Updating the Debate on Behavioral Competency Development: State of the Art and Future Challenges.
Emotional, social, and cognitive intelligence competencies have been recognized as the most critical capabilities for organizations to acquire at all levels. For this reason, a wide body of research since the 1980s has demonstrated their positive impact on individual performance, career success, and wellbeing across sectors and professional roles, and a large number of theoretical contributions on how these competencies can be effectively developed has emerged over time. We focus attention on the developmental and learning processes of emotional, social, and cognitive intelligence competencies that occur after formal training or educational courses provided by universities or certified organizations and directed to students or practitioners. Specifically, we conduct an exploratory literature review on the existing academic studies in order to identify the scholars and the pieces of research contributing most to the debate under investigation. This article aims at analyzing this body of research through a systematic review of the literature in order to: (i) provide a comprehensive critical analysis of the distinctive features of the theoretical and methodological frameworks adopted to develop these competencies; (ii) review the contexts in which the training initiatives analyzed by the literature have been delivered and the categories of learner involved; (iii) discuss the learning outcomes of these educational programs and how they have been assessed; (iv) identify gaps and inconsistencies in the current state of the literature, suggesting promising paths for future research; and (v) stimulate insights for educators, human resource managers, executives, and policymakers by organizing and critically analyzing the extant contributions on competency development. This review represents the first attempt to systematize the methodologies of the educational programs for competency development and to assess their effectiveness in order to assist educators and executives in their ongoing efforts to equip students and employees with the relevant skills needed to achieve superior performance in the workplace. At the institutional level, policymakers should promote a dedicated agenda with concrete actions to equip people with emotional and social intelligence competencies.


The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection.
For individuals with human immunodeficiency virus (HIV) infection to fully benefit from potent combination antiretroviral therapy, they need to know that they are HIV infected, be engaged in regular HIV care, and receive and adhere to effective antiretroviral therapy. Test-and-treat strategies for HIV prevention posit that expanded testing and earlier treatment of HIV infection could markedly decrease ongoing HIV transmission, stemming the HIV epidemic. However, poor engagement in care for HIV-infected individuals will substantially limit the effectiveness of test-and-treat strategies. We review the spectrum of engagement in care for HIV-infected individuals in the United States and apply this information to help understand the magnitude of the challenges that poor engagement in care will pose to test-and-treat strategies for HIV prevention.


Incidence and Management of Infusion Reactions to Infliximab in a Prospective Real-world Community Registry.
Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-α indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions. RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions. There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p < 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007). This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with their use.


Recurrent, nodular lesions over the vulva: A diagnostic challenge.
Angiokeratomas are benign tumors characterized by proliferation and dilatation of blood vessels in the upper dermis. They are divided into widespread and localized forms. The localized forms are further classified as angiokeratoma of Fordyce, angiokeratoma circumscriptum neviforme, circumscribed angiokeratoma, and angiokeratoma of Mibelli, of which angiokeratoma of Fordyce is the most common. A 38-year-old female, with no systemic comorbidities presented with recurrent, asymptomatic dark, raised lesions over the vulva for 15 years, progressively increasing in size and number. There were no similar complaints in the family or spouse. On examination, multiple pedunculated hyperpigmented papules and nodular lesions with a verrucous surface were present over the bilateral labia majora and pubic area. Per speculum examination revealed no abnormalities. The oral, conjunctival, and genital mucosae were normal. There were no similar lesions elsewhere over the body. Histopathological examination revealed marked dilatation of papillary dermal vessels forming large, blood-filled cavernous channels, suggestive of angiokeratoma. The lesions were removed using radiofrequency. We present this case due to the rarity of its occurrence and to emphasize the importance of ruling out nonvenereal causes of genital lesions.


Electrowetting-based microfluidics for analysis of peptides and proteins by matrix-assisted laser desorption/ionization mass spectrometry.
A new technique for preparing samples for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is reported. The technique relies on electrowetting-on-dielectric (EWOD) to move droplets containing proteins or peptides and matrix to specific locations on an array of electrodes for analysis. Standard MALDI-MS reagents, analytes, concentrations, and recipes are demonstrated to be compatible with the technique. Mass spectra are comparable to those collected by conventional methods. Nonspecific adsorption of analytes to device surfaces is demonstrated to be negligible. The results suggest that EWOD may be a useful tool for automating sample preparation for high-throughput proteomics and other applications of MALDI-MS.


Subunit interactions and organization of the Chlamydomonas reinhardtii intraflagellar transport complex A proteins.
Chlamydomonas reinhardtii intraflagellar transport (IFT) particles can be biochemically resolved into two smaller assemblies, complexes A and B, that contain up to six and 15 protein subunits, respectively. We provide here the proteomic and immunological analyses that verify the identity of all six Chlamydomonas A proteins. Using sucrose density gradient centrifugation and antibody pulldowns, we show that all six A subunits are associated in a 16 S complex in both the cell bodies and flagella. A significant fraction of the cell body IFT43, however, exhibits a much slower sedimentation of ∼2 S and is not associated with the IFT A complex. To identify interactions between the six A proteins, we combined exhaustive yeast-based two-hybrid analysis, heterologous recombinant protein expression in Escherichia coli, and analysis of the newly identified complex A mutants, ift121 and ift122. We show that IFT121 and IFT43 interact directly and provide evidence for additional interactions between IFT121 and IFT139, IFT121 and IFT122, IFT140 and IFT122, and IFT140 and IFT144. The mutant analysis further allows us to propose that a subset of complex A proteins, IFT144/140/122, can form a stable 12 S subcomplex that we refer to as the IFT A core. Based on these results, we propose a model for the spatial arrangement of the six IFT A components.


Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults.
Recent evidence suggests a significant overlap in biological changes between major depression and aging across the lifespan. We aim to evaluate the impact of a major depressive episode on the Senescence-Associated Secretory Phenotype (SASP) index, a dynamic secretory molecular pattern indicative of cellular senescence. We also tested the potential moderators of the association between major depression and the SASP index. We included 1165 young and middle-aged adults (527 with a current major depressive episode (cMDE) and 638 with no lifetime history of depression) from a community-based cohort from the Netherlands. We calculated the SASP index based on a previously developed composite index involving 19 biomarkers. cMDE had higher SASP index values (t(1163) = 2.93, p = 0.003) compared to controls in the univariate analysis. After controlling for sociodemographic and somatic health covariates, there was no significant association between cMDE and SASP index (F(1,1158) = 1.09, p = 0.29). Those with the most severe depressive episodes had significantly higher SASP indices compared to those with mild-to-moderate cMDE and controls (F(2,1162) = 6.73, p = 0.001). We found a significant interaction between cMDE and overweight (F(1,1164) = 5.1, p = 0.028): those with comorbid cMDE and overweight had the highest SASP index. Our study demonstrated a complex interaction between cMDE and medical morbidity, especially overweight, on the SASP index, suggesting that their coexistence aggravate age-related biological processes. Moreover, higher SASP index can be a biomarker for more severe depressive episodes.


Building a model using bayesian network for assessment of posterior probabilities of falling from height at workplaces.
Falls from height are one of the main causes of fatal occupational injuries. The objective of this study was to present a model for estimating occurrence probability of falling from height. In order to make a list of factors affecting falls, we used four expert group's judgment, literature review and an available database. Then the validity and reliability of designed questionnaire were determined and Bayesian networks were built. The built network, nodes and curves were quantified. For network sensitivity analysis, four types of analysis carried out. A Bayesian network for assessment of posterior probabilities of falling from height proposed. The presented Bayesian network model shows the interrelationships among 37 causes affecting the falling from height and can calculate its posterior probabilities. The most important factors affecting falling were Non-compliance with safety instructions for work at height (0.127), Lack of safety equipment for work at height (0.094) and Lack of safety instructions for work at height (0.071) respectively. The proposed Bayesian network used to determine how different causes could affect the falling from height at work. The findings of this study can be used to decide on the falling accident prevention programs.


Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis.
Isolated monoarthritis caused by Mycobacterium tuberculosis in the absence of clinical pulmonary disease is extremely rare in North America. After decades of consistent declines in incidence, a remarkable resurgence of tuberculosis (TB) is occurring in North America. It must always be considered in the differential diagnosis of chronic monoarthritis if devastating sequelae are to be avoided. We describe 2 cases of tuberculous arthritis in young children presenting with monoarthritis of the knee. The presumptive diagnosis in each case was oligoarticular onset juvenile rheumatoid arthritis (JRA). Each had an atypical course for JRA, with lack of response to intraarticular corticosteroid. The diagnosis of TB arthritis was made only with synovial biopsy.


UV-induced DNA damage and repair: a review.
Increases in ultraviolet radiation at the Earth's surface due to the depletion of the stratospheric ozone layer have recently fuelled interest in the mechanisms of various effects it might have on organisms. DNA is certainly one of the key targets for UV-induced damage in a variety of organisms ranging from bacteria to humans. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) and their Dewar valence Isomers. However, cells have developed a number of repair or tolerance mechanism to counteract the DNA damage caused by UV or any other stressors. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also plays an important role in DNA repair in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with UV-induced DNA damage and the associated repair mechanisms as well as methods of detecting DNA damage and its future perspectives.


