of dexamethasone, but the percent gamma delta T cells recovered to only 14% WC1+ PBMC by the final day of the study. During its maximum effects on WC1, dexamethasone also caused a profound decrease of L-selectin MFI on remaining PBMC (mostly alpha beta T cells and monocyte/macrophages). In a second trial, two-color analyses determined that dexamethasone did not increase apoptosis in WC1+ cells and did not reduce L-selectin MFI on either CD2+ of WC1+ cells. The cumulative results suggested that dexamethasone promoted gamma delta T cell migration out of peripheral blood via an L-selectin-independent mechanism and that dexamethasone did not alter alpha beta T cell migration kinetics.


Trifluoperazine and dibucaine-induced inhibition of glutamate-induced mitochondrial depolarization in rat cultured forebrain neurones.
1. Glutamate receptor activation has been previously shown to result in mitochondrial depolarization and activation of the mitochondrial permeability transition pore in cultured neurones. In this study, we characterized the effects of two putative permeability transition inhibitors, namely trifluoperazine and dibucaine, on mitochondrial depolarization in rat intact, cultured forebrain neurones. 2. Permeability transition was monitored by following mitochondrial depolarization in neurones loaded with the mitochondrial membrane potential-sensitive fluorescent indicator, JC-1. Trifluoperazine (10 20 microM) and dibucaine (50-100 microM) inhibited or delayed the onset of glutamate-induced permeability transition. 3. We also investigated the effects of trifluoperazine and dibucaine on neuronal recovery from glutamate-induced Ca2+ loads. Trifluoperazine affected Ca2+ recovery in a manner similar to the mitochondrial Na+/Ca2+ exchange inhibitor, CGP-37157, while dibucaine had no apparent effect on Ca2+ recovery. Therefore, inhibition of permeability transition does not appear to be involved in Ca2+ recovery from glutamate-induced Ca2+ loads. 4. Trifluoperazine and dibucaine did not inhibit [3H]-dizocilpine binding at the concentrations that prevented mitochondrial depolarization. 5. These studies suggest that trifluoperazine and dibucaine inhibit permeability transition in intact neurones. Trifluoperazine also appears to inhibit mitochondrial Na+/Ca2+ exchange. These drugs should prove to be valuable tools in the further study of the role of mitochondrial permeability transition in glutamate-induced neuronal death.


Recent Advances in Engineering of In Vivo Haploid Induction Systems.
Doubled haploid (DH) technology is an important approach to accelerate genetic gain via a shortened breeding cycle, which relies on the ability to generate haploid cells that develop into haploids or doubled haploid embryos and plants. Both in vitro and in vivo (in seed) methods can be used for haploid production. In vitro culture of gametophytes (microspores and megaspores) or their surrounding floral tissues or organs (anthers, ovaries, or ovules) has generated haploid plants in wheat, rice, cucumber, tomato, and many other crops. In vivo methods utilize pollen irradiation or wide crossing or in certain species leverage genetic mutant haploid inducer lines. Haploid inducers were widespread in corn and barley, and recent cloning of the inducer genes and identification of the causal mutations in corn have led to the establishment of in vivo haploid inducer systems via genome editing of orthologous genes in more diverse species. Further combination of DH and genome editing technology led to the development of novel breeding technologies such as HI-EDIT™. In this chapter, we will review in vivo haploid induction and new breeding technologies that combine haploid induction and genome editing.


Control of S phase duration: a replication capacity model with E2F transcription at its heart.
DNA replication capacity, the maximal amount of DNA a cell can synthesize at any given time during S phase, is controlled by E2F-dependent transcription. Controlling replication capacity limits the replication rate and provides a robust mechanism to keep replication fork speed within an optimal range whilst ensuring timely completion of genome duplication.


