How Does the Severity of Neuroforaminal Compression in Cervical Radiculopathy Affect Outcomes of Anterior Cervical Discectomy and Fusion.
This study is a retrospective cohort study. This study aims to determine whether preoperative neuroforaminal stenosis (FS) severity is associated with motor function patient-reported outcome measures (PROMs) following anterior cervical discectomy and fusion (ACDF). Cervical FS can significantly contribute to patient symptoms. While magnetic resonance imaging (MRI) has been used to classify FS, there has been limited research into the impact of FS severity on patient outcomes. Patients undergoing primary, elective 1-3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, p =0.022). Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.


Asian American Access to Care in the Affordable Care Act Era: Findings from a Population-Based Survey in California.
Though Asian Americans made gains in coverage following the Affordable Care Act (ACA), substantial variations in access to care remain across different ethnic subgroups. Several states are considering adoption of policies to collect health data for Asian Americans that is disaggregated by ethnic subgroup, which may identify disparities in access to care. We examined coverage and access to care between non-Hispanic White and Asian American adults following the ACA in California. We first compared outcomes in non-Hispanic White adults with all Asian Americans in our sample, and then evaluated whether we detect disparities when data is disaggregated into five of the most populous ethnic subgroups (Chinese, Korean, Filipino, Vietnamese, and Japanese). Cross-sectional California Health Interview Survey data were collected between January 2014 and December 2016. Our sample included 19,201 non-Hispanic White and 3077 Asian American non-elderly adults age 18 to 64 living in California. Our outcomes were (1) being uninsured, (2) having a usual source of care, (3) delaying necessary medical care, and (4) delaying necessary prescription medications. Using multivariable logistic regression models, we examined our outcomes, adjusting for predisposing, enabling, need, and acculturation factors. Compared with non-Hispanic Whites, some subgroups of Asian Americans reported significantly worse access to care: disaggregated, adjusted analyses revealed that Koreans were significantly less likely to report a usual source of care (adjusted odds ratio [AOR] = 0.31, p < 0.01) relative to non-Hispanic Whites. Chinese (AOR = 0.42, p < 0.01) and Vietnamese (AOR = 0.34, p < 0.01) adults were significantly less likely to delay necessary care. Disaggregated analyses identified differences in access to care for Asian American subgroups following the ACA. State policies to collect disaggregated health data for Asian Americans may reveal heterogeneity in experiences of care and inform specific policies to reduce disparities in access to care.


Consensus on validation of forensic voice comparison.
Since the 1960s, there have been calls for forensic voice comparison to be empirically validated under casework conditions. Since around 2000, there have been an increasing number of researchers and practitioners who conduct forensic-voice-comparison research and casework within the likelihood-ratio framework. In recent years, this community of researchers and practitioners has made substantial progress toward validation under casework conditions becoming a standard part of practice: Procedures for conducting validation have been developed, along with graphics and metrics for representing the results, and an increasing number of papers are being published that include empirical validation of forensic-voice-comparison systems under conditions reflecting casework conditions. An outstanding question, however, is: In the context of a case, given the results of an empirical validation of a forensic-voice-comparison system, how can one decide whether the system is good enough for its output to be used in court? This paper provides a statement of consensus developed in response to this question. Contributors included individuals who had knowledge and experience of validating forensic-voice-comparison systems in research and/or casework contexts, and individuals who had actually presented validation results to courts. They also included individuals who could bring a legal perspective on these matters, and individuals with knowledge and experience of validation in forensic science more broadly. We provide recommendations on what practitioners should do when conducting evaluations and validations, and what they should present to the court. Although our focus is explicitly on forensic voice comparison, we hope that this contribution will be of interest to an audience concerned with validation in forensic science more broadly. Although not written specifically for a legal audience, we hope that this contribution will still be of interest to lawyers.


Targeting DLL4 in tumors shows preclinical activity but potentially significant toxicity.
Evaluation of: Yan M, Callahan CA, Beyer JC et al.: Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6-E7 (2010). Delta-like ligand 4 (DLL4) is a Notch ligand that is critical in the formation of a functional vascular network in tumors. Blockade of DLL4-mediated Notch signaling strikingly increases nonproductive angiogenesis, but significantly inhibits tumor growth in preclinical mouse models. Thus, DLL4 has emerged as an attractive target for cancer therapy. Anti-DLL4 antibodies have recently entered clinical trials. However, the potential toxic effects of anti-DLL4 are poorly understood. In this article, Yan et al. reported that chronic DLL4 blockade abnormally activates endothelial cells, causes pathological changes of multiple organs and induces vascular neoplasms. The findings need confirmation in further studies using different tumor-bearing animals but, nevertheless, raise important safety concerns regarding the use of anti-DLL4 agents and warrant monitoring for these effects in clinical trials for targeting DLL4.


Experiences with ureteroscopy.
Thirty-nine patients underwent 44 ureteroscopic procedures between January 1985 and August 1988 for diagnostic and therapeutic purposes. Twenty six procedures were undertaken on 23 patients for extraction of ureteric calculi and were successful on the initial attempt in 14 (61%). Four stones not removed on the first attempt were however disimpacted and subsequently passed spontaneously, and three more were removed at a second ureteroscopy. The overall success rate therefore was 91%. Only two patients required ureterolithotomy. Ureteroscopic stone extraction is therefore an effective technique with minimal morbidity and allows rapid return of servicemen to high category medical fitness.


Cytotoxicity and apoptosis of ovarian and breast cancer cell lines induced by OVS1 monoclonal antibody and paclitaxel.
OVS1 monoclonal antibody (MAb) produced against ovarian cancer is currently used to identify mucinous cystadenocarcinoma antigen as a tumor marker secreted in serum. The potential of OVS1 MAb in ovarian cancer treatment was studied by evaluating the induction of cytotoxicity and apoptosis of SKOV3 ovarian cancer and BT549 breast cancer cell lines induced by OVS1. Paclitaxel, an antitumor drug, was used as positive control and applied as a combined drug together with OVS1 MAb. OVS1 MAb and paclitaxel were found by MTT assay to induce cytotoxicity against both cell lines. The ED50 of OVS1 MAb were 26.25 and 25.00 microg/ml and of paclitaxel were 21.88 and 9.20 nM against SKOV3 and BT549 cell lines, respectively. The quantitative amount of cells determined by fluorimetric assay was correlated to the results of the MTT assay. The combined application of OVS1 MAb and paclitaxel on these two cell lines resulted in a greater cytotoxicity than observed by either agent alone. OVS1 MAb and paclitaxel applied against both cell lines induced the morphological changes of apoptotic cell death at 24 hours visualized by two color fluorescence dyes, Ho33342 and propidium iodide. Combination of the two substances enhanced the rate of apoptosis compared to either OVS1 MAb or paclitaxel given alone. DNA fragmentation was detected in an agarose gel electrophoresis after treating cells with OVS1 MAb and paclitaxel at 24 hours. These findings on the induction of cytotoxicity and apoptosis by OVS1 MAb on cancer cell lines have implications on the potential application of OVS1 MAb for clinical therapy.


[Hygiene and urban health as seen by physicians, architects and planners during the first half of the twentieth century].
Physicians took part in the promotion of public policies that regulated urban and architectural work, before engineers, architects, planners, and even before the State had a chance to take part in the formulation of such policies. Starting in the late nineteenth century, and especially during the first decade of the twentieth century, the State began to lead on the issue of hygiene and public health. This paper focuses on the role of these professionals, who generated debates within their respective disciplines, or provided -as ministries, public servants or consultants- technical knowledge to the central government. These debates are still relevant for two reasons. First, they serve as reminders of the way in which the voice of these professionals was crucial not only within their respective disciplines, but also in order to place the issue of hygiene and public health on the agenda and to promote public policies related to the urban environment and its population. Secondly, these debates represent a challenge to current planners, as this historic context provides insight on the complex relationship between public health and planning, which hitherto has received little attention.


Neck masses in children: etiopathology in a tertiary center.
Neck masses are common in children; they could present diagnostic challenges, and some may be malignant. This study determines the etiology, histopathology, and outcome of treatment in a Nigerian tertiary center. This is a three-year retrospective study of children managed with neck masses at the University of Benin Teaching Hospital between January 2007 and December 2009. The biodata, side distribution of the masses, clinical conditions of the children at presentation, methods of biopsy, histopathology results, definitive treatment options, follow-up, and outcome were analyzed. A total of 35 children who were aged between one month and 16 years (mean, 8.1 ± 2.6 years) with a male : female ratio of 1.9 : 1 (23 males to 12 females) were managed with 26 (74.3%) acquired and nine (25.7%) congenital neck masses. The masses were located in the anterior triangle in 14 (40%) cases, right side of the neck in 12 (34.3%), and left side of the neck in seven (20%), with two (5.7%) bilateral/confluent. Twelve (34.3%) cases were enlarged lymph nodes; five (41.7%) of them due to malignant lesions. Except for the neck mass, 16 (45.7%) of the children enjoyed clinically stable health on presentation. Twenty (57.1%) acquired tumors were malignant compared with 15 (42.9%) mainly congenital tumors which were benign. Four malignant tumors (11.4%) were rare in anterior triangle. Hodgkin's lymphoma, 9 (25.7%), and thyroglossal duct cyst, 5 (14.3%), were most common malignant and nonmalignant masses, respectively. Surgical excision was curative in 12 (34.3%) cases, but others required additional chemo and/or radiotherapy, with two (5.7%) mortality recorded due to late referral of children with Hodgkin's lymphoma. Many neck masses in otherwise healthy children in our setting were malignant. We advocate early surgical consultation and thorough histopathologic analysis of neck masses in children in our subregion.