The difficult neonatal airway.
Airway management is one of the most crucial aspects of neonatal care. The occurrence of a difficult airway is more common in neonates than in any other age group, and any neonatal intubation can develop into a difficult airway scenario. Understanding the intricacies of the difficult neonatal airway is paramount for healthcare professionals involved in the care of newborns. This chapter explores the multifaceted aspects of the difficult neonatal airway. We begin with a review of the definition and incidence of difficult airway in the neonate. Then, we explore factors contributing to a difficult neonatal airway. We next examine diagnostic considerations specific to the difficult neonatal airway, including prenatal imaging. Finally, we review management strategies. The importance of a multidisciplinary team approach and the role of communication and collaboration in achieving optimal outcomes are emphasized.


Large-scale survey of Campylobacter species in human gastroenteritis by PCR and PCR-enzyme-linked immunosorbent assay.
A PCR-based study of the incidence of enteropathogenic campylobacter infection in humans was done on the basis of a detection and identification algorithm consisting of screening PCRs and species identification by PCR-enzyme-linked immunosorbent assay. This was applied to DNA extracted from 3,738 fecal samples from patients with sporadic cases of acute gastroenteritis, submitted by seven regional Public Health Laboratories in England and Wales over a 2-year period. The sending laboratories had cultured "Campylobacter spp." from 464 samples. The PCR methodologies detected 492 Campylobacter-positive samples, and the combination of culture and PCR yielded 543 Campylobacter-positive samples. There was identity (overlap) for 413 samples, but 79 PCR-positive samples were culture negative, and 51 culture-positive samples were PCR negative. While there was no statistically significant difference between PCR and culture in detection of C. jejuni-C. coli (PCR, 478 samples; culture, 461 samples), PCR provided unique data about mixed infections and non-C. jejuni and non- C. coli campylobacters. Mixed infections with C. jejuni and C. coli were found in 19 samples, and mixed infection with C. jejuni and C. upsaliensis was found in one sample; this was not apparent from culture. Eleven cases of gastroenteritis were attributed to C. upsaliensis by PCR, three cases were attributed to C. hyointestinalis, and one case was attributed to C. lari. This represents the highest incidence of C. hyointestinalis yet reported from human gastroenteritis, while the low incidence of C. lari suggests that it is less important in this context.


The 1990 to 1991 Sudan earthquake sequence and the extent of the East african rift system.
One of the largest earthquakes ever recorded in Africa (surface wave magnitude M(s) = 7.2) occurred about 50 kilometers east of the Upper River Nile on 20 May 1990. Four days later, two more large earthquakes (M(s) = 6.4 and 7.0) occurred about 50 kilometers to the northwest in the Nile Valley. In the following months, a further 60 events were recorded by seismic stations worldwide. The earthquakes are associated with two fault systems: one east of the Nile with azimuth southeast and one along the Nile Valley with azimuth north-northeast. The activity alternated between the two fault systems and indicates that the northern extremity of the western branch of the East African Rift System extends at least 350 kilometers north of Lake Albert.


Analysis of Emotion and Recall in COVID-19 Advertisements: A Neuroscientific Study.
In this research, neuroscience techniques are applied to the field of marketing in the analysis of advertisements that include the COVID-19 pandemic in their stories. A study of emotion and memory in these audiovisual productions is carried out as two fundamental factors for the knowledge of consumer habits and decision making. By means of facial recognition biosensor systems (AFFDEX) and various tests, six informative and narrative, emotional and rational advertisements are presented to the subjects of the experiment to detect which emotions predominate; how they affect variables such as neuroticism, psychoticism or extroversion, among others; or what is remembered about the different works, brands and advertisers. Outstanding results are obtained in both emotional and cognitive analysis. Thus, in the field of public health, it is found that messages referring to COVID-19 included in advertisements are remembered more than other narratives or even the brands, products or services themselves. Likewise, joy is the predominant emotion, and its significance in such varied advertising stories stands out. Finally, it is clear that neuroscience research applied to marketing requires new methods and integrated applications to obtain satisfactory results in the advertising field.


A novel Epstein-Barr virus-like virus, HV(MNE), in a Macaca nemestrina with mycosis fungoides.
Epstein-Barr virus (EBV) infection of humans has been associated with the development of lymphoid malignancies mainly of B-cell lineage, although occasionally T-cell lymphomas have been reported. We describe here the characterization of a novel EBV-like virus (HV(MNE)) isolated from a simian T-cell lymphotropic virus type I/II (STLV-I/II) seronegative pigtailed macaque (Macaca nemestrina) with a cutaneous T-cell lymphoma. Immunohistochemistry studies on the skin lesions demonstrated that the infiltrating cells were of the CD3(+)/CD8(+) phenotype. Two primary transformed CD8(+) T-cell lines were obtained from cultures of peripheral blood mononuclear cells (PBMC) and skin, and, with time, both cell lines became interleukin-2-independent and acquired the constitutive activation of STAT proteins. Polymerase chain reaction analysis of the DNA from the cell lines and tissues from the lymphomatous animal demonstrated the presence of a 536-bp DNA fragment that was 90% identical to EBV polymerase gene sequences, whereas the same DNA was consistently negative for STLV-I/II sequences. Electron microscopy performed on both cell lines, after sodium butyrate treatment, showed the presence of a herpes-like virus that was designated HV(MNE) according to the existing nomenclature. In situ hybridization studies using EBV Epstein-Barr viral-encoded RNA probes showed viral RNA expression in both CD8(+) T-cell lines as well as in the infiltrating CD8(+) T cells of skin-tissue biopsies. Phylogenetic analysis of a 465-bp fragment from the polymerase gene of HV(MNE) placed this virus within the Lymphocryptovirus genus and demonstrated that HV(MNE) is a distinct virus, clearly related to human EBV and other EBV-like herpesviruses found in nonhuman primates.


Intercostal Neuralgia Occurring as a Complication of Splanchnic Nerve Radiofrequency Ablation in a Patient with Chronic Pancreatitis.
Our intent is to report a case of intercostal neuralgia occuring as a complication of splanchnic radiofreqency ablation (RFA), due to a breach in the integrity of the insulating sheath of the RFA needle.A 48-year-old man presented to our pain clinic with upper abdominal pain due to chronic pancreatitis, recalcitrant to medical management. We decided to perform bilateral splanchnic nerve RFA in this patient. After confirmation of bilateral correct needle placement under fluoroscopic guidance and sensorimotor testing, RFA was performed on the right side uneventfully. However, during RFA on the left side, the patient experienced severe pain in the epigastric region. A bolus of fentanyl 50 µg was given intravenously in order to minimise discomfort, and RFA was performed. In the post-procedure period, the patient described severe pain in the left subcostal and epigastric region, with features suggestive of intercostal neuralgia of the left 11th intercostal nerve. We went back and analysed all the fluoroscopic images again. Convinced of correct needle placement, we examined the RFA needles which had been used for ablation in this patient. One of the needles was discovered to have a fine breach in its insulating sheath, at a distance of approximately 30 mm from the active tip. It is of utmost importance for all interventional pain physicians to perform a thorough pre-use check of the equipment prior to any RFA procedure, with special emphasis on ensuring the integrity of the insulating sheath of the needles which are to be used, in order to prevent injury of non target nerves. Splanchnic nerve block, radiofrequency ablation, intercostal neuralgia, radiofrequency ablation complications, radiofrequency equipment check, radiofrequency needle.


Finger interaction during maximal radial and ulnar deviation efforts: experimental data and linear neural network modeling.
The purpose of this study was to characterize finger interactions during radial/ulnar deviation, including interactions with flexion movements. Subjects performed single-finger and multi-finger maximal voluntary contraction (MVC), and maximal forces and various indices of interaction among the fingers were quantified. MVCs in radial/ulnar deviation were 50-80% as strong as in flexion. Along with the 'master' fingers (i.e., those explicitly instructed to produce force), substantial force production was also observed in 'slave' fingers (i.e., those not explicitly instructed to produce force), a phenomenon termed: force 'enslaving'. In addition, a drop in MVC during multi-finger tasks as compared to single finger tasks (force 'deficit') was also observed. A previously unreported phenomenon that we term: 'preferred direction enslaving' was also apparent; both master and slave fingers produced force in the instructed direction with a non-zero perpendicular component. Due to the architectural separation of the involved muscles, preferred direction enslaving provides strong evidence that enslaving results from neural rather than biomechanical factors. A final new phenomenon: 'negative deficit', or force 'facilitation' was observed in 46.4% of the trials in 21 out of 23 subjects during multi-finger lateral efforts and was further demonstrative of extensive interconnection among neurons serving hand muscles. The data were modeled with high accuracy (approximately 4% mean square error) using a linear neural network with motor 'commands' as inputs and finger forces as outputs. The proposed network, equivalent to linear regression, can be used to determine the extent to which finger forces are influenced by peripheral constraints during functional prehensile activities.


An alternative to the hand searching gold standard: validating methodological search filters using relative recall.
Search filters or hedges play an important role in evidence-based medicine but their development depends on the availability of a "gold standard"--a reference standard against which to establish the performance of the filter. We demonstrate the feasibility of using relative recall of included studies from multiple systematic reviews to validate methodological search filters as an alternative to validation against a gold standard formed through hand searching. We identified 105 Cochrane reviews that used the Highly Sensitive Search Strategy (HSSS), included randomized or quasi-randomized controlled trials, and reported their included studies. We measured the ability of two published and one novel variant of the HSSS to retrieve the MEDLINE-index studies included in these reviews. The systematic reviews were comprehensive in their searches. 72% of included primary studies were indexed in MEDLINE. Relative recall of the three strategies ranged from .98 to .91 across all reviews and more comprehensive strategies showed higher recall. An approach using relative recall instead of a hand searching gold standard proved feasible and produced recall figures that were congruent with previously published figures for the HSSS. This technique would permit validation of a methodological filter using a collection of approximately 100 studies of the chosen design drawn from the included studies of multiple systematic reviews that used comprehensive search strategies.


