Insights into the diversity of Hormogastridae (Annelida, Oligochaeta) with descriptions of six new species.
The earthworm family Hormogastridae is a relatively diverse group in the Western Mediterranean basin. Since 1887, around thirty species have been described and assigned to four genera. However, from 2010 on, molecular, ecological and morphological studies have questioned the validity of those genera. Meanwhile, new species were discovered and assigned to them, pending a formal systematic revision; such a revision has been performed recently by integrating all the existing sources of information. The resulting classification consists of nine genera, including four newly erected ones. This revised systematic background is used in the current work as a base for the description of six new hormogastrid species: Diazcosinia sacrarium Marchán, Fernández, Díaz Cosín Novo, sp. nov., Boucheona martae Marchán, Fernández Díaz Cosín, sp. nov., Boucheona rosae Marchán, Díaz Cosín Novo, sp. nov., Norana emiliae Marchán, Fernández, Díaz Cosín Novo, sp. nov., Norana xylocerasi Marchán, Fernández, Díaz Cosín Novo, sp. nov., and Norana beatrizae Marchán, Fernández, Díaz Cosín Novo, sp. nov. Norana is a new replacement name for the preoccupied Nora Marchán, Fernández, Díaz Cosín Novo, 2018. Likewise, Xanina is proposed to replace the preoccupied Xana Díaz Cosín, Briones Trigo, 1989. We provide an overview of the currently known diversity of the different genera, and we further propose common names in several languages for some of the species of Hormogastridae.


Norrish Type I surface photochemistry for butyrophenone on TiO2(110).
The photofragmentation of butyrophenone yields benzoate and a propyl radical on oxidized TiO2(110). Oxygen dissociates in native oxygen vacancies to produce reactive oxygen adatoms which react with butyrophenone to create photoactive butyrophenone-O complexes that are sensitive to hole oxidation created upon UV illumination. The same O adatoms also trap one of the primary photoproducts, phenyl-CO, to produce benzoate. The reaction proceeds via a Norrish Type I like process involving α-CC cleavage on the surface, in contrast to the gas phase where a Norrish Type II pathway predominates. The mechanism is probed using mass spectrometry and, for the first time, scanning tunneling microscopy (STM). Our STM experiments show that there is a 1-to-1 correspondence between the immobile butyrophenone-O complex and formation of a benzoate on the surface. We also demonstrate that the benzoate species is in close proximity to the original butyrophenone complex, indicating that benzoate is produced on a time scale more rapid than diffusion of the photoproducts. While the photoproducts of butyrophenone decomposition are similar to ketone oxidation reported previously, butyrophenone reacts via a different starting ground state, based on STM and density functional theory studies. Specifically, butyrophenone does not produce a dioxyalkylene species, which has been proposed to be the photoactive state for other ketones. Based on a combination of STM experiments and density functional theory, we propose that a peroxy-like configuration where the oxygen adatom stabilizes the butyrophenone through its carbonyl oxygen is the surface intermediate that photodecomposes. These results demonstrate the importance of the excited state in determining the photochemistry of ketones on surfaces.


Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice.
Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g-1 vs. 3801.30 ± 27.34 pg g-1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.


Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome.
We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud's phenomenon, and hypermobility. She was found to have a 6074A > T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient's symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome (EDS). At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A > T nucleotide transition in the TNXB gene may be classified as disease-causing for EDS due to tenascin-X deficiency.


Tissue characterization of benign cardiac tumors by cardiac magnetic resonance imaging, a review of core imaging protocol and benign cardiac tumors.
Generally, cardiac masses are initially suspected on routine echocardiography. Cardiac magnetic resonance (CMR) imaging is further performed to differentiate tumors from pseudo-tumors and to characterize the cardiac masses based on their appearance on T1/T2-weighted images, detection of perfusion and demonstration of gadolinium-based contrast agent uptake on early and late gadolinium enhancement images. Further evaluation of cardiac masses by CMR is critical because unnecessary surgery can be avoided by better tissue characterization. Different cardiac tissues have different T1 and T2 relaxation times, principally owing to different internal biochemical environments surrounding the protons. In CMR, the signal intensity from a particular tissue depends on its T1 and T2 relaxation times and its proton density. CMR uses this principle to differentiate between various tissue types by weighting images based on their T1 or T2 relaxation times. Generally, tumor cells are larger, edematous, and have associated inflammatory reactions. Higher free water content of the neoplastic cells and other changes in tissue composition lead to prolonged T1/T2 relaxation times and thus an inherent contrast between tumors and normal tissue exists. Overall, these biochemical changes create an environment where different cardiac masses produce different signal intensity on their T1- weighted and T2- weighted images that help to discriminate between them. In this review article, we have provided a detailed description of the core CMR imaging protocol for evaluation of cardiac masses. We have also discussed the basic features of benign cardiac tumors as well as the role of CMR in evaluation and further tissue characterization of these tumors.


[A new method using the technique of cubic spline interpolation to remove baseline wander].
The present methods available for correction of baseline wander with cubic spline interpolation technique all determine the fiducial points from P-R intervals. However, the determination of the fiducial points can be adversely affected by a noisy signal or an uneven P-R interval. In this paper, we introduce a new method of determining fiducial points by using the feature of high frequency of QRS wave. First, we correct the baseline approximately by using a FIR filter, then find the position of R peak and its amplitude change after filtering. The experiments demonstrate that the previous position and amplitude change can be looked as the position and amplitude of a fiducial point. Finally, we estimate a continuous baseline by joining fiducial points with spline. Our experiment results show that this is a better filtering method in comparison with the one introduced in reference paper [3].


Expression, purification, and characterization of the oligomeric states of rubredoxin oxidoreductase from Methanobacterium thermoautotrophicum.
The rubredoxin oxidoreductase from Methanobacterium thermoautotrophicum was successfully overexpressed in Escherichia coli with 6x His-Tag and purified by using Ni-NTA technology. It was characterized by SDS and native polyacrylamide gel electrophoresis (PAGE), as well as size-exclusion chromatography. The protein was pure, judged by SDS-PAGE, but three or more oligomeric species were observed by native PAGE and size-exclusion chromatography. The smallest rubredoxin oxidoreductase species is the dimer. The multiple species are stable and remain in their respective oligomeric states, judged by the chromatographic and electrophoretic results. A model is proposed in order to explain the structural basis for these results.


Dynamic competition between catch and slip bonds in selectins bound to ligands.
Atomic force measurements of unbinding rates (or off-rates) of ligands bound to a class of cell adhesion molecules from the selectin family show a transition from catch to slip bonds as the value of external force (f) is increased. At low forces (<10 pN), the unbinding rates decrease (catch regime), while, at high forces, the rates increase in accord with the Bell model (slip regime). The energy landscape underlying the catch-slip transition can be captured by a two-state model that considers the possibility of redistribution of population from the force-free bound state to the force-stabilized bound state. The excellent agreement between theory and experiments is used to extract the parameters characterizing the energy landscape of the complex by fitting the calculated curves to lifetime data (obtained at constant f) for the monomeric form of PSGL-1 (sPSGL-1). We used the constant force parameters to predict the distributions of unbinding times and unbinding forces as a function of the loading rate. The general two-state model, which also correctly predicts the absence of catch bonds in the binding of antibodies to selectins, is used to resolve the energy landscape parameters characterizing adhesive interactions of P- and L-selectins with physiological ligands such as sPSGL-1 and endoglycan and antibodies such as G1 and DREG56. Despite high sequence similarity, the underlying shapes of the energy landscape of P-selectin and L-selectin interacting with sPSGL-1 are markedly different. The underlying energy landscape of the selectin cell adhesion complex is sensitive to the nature of the ligand. The unified description of selectins bound to physiological ligands and antibodies in conjunction with experimental data can be used to extract the key parameters that describe the dynamics of cell adhesion complexes.


Constructiveness where it counts.
I hope that this response to Scofield's paper has accomplished two goals: 1) it helps put to rest unreal discussion of a "profession" of clinical ethics and 2) it helps to focus on the most important issues raised by Scofield upon which action can be taken. It is true that "ethics is everybody's business" and ethicists must restrain their bias when it comes to the decision-making process. But special knowledge and skills are required to nurture the elements of a clinical ethics program, to unite the efforts of its multitalented members, and to relate the literature of a rapidly growing activity in healthcare to practical projects. The issues raised in the constructive parts of Scofield's paper are an excellent point of departure for debate on how best to shape the education, training, and standards of practice for clinical ethics.


Work-related factors, job satisfaction and intent to leave the current job among United States nurses.
To examine the relationships of work-related factors (e.g., autonomy, work schedule, supervisory and peer support) to nurses' job satisfaction and intent to leave their current position. Low job satisfaction and high turnover of nurses are major problems for health care. To improve nurse retention, work-related factors associated with job satisfaction and intent to leave should be investigated. A cross-sectional secondary data analysis. Data were obtained in 2004 from Wave 3 of the Nurses' Worklife and Health Study. A random sample of 5000 actively licenced nurses in Illinois and North Carolina (two U.S. states) were sent the survey in wave 1, of which 1641 actively working bedside nurses participated in wave 3. We examined associations of various work-related factors with job satisfaction and intent to leave the current position. Nurses who were dissatisfied with their job reported significantly higher psychological demands and lower autonomy than nurses who were satisfied. Nurses were significantly less satisfied with their jobs when they worked longer hours with inadequate breaks or sick days. Lack of support from peers and supervisors was also related to significantly lower odds of job satisfaction. For intention to leave, nurses who said they planned to leave their current job reported significantly lower autonomy and less support from their peers than nurses who intended to stay. A variety of modifiable work-related factors were significantly related to job satisfaction and intention to leave the current job among nurses. Future research should focus on developing interventions that could mitigate these factors (e.g., by improving work schedules, increasing autonomy and/or nurse support). The impact of such interventions on job satisfaction and intention to leave the current position could then be evaluated. To increase nurse retention, improved schedules, autonomy and supportive work environments should be promoted.