Role of the phloem in the biochemistry and ecophysiology of benzylisoquinoline alkaloid metabolism.
Benzylisoquinoline alkaloids (BIAs) are a diverse group of biologically active specialized metabolites produced mainly in four plant families. BIA metabolism is likely of monophyletic origin and involves multiple enzymes yielding structurally diverse compounds. Several BIAs possess defensive properties against pathogenic microorganisms and herbivores. Opium poppy (Papaver somniferum: Papaveraceae) has emerged as a model system to investigate the cellular localization of BIA biosynthesis. Although alkaloids accumulate in the laticifer cytoplasm (latex) of opium poppy, corresponding biosynthetic enzymes and gene transcripts are localized to proximal sieve elements and companion cells, respectively. In contrast, BIA metabolism in the non-laticiferous meadow rue (Thalictrum flavum; Ranunculaceae) occurs independent of the phloem. Evidence points toward the adoption of diverse strategies for the biosynthesis and accumulation of alkaloids as defensive compounds. Recruitment of cell types involved in BIA metabolism, both within and external to the phloem, was likely driven by selection pressures unique to different taxa. The biochemistry, cell biology, ecophysiology, and evolution of BIA metabolism are considered in this context.


Receptor binding of guinea pig and pig vasoactive intestinal peptides by rat lung.
Guinea pig vasoactive intestinal peptide (gpVIP) differs from other mammalian VIPs in four of its 28 amino acid residues. In the present study, the gpVIP displaced 125I-labelled pig VIP (pVIP) binding by rat lung membranes with 7.7-fold lower potency than pVIP. Degradation of gpVIP by rat lung membranes, assessed by radioimmunoassay and h.p.l.c., was 1.9-fold greater than that of pVIP. This difference in degradation of the two peptides was not large enough to account for the lower receptor-binding potency of gpVIP. The amino acid residues that distinguish pVIP from gpVIP are likely to contribute to the interaction of VIP with receptors and peptide hydrolases in lung membranes.


Joint inference of microsatellite mutation models, population history and genealogies using transdimensional Markov Chain Monte Carlo.
We provide a framework for Bayesian coalescent inference from microsatellite data that enables inference of population history parameters averaged over microsatellite mutation models. To achieve this we first implemented a rich family of microsatellite mutation models and related components in the software package BEAST. BEAST is a powerful tool that performs Bayesian MCMC analysis on molecular data to make coalescent and evolutionary inferences. Our implementation permits the application of existing nonparametric methods to microsatellite data. The implemented microsatellite models are based on the replication slippage mechanism and focus on three properties of microsatellite mutation: length dependency of mutation rate, mutational bias toward expansion or contraction, and number of repeat units changed in a single mutation event. We develop a new model that facilitates microsatellite model averaging and Bayesian model selection by transdimensional MCMC. With Bayesian model averaging, the posterior distributions of population history parameters are integrated across a set of microsatellite models and thus account for model uncertainty. Simulated data are used to evaluate our method in terms of accuracy and precision of estimation and also identification of the true mutation model. Finally we apply our method to a red colobus monkey data set as an example.


Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development.
The study of antigenic targets of naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies to 38 P. vivax antigens, investigating their relationship with prospective risk of malaria in a cohort of 1-3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy of antibodies to multiple antigen-combinations, and the antibody thresholds associated with protection were investigated for the first time. High antibody levels to multiple known and newly identified proteins were strongly associated with protection (IRR 0.44-0.74, p<0.001-0.041). Among five-antigen combinations with the strongest protective effect (>90%), EBP, DBPII, RBP1a, CyRPA, and PVX_081550 were most frequently identified; several of them requiring very low antibody levels to show a protective association. These data identify individual antigens that should be prioritized for further functional testing and establish a clear path to testing a multicomponent P. vivax vaccine.


Potentially inappropriate medications and anticholinergic and sedative burden in older patients with haemophilia or von Willebrand disease: The M'HEMORRH-AGE study.
In older patients, multiple chronic conditions lead to the intake of multiple medications and a higher risk of adverse drug events. The exposure to inappropriate medications in older patients with bleeding disorders is poorly explored. The aim of this study was to describe the exposure to potentially inappropriate medications (PIMs) and medications with anticholinergic and sedative properties in older community-dwelling patients with haemophilia or von Willebrand Disease (VWD). The M'HEMORRH-AGE study (Medication in AGEd patients with HAEMORRHagic disease) is a multicentre prospective observational study. Community-dwelling patients over 65 years with haemophilia or VWD were included in the study. PIMs were identified using the EU(7)-PIM list, and the anticholinergic and sedative drug exposure was measured using the Drug Burden Index. 142 older community-dwelling patients with haemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 ± 5.8 years). PIMs were used by 45.8% of older patients and were mainly represented by cardiovascular (34.9%), nervous systems (26.7%) and alimentary tract and metabolism PIMs (25.6%). Regarding anticholinergic and/or sedative medications, 37.3% of older patients were exposed mainly due to nervous system medications (68.3%), for example analgesics. The M'HEMORRH-AGE study showed the exposure to PIMs and anticholinergic/sedative medications was high in older community-dwelling patients with haemophilia or VWD. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.


Inhibition of cellular transport processes by 5-thio-D-glucopyranose.
5-Thio-d-glucopyranose, the nearest analogue of normal d-glucose, which is proving a useful tool in examinations of d-glucose biochemistry, affects active and facilitated-diffusion transport processes. 5-Thio-d-glucose is readily transported in rabbit kidney-cortex slices and reaches a tissue/medium ratio of 6.5 within 40min. The sulphur analogue shows typical saturation kinetics with a K(m) value of 2.4mm and V(max.) value of 70mumol/h per g of cell water. Uptake of 5-thio-d-glucose is phlorrhizin-sensitive, Na(+)-dependent and energy-dependent. d-Galactose and methyl alpha-d-glucopyranoside transport is competitively inhibited by 5-thio-d-glucose with K(i) values of 4.8 and 9.7mm respectively. 5-Thio-d-glucose thus shows all of the characteristics of active transport in kidney cortex. Transport of neutral amino acids in rat kidney cortex is inhibited by 5-thio-d-glucose. Thus 5.6mm-5-thio-d-glucose causes a 25-30% inhibition of the transport of glycine and the non-metabolized amino acids cycloleucine and alpha-aminoisobutyric acid. 5-Thio-d-glucose is freely taken up by the facilitated-diffusion transport system in rat diaphragm muscle. The sulphur analogue inhibits the transport of d-xylose in this tissue but has no effect on the uptake of d-arabinose. It is concluded that the ring heteroatom is not an effector of binding in the transport processes examined and causes no important alteration in the conformation of the sugar. The diabetogenic action produced by 5-thio-d-glucose is due, in part, to the ability of the analogue to interfere with cellular transport processes that use d-glucose.


Specific and Sensitive Diagnosis of BCOR-ITD in Various Cancers by Digital PCR.
BCOR is an epigenetic regulator altered by various mechanisms including BCOR-internal tandem duplication (BCOR-ITD) in a wide range of cancers. Six different BCOR-ITD in the 3'-part of the coding sequence of exon 15 have been reported ranging from 89 to 114 bp in length. BCOR-ITD is a common genetic alteration found in clear cell sarcoma of the kidney and primitive myxoid mesenchymal tumor of infancy (PMMTI) and it characterizes a new type of central nervous system tumor: "CNS tumor with BCOR-ITD". It can also be detected in undifferentiated round cell sarcoma (URCS) and in high-grade endometrial stromal sarcoma (HGESS). Therefore, it is of utmost importance to search for this genetic alteration in these cancers with the most frequent technique being RNA-sequencing. Here, we developed a new droplet PCR assay (dPCR) to detect the six sequences characterizing BCOR-ITD. To achieve this goal, we used a single colored probe to detect both the duplicated region and the normal sequence that acts as a reference. We first generated seven synthetic DNA sequences: ITD0 (the normal sequence) and ITD1 to ITD6 (the duplicated sequences described in the literature) and then we set up the optima dPCR conditions. We validated our assay on 19 samples from a representative panel of human tumors (9 HGNET-BCOR, 5 URCS, 3 HGESS, and 2 PMMTI) in which BCOR-ITD status was known using at least one other method including RNA sequencing, RT-PCR or DNA-methylation profiling for CNS tumors. Our results showed that our technique was 100% sensitive and specific. DPCR detected BCOR-ITD in 13/19 of the cases; in the remaining 6 cases additional RNA-sequencing revealed BCOR gene fusions. To conclude, in the era of histomolecular classification of human tumors, our modified dPCR assay is of particular interest to detect BCOR-ITD since it is a robust and less expensive test that can be applied to a broad spectrum of cancers that share this alteration.


Genetic architecture and functional characterization of genes underlying the rapid diversification of male external genitalia between Drosophila simulans and Drosophila mauritiana.
Male sexual characters are often among the first traits to diverge between closely related species and identifying the genetic basis of such changes can contribute to our understanding of their evolutionary history. However, little is known about the genetic architecture or the specific genes underlying the evolution of male genitalia. The morphology of the claspers, posterior lobes, and anal plates exhibit striking differences between Drosophila mauritiana and D. simulans. Using QTL and introgression-based high-resolution mapping, we identified several small regions on chromosome arms 3L and 3R that contribute to differences in these traits. However, we found that the loci underlying the evolution of clasper differences between these two species are independent from those that contribute to posterior lobe and anal plate divergence. Furthermore, while most of the loci affect each trait in the same direction and act additively, we also found evidence for epistasis between loci for clasper bristle number. In addition, we conducted an RNAi screen in D. melanogaster to investigate if positional and expression candidate genes located on chromosome 3L, are also involved in genital development. We found that six of these genes, including components of Wnt signaling and male-specific lethal 3 (msl3), regulate the development of genital traits consistent with the effects of the introgressed regions where they are located and that thus represent promising candidate genes for the evolution these traits.