Phylogenetic relationships and macro-evolutionary patterns within the Drosophila tripunctata "radiation" (Diptera: Drosophilidae).
Despite previous efforts, the evolutionary history of the immigrans-tripunctata clade remains obscure in part due to its hypothesized origin through a rapid radiation. We performed a supermatrix analysis (3,243 base pairs) coupled with richness patterns, environmental phylogenetic signal and radiation tests in order to address phylogenetic relationships and macro-evolutionary hypotheses within this complex group of species. We propose a well-supported evolutionary scenario for the immigrans-tripunctata clade species, in which the tripunctata "radiation" was monophyletic and subdivided into three main lineages: the first including D. pallidipennis (pallidipennis group) imbedded among members of the tripunctata group; the second clustering the cardini and guarani groups; and the third grouping representatives from the tripunctata, calloptera and guaramunu groups. Therefore, we hypothesize that the tripunctata group encompasses a diphyletic taxon, with one clade including the pallidipennis group and the other showing a close affinity to the calloptera and guaramunu groups. Our results also suggest that niche evolution seems to have played a central role in the evolutionary history of the tripunctata species "radiation" allowing effective dispersion and diversification in the Neotropics, possibly in a southwards direction. Although the data as a whole support the notion that this occurred through rapid and successive speciation events, the radiation hypothesis remains to be further corroborated.


Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas.
Ischaemia impairs organ quality during preservation in a time-dependent manner, due to a lack of oxygen supply. Its impact on pancreas and islet transplantation outcome has been demonstrated by a correlation between cold ischaemia time and poor islet isolation efficiency. Our goal in the present study was to improve pancreas and islet quality using a novel natural oxygen carrier (M101, 2 g/L), which has been proven safe and efficient in other clinical applications, including kidney transplantation, and for several pre-clinical transplantation models. When M101 was added to the preservation solution of rat pancreas during ischaemia, a decrease in oxidative stress (ROS), necrosis (HMGB1), and cellular stress pathway (p38 MAPK)activity was observed. Freshly isolated islets had improved function when M101 was injected in the pancreas. Additionally, human pancreases exposed to M101 for 3 hours had an increase in complex 1 mitochondrial activity, as well as activation of AKT activity, a cell survival marker. Insulin secretion was also up-regulated for isolated islets. In summary, these results demonstrate a positive effect of the oxygen carrier M101 on rat and human pancreas during preservation, with an overall improvement in post-isolation islet quality.


An exploratory, intra- and interindividual comparison of the deep neural network automatically measured calf surface radiation temperature during cardiopulmonary running and cycling exercise testing: A preliminary study.
Non-invasive and contactless infrared thermography (IRT) measurements have been claimed to indicate acute neural, cardiovascular, and thermoregulatory adaptations during exercise. Due to challenging comparability, reproducibility, and objectivity, investigations considering different exercise types and intensities, and automatic ROI analysis are currently needed. Thus, we aimed to examine surface radiation temperature (Tsr) variations during different exercise types and intensities in the same individuals, ROI, and environmental conditions. Ten healthy, active males performed a cardiopulmonary exercise test on a treadmill in the first week and on a cycling ergometer the following week. Respiration, heart rate, lactate, rated perceived exertion, the mean, minimum, and maximum Tsr of the right calf (CTsr (°C)), and the surface radiation temperature pattern (CPsr) were explored. We executed two-way rmANOVA and Spearman's rho correlation analyses. Across all IRT parameters, mean CTsr showed the highest association to cardiopulmonary parameters (E.g., oxygen consumption: rs = -0.612 (running); -0.663 (cycling); p < .001). A global significant difference of CTsr was identified between all relevant exercise test increments for both exercise-types (p < .001; η2p = .842) and between both exercise-types (p = .045; η2p = .205). Differences in CTsr between running and cycling significantly appeared after a 3-min recovery period, whereas lactate, heart rate, and oxygen consumption were not different. High correlations between the CTsr values extracted manually and the CTsr values processed automatically by a deep neural network were identified. The applied objective time series analysis enables crucial insights into intra- and interindividual differences between both tests. CTsr variations indicate different physiological demands between incremental running and cycling exercise testing. Further studies applying automatic ROI analyses are needed to enable the extensive analysis of inter- and intraindividual factors influencing the CTsr variation during exercise to allow determine the criterion and predictive validity of IRT parameters in exercise physiology.