The biological assay of human somatomedin A: improvement by small molecular weight natural molecules.
Somatomedin activity is often measured by 35SO4 uptake in pelvic chick embryo cartilage. This assay gives good results when the somatomedin activity is measured in serum, but often gives uninterpretable results for purified somatomedin. An ultrafiltrate (UF 1000) obtained from human normal serum, added to the incubation medium allows measurement of biological somatomedin activity even when somatomedin is highly purified. UF 1000 contains some compounds of molecular weight lower than 1000 daltons. UF 1000 acts either when used simultaneously with somatomedin or in pre-incubation with cartilage before testing biological activity. So, we chose to use it in pre-incubation (1 h) at the optimal concentration of 10% (v/v), the standard curves being realized with normal serum retentates . In these conditions, the proper action of UF 1000 does not interfere with calculation of somatomedin activity. This method has enabled us to show that a diminution of serum somatomedin activity can be linked either to an anomaly of UF 1000 or to a somatomedin deficiency.


Further evidence for discrete-state mediation in recognition memory.
The two high threshold model (2HTM) of recognition memory makes strong predictions regarding differences between receiver operating characteristics (ROC) functions across strength manipulations. Province and Rouder (2012) tested these predictions and showed that the 2HTM provided a better account of the data than a continuous signal detection model using an extended two-alternative forced-choice task. The present study replicates and extends Province and Rouder's findings at the level of confidence-rating responses as well as their associated response times. Model-mimicry simulations are also reported, ascertaining that the models can be well discriminated in this experimental design.


Clinical and biochemical characteristics of postpancreatitis diabetes mellitus: A cross-sectional study from the Danish nationwide DD2 cohort.
Postpancreatitis diabetes mellitus (PPDM) is a common metabolic sequalae of acute and chronic pancreatitis. We conducted a cross-sectional study to examine the proportion of PPDM among patients clinically diagnosed with type 2 diabetes (T2D) in Denmark and their clinical and biochemical characteristics. We identified all past diagnoses of pancreatitis among patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort through linkage with national health registries. Using International Classification of Diseases, Tenth Revision codes we categorized patients as PPDM and further divided them into acute/chronic subtypes (PPDM-A and PPDM-C). We assessed PPDM prevalence and examined associations with clinical and biochemical parameters using log binomial or Poisson regression to calculate age-/sex-adjusted prevalence ratios (aPRs). Among 5564 patients with a clinical diagnosis of T2D, 78 (1.4%) had PPDM. Compared to T2D, PPDM patients were more often underweight or normal weight (body mass index ≤25.0 kg/m2 : aPR 2.3; 95% confidence interval [CI]: 1.6-3.2) and had lower waist-to-hip ratio (≤0.95/≤0.80 in men/women: aPRs 1.8; 95% CI: 1.2-2.7). PPDM patients had lower plasma amylase levels (<17 U/L: aPRs 2.2; 95% CI: 1.1-4.3), higher insulin sensitivity (homeostatic model assessment 2S [HOMA2S] >63: aPR 2.0; 95% CI: 1.2-3.2) and tended to have worse glycaemic control (HbA1c ≥8.0%: aPRs 1.4; 95% CI: 0.8-2.4). PPDM-A was largely indistinguishable from T2D, whereas PPDM-C had impaired insulin secretion, higher insulin sensitivity, and worse glycemic control. The proportion of PPDM among patients with clinically diagnosed T2D is ~1.5% in an everyday clinical care setting. Glucose metabolism of PPDM-A is largely indistinguishable from T2D, whereas PPDM-C differs in relation to insulin secretion and sensitivity.


[Iniencephalus apertus. Report of a case (author's transl)].
A macro and microscopic study carried out on an iniencephalic fetus weighing 650 g. is reported. This fetus is especially interesting as it presents anencephaly, supporting the view of classifying together iniencephaly and anencephaly with retroflexion. The main malformations present were: supernumerary ectopical thymus, esophageal atresia with inferior T-E fistula (Type V of Ladd), pulmonary hypoplasia with accessory lung, transposition of the large vessels, rectal atresia, single kidney, persistence of the urogenital sinus and single umbilical artery. The possible etiopathogenic causes are discussed and an embryological interpretation of the principal malformations is given.


Genetic association between germline JAK2 polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case-control study.
Myeloproliferative neoplasms (MPNs) are a group of haematological malignancies that can be characterised by a somatic mutation (JAK2V617F). This mutation causes the bone marrow to produce excessive blood cells and is found in polycythaemia vera (~95%), essential thrombocythaemia and primary myelofibrosis (both ~50%). It is considered as a major genetic factor contributing to the development of these MPNs. No genetic association study of MPN in the Hong Kong population has so far been reported. Here, we investigated the relationship between germline JAK2 polymorphisms and MPNs in Hong Kong Chinese to find causal variants that contribute to MPN development. We analysed 19 tag single nucleotide polymorphisms (SNPs) within the JAK2 locus in 172 MPN patients and 470 healthy controls. Three of these 19 SNPs defined the reported JAK2 46/1 haplotype: rs10974944, rs12343867 and rs12340895. Allele and haplotype frequencies were compared between patients and controls by logistic regression adjusted for sex and age. Permutation test was used to correct for multiple comparisons. With significant findings from the 19 SNPs, we then examined 76 additional SNPs across the 148.7-kb region of JAK2 via imputation with the SNP data from the 1000 Genomes Project. In single-marker analysis, 15 SNPs showed association with JAK2V617F-positive MPNs (n = 128), and 8 of these were novel MPN-associated SNPs not previously reported. Exhaustive variable-sized sliding-window haplotype analysis identified 184 haplotypes showing significant differences (P < 0.05) in frequencies between patients and controls even after multiple-testing correction. However, single-marker alleles exhibited the strongest association with V617F-positive MPNs. In local Hong Kong Chinese, rs12342421 showed the strongest association signal: asymptotic P = 3.76 × 10-15, empirical P = 2.00 × 10-5 for 50,000 permutations, OR = 3.55 for the minor allele C, and 95% CI, 2.59-4.87. Conditional logistic regression also signified an independent effect of rs12342421 in significant haplotype windows, and this independent effect remained unchanged even with the imputation of additional 76 SNPs. No significant association was found between V617F-negative MPNs and JAK2 SNPs. With a large sample size, we reported the association between JAK2V617F-positive MPNs and 15 tag JAK2 SNPs and the association of rs12342421 being independent of the JAK2 46/1 haplotype in Hong Kong Chinese population.


Physician specialty and variation in carotid revascularization technique selected for Medicare patients.
Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA) for select patients with carotid atherosclerosis. We hypothesized that the choice of CAS vs CEA varies as a function of treating physician specialty, which would result in regional variation in the relative use of these treatment types. We used Medicare claims (2002-2010) to calculate annual rates of CAS and CEA and examined changes by procedure type over time. To assess regional preferences surrounding CAS, we calculated the proportion of revascularizations by CAS, across hospital referral regions, defined according to the Dartmouth Atlas of Healthcare. We then examined relationships between patient factors, physician specialty, and regional use of CAS. The annual number of all carotid revascularization procedures decreased by 30% from 2002 to 2010 (3.2 to 2.3 per 1000; P = .005). Whereas rates of CEA declined by 35% during these 8 years (3.0 to 1.9 per 1000; P < .001), CAS utilization increased by 5% during the same interval (0.30 to 0.32 per 1000; P = .014). Variation in utilization of carotid revascularization varied across the Unites States, with some regions performing as few as 0.7 carotid procedure per 1000 beneficiaries (Honolulu, Hawaii) and others performing nearly 8 times as many (5.3 per 1000 in Houma, La). Variation in procedure type (CEA vs CAS) was evident as well, as the proportion of carotid revascularization procedures that were constituted by CAS varied from 0% (Casper, Wyo, and Meridian, Miss) to 53% (Bend, Ore). The majority of CAS procedures were performed by cardiologists (49% of all CAS cases), who doubled their rates of CAS during the study period from 0.07 per 1000 in 2002 to 0.15 per 1000 in 2010. Variation in rates of carotid revascularization exists. Whereas rates of carotid revascularization have declined by more than 30% in recent years, utilization of CAS has increased. The proportion of all carotid revascularization procedures performed as CAS varies markedly by geographic region, and regions with the highest proportion of cardiologists perform the most CAS procedures. Evidence-based guidelines for carotid revascularization will require a multidisciplinary approach to ensure uniform adoption across specialties that care for patients with carotid artery disease.


Neuro-ophthalmologic findings in humans with quadrupedal locomotion.
To report the neuro-ophthalmologic findings in four patients from the same family with cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ)2 associated with quadrupedal locomotion. A case series. All four patients carry the private missense mutation, WDR81 p.P856L. The brain Magnetic Resonance Imaging (MRI) of these patients revealed morphological abnormalities including mild hypoplasia of the corpus callosum, and atrophy of superior, middle, and inferior peduncles of the cerebellum. All patients had down-beat nystagmus, while two male patients additionally had bilateral temporal disc pallor along with ring-shaped macular atrophy. The neuro-ophthalmic examination in CAMRQ2 revealed downbeat nystagmus in all patients, and temporal disc pallor and macular atrophy in two patients. It remains to be determined whether these findings are consistent in other forms of CAMRQ with mutations in VLDLR or CA8.