SCID mouse models of human stem cell engraftment.
The discovery of the severe combined immunodeficiency (scid) mouse mutation has provided a tool for establishment of small animal models as hosts for the in vivo analysis of normal and malignant human pluripotent hemopoietic stem cells. Intravenous injection of irradiated scid mice with human bone marrow, cord blood, or G-CSF cytokine-mobilized peripheral blood mononuclear cells, all rich in human hemopoietic stem cell activity, results in the engraftment of a human hemopoietic system in the murine recipient. This model has been used to identify a pluripotent stem cell, termed "scid-repopulating cell" (SRC) that is more primitive than any of the hemopoietic stem cell populations identified using the currently available in vitro methodology. In this review, we describe the development and use of this model system, termed Hu-SRC-SCID, and summarize the discoveries that have resulted from the investigation of human stem cells in this model. Finally, we detail the recent extension of the original Hu-SRC-SCID model system based on the C.B-17-scid mouse as the murine host to the Hu-SRC-NOD-SCID model based on the NOD-scid mouse as the host. The engraftment of human stem cells in the Hu-SRC-NOD-SCID model is enhanced over that observed in the Hu-SRC-SCID model and results in exceptionally high levels of human hemopoietic cells in the murine recipient. Future directions to further improve the Hu-SRC-NOD-SCID model system and the potential utility of this model in the preclinical and diagnostic arenas of hematology and oncology are discussed.


Hydrogen-rich water and caffeine for alertness and brain metabolism in sleep-deprived habitual coffee drinkers.
The main aim of this randomized-controlled cross-over interventional trial was to assess the acute effects of taking a single dose of hydrogen-rich water (HRW), and compare it with caffeine, HRW plus caffeine, and control water, for alertness, brain metabolism, brain and oxygen saturation, and self-reported adverse events in healthy men and women who were habitual coffee drinkers and were sleep-deprived for 24 hr. Sixteen apparently healthy young adults (8 men and 8 women; age 24.0 ± 3.5 years) were allocated in a cross-over design to receive a single-dose drink of HRW (8 ppm), caffeine (50 mg), HRW plus caffeine, or control drink (tap water) in the morning after 24-hr sleep deprivation and 12-hr fasting. The primary and secondary outcomes were assessed at baseline (pre-intervention) and 15-min follow-up. Significantly less time was needed to complete trail-making test after both HRW and HRW plus caffeine compared with the control drink (p < .05). The number of errors in the symbol digit modalities test was significantly lower after drinking HRW or caffeine than control drink (p < .05). Both HRW and caffeine significantly increased the choline-to-creatine ratio in several brain regions (frontal white and gray matter), while HRW and the combination intervention also affected brain metabolism in the paracentral brain. No participants reported any side effects from any intervention. The attention enhancement driven by HRW appears along with changes in brain metabolism. Being generally recognized as a safe intervention, hydrogen could be thus recommended as a novel intervention that upholds attention in stressed conditions, with its metabolic footprint likely different from caffeine.


The need for speed in advanced non-small cell lung cancer: A population kinetics assessment.
Systemic therapy prolongs overall survival (OS) in advanced non-small cell lung cancer (NSCLC), but diagnostic tests, staging and molecular profiling take time, and this can delay therapy initiation. OS approximates first-order kinetics. We used OS of chemo-naive NSCLC patients on a placebo/best supportive care trial arm to estimate % of patients dying while awaiting therapy. We digitized survival curves from eight studies, calculated OS half-life, then estimated the proportion surviving after different times of interest (tn ) using the formula: X=exp-tn∗0.693/t1/2 , where EXP signifies exponential, * indicates multiplication, 0.693 is the natural log of 2, and t1/2 is the survival half-life in weeks. Across trials, the OS half-life for placebo/best supportive care in previously untreated NSCLC was 19.5 weeks. Hence, based on calculations using the formula above, if therapy were delayed by 1, 2, 3, or 4 weeks then 4%, 7%, 10%, and 13% of all patients, respectively, would die while awaiting treatment. Others would become too sick to consider therapy even if still alive. This quantifies why rapid baseline testing and prompt therapy initiation are important in advanced NSCLC. It also illustrates why screening procedures for clinical trial inclusion must be faster. Otherwise, it is potentially hazardous for a patient to be considered for a trial due to risk of death or deterioration while awaiting eligibility assessment. It is also important to not delay initiation of systemic therapy for procedures that add relatively little value, such as radiotherapy for small, asymptomatic brain metastases.


Five-year follow-up of drug-eluting stents implantation vs minimally invasive direct coronary artery bypass for left anterior descending artery disease: a propensity score analysis.
The spread of drug-eluting stents (DES) has reduced the incidence of early restenosis following percutaneous coronary interventions (PCI). Meanwhile, development of minimally invasive coronary artery bypass surgery (MIDCAB) has offered a valuable alternative to conventional sternotomy with preservation of the benefit of the internal mammary artery use. Therefore, the revascularization of the left anterior descending (LAD) artery is suitable for both techniques. However, few data with long-term comparison of these two techniques exist. Prospective data were collected for 456 patients undergoing isolated LAD revascularization between 1997 and 2011. Two hundred and sixty patients were treated with MIDCAB and 196 with first-generation DES implantation. A propensity score model was created to adjust for 19 relevant confounding variables. Primary and secondary end-points were, respectively, 5-year survival and freedom from major adverse cerebro-cardiovascular events (MACCE). Both groups were similar in age, EuroSCORE and mean duration of follow-up. Five-year survival was similar after MIDCAB or DES (hazard ratio (HR): 0.95; P = 0.89). Freedom from MACCE was significantly in favour of the MIDCAB group (HR: 0.32, P < 0.0001), mainly triggered by high subsequent need for revascularization of the targeted vessel in the DES group (HR: 0.17, P < 0.0001). MIDCAB and DES implantation showed similar rates of survival but despite an expected lower rate of reintervention on the targeted vessel with DES use, a highly significant higher MACCE rate was observed in the PCI group at 5-year follow-up.


An overview of studies on early development, cognition, and psychosocial well-being in children born after in vitro fertilization.
To examine whether sufficient research has been done and definite conclusions can be drawn on the psychological outcome of children born after in vitro fertilization (IVF), a review was performed of studies on early development, cognition, and psychosocial well-being in IVF children. PubMed and PsycINFO databases were searched. All English language studies up to 2006 addressing these topics were included. After 25 years of follow-up studies on the development, school outcome, and psychosocial well-being of IVF children, it seems that mental and psychomotor development during the first year and preschool years and cognitive development at 5 years are not deviant. At 6-12 years of age, no differences were observed in cognitive and school performance compared with naturally conceived children; however, the number of studies in this age group is limited. No studies are available that evaluate cognitive aspects and school performance at secondary school age. Overall, positive parent-child relationships were reported in IVF families. In some studies, IVF mothers report more difficulties with their child's behavior only in the child's first year. With regard to the children's psychosocial well-being, no differences were found up to the age of 8 years. Although after that age, slight indications for some socioemotional and behavioral problems emerged, a large study on the onset of puberty reported that psychosocial functioning was reassuring. Data for adolescents are still lacking. Psychological functioning of those born after IVF is reassuring. However, follow-up should be continued and studies should focus on specific cognitive abilities, school performance, and emotional functioning in adolescence.


Utilizing extracorporeal membrane oxygenation and surfactant in the management of severe acute respiratory distress syndrome due to hydrocarbon pneumonitis.
Severe cases of hydrocarbon aspiration requiring Extracorporeal Membrane Oxygenation (ECMO) are rarely reported in pediatrics, and 90% of hospitalized patients have a relatively benign clinical course. We describe a 14 month-old female with accidental hydrocarbon ingestion and aspiration due to organic makeup brush cleaner that suffered severe ARDS and multiorgan failure, successfully managed with ECMO and surfactant. She was decannulated after a total of 72 hours on ECMO, extubated on hospital day 15 (HD 15), and discharged home in her normal state of health after one month in the hospital. ECMO and adjunctive therapies such as surfactant may be helpful in the management of severe hydrocarbon pneumonitis and there are limited reports of ECMO as a supportive method for these pediatric patients.


Dynein tethers and stabilizes dynamic microtubule plus ends.
Microtubules undergo alternating periods of growth and shortening, known as dynamic instability. These dynamics allow microtubule plus ends to explore cellular space. The "search and capture" model posits that selective anchoring of microtubule plus ends at the cell cortex may contribute to cell polarization, spindle orientation, or targeted trafficking to specific cellular domains. Whereas cytoplasmic dynein is primarily known as a minus-end-directed microtubule motor for organelle transport, cortically localized dynein has been shown to capture and tether microtubules at the cell periphery in both dividing and interphase cells. To explore the mechanism involved, we developed a minimal in vitro system, with dynein-bound beads positioned near microtubule plus ends using an optical trap. Dynein induced a significant reduction in the lateral diffusion of microtubule ends, distinct from the effects of other microtubule-associated proteins such as kinesin-1 and EB1. In assays with dynamic microtubules, dynein delayed barrier-induced catastrophe of microtubules. This effect was ATP dependent, indicating that dynein motor activity was required. Computational modeling suggests that dynein delays catastrophe by exerting tension on individual protofilaments, leading to microtubule stabilization. Thus, dynein-mediated capture and tethering of microtubules at the cortex can lead to enhanced stability of dynamic plus ends.


Separation of solid tumor cell populations.
Separation of subpopulations of cells from mouse solid tumors has been achieved with two methods: centrifugal elutriation and equilibrium density centrifugation. Elutriation resulted in enrichment of normal cells, and of tumor cells in specific cell cycle phases. Density centrifugation appeared to separate the well-oxygenated from the chronically hypoxic cells. These methods have been used to determine in vivo the cell-cycle phase-dependent cytotoxicity of chemotherapeutic drugs toward tumor cells.