Serum vascular endothelial growth factor levels in patients with medullary thyroid carcinoma.
High levels of vascular endothelial growth factor (VEGF) have been reported in patients with cancers of different origins. There are no data comparing serum VEGF levels of medullary thyroid carcinoma (MTC) patients with that of the healthy subjects. We tried to assess whether serum VEGF concentration in MTC patients is correlated with tumour extension and whether this marker might be used to further refine the selection of candidates for future therapies with receptor tyrosine kinase inhibitors. Sera from 57 individuals divided into five groups: group I, healthy individuals (n=14); group II, MTC patients in remission (n=10); group III, MTC patients with residual disease (n=12); group IV, MTC patients with loco-regional disease (n=11) and group V, MTC patients with distant metastases (n=10) were analysed for serum VEGF and calcitonin (CT) levels. Analysis of serum VEGF did not disclose significant differences among the five groups. Mean serum VEGF level of patients with distant metastases was not significantly different from that observed in healthy individuals (319.4+/-49.78 vs 313.7+/-43.13 ng/l). Serum VEGF levels correlated positively with serum CT (r=0.4891; P=0.0394) for CT values below 2500 ng/l whereas there was no correlation for CT values above this threshold. Serum VEGF levels in MTC patients are not significantly different from those found in healthy individuals and did not correlate with the extension of disease.


Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6.
RNA interference (RNAi) using short interfering RNA (siRNA) is an attractive therapeutic approach for treatment of dominant-negative mutations. Some rare missense dominant-negative mutations lead to congenital-hearing impairments. A variety of viral vectors have been tested with variable efficacy for modulating gene expression in inner ear. However, there is concern regarding their safety for clinical use. Here, we report a novel cell-penetrating peptide (CPP)-based nonviral approach for delivering siRNA into inner ear tissue using organotypic cultures as model system. PepFect6 (PF6), a variant of stearyl-TP10, was specially designed for improved delivery of siRNA by facilitating endosomal release. We show that PF6 was internalized by all cells without inducing cytotoxicity in cochlear cultures. PF6/siRNA nanoparticles lead to knockdown of target genes, a housekeeping gene and supporting cell-specific connexin 26. Interestingly, application of PF6/connexin 26 siRNA exhibited knockdown of both connexin 26 and 30 mRNA and their absence led to impaired intercellular communication as demonstrated by reduced transfer of calcein among the PF6/connexin 26-siRNA-treated cells. Thus, we conclude that PF6 is an efficient nonviral vector for delivery of siRNA, which can be applied as a tool for the development of siRNA-based therapeutic applications for hearing impairments.Molecular Therapy - Nucleic Acids (2012) 1, e61; doi:10.1038/mtna.2012.50; published online 11 December 2012.


Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions: One-Year Results of the Prospective, Multicenter NAVIGATE Study.
Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown. NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016. The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively. NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate.


Efficacy in myopia control.
There is rapidly expanding interest in interventions to slow myopia progression in children and teenagers, with the intent of reducing risk of myopia-associated complications later in life. Despite many publications dedicated to the topic, little attention has been devoted to understanding 'efficacy' in myopia control and its application. Treatment effect has been expressed in multiple ways, making comparison between therapies and prognosis for an individual patient difficult. Available efficacy data are generally limited to two to three years making long-term treatment effect uncertain. From an evidence-based perspective, efficacy projection should be conservative and not extend beyond that which has been empirically established. Using this principle, review of the literature, data from our own clinical studies, assessment of demonstrated myopia control treatments and allowance for the limitations and context of available data, we arrive at the following important interpretations: (i) axial elongation is the preferred endpoint for assessing myopic progression; (ii) there is insufficient evidence to suggest that faster progressors, or younger myopes, derive greater benefit from treatment; (iii) the initial rate of reduction of axial elongation by myopia control treatments is not sustained; (iv) consequently, using percentage reduction in progression as an index to describe treatment effect can be very misleading and (v) cumulative absolute reduction in axial elongation (CARE) emerges as a preferred efficacy metric; (vi) maximum CARE that has been measured for existing myopia control treatments is 0.44 mm (which equates to about 1 D); (vii) there is no apparent superior method of treatment, although commonly prescribed therapies such as 0.01% atropine and progressive addition spectacles lenses have not consistently provided clinically important effects; (viii) while different treatments have shown divergent efficacy in the first year, they have shown only small differences after this; (ix) rebound should be assumed until proven otherwise; (x) an illusion of inflated efficacy is created by measurement error in refraction, sample bias in only treating 'measured' fast progressors and regression to the mean; (xi) decision to treat should be based on age of onset (or refraction at a given age), not past progression; (xii) the decreased risk of complications later in life provided by even modest reductions in progression suggest treatment is advised for all young myopes and, because of limitations of available interventions, should be aggressive.


The use of vitamin A-deficient diets and jugular vein ligation to increase intracranial pressure in chickens (Gallus gallus).
A technique was developed to record intracranial cerebrospinal fluid pressure (iCSFp) in chicks and mature chickens. Using that procedure, 2 methods were found to effect a significant elevation in intracranial pressure: 1) feeding a purified diet to roosters for 40 d containing 25% of the bird's requirement for vitamin A, and 2) ligating both jugular veins in birds. The purified diet significantly reduced plasma retinol levels from 1.080 to 0.046 microg/mL, and iCSFp was significantly elevated from 63.0 to 106.0 mmH2O (P < or = 0.05). Two limitations for using hypovitaminosis A diets were capillary fragility and a cisterna magna that did not develop to the size of that structure in birds of the same age fed control diets with adequate vitamin A content. The second procedure, a reversible surgical technique, showed that within 2.5 h from jugular vein ligation, intracranial pressure rose to 109.7 mmH2O, comparable with levels attained following feeding a vitamin A deficient diet to roosters. Bilateral clamping of the jugular veins overnight resulted in an elevation of iCSFp to 127 +/- 8.86 mmH2O. Results suggest that the chicken may be a useful animal model to investigate intracranial hypertension and its accompanying headaches known to occur in humans.


Improving the antenatal and post-partum management of women presenting to Sexual Health Services with positive syphilis serology through audit.
The incidence of congenital syphilis remains low in the UK, but the morbidity and mortality to babies born to women who are untreated for the condition make testing for the disease antenatally one of the most cost-effective screening programmes. Women attending North Middlesex Hospital, UK with a positive syphilis test at their antenatal booking visit are referred to St Ann's Sexual Health Clinic, London, for management and contact tracing. We were concerned that our initial audit revealed that a large proportion of women referred to our service never attended and recorded partner notification was poor. Following the implementation of recommendations, specifically the introduction of an electronic referral system, re-audit showed an improvement in attendance, contact tracing, documentation and communication.


Premature weaning-induced changes of cholesterol metabolism in guinea pigs.
Premature weaning in animals causes higher serum cholesterol levels and a relative inability to handle cholesterol challenge in adult life. The mechanisms responsible for these delayed effects of premature weaning are not clear. The aims of this investigation were to 1) determine the effect of premature weaning on the activity of hepatic cholesterol 7 alpha-hydroxylase and plasma cholesterol changes and 2) determine whether addition of cholesterol to the diet will restore premature weaning-induced changes. Premature weaning did not prevent the phenomenon of neonatal hypercholesterolemia noted in day 5 of normally weaned guinea pigs. At day 10, prematurely weaned animals had lower serum cholesterol when compared with normally weaned animals. Premature weaning caused (without or with cholesterol in diet) a significant decrease in the hepatic activity of cholesterol 7 alpha-hydroxylase, and this difference persisted (after 1 mo) when fed the stock diet. These studies demonstrate 1) premature weaning on day 2 does not prevent neonatal hypercholesterolemia on day 5, 2) premature weaning causes a decrease in hepatic cholesterol 7 alpha-hydroxylase activity that persists into adult life, and 3) dietary cholesterol intake in early life is unable to negate premature weaning-induced changes.


Earth, Wind, Fire, and Pollution: Aerosol Nutrient Sources and Impacts on Ocean Biogeochemistry.
A key Earth system science question is the role of atmospheric deposition in supplying vital nutrients to the phytoplankton that form the base of marine food webs. Industrial and vehicular pollution, wildfires, volcanoes, biogenic debris, and desert dust all carry nutrients within their plumes throughout the globe. In remote ocean ecosystems, aerosol deposition represents an essential new source of nutrients for primary production. The large spatiotemporal variability in aerosols from myriad sources combined with the differential responses of marine biota to changing fluxes makes it crucially important to understand where, when, and how much nutrients from the atmosphere enter marine ecosystems. This review brings together existing literature, experimental evidence of impacts, and new atmospheric nutrient observations that can be compared with atmospheric and ocean biogeochemistry modeling. We evaluate the contribution and spatiotemporal variability of nutrient-bearing aerosols from desert dust, wildfire, volcanic, and anthropogenic sources, including the organic component, deposition fluxes, and oceanic impacts.