A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu, China.
The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu, China. Epidemiological studies indicate a dose-, level- and duration-dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality. Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes. A randomized controlled trial was conducted. Coronary heart disease patients (n = 167) who met the sampling criteria in two tertiary medical centres in Chengdu, south-west China, were randomly assigned to either an intervention group (the cardiac rehabilitation programme) or control group (the routine care). The change of health behaviours (walking performance, step II diet adherence, medication adherence, smoking cessation) and physiological risk parameters (serum lipids, blood pressure, body weight) were assessed to evaluate the programme effect. Patients in the intervention group demonstrated a significantly better performance in walking, step II diet adherence, medication adherence; a significantly greater reduction in serum lipids including triglyceride, total cholesterol, low-density lipoprotein; and significantly better control of systolic and diastolic blood pressure at three months. The majority of these positive impacts were maintained at six months. The effect of the programme on smoking cessation, body weight, serum high-density lipoprotein, was not confirmed. A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients. Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease. This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients. Furthermore, the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care.


[Expression of matrix extracellular phosphoglycoprotein mRNA in human periodontal ligament cell osteogenic differentiation].
To investigate the mineralization capacity of periodontal ligament stem cells (PDLC) by determining the mRNA expressions of alkaline phosphatase (ALP), osteocalcin (OCN) and matrix extracellular phosphoglycoprotein (MEPE) and to explore the potential of MEPE as a differentiation marker for PDLC, and its possible function in PDLC osteogenic differentiation. PDLC were digested and cultured by a solution containing collagenase type I and dispase. PDLC were preceded to osteogenic induction for 7, 14 and 21 days respectively, and the cells before induction served as controls. Mineralization nodules and the expression of OCN in PDLC were investigated by alizarin red and immunohistochemistry respectively. The expressions of ALP, OCN and MEPE mRNA were investigated by quantitative real-time RT-PCR analysis. Statistical analysis was performed to compare the differences of mRNA expression levels among cell samples collected at different time points. The mRNA expressions of ALP, OCN and MEPE in PDLC before induction were 72, 1.1 and 534 respectively, but increased time-dependently in the induction cultures. The mRNA expressions of ALP, OCN and MEPE were 78, 9.56 and 629.6 on day 7; 290, 133 and 638.3 on day 14; 1108, 925 and 2261.1 on day 21 respectively. The relative mRNA levels of OCN, ALP on day 14 and 21, MEPE on day 21 were significantly higher than control group (P < 0.05). PDLC showed analogously temporal expression of ALP, OCN and MEPE mRNA while differentiating into cementoblast/osteoblast-like cells in vitro. MEPE may play a regulatory role in PDLC osteogenic differentiation, and may be a potential osteogenic differentiation marker along with ALP and OCN.


Formulation study for lansoprazole fast-disintegrating tablet. III. Design of rapidly disintegrating tablets.
Lansoprazole fast-disintegrating tablets (LFDT) are a patient-friendly formulation that rapidly disintegrates in the mouth. LFDT consist of enteric-coated microgranules (mean particle size, approximately 300 microm) and inactive granules. In the design of the inactive granules, mannitol was used as a basic excipient. Microcrystalline cellulose, low-substituted hydroxypropyl cellulose (L-HPC), and crospovidone were used as binders and disintegrants. A new grade of L-HPC (L-HPC-33), with a hydroxypropoxy group content of 5.0-6.9%, was developed and it has no rough texture due to a decrease in water absorption. It was clarified that L-HPC-33 could be useful as a binder and disintegrant in rapidly disintegrating tablets. LFDT contain enteric-coated microgranules in tablet form. The enteric-coated microgranule content in LFDT affect qualities such as tensile strength, disintegration time in the mouth, and dissolution behavior in the acid stage and in the buffer stage of LFDT. The 47.4% content of the enteric-coated microgranules was selected to give sufficient tensile strength (not less than 30 N/cm(2)), rapid disintegration time in the mouth (not more than 30 s), and dissolution behavior in the acid stage and buffer stage similar to current lansoprazole capsules. Compression force affected the tensile strength and the disintegration time in the mouth, but did not affect the dissolution behavior in the acid and buffer stages.


Candidate name order effects in New Hampshire: Evidence from primaries and from general elections with party column ballots.
Research in a few U.S. states has shown that candidates listed first on ballots gain extra votes as a result. This study explored name order effects for the first time in New Hampshire, where such effects might be weak or entirely absent because of high political engagement and the use of party column ballots. In general elections (in 2012 and 2016) for federal offices and the governorship and in primaries (in 2000, 2002, and 2004), evidence of primacy effects appeared in 86% of the 84 tests, including the 2016 presidential race, when Donald Trump gained 1.7 percentage points from first listing, and Hillary Clinton gained 1.5 percentage points. Consistent with theoretical predictions, primacy effects were larger in primaries and for major-party candidates in general elections than for non-major-party candidates in general elections, more pronounced in less publicized contests, and stronger in contests without an incumbent running. All of this constitutes evidence of the reliability and generalizability of evidence on candidate name order effects and their moderators.


[The research of virtual hepatectomy].
To investigate the methodology of mimic resection system on liver. Hepatic arteries, portal vein, inferior cava vein, hepatic veins and biliary ducts of liver with integrate hepatic portal were perfused with filling materials in different colors. And then the sample was embedded, frozen and slice-cut to obtain serial sectional images. After image registration and segmentation, the 3D reconstruction model which contained the liver's surface and its internal structures was constructed with MIMICS 9.0. Based on the freeform modeling system and its accessories (the software GHOST and the force-feedback equipment PHANTOM), the virtual hepatectomy system was established which could manipulate the virtual scalpel to perform optional resection on virtual liver model. After slice-cutting the cast liver, 910 serial cross-section images were obtained sharply and clearly. The 3D reconstructed liver model looked like the liver sample exactly, and could be magnified, contracted and rotated. In the virtual surgery system with good interaction, powerful immersion and great imagination, the virtual scalpel could be manipulated to perform optional resection on 3D liver model with the haptic device (PHANTOM). The 3D visualized liver and the virtual hepatectomy system has been satisfactorily developed using the hepatic serial sectional images. The process of simulation operation was consistent with clinical practice.


Synergistic effect of bromocriptine and tumor necrosis factor-alpha on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm.
To investigate the effect of bromocriptine (BCT) and tumor necrosis factor-alpha (TNF-alpha) on hepatocellular carcinoma (HCC) multidrug resistance (MDR) in nude mouse MDR model of liver neoplasm. Human hepatocarcinoma cell line HepG(2), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (ADM) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established (HepG(2), ADM, TNF, BCT groups). Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor histological character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups, and similar to HepG(2) group (54%). MDR1 and LRPmRNA could be detected in all groups, but TNF-alpha was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. BCT and TNF-alpha can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm.


Antimicrobial susceptibility, pulsed-field gel electrophoresis, and multi-locus sequence typing of Campylobacter coli in swine before, during, and after the slaughter process.
The objective of this study was to determine persistence of clonal strains from farm to retail by assessing the clonal relatedness of Campylobacter coli isolated on farm, peri-harvest, and at processing from 11 individually identified pigs. Phenotypic (antimicrobial susceptibility) and genotypic (pulsed field gel electrophoresis [PFGE] and multi-locus sequence typing [MLST]) characterization of isolates was conducted. There was high genetic diversity of Campylobacter isolates from on-farm fecal samples. Campylobacter isolates from farm, post-evisceration, hide, and carcass samples showed similar phenotypes and belonged to the same genotypic clusters based on PFGE and sequence types (STs) based on MLST. Five STs that have not been previously reported were identified (ST-4083, ST-4084, ST-4085, ST-4086, ST-4087). Despite high genotypic diversity of C. coli on farm, retail meat products were consistently contaminated with isolates of the same STs, particularly ST854 and ST1056, as isolates collected from previous stages confirming persistence of strains from pre- to post-harvest.


A review of patient and carer participation and the use of qualitative research in the development of core outcome sets.
To be meaningful, a core outcome set (COS) should be relevant to all stakeholders including patients and carers. This review aimed to explore the methods by which patients and carers have been included as participants in COS development exercises and, in particular, the use and reporting of qualitative methods. In August 2015, a search of the Core Outcomes Measures in Effectiveness Trials (COMET) database was undertaken to identify papers involving patients and carers in COS development. Data were extracted to identify the data collection methods used in COS development, the number of health professionals, patients and carers participating in these, and the reported details of qualitative research undertaken. Fifty-nine papers reporting patient and carer participation were included in the review, ten of which reported using qualitative methods. Although patients and carers participated in outcome elicitation for inclusion in COS processes, health professionals tended to dominate the prioritisation exercises. Of the ten qualitative papers, only three were reported as a clear pre-designed part of a COS process. Qualitative data were collected using interviews, focus groups or a combination of these. None of the qualitative papers reported an underpinning methodological framework and details regarding data saturation, reflexivity and resource use associated with data collection were often poorly reported. Five papers reported difficulty in achieving a diverse sample of participants and two reported that a large and varied range of outcomes were often identified by participants making subsequent rating and ranking difficult. Consideration of the best way to include patients and carers throughout the COS development process is needed. Additionally, further work is required to assess the potential role of qualitative methods in COS, to explore the knowledge produced by different qualitative data collection methods, and to evaluate the time and resources required to incorporate qualitative methods into COS development.