Microplastic pollution in lakes and lake shoreline sediments - A case study on Lake Bolsena and Lake Chiusi (central Italy).
Rivers and effluents have been identified as major pathways for microplastics of terrestrial sources. Moreover, lakes of different dimensions and even in remote locations contain microplastics in striking abundances. This study investigates concentrations of microplastic particles at two lakes in central Italy (Lake Bolsena, Lake Chiusi). A total number of six Manta Trawls have been carried out, two of them one day after heavy winds occurred on Lake Bolsena showing effects on particle distribution of fragments and fibers of varying size categories. Additionally, 36 sediment samples from lakeshores were analyzed for microplastic content. In the surface waters 2.68 to 3.36 particles/m(3) (Lake Chiusi) and 0.82 to 4.42 particles/m(3) (Lake Bolsena) were detected, respectively. Main differences between the lakes are attributed to lake characteristics such as surface and catchment area, depth and the presence of local wind patterns and tide range at Lake Bolsena. An event of heavy winds and moderate rainfall prior to one sampling led to an increase of concentrations at Lake Bolsena which is most probable related to lateral land-based and sewage effluent inputs. The abundances of microplastic particles in sediments vary from mean values of 112 (Lake Bolsena) to 234 particles/kg dry weight (Lake Chiusi). Lake Chiusi results reveal elevated fiber concentrations compared to those of Lake Bolsena what might be a result of higher organic content and a shift in grain size distribution towards the silt and clay fraction at the shallow and highly eutrophic Lake Chiusi. The distribution of particles along different beach levels revealed no significant differences.


Challenges to evidence-based health promotion: a case study of a Food Security Coalition in Ontario, Canada.
Developing the evidence base for health promotion can be challenging because interventions often have to target competing determinants of health, including social, structural, environmental and political determinants; all of which are difficult to measure and thus evaluate. Drawing on a case study of food insecurity, which refers to inadequate access to food due to financial constraints, we illustrate the challenges faced by community-based organizations in collecting data to form an evidence base for the development and evaluation of collective programmes aimed at addressing food insecurity. Interviews were conducted with members of a multi-stakeholder coalition (n = 22 interviewees; n = 10 organizations) who collectively work to address food insecurity in their community through a range of community-based programmes and services. Member organizations also provided a list of measures currently used to inform programme and service development and evaluation. Data were collected in a city in Southern Ontario, Canada between May and September 2015. Participants identified four barriers to collecting data: Organizational needs and philosophies; concerns surrounding clientele wellbeing and dignity; issues of feasibility; and restrictive requirements imposed by funding bodies. Participants also discussed their previous successes in collecting meaningful data for identifying impact. Our results point to the challenge of generating data suitable for developing and evaluating programmes aimed at broader determinants of health, while maintaining the primary goal of meeting clients' needs. Documenting change at intermediate- and macro-levels would provide evidence for the collective effectiveness of current programmes and services offered. However, appropriate resources need to be invested to allow for scientific evaluation.


Modulating the hydrophobicity of cellulose by lipase-catalyzed transesterification.
The production of hydrophobic and oil resistant cellulosic fibers usually requires severe chemical treatments and generates toxic by-products. Alternative approaches such as biocatalysis use milder conditions; lipase-catalyzed methods for grafting nanocellulose with hydrophobic ester moieties have been reported. Here, we investigate the lipase-catalyzed esterification of cellulose fibers, in native form or pretreated with 1,4-β-glucanases, and cellulose nanocrystals (CNC) in solvent-free conditions. The fibers were compared for degree of ester formation after incubation with methyl myristate and lipase at 50 °C. After washing, the grafting of fatty esters on cellulose was confirmed by ATR-FTIR and the degree of substitution determined by 13C CP/MAS NMR (from 0.04 up to DS 0.1) confirming successful esterification. Optical photothermal infrared (O-PTIR) spectroscopy showed strongly localized presence of ester moieties on cellulose. Functional properties mirrored the degree of substitution of the cellulose materials whereby cellulose esters made with glucanase-pretreatment produced the highest water contact angle of 117° ± 9 and esterified cellulose blended at 10 % w/w content in paper composites showed significant differences in hydrophobicity and lipophilicity compared to plain paper. The esterification of cellulose was completely reversed by lipase treatment in aqueous media. These ester-functionalized fibers show potential in a wide range of packaging applications.


Bioenergetic and autophagic control by Sirt3 in response to nutrient deprivation in mouse embryonic fibroblasts.
Sirt3 (sirtuin 3) is an NAD-dependent deacetylase localized to mitochondria. Sirt3 expression is increased in mouse muscle and liver by starvation, which could protect against the starvation-dependent increase in oxidative stress and protein damage. Damaged proteins and organelles depend on autophagy for removal and this is critical for cell survival, but the role of Sirt3 is unclear. To examine this, we used Sirt3-KO (knockout) mouse embryonic fibroblast cells, and found that, under basal conditions, Sirt3-KO cells exhibited increased autophagy flux compared with WT (wild-type) cells. In response to nutrient deprivation, both WT and KO cells exhibited increased basal and ATP-linked mitochondrial respiration, indicating an increased energy demand. Both cells exhibited lower levels of phosphorylated mTOR (mammalian target of rapamycin) and higher autophagy flux, with KO cells exhibiting lower maximal mitochondrial respiration and reserve capacity, and higher levels of autophagy than WT cells. KO cells exhibit higher phospho-JNK (c-Jun N-terminal kinase) and phospho-c-Jun than WT cells under starvation conditions. However, inhibition of JNK activity in Sirt3-KO cells did not affect LC3-I (light chain 3-I) and LC3-II levels, indicating that Sirt3-regulated autophagy is independent of the JNK pathway. Caspase 3 activation and cell death are significantly higher in Sirt3-KO cells compared with WT cells in response to nutrient deprivation. Inhibition of autophagy by chloroquine exacerbated cell death in both WT and Sirt3-KO cells, and by 3-methyadenine exacerbated cell death in Sirt3-KO cells. These data suggest that nutrient deprivation-induced autophagy plays a protective role in cell survival, and Sirt3 decreases the requirement for enhanced autophagy and improves cellular bioenergetics.


Conditions of pressure scanning of a Fabry-Perot interferometer over a wide spectrum range.
The association of a Michelson interferometer and a Fabry-Perot etalon enables the control of the displacement of the peaks of Fabry-Perot transmittance by pressure scanning through Michelson fringes counting. Assuming the variations of the refractive index of gas as a function of wavenumber, pressure, and temperature are known, we show that it is perfectly possible to compute the number of fringes to shift in order to position a chosen peak of Fabry-Perot transmittance for any point in the spectrum. These possibilities enable us to build a real spectrometer whose accuracy is better than 0.05 cm(-1) in the whole visible range.


Regulation of intracellular pH in avian renal proximal tubules.
In proximal tubules isolated from chicken transitional nephrons, intracellular pH (pHi), measured with the pH-sensitive fluorescent dye 2'.7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF), was approximately 7.3-7.4 under control conditions [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium with pH 7.4 at 39 degrees C] and was reduced to approximately 6.8 in response to NH4Cl pulse. The rate of recovery of pHi (dpHi/dt) from this acid level to the resting level and the resting pHi were 1) significantly reduced by the removal of Na+ from the bath, 2) significantly increased by the removal of Cl from the bath, and 3) unchanged by the removal of both Na+ and Cl from the bath. The addition of either amiloride or 4,4'-diisothiocyanostilbene-2,2'-disulfonate to the bath reduced dpHi/dt to about the same extent as the removal of Na+. These data suggest that both Na(+)-coupled and Cl-coupled acid-base fluxes at the basolateral membrane are involved in determining the resting pHi and the rate of recovery of pHi after acidification. The most likely possibilities appear to be a basolateral Na+/Hi exchanger, a basolateral Na(+)-coupled Cl/HCO3 exchanger, a basolateral Na(+)-HCO3(-)CO(3)2 cotransporter, and a basolateral Na(+)-independent Cl-/HCO3 exchanger.


"Doing" mindsets in the classroom: A coding scheme for teacher and student mindset-related verbalizations.
There is a growing body of research showing the crucial role that students' growth versus fixed ability-mindsets have in their school achievement, enjoyment, and resilience. The overwhelming majority of this research adopts a variable-oriented approach. As a result, little is known about how teachers and students coregulate each other's mindsets within classroom interactions. This manuscript addresses the need for more person-oriented research that examines how teachers and students do mindsets in naturalistic settings, i.e., their mindsetrelated verbalizations. In this manuscript, we provide a coding scheme to study the moment-to-moment dynamics of mindset-related verbalizations of both teachers and students within Science, Technology, Engineering, and Mathematics (STEM) contexts: The STEAM (Student-TEAcherMindset) coding scheme. We demonstrate the utility of the coding system through content and ecological validity, inter-rater reliability, and a case study of STEAM-generated time-series data. We show how these data can be used to chart moment-to-moment dynamics that occur between teacher and student. The coding scheme provides teachers and researchers with a practical tool for analyzing how person-specific mindset-related language can wax and wane in the context of peer and teacher interactions within STEM lessons.


