Highly Stretchable, Directionally Oriented Carbon Nanotube/PDMS Conductive Films with Enhanced Sensitivity as Wearable Strain Sensors.
Recent interest in the fields of human motion monitoring, electronic skin, and human-machine interface technology demands strain sensors with high stretchability/compressibility (ε > 50%), high sensitivity (or gauge factor (GF > 100)), and long-lasting electromechanical compliance. However, current metal- and semiconductor-based strain sensors have very low (ε < 5%) stretchability or low sensitivity (GF < 2), typically sacrificing the stretchability for high sensitivity. Composite elastomer sensors are a solution where the challenge is to improve the sensitivity to GF > 100. We propose a simple, low-cost fabrication of mechanically compliant, physically robust metallic carbon nanotube (CNT)-polydimethylsiloxane (PDMS) strain sensors. The process allows the alignment of CNTs within the PDMS elastomer, permitting directional sensing. Aligning CNTs horizontally (HA-CNTs) on the substrate before embedding in the PDMS reduces the number of CNT junctions and introduces scale-like features on the CNT film perpendicular to the tensile strain direction, resulting in improved sensitivity compared to vertically-aligned CNT-(VA-CNT)-PDMS strain sensors under tension. The CNT alignment and the scale-like features modulate the electron conduction pathway, affecting the electrical sensitivity. Resulting GF values are 594 at 15% and 65 at 50% strains for HA-CNT-PDMS and 326 at 25% and 52 at 50% strains for VA-CNT-PDMS sensors. Under compression, VA-CNT-PDMS sensors show more sensitivity to small-scale deformation than HA-CNT-PDMS sensors due to the CNT orientation and the continuous morphology of the film, demonstrating that the sensing ability can be improved by aligning the CNTs in certain directions. Furthermore, mechanical robustness and electromechanical durability are tested for over 6000 cycles up to 50% tensile and compressive strains, with good frequency responses with negligible hysteresis. Finally, both types of sensors are shown to detect small-scale human motions, successfully distinguishing various human motions with reaction and recovery times of as low as 130 ms and 0.5 s, respectively.