Scan-layered reconstructions: A pilot study of a nondestructive dental histoanatomical analysis method and digital workflow to create restorations driven by natural dentin and enamel morphology.
This work aims to present a pilot study of a non-destructive dental histo-anatomical analysis technique as well as to push the boundaries of the presently available restorative workflows for the fabrication of highly customized ceramic restorations. An extracted human maxillary central incisor was subject to a micro computed tomography scan and the acquired data was transferred into a workstation, reconstructed, segmented, evaluated and later imported into a Computer-Aided Design/Computer-Aided Manufacturing software for the fabrication of a ceramic resin-bonded prosthesis. The obtained prosthesis presented an encouraging optical behavior and was used clinically as final restoration. The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. New clinical and laboratory-fabricated, biologically inspired digital restorative protocols are to be expected in the near future. The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. This pilot study may represent a stimulus for future research and applications of digital imaging as well as digital restorative workflows in service of esthetic dentistry.


Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States, 2000-2017.
Limited population-based data exist for the brainstem gliomas for children ages ≤19 years, which includes high-grade aggressively growing tumors such as diffuse intrinsic pontine glioma (DIPG). We examined the overall incidence and survival patterns in children with brainstem high-grade glioma (HGG) by age, sex, and race and ethnicity. We used data from Central Brain Tumor Registry of the United States (CBTRUS), obtained through data use agreements with the Centers for Disease Control (CDC) and the National Cancer Institute (NCI) from 2000 to 2017, and survival data from the CDCs National Program of Cancer Registries (NPCR), from 2001 to 2016 for malignant brainstem HGG for ages ≤19 years (per WHO ICD-O-3 codes). HGG was determined by established histologic and/or imaging criteria. Age-adjusted incidence rates and survival data were used to assess differences overall and by age, sex race, and ethnicity. The incidence of brainstem HGG was higher among the female and Non-Hispanic population. Majority (69.8%) of these tumors were diagnosed radiographically. Incidence was higher in children aged 1-9 years compared to older children. Whites had a higher incidence compared to Blacks. However, the risk of death was higher among Blacks and Other race compared to Whites. There was no difference in survival by sex. We report the most comprehensive incidence and survival data on these lethal brainstem HGGs. Incidence and survival among patients with brainstem HGGs differed significantly by race, ethnicity, age-groups, and grade.


Streptococcus Intermedius as the cause of sphenoid sinusitis & associated extensive skull base and neck thrombophlebitis & thrombosis.
Acute bacterial sinusitis may be complicated by orbital and intracranial involvement and by thrombophlebitis. Its spread across multiple anatomic compartments is facilitated by the interconnected venous anatomy of the head and neck and the virulence of the primary pathogen. We present a rare case of Streptococcus Intermedius (S. Intermedius) acute bacterial sinusitis complicated by extensive skull base involvement including cavernous sinuses and neck vein thrombophlebitis and thrombosis.


Is there an increased risk of cesarean section in obese women after induction of labor? A retrospective cohort study.
Obesity is increasing in Sweden and is also of huge global concern. Obesity increases the risk of complications during pregnancy and the need for the induction of labor. Induction of labor increases the number of complications during delivery, leading to women with more negative birth experience. This study investigated how maternal body mass index (BMI) during antenatal care enrollment affects labor outcomes (proportion of cesarean section at induction of labor). This was a retrospective cohort study of 3772 women with mixed parity and induction of labor at Soderhospital, Stockholm, in 2009-2010 and 2012-2013. The inclusion criteria were simplex, ≥34 gestational weeks, cephalic presentation and no previous cesarean section. The women were grouped according to BMI, and statistical analyzes were performed to compare the proportion of cesarean sections after induction of labor. The primary outcome was the proportion of cesarean section after induction of labor divided by group of maternal BMI. The secondary outcomes were postpartum hemorrhage >1000 ml, time of labor, fetal outcome data, and indication for emergency cesarean section. The induction of labor in women with a high BMI resulted in a significantly increased risk of cesarean section, with 18.4-24.1% of deliveries, depending on the BMI group. This outcome persisted after adjustment in women with BMI 25-29.9 (aOR 1.4; 95% CI; 1.1-1.7) and BMI 30-34.9 (aOR 1.5; 95% CI; 1.1-2.1). There was also a significantly higher risk for CS among primiparous women (aOR 3.6; 95% CI; 2.9-45) and if the newborn weighted ≥ four kilos (aOR 1.6; 95% CI; 1.3-2.0). Our findings show that a higher BMI increased the risk of cesarean section after induction of labor in the groups with BMI 25-34.9. Parity seems to be the strongest risk factor for CS regardless other variables.


Phenylpyrrolidine structural mimics of pirfenidone lacking antifibrotic activity: A new tool for mechanism of action studies.
Pirfenidone recently received FDA approval as one of the first two drugs designed to treat idiopathic pulmonary fibrosis. While the clinical data continues to support the efficacy of pirfenidone, the specific molecular mechanism of action of this drug has not been fully defined. From a chemical perspective the comparatively simple and lipophilic structure of pirfenidone combined with its administration at high doses, both experimentally and clinically, complicates some of the basic tenants of drug action and drug design. Our objective here was to identify a commercially available structural mimic of pirfenidone which retains key aspects of its physical chemical properties but does not display any of its antifibrotic effects. We tested these molecules using lung fibroblasts derived from patients with idiopathic pulmonary fibrosis and found phenylpyrrolidine based analogs of pirfenidone that were non-toxic and lacked antifibrotic activity even when applied at millimolar concentrations. Based on our findings, these molecules represent pharmacological tools for future studies delineating pirfenidone's mechanism of action.


A Cross-Sectional Survey of the Workplace Factors Contributing to Symptoms of Anxiety and Depression Among Nurses and Physicians During the First Wave of COVID-19 Pandemic in Two US Healthcare Systems.
Anxiety and depression among physicians and nurses during the COVID-19 pandemic in the USA are not well described and their modifiable causes are poorly understood. We conducted a cross-sectional survey of symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) among physicians and nurses in two US healthcare systems in June through September 2020; participation rate was 5-10%. We described features of work as well as their perceptions and associated concerns in relation to the risk of anxiety and depression, while controlling for health history via regression and path analyses. About a third of 684 nurses and 185 physicians surveyed showed symptoms of anxiety or depression, and the excess of symptoms of mood disorders was particularly prominent in nurses. The belief that one was infected was a dominant correlate of both anxiety and depression. This belief was more associated with history of symptoms of pneumonia than the contact with COVID-19 diagnosed patients. Factors found to be associated with reduced anxiety and depression in this working environment were having confidence in the competent use of and access to personal protective equipment, maintaining usual working hours, being surrounded by colleagues who were both sufficient in numbers and not stressed, and the support of immediate family and religious communities. Involvement in aerosol-generating procedures with infected patients was linked with lower depression in nurses but higher among physicians. Likewise, the setting of recent patient encounters affected risk of anxiety and depression differently for physicians and nurses. Our findings may help develop mitigation measures and underscore the need to help nurses and physicians bear the psychological burden of the COVID-19 pandemic and similar events in the future.


11th GCC Closed Forum: cumulative stability; matrix stability; immunogenicity assays; laboratory manuals; biosimilars; chiral methods; hybrid LBA/LCMS assays; fit-for-purpose validation; China Food and Drug Administration bioanalytical method validation.
The 11th Global CRO Council Closed Forum was held in Universal City, CA, USA on 3 April 2017. Representatives from international CRO members offering bioanalytical services were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The second CRO-Pharma Scientific Interchange Meeting was held on 7 April 2017, which included Pharma representatives' sharing perspectives on the topics discussed earlier in the week with the CRO members. The issues discussed at the meetings included cumulative stability evaluations, matrix stability evaluations, the 2016 US FDA Immunogenicity Guidance and recent and unexpected FDA Form 483s on immunogenicity assays, the bioanalytical laboratory's role in writing PK sample collection instructions, biosimilars, CRO perspectives on the use of chiral versus achiral methods, hybrid LBA/LCMS assays, applications of fit-for-purpose validation and, at the Global CRO Council Closed Forum only, the status and trend of current regulated bioanalytical practice in China under CFDA's new BMV policy. Conclusions from discussions of these topics at both meetings are included in this report.