Characterization of endothelial basement membrane nanotopography in rhesus macaque as a guide for vessel tissue engineering.
Basement membranes have many features that greatly influence vascular endothelial cell function, including a complex three-dimensional topography. As a first step in the design and development of vascular prosthetics, we undertook a thorough characterization of the topographic features of endothelial vascular basement membranes utilizing transmission electron microscopy and scanning electron microscopy. Specifically, we quantitatively analyzed the topographic features present in the aorta, carotid, saphenous, and inferior vena cava vessels in the rhesus macaque. Our results indicate that vascular basement membranes are composed of a complex meshwork consisting of pores and fibers in the submicron (100-1000 nm) and nanoscale (1-100 nm) range, consistent with what has previously been reported in basement membranes of other tissues. We found significant differences (p<0.05) in basement membrane thickness and pore and fiber diameter depending on the location and physical properties of the vessel. These results have relevance to our fundamental understanding of vascular endothelial cell-matrix interactions in health and disease, evolving strategies in cell and tissue engineering and the design of cardiovascular prosthetic devices.


Residents' perspectives on the learning environment: data from the Accreditation Council for Graduate Medical Education resident survey.
Residents' assessment of their learning environment is an important element of residency accreditation and a strong predictor of resident satisfaction. The authors examined the reliability and validity of a resident/fellow survey and explored the relationship between reported duty hours noncompliance and residents' perceptions of other aspects of their learning environments. The Accreditation Council for Graduate Medical Education (ACGME) administered a 29-item Web-based survey in 2007 and 2008 to 91,073 residents in 5,610 programs. Aggregate data from the survey comprised indicators of substantial compliance or noncompliance. The authors examined relationships among duty hours and aspects of the educational environment, as well as the relationship of the survey results to citations from accreditation reviews. The survey demonstrated a high degree of internal reliability (Cronbach alpha, 0.84). Common factor analysis revealed two factors, educational environment and resident duty hours (eigenvalues of 5.49 and 2.42, respectively). Programs having resident-identified duty hours issues were more likely than those without such issues to have received duty hours citations from residency review committees (odds ratio: 2.04; 95% CI: 1.03, 3.05). The ACGME Resident/Fellow Survey is a reliable, valid, and useful tool for evaluating residency programs. There are strong relationships between duty hours noncompliance and noncompliance in other aspects of the program environment.


Emotional change-associated T cell mobilization at the early stage of a mouse model of multiple sclerosis.
Autoimmune diseases like multiple sclerosis (MS) are known to be associated with debilitating emotional disorders that manifest long before the flaring of motor dysfunctions. Given the emerging role of T cells in controlling both emotions and autoimmunity, in this study we explored possible correlation between T cell activation and changes in emotional behavior in a mouse model of MS. Our results showed a significant increase in blood circulating T cells as soon as at day 4 post immunization. This lymphocytosis remained stable with time and preceded the infiltration of T cell in the CNS. The kinetic of T cell entry in the blood matched the kinetic of changes in behavior measured using the open field test. Treatment with glatiramer acetate, a well-known immunomodulatory drug for MS, suppressed behavioral changes while retaining the T cells in the draining lymph nodes. Together these results provide evidence of a positive correlation between the emigration of T cells in circulation and changes in emotions during chronic inflammatory diseases. The validation of these findings in the clinic might help to better understand the cause of the emotional and psychological burden of patients suffering MS or other autoimmune diseases. Most importantly our study suggests novel therapeutic venues for the treatment of the emotional changes associated with autoimmunity.


Suicidal ideation in college students varies across semesters: the mediating role of belongingness.
The interpersonal-psychological theory of suicidal behavior (Joiner, 2005) proposes that the need to belong is fundamental; when met it can prevent suicide and when thwarted it can substantially increase the risk for suicide. We investigate one source of group-wide variation in belongingness among college students--changes in the social composition of college campuses across academic semesters--as an explanation for variation in suicidal ideation across the academic year. Our results indicate that in a sample of college students at a large southern state university (n = 309), suicidal ideation varied across academic semesters, with highest levels in summer compared to both spring and fall. Differences in suicidal ideation between summer and spring were, in large part, accounted for by belongingness. Theoretical, as well as practical, implications are discussed regarding mechanisms for seasonal variation in suicidal ideation.


Monte Carlo study of degenerate ground states and residual entropy in a frustrated honeycomb lattice Ising model.
We study a classical fully frustrated honeycomb lattice Ising model using Markov-chain Monte Carlo methods and exact calculations. The Hamiltonian realizes a degenerate ground-state manifold of equal-energy states, where each hexagonal plaquette of the lattice has one and only one unsatisfied bond, with an extensive residual entropy that grows as the number of spins N. Traditional single-spin-flip Monte Carlo methods fail to sample all possible spin configurations in this ground state efficiently, due to their separation by large energy barriers. We develop a nonlocal "chain-flip" algorithm that solves this problem, and demonstrate its effectiveness on the Ising Hamiltonian with and without perturbative interactions. The two perturbations considered are a slightly weakened bond and an external magnetic field h. For some cases, the chain-flip move is necessary for the simulation to find an ordered ground state. In the case of the magnetic field, two magnetized ground states with nonextensive entropy are found, and two special values of h exist where the residual entropy again becomes extensive, scaling proportionally to N ln phi, where phi is the golden ratio.


A phase 1-2 study of imexon plus dacarbazine in patients with unresectable metastatic melanoma.
Imexon (Amplimexon) is an aziridine compound that increases reactive oxygen species, disrupts mitochondrial membranes, and induces apoptosis. Preclinical studies showed activity against melanoma cell lines and models in mice, and synergy with dacarbazine. The authors evaluated standard doses of dacarbazine combined with increasing doses of imexon to determine the maximal tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy. Sixty-eight chemotherapy-naive melanoma patients (1 inoperable stage III and 67 stage IV) were treated with dacarbazine (250 mg/m2) and imexon (570-1300 mg/m2), both daily for 5 days every 3 weeks. There were 18 patients in the phase 1, and 50 in the phase 2 component of the study. The MTD of imexon with dacarbazine was 1000 mg/m2. Dose-limiting toxicities were pulmonary edema and hepatorenal failure. At the MTD, therapy was well tolerated. The most common toxicities (any grade) were vomiting, diarrhea, anemia, thrombocytopenia, anorexia, fever, and constipation. Among 68 patients, there were 7 treatment-related serious adverse events. Partial response and stable disease rates were 5.9% and 25% for all subjects and 2% and 30% for the phase 2 patients, respectively. Median progression-free and overall survival of all patients were 2.0 and 11.7 months and 2 and 7.5 months for the phase 2 patients, respectively. Overall survival of the 31 patients with normal lactate dehydrogenase levels was >22.5 months. Pharmacokinetics of both drugs were similar to previous reports. Imexon plus dacarbazine was well tolerated. The survival data suggest further evaluation in a randomized phase 2 study.


Pediatric Lymphoma and Solid Tumors Associated With Cancer Susceptibility Syndromes.
The aim of this study was to determine cancer susceptibility syndromes (CSSs) in children with lymphoma and solid tumors and to evaluate their effects on overall survival rates. Between 2006 and 2019, the oncologic charts of 672 patients who were followed-up with a diagnosis of lymphoma and solid tumor in our clinic were retrospectively reviewed. CSSs were detected in 42 children (6.25%). The most common CSS was DNA damage repair defects/genetic instability (in 18 of 42 patients with CSSs, 42.8%). In the patients with CSSs, 48 different cancers developed. The most common types of cancer were lymphoma (n: 10, 21%) and high-grade glial tumor (n: 9, 19%). The lymphoma subgroups were very rare childhood lymphomas, such as gray zone lymphoma and marginal zone lymphoma. The overall survival rates for patients with DNA damage repair defects/genetic instability; with CSSs other than DNA damage repair defects/patients with genetic instability syndrome; and without any CSS, were 9.7%, 65.1%, and 68.7%, respectively. The overall survival rate for patients with DNA damage repair defects/patients with genetic instability syndrome was lower than both patients with CSSs other than DNA damage repair defects/genetic instability syndrome (P=0.002) and those without any CSS (P<0.0001). CSSs should be kept in mind in children with cafe au lait spots; syndromic features; a family history of cancer, especially in siblings; and rare childhood cancers.


Thyroid hypoplasia as a cause of congenital hypothyroidism in Williams syndrome.
In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. However, the frequency of biochemical thyroid assessment, particularly in the first year of life, is being debated. In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. Therefore, treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.


Sharing is Caring: Exploring machine learning-enabled methods for regional medical imaging exchange using procedure metadata.
Seamless sharing between imaging facilities of medical images obtained on the same patient is crucial in providing accurate and efficient care to patients. However, the terminology used to describe semantically similar examinations can vary widely between facilities. Current practice is manual table-based mapping to a standard terminology, which has substantial potential for mislabelled and missing examinations. In this work, we establish several baseline methods for automating the mapping of radiology imaging procedure descriptions to a SNOMED CT based standard terminology. Our best performing baseline, consisting of a bag of words representation and shallow neural network, achieved 96.3% accuracy. In addition, we explore an unsupervised clustering method that explores relevancy matching without the need for an intervening standard. Lastly, we make the procedure name dataset used in this work available to encourage extension of this application.


Current perspectives on indications and limitations of mammography.
Women have a 7 percent natural lifetime risk of developing breast cancer, which is the leading cause of death in women aged 40 to 50 years. Most data suggest that the earlier the disease is diagnosed, the better the chance for cure. Women with "minimal breast cancer" have an actuarial 20-year survival rate of 93.2 percent. The majority of these breast cancers are diagnosed by mammography. The radiation doses from this technique have been dramatically decreased over the last ten years to about 0.1 to 0.6 rads per study. The two largest breast cancer screening studies, the Health Insurance Plan of Greater New York and the Breast Cancer Detection Demonstration Project, have shown conclusively that women over 50 years old can benefit from annual mammography and that certain groups can benefit from mammography at close intervals before the age of 50 years. This article describes the development of mammography and outlines current perspectives on its indications and limitations.


How Do People Who Are Homeless Find Out about Local Health and Social Care Services: A Mixed Method Study.
There are significant numbers of people experiencing homelessness both in the UK and internationally. People who are homeless are much more likely to die prematurely and, therefore, need strong access to ongoing health and social care support if we hope to address the health disparity they face. The aim of the research was to explore how people who are homeless identify and locate appropriate health and social care services. A mixed methods research study was applied on people who are currently homeless or had previously experienced homelessness. The research study was based in an urban area in the southwest of England. The area was chosen as it was identified to be in the top 24 local authorities for the number of homeless individuals. A hundred individuals participated in the survey, of those 32% were living on the streets whilst 68% were living in temporary accommodation such as a charity home, shelter or a hotel paid for by the local authority. In addition, 16 participated in either a focus group or one-to-one interview Methods: The quantitative component consisted of a paper-based questionnaire whilst the qualitative aspect was focus groups/one-to-one interviews. The COREQ criteria were used in the report of the qualitative aspects of the study. Quantitative data identified poor health in 90% of the sample. Access to both healthcare and wider wellbeing services (housing and food) was problematic and support for this was largely through third sector charity organisations. Qualitative data identified numerous systemic, individual and cultural obstacles, leaving difficulty for people in terms of knowing who to contact and how to access services, largely relying on word of mouth of other people who are homeless. In order to address health inequities experienced by people who are homeless, there is a need to review how information regarding local health and wider wellbeing services is provided in local communities.


Evaluation of the Storz CMAC®, Glidescope® GVL, AirTraq®, King LTS-D™, and direct laryngoscopy in a simulated difficult airway.
The aim of this study was to compare first-attempt and overall success rates and success rates in relation to placement time among 5 different airway management devices: Storz CMAC, Glidescope GVL, AirTraq, King LTS-D, and direct laryngoscopy (DL). Emergency medical technician basic (EMT-B), EMT-paramedics (EMT-P), and emergency medicine residents and staff physicians placed each of the 5 devices in a random order into an AirSim (TruCorp, Belfast, UK) part-task training manikin. The difficult airway scenario was created by fixing the manikin head to a stationary object and introducing simulated emesis into the hypopharynx. First-attempt and overall success and success in relation to placement time were compared. Provider feedback about device performance was also evaluated. Ninety-four providers (16 EMT-basics, 54 EMT-paramedics, and 24 emergency department doctors of medicine) consented to participation. First-attempt and overall success rates for DL, King LTS-D, GVL, and CMAC were not statistically different. Compared with DL, the AirTraq was 96% less likely to be placed successfully (odds ratio, 0.04; 95% confidence interval [CI], 0.01-0.14). When time was factored into the model, the odds of successful placement of the King LTS-D were higher compared with DL (hazard ratio [HR], 1.80; 95% CI, 1.34-2.42) and lower for GVL (HR, 0.59; 95% CI, 0.44-0.80) and AirTraq (HR, 0.228; 95% CI, 0.16-0.325). Providers ranked the CMAC first in terms of performance and preference for use in their practice setting. Overall success rates for DL, King-LTS-D, and both video laryngoscope systems were not different. When time was factored into the model, the King LTS-D was more likely to be placed successfully.


Physical mapping of temperature-sensitive mutations of herpes simplex virus type 1 using cloned restriction endonuclease fragments.
Sequences from the whole of the HSV-1 strain 17 genome were cloned into bacterial plasmid vectors, with the exception of part of BamHI v which was deleted in all cloned DNAs spanning this region of the virus DNA. The cloned DNAs were used in intratypic marker rescue experiments to map temperature-sensitive (ts) mutations on to the virus genome. Since the sequences of these DNAs overlapped, any mutation could be rapidly assigned a physical map position. This approach is particularly useful for mapping spontaneous mutations and lesions induced by mutagenesis of whole virus DNA. In this study, we mapped ten ts mutations comprising eight different complementation groups. Five lesions, representing three different cistrons, were located within BglII k (map units 0.098 to 0.166), and three mapped within EcoRIf (map units 0.321 to 0.414), two of which were in previously unidentified cistrons of HSV-1 strain 17. One mutation analysed had a defect within the short repeat region and another had a mutation within EcoRI i (map units 0.632 to 0.720).


Multiple assessment and serum neutralization of arbovirus mixtures.
Mixtures of Venezuelan equine encephalomyelitis, Rift Valley fever, and chikungunya viruses may be assayed by selective immunofluorescence staining of infected cell monolayers. A multiple serum neutralization test is described for quantifying reactions of these viruses with mixtures of serum antibodies.


Biomimetic Multi-Functional Superamphiphobic FOTS-TiO2 Particles beyond Lotus Leaf.
It is widely known that natural examples like lotus leaves can only repel room-temperature water but cannot repel hot water and oils. Even though superamphiphobic surfaces composed of re-entrant "mushroom-like" or "T-shaped" structures are promising, they are generally regarded as substrate-dependent and difficult to fabricate, and hence, their practical use on various materials has been limited. Here, we synthesize a flower-like superamphiphobic FOTS-TiO2 powder by solvothermal process and self-assembly functionalization. These structured and functionalized submicron particles can repel the liquids with surface tension as low as 23.8 mN·m-1 (n-decane), which is the lowest among powder samples. With respect to the biomimetic aspect, the surface morphology of FOTS-TiO2 particle is similar to the hierarchical micro/nano-structures of the lotus leaf surface, but it is beyond the lotus leaf for superoleophobic capacity. The difference in the oleophobicity is suggested to be the interplay of quasi-spherical re-entrant structure and perfluorined modification. Because of superior superamphiphobicity of the powder, a facile yet versatile strategy is developed, adhesive-assisted sieve deposition fabrication (AASDF), for preparing superamphiphobic coatings on various substrates. The investigation results pertaining to the water/oil proofing, mechanical durability, self-cleaning, and antifouling performances prove that the FOTS-TiO2 coating is robust and multifunctional, which will enable more opportunities for practical applications. Apart from these general applications, we find that the superamphiphobic FOTS-TiO2 powders when coated on sponge as anti-icing surface have good ice delay and icephobic performances. Furthermore, they can be used to prepare magnetic Fe3O4&FOTS-TiO2 composite particles through liquid marbles, implying significant scientific value.


Structural characterisation of phosphate materials: new insights into the spatial proximities between phosphorus and quadrupolar nuclei using the D-HMQC MAS NMR technique.
We show in this article how the spatial proximity between phosphorus and quadrupolar nuclei can be efficiently and easily investigated with the D-HMQC (Dipolar Hetero-nuclear Multiple-Quantum Coherences) NMR technique. Compared to the commonly used CP-HETCOR (Cross-Polarisation HETero-nuclear CORrelation) sequence, the D-HMQC pulse scheme exhibits a higher sensitivity and a better robustness with respect to spinning frequency, electronic shielding and quadrupole interaction, and thus does not require time-consuming and complicated optimisation procedures. The advantages of the D-HMQC are demonstrated in this article through the acquisition of (31)P/S through-space two-dimensional correlation NMR spectra providing unreported structural information on (i) a sodium alumino-silicate glass doped with only 3% of P(2)O(5), (ii) a potassium boro-phosphate glass containing BO(3) and BO(4) groups and (iii) a crystalline zirconium vanado-phosphate. All these systems, representative of the most important mixed phosphate network materials, cannot be correctly investigated with the conventional CP-HETCOR NMR technique.


Establishment and characteristics of GWH04, a new primary human glioblastoma cell line.
Glioblastoma multiforme (GBM) is a common and fatal disease of the central nervous system. GBM cell lines are fundamental tools used in GBM research. The establishment of novel continuous GBM cell lines with clear genetic backgrounds could facilitate the exploration of molecular mechanisms and the screening and evaluation of antitumor drugs in GBM studies. In the present study, a novel primary glioblastoma cell line was established, named GWH04, from a patient with GBM, and its STR genotype and various tumor parameters were examined. The STR information of GWH04 was identical to that of the original primary tumor tissue. Compared with existing cell lines, GWH04 had a similar in vitro proliferation rate as the U87 cell line, but a faster rate than the GL15 cell line, and substantial soft agar clone‑formation capacity and subcutaneous and intracranial tumorigenic capacity. For drug sensitivity test, half maximal inhibitory concentration assays for multiple drugs were performed in these three cell lines, and GWH04 cells were found to be resistant to temozolomide. Aneuploid karyotype with a median of 84 chromosomes was possessed by GWH04, as well as chromosomal structural abnormalities, such as broken chromosomes, double centromere chromosomes, homogeneous staining regions, and double microbodies. Gene sequencing further revealed the mutational status of genes TP53, PTEN, PDGFRA, ERBB2, BRCA1, NF1, and MLH1 and the promoter region of telomerase reverse transcriptase (C228T) in this cell line. Altogether, these results indicated that GWH04 will be a useful tool for human GBM studies both in vitro and in vivo.


Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders.
The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic resonance images of the brain and spinal cord were studied in 57 Japanese patients with multiple sclerosis (MS). Twenty-three patients clinically displayed selective involvement of the optic nerve and spinal cord and were classified as having Asian-type MS. The other 34 patients had disseminated central nervous system involvement and were classified as having Western-type MS. Patients with Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but more gadolinium-enhanced spinal cord lesions than did patients with Western-type MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101 allele were associated with Western-type MS (41.2%), but not with either Asian-type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS thus suggests the presence of two etiologically distinct diseases in Asians.


Unresolved Complexity in the Gene Regulatory Network Underlying EMT.
Epithelial to mesenchymal transition (EMT) is the process whereby a polarized epithelial cell ceases to maintain cell-cell contacts, loses expression of characteristic epithelial cell markers, and acquires mesenchymal cell markers and properties such as motility, contractile ability, and invasiveness. A complex process that occurs during development and many disease states, EMT involves a plethora of transcription factors (TFs) and signaling pathways. Whilst great advances have been made in both our understanding of the progressive cell-fate changes during EMT and the gene regulatory networks that drive this process, there are still gaps in our knowledge. Epigenetic modifications are dynamic, chromatin modifying enzymes are vast and varied, transcription factors are pleiotropic, and signaling pathways are multifaceted and rarely act alone. Therefore, it is of great importance that we decipher and understand each intricate step of the process and how these players at different levels crosstalk with each other to successfully orchestrate EMT. A delicate balance and fine-tuned cooperation of gene regulatory mechanisms is required for EMT to occur successfully, and until we resolve the unknowns in this network, we cannot hope to develop effective therapies against diseases that involve aberrant EMT such as cancer. In this review, we focus on data that challenge these unknown entities underlying EMT, starting with EMT stimuli followed by intracellular signaling through to epigenetic mechanisms and chromatin remodeling.


Evaluation of predictive factors related to the presence or absence of supplemental oxygen therapy and comparison of physical functions after video-assisted thoracic surgery.
We performed a retrospective study of 102 individuals to evaluate predictive factors for needing supplemental oxygen therapy following video-assisted thoracic surgery (VATS) and to compare patients' physical functions before and after surgery. Prior to surgery, we evaluated quadriceps torque, 6-minute walk distance (6MWD), timed up and go test, and grip strength. During the 6MWD, patients' oxygen saturation was recorded every minute. Quadriceps torque and 6MWD were evaluated again following surgery. The indication for supplemental oxygen therapy was determined based on desaturation (<85%) during the 6MWD in room air. A total of 14 patients needed oxygen therapy at discharge (group A), while 88 patients did not need oxygen therapy (group B). In group A, the postoperative 6MWD was repeated with supplemental oxygen. Compared with the same parameters in group B, in group A the percentage diffusing capacity for carbon monoxide was significantly lower (p=0.011), while a history of smoking (p=0.016), exercise-induced hypoxemia (EIH, p<0.001), chronic obstructive pulmonary disease (p<0.001), and interstitial pneumonia (p=0.008) were significantly higher. Logistic regression analysis showed that EIH was an independent risk factor for requiring supplemental oxygen therapy following surgery (odds ratio: 46.2, 95% CI: 9-237.1; p<0.001). In group A, patients' minimum oxygen saturation was significantly improved by oxygen administration (83.4±3.4 vs. 87.7±3.3, p=0.002), but there was no difference in walking distance (359.5±64.2 vs. 353.6±41.6, p=0.482). Our data indicate that patients should be preoperatively evaluated to predict postoperative hypoxemia and that this evaluation could complement the prediction of postoperative need for oxygen therapy.


Response of B-type natriuretic peptide to exercise in hypertensive patients with suspected diastolic heart failure: correlation with cardiac function, hemodynamics, and workload.
Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (Sa) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/ 90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 +/- 57 to 74 +/- 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise Sa, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.


Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib.
A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors.


Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening.
Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic tyrosine kinases (TK) has led to well-tolerated, targeted therapies for a growing number of cancer types. To identify selective Met TK inhibitors, we used a high-throughput virtual screen of the 13.5 million compound ChemNavigator database to find compounds most likely to bind to the Met ATP binding site and to form several critical interactions with binding site residues predicted to stabilize the kinase domain in its inactive conformation. Subsequent biological screening of 70 in silico hit structures using cell-free and intact cell assays identified three active compounds with micromolar IC(50) values. The predicted binding modes and target selectivity of these compounds are discussed and compared to other known Met TK inhibitors.


Pulmonary hypertension and thyroid disease.
The association between thyroid dysfunction and pulmonary hypertension (PH) has not been well characterized. This retrospective study comprised 356 consecutive PH patients seen at Mayo Clinic Jacksonville Pulmonary Hypertension Center from 1992 to 2006 and 698 sex-matched control subjects without PH. Thyroid disease was defined as an abnormal thyroid-stimulating hormone level, with or without an abnormal free or total thyroxine level, a history of thyroid disease on replacement, or an elevated thyroperoxidase antibody level. The main outcome measure was prevalence of thyroid disease in each group. Median age of the 356 PH patients was 65 years; 230 patients (65%) were female. The control group of 698 patients had the same sex ratio and median age of 68 years. Most PH patients had severe PH, as categorized by World Health Organization (WHO) class (74% class 3-4) and pulmonary artery systolic pressure. Among those with PH, 85 patients (24%) had thyroid disease vs 107 control patients (15%). After adjusting for age and sex, the prevalence of thyroid disease was increased in PH patients compared with control patients. Increased prevalence was most prominent in WHO group 1, pulmonary artery hypertension confirmed by right-heart catheterization (odds ratio, 2.53; 95% confidence interval, 1.55 to 4.08; p < 0.001). Most patients had mild thyroid disease and were hypothyroid. Only 14 of 85 patients (16%) had previously undiagnosed thyroid disease. Patients with PH have a higher prevalence of thyroid disease than other pulmonary patients. Evaluation of thyroid function in PH patients may be warranted to detect and assess coexisting thyroid disease.


Early-warning of Cardiac Condition through Detection of Murmur in Heart Sound - A Case Study.
Cardiovascular disease, particularly Rheumatic Heart Disease (RHD), is one of the leading causes of death in many developing countries. RHD is manageable and treatable with early detection. However, multiple countries across the globe suffer from a scarcity of experienced physicians who can perform screening at large scales. Advancements in machine learning and signal processing have paved way for Phonocardiogram (PCG)-based automatic heart sound classification. The direct implication of such methods is that it is possible to enable a person without specialized training to detect potential cardiac conditions with just a digital stethoscope. Hospitalization or life-threatening situations can be dramatically reduced via such early screenings. Towards this, we conducted a case study amongst a population from a particular geography using machine learning and deep learning methods for the detection of murmur in heart sounds. The methodology consists of first pre-processing and identifying normal vs. abnormal heart sound signals using 3 state-of-the-art methods. The second step further identifies the murmur to be systolic or diastolic by capturing the auscultation location. Abnormal findings are then sent for early attention of clinicians for proper diagnosis. The case study investigates the efficacy of the automated method employed for early screening of potential RHD and initial encouraging results of the study are presented.


[Myocardial infarct patients with and without intensive nutrition consultation over several years-- comparison of physiological and social variables].
After three years of experience with change of nutrition in 300 infarction patients of the Höhenried long-term study (150 patients with intensive change of nutrition and 150 patients serving as control group) and 50 randomized study participants from the control group, the following results could be found: 1. In infarction patients, who underwent rehabilitation and follow-up examinations (group with change of nutrition), the increase of the P/S quotient causes no serum cholesterol and serum triglyceride decrease compared with the control group. 2. Alcohol and nicotine consumption cannot be further decreased by intensive nutrition consultation compared with the lasting effect of the comprehensive care. 3. As well, no further weight reduction (no less than the patient obtained during the rehabilitation phase) can be attained in the "nutrition change" and the control group. 4. From the "nutrition change" group more patients took up work again after the infarction compared with the control group, although age and social status are identical in both groups. These results are contradictory to nearly all other studies. We explain this difference by the fact that both groups were under comprehensive care. The care of the patient is a very decisive factor, which is the reason for keeping low the mentioned risk factors.


Dissociative Dimensions and Their Implications for Emotional Dysregulation Underlying Borderline Personality Disorder Features.
Emotion dysregulation is considered a core feature of borderline personality disorder (BPD). The role of dissociation in BPD has been discussed from different perspectives. Nevertheless, implications of dissociation for BPD features are not clear. The current study estimated mediation effects of dissociative dimensions on the relationships between several emotion regulation strategies (ERSs) and BPD features among 281 adults recruited from the general population. The online survey administered a comprehensive self-report battery for the assessment of maladaptive and adaptive ERSs together with dissociative dimensions. Borderline personality disorder features were also self-report screened. Results showed significant indirect effects of dissociation on the relationships between ERSs and BPD features. Dissociation was a full mediator of the relationship between deficits with problem-solving skills and BPD criteria. The study confirmed that emotion dysregulation is a core feature of BPD and that the dissociative dimensions should be included as relevant maladaptive mechanisms sustaining BPD emotional difficulties.


Methods for viral isolation and DNA extraction for a penaeid shrimp baculovirus.
Procedures for the purification of virions and nucleocapsids of Baculovirus penaei (BP) of penaeid shrimp and subsequent extraction of the viral nucleic acid are described. BP-infected hepatopancrata, from two species of shrimp from different geographical locations in the Americas, were removed and homogenized in a solution of TN buffer (0.01 M Tris-HCl, 0.10 M NaCl, pH 8.0). The homogenized mixture was strained through a 100-mesh screen to remove large pieces of tissue and centrifuged to concentrate the remaining material. The pellet was suspended in TN buffer and layered on to a handmade CsCl gradient. Fractions were collected according to the bands observed in the gradient, and the optical density at 254 nm was recorded for each fraction. The resultant data was tabulated and graphed. Additionally, each fraction was examined by transmission electron microscopy to determine relative numbers of viral particles present. Large amounts of virus consistently corresponded to a specific band in the gradient, which produced a peak when the spectrophometric data was graphed. Nucleic acid was then extracted from the purified viral particles. Removal of polysaccharides was accomplished with the addition of CTAB/NaCl. The BP DNA was visualized on an agarose gel with phage lambda DNA markers for size estimation, and a preliminary endonuclease digestion was performed using BamHI.


Chicoric acid ameliorates LPS-induced inflammatory injury in bovine lamellar keratinocytes by modulating the TLR4/MAPK/NF-κB signaling pathway.
Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P < 0.01), down-regulated the expression of TLR4, MyD88, p-ERK, p-p38, IKKβ, p-p65, p-p50 (P < 0.05), and increased the IκBα protein expression (P < 0.05). In conclusion, Chicoric acid successfully protected cow lamellar keratinocytes from LPS-induced inflammatory responses by modulating the TLR4/MAPK/NF-κB signaling pathway and downregulating inflammatory mediators.


Use of dialectical behavior therapy in a partial hospital program for women with borderline personality disorder.
Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women. Patients attend the program for a minimum of five days of individual and group therapy, and full census is 12 women. About 65 percent of participants meet at least three criteria for borderline personality disorder, and most have suicidal and self-injurious behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety disorders, severe eating disorders, substance abuse, and depression. The partial hospital program is linked to an aftercare program offering six months of outpatient skills training based on dialectical behavior therapy. Both programs focus on teaching patients four skills: mindfulness (attention to one's experience), interpersonal effectiveness, emotional regulation, and distress tolerance. Two years of operation of the women's partial hospital program provides promising anecdotal evidence that dialectical behavioral therapy, an outpatient approach, can be effectively modified for partial hospital settings and a more diverse population.


Transradial access for coronary diagnostic and interventional procedures: Consensus statement and recommendations for India: Advancing Complex CoronariES Sciences through TransRADIAL intervention in India - ACCESS RADIAL™: Clinical consensus recommendations in collaboration with Cardiological Society of India (CSI).
Radial access for cardiac catheterization and intervention in India has been growing steadily over the last decade with favorable clinical outcomes. However, its usage by interventional cardiologists varies greatly among Indian operators and hospitals due to large geographic disparities in health care delivery systems and practice patterns. It also remains unclear whether the advantages, as well as limitations of transradial (TR) intervention (as reported in the western literature), are applicable to developing countries like India or not. An evidence-based review involving various facets of radial procedure for cardiac catheterization, including practical, patient-related and technical issues was conducted by an expert committee that formed a part of Advancing Complex CoronariES Sciences through TransRADIAL intervention (ACCESS RADIAL™) Advisory Board. Emerging challenges in redefining TR management based on evidence supporting practices were discussed to formulate these final recommendations through consensus.


Plasmids of phage-Group-II Staphylococcus aureus.
Most phage-Group-II Staphylococcus aureus have been shown to carry at least one plasmid. The proportion of strains that are resistant to tetracycline appears to have increased during the last 17 years. Restriction maps of several of the small plasmids isolated from Group-II strains are presented and compared with those known for staphylococcal plasmids. These small plasmids are similar to previously characterised plasmids from staphylococci of other phage groups.


Labeling of antibodies with 3H-acetate.
Antibodies can be labeled with (3)H-iodoacetate at pH 9.8 without significant loss of biological activity, and the labeled antibody can be used to detect viral antigens.


ATP-sensitive K+ channel openers: old drugs with new clinical benefits for the heart.
Different types of ATP-sensitive K+ (K(ATP)) channels have been identified in cardiomyocytes, vascular smooth muscle cells, pancreatic beta-cells, neurons and mitochondria. Years before the discovery of the K(ATP) channel in cardiomyocytes, pharmacological openers of this channel had been developed for the treatment of angina pectoris and hypertension. The K(ATP) channel plays an important role not only in coronary blood flow regulation but also in protection of cardiovascular cells from ischemia/reperfusion injury. In animal models of myocardial ischemia/reperfusion, activation of the mitochondrial K(ATP) channels by their pharmacological openers has been shown to attenuate endothelial dysfunction and to reduce myocardial necrosis. Conversely, blockade of the K(ATP) channel aggravates microvascular necrosis and the no-reflow phenomenon after ischemia/reperfusion, resulting in augmentation of post-infarct ventricular dysfunction. Recent clinical studies have shown that a combination of coronary reperfusion therapy and infusion of nicorandil, a hybrid of K(ATP) channel opener and nitrate, improved left ventricular function in patients with acute myocardial infarction. Furthermore, chronic treatment with nicorandil has been shown to significantly improve prognosis of patients with high-risk stable angina pectoris. Both of these clinical benefits cannot be attributed to the nitrate property of nicorandil. However, a recent basic investigation has suggested that the protective function of K(ATP) channel openers is compromised by concurrent hypercholesterolemia and administration of sulfonylureas for diabetes mellitus. These interferences in the beneficial action of K(ATP) channel openers by concurrent illness and pharmacological agents need to be further investigated to allow a more effective use of K(ATP) channel openers in patients with coronary artery diseases.


Mechanism of tobacco mosaic virus assembly: Incorporation of 4S and 20S protein at pH 7.0 and 20 degrees C.
The mechanism of assembly of tobacco mosaic virus (TMV) has been investigated at pH 7.0 and 20 degrees C by analytical ultracentrifugation. Under these conditions the overall rates of interconversion of 4S and 20S TMV coat protein are sufficiently slow to make possible measurements of the concentrations of remaining 4S and 20S TMV coat protein after addition of homologous RNA to solutions containing, initially, various mass ratios of 20S protein to 4S protein. It has been possible to measure, by schlieren boundary analysis, the relative rates of incorporation of 4S and 20S TMV protein into the growing nucleoprotein rod over the range of initial 20S:4S protein mass ratios from 93:7 to 18:82. The results show that the amount of incorporation of 20S TMV protein depends on the initial 20S:4S mass ratio between approximately 100% and 60% 20S protein but that reconstitution can proceed with approximately 100% 20S TMV protein to form full virus-size rods. However, when the initial protein solutions have less than 60% 20S protein, approximately 80% of the reconstituted nucleoprotein is preferentially formed from 4S coat protein. The remaining approximately 20% appears to require preformed 20S coat protein. These results suggest that a larger region of RNA than previously estimated is involved in the rate-limiting nucleation step in assembly and may explain previously conflicting results concerning the elongation phase of assembly when starting with partially assembled rods.


Promoting water consumption among Dutch children: an evaluation of the social network intervention Share H2O.
There is a need to develop and improve interventions promoting healthy drinking behaviors among children. A promising method could be to stimulate peer influence within children's social networks. In the Share H2O social network intervention (SNI), peer influence was utilized by selecting a subset of influential children and training them as 'influence agents' to promote water consumption-as an alternative to SSBs. Previous research has mainly focused on the process of selecting influence agents. However, the process of motivating influence agents to promote the behavior has hardly received any research attention. Therefore, in the SNI Share H2O SNI, this motivation process was emphasized and grounded in the self-determination theory (SDT). This study evaluated the implementation of the Share H2O SNI, focusing on whether and how applying SDT-based techniques can motivate the influence agents and, indirectly, their peers. This study included data collected in the Netherlands from both the influence agents (n = 37) and the peers (n = 112) in the classroom networks of the influence agents. Self-reported measurements assessed the influence agents' enjoyment of the training, duration and perceived autonomy support during the training, and changes in their intrinsic motivation and water consumption before and after the start of the intervention. Changes in the peers' intrinsic motivation, perceived social support, and social norms were measured before and after the start of the intervention. The influence agents enjoyed the training, the duration was adequate, and perceived it as autonomy supportive. There was an increase in the influence agents' intrinsic motivation to drink water and their actual water consumption. Providing personal meaningful rationales seemed to have motivated the influence agents. The intrinsic motivation and perceived descriptive norm of the peers remained stable. The peers reported an increase in their perceived social support and injunctive norm concerning water drinking after the intervention. Influence agents appeared to mainly use face-to-face strategies, such as modeling, talking to peers, and providing social support to promote the behavior. The current findings provided preliminary evidence of the promising effects of using SDT-based techniques in an SNI to motivate the influence agents and, indirectly, their peers. NTR, NL6905, Registered 9 January 2018, https://www.trialregister.nl/trial/6905.


Seasonal hypoxia in the bottom water off the Mississippi River delta.
Hypoxia (oxygen concentration less than 2 mg L-1 or 62.5 mmol m-3) occurs on the Louisiana continental shelf during summer when the consumption of oxygen by sediment and water column respiration exceed resupply by photosynthesis and mixing. Biological processes that consume or produce oxygen have been summarized in a budget that can be used to quantify the degree to which consumption in deep water and in the sediments exceeds net production and thus the time it takes to reach hypoxic conditions following the spring onset of stratification. The net consumption rate by the sea floor biota (sediment oxygen consumption, SOC) is inversely related to oxygen concentration and directly related to temperature. Photosynthesis is of potential importance throughout the deep water column and on the sea floor when light is adequate. A non-steady state, time-dependent numerical simulation model is used to compare biological and physical processes with shipboard measurements and continuous near-bottom records. The simulations illustrate possible variations in oxygen concentration on time scales of hours to months, and these in general match much of the variability in the direct observations at time scales of days to weeks. The frequently observed unremitting anoxia lasting weeks at some locations is not produced in the present simulations. A possible explanation is the chemical oxidation in the water column of reduced metabolic end-products produced in the sediments by anaerobic metabolism. Direct measurements of biological processes could lead to better understanding of how extrinsic forcing functions can best be managed to improve water quality.


Peribulbar anesthesia and sub-Tenon injection for vitreoretinal surgery: 300 cases.
We carried out a prospective study in order to evaluate the efficacy and safety of peribulbar anaesthesia supplemented by a sub-Tenon injection in case of inadequate analgesia during vitreoretinal surgery. We performed 300 consecutive vitreoretinal procedures. Patients received a mean volume of 17+/-4.5 ml of a mixture of etidocaine 1%, bupivacaine 0.50% and hyaluronidase (25 UI/ml). Supplementation was represented by a sub-Tenon infiltration of lidocaine 2% (2 or 3 ml). This volume was not included in the mean volume. Analgesia was adequate throughout surgery without any supplementation in 85% of cases and with a sub-Tenon infiltration in 99%. Akinesia was complete in 82%, mild in 15% and absent in 3% of cases. The sub-Tenon injection was performed immediately before starting the procedure in 58% of cases and during the surgery with a delay of 80+/-21 min in 42%. Eleven patients (3.66%) were agitated during surgery and two of them needed a general anaesthesia to allow for the procedure. Generalised epilepsy was encountered in two patients (0.66%) immediately after the peribulbar injection in one patient and 15 min later in the other. The systolic blood pressure severely decreased between 60 to 70 mm Hg 40 min after the accomplishment of the peribulbar in 2 patients and at 90 min in 2 others. Our results demonstrate that peribulbar anaesthesia alone offers excellent analgesia in 85% of patients and supplemented by a sub-Tenon injection in 99%.


Phase-driven charge manipulation in Hybrid Single-Electron Transistor.
Phase-tunable hybrid devices, built upon nanostructures combining normal metal and superconductors, have been the subject of intense studies due to their numerous combinations of different charge and heat transport configurations. They exhibit solid applications in quantum metrology and coherent caloritronics. Here we propose and realize a new kind of hybrid device with potential application in single charge manipulation and quantized current generation. We show that by tuning superconductivity on two proximized nanowires, coupled via a Coulombic normal-metal island, we are able to control its charge state configuration. This device supports a one-control-parameter cycle being actuated by the sole magnetic flux. In a voltage biased regime, the phase-tunable superconducting gaps can act as energy barriers for charge quanta leading to an additional degree of freedom in single electronics. The resulting configuration is fully electrostatic and the current across the device is governed by the quasiparticle populations in the source and drain leads. Notably, the proposed device can be realized using standard nanotechniques opening the possibility to a straightforward coupling with the nowadays well developed superconducting electronics.


Supplementation to meet metabolizable protein requirements of primiparous beef heifers: II. Pregnancy and economics.
Metabolizable protein (MP) requirements of spring calving heifers increase over the winter due to advancing gestation. The MP content of grazed winter forage is low, which may result in an MP deficiency. The objective was to compare the response of supplementing pregnant yearling heifers to meet MP requirements versus conventional CP supplementation. In 1997-98 and in 1998-99, pregnant, March-calving heifers (2,120 animals; 358 kg) at two locations of a commercial ranch in the Nebraska Sandhills, were used following breeding through calving as 2-yr-olds (cows). Heifers were randomly allotted to one of two supplementation treatments (about 265 heifers/treatment) each year at each of two locations (Ashby and Whitman, NE). Treatments were 1) supplementation to meet MP requirements (MPR) or 2) supplementation to meet CP requirements (CPR). Heifers grazed upland range and meadow and were offered supplements three times weekly from mid-September to mid- or late-February. Increasing amounts of meadow hay were fed from mid-December through calving. After supplementation ended in February, heifers were managed in one group at each location until the following October. Body weights and body condition scores were taken in September, February, and October. Two-yr-old pregnancy rates were determined via rectal palpation in October. Capital budgeting techniques were used to determine the economic return of supplementation strategies. There were no differences in BW (P = 0.41) or body condition score (P = 0.99) change during the winter among treatment groups across years and locations, but MPR cows were heavier (425 kg) than CPR cows (421 kg) at the time of 2-yr-old pregnancy testing (P = 0.07). Pregnancy rate was higher (P = 0.001) in the MPR (91%) compared to the CPR treatment (86%). Regression analysis showed that the response of the MPR treatment on pregancy rates tended to be negatively correlated with precalving body condition score (P = 0.11), body condition score loss over the winter (P = 0.07), and body condition score at weaning of the first calf (P = 0.08). The improvement in 2-yr-old pregnancy by supplementing to meet MP requirements improved the value of each bred heifer by 13.64 dollars. We conclude that balancing MP requirements during gestation may result in a subsequent increase in 2-yr-old pregnancy and increase the value of young females.


Evaluation of the performance of VIPAR polymer gels using a variety of x-ray and electron beams.
The aim of this investigation was the evaluation of the usefulness of N-vinyl pyrrolidone argon (VIPAR) polymer gel dosimetry for relative dose measurements using the majority of types and energies of radiation beams used in clinical practice. For this reason, VIPAR polymer gels were irradiated with the following beams: 6 and 23 MV photons (maximum dose: 15 Gy) and 6, 9, 12, 15, 18 and 21 MeV electrons (90% dose: 15 Gy). Using 6 MV x-rays, a linear gel dose response was verified for doses up to 20 Gy. Assuming linearity of response for the rest of the photon and electron beams used in this study, percentage depth dose measurements were derived. For all beams used and the range of relative doses studied, a satisfying agreement was observed between percentage depth dose measurements performed using the VIPAR gel-MRI method and an ion chamber, validating the assumption that a linear gel dose response holds for all photon and electron beams studied. VIPAR gels, therefore, can be used for relative dose distribution measurements using photons or electrons of any typical energy used in external radiotherapy applications. It is also demonstrated that two-dimensional dose distribution measurements through an irradiated (9 MeV electrons, 3 cm x 3 cm cone) VIPAR gel volume can be easily obtained.


Coping with disfigurement/dysfunction and length of hospital stay after head and neck cancer surgery.
The purpose of this study is to determine if an individual's use of coping strategies prior to sustaining facial disfigurement/dysfunction is predictive of coping effectiveness after head and neck cancer surgery. The specific aims of the study are as follows: (1) describe the relationship between demographic data, preoperative coping strategies, severity of disfigurement/dysfunction, postoperative healing progress, and length of postoperative hospital stay; (2) describe the relationship between demographic data, preoperative coping strategies, and postoperative coping behaviors; (3) determine the relationship between postoperative coping behaviors and length of hospital stay. The Stress-Coping Model of Scott, Oberst and Dropkin (1980) provides the theoretical framework for this study. The sample consisted of 117 adults who were about to undergo head and neck cancer surgery associated with disfigurement/dysfunction. Zero-order correlations were computed among the variables, including preoperative use of coping strategies, degree of postoperative disfigurement/dysfunction, postoperative coping behaviors, postoperative complications, and length of hospital stay. Multiple regression analyses were conducted on the major outcome variables: length of stay and postoperative coping behaviors. Gender (female), preoperative radiation therapy, preoperative chemotherapy and postoperative problems were found to significantly increase length of stay. The 16 predictors in this study contributed to 56% of the variance in length of stay. Fifteen predictors accounted for 25% of the variance in postoperative coping.


Does obesity affect the outcomes of pulmonary resections for lung cancer? A National Surgical Quality Improvement Program analysis.
Obesity has increased dramatically in the American population during the past 2 decades. Approximately 35% of adults are obese. Although obesity represents a major health issue, the association between obesity and operative outcomes has been a subject of controversy. We queried the National Surgical Quality Improvement Program (NSQIP) database to determine whether an increased body mass index (BMI) affects the outcomes of pulmonary resection for lung cancer. We identified 6,567 patients with a diagnosis of lung cancer who underwent pulmonary resection from 2005 to 2012 in the NSQIP database. We stratified this population into 6 BMI groups according to the World Health Organization classification. The primary outcome measured was 30-day mortality; secondary outcomes included length of stay (LOS), operative time, and NSQIP-measured postoperative complications. We performed both unadjusted analysis and adjusted multivariable analysis, controlling for statistically significant variables. Adjusted multivariable logistic regression showed no increase in 30-day mortality, overall morbidity, and serious morbidity among obese patients. Adjusted Poisson regression revealed greater operative times for both obese and underweight patients compared with normal weight patients. Overall, obese patients were younger and had a greater percentage of preoperative comorbidities, including diabetes, hypertension, dyspnea, renal disease, and history of previous cardiac surgery. The prevalence of active smokers was greater among patients with low and normal BMI. Underweight patients had a greater risk-adjusted LOS relative to normal weight patients, whereas overweight and mildly obese patients had lesser risk-adjusted LOS. The results of our analysis suggest that obesity does not confer greater mortality and morbidity after lung resection.


Cytological evaluation of adenoviral follicular conjunctivitis by cytobrush.
Conjunctival brush samples from 38 patients with acute conjunctivitis were examined to determine whether cellular features could be utilized for cytodiagnosis. Of all cases, 32 (84%) patients showed a characteristic cell pattern for adenoviral follicular conjunctivitis (AFC) and in the remaining 6 (16%) patients herpetic infection was suggested cytologically. The background of the conjunctival smears from patients with AFC was characterized by the predominance of lymphocytes with little fibrinous discharge. In addition, two types of nuclear alterations were demonstrated i.e. intranuclear inclusions and a so-called ground-glass nuclear appearance. Ground-glass nuclei occurred more frequently than intranuclear inclusions in patients with AFC. However, the presence of lymphocytes in conjunctival smears was a useful criterion for making the differential diagnosis between herpetic and adenoviral infections. Thus, in the absence of these three cellular changes, i.e. ground-glass nuclei, intranuclear inclusions and lymphocytic background, infectious conditions other than AFC may be considered, regardless of the numbers of conjunctival cells present. Emphasis is placed on the value of conjunctival brush cytology for the rapid diagnosis of cases of suspected AFC.


Using the general practice EMR for improving blood pressure medication adherence.
Analysis of practice electronic medical records (EMRs) demonstrated widespread antihypertensive medication adherence problems in a Pacific-led general practice serving a predominantly Pacific (majority Samoan) caseload in suburban New Zealand. Adherence was quantified in terms of medication possession ratio (MPR, percent of days covered by medication supply) from the practice's prescribing data. We studied the effectiveness of general practice staff follow-up guided by EMR data to improve medication adherence. A framework for identification of suboptimal long-term condition management from routinely-collected EMR data, the ChronoMedIt (Chronological Medical Audit) tool, was applied to data of two Pacific-led general practices to identify patients with low MPR. One practice undertook intervention, the other provided usual care. A cohort was based on MPR<80% for antihypertensive medication in a baseline 6-month period. At the intervention practice a team was established to provide reminders and motivation for these patients and discuss their specific needs for assistance to improve adherence for 12 months. MPR and systolic blood pressure (SBP) was collected at baseline and for last six months of intervention based on practice EMRs; national claims data provided assessment of MPR based on dispensing. Nursing notes were analysed, and patient and provider focus groups were conducted. Of the 252 intervention patients with MPR<80% initially, MPR improved 12.0% (p=0.0002) and systolic blood pressure was 3.5mmHg lower (p=0.07) as compared to the control cohort. MPR from national claims data improved by 11.5% (p=0.0001) as compared to the control. Patients welcomed the approach as caring and useful. Providers felt the approach worthy of wider deployment but that it required dedicated staffing. Systematic follow-up of patients with demonstrated poor medication possession appears effective in the context of a Pacific-led general practice serving a largely Pacific caseload. It was possible to exploit the EMR database to identify patients with low antihypertensive medication possession and to raise their level of medication possession significantly. The measured effect on systolic BP was only marginally significant, leaving open the question of the precise value of the intervention in terms of morbidity and mortality. The intervention was found to be feasible and was met with good acceptance from the intervention patients, who appreciated the concern reflected in the follow-up effort. The intervention practice is continuing use of ChronoMedIt to guide long-term condition management with extension to cholesterol and blood sugar.


Dual-task slowing and the effects of cross-task compatibility.
Recent studies have shown that visual encoding requires central processing, evidenced in the form of dual-task interference on response processes of a reaction time (RT) task. We report two experiments examining such dual-task interference: (1) at global level, to establish that visual encoding indeed requires central processing; and (2) at code level, to see whether two tasks may share the same representational codes. To this end, we manipulated the compatibility relation between the response codes for an auditory choice RTtask and the stimulus codes for a logically independent visual motion detection task. The results showed significant dual-task slowing of the response for the auditory task, demonstrating the interference at a global level. The effects of cross-task compatibility (CTC) were obtained at the short stimulus onset asynchrony (SOA), showing that the RTs were faster for compatible trials. Furthermore, the CTC effect remained even when the visual stimulus did not need to be "consolidated" (Jolicoeur & Dell'Acqua, 1998) for reporting, while the response postponement effect was greatly reduced. We interpret these results as indicating that the present two tasks share both "central" processes and common representational codes, but that these two levels of dual-task interference can be dissociated.


Correlation between Ionic Liquid Cytotoxicity and Liposome-Ionic Liquid Interactions.
This study aims at extending the understanding of the toxicity mechanism of ionic liquids (ILs) using various analytical methods and cytotoxicity assays. The cytotoxicity of eight ILs and one zwitterionic compound was determined using mammalian and bacterial cells. The time dependency of the IL toxicity was assessed using human corneal epithelial cells. Hemolysis was performed using human red blood cells and the results were compared with destabilization data of synthetic liposomes upon addition of ILs. The effect of the ILs on the size and zeta potential of liposomes revealed information on changes in the lipid bilayer. Differential scanning calorimetry was used to study the penetration of the ILs into the lipid bilayer. Pulsed field gradient nuclear magnetic resonance spectroscopy was used to determine whether the ILs occurred as unimers, micelles, or if they were bound to liposomes. The results show that the investigated ILs can be divided into three groups based on the cytotoxicity mechanism: cell wall disrupting ILs, ILs exerting toxicity through both cell wall penetration and metabolic alteration, and ILs affecting solely on cell metabolism.


Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
As an extension of our human cDNA project for accumulating sequence information on the coding sequences of unidentified genes, we here present the entire sequences of 100 cDNA clones of unidentified genes, named KIAA1673-KIAA1772, from three sets of size-fractionated cDNA libraries derived from human adult whole brain, hippocampus, and fetal whole brain. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here were 4.9 kb and 2.7 kb (corresponding to 895 amino acid residues), respectively. By computer-assisted analysis of the deduced amino acid sequences, 44 predicted gene products were classified into five functional categories of proteins relating to cell signaling/communication, nucleic acid management, cell structure/motility, protein management, and metabolism. Furthermore, the expression profiles of the genes were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse-transcription-coupled polymerase chain reaction, the products of which were quantified by enzyme-linked immunosorbent assay.


The homogeneous ice nucleation rate of water droplets produced in a microfluidic device and the role of temperature uncertainty.
Ice nucleation was investigated experimentally in water droplets with diameters between 53 and 96 micrometres. The droplets were produced in a microfluidic device in which a flow of methyl-cyclohexane and water was combined at the T-junction of micro-channels yielding inverse (water-in-oil) emulsions consisting of water droplets with small standard deviations. In cryo-microscopic experiments we confirmed that upon cooling of such emulsion samples ice nucleation in individual droplets occurred independently of each other as required for the investigation of a stochastic process. The emulsion samples were then subjected to cooling at 1 Kelvin per minute in a differential scanning calorimeter with high temperature accuracy. From the latent heat released by freezing water droplets we inferred the volume-dependent homogeneous ice nucleation rate coefficient of water at temperatures between 236.5 and 237.9 Kelvin. A comparison of our newly derived values to existing rate coefficients from other studies suggests that the volume-dependent ice nucleation rate in supercooled water is slightly lower than previously thought. Moreover, a comprehensive error analysis suggests that absolute temperature accuracy is the single most important experimental parameter determining the uncertainty of the derived ice nucleation rates in our experiments, and presumably also in many previous experiments. Our analysis, thus, also provides a route for improving the accuracy of future ice nucleation rate measurements.


Quality Assessment of Ambulatory ECG Using Wavelet Entropy of the HRV Signal.
Data in recordings obtained from ambulatory patients using wearable sensors are often corrupted by motion artefact and are, in general, noisier than the data obtained from the nonmobile patients. Identifying and ignoring erroneous measurements from these data is very important, if wearable sensors are to be incorporated into clinical practice. In this paper, we propose a novel Signal Quality Index, intended to assess whether reliable heart rates can be obtained from a single channel of ECG collected from ambulatory patients, using wearable sensors. The proposed system is based on wavelet entropy measurements of the heart rate variability signal. The system was trained and tested on expert-labeled data from a particular wearable sensor and was also tested on labeled data from a different sensor. The sensitivities and specificities achieved were 94% and 98%, respectively, on data from the same sensor as the training set, and 91% and 97%, respectively, on data from a different sensor, indicating the potential of the system to generalize across different sensors. Because the system relies on a single channel of ECG, it has the potential for inclusion in applications using wearable sensors and in the most basic clinical environments.


Immunomodulation and therapeutic effects of the oral use of interferon-alpha: mechanism of action.
It is now well accepted that type 1 interferons (IFNs), IFN-alpha and IFN-beta, in addition to being molecules with powerful antiviral activity, play a critical role in modulating immune responses to foreign and self-antigens. This review of the literature documents the immunomodulatory effects of IFN-alpha and discusses its position and importance in the cytokine cascade. In addition, this review attempts to organize the literature describing local and systemic immunomodulatory effects of orally administered low doses of IFN-alpha, and provide a physiological explanation for the mechanism of action. Evidence suggests that, early in the process of antigen presentation to T helper (Th) cells, IFN-alpha derived principally from the antigen-presenting cells (APC) provides an important signal for Th precursor differentiation in favor of a Th1 immune response. IFN-alpha, perhaps via upregulation of the high-alphaffinity interleukin-12beta1/beta2 (IL-12beta1/beta2) receptor, renders Th1 cells responsive to IL-12 resulting in production of high levels of IFN-gamma crucial to the development of Th1 immune responses. In addition to being instrumental in the development of Th1 immune responses, IFN-alpha appears to be the major cytokine responsible for the amplification of the CD8+ T cell response and resistance to viral infections. Orally administered IFN-alpha induces similar Th1 cytokine responses in buccal mucosal lymph nodes (LN), including upregulation of IFN-gamma expression and downregulation of IL-4. Moreover, reports of systemic immune effects such as decreased autoimmune responses, increased antiviral and antibacterial responses, and generalized immune function changes after oral IFN-alpha administration are consistent with the known immunomodulatory role of IFN-alpha in a physiological setting. Responses to orally administered low doses of IFN-alpha also adhere to the principle of low-dose priming and high-dose anergy that dictates the cellular and cytokine responses to exogenously added cytokines both in vivo and in vitro. These observations collectively suggest that IFN-alpha administered to mucosal-associated immune tissue replicates the known physiological role of IFN-alpha, including regulation of CD4+ Th1 immunomodulatory cells and activation of CD8+ effector cells, which are both crucial to development of protective immune responses. What remains to be determined is how local mucosal immune responses to IFN-alpha given orally are translated into systemic immune responses and resistance to disease. This important question, the answer to which will have profound implications for new immunotherapies for immune-based diseases, is the focus of current research.


Veterinary clinical research database for homeopathy: placebo-controlled trials.
Veterinary homeopathy has led a somewhat shadowy existence since its first introduction. Only in the last three decades has the number of clinical trials increased considerably. This literature is generally not well perceived, which may be partly a consequence of the diffuse and somewhat inaccessible nature of some of the relevant research publications. The Veterinary Clinical Research Database for Homeopathy (VetCR) was launched in 2006 to provide information on existing clinical research in veterinary homeopathy and to facilitate the preparation of systematic reviews. The aim of the present report is to provide an overview of this first database on clinical research in veterinary homeopathy, with a special focus on its content of placebo controlled clinical trials and summarising what is known about placebo effects in animals. In April 2012, the VetCR database contained 302 data records. Among these, 203 controlled trials were identified: 146 randomised and 57 non-randomised. In 97 of those 203 trials, the homeopathic medical intervention was compared to placebo. A program of formal systematic reviews of peer-reviewed randomised controlled trials in veterinary homeopathy is now underway; detailed findings from the program's data extraction and appraisal approach, including the assessment of trial quality (risk of bias), will be reported in due course.


Mass spectrometry method to identify aging pathways of Sp- and Rp-tabun adducts on human butyrylcholinesterase based on the acid labile P-N bond.
The phosphoramidate nerve agent tabun inhibits butyrylcholinesterase (BChE) and acetylcholinesterase by making a covalent bond on the active site serine. The adduct loses an alkyl group in a process called aging. The mechanism of aging of the tabun adduct is controversial. Some studies claim that aging proceeds through deamination, whereas crystal structure studies show aging by O-dealkylation. Our goal was to develop a method that clearly distinguishes between deamination and O-dealkylation. We began by studying the tetraisopropyl pyrophosphoramide adduct of BChE because this adduct has two P-N bonds. Mass spectra showed that the P-N bonds were stable during trypsin digestion at pH 8 but were cleaved during pepsin digestion at pH 2. The P-N bond in tabun was also acid labile, whereas the P-O bond was stable. A scheme to distinguish aging by deamination from aging by O-dealkylation was based on the acid labile P-N bond. BChE was inhibited with Sp- and Rp-tabun thiocholine nerve agent model compounds to make adducts identical to those of tabun with known stereochemistry. After aging and digestion with pepsin at pH 2, peptide FGES198AGAAS from Sp-tabun thiocholine had a mass of 902.2 m/z in negative mode, indicating that it had aged by deamination, whereas peptide FGES198AGAAS from Rp-tabun thiocholine had a mass of 874.2 m/z in negative mode, indicating that it had aged by O-dealkylation. BChE inhibited by authentic, racemic tabun yielded both 902.2 and 874.2 m/z peptides, indicating that both stereoisomers reacted with BChE and aged either by deamination or dealkylation.


The economics of improved cancer survival rates: better outcomes, higher costs.
In 2006, over three million new cases of cancer were diagnosed in Europe. This number will increase in the coming years as a result of an aging population and population growth. Advances in the diagnosis and treatment of cancer have resulted in increased survival rates. Simultaneously, increasing costs of screening, diagnosis and the treatment of cancer could threaten the ability to ensure high-quality care and provide access to care for all patients. New genetic tests and biomarkers may help to identify those subtypes of patients that would be most likely to benefit from new cancer drugs. In our opinion, there is still much to gain in cancer diagnosis and treatment but these gains should be worth the costs.


Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer.
Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC-siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC-siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC-siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer.


Distribution of type A and B synoviocytes in the adhesive and shortened synovial membrane during immobilization of the knee joint in rats.
Joint immobilization is commonly used for the treatment of joint injuries and diseases, but it also causes unfavorable outcomes such as joint contracture. The purpose of this study was to examine the morphological changes of the synovial membrane that is suspected as a cause of joint contracture, and localization of type A (macrophage-like) and type B (fibroblast-like) synoviocytes in the capsule after joint immobilization. Male Sprague-Dawley rats were used in this study. Unilateral knee joints were rigidly immobilized at 150 degrees of flexion with internal fixators for 3 days, 1, 2, 4, 8, and 16 weeks (7 rats/each immobilized group), while 42 rats were sham-operated. Sagittal sections of 5 mum were prepared from the medial midcondylar region of the knee joints and assessed with histological, histomorphometric, and immunohistochemical methods. Adhesions were observed both in the anterior and posterior synovial membranes in the immobilized group after 2 weeks. In the adhesion area, the cells were mainly composed of type A synoviocytes that were positive for CD68 and type B synoviocytes positive for prolyl 4-hydroxylase subunit beta. The length of synovial membrane in the immobilized group was significantly shorter than that in the control group after 2 and 4 weeks. After 8 weeks, the adhesion area in the immobilized group became fibrous and hypocellular. The staining intensity of hyaluronic acid-binding protein was increased after 16 weeks. Adhesion and shortening of the synovial membrane and the structural changes of the adhesion area may contribute to the development of joint contracture.


Is albumin a predictor of severity and mortality in patients with abdominal sepsis?
Patients with a lower level of albumin have a more severe infection, the level of said biomarker is a strong predictor of mortality. To determine the usefulness of the serum albumin level as a predictor of severity and mortality. Retrospective, descriptive, cross-sectional study of patients diagnosed with abdominal sepsis. During the period from April 2016-February 2017. The severity was determined by Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), Mannheim and mortality. The sample was divided into those with albumin > 2.9 mg/dl and < 2.8 mg/dl. We included 155 cases, 62 female and 93 male; the main organ causing abdominal sepsis was the appendix 42%. The average albumin for the sample was 3.2 mg/dl (DE ± 0.9). The findings, subjected to statistical verification by means of the Mann-Whitney test, showed statistical significance among the cases with albumin < 2.8 mg/dl with those have ranged Mannheim > 26 points (p = 0.001), APACHE > 15 (p = 0.015) and SOFA > 6 (p = 0.001), No statistical significance was obtained between albumin level < 2.8, and mortality (p = 0.052). Albumin can be considered as a predictor of severity, although not as a predictor of mortality.


Engineering Human-Scale Artificial Bone Grafts for Treating Critical-Size Bone Defects.
The manufacturing of artificial bone grafts can potentially circumvent the issues associated with current bone grafting treatments for critical-size bone defects caused by pathological disorders, trauma, or massive tumor ablation. In this study, we report on a potentially patient-specific fabrication process in which replicas of bone defects, in particular zygomatic and mandibular bones and phalanxes of a hand finger, were manufactured by laser stereolithography and used as templates for the creation of PDMS molds. Gas-in-water foams were cast in the molds, rapidly frozen, freeze-dried, and cross-linked. Since bone matrix consists essentially of collagen and hydroxyapatite, biomimetic scaffolds were fabricated using gelatin and hydroxyapatite in a ratio very similar to that found in bone. The obtained composite scaffolds were excellent replicas of the original bone defects models and presented both a superficial and internal porous texture adequate for cellular and blood vessels infiltration. In particular, scaffolds exhibited a porous texture consisting of pores and interconnects with average size of about 300 and 100 μm, respectively, and a porosity of 90%. In vitro culture tests using hMSCs demonstrated scaffold biocompatibility and capacity in inducing differentiation toward osteoblasts progenitors. In vivo cellularized implants showed bone matrix deposition and recruitment of blood vessels. Overall, the technique/materials combination used in this work led to the fabrication of promising mechanically stable, bioactive, and biocompatible composite scaffolds with well-defined architectures potentially valuable in the regeneration of patient-specific bone defects.


CT and MRI evaluation of musculoskeletal infection.
While the plain film and nuclear medicine bone scan are still the traditional imaging modalities used in the evaluation of musculoskeletal infection, the cross-sectional imaging modalities, computed tomography (CT) and magnetic resonance imaging (MRI), have become critical in the delineation of many types of musculoskeletal infection. In particular, the evaluation of soft tissue infections, including cellulitus, myositis, fasciitis, abscess, and septic arthritis are often best evaluated by MRI or CT due to their excellent anatomic resolution and soft tissue contrast. Even in osseous infection, CT and MRI can give better anatomic delineation of the extent of infection. In cases where the plain film and nuclear medicine bone scan findings are complicated due to previous surgery, trauma, or underlying illness, the anatomic resolution and soft tissue contrast provided by MRI and CT are often necessary to determine if underlying infection exists. MRI's visualization of the bone marrow allows for the sensitive detection of osteomyelitis, although specificity for the diagnosis of osteomyelitis is aided by other findings, including cortical destruction. The CT and MRI findings in the spectrum of musculoskeletal infections are discussed and contrasted, and pitfalls in their evaluation of musculoskeletal infection are described.


Improved stomatal regulation and ion partitioning boosts salt tolerance in grafted melon.
Grafted plants are often more tolerant to salinity than nongrafted controls. In order to distinguish differential response components in grafted melon (Cucumis melo L.), salt stress was imposed on several rootstock-scion combinations in four experiments. The rootstock used was an interspecific squash (Cucurbita maxima Duch.×Cucurbita moschate Duch.), RS841, combined with two cantaloupe (C. melo var. cantalupensis) cultivars, namely London and Brennus, against both self-grafted and nongrafted controls. Physiological, morphological and biochemical adaptations to 0, 40 and 80mM NaCl were monitored. Upon salinity, plant biomass and leaf area were improved by grafting per se, since self-grafted plants performed similarly to the heterografted ones. However, improvements in the exclusion of Na+ and the uptake of K+ were due only to the rootstock genotype, since ionic composition was similar in self-grafted and nongrafted plants. These results indicate that the favourable effects of grafting on plant growth cannot be ascribed to a more efficient exclusion of Na+ or enhanced nutrient uptake. On the other hand, growth improvements in both self- and heterografted plants were associated with a more efficient control of stomatal functions (changes in stomatal index and water relations), which may indicate that the grafting incision may alter hormonal signalling between roots and shoots.


Biosafety risk assessment for production of candidate vaccine viruses to protect humans from zoonotic highly pathogenic avian influenza viruses.
A major lesson learned from the public health response to the 2009 H1N1 pandemic was the need to shorten the vaccine delivery timeline to achieve the best pandemic mitigation results. A gap analysis of previous pre-pandemic vaccine development activities identified possible changes in the Select Agent exclusion process that would maintain safety and shorten the timeline to develop candidate vaccine viruses (CVVs) for use in pandemic vaccine manufacture. Here, we review the biosafety characteristics of CVVs developed in the past 15 years to support a shortened preparedness timeline for A(H5) and A(H7) subtype highly pathogenic avian influenza (HPAI) CVVs. Extensive biosafety experimental evidence supported recent changes in the implementation of Select Agent regulations that eliminated the mandatory chicken pathotype testing requirements and expedited distribution of CVVs to shorten pre-pandemic and pandemic vaccine manufacturing by up to 3 weeks.


Generation, Expansion, and Differentiation of Human Pluripotent Stem Cell (hPSC) Derived Neural Progenitor Cells (NPCs).
Human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for neural-related cell-based therapies and disease modeling. However, the use of NPCs for the study and treatment of a variety of debilitating neurological diseases requires the development of scalable and reproducible protocols for their generation, expansion, characterization, and neuronal differentiation. Here, we describe a serum-free method for the stepwise generation of NPCs from hPSCs through the sequential formation of embryoid bodies (EBs) and neuro-epithelial-like rosettes. NPCs isolated from neural rosette cultures can be homogenously expanded while maintaining high expression of pan-neural markers such as SOX1, SOX2, and Nestin. Finally, this protocol allows for the robust differentiation of NPCs into microtubule-associated protein 2 (MAP2) and β-Tubulin-III (β3T) positive neurons.


Treating renal disease: a history.
As dialysis technology advanced, physicians trained in the new specialty of nephrology set up dialysis programs in hospitals throughout New Jersey. Physicians, state legislators, organizations, and patients contributed to the growth of a life-saving technology.


Transmission of different strains of Plasmodium cynomolgi to Aotus nancymaae monkeys and relapse.
Forty-four splenectomized Aotus nancymaae monkeys were infected with 6 different strains of Plasmodium cynomolgi, 11 via trophozoites and 33 via sporozoites. Sporozoites from Anopheles dirus, Anopheles freeborni, Anopheles gambiae, Anopheles maculatus, and Anopheles stephensi resulted in prepatent periods ranging from 9 to 39 days (median of 15 days). Importantly, relapse was demonstrated in 5 of 5 sporozoite-induced infections with the Rossan strain following treatment with chloroquine.


A New Type of Motor: Pneumatic Step Motor.
This paper presents a new type of pneumatic motor, a pneumatic step motor (PneuStep). Directional rotary motion of discrete displacement is achieved by sequentially pressurizing the three ports of the motor. Pulsed pressure waves are generated by a remote pneumatic distributor. The motor assembly includes a motor, gearhead, and incremental position encoder in a compact, central bore construction. A special electronic driver is used to control the new motor with electric stepper indexers and standard motion control cards. The motor accepts open-loop step operation as well as closed-loop control with position feedback from the enclosed sensor. A special control feature is implemented to adapt classic control algorithms to the new motor, and is experimentally validated. The speed performance of the motor degrades with the length of the pneumatic hoses between the distributor and motor. Experimental results are presented to reveal this behavior and set the expectation level. Nevertheless, the stepper achieves easily controllable precise motion unlike other pneumatic motors. The motor was designed to be compatible with magnetic resonance medical imaging equipment, for actuating an image-guided intervention robot, for medical applications. For this reason, the motors were entirely made of nonmagnetic and dielectric materials such as plastics, ceramics, and rubbers. Encoding was performed with fiber optics, so that the motors are electricity free, exclusively using pressure and light. PneuStep is readily applicable to other pneumatic or hydraulic precision-motion applications.


Does dementia predict adverse hospitalization outcomes? A prospective study in aged inpatients.
Dementia is often considered a predictor of adverse hospitalization outcomes. However, the relative contributions of dementia and other risk factors remain unclear. To assess, in a prospective study, the relative value of dementia for predicting hospitalization outcomes, taking into account comorbidity, functional and nutritional status in 435 inpatients (age 85.3 +/- 6.7; 207 cognitively normal, 48 with mild cognitive impairment and 180 demented) from the acute and rehabilitation geriatric hospital of Geneva. Hospitalization outcomes (death in hospital, length of stay, institutionalisation and formal home care needs) were predicted using logistic regression models with sociodemographic characteristics, cognitive status, comorbid Charlson index-CCI, functional and nutritional status as independent variables. Moderate and severe dementia and poor physical function strongly predicted longer hospital stay, institutionalization and greater home care needs in univariate analyses. CCI was the best single predictor, with a four-fold difference in mortality rates between the highest and lowest scores. In multivariate analysis, the best predictor of institutionalisation was dementia, whereas the best predictor of death in hospital or longer hospital stay was higher comorbidity score, regardless of cognitive status. Functional status was the best predictor of greater home care needs. Dementia in very old medically ill inpatients was predictive only of discharge to a nursing home. Higher levels of comorbidity and poor functional status were more predictive than dementia for the other three hospitalization outcomes. Thus, comorbid medical conditions, functional and nutritional status should be considered, together with cognitive assessment, when predicting hospitalization outcome.


Improved detection of hepatitis C virus infection by transcription-mediated amplification technology in dialysis population.
Hepatitis C virus (HCV) infection remains common among patients undergoing maintenance dialysis and plays an adverse effect on survival in this population. Accurate detection of HCV viremia (HCV RNA) in dialysis patients requires a sensitive and specific diagnostic test. The Versant HCV RNA Qualitative Assay, based on transcription-mediated amplification (TMA) technique, was prospectively evaluated in 112 dialysis patients. Performance characteristics of the Versant HCV TMA Assay were evaluated in comparison to the Amplicor((R)) 2.0 HCV test based on polymerase chain reaction (PCR) technique. In addition, anti-HCV serologic tests including third-generation enzyme immunoassay and Recombinant Immunoblot Assay were performed. Of the 112 specimens tested, 29 were reactive by Versant HCV TMA Assay, yielding an overall prevalence of HCV viremia of 25.9%. The concordance between TMA and PCR techniques was excellent [91% (101/112)]. Eleven specimens (10%) were invalid or equivocal by PCR due to interference phenomena; all 11 specimens had valid TMA results (2 patients being TMA reactive and 9 nonreactive). Four specimens [3.6% (4/112)] that tested PCR-negative and HCV TMA nonreactive were anti-HCV seropositive, consistent with resolved HCV infection. In the group of seronegative samples, one was reactive by TMA Assay [1.25% (1/80)]. The HCV TMA technology seems a highly sensitive tool for detecting HCV RNA in the dialysis population, with no evidence of specimen interference. One EIA-negative but HCV-RNA-positive patient by Versant HCV TMA Assay was identified. Prospective clinical trials are under way to assess the clinical impact related to the use of HCV TMA technology in dialysis population.