Secretory Carcinoma of Breast: A Population-Based Study.
In this study, it was aimed to evaluate the characteristic features and survival of secretory carcinoma of the breast (SCB), which is one of the rare malignant tumors of the breast. Data of patients with histopathological diagnosis of SCB between 2010 and 2019 were extracted from the SEER database. These patients were evaluated in terms of age, race, molecular subtype, grade, estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, TNM stage, surgical status, chemotherapy and radiotherapy treatment. Overall survival (OS) and breast cancer-specific survival (BCSS) of the whole population and subgroups [in terms of surgery procedure (mastectomy/breast-conserving surgery), and hormone receptor status (positive/negative)] were analyzed. 70 patients were included in the study. The mean age was 57 years (range 2-82). 32.9% of the patients were diagnosed under the age of 50. 97.1% of the patients were female; 2.9% were male. The vast majority of patients were white race (81.4%). Although the rates of localization were higher in the upper outer quadrant (31.4%), centrally located tumors (18.5%) were also quite common. The most frequently detected molecular subtype was hormone positive/HER2 negative. All patients were non-metastatic, 81.4% of patients did not have lymph node metastases, and most of the patients were stage IA. Median follow-up was 37 months (range 0-118 months). Considering all patients, OS was 76.3%, 5-year OS was 91.8%, and BCSS was 88%, 5-year BCSS was 97.8%. There was no statistically significant difference in OS and BCSS according to subgroups (P > .01). SCB, a rare histopathologic type, has high OS and BCSS rates.


Anticoagulation clinics: the Italian experience.
The clinical quality of oral anticoagulant therapy (OAT) depends on how successful physicians and patients are in achieving and maintaining levels of anticoagulation capable of preventing thromboembolic events without increasing the risk of hemorrhagic complications. Concerning the patient, education and compliance are the major problems. As for the physician, on the other hand, the management of patients receiving OAT is a complex task that requires frequent laboratory testing, dosage regulation, prompt diagnosis and treatment of thromboembolic and hemorrhagic events. It requires educated and skilled personnel and a well-organized framework of services. Anticoagulation clinics, which provide patient education, close monitoring of prothrombin time and continuous clinical surveillance, may help in improving the overall quality of OAT. The authors have been working in this field contributing, original papers. In addition, the material examined in this article includes articles published in the journals covered by the Science Citation Index and Medline. The concept of a coordinated network of medical services specifically devoted to the control of OAT was developed in the Netherlands following the model created by the late Professor Jordan, who in 1949 founded the first thrombosis center at the University of Utrecht. Many other anticoagulant clinics were organized on, a voluntary basis in the following decades in the Netherlands. The Dutch Federation of Thrombosis Centers was founded in 1971 and each affiliated Center is formally recognized and supported by the central Government. Today, there is a nation-wide system of regionally centralized anticoagulant control for outpatients and home patients that counts approximately 70 anticoagulant clinics (thrombosis centers), covering more than 90% of the country. Similar global approaches to the management of patients receiving OAT were proposed in other countries. In the 1950's, a group of internists and surgeons at the University of Michigan, USA, developed a unit specifically devoted to the diagnosis and treatment of thromboembolic disease, and proposed common strategies, teaching and research programs. In 1959, Sevitt and Gallagher were the first to propose a formal recognition of an anticoagulant unit in Great Britain. Finally, the Italian Federation of Centers for the Surveillance of Anticoagulant (FCSA) therapies was founded in 1989. Nowadays, Italian anticoagulation clinics operating in the framework of the FCSA are still voluntary organizations which provide a specific medical service by continuously reorganizing the personnel, structures and resources available to meet increasing demands. Since OAT has a profound social impact, its control should not be left to the good will of dedicated people, but should instead represent a specific task of the public health system. The achievement of a formal recognition of federated centers is essential for their growth, but the unavoidable increase of the expenses needed to support anticoagulation clinics is difficult to bear in a public care system which is currently facing a substantial reduction of financial resources. In a fixed health care budget, a redistribution of existing resources is the only possible solution, but to achieve this goal, public authorities have to be convinced that the management of OAT in specific anticoagulation clinics is cost-effective. A more accurate estimate of costs is needed and should be performed by the FCSA. Finally, the FCSA should strengthen its contacts with patient organizations and other scientific associations in order to develop common action strategies for improving the quality of OAT.


Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.
Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.


Status of the Regional Nodal Basin Remains Highly Prognostic in Melanoma Patients with In-Transit Disease.
The role of SLNB for in-transit (IT) melanoma is controversial. The objective of this study was to determine the rate and prognostic significance of occult nodal disease in patients undergoing surgical nodal staging for IT disease. We conducted a retrospective review of patients with IT melanoma from May 2005 through September 2014. Analysis was limited to patients with a first-time IT event who underwent surgical excision. Associations between clinicopathologic characteristics, patterns of recurrence, and survival were analyzed. A total of 261 patients treated at our center were identified and 157 met inclusion criteria, of which 135 (86%) presented with no evidence of nodal disease. At the time of surgical excision of the IT lesion, 80 (58%) clinically node-negative patients underwent observation of the nodal basin and 55 (41%) surgical nodal staging. Twenty (36%) clinically node-negative but surgically staged patients were found to have nodal disease. Distant metastasis-free survival was 70.8 months for surgically staged node-negative patients, 19.2 months for surgically staged node-positive patients, 22.8 months for those staged node-negative by clinical examination only and 4.8 months for those with clinical nodal disease (p = 0.01). The regional nodal basin was the first site of failure in 14 of 66 (21%) clinically staged patients, 5 of 50 (10%) for those surgically staged, and 6 of 16 (38%) for those with clinical nodal disease. Patients with IT disease are at high risk for occult nodal metastasis. Because clinical staging is unreliable, SLNB should be considered. For patients with IT recurrence, the status of the regional basin is strongly prognostic and stratifies patients into low-, intermediate-, and high-risk groups.


Identification of a novel inhibitor of dengue virus protease through use of a virtual screening drug discovery Web portal.
We report the discovery of a novel small-molecule inhibitor of the dengue virus (DENV) protease (NS2B-NS3pro) using a newly constructed Web-based portal (DrugDiscovery@TACC) for structure-based virtual screening. Our drug discovery portal, an extension of virtual screening studies performed using IBM's World Community Grid, facilitated access to supercomputer resources managed by the Texas Advanced Computing Center (TACC) and enabled druglike commercially available small-molecule libraries to be rapidly screened against several high-resolution DENV NS2B-NS3pro crystallographic structures. Detailed analysis of virtual screening docking scores and hydrogen-bonding interactions between each docked ligand and the NS2B-NS3pro Ser135 side chain were used to select molecules for experimental validation. Compounds were ordered from established chemical companies, and compounds with established aqueous solubility were tested for their ability to inhibit DENV NS2B-NS3pro cleavage of a model substrate in kinetic studies. As a proof-of-concept, we validated a small-molecule dihydronaphthalenone hit as a single-digit-micromolar mixed noncompetitive inhibitor of the DENV protease. Since the dihydronaphthalenone was predicted to interact with NS2B-NS3pro residues that are largely conserved between DENV and the related West Nile virus (WNV), we tested this inhibitor against WNV NS2B-NS3pro and observed a similar mixed noncompetitive inhibition mechanism. However, the inhibition constants were ∼10-fold larger against the WNV protease relative to the DENV protease. This novel validated lead had no chemical features or pharmacophores associated with adverse toxicity, carcinogenicity, or mutagenicity risks and thus is attractive for additional characterization and optimization.


Nanometer-Resolved Fluidity of an Oleophilic Monomer between Silica Surfaces Modified with Fluorinated Monolayers for Nanoimprinting.
Ultraviolet (UV) nanoimprinting has the potential to fabricate sub-15 nm resin patterns, but the interfacial fluidity of organic monomers near monomer liquid/mold solid interfaces related to filling nanoscale mold recesses with UV-curable resins still remains unclear. In this study, we demonstrated that surface forces and resonance shear measurements were helpful to select a surface modifier appropriate for silica mold surfaces for UV nanoimprinting with the low-viscosity monomer 1,10-decanediol diacrylate. Surface forces between silica surfaces mediated with the diacrylate monomer and fluidities of the monomer were investigated with nanometer resolution. Chemical vapor surface modification of silica surfaces with chlorodimethyl(3,3,3-trifluoropropyl)silane (FAS3-Cl) and tridecafluoro-1,1,2,2-tetrahydrooctyltrimethoxysilane (FAS13) gave fluorinated silica surfaces with root-mean-square roughness of less than 0.24 nm suitable for the measurements. When the distance D between two silica surfaces was decreased stepwise in the range of 0-30 nm, monomer viscosity between cleaned silica surfaces increased markedly at D < 6 nm. Surface modification with FAS3-Cl suppressed this increase of interfacial monomer viscosity. In contrast, FAS13-modified silica surfaces caused a jump-in phenomenon at approximately D = 7-9 nm, suddenly decreasing to D = 1 nm as the monomer fluid layer was squeezed out. We concluded that FAS3-Cl was appropriate as a fluorinated surface modifier for silica molds used in UV nanoimprinting with an oleophilic low-viscosity monomer, because the chemisorbed monolayer maintained low monomer viscosity near the surface/monomer interface, in addition to its low surface free energy and short CF3CH2CH2- group.


The cancer prevention and control research network: An interactive systems approach to advancing cancer control implementation research and practice.
Although cancer research has advanced at a rapid pace, a gap remains between what is known about how to improve cancer prevention and control (CPC) and what is implemented as best practices within health care systems and communities. The Cancer Prevention and Control Research Network (CPCRN), with more than 10 years of dissemination and implementation research experience, aims to accelerate the uptake and use of evidence-based CPC interventions. The collective work of the CPCRN has facilitated the analysis and categorization of research and implementation efforts according to the Interactive Systems Framework for Dissemination and Implementation (ISF), providing a useful heuristic for bridging the gap between prevention research and practice. The ISF authors have called for examples of its application as input to help refine the model. We provide examples of how the collaborative activities supported by the CPCRN, using community-engaged processes, accelerated the synthesis and translation of evidence, built both general and innovation-specific capacity, and worked with delivery systems to advance cancer control research and practice. The work of the CPCRN has provided real-world examples of the application of the ISF and demonstrated that synthesizing and translating evidence can increase the potential that evidence-based CPC programs will be used and that capacity building for both the support system and the delivery system is crucial for the successful implementation and maintenance of evidence-based cancer control. Adoption and implementation of CPC can be enhanced by better understanding ISF systems and intervening to improve them.