An infant with γ-globulin-induced hypersensitivity syndrome who developed Evans' syndrome after a second γ-globulin treatment.
Abstract One month after treatment with γ-globulin for Kawasaki disease, an 18-month-old girl developed Evans' syndrome in addition to drug-induced hypersensitivity syndrome (DIHS) after a second γ-globulin treatment. She suffered from hyperbilirubinemia, hemolytic anemia, and thrombocytopenia. The findings and her clinical course involved plasma exchange and treatment with prednisolone, with good results. Peripheral lymphocyte stimulation tests indicated that γ-globulin was the likeliest cause of the DIHS. A real-time polymerase chain reaction test showed the human herpes virus (HHV)-6 genome in peripheral blood. We demonstrated that a primary infection or infection reactivation by the HHV-6 virus was involved in the development of γ-globulin-induced hypersensitivity and Evans' syndrome.


The effect of a live vaccine on the horizontal transmission of Mycoplasma gallisepticum.
The effect of a live Mycoplasma gallisepticum vaccine on the horizontal transmission of this Mycoplasma species was quantified in an experimental animal transmission model in specific pathogen free White Layers. Two identical trials were performed, each consisting of two experimental groups and one control group. The experimental groups each consisted of 20 birds 21 weeks of age, which were housed following a pair-wise design. One group was vaccinated twice with a commercially available live attenuated M. gallisepticum vaccine, while the other group was not vaccinated. Each pair of the experimental group consisted of a challenged chicken (10(4) colony-forming units intratracheally) and a susceptible in-contact bird. The control group consisted of 10 twice-vaccinated birds housed in pairs and five individually housed non-vaccinated birds. The infection was monitored by serology, culture and quantitative polymerase chain reaction. The vaccine strain and the challenge strain were distinguished by a specific polymerase chain reaction and by random amplified polymorphic DNA analysis. In both experiments, all non-vaccinated challenged chickens and their in-contact 'partners' became infected with M. gallisepticum. In the vaccinated challenged and corresponding in-contact birds, a total of 19 and 13 chickens, respectively, became infected with M. gallisepticum. Analysis of the M. gallisepticum shedding patterns showed a significant effect of vaccination on the shedding levels of the vaccinated in-contact chickens. Moreover, the Cox Proportional Hazard analysis indicated that the rate of M. gallisepticum transmission from challenged to in-contact birds in the vaccinated group was 0.356 times that of the non-vaccinated group. In addition, the overall estimate of R (the average number of secondary cases infected by one typical infectious case) of the vaccinated group (R = 4.3, 95% confidence interval = 1.6 to 49.9) was significantly lower than that of the non-vaccinated group (R = infinity, 95% confidence interval = 9.9 to infinity). However, the overall estimate of R in the vaccinated group still exceeded 1, which indicates that the effect of the vaccination on the horizontal transmission M. gallisepticum is insufficient to stop its spread under these experimental conditions.


Unilateral endolymphatic hydrops and associated abnormalities.
A case of unilateral endolymphatic hydrops is presented in which several significant histopathological findings are observed in the affected inner ear and are absent in the opposite ear. Moderate endolymphatic hydrops is present in all cochlear turns on the involved side. Atrophic changes in the cochlear and vestibular end-organs, partial collapse and infolding of Reissner's and the saccular membranes, and collapse of the posterior canal membrane are also seen. There is also marked narrowing of the proximal rugose portion of the endolymphatic sac, associated with a flattened, epithelial lining, dense fibrotic connective tissue, brown pigment deposition, and poor vascularity in a relatively narrowed and straightened vestibular aqueduct. Fibrosis, loss of vascularity, and brown pigment deposition are also observed in the bony channels surrounding the vestibular aqueduct.


Label-Free Neuropeptide Detection beyond the Debye Length Limit.
Biosensors with high selectivity, high sensitivity, and real-time detection capabilities are of significant interest for diagnostic applications as well as human health and performance monitoring. Graphene field-effect transistor (GFET) based biosensors are suitable for integration into wearable sensor technology and can potentially demonstrate the sensitivity and selectivity necessary for real-time detection and monitoring of biomarkers. Previously reported DC-mode GFET biosensors showed a high sensitivity for sensing biomarkers in solutions with a low salt concentration. However, due to Debye length screening, the sensitivity of the DC-mode GFET biosensors decreases significantly during operation in a physiological fluid such as sweat or interstitial fluid. To overcome the Debye screening length limitation, we report here alternating current (AC) mode heterodyne-based GFET biosensors for sensing neuropeptide-Y (NPY), a key stress biomarker, in artificial sweat at physiologically relevant ionic concentrations. Our AC-mode GFET biosensors show a record ultralow detection limit of 2 × 10-18 M with an extensive dynamic range of 10 orders of magnitude in sensor response to target NPY concentration. The sensors were characterized for various carrier frequencies (ranging from 30 kHz to 2 MHz) of the applied AC voltages and various salt concentrations (10, 50, and 100 mM). Contrary to DC-mode sensing, the AC-mode sensor response increases with an increase in salt concentration in the electrolyte. The sensor response can be further enhanced by tuning the carrier frequency of the applied AC voltage. The optimum response frequency of our sensor is approximately 400-600 kHz for salt concentrations of 50 and 100 mM, respectively. The salt-concentration- and frequency-dependent sensor response can be explained by an electrolyte-gated capacitance model.


An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings.
Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20 and 30%, compared to docking scoring or to standard MM-GBSA rescoring.


Perceptual context effects of speech and nonspeech sounds: the role of auditory categories.
Williams [(1986). "Role of dynamic information in the perception of coarticulated vowels," Ph.D. thesis, University of Connecticut, Standford, CT] demonstrated that nonspeech contexts had no influence on pitch judgments of nonspeech targets, whereas context effects were obtained when instructed to perceive the sounds as speech. On the other hand, Holt et al. [(2000). "Neighboring spectral content influences vowel identification," J. Acoust. Soc. Am. 108, 710-722] showed that nonspeech contexts were sufficient to elicit context effects in speech targets. The current study was to test a hypothesis that could explain the varying effectiveness of nonspeech contexts: Context effects are obtained only when there are well-established perceptual categories for the target stimuli. Experiment 1 examined context effects in speech and nonspeech signals using four series of stimuli: steady-state vowels that perceptually spanned from /inverted ohm/-/I/ in isolation and in the context of /w/ (with no steady-state portion) and two nonspeech sine-wave series that mimicked the acoustics of the speech series. In agreement with previous work context effects were obtained for speech contexts and targets but not for nonspeech analogs. Experiment 2 tested predictions of the hypothesis by testing for nonspeech context effects after the listeners had been trained to categorize the sounds. Following training, context-dependent categorization was obtained for nonspeech stimuli in the training group. These results are presented within a general perceptual-cognitive framework for speech perception research.


Molecular dynamics simulation study of distribution and dynamics of aqueous solutions of uranyl ions: the effect of varying temperature and concentration.
Investigating the characteristics of actinyl ions has been of great interest due to their direct relevance in the nuclear fuel cycle. All-atom molecular dynamics simulations have been employed to study the orientational structure and dynamics of aqueous solutions of uranyl ions of various concentrations. The orientational structure of water around a uranyl ion has been thoroughly investigated by calculating different orientational probability distributions corresponding to different molecular axes of water. The orientational distribution of water molecules in the first coordination shell of a uranyl ion is found to be markedly different from that in bulk water. Analysis of counterion distribution around the uranyl ion reveals the presence of nitrate ions along with water molecules in the first solvation shell. From the comparison of the number of coordinated water and nitrate ions at various uranyl nitrate concentrations, it is evident that these two species compete for occupying the first solvation shell of the uranyl ion. Orientational dynamics of water molecules about different molecular axes of water in the vicinity of uranyl ions have also been investigated and decreasing orientational mobility of water with increasing uranyl concentration has been found. However, it is observed that the orientational dynamics remains more or less the same whether we consider all the water molecules in the aqueous solution or only the solvation shell water molecules. The effect of temperature on the translational and orientational characteristics of the aqueous uranyl solutions has also been studied in detail.


Global Survey, Expressions and Association Analysis of CBLL Genes in Peanut.
Cystathionine γ-synthase (CGS), methionine γ-lyase (MGL), cystathionine β-lyase (CBL) and cystathionine γ-lyase (CGL) share the Cys_Met_Meta_PP domain and play important roles in plant stress response and development. In this study, we defined the genes containing the Cys_Met_Meta_PP domain (PF01053.20) as CBL-like genes (CBLL). Twenty-nine CBLL genes were identified in the peanut genome, including 12 from cultivated peanut and 17 from wild species. These genes were distributed unevenly at the ends of different chromosomes. Evolution, gene structure, and motif analysis revealed that CBLL proteins were composed of five different evolutionary branches. Chromosome distribution pattern and synteny analysis strongly indicated that whole-genome duplication (allopolyploidization) contributed to the expansion of CBLL genes. Comparative genomics analysis showed that there were three common collinear CBLL gene pairs among peanut, Arabidopsis, grape, and soybean, but no collinear CBLL gene pairs between peanut and rice. The prediction results of cis-acting elements showed that AhCBLLs, AdCBLLs, and AiCBLLs contained different proportions of plant growth, abiotic stress, plant hormones, and light response elements. Spatial expression profiles revealed that almost all AhCBLLs had significantly higher expression in pods and seeds. All AhCBLLs could respond to heat stress, and some of them could be rapidly induced by cold, salt, submergence, heat and drought stress. Furthermore, one polymorphic site in AiCBLL7 was identified by association analysis which was closely associated with pod length (PL), pod width (PW), hundred pod weight (HPW) and hundred seed weight (HSW). The results of this study provide a foundation for further research on the function of the CBLL gene family in peanut.