Sol-gel and Pechini niobium modified: synthesis, characterization and application in the 2,4-D herbicide degradation.
In this work, a comparison was made between the synthesis of niobium-based materials (Nb2O5), both in terms of material characterization and catalytic performance. The methods used were chemical mixtures: modified sol-gel and Pechini. The materials were calcined at different temperatures (753, 873 and 993K) and characterized by the following techniques: photoacousticspectroscopy (PAS), zero charge point (pHPZC), scanning electron microscopy (SEM/EDS), thermogravimetric analysis (TGA/DTG) and X-ray diffraction (XRD). The photocatalytic process was carried out to evaluate the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) under UV radiation (250 W mercury vapor lamp) and different experimental conditions. In addition, to better understand the influence of parameters such as pH, catalyst concentration (0.2, 0.5 and 0.8 g L-1) and calcination temperature, a Design of Experiments (DoE) was used. The results indicated that despite having similar structures and phases in the XRD analysis, the morphology presents two distinct surfaces, due to the preparation method. Differences in the synthesis method affected the catalytic activity in the parameters studied. Although the zero charge point values are close (6.18-6.36), we observed differences in the band gap depending on the calcination temperature. In the optimal condition studied, the catalyst prepared by the sol-gel method obtained the best results.


Preliminary study about the relationship between estimated training status and RAS polymorphisms on blood pressure and ACE activity in the elderly.
Polymorphisms of the renin angiotensin system (RAS) are associated with increases in blood pressure (BP). Physical exercise has been considered the main strategy to prevent this increase. This study aimed to investigate the relationship between estimated training status (TS), BP and angiotensin-converting enzyme (ACE) activity in elderly people classified as low or high risk to develop hypertension according to genetic profile. A total of 155 elderly participants performed the following assessments: general functional fitness index (GFFI), systolic BP (SBP) and diastolic BP (DBP), blood collection for ACE activity and analyses of the RAS polymorphisms. Uncontrolled hypertensive (UHT) participants presented higher values of SBP and DBP compared with normotensive (NT) and controlled hypertensive (CHT) participants. No differences were found in ACE activity and GFFI between groups. In the high risk group, UHT presented higher values of SBP and DBP compared with other groups. CHT presented higher values of SBP compared with NT. Furthermore, UHT presented higher values of ACE activity compared with CHT and lower values of GFFI compared with NT. MDA, TIA and TIC genetic combinations were associated with high risk of developing hypertension while the maintenance of good levels of TS was associated with lower BP values and ACE activity.


OCULAR PERFUSION PRESSURE AND CHOROIDAL THICKNESS IN CENTRAL SEROUS CHORIORETINOPATHY AND PIGMENT EPITHELIOPATHY.
To investigate ocular perfusion pressure (OPP) in patients with central serous chorioretinopathy (CSC) and pigment epitheliopathy (PE). In this retrospective study, we included patients with acute idiopathic unilateral CSC and age- and sex-matched normal controls. The patients with CSC were classified into two groups according to the PE presence on their fellow eyes. We compared OPP among CSC patients with or without PE and normal controls. Among a total of 47 patients with CSC, 21 were classified into the PE group and 26 into the non-PE group. The mean OPP (±SD) of CSC and fellow eyes in the PE group (50.02 ± 4.98 and 50.83 ± 4.12 mmHg, respectively) was greater than that in the non-PE group (43.69 ± 6.88 and 44.0 ± 6.57 mmHg, respectively) and normal controls (45.64 ± 8.73 mmHg) (all, P < 0.05). The mean macular choroidal thickness of CSC and fellow eyes in the PE group (344.4 ± 31.8 and 310.1 ± 37.0 μm, respectively) was thicker than that in the non-PE group (318.5 ± 43.8 and 282.8 ± 36.1 μm, respectively) (all, P < 0.05). Greater macular choroidal thickness and higher OPP were associated with PE (P = 0.002 and P = 0.003). Forty-five percent of the patients with acute unilateral CSC had PE in their fellow eyes. Increased OPP may influence the development of bilateral CSC characteristics.


The patient perspective on overactive bladder: a mixed-methods needs assessment.
While overactive bladder is often managed in the primary care setting, a number of barriers including embarrassment, poor communication, and low patient adherence contribute to the under-treatment of patients with burdensome urinary symptoms. In order to address these challenges, it is crucial to have a fundamental understanding of patient perspectives toward OAB and urinary symptoms. To meet this aim, researchers designed and conducted a study to identify patients' knowledge, experiences and attitudes, barriers to treatment adherence, and desires and tendencies regarding patient/clinician communications. A mixed-methods qualitative/quantitative needs assessment of patients with overactive bladder and/or urinary symptoms. Researchers conducted in-depth qualitative interviews via telephone with 40 patients. Interview results informed the design and dissemination of a quantitative survey, which was completed by 200 self-selected respondents who had previously identified themselves as having overactive bladder or bladder problems. Statistical and qualitative analysis of results were conducted. Among survey respondents, an average of 3.5 years elapsed between symptom onset and seeking diagnosis by a physician. In the long term most patients do not experience improvement in symptoms. Medication non-adherence is common and is related to therapy effectiveness and adverse effects. Patients clearly indicate that communication and patient/physician relationships are important to them and they would prefer the clinician initiate the conversation on overactive bladder. Patient experiences, perspectives, and attitudes toward their bladder symptoms differ in many ways from clinicians' assumptions. The significant time gap between symptom onset and diagnosis indicates ongoing need for screening and diagnosis of overactive bladder. Contrary to guideline recommendations, urinalysis and physical examination are not widely used in clinical practice. Many patients experience no improvement in symptoms over time. Patients indicate that clinician/patient relationships and communication regarding their condition are important.


[Epidermal Growth Factor Mediates Up-regulation of URGCP Oncogene in Human Hepatoma Cancer Cells].
Hepatocellular Carcinoma (HCC) is the fourth leading cause of cancer-related death in the World. Epidermal Growth Factor Receptor (EGFR) pathway plays an important role in HCC tumorigenesis. In the tumor microenvironment of HCC, the expression of EGF is aberrant. Here we describe the EGF-dependent regulation of URGCP gene in Human Hepatoma cancer cells (Hep3B). The effect of EGF cytokine on Hep3B proliferation was shown using MTT method. EGF-mediated URGCP expression was determined at mRNA and protein level with qRT-PCR analyses and Western blotting method, respectively. Different lengths of URGCP promoter constructs were transient transfected in to Hep3B cells and the basal promoter activities were determined in the presence of EGF. In addition, some pathway analyses were performed to find out the mechanism of EGF mediated up-regulation of the URGCP gene. In the presence of EGF, URGCP expression increases in concentration and time dependent manner. EGF mediated URGCP up-regulation might depend on a cis-acting element located between -344 and -482 positions in its promoter.


Interactions between Asaia, Plasmodium and Anopheles: new insights into mosquito symbiosis and implications in malaria symbiotic control.
Malaria represents one of the most devastating infectious diseases. The lack of an effective vaccine and the emergence of drug resistance make necessary the development of new effective control methods. The recent identification of bacteria of the genus Asaia, associated with larvae and adults of malaria vectors, designates them as suitable candidates for malaria paratransgenic control.To better characterize the interactions between Asaia, Plasmodium and the mosquito immune system we performed an integrated experimental approach. Quantitative PCR analysis of the amount of native Asaia was performed on individual Anopheles stephensi specimens. Mosquito infection was carried out with the strain PbGFPCON and the number of parasites in the midgut was counted by fluorescent microscopy.The colonisation of infected mosquitoes was achieved using GFP or DsRed tagged-Asaia strains.Reverse transcriptase-PCR analysis, growth and phagocytosis tests were performed using An. stephensi and Drosophila melanogaster haemocyte cultures and DsRed tagged-Asaia and Escherichia coli strains. Using quantitative PCR we have quantified the relative amount of Asaia in infected and uninfected mosquitoes, showing that the parasite does not interfere with bacterial blooming. The correlation curves have confirmed the active replication of Asaia, while at the same time, the intense decrease of the parasite.The 'in vitro' immunological studies have shown that Asaia induces the expression of antimicrobial peptides, however, the growth curves in conditioned medium as well as a phagocytosis test, indicated that the bacterium is not an immune-target.Using fluorescent strains of Asaia and Plasmodium we defined their co-localisation in the mosquito midgut and salivary glands. We have provided important information about the relationship of Asaia with both Plasmodium and Anopheles. First, physiological changes in the midgut following an infected or uninfected blood meal do not negatively affect the residing Asaia population that seems to benefit from this condition. Second, Asaia can act as an immune-modulator activating antimicrobial peptide expression and seems to be adapted to the host immune response. Last, the co-localization of Asaia and Plasmodium highlights the possibility of reducing vectorial competence using bacterial recombinant strains capable of releasing anti-parasite molecules.


MRI tracking of FePro labeled fresh and cryopreserved long term in vitro expanded human cord blood AC133+ endothelial progenitor cells in rat glioma.
Endothelial progenitors cells (EPCs) are important for the development of cell therapies for various diseases. However, the major obstacles in developing such therapies are low quantities of EPCs that can be generated from the patient and the lack of adequate non-invasive imaging approach for in vivo monitoring of transplanted cells. The objective of this project was to determine the ability of cord blood (CB) AC133+ EPCs to differentiate, in vitro and in vivo, toward mature endothelial cells (ECs) after long term in vitro expansion and cryopreservation and to use magnetic resonance imaging (MRI) to assess the in vivo migratory potential of ex vivo expanded and cryopreserved CB AC133+ EPCs in an orthotopic glioma rat model. The primary CB AC133+ EPC culture contained mainly EPCs and long term in vitro conditions facilitated the maintenance of these cells in a state of commitment toward endothelial lineage. At days 15-20 and 25-30 of the primary culture, the cells were labeled with FePro and cryopreserved for a few weeks. Cryopreserved cells were thawed and in vitro differentiated or i.v. administered to glioma bearing rats. Different groups of rats also received long-term cultured, magnetically labeled fresh EPCs and both groups of animals underwent MRI 7 days after i.v. administration of EPCs. Fluorescent microscopy showed that in vitro differentiation of EPCs was not affected by FePro labeling and cryopreservation. MRI analysis demonstrated that in vivo accumulation of previously cryopreserved transplanted cells resulted in significantly higher R2 and R2* values indicating a higher rate of migration and incorporation into tumor neovascularization of previously cryopreserved CB AC133+ EPCs to glioma sites, compared to non-cryopreserved cells. Magnetically labeled CB EPCs can be in vitro expanded and cryopreserved for future use as MRI probes for monitoring the migration and incorporation to the sites of neovascularization.


Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons.
A growing body of evidence suggests a role for soluble alpha-amyloid precursor protein (sAPPalpha) in pathomechanisms of Alzheimer disease (AD). This cleavage product of APP was identified to have neurotrophic properties. However, it remained enigmatic what proteins, targeted by sAPPalpha, might be involved in such neuroprotective actions. Here, we used high-resolution two-dimensional polyacrylamide gel electrophoresis to analyze proteome changes downstream of sAPPalpha in neurons. We present evidence that sAPPalpha regulates expression and activity of CDK5, a kinase that plays an important role in AD pathology. We also identified the cytoprotective chaperone ORP150 to be induced by sAPPalpha as part of this protective response. Finally, we present functional evidence that the sAPPalpha receptor SORLA is essential to mediate such molecular functions of sAPPalpha in neurons.


Classification of Fatigue Phases in Healthy and Diabetic Adults Using Wearable Sensor.
Fatigue is defined as "a loss of force-generating capacity" in a muscle that can intensify tremor. Tremor quantification can facilitate early detection of fatigue onset so that preventative or corrective controls can be taken to minimize work-related injuries and improve the performance of tasks that require high-levels of accuracy. We focused on developing a system that recognizes and classifies voluntary effort and detects phases of fatigue. The experiment was designed to extract and evaluate hand-tremor data during the performance of both rest and effort tasks. The data were collected from the wrist and finger of the participant's dominant hand. To investigate tremor, time, frequency domain features were extracted from the accelerometer signal for segments of 45 and 90 samples/window. Analysis using advanced signal processing and machine-learning techniques such as decision tree, k-nearest neighbor, support vector machine, and ensemble classifiers were applied to discover models to classify rest and effort tasks and the phases of fatigue. Evaluation of the classifier's performance was assessed based on various metrics using 5-fold cross-validation. The recognition of rest and effort tasks using an ensemble classifier based on the random subspace and window length of 45 samples was deemed to be the most accurate (96.1%). The highest accuracy (~98%) that distinguished between early and late fatigue phases was achieved using the same classifier and window length.


The importance of the glucose-to-lymphocyte ratio in patients with hepatocellular carcinoma treated with sorafenib.
Aim: To show the prognostic significance of the glucose-to-lymphocyte ratio (GLR) in hepatocellular carcinoma (HCC). Patients & methods: A total of 150 patients with advanced HCC who were treated with sorafenib in our center between January 2011 and December 2019 were included in the study retrospectively. Neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and GLR were analyzed to assess their prognostic value using Kaplan-Meier and Cox regression analysis before and after propensity score matching (PSM). Results: In univariate analysis before and after PSM, albumin-bilirubin grade, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, prognostic nutritional index, AFP level and GLR were found to be significantly associated with both progression-free and overall survival. In multivariate analysis before and after PSM, GLR, albumin-bilirubin grade and AFP were determined to be independent prognostic factors for progression-free and overall survival. Conclusion: The GLR prior to sorafenib treatment is a new prognostic biomarker that may predict survival in advanced HCC.


Suppression of leaf feeding and oviposition of phytophagous ladybird beetles (Coleoptera: Coccinellidae) by chitinase gene-transformed phylloplane bacteria and their specific bacteriophages entrapped in alginate gel beads.
The chitinase gene-transformed strain KPM-007E/chi of Enterobacter cloacae was vitally entrapped in sodium alginate gel beads with its specific virulent bacteriophage EcP-01 to provide a new method for microbially digesting chitinous peritrophic membranes of phytophagous ladybird beetles Epilachna vigintioctopunctata. First, chitinase SH1 from a gram-positive bacterium Kurthia zopfii was overproduced by Escherichia coli cells and purified by affinity column chromatography. The purified enzyme effectively digested peritrophic membranes dissected from the ladybird beetles to expose epithelial tissues beneath the peritrophic membrane, and the beetles that had ingested chitinase after submergence in chitinase solution had considerably reduced their feeding on tomato leaves. KPM-007E/chi, entrapped in the alginate beads, released the chitinase. More chitinase was released when KPM-007E/chi was present with their specific virulent bacteriophage EcP-01 in the beads because of lysis of bacterial cells infected with the bacteriophages. This chitinase release from the microbial beads (containing KPM-007E/chi and EcP-01) was sufficient to digest the peritrophic membrane as well as to suppress feeding of bead-sprayed tomato leaves by the ladybird beetles. A daily supply of tomato leaves treated with the microbial beads considerably suppressed leaf feeding and oviposition by the ladybird beetles, suggesting a possible application of chitinase-secreting bacteria for suppressing herbivorous insect pests.


[Cytomorphological characteristics of continous lymphoid cell culture invaded by Theileria].
Cell types and morphological characteristics of Theileria annulate-invaded cell lines from spleen, thymus, and lymph nodes were studied. Parasites in the form of macroschizonts were shown to invade three main cell groups: small lymphocyte type, monocyte type, and large reticulum cell type. Theilerias were found in the cytoplasm of these cells. Fibroblast-like cells present in the culture were free from Theileria. During mitotic division of a host cell, parasites were found to be distributed between daughter cells. Continuous cell lines invaded with Theileria can be used as a laboratory model to study some aspects of parasite-host cell interaction.


A qualitative study examining the preparedness of dental hygiene students for a service-learning placement in residential aged care.
The aim of this qualitative study was to measure the effect of a specifically designed orientation re-enactment DVD used to facilitate dental hygiene students transition from the classroom to a Residential Aged Care Facility (RACF) service-learning placement with less personal anxiety and more confidence in their role during the placement. Final year students (n = 47) were randomly allocated to one of 17 RACFs on the NSW, Central Coast, Australia. All students were then randomly allocated to a two-group study with the active group assigned to view the DVD prior to their placement. Students who viewed the DVD were asked not to discuss the content with students who were assigned to the control group. Post-placement focus groups were organized, recorded and transcribed verbatim. Data were collated, analysed and unitized into emergent themes. Representative quotes are presented in the results. The study was informed by 4 years of previous quantitative and qualitative process evaluation of the RACF programme. Focus group discussions identified that those students who had seen the DVD reported a shorter timeframe to successfully transition from the classroom to the RACF and stated that the DVD provided them with a realistic expectation of the RACF environment and their role in the placement experience. The orientation DVD reduced student anxiety and improved student confidence in their role during the placement by providing a realistic orientation of the RACF environment.


The use of statistical techniques in par-level management.
The total quality management movement has allowed the reintroduction of statistics in the materials management workplace. Statistical methods can be applied to the par level management process with significant results.


Motion-Sensitive Anchor Identification of Least-Squares Meshes from Examples.
A least-squares mesh is a surface representation consisting of a small set of anchor points and the differential and topological properties of the surface. In this paper, we present a novel method to identify motion-sensitive anchor points for least-squares meshes from a set of examples. We present a new method, called clustered teleconnection analysis, to identify the maximally excited points in a subset of basis vectors deduced using principal component analysis. We demonstrate by means of examples that our approach has a smaller reconstruction error and equivalent performance to the current best approaches.


Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms.
Fruits and vegetables are rich in flavonoids, and ample epidemiological data show that diets rich in fruits and vegetables confer protection against cardiovascular, neurodegenerative and inflammatory diseases, and cancer. However, flavonoid bioavailability is reportedly very low in mammals and the molecular mechanisms of their action are still poorly known. This review focuses on membrane transport of flavonoids, a critical determinant of their bioavailability. Cellular influx and efflux transporters are reviewed for their involvement in the absorption of flavonoids from the gastro-intestinal tract and their subsequent tissue distribution. A focus on the mammalian bilirubin transporter bilitranslocase (TCDB 2.A.65.1.1) provides further insight into flavonoid bioavailability and its relationship with plasma bilirubin (an endogenous antioxidant). The general function of bilitranslocase as a flavonoid membrane transporter is further demonstrated by the occurrence of a plant homologue in organs (petals, berries) where flavonoid biosynthesis is most active. Bilitranslocase appears associated with sub-cellular membrane compartments and operates as a flavonoid membrane transporter.


Organization of the Bacillus subtilis 168 chromosome between kdg and the attachment site of the SP beta prophage: use of Long Accurate PCR and yeast artificial chromosomes for sequencing.
Within the Bacillus subtilis genome sequencing project, the region between lysA and ilvA was assigned to our laboratory. In this report we present the sequence of the last 36 kb of this region, between the kdg operon and the attachment site of the SP beta prophage. A two-step strategy was used for the sequencing. In the first step, total chromosomal DNA was cloned in phage M13-based vectors and the clones carrying inserts from the target region were identified by hybridization with a cognate yeast artificial chromosome (YAC) from our collection. Sequencing of the clones allowed us to establish a number of contigs. In the second step the contigs were mapped by Long Accurate (LA) PCR and the remaining gaps closed by sequencing of the PCR products. The level of sequence inaccuracy due to LA PCR errors appeared to be about 1 in 10,000, which does not affect significantly the final sequence quality. This two-step strategy is efficient and we suggest that it can be applied to sequencing of longer chromosomal regions. The 36 kb sequence contains 38 coding sequences (CDSs), 19 of which encode unknown proteins. Seven genetic loci already mapped in this region, xpt, metB, ilvA, ilvD, thyB, dfrA and degR were identified. Eleven CDSs were found to display significant similarities to known proteins from the data banks, suggesting possible functions for some of the novel genes: cspD may encode a cold shock protein; bcsA, the first bacterial homologue of chalcone synthase; exol, a 5' to 3' exonuclease, similar to that of DNA polymerase I of Escherichia coli; and bsaA, a stress-response-associated protein. The protein encoded by yplP has homology with the transcriptional NifA-like regulators. The arrangement of the genes relative to possible promoters and terminators suggests 19 potential transcription units.


[Postoperative maxillary cyst].
We presented the case report of a postoperative maxillary cyst, which developed 26 years after the radical Caldwel-Luc procedure in the maxillary sinus. This is a rare case in non-oriental population but it has been described well in Japanese literature. Considering the size and damage found in clinical and radiological examination, we suspected a malignant lesion.


Effects of macrophage colony-stimulating factor and phorbol myristate acetate on 2-D-deoxyglucose transport and superoxide production in rat peritoneal macrophages.
2-D-Deoxyglucose (2-dGlc) uptake and accumulation into rat peritoneal macrophages was increased by colony-stimulating factor (mCSF) by stimulating the coupling between endofacial hexokinase activity and the sugar transporter. The evidence for this is as follows: (1) mCSF significantly decreased the Km for zero-trans uptake (P less than 0.05), without altering Vmax.; (2) the accumulation of free 2-dGlc was increased by mCSF (P less than 0.05); (3) mCSF retarded the rate of exit of accumulated free 2-dGlc. The mCSF-dependent increase in 2-dGlc uptake by macrophages was enhanced by preincubation of the cells in mCSF-free solution. The activity of the hexose monophosphate shunt (HMPS) measured by the differential uptake of 2-d[1-3H]Glc and 2-d[2,6-3H]Glc was not stimulated by mCSF. Also, in quiescent cells, superoxide production, as determined by cytochrome c reduction, was unaffected by mCSF. Phorbol myristate acetate (PMA; 40 nM) stimulated both the HMPS activity and superoxide production. Both these effects were dependent on the uptake of external sugar (2-dGlc). Incubation of the macrophages with mCSF enhanced the sugar transport and PMA-dependent stimulation of HMPS activity and superoxide production, indicating a role for mCSF in the 'priming' of macrophage functions. Both HMPS activity and superoxide production are entirely dependent on uptake of exogenous sugar, since the potent sugar-transport inhibitor cytochalasin B competitively inhibited 2-dGlc uptake, HMPS activity and superoxide generation in PMA-activated cells (Ki approximately 0.3 microM for all three processes). Over a wide range of 2-dGlc concentrations, 4 mol of superoxide were generated/mol of 2-dGlc metabolized in the HMPS pathway, indicating coupling between these processes. The Km of 2-d[2,6-3H]Glc uptake in PMA-treated cells was 0.45 +/- 0.07 mM, and Vmax. was 1.32 +/- 0.05 mumol.min-1.ml of cell water-1. It is evident that there is a large degree of slippage between HMPS activity and membrane-associated hexokinase activity, since the Km for HMPS activity was 0.06 +/- 0.02 mM and the Vmax. was 0.10 +/- 0.03 mumol.min-1.ml of cell water-1.


p-Phenyleneethynylene molecular wires: influence of structure on photoinduced electron-transfer properties.
A series of donor-acceptor arrays (exTTF-oPPE-C60) containing pi-conjugated oligo(phenyleneethynylene) wires (oPPE) of different length between pi-extended tetrathiafulvalene (exTTF) as electron donor and fullerene (C60) as electron acceptor has been prepared by following a convergent synthesis. The key reaction in these approaches is the bromo-iodo selectivity of the Hagihara-Sonogashira reaction and the deprotecting of acetylenes with different silyl groups to afford the corresponding donor-acceptor conjugates in moderate yields. The electronic interactions between the three electroactive species were determined by using UV-visible spectroscopy and cyclic voltammetry. Our studies clearly confirm that, although the C60 units are connected to the exTTF donor through pi-conjugated oPPE frameworks, no significant electronic interactions are observed in the ground state. Theoretical calculations predict how a simple exchange from C=C double bonds (i.e., oligo(p-phenylenevinylene) to C triple chemical bond C triple bonds (i.e., oPPE) in the electron donor-acceptor conjugates considerably alters long-range electron transfer. Photoexcitation of exTTF-oPPE-C60 leads to the following features: a transient photoproduct with maxima at 660 and 1000 nm, which are unambiguously attributed to the photolytically generated radical-ion-pair state, [exTTF*+-oPPE-C60*]. Both charge-separation and charge-recombination processes give rise to a molecular-wire behaviour of the oPPE moiety with an attenuation factor (beta) of (0.2+/-0.05) A(-1).


NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane.
Na(+)/H(+) exchanger 3 regulating factor 1/ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (NHERF1/EBP50), an adaptor molecule that interacts with the ERM-neurofibromatosis type 2 family of cytoskeletal proteins through its ERM-binding region and with phosphatase and tensin homolog (PTEN) and β-catenin through its PDZ domains, has been recently implicated in the progression of various human malignancies, including colorectal cancer (CRC). We report here that NHERF1 controls gland morphogenesis, as demonstrated in three-dimensional (3D) human intestinal glands developing from a single nonpolarized cell. Starting from the early two-cell developmental stage, NHERF1 concentrates at the cellular interface in a central membrane disc that marks the apical pole delimiting the forming lumen. NHERF1 depletion leads to severe disruption of the apical-basal polarity, with formation of enlarged and distorted cell spheroids devoid of a central lumen. This characteristic and the increased number of mitoses in NHERF1-depleted spheroids, including multipolar ones, mimic high-grade dysplasia lesions observed in CRC progression. NHERF1 ERM-binding or PDZ-domain mutants fail to localize apically and impair gland formation most likely by outcompeting endogenous ligands, with the latter mutant completely aborting gland development. Examination of NHERF1 ligands showed that even if both ezrin and moesin colocalized with NHERF1 at the apical membrane, moesin but not ezrin depletion disrupted morphogenesis similarly to NHERF1. NHERF1 depletion resulted also in membrane displacement of PTEN and nuclear translocation of β-catenin, events contributing to polarity loss and increased proliferation. These findings reveal an essential role of NHERF1 in epithelial morphogenesis and polarity and validate this 3D system for modeling the molecular changes observed in CRC.


The safety and efficacy of approaches to liver resection: a meta-analysis.
The aim of this study is to compare the safety and efficacy of conventional laparotomy with those of robotic and laparoscopic approaches to hepatectomy. Independent reviewers conducted a systematic review of publications in PubMed and Embase, with searches limited to comparative articles of laparoscopic hepatectomy with either conventional or robotic liver approaches. Outcomes included total operative time, estimated blood loss, length of hospitalization, resection margins, postoperative complications, perioperative mortality rates, and cost measures. Outcome comparisons were calculated using random-effects models to pool estimates of mean net differences or of the relative risk between group outcomes. Forty-nine articles, representing 3702 patients, comprise this analysis: 1901 (51.35%) underwent a laparoscopic approach, 1741 (47.03%) underwent an open approach, and 60 (1.62%) underwent a robotic approach. There was no difference in total operative times, surgical margins, or perioperative mortality rates among groups. Across all outcome measures, laparoscopic and robotic approaches showed no difference. As compared with the minimally invasive groups, patients undergoing laparotomy had a greater estimated blood loss (pooled mean net change, 152.0 mL; 95% confidence interval, 103.3-200.8 mL), a longer length of hospital stay (pooled mean difference, 2.22 days; 95% confidence interval, 1.78-2.66 days), and a higher total complication rate (odds ratio, 0.5; 95% confidence interval, 0.42-0.57). Minimally invasive approaches to liver resection are as safe as conventional laparotomy, affording less estimated blood loss, shorter lengths of hospitalization, lower perioperative complication rates, and equitable oncologic integrity and postoperative mortality rates. There was no proven advantage of robotic approaches compared with laparoscopic approaches.


Assessing Item-Level Fit for Higher Order Item Response Theory Models.
Testing item-level fit is important in scale development to guide item revision/deletion. Many item-level fit indices have been proposed in literature, yet none of them were directly applicable to an important family of models, namely, the higher order item response theory (HO-IRT) models. In this study, chi-square-based fit indices (i.e., Yen's Q 1, McKinley and Mill's G 2, Orlando and Thissen's S-X 2, and S-G 2) were extended to HO-IRT models. Their performances are evaluated via simulation studies in terms of false positive rates and correct detection rates. The manipulated factors include test structure (i.e., test length and number of dimensions), sample size, level of correlations among dimensions, and the proportion of misfitting items. For misfitting items, the sources of misfit, including the misfitting item response functions, and misspecifying factor structures were also manipulated. The results from simulation studies demonstrate that the S-G 2 is promising for higher order items.


Association between Intracranial Atherosclerotic Calcium Burden and Angiographic Luminal Stenosis Measurements.
Calcification of the intracranial vasculature is an independent risk factor for stroke. The relationship between luminal stenosis and calcium burden in the intracranial circulation is incompletely understood. We evaluated the relationship between atherosclerotic calcification and luminal stenosis in the intracranial ICAs. Using a prospective stroke registry, we identified patients who had both NCCT and CTA or MRA examinations as part of a diagnostic evaluation for ischemic stroke. We used NCCTs to qualitatively (modified Woodcock Visual Score) and quantitatively (Agatston-Janowitz Calcium Score) measure ICA calcium burden and used angiography to measure arterial stenosis. We calculated correlation coefficients between the degree of narrowing and calcium burden measures. In 470 unique carotid arteries (235 patients), 372 (79.1%) had atherosclerotic calcification detectable on CT compared with 160 (34%) with measurable arterial stenosis on CTA or MRA (P < .001). We found a weak linear correlation between qualitative (R = 0.48) and quantitative (R = 0.42) measures of calcium burden and the degree of luminal stenosis (P < .001 for both). Of 310 ICAs with 0% luminal stenosis, 216 (69.7%) had measurable calcium scores. There is a weak correlation between intracranial atherosclerotic calcium scores and luminal narrowing, which may be explained by the greater sensitivity of CT than angiography in detecting the presence of measurable atherosclerotic disease. Future studies are warranted to evaluate the relationship between stenosis and calcium burden in predicting stroke risk.


A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales.
Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals.


Inhibition by beta-caryophyllene of ethyl methanesulfonate-induced clastogenicity in cultured human lymphocytes.
beta-Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A variety of biological activities have been ascribed to this compound. In particular, it seems to possess anti-carcinogenic properties, due to its capability to induce detoxifying enzymes or to enhance, in vitro and in vivo, the natural killer cell-induced cytotoxicity against tumours. Conversely, the knowledge on the DNA-damaging activity of the substance and its modulation is scanty. Therefore, in this study, we aimed at evaluating the capability of beta-caryophyllene to protect cultured human lymphocytes from the genotoxic damage induced by ethyl methanesulfonate (EMS) and colcemid (COL) in the micronucleus assay. To investigate the mechanisms of action of this sesquiterpene, the cultures were treated with the compound before (pre-treatment), during (co-treatment) and after (post-treatment) treatment with the mutagens. Up to 100 microg/ml, beta-caryophyllene by itself did not produce any cytotoxic and genotoxic effect, as shown by the value of the nuclear division index (NDI) and the frequency of micronuclei (MN). The test compound (0.1-100 microg/ml) significantly reduced the MN frequency induced by EMS in pre- and co-treatment protocols (up to 64.4% and 87% reduction, respectively). In the post-treatment protocol, beta-caryophyllene was not effective as an antimutagen. No significant reduction of COL-induced MN frequency was found. The antigenotoxic activity of beta-caryophyllene observed here suggests that this compound could act by chemical interaction with the mutagen in the growth medium (co-treatment) or in the cytoplasm of lymphocytes (pre-treatment), so acting as a desmutagen. These data encourage further studies to investigate the mode of action and the potential use of this compound as a chemopreventive agent.


Residual activity after radioembolization of liver tumours with 90Y resin microspheres. A safe calculation method.
The actual number of resin microspheres is approximately 30-60 times higher than glass microspheres per 3 GBq vial. Thus, radioembolization (RE) with resin microspheres exerts an embolization effect besides the radiation effect. This embolization effect can occasionally cause early back flow of the microspheres before application of the entire calculated dose. To avoid these adverse side effects, RE has to be terminated at an earlier time point. Measurement of the residual activity in the delivery box, which includes the v-vial, tube and catheter, to calculate the achieved target dose is often challenging. The aim of the current study was to establish a post-RE measurement method comparable to the glass microspheres method without unnecessary radiation exposure to the staff and risk of contamination. Two different measurements were performed. First, total radioactivity in the shipping vial was measured in an ion chamber and then it was put in the delivery box and the radiation was measured from a 30 cm distance from the centre of the box with a dosimeter. The required radioactivity was then transferred to the v-vial, and the shipping vial was measured again. After that, the v-vial was measured from the same distance from the centre of the box with dosimeter. Altogether 62 times the shipping vial with different activities were measured with a significant positive correlation between the amount of the activity measured in the iron chamber and the radiation dose, measured with dosimeter (r² = 0.98; p< 0.001). There was also a strong positive correlation between these measurements of the v-vial (r² = 0.98; p< 0.001). With measurement of the residual activity in the delivery box using a dosimeter the percentage of the whole injected activity can be easily calculated. This facilitates the calculation of the actual, achieved target and non-target dose in those cases, where therapy had to be stopped because of eminent flow reversal or obstruction.


Pinwheel-dipole configuration in cat early visual cortex.
In the early visual cortex, information is processed within functional maps whose layouts are thought to underlie visual perception. However, the precise organization of these functional maps as well as their interrelationships remain unsettled. Here, we show that spatial frequency representation in cat early visual cortex exhibits singularities around which the map organizes like an electric dipole potential. These singularities are precisely co-located with singularities of the orientation map: the pinwheel centers. To show this, we used high resolution intrinsic optical imaging in cat areas 17 and 18. First, we show that a majority of pinwheel centers exhibit in their neighborhood both semi-global maximum and minimum in the spatial frequency map (i.e. extreme values of the spatial frequency in a hypercolumn). This contradicts pioneering studies suggesting that pinwheel centers are placed at the locus of a single spatial frequency extremum. Based on an analogy with electromagnetism, we proposed a mathematical model for a dipolar structure, accurately fitting optical imaging data. We conclude that a majority of orientation pinwheel centers form spatial frequency dipoles in cat early visual cortex. Given the functional specificities of neurons at singularities in the visual cortex, it is argued that the dipolar organization of spatial frequency around pinwheel centers could be fundamental for visual processing.


Harnessing chemoselective imine ligation for tethering bioactive molecules to platinum(IV) prodrugs.
Platinum(II) anticancer drugs are among the most effective and often used chemotherapeutic drugs. In recent years, there has been increasing interest in exploiting inert platinum(IV) scaffolds as a prodrug strategy to mitigate the limitations of platinum(II) anticancer complexes. In this prodrug strategy, the axial ligands are released concomitantly upon intracellular reduction to the active platinum(II) congener, offering the possibility of conjugating bioactive co-drugs which may synergistically enhance cytotoxicity on cancer cells. Existing techniques of tethering bioactive molecules to the axial positions of platinum(IV) prodrugs suffer from limited scope, poor yields and low reliability. This report explores the applications of current chemoselective ligation chemistries to platinum(IV) anticancer complexes with the aim of addressing the aforementioned limitations. Here, we describe the synthesis of a platinum(IV) complex bearing an aromatic aldehyde functionality and explored the scope of imine ligation with various hydrazide and aminooxy functionalized substrates. As a proof of concept, we tethered a six sequence long peptide mimetic (AMVSEF) of the anti-inflammatory protein, ANXA1.


Contributions of selected fundamental factors to basketball performance in adult players with mental retardation.
The purpose of this study was to determine the contributions of selected fundamental factors to basketball performance in adult players with mental retardation (MR). Fourteen trained male players with MR (32.1 +/- 7.4 years) were recruited. The athletes' performances were assessed using adapted basketball tests that assessed 4 ability levels of increasing difficulty (from I to IV), each one characterized by the analysis of 4 fundamental areas: ball handling, reception, passing, and shooting. The fundamental factors included anthropometric measurements (height, weight, and body mass index), static balance, muscular strength and endurance, explosive leg power, cardiovascular endurance, and motor coordination. This study showed that greater explosive leg power and upper-body muscular strength and endurance had significant contributions to ball handling (85%, p < 0.01), and explosive leg power had significant positive contribution in reception (59%, p < 0.05) and shooting (64%, p = 0.01). The forearm muscular strength and upper-body muscular strength and endurance had significant contributions to passing (78%, p = 0.01). Moreover, the greater explosive leg power had significant contribution in level II (46%, p < 0.05), in level III (52%, p < 0.05), and in global score (60%, p < 0.05). In conclusion, the results showed the possibility to determine the contribution of selected fundamental factors to basketball performance. Therefore, the basketball coach could improve a selected fundamental factor to increase specific basketball ability. This should be addressed in a specific training to help players with MR to perform successfully in their competitions.


Improving Electrocatalytic Oxygen Evolution through Local Field Distortion in Mg/Fe Dual-site Catalysts.
Transition metal single atom electrocatalysts (SACs) with metal-nitrogen-carbon (M-N-C) configuration show great potential in oxygen evolution reaction (OER), whereby the spin-dependent electrons must be allowed to transfer along reactants (OH- /H2 O, singlet spin state) and products (O2 , triplet spin state). Therefore, it is imperative to modulate the spin configuration in M-N-C to enhance the spin-sensitive OER energetics, which however remains a significant challenge. Herein, we report a local field distortion induced intermediate to low spin transition by introducing a main-group element (Mg) into the Fe-N-C architecture, and decode the underlying origin of the enhanced OER activity. We unveil that, the large ionic radii mismatch between Mg2+ and Fe2+ can cause a FeN4 in-plane square local field deformation, which triggers a favorable spin transition of Fe2+ from intermediate (dxy 2 dxz 2 dyz 1 dz2 1 , 2.96 μB ) to low spin (dxy 2 dxz 2 dyz 2 , 0.95 μB ), and consequently regulate the thermodyna-mics of the elementary step with desired Gibbs free energies. The as-obtained Mg/Fe dual-site catalyst demonstrates a superior OER activity with an overpotential of 224 mV at 10 mA cm-2 and an electrolysis voltage of only 1.542 V at 10 mA cm-2 in the overall water splitting, which outperforms those of the state-of-the-art transition metal SACs.


Inherited dimorphism in cleistogamous flower production in Portulaca oleracea: a comparison of 16 populations growing under different environmental conditions.
Cleistogamy is considered to be an adaptive strategy resulting in plasticity in chasmogamous (CH) and cleistogamous (CL) flower production depending on environmental conditions and plant size. The aim of this study was to investigate whether CH and CL flower production in Portulaca oleracea is genetically differentiated among populations in association with climatic conditions. First, we conducted growth experiments with P. oleracea seedlings from 16 populations under two temperature conditions. Secondly, we sowed seeds originating from the parents in the first experiment and grew the resulting plants to investigate whether flower production is heritable and whether plants in the same population show the same pattern of flower production. Two types of plants that produced only CH or CL flowers (referred to as CH and CL plants, respectively) were mainly observed, and the growing temperature conditions did not affect flower production. The frequency of CL plants increased with a decrease in the mean temperature in the original population. The CL plants tended to begin reproduction earlier than the CH plants, and the probability that a CH plant would flower decreased under the low growing temperature condition. Thus, CL plants may have some advantages in unfavourable environments in which early reproduction is necessary due to a short growing season and/or when CH flowers cannot open due to low temperatures. The progeny originating from CH and CL plants also produced only CH and CL flowers, respectively, suggesting that there is a genetic basis for the dimorphism in flower production in P. oleracea, represented by CH and CL plants. In contrast to the previous hypothesis that the production of both CH and CL flowers would be plastic, the genotypes producing either CH or CL flowers occurred at different frequencies under varying climatic conditions.


Parvalbumin expressing interneurons control spike-phase coupling of hippocampal cells to theta oscillations.
Encoding of information by hippocampal neurons is defined by the number and the timing of action potentials generated relative to ongoing network oscillations in the theta (5-14 Hz), gamma (30-80 Hz) and ripple frequency range (150-200 Hz). The exact mechanisms underlying the temporal coupling of action potentials of hippocampal cells to the phase of rhythmic network activity are not fully understood. One critical determinant of action potential timing is synaptic inhibition provided by a complex network of Gamma-amino-hydroxy-butyric acid releasing (GABAergic) interneurons. Among the various GABAergic cell types, particularly Parvalbumin-expressing cells are powerful regulators of neuronal activity. Here we silenced Parvalbumin-expressing interneurons in hippocampal areas CA1 and the dentate gyrus in freely moving mice using the optogenetic silencing tool eNpHR to determine their influence on spike timing in principal cells. During optogenetic inhibition of Parvalbumin-expressing cells, local field potential recordings revealed no change in power or frequency of CA1 or dentate gyrus network oscillations. However, CA1 pyramidal neurons exhibited significantly reduced spike-phase coupling to CA1 theta, but not gamma or ripple oscillations. These data suggest that hippocampal Parvalbumin-expressing interneurons are particularly important for an intact theta-based temporal coding scheme of hippocampal principal cell populations.


Immunological and clinical follow up of hepatitis C virus associated cryoglobulinaemic vasculitis.
To study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV). Serial serum samples from eight patients with newly diagnosed HCV associated CV were followed during interferon alpha treatment induced remission of the CV. Vasculitis activity and disease extent were evaluated with the Birmingham vasculitis activity score (BVAS) and disease extent index (DEI). Cryoglobulinaemia, complement levels (C3c, C4, and CH50), rheumatoid factor (RF), autoantibodies such as antinuclear antibodies, soluble interleukin 2 receptor (sIL2r), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble CD30 (sCD30) were determined. All patients achieved either complete or partial remission of their CV during interferon alpha treatment. There was a significant reduction in vasculitis activity and disease extent (BVAS, DEI), cryoglobulinaemia, RF, sIL2r, sICAM-1, and sCD30. Complement C3c levels increased significantly during this period. Erythrocyte sedimentation rate and levels of complement C4 and CH50 did not change significantly. Both clinical measures (BVAS and DEI) correlated significantly only with C3c and sCD30. Although this study was of only a small group of patients, it shows that BVAS and DEI as clinical measures and C3c and sCD30 as immunological markers may be useful in the follow up of disease activity of HCV associated CV. The data indicate that activity of the humoral (cryoglobulinaemia, RF, autoantibodies) and cellular (sIL2r, sICAM-1, sCD30) immune response and endothelial damage (sICAM-1) are found in HCV associated CV.


[Surgical treatment of the occipital condyle fracture: case report].
We present a case of fracture of the occipital condyle showing neck pain, lesion of IX, X and XII cranial nerves and pyramidal syndrome of the four members. A review of the literature about the surgical treatment of the occipital condyle fracture is done.


Ovarian fibrosarcoma: A single-institution experience and a review of the literature.
Ovarian fibrosarcoma is an extremely rare and malignant sex cord-stromal tumor. Due to its low incidence and poor prognosis, until now, very few cases have been reported, and most of the reported cases have been sporadic. Therefore, the treatments and prognostic factors of ovarian fibrosarcoma are still debatable. Here, we report 5 cases of ovarian fibrosarcoma that presented at Peking Union Medical College Hospital over the past 20 years. The 5 patients were 41, 51, 54, 76, and 76 years of age when initial symptoms of pelvic mass or pain appeared. On ultrasound, this disease usually manifests as unilateral pelvic masses, within which uneven echo enhancement and some blood flow signals are observed. No significant increase was observed in the levels of preoperative tumor markers, such as serum CA125 and sex hormones. The final diagnosis depends on postoperative histopathological results since these tumors are easily misdiagnosed when intraoperative frozen sections are used for examination. Pathologic examinations showed that the tumor cells were spindle-shaped with moderate to severe atypia and high mitotic counts. The immunohistochemistry profile is not specific, but the positive rate of Ki-67 was consistent with the degree of malignancy and the prognosis of patients with this tumor. In addition, the tumor may also be positive for Vimentin, α-inhibin, SMA, estrogen receptor and progesterone receptor. Significant differences were observed in the surgical methods used, and no unified chemotherapy regimen has been established. The overall survival was > 15, >7, > 6, <1, and < 1 year for each patient. After reviewing the literature, evidence-based large-scale case studies were lacking. For treatments, complete cytoreductive surgery plus regimens typically used against malignant sex cord-stromal tumors, as described in the NCCN guidelines, are recommended. Due to its low incidence, both multicenter clinical studies and molecular studies are required to provide gynecologists with a better understanding and guidance for future management of patients with ovarian fibrosarcoma.


[Infection due to hepatitis B virus and host immune response].
Cell-mediated immunity (CMI) to hepatitis B surface antigen (HBsAg) was investigated in patients who recovered from acute hepatitis B and in chronic carriers of the antigen, either with or without liver disease. The study was performed using leucocyte migration inhibition test and purified HBsAg. In antigen-negative post-hepatitis patients the frequency of cellular immunity to HBsAg (63.6%) showed a significant difference to controls. On the other hand, only one out of 5 antigen-positive post-hepatitis patients showed sensitisation to HBsAg; four out of these cases had chronic hepatitis at liver biopsy. In HBsAg-chronic carriers, with or without liver disease, the frequency of CMI to HBsAg was not significant to controls. A significant correlation was noted between inflammatory activity and inhibition of migration. Our results suggest that a normal cellular immune response to HBsAg is necessary for the recovery from acute hepatitis B and for the clearance of the virus. In HBsAg-chronic carriers this response seems to be absent or inadequate, leading to the state of healthy chronic carriers or to the evolution to HBsAg-chronic hepatitis, respectively. The high frequency of CMI in HBsAg-negative chronic active hepatitis, suggests that hepatitis B virus infection may play a role in the ethiology of the disease.


Two new dammarane-type ginsenosides from Panax ginseng.
Two new dammarane-type ginsenosides elucidated as 3-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]-20-O-[α-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl]-20(S)-protopanaxadiol, named Ginsenoside Rb6(2); (Z)-6-O-β-D-glucopyranosyl-dammar-20(22), 24-diene-3β, 6α, 12β-triol, named (20Z)-Ginsenoside Rh4 (4); along with five known ginsenosides(1, 3, 5, 6, 7) were isolated from the radix and rhizome of wild ginseng (Panax ginseng). The structures were determined by chemical and comprehensive spectroscopic analysis, including 1D, 2D NMR, HR-ESI-MS and hydrolysis reaction.


Quantification of tunicamycin-induced protein expression and N-glycosylation changes in yeast.
Tunicamycin is a potent protein N-glycosylation inhibitor that has frequently been used to manipulate protein glycosylation in cells. However, protein expression and glycosylation changes as a result of tunicamycin treatment are still unclear. Using yeast as a model system, we systematically investigated the cellular response to tunicamycin at the proteome and N-glycoproteome levels. By utilizing modern mass spectrometry-based proteomics, we quantified 4259 proteins, which nearly covers the entire yeast proteome. After the three-hour tunicamycin treatment, more than 5% of proteins were down-regulated by at least 2 fold, among which proteins related to several glycan metabolism and glycolysis-related pathways were highly enriched. Furthermore, several proteins in the canonical unfolded protein response pathway were up-regulated because the inhibition of protein N-glycosylation impacts protein folding and trafficking. We also comprehensively quantified protein glycosylation changes in tunicamycin-treated cells, and more than one third of quantified unique glycopeptides (168 of 465 peptides) were down-regulated. Proteins containing down-regulated glycopeptides were related to glycosylation, glycoprotein metabolic processes, carbohydrate processes, and cell wall organization according to gene ontology clustering. The current results provide the first global view of the cellular response to tunicamycin at the proteome and glycoproteome levels.