Does enthesopathy relate to M694V gene mutation in patients with Familial Mediterranean fever?
Familial Mediterranean fever (FMF) is a systemic hereditary autoinflammatory disorder. The present study aimed to investigate the relationship of enthesitis to FMF and to search the potential association between enthesitis and MEFV gene missense variations in patients with FMF. The study consisted of 72 FMF patients (mean age 29.12 ± 11.47 years, 32 females), 29 patients with ankylosing spondylitis (AS) (mean age 34.14 ± 11.73 years, 16 females), and 34 healthy volunteers (mean age 23.06 ± 6.41 years, 8 females). FMF patients were classified according to the kind of MEFV gene mutation. Doppler ultrasound was used to determine enthesitis based on the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system. OMERACT score was significantly different between FMF patients and control group (p < 0.001 in all patients, p = 0.009 in men, and p = 0.002 in women). However, it was not significantly different between FMF and AS patients in both sexes. OMERACT score did not differ between FMF patients with and without M694V gene mutation. The best cutoff point of OMERACT score to predict enthesitis was found as ≥0.5 with sensitivity of 29 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 40 %.


Bioavailability of Micronutrients from Plant Foods: An Update.
Deficiencies of iron, zinc, iodine and vitamin A are widespread in the developing countries, poor bioavailability of these micronutrients from plant-based foods being the major reason for their wide prevalence. Diets predominantly vegetarian are composed of components that enhance as well as inhibit mineral bioavailability, the latter being predominant. However, prudent cooking practices and use of ideal combinations of food components can significantly improve micronutrient bioavailability. Household processing such as heat treatment, sprouting, fermentation and malting have been evidenced to enhance the bioavailability of iron and β-carotene from plant foods. Food acidulants amchur and lime are also shown to enhance the bioavailability of not only iron and zinc, but also of β-carotene. Recently indentified newer enhancers of micronutrient bioaccessibility include sulphur compound-rich Allium spices-onion and garlic, which also possess antioxidant properties, β-carotene-rich vegetables-carrot and amaranth, and pungent spices-pepper (both red and black) as well as ginger. Information on the beneficial effect of these dietary compounds on micronutrient bioaccessibility is novel. These food components evidenced to improve the bioavailability of micronutrients are common ingredients of Indian culinary, and probably of other tropical countries. Fruits such as mango and papaya, when consumed in combination with milk, provide significantly higher amounts of bioavailable β-carotene. Awareness of the beneficial influence of these common dietary ingredients on the bioavailability of micronutrients would help in devising dietary strategies to improve the bioavailability of these vital nutrients.


Reovirus virion-like particles obtained by recoating infectious subvirion particles with baculovirus-expressed sigma3 protein: an approach for analyzing sigma3 functions during virus entry.
Structure-function studies with mammalian reoviruses have been limited by the lack of a reverse-genetic system for engineering mutations into the viral genome. To circumvent this limitation in a partial way for the major outer-capsid protein sigma3, we obtained in vitro assembly of large numbers of virion-like particles by binding baculovirus-expressed sigma3 protein to infectious subvirion particles (ISVPs) that lack sigma3. A level of sigma3 binding approaching 100% of that in native virions was routinely achieved. The sigma3 coat in these recoated ISVPs (rcISVPs) appeared very similar to that in virions by electron microscopy and three-dimensional image reconstruction. rcISVPs retained full infectivity in murine L cells, allowing their use to study sigma3 functions in virus entry. Upon infection, rcISVPs behaved identically to virions in showing an extended lag phase prior to exponential growth and in being inhibited from entering cells by either the weak base NH4Cl or the cysteine proteinase inhibitor E-64. rcISVPs also mimicked virions in being incapable of in vitro activation to mediate lysis of erythrocytes and transcription of the viral mRNAs. Last, rcISVPs behaved like virions in showing minor loss of infectivity at 52 degrees C. Since rcISVPs contain virion-like levels of sigma3 but contain outer-capsid protein mu1/mu1C mostly cleaved at the delta-phi junction as in ISVPs, the fact that rcISVPs behaved like virions (and not ISVPs) in all of the assays that we performed suggests that sigma3, and not the delta-phi cleavage of mu1/mu1C, determines the observed differences in behavior between virions and ISVPs. To demonstrate the applicability of rcISVPs for genetic studies of protein functions in reovirus entry (an approach that we call recoating genetics), we used chimeric sigma3 proteins to localize the primary determinants of a strain-dependent difference in sigma3 cleavage rate to a carboxy-terminal region of the ISVP-bound protein.


Chronic illness self-care and the family lives of older adults: a synthetic review across four ethnic groups.
The purpose of this paper is to integrate the literature on family and social ties among older ethnic minority men and women with the literature on chronic illness self-care among elders in these groups, in order to increase understanding of social influences on self-care behavior, raise questions for future research, and inform culturally appropriate interventions to maximize the health-promoting potential of social relationships. The paper presents demographic and chronic illness prevalence information, and then summarizes literature about patterns of chronic illness self-care behaviors for older African-Americans, Latinos, Asian-Americans, and American Indians in the U.S. For each group, the sociological literature about residential, cultural, and socioeconomic patterns, family lives, and other social ties is then reviewed, and the self-care literature that has accounted for these patterns is discussed. Finally, six themes are outlined and related questions are identified to further illuminate the social context of older adults' chronic illness self-care.


Socioeconomic status differences in health behaviors related to obesity: the Healthy Worker Project.
Obesity and health behaviors that influence energy balance (diet, exercise, and dieting to lose weight) were examined in a population of 2108 and 2539 working men and women in relation to socioeconomic status (SES). The hypothesis investigated was that the inverse relationship between SES and obesity observed in a number of studies is due to the fact that the distribution of obesity relevant health behaviors differs by social class. Body mass index (BMI), as expected, was found to be inversely related to SES. Higher SES was also associated with several behaviors that contribute importantly to energy balance. High SES respondents reported a lower fat diet, more exercise, and a higher prevalence of dieting to control weight. However, lower smoking rates were observed in upper SES men and women and higher alcohol consumption was reported in upper SES women. Both of these associations appear to be inconsistent with the hypothesis that the inverse association between SES and obesity is caused by differences in health behaviors. In multiple regression analyses, SES remained a significant predictor of BMI after controlling for all measured health behaviors. Weaknesses in the methodologies for measuring health behaviors and possible effects of obesity itself on social mobility are suggested as possible explanations for the residual association between obesity and SES.


Pregnancy-induced hypertension and neonatal outcomes: a systematic review and meta-analysis.
Pregnancy-induced hypertension (PIH) is associated with preterm delivery but its independent impact on neonatal outcomes remains unclear. We sought to systematically review and meta-analyze clinical outcomes of preterm infants <37 weeks' gestation born to mothers with and without PIH. Medline, Embase, PsychINFO and CINAHL were searched from January 2000 to October 2016. Studies with low-moderate risk of bias reporting neonatal outcomes based on PIH as primary exposure variable were included. Data were extracted independently by two co-authors. PIH was associated with lower mortality (3 studies; adjusted odds ratio (aOR) 0.65; 95% confidence interval (CI) 0.54 to 0.79), lower severe retinopathy of prematurity (ROP) (2 studies; aOR 0.83; 0.72 to 0.96) and lower severe brain injury (2 studies; unadjusted OR (uOR) 0.57; 0.49 to 0.66). No association between PIH and short-term respiratory outcomes, bronchopulmonary dysplasia (BPD) or necrotizing enterocolitis (NEC) was identified. In subgroup analysis among infants <29 weeks' gestation, BPD odds were higher (3 studies; aOR 1.15; 1.06 to 1.26), whereas mortality lower (2 studies; aOR 0.73; 0.69 to 0.77). In subgroup analysis limited to severe PIH, odds of mortality (3 studies; uOR 2.36; 1.07 to 5.22) and invasive ventilation (3 studies; uOR 3.26; 1.11 to 9.61) were higher. In subgroup analysis limited to preeclampsia, odds of BPD (3 studies; uOR 1.21; 95% CI:1.03 to 1.43) and NEC were higher (3 studies; uOR 2.79; 95% CI:1.57 to 4.96). PIH was associated with reduced odds of mortality and ROP (all infants), but higher odds for BPD (<29 weeks' gestation). The paradoxical reduction in mortality may be due to survival bias and deserves further exploration in future studies.


Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn.
In 1992, the Committee on Infectious Diseases and Committee on Fetus and Newborn of the American Academy of Pediatrics provided guidelines for prevention of early-onset group B streptococcal (GBS) disease through intrapartum chemoprophylaxis of selected maternal GBS carriers. The guidelines were based on demonstrated efficacy in randomized, controlled clinical trials and selected only women with GBS colonization who had an obstetric risk factor. The guidelines were controversial and their implementation incomplete. Since 1992, additional data have become available, and experience with the guidelines has been gained in numerous medical centers. Recently, consensus guidelines were developed by obstetricians, pediatricians, family practitioners, and public health authorities and published by the Centers for Disease Control and Prevention. These recommendations are supported by the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics. This statement reviews the selection of pregnant women for chemoprophylaxis and provides an algorithm for management of their newborns.


IL-2-granzyme A chimeric protein overcomes multidrug resistance (MDR) through a caspase 3-independent apoptotic pathway.
One of the main problems of conventional anticancer therapy is multidrug resistance (MDR), whereby cells acquire resistance to structurally and functionally unrelated drugs following chemotherapeutic treatment. One of the main causes of MDR is overexpression of the P-glycoprotein transporter. In addition to extruding the chemotherapeutic drugs, it also inhibits apoptosis through the inhibition of caspases. To overcome MDR, we constructed a novel chimeric protein, interleukin (IL)-2 granzyme A (IGA), using IL-2 as a targeting moiety and granzyme A as a killing moiety, fused at the cDNA level. IL-2 binds to the high-affinity IL-2 receptor that is expressed in an array of abnormal cells, including malignant cells. Granzyme A is known to cause caspase 3-independent cell death. We show here that the IGA chimeric protein enters the target sensitive and MDR cancer cells overexpressing IL-2 receptor and induces caspase 3-independent cell death. Specifically, after its entry, IGA causes a decrease in the mitochondrial potential, triggers translocation of nm23-H1, a granzyme A-dependent DNase, from the cytoplasm to the nucleus, where it causes single-strand DNA nicks, thus causing cell death. Moreover, IGA is able to overcome MDR and kill cells resistant to chemotherapeutic drugs. We believe that overcoming MDR with targeted molecules such as IGA chimeric protein that causes caspase-independent apoptotic cell death could be applied to many other resistant types of tumors using the appropriate targeting moiety. Thus, this novel class of targeted molecules could open up new vistas in the fight against human cancer.


[Updating of the distribution of Aedes albopictus in Brazil (1997-2002)].
Updating regarding the distribution of Aedes albopictus in Brazil is presented for the period from 1997 to 2002. Data from the yellow fever and dengue information system of the National Health Foundation is utilized. It can be seen that this species is present in 20 of the 27 Brazilian states.


Natural transformation of Myxococcus xanthus.
Myxococcus xanthus belongs to the delta class of the proteobacteria and is notable for its complex life-style with social behaviors and relatively large genome. Although previous observations have suggested the existence of horizontal gene transfer in M. xanthus, its ability to take up exogenous DNA via natural transformation has not been experimentally demonstrated. In this study, we achieved natural transformation in M. xanthus using the autonomously replicating myxobacterial plasmid pZJY41 as donor DNA. M. xanthus exopolysaccharide (EPS) was shown to be an extracellular barrier for transformation. Cells deficient in EPS production, e.g., mutant strains carrying ΔdifA or ΔepsA, became naturally transformable. Among the inner barriers to transformation were restriction-modification systems in M. xanthus, which could be partially overcome by methylating DNA in vitro using cell extracts of M. xanthus prior to transformation. In addition, the incubation time of DNA with cells and the presence of divalent magnesium ion affected transformation frequency of M. xanthus. Furthermore, we also observed a potential involvement of the type IV pilus system in the DNA uptake machinery of M. xanthus. The natural transformation was totally eliminated in the ΔpilQ/epsA and Δtgl/epsA mutants, and null mutation of pilB or pilC in an ΔepsA background diminished the transformation rate. Our study, to the best of our knowledge, provides the first example of a naturally transformable species among deltaproteobacteria.


Complement-Dependent Activity of CD20-Specific IgG Correlates With Bivalent Antigen Binding and C1q Binding Strength.
Monoclonal antibodies directed against the CD20 surface antigen on B cells are widely used in the therapy of B cell malignancies. Upon administration, the antibodies bind to CD20 expressing B cells and induce their depletion via cell- and complement-dependent cytotoxicity or by induction of direct cell killing. The three antibodies currently most often used in the clinic are Rituximab (RTX), Ofatumumab (OFA) and Obinutuzumab (OBI). Even though these antibodies are all of the human IgG1 subclass, they have previously been described to vary considerably in the effector functions involved in therapeutic B cell depletion, especially in regards to complement activation. Whereas OFA is known to strongly induce complement-dependent cytotoxicity, OBI is described to be far less efficient. In contrast, the role of complement in RTX-induced B cell depletion is still under debate. Some of this dissent might come from the use of different in vitro systems for characterization of antibody effector functions. We therefore set out to systematically compare antibody as well as C1q binding and complement-activation by RTX, OFA and OBI on human B cell lines that differ in expression levels of CD20 and complement-regulatory proteins as well as human primary B cells. Applying real-time interaction analysis, we show that the overall strength of C1q binding to live target cells coated with antibodies positively correlated with the degree of bivalent binding for the antibodies to CD20. Kinetic analysis revealed that C1q exhibits two binding modes with distinct affinities and binding stabilities, with exact numbers varying both between antibodies and cell lines. Furthermore, complement-dependent cell killing by RTX and OBI was highly cell-line dependent, whereas the superior complement-dependent cytotoxicity by OFA was independent of the target B cells. All three antibodies were able to initiate deposition of C3b on the B cell surface, although to varying extent. This suggests that complement activation occurs but might not necessarily lead to induction of complement-dependent cytotoxicity. This activation could, however, initiate complement-dependent phagocytosis as an alternative mechanism of therapeutic B cell depletion.


Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions.
Molecular pathological epidemiology (MPE) is an integrative molecular and population health science that addresses the molecular pathogenesis and heterogeneity of disease processes. The MPE of colonic and rectal premalignant lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas, villous adenomas, traditional serrated adenomas, sessile serrated adenomas/sessile serrated polyps, and hamartomatous polyps) can provide unique opportunities for examining the influence of diet, lifestyle, and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model by which both malignant epithelial tumor (carcinoma) and its precursor are subjected to molecular pathological analyses. KRAS, BRAF, and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation are commonly examined tumor biomarkers. Future opportunities include interrogation of comprehensive genomic, epigenomic, or panomic datasets, and the adoption of in vivo pathology techniques. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed information on tumor location is important. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. The MPE of colorectal premalignant lesions can identify etiologic exposures associated with neoplastic initiation and progression, help us better understand colorectal carcinogenesis, and facilitate personalized prevention, screening, and therapy.


[CT-guided percutaneous intratumoral chemotherapy with a novel cisplatin/epinephrine injectable gel for the treatment of inoperable malignant liver tumors].
To evaluate prospectively the volumetric changes of tumor and necrosis in unresectable malignant liver tumors and the clinical aspects after CT-guided direct intratumoral administration of a novel cisplatin/epinephrine injectable gel in a clinical phase II study. 8 patients with 17 colorectal liver metastases with a mean volume of 42 ml were treated with a mean of 5.1 injections and 8 patients with 11 HCC nodules (mean volume of 22.1 ml) with a mean of 3.25 treatments with CT-guided local administration of a novel cisplatin/epinephrine gel. This method of administration provides a higher local and lower systemic drug concentration. Volumes of tumor and necrosis prior to and after treatment were measured by computer-generated volumetric analysis. Contrast-enhanced studies verified pretherapeutic tumor necrosis with a value of 12.6% in the metastases and 0.6% in the HCC nodules. Intratumoral drug administration resulted in a necrotic volume of 110% in metastases and 128% in HCC versus the mean initial tumor volume, at least 4 treatments resulted in 122% necrosis in metastases and 130% in HCC. Local therapy control rate for the follow-up to 6 months was 38% and 83.3% for the group of metastases and HCC, respectively. Direct intratumoral injection of a novel cisplatin/epinephrine injectable gel results in an induction of a relevant necrosis in malignant liver tumors, with a substantially higher local therapy control rate for HCC compared to colorectal metastases.


Microfocus x-ray imaging of traceable pointlike (22)Na sources for quality control.
The purpose of this study is to propose a microfocus x-ray imaging technique for observing the internal structure of small radioactive sources and evaluating geometrical errors quantitatively, and to apply this technique to traceable pointlike (22)Na sources, which were designed for positron emission tomography calibration, for the purpose of quality control of the pointlike sources. A microfocus x-ray imaging system with a focus size of 0.001 mm was used to obtain projection x-ray images and x-ray CT images of five pointlike source samples, which were manufactured during 2009-2012. The obtained projection and tomographic images were used to observe the internal structure and evaluate geometrical errors quantitatively. Monte Carlo simulation was used to evaluate the effect of possible geometrical errors on the intensity and uniformity of 0.511 MeV annihilation photon pairs emitted from the sources. Geometrical errors were evaluated with sufficient precision using projection x-ray images. CT images were used for observing the internal structure intuitively. As a result, four of the five examined samples were within the tolerance to maintain the total uncertainty below ±0.5%, given the source radioactivity; however, one sample was found to be defective. This quality control procedure is crucial and offers an important basis for using the pointlike (22)Na source as a basic calibration tool. The microfocus x-ray imaging approach is a promising technique for visual and quantitative evaluation of the internal geometry of small radioactive sources.


Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function.
Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development.


Nursing Students' Lived Experiences of Attending LeBoyer Birth.
The purpose of this study was to understand the lived experiences of nursing students' during Leboyer. Eleven senior nursing students were recruited from April to June in 2010. After completing informed consents, data were collected through in-depth interviews. All interviews were recorded and transcribed verbatim before analyzing. Nursing students were asked about their observational experiences during Leboyer births. Data were analyzed by using the Colaizzi style. Interviews revealed 4 categories and 9 themes. The categories were: 'Respecting and blessing new baby', 'Keeping calm and joyful birth atmosphere', 'Reminding the meaning of nursing', 'Comparing Leboyer and convenience birth and making up their mind'. This study showed that observation of Leboyer birth is helpful for nursing students in order to have positive impression about childbirth. Furthermore, it is suggested that an exploration of the experiences of women and their husbands during Leboyer births would be helpful. On the basis of this study, it is concluded that the Leboyer birth, which focuses on baby's human right, should be introduced women's health nursing field as an effective birth strategy.


Synthesis, restriction analysis, and molecular cloning of near full length DNA complementary to bovine parathyroid hormone mRNA.
DNA complementary (cDNA) to a partially purified preparation of bovine parathyroid hormone mRNA was synthesized using avian myeloblastosis viral reverse transcriptase. The PTH cDNA contained about 750 bases and was greater than 95% sensitive to digestion by S1 nuclease. Analysis of the mRNA preparation by excess RNA hybridization to the PTH cDNA revealed one rapidly hybridizing component consisting of 50% of the PTH cDNA. Sequential incubation of the PTH mRNA with reverse transcriptase and E. coli DNA polymerase I produced near full length double-stranded PTH cDNA. Of the 22 restriction endonucleases tested, double-stranded PTH cDNA could be cleaved with Alu I, Mbo II, Sau 3A, Sst I, and Taq I. The restriction fragments corresponding to the 5' terminus of the sense strand were identified for the last three enzymes by comparing the size of fragments obtained from PTH cDNA before and after cleavage of the hairpin loop connecting the two strands by S1 nuclease. The restriction map of the cDNA was used to detect clones of bacteria containing recombinant plasmids with near full length PTH cDNA inserts.


Changing experiences of work dirtiness, occupational disidentification, and employee withdrawal.
Research and theory concerning "dirty work" has largely focused on how employees cope with stable features of their jobs. From a study of employees' experiences across 6 weekly repeated measurements, we found that within-person increases in experienced dirtiness were positively related to their withdrawal behaviors and job change propensity indirectly through occupational disidentification. Assessed at the between-subjects level, team-oriented leadership moderated the indirect within-person effects of work dirtiness experiences on these outcomes. The relationships between elevations in experienced work dirtiness and occupational disidentification were more strongly positive at lower levels of team-oriented leadership. Analyses also showed that individuals' perceptions of occupational stigma independently moderated the within-person relationship between experienced dirtiness and occupational disidentification. We discuss theoretical implications for the literature on dirty work and practical implications for mitigating the adverse outcomes associated with experienced work dirtiness. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Comparison of pain responses in infants of different gestational ages.
There is a plethora of infant pain measures; however, none of them have been validated for extremely low for gestational age (ELGA) infants (<27 weeks' gestation). To date, clinicians, researchers and parents use information gleaned from more mature infants to make inferences about pain in ELGA infants. Using physiological or behavioral pain indicators derived from more mature infants may lead to inaccurate assessments and management. To compare physiological (heart rate, oxygen saturation) and behavioral (9 facial activities, cry) pain indicators of ELGA infants with infants of varying more mature gestational ages (GAs). The aim was to determine the effects of GA on pain response. GA was categorized into four mutually exclusive strata: <27 6/7 weeks, 28-31 6/7 weeks, 32-35 6/7 weeks and >36 weeks. Physiological data during four phases of a routine heel lance were collected by placing disposable ECG electrodes and pulse oximetry probes on the infant's chest. Behavioral data were collected by videotaping facial activities, and cry data were collected by audio recording. Four facial activities (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch) in response to acute pain were present in ELGA infants. Facial activities increased following painful procedures and the magnitude of responses was proportional to GA with the youngest infants (<27 6/7 weeks GA) showing the least amount of change. Decreased oxygen saturation and increased heart rate were associated with the most invasive phase of the heel lance; however, the differences were neither clinically or statistically significant across age groups. Cry was not a sensitive pain indicator in ELGA infants, due to the presence of endotracheal tubes in this high-risk population. ELGA infants have similar pain responses to older infants, but the responses are dampened. Other factors such as severity of illness, frequency of painful procedures or medication use should be examined, as they may influence the pain responses in ELGA infants.


Multicenter study with ketanserin in essential hypertension: an Argentine experiment.
One thousand eleven patients with essential hypertension (H) were evaluated upon compliance with the following inclusion criteria: (a) mild to moderate uncomplicated H, with supine diastolic blood pressure (Su DBP) greater than 90 mm Hg at the end of the placebo period, with or without antihypertensive treatment; (b) greater than 20 years old. The dosage of ketanserin (K) was 20 mg b.i.d. up to the fourth week. Afterwards, if the patients normalized, we continued with the same schedule. If this did not occur, the dosage was increased (40 mg b.i.d.) up to the eighth week. Four hundred fifty-one men and 560 women were included, with a mean age of 56.6 years, mean body weight 74.8 kg, and mean height 166.30 cm. At the end of the eighth week, the percentage of normalization was 75.5% of the patients, and the percentage of partial responders was 5.6%. The decrease of the blood pressure (diastolic and systolic) was significant at the second week (paired t test, two-tailed probability, p less than or equal to 0.001). There were 62 dropouts: 10 due to inefficacy, 14 due to adverse reaction, and 38 due to other reasons. Laboratory examinations were performed before and after treatment and did not show statistical differences. Also, a 12-lead ECG was performed before and after treatment with K. The QTc was analyzed in a sample of 140 patients and did not show statistically significant changes. The incidence of side effects was minimal (24% of the patients, n = 224), mild, and transient; only 1% of the patients dropped out due to adverse reactions. In our experience, ketanserin was an effective and safe drug, to be used primarily for the treatment of mild to moderate H.


Chemotherapy for advanced ovarian cancer. Advanced Ovarian Cancer Trialists Group.
Ovarian carcinoma is the seventh most common cancer of women in the world and is responsible for the greatest number of deaths from gynaecological malignancy in Europe and North America. Although many studies have explored the use of chemotherapy in this disease, most individual trials have been too small to show clear benefit of one type of chemotherapy over another. The type and intensity of chemotherapy used routinely for women with advanced ovarian cancer has varied because of uncertainty about the effectiveness of the different regimens. The objective of this review was to compare single drugs versus combinations of drugs, platinum versus non-platinum, and carboplatin versus cisplatin-based chemotherapy in women with advanced ovarian cancer. Search strategy: We searched MEDLINE, and CancerLit bibliographic databases and the National Cancer Institute and the UK Co-ordinating Committee on Cancer Research registers of trials. We also handsearched the proceedings of meetings and contacted experts in the field and drug companies. Randomised trials of: (1) single non-platinum versus non-platinum combination chemotherapy (2) single non-platinum versus platinum combination chemotherapy (3) non-platinum regimen versus the same regimen plus cisplatin (4) single platinum versus platinum combination chemotherapy (5) cisplatin versus carboplatin-based chemotherapy in women with advanced ovarian cancer. Individual patient data were obtained from the trial investigators, checked by the reviewers and finally verified by the trial investigator. Main results: 49 trials involving 8763 women were included. The data were combined to calculate hazard ratios (HR) for survival on an intention-to-treat basis. For single non-platinum versus platinum combination chemotherapy the overall HR for survival was 0.93, 95% confidence interval (CI) 0.83-1.05 in favour of platinum-based combination chemotherapy. For non-platinum regimens compared with the same regimen plus cisplatin the survival HR was 0.88, 95% CI 0.79- 0.98 in favour of the addition of platinum to drug regimens. Single platinum compared with platinum combination therapy gave a HR of 0.91, 95% CI 0.79-1.05 in favour of combination chemotherapy. Cisplatin versus carboplatin gave a HR of 1.02, 95% CI 0.93-1.12. Sub-group analyses for age, stage, grade, histology, resection, bulk of residual tumour and performance status were undertaken for cisplatin versus carboplatin only. No difference in effect was found. The available evidence, although not conclusive, suggests that platinum-based chemotherapy is better than non-platinum therapy. There is some evidence that combination therapy improves survival compared with platinum alone. No difference in effect has been shown between cisplatin and carboplatin.


Identification and quantification of phenolic and flavonoid components in straw and seed husk of some rice varieties (Oryza sativa L.) and their antioxidant properties.
Plant foods are rich sources of bioactive compounds that can act as antioxidants to prevent heart disease, reduce inflammation, reduce the incidence of cancers and diabetes. This study aimed to determine the phenolics and flavonoids profiling in three varieties of rice straw and five varieties of the seed husk of Iranian rice using high-performance liquid chromatography (HPLC). Furthermore, the antioxidant activities of the extracts were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and nitric oxide assays. HPLC analyses showed that the gallic acid, pyrogallol, apigenin and rutin were the main phenolic and flavonoid compounds in all varieties of rice. In addition, the methanolic extracts of Hashemi and Ali Kazemi varieties showed the highest amounts of phenolic and flavonoid contents, respectively. Rice straw and husk of Iranian varieties showed considerable antioxidant activity and Hashemi indicated significantly (P < 0.01) higher DPPH and nitric oxide free radical scavenging activities when compared to the other varieties. The present study revealed that rice straw and seed husk of Iranian varieties shows high antioxidant activities and they contain various types of phenolic and flavonoid compounds that could be use in food and medical industries.


Antioxidant effect of retinoic acid on PC12 rat pheochromocytoma.
Retinoic acid is a naturally occurring metabolite of vitamin A that influences the differentiation of a variety of neural cells in vitro. In the LA-N-1 human neuroblastoma line, retinoic acid treatment increases the binding of nerve growth factor (Bmax). The purpose of this study was to examine the effects of retinoic acid on PC12 rat pheochromocytoma, a neural crest-derived cell line that can be induced to express a sympathetic neuroblast-like phenotype by nerve growth factor treatment. In contrast to the differentiating effects of nerve growth factor, retinoic acid treatment of PC12 cells had a negligible effect on cellular morphology. However, treatment with retinoic acid enhanced the survival of PC12 cells following oxidative injury generated by H2O2 treatment in a manner that is qualitatively similar to that observed after nerve growth factor treatment. Also, there was an increase in 125I-nerve growth factor binding activity in solubilized PC12 membrane preparations derived from retinoic acid-treated PC12 cells. These data suggest that retinoic acid may play a role in neuronal development and in neuronal injury by stimulating the ability of neurons to cope with oxidative stress and/or by enhancing neuronal responsiveness to trophic factors such as the nerve growth factor.