Normal-mode spectrum of finite-sized granular systems: The effects of fluid viscosity at the grain contacts.
We investigate the effects of adsorbed films on the attenuative properties of loose granular media occupying a finite-sized rigid container that is open at the top. We measure the effective mass, M[over ̃](ω), of loose tungsten particles prepared under two different sets of conditions: (i) We lightly coat tungsten grains with a fixed volume fraction of silicone oil (polydimethylsiloxane, PDMS), where the liquid viscosity is varied for individual realizations, and (ii) in the other set of experiments we vary the humidity. On a theoretical level, we are able to decompose the effective mass into a sum over the contributions from each of the normal modes of the granular medium. Our results indicate that increasing either the PDMS viscosity or the humidity, as the case may be, markedly increases the damping rate of each normal mode relevant to our measurements. However, there is appreciable damping even in the absence of any macroscopic film. With a notable exception in the case of the highest humidity in the humidity-controlled experiments, all the relevant modes are weakly damped in the sense of a microscopic theory based on damped contact forces between rigid particles.


Eccrine porocarcinoma (malignant eccrine poroma): a case report.
Eccrine porocarcinoma is a rare malignancy of eccrine sweat gland usually presenting as a long-standing growth on the lower extremity. It is more common in females. It may arise in a pre-existing eccrine poroma. A case presenting as nodular swelling over the dorsum of left hand in a 56-year-old man is described. Cytologic and histologic examination along with flow cytometric analysis is presented.


Increased oxidative stress in dilated cardiomyopathic heart failure.
In the present study, we assessed oxidative stress in patients with dilated cardiomyopathy of ischemic or idiopathic etiology. For this reason we measured whole blood reduced glutathione, erythrocyte superoxide dismutase, susceptibility of erythrocyte membranes and erythrocytes to peroxidation, and SH content of erythrocyte membranes in 12 patients (8 men and 4 women, ages 31 to 66 years) with idiopathic dilated cardiomyopathy, in 11 patients (8 men and 3 women, ages 32 to 65 years) with ischemic dilated cardiomyopathy, and in 21 healthy volunteers (12 men and 9 women, ages 25 to 67 years). There was no statistically significant difference between the two patient groups for the indicators studied (P >0.05). Blood glutathione, erythrocyte superoxide dismutase, and membrane SH content of both groups of patients was decreased compared with controls (P <0.05), whereas erythrocyte and membrane susceptibility to peroxidation were increased (P <0.05). We conclude that patients with idiopathic or ischemic dilated cardiomyopathy exhibit abnormalities of a range of markers of increased oxidative stress. These abnormalities may contribute to contractile dysfunction, increased incidence of fatal arrhythmias, and sudden death.


Influence of the jaw tracking technique on the dose calculation accuracy of small field VMAT plans.
The aim of this study was to evaluate experimentally the accuracy of the dose calculation algorithm AcurosXB in small field highly modulated Volumetric Modulated Arc Therapy (VMAT). The 1000SRS detector array inserted in the rotational Octavius 4D phantom (PTW) was used for 3D dose verification of VMAT treatments characterized by small to very small targets. Clinical treatment plans (n = 28) were recalculated on the phantom CT data set in the Eclipse TPS. All measurements were done on a Varian TrueBeamSTx, which can provide the jaw tracking technique (JTT). The effect of disabling the JTT, thereby fixing the jaws at static field size of 3 × 3 cm2 and applying the MLC to shape the smallest apertures, was investigated for static fields between 0.5 × 0.5-3 × 3 cm2 and for seven VMAT patients with small brain metastases. The dose calculation accuracy has been evaluated by comparing the measured and calculated dose outputs and dose distributions. The dosimetric agreement has been presented by a local gamma evaluation criterion of 2%/2 mm. Regarding the clinical plans, the mean ± SD of the volumetric gamma evaluation scores considering the dose levels for evaluation of 10%, 50%, 80% and 95% are (96.0 ± 6.9)%, (95.2 ± 6.8)%, (86.7 ± 14.8)% and (56.3 ± 42.3)% respectively. For the smallest field VMAT treatments, discrepancies between calculated and measured doses up to 16% are obtained. The difference between the 1000SRS central chamber measurements compared to the calculated dose outputs for static fields 3 × 3, 2 × 2, 1 × 1 and 0.5 × 0.5 cm2 collimated with MLC whereby jaws are fixed at 3 × 3 cm2 and for static fields shaped with the collimator jaws only (MLC retracted), is on average respectively, 0.2%, 0.8%, 6.8%, 5.7% (6 MV) and 0.1%, 1.3%, 11.7%, 21.6% (10 MV). For the seven brain mets patients was found that the smaller the target volumes, the higher the improvement in agreement between measured and calculated doses after disabling the JTT. Fixing the jaws at 3 × 3 cm2 and using the MLC with high positional accuracy to shape the smallest apertures in contrast to the JTT is currently found to be the most accurate treatment technique.


hGSuite HyperBrowser: A web-based toolkit for hierarchical metadata-informed analysis of genomic tracks.
Many high-throughput sequencing datasets can be represented as objects with coordinates along a reference genome. Currently, biological investigations often involve a large number of such datasets, for example representing different cell types or epigenetic factors. Drawing overall conclusions from a large collection of results for individual datasets may be challenging and time-consuming. Meaningful interpretation often requires the results to be aggregated according to metadata that represents biological characteristics of interest. In this light, we here propose the hierarchical Genomic Suite HyperBrowser (hGSuite), an open-source extension to the GSuite HyperBrowser platform, which aims to provide a means for extracting key results from an aggregated collection of high-throughput DNA sequencing data. The hGSuite utilizes a metadata-informed data cube to calculate various statistics across the multiple dimensions of the datasets. With this work, we show that the hGSuite and its associated data cube methodology offers a quick and accessible way for exploratory analysis of large genomic datasets. The web-based toolkit named hGsuite Hyperbrowser is available at https://hyperbrowser.uio.no/hgsuite under a GPLv3 license.


Marginal Accuracy and Internal Fit of Dental Copings Fabricated by Modern Additive and Subtractive Digital Technologies.
The margins of copings for crowns and retainers of fixed partial dentures affect the progress of microleakage and dental caries. Failures occur due to altered fit which is also influenced by the method of fabrication. An in-vitro study was conducted to determine among the cast base metal, copy milled zirconia, computer aided designing computer aided machining/manufacturing zirconia and direct metal laser sintered copings which showed best marginal accuracy and internal fit. Forty extracted maxillary premolars were mounted on an acrylic model and reduced occlusally using a milling machine up to a final tooth height of 4 mm from the cementoenamel junction. Axial reduction was accomplished on a surveyor and a chamfer finish line was given. The impressions and dies were made for fabrication of copings which were luted on the prepared teeth under standardized loading, embedded in self-cure acrylic resin, sectioned and observed using scanning electron microscope for internal gap and marginal accuracy. The copings fabricated using direct metal laser sintering technique exhibited best marginal accuracy and internal fit. Comparison of mean between the four groups by ANOVA and post-hoc Tukey HSD tests showed a statistically significant difference between all the groups (p⟨0.05). It was concluded that the copings fabricated using direct metal laser sintering technique exhibited best marginal accuracy and internal fit. Additive digital technologies such as direct metal laser sintering could be cost-effective for the clinician, minimize failures related to fit and increase longevity of teeth and prostheses.


Accuracy of second order perturbation theory in the polaron and variational polaron frames.
In the study of open quantum systems, the polaron transformation has recently attracted a renewed interest as it offers the possibility to explore the strong system-bath coupling regime. Despite this interest, a clear and unambiguous analysis of the regimes of validity of the polaron transformation is still lacking. Here we provide such a benchmark, comparing second order perturbation theory results in the original untransformed frame, the polaron frame, and the variational extension with numerically exact path integral calculations of the equilibrium reduced density matrix. Equilibrium quantities allow a direct comparison of the three methods without invoking any further approximations as is usually required in deriving master equations. It is found that the second order results in the original frame are accurate for weak system-bath coupling; the results deteriorate when the bath cut-off frequency decreases. The full polaron results are accurate for the entire range of coupling for a fast bath but only in the strong coupling regime for a slow bath. The variational method is capable of interpolating between these two methods and is valid over a much broader range of parameters.


[Factors associated with cross-nursing].
This article aims to estimate the prevalence and analyze the factors associated with cross-nursing. A cross-sectional study was conducted in 2013 with interviews with a representative sample of mothers of infants less than one-year-old (n' = 695) attended in nine primary health units in Rio de Janeiro, Brazil. Sociodemographic characteristics were studied; pregnancy, childbirth and primary care assistance; maternal habits and baby features. Adjusted prevalence ratios (PR) were obtained by Poisson Regression, retaining variables associated with the outcome in the final model (p ≤ 0.05). Cross-nursing was practiced by 29.4% of the mothers. Most practitioner mothers were relatives or friends. The following variables were directly associated with cross-nursing: being an adolescent mother (PR' = 1.595), smoking (PR' = 1.396), alcohol consumption (PR' = 1.613), inappropriate baby feeding habits (PR' = 1.371) and infant's age in months (PR' = 1.066). Maternal formal employment was inversely associated with the practice (PR' = 0.579). Cross-nursing has a relevant prevalence among mothers assisted by primary health care units in Rio de Janeiro City. This issue should be addressed, especially among the most vulnerable groups, due to the association with adolescence and with unhealthy habits.


Tentative Characterization of Polyphenolic Compounds in the Male Flowers of Phoenix dactylifera by Liquid Chromatography Coupled with Mass Spectrometry and DFT.
Phoenix dacylifera is an ancient palm species rich in (poly)phenols. These phenolic compounds were tentatively identified by using liquid chromatography coupled with ion spray mass spectrometry in tandem mode (LC/MS/MS) with negative ion detection. Negative identification of the compounds was based on their retention times and mass spectra in full scan mode (MS), and in different MS/MS modes. For the first time, complete hypothesis, and routs for both p-coumaroylshikimic acids (CoSA) and caffeoylshikimic acids (CSA) were suggested and confirmed by Density Fonctional Theory (DFT) study. Notably, of the 53 compounds characterized, 19 hydroxycinnamates derivatives were tentativelycharacterized in male flowers of date palm and 15 of them were recorded for the first time. In addition, five organic acids, six B-type proanthocyanidins, two anthocyanidin and 21 flavonoid derivatives have been tentatively characterized. Identification of B-type proanthocyanidins were based on the diagnostic ions resulting from heterocyclic ring fission (HRF) and retro-Diels-Alder (RDA) reaction of flavan-3-ol provided information on the hydroxylation pattern and the type of inter-flavan bond proanthocyanidins. The sequence of proanthocyanidins was detected through ions extracted from quinone methide (QM) cleavage of the inter-flavan bond.


What fluids are given during air ambulance treatment of patients with trauma in the UK, and what might this mean for the future? Results from the RESCUER observational cohort study.
We investigated how often intravenous fluids have been delivered during physician-led prehospital treatment of patients with hypotensive trauma in the UK and which fluids were given. These data were used to estimate the potential national requirement for prehospital blood products (PHBP) if evidence from ongoing trials were to report clinical superiority. The Regional Exploration of Standard Care during Evacuation Resuscitation (RESCUER) retrospective observational study was a collaboration between 11 UK air ambulance services. Each was invited to provide up to 5 years of data and total number of taskings during the same period. Patients with hypotensive trauma (systolic blood pressure <90 mm Hg or absent radial pulse) attended by a doctor. The primary outcome was the number of patients with hypotensive trauma given prehospital fluids. Secondary outcomes were types and volumes of fluids. These data were combined with published data to estimate potential national eligibility for PHBP. Of 29 037 taskings, 729 (2.5%) were for patients with hypotensive trauma attended by a physician. Half were aged 21-50 years; 73.4% were male. A total of 537 out of 729 (73.7%) were given fluids. Five hundred and ten patients were given a single type of fluid; 27 received >1 type. The most common fluid was 0.9% saline, given to 486/537 (90.5%) of patients who received fluids, at a median volume of 750 (IQR 300-1500) mL. Three per cent of patients received PHBP. Estimated projections for patients eligible for PHBP at these 11 services and in the whole UK were 313 and 794 patients per year, respectively. One in 40 air ambulance taskings were manned by physicians to retrievepatients with hypotensive trauma. The most common fluid delivered was 0.9% saline. If evidence justifies universal provision of PHBP, approximately 800 patients/year would be eligible in the UK, based on our data combined with others published. Prospective investigations are required to confirm or adjust these estimations.


Small GTPase determinants for the Golgi processing and plasmalemmal expression of human ether-a-go-go related (hERG) K+ channels.
The pro-arrhythmic Long QT syndrome (LQT) is linked to 10 different genes (LQT1-10). Approximately 40% of genotype-positive LQT patients have LQT2, which is characterized by mutations in the human ether-a-go-go related gene (hERG). hERG encodes the voltage-gated K(+) channel alpha-subunits that form the pore of the rapidly activating delayed rectifier K(+) current in the heart. The purpose of this study was to elucidate the mechanisms that regulate the intracellular transport or trafficking of hERG, because trafficking is impaired for about 90% of LQT2 missense mutations. Protein trafficking is regulated by small GTPases. To identify the small GTPases that are critical for hERG trafficking, we coexpressed hERG and dominant negative (DN) GTPase mutations in HEK293 cells. The GTPases Sar1 and ARF1 regulate the endoplasmic reticulum (ER) export of proteins in COPII and COPI vesicles, respectively. Expression of DN Sar1 inhibited the Golgi processing of hERG, decreased hERG current (I(hERG)) by 85% (n > or = 8 cells per group, *, p < 0.01), and reduced the plasmalemmal staining of hERG. The coexpression of DN ARF1 had relatively small effects on hERG trafficking. Surprisingly, the coexpression of DN Rab11B, which regulates the endosomal recycling, inhibited the Golgi processing of hERG, decreased I(hERG) by 79% (n > or = 8 cells per group; *, p < 0.01), and reduced the plasmalemmal staining of hERG. These data suggest that hERG undergoes ER export in COPII vesicles and endosomal recycling prior to being processed in the Golgi. We conclude that hERG trafficking involves a pathway between the ER and endosomal compartments that influences expression in the plasmalemma.


First Report of Phyllosticta capitalensis Causing Black Spot on Radermachera hainanensis Merr. in China.
Radermachera hainanensis Merr. plants are native in south-central and southeast of China. Plants produce large flowers, and are widely cultivated in China as ornamentals. In April 2020, R. hainanensis Merr. plants grown in Cixi Lvpin Garden (30°26'54″N, 121°25'48″E), Zhejiang Province, were found to have many black circular necrotic lesions. In the early infection stage, the lesions appeared in lower leaves as small black circular spots which developed later into large spots (11 to 38 mm diameter) with grey centers and chlorotic edges. Ultimately, the spots spread and merged. Moreover, infected leaves showed premature leaf fall. Disease intensity reached approximately 20% of plants in the affected field (0.5 ha). After effective chemical control, this disease did not spread to other healthy plants in the same garden. To identify the causative pathogen associated with the disease, ten symptomatic leaves were collected from ten different plants. Leaf tissues were cut from the lesion margins and sterilized as follows: surface sterilized with 75% ethanol for 30 seconds and washed three times in sterile distilled water. The leaf tissues were then dipped into 10% sodium hypochlorite for 3-4 minutes, then washed three times in distilled water and dried on a sterile filter paper. After drying, the surface-sterilized leaf discs were cut to small pieces (3×3 mm) and transferred to potato dextrose agar (PDA) plates and incubated at 28°C for 2 to 3 days under 12 h photoperiod. A total of 15 isolates were obtained from the affected leaves, and all the isolates displayed the same colony characteristics. Then, three single-spore isolates were randomly selected (F2, F5 and F8) for further study. The fungal colonies were dark green with a granular surface, and irregular white edges, later turning black. Conidia were one-celled, oval, and narrow at the end with a single apical end, measuring from 7.8 to 11.1 × 4.6 to 5.9 μm (av. 9.5 × 5.2 μm, n=50). These morphological characteristics were consistent with the description of Phyllosticta capitalensis (Wikee et al. 2013; Guarnaccia et al. 2017). The identity of three representative isolates were confirmed by a multilocus approach. The DNA of three isolates were extracted and partial sequences of ribosomal internal transcribed spacer (ITS), actin (ACT), and translation elongation factor 1-alpha (TEF1-α) were amplified and sequenced as previously described (White et al. 1990; O'Donnell et al. 1998; Carbone & Kohn et al. 1999). The three selected isolates shared 100% identical sequence of ITS, ACT and TEF1-α. Then representative isolate F8 was selected for further study. BLAST analysis in GenBank showed that the obtained sequence of ITS (MZ317550) had 99% identity to P. elongata isolate eSX25240811. Other two sequences of ACT (MZ326837) and TEF1-α(MZ326839) showed 99% and 98% identity to P. capitalensis isolate YLWB01, respectively. The phylogenetic trees were constructed by Bootstrap method with 1000 replications using Maximum Likelihood model implemented in the MEGA 7. Results showed that the isolate F8 clustered with P. capitalensis with 100% bootstrap support. Pathogenicity of strain F8 was tested by Koch's postulates. A pathogenicity test was performed in a greenhouse with 80% relative humidity at 28°C. 20 healthy plants were sprayed with a 1×106 conidia ml-1 suspension (three leaves from each individual plants) and another 20 healthy plants were sprayed with sterile distilled water (three leaves from each individual plant) as control. Conidia was obtained from PDA plates after 7 days of incubation in the biochemical incubator at 28°C and concentration was counted in hemacytometer. After 15 days, disease symptoms were observed on all inoculated leaves, whereas the control plants remained asymptomatic. After that, P. capitalensis was re-isolated only from the infected leaves and identified by morphological and sequence analyses. Early identification of P. capitalensis as a causal agent for black spot is crucial to employ effective disease management strategies to control disease in the field. P. capitalensis has been reported on many crops in China (Cheng et al. 2019; Tang et al. 2020; Liao et al. 2020). However, to our knowledge, this is the first report of black spot disease caused by P. capitalensis on Radermachera hainanensis Merr. in China.


Age-related differences on a new test of temporal order memory for everyday events.
We developed a new test to examine incidental temporal order memory for a self-generated sequence of tasks one might complete in everyday life. Young and older adults were given 10 cards, each listing a task one might accomplish in a typical day. Participants were asked to self-generate a "to do" list by placing the 10 cards in a sequence representing the order in which they would accomplish the tasks, but were not informed of a subsequent memory test. We assessed immediate free recall, delayed free recall, and delayed cued recall for the order of the tasks in the sequence. Older adults were significantly impaired relative to young adults on immediate free recall, delayed free recall, and delayed cued recall. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity for our test, which is portable and can be rapidly administered in clinical or laboratory settings.


Combination of zymography and immunodetection to analyze proteins in complex culture supernatants.
The physiological function of an allergen might be an important factor for the allergenicity. The major grass pollen allergen Phl p 1 shows sequence similarities to the consensus sequences of cysteine proteases. However, up to now, the proteolytic activity of Phl p 1 is controversial. The culture supernatant of Phl p 1-transfected clones from Pichia pastoris showed a proteolytic activity but this might be due to Phl p 1 or irrelevant yeast contaminants. To solve this question, we made use of the zymogram technique and improved it. Substrate as well as substrate concentration was changed from 1% casein to 0.25% skimmed milk powder. For staining, we used a colloidal Coomassie stain (RotiBlue) with a higher sensitivity and better practicability than the conventional Coomassie staining. The proteins in the zymogels and in the SDS-PAGE gels showed similar electrophoretic mobility. Furthermore, the zymogels could be blotted and immunostained. Thus, the molecular mass of the proteolytic bands could be determined and directly compared with immunoblotting results. To clearly assign the protease, we separated the culture supernatant of the Phl p 1-transfected P. pastoris clone by affinity chromatography with monoclonal antibody. Our studies demonstrate that the proteolytic activity did not belong to the recombinant allergen but to the yeast proteins. The enzyme was classified by zymogram inhibition tests as a strong serine protease.


New universality class for the fragmentation of plastic materials.
We present an experimental and theoretical study of the fragmentation of polymeric materials by impacting polypropylene particles of spherical shape against a hard wall. Experiments reveal a power law mass distribution of fragments with an exponent close to 1.2, which is significantly different from the known exponents of three-dimensional bulk materials. A 3D discrete element model is introduced which reproduces both the large permanent deformation of the polymer during impact and the novel value of the mass distribution exponent. We demonstrate that the dominance of shear in the crack formation and the plastic response of the material are the key features which give rise to the emergence of the novel universality class of fragmentation phenomena.


Stingray spear injury to the pediatric spinal cord: case report and review of the literature.
Stingray injuries are rare, mostly causing injuries to the lower extremities but occasionally fatal if there is direct puncture of the thorax, abdomen, or neck. Direct combined stingray injury to the central nervous system has not been reported in the literature. Herein we present the case of a 12-year-old boy who, while wading at the seashore of the Costa Rica's Pacific Ocean, sustained a combined oblique penetrating injury to the C6 vertebra caused by a Stingray. He initially presented to the hospital with a complete asymmetric right C6/left T1 ASIA A examination, priapism, and loss of anal sphincter tone. Imaging revealed fracture of the posterior elements of C6 with an oblique trajectory into the left radicular foramen. T2W images did not reveal anatomical section but rather edema and minor bleeding in the epidural space. The patient underwent medical management and serial imaging. During the next 3 months, there was recovery of sensation on the right hemi body, bilateral paresthesias and asymmetric progressive improvement in strength on both legs. Acute care management and midterm term follow up are provided, along with a review of the literature for salient management considerations when evaluating and treating combined penetrating and envenomation injuries caused by stingrays. To our knowledge, this is the first report of such injury to the spine.


Social rank-dependent expression of arginine vasotocin in distinct preoptic regions in male Oryzias latipes.
This study examined arginine vasotocin (AVT) expression in the brains of dominant and subordinate male medaka Oryzias latipes after short- and long-term competition. High AVT expression in distinct preoptic regions was found in dominants and subordinates within minutes of encountering each other. During long-term competition, AVT expression remained high in dominants but not in subordinates.


Epidemiologic Modeling of HIV/AIDS: Use of Computational Models to Study the Population Dynamics of the Disease to Assess Effective Intervention Strategies for Decision-making.
Computational models and simulations are becoming central research tools in epidemiology, biology, and other fields. Epidemiologic research involves the study of a complex set of host, environment and causative agent factors as these interact to impact health and diseases in any population. The most advanced of these efforts have focused on micro (cellular) or macro (human) population levels. The dynamic interplay of HIV with a focus in its hosts at the cellular level provides the micro-epidemiologic basis, while the dynamic interplay of multifactorial determinants: biomedical, behavioral, and socioeconomic factors provide the macro-epidemiologic basis at the human population level. We have developed the computational tools and mathematical approaches to study the population-level effects of various drugs on HIV to integrate models from micro to macro- levels in a seamless fashion. The critical variables that facilitate transmission of HIV and intracellular interactions and molecular kinetics were considered. Such multilevel models are essential if we are to develop quantitative, predictive models of complex biological systems such as HIV/AIDS.


Enhanced solubilization and intestinal absorption of cholesterol by oxidized linoleic acid.
Solubilization of cholesterol in the intestinal lumen by bile acids and the subsequent formation of mixed micelles is an important step in the absorption of cholesterol. We propose that oxidized fatty acids (ox-FA) may mimic bile acids and form mixed micelles with cholesterol much more efficiently, as compared with unoxidized fatty acids, thereby increasing there absorption. In an in vitro assay at concentrations of 1, 5, and 10 mM, oxidized linoleic acid (ox-18:2) increased the solubilization of cholesterol (3.06, 8.16, and 15.46 nmol/ml) in a dose dependent manner compared with a 10 mM unoxidized linoleic acid (unox-18:2 at 0.97 nmol/ml). The uptake of cholesterol solubilized in the presence of ox-18:2 by Caco-2 cells and everted rat intestinal sacs was greater (1.78 and 1.95 nmol/ml respectively) as compared with the cholesterol solubilized in the presence of unox-18:2 (0.29 and 0.61 nmol/ml; P = 0.05). In addition, when LDL receptor deficient mice were fed a high fat diet along with ox-18:2 their plasma cholesterol levels were greater than animals fed the high fat diet alone (1290 mg/dl vs. 1549 mg/dl, P = 0.013). From these results, we suggest that ox-FA, by enhancing the solubilization of luminal cholesterol, increases the uptake of cholesterol that might lead to hypercholesterolemia and atherosclerosis.


Trends in vaping and smoking behavior before and during the COVID-19 pandemic in Canada: Beneficial and potentially detrimental changes.
E-cigarette and cigarette use may have changed during the COVID-19 pandemic, however, there is no consensus in existing literature, and current Canadian studies have not used representative samples. Thus, there is a need for robust national estimates. The primary objective was to describe the 30-day period prevalence of smoking and vaping before and during the COVID-19 pandemic in Canada. This study analyzed three years of the cross-sectional Canadian Tobacco and Nicotine Survey: 2019 (pre-pandemic), 2020 (9 months into the pandemic) and 2021 (21 months into pandemic). Thirty-day period prevalence of vaping over the 2019, 2020, and 2021 study periods were 4.8 (95%CI: 4.2-5.3), 4.6% (95%CI: 4.1-5.2), and 5.2% (95%CI: 4.7-5.7), respectively. The 30-day period prevalence of smoking over the 2019, 2020, and 2021 study periods were 11.9% (95%CI: 10.9-12.7), 10.3% (95%CI: 9.4-11.2), and 10.3% (95%CI: 9.4-11.1), respectively. Notably, estimates of smoking for females decreased considerably from 2019 (11.0%; 95%CI: 9.9--12.2%) to 2020 (8.6%; 95%CI: 7.5-9.7). Estimates of vaping in those aged 20-24 increased substantially from 2020 (13.0%; 95%CI: 10.9-15.1) to 2021 (17.2%; 95%CI: 15.4-18.9). Changes to smoking and vaping were restricted to subsets within the population. In those aged 20-24, there was a modest increase in vaping from 2020 to 2021. In females, there was a decrease in smoking from 2019 to 2020, which persisted in 2021.


Reclassification of Thiobacillus aquaesulis (Wood & Kelly, 1995) as Annwoodia aquaesulis gen. nov., comb. nov., transfer of Thiobacillus (Beijerinck, 1904) from the Hydrogenophilales to the Nitrosomonadales, proposal of Hydrogenophilalia class. nov. within the 'Proteobacteria', and four new families within the orders Nitrosomonadales and Rhodocyclales.
The genus Thiobacillus comprises four species with validly published names, of which Thiobacillus aquaesulis DSM 4255T (=ATCC 43788T) is the only species that can grow heterotrophically or mixotrophically - the rest being obligate autotrophs - and has a significant metabolic difference in not producing tetrathionate during the oxidation of thiosulfate during autotrophic growth. On the basis of this and differential chemotaxonomic properties and a 16S rRNA gene sequence similarity of 93.4 % to the type species Thiobacillus thioparus DSM 505T, we propose that it is moved to a novel genus, Annwoodia gen. nov., for which the type species is Annwoodia aquaesulis gen. nov., comb. nov. We confirm that the position of the genus Thiobacillus in the Betaproteobacteria falls within the Nitrosomonadales rather than the Hydrogenophilales as previously proposed. Within the Nitrosomonadales we propose the circumscription of genera to form the Thiobacilliaceae fam. nov. and the Sterolibacteriaceae fam. nov. We propose the merging of the family Methylophilaceae into the Nitrosomonadales, and that the Sulfuricellaceae be merged into the Gallionellaceae, leaving the orders Methylophilales and Sulfuricellales defunct. In the Rhodocyclales we propose the Azonexaceae fam. nov. and the Zoogloeaceae fam. nov. We also reject the Hydrogenophilales from the Betaproteobacteria on the basis of a very low 16S rRNA gene sequence similarity with the class-proper as well as physiological properties, forming the Hydrogenophilalia class. nov. in the 'Proteobacteria'. We provide emended descriptions of Thiobacillus, Hydrogenophilales, Hydrogenophilaceae, Nitrosomonadales, Gallionellaceae, Rhodocyclaceae and the Betaproteobacteria.


Promoter Escape by Escherichia coli RNA Polymerase.
Promoter escape is the process that an initiated RNA polymerase (RNAP) molecule undergoes to achieve the initiation-elongation transition. Having made this transition, an RNAP molecule would be relinquished from its promoter hold to perform productive (full-length) transcription. Prior to the transition, this process is accompanied by abortive RNA formation-the amount and pattern of which is controlled by the promoter sequence information. Qualitative and quantitative analysis of abortive/productive transcription from several Escherichia coli promoters and their sequence variants led to the understanding that a strong (RNAP-binding) promoter is more likely to be rate limited (during transcription initiation) at the escape step and produce abortive transcripts. Of the two subelements in a promoter, the PRR (the core Promoter Recognition Region) was found to set the initiation frequency and the rate-limiting step, while the ITS (the Initial Transcribed Sequence region) modulated the ratio of abortive versus productive transcription. The highly abortive behavior of E. coli RNAP could be ameliorated by the presence of Gre (transcript cleavage stimulatory) factor(s), linking the first step in abortive RNA formation by the initial transcribing complexes (ITC) to RNAP backtracking. The discovery that translocation during the initiation stage occurs via DNA scrunching provided the source of energy that converts each ITC into a highly unstable "stressed intermediate." Mapping all of the biochemical information onto an X-ray crystallographic structural model of an open complex gave rise to a plausible mechanism of transcription initiation. The chapter concludes with contemplations of the kinetics and thermodynamics of abortive initiation-promoter escape.


Electronically tuned chiral ruthenium porphyrins: extremely stable and selective catalysts for asymmetric epoxidation and cyclopropanation.
We report the use of three enantiomerically pure and electronically tuned ruthenium carbonyl porphyrin catalysts for the asymmetric cyclopropanation and epoxidation of a variety of olefinic substrates. The D(4)-symmetric ligands carry a methoxy, a methyl or a trifluoromethyl group at the 10-position of each of the 9-[anti-(1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene)]-substituents at the meso-positions of the porphyrin. Introduction of a CF(3)-substituent in this remote position resulted in greatly improved catalyst stability, and turnover numbers of up to 7500 were achieved for cyclopropanation, and up to 14,200 for epoxidation, with ee values typically >90 % and approximately equal to 80 %, respectively. In one example, the axial CO ligand at the ruthenium was exchanged for PF(3), resulting in the first chiral ruthenium porphyrin with a PF(3) ligand reported to date. In cyclopropanations with ethyl diazoacetate, the latter catalyst performed exceedingly well, and gave a 95 % ee in the case of 1,1-diphenylethylene as substrate.


Perception of illusory surfaces and contours in goldfish.
Goldfish (Carassius auratus) were trained to discriminate triangles and squares using a two choice procedure. In the first experiment, three goldfish were trained with food reward on a black outline triangle on a white background, while a black outline square was shown for comparison. In transfer tests, a Kanizsa triangle and a Kanizsa square were presented, perceived by humans as an illusory triangle- or square-shaped surface of slightly higher brightness than the background. The choice behavior in this situation indicates that goldfish are able to discriminate between both figures in almost the same way as in the training situation. In control experiments goldfish did not discriminate between shapes in which humans do not perceive the illusion. A series of generalization experiments was performed indicating the similarity between the tested shapes and the training triangle. From all these findings we conclude that goldfish are able to perceive an illusory triangle or square within the Kanizsa figures. In a second experiment, four goldfish were trained on a white outline triangle versus a white outline square, both on black background with white diagonal lines. In transfer tests in which the shapes were replaced by gaps within the white diagonal lines, goldfish were clearly able to discriminate between the two patterns based on the illusory contours. This was not the case in transfer tests with phase shifted abutting lines.


Elevated Complement C3 and C4 Levels are Associated with Postnatal Pregnancy-Related Venous Thrombosis.
High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case-control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1-3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2-3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8-5.0), and for high C4 of 2.6 (95% CI, 1.5-4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.


Potential relationship between Helicobacter pylori and ischemic heart disease: any pathogenic model?
Helicobacter pylori (H.pylori), causal agent of several gastroduodenal diseases, has been involved in diverse aspects of many extragastric manifestations, including ischemic heart disease (IHD). The present paper focuses on the potential pathogenic mechanisms relating H. pylori to IHD. Since H. pylori DNA has been detected in the coronary arteries only in sporadic occasions, and considering that long-term inflammation might raise cytokine levels in the bloodstream, an indirect pathway is more plausible. Moreover, the evidence that some strains of H. pylori induce platelet aggregation supports a role in the acute phase of IHD. In conclusion, because IHD is a multifactorial disease, it is evident that H. pylori is not the only cause. Thus, the definition of H. pylori or other infectious agents as culprits requires a multidisciplinary approach.


Identification of Betulinic Acid Derivatives as Potent TGR5 Agonists with Antidiabetic Effects via Humanized TGR5H88Y Mutant Mice.
Takeda G protein-coupled receptor 5 (TGR5) is a promising target for treating metabolic syndrome and inflammatory diseases. Herein, we identified a new series of betulinic acid derivatives as potent TGR5 agonists, which show remarkable activity on human (h) and canine (c) TGR5 but exhibit unpromising activity on murine (m) TGR5. Species difference was also observed with many other reported TGR5 agonists. Therefore, we screened 29 amino acids which were conserved in hTGR5 and cTGR5 but different in mTGR5 and found a key amino acid, H88 in mTGR5 (Y89 in hTGR5), which contributed to the species difference. With the CRISPR/Cas9 system, the mTGR5H88Y mutation was introduced into mice, and the optimized compound 11d-Na displayed a significant glucose-lowering effect and stimulated GLP-1 and insulin secretion in TGR5H88Y mice but not in wild-type animals. Taken together, our study provides a useful tool to bridge the gap of species difference and discovers a potent TGR5 agonist for further investigation.


The sensitive and selective adsorption of aromatic compounds with highly crosslinked polymer nanoparticles.
This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar organic pollutants by means of solid-phase microextraction (SPME). Owing to its high hydrophobicity, diverse pore size distribution and highly conjugated structure, a 10 μm HCP coating exhibited excellent adsorption abilities towards benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP-nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five PAHs in environmental water samples and satisfactory recoveries were achieved. The findings could provide a new benchmark for the exploitation of superb HCPs as effective adsorbents for SPME or other adsorption applications.


Public health insurance, frailty, and lack of home support predict rehab discharge following elective anterior cervical discectomy and fusion.
Anterior cervical discectomy and fusion (ACDF) is a commonly-performed and generally well-tolerated procedure used to treat cervical disc herniation. Rarely, patients require discharge to inpatient rehab, leading to inconvenience for the patient and increased healthcare expenditure for the medical system. The objective of this study was to create an accurate and practical predictive model for, as well as delineate associated factors with, rehab discharge following elective ACDF. This was a retrospective, single-center, cohort study. Patients who underwent ACDF between 2012 and 2022 were included. Those with confounding diagnoses or who underwent concurrent, staged, or nonelective procedures were excluded. Primary outcomes for this study included measurements of accuracy for predicting rehab discharge. Secondary outcomes included associations of variables with rehab discharge. Current Procedural Terminology codes identified patients. Charts were reviewed to obtain additional demographic and clinical characteristics on which an initial univariate analysis was performed. Two logistic regression and two machine learning models were trained and evaluated on the data using cross-validation. A multimodel logistic regression was implemented to analyze independent variable associations with rehab discharge. A total of 466 patients were included in the study. The logistic regression model with minimum corrected Akaike information criterion score performed best overall, with the highest values for area under the receiver operating characteristic curve (0.83), Youden's J statistic (0.71), balanced accuracy (85.7%), sensitivity (90.3%), and positive predictive value (38.5%). Rehab discharge was associated with a modified frailty index of 2 (p=.007), lack of home support (p=.002), and having Medicare or Medicaid insurance (p=.007) after correction for multiple hypotheses. Nonmedical social determinants of health, such as having public insurance or a lack of support at home, may play a role in rehab discharge following elective ACDF. In combination with the modified frailty index and other variables, these factors can be used to predict rehab discharge with high accuracy, improving the patient experience and reducing healthcare costs.


Nutritionally deficient Streptococcus: investigation of the hidden culprit in culture-negative endocarditis.
Subacute bacterial endocarditis in a 72-year-old woman was found to be caused by nutritionally deficient ("satelliting") Streptococcus sanguis. The organism, which required pyridoxal compounds or thiol substitutes, was identified after the application of relatively unusual but simple laboratory procedures. Normally, the organism's nutritional requirements would be fulfilled by components of the human blood that are used to inoculate clinical blood cultures, provided that the dilutional effect of the media is less than 10. The difficulty of diagnosis in such cases appears to lie in the laboratory inability to identify the organisms, rather than in failure to grow in properly obtained blood cultures.


Analysis of multilocus zygotic associations.
While nonrandom associations between zygotes at different loci (zygotic associations) frequently occur in Hardy-Weinberg disequilibrium populations, statistical analysis of such associations has received little attention. In this article, we describe the joint distributions of zygotes at multiple loci, which are completely characterized by heterozygosities at individual loci and various multilocus zygotic associations. These zygotic associations are defined in the same fashion as the usual multilocus linkage (gametic) disequilibria on the basis of gametic and allelic frequencies. The estimation and test procedures are described with details being given for three loci. The sampling properties of the estimates are examined through Monte Carlo simulation. The estimates of three-locus associations are not free of bias due to the presence of two-locus associations and vice versa. The power of detecting the zygotic associations is small unless different loci are strongly associated and/or sample sizes are large (>100). The analysis of zygotic associations not only offers an effective means of packaging numerous genic disequilibria required for a complete characterization of multilocus structure, but also provides opportunities for making inference about evolutionary and demographic processes through a comparative assessment of zygotic association vs. gametic disequilibrium for the same set of loci in nonequilibrium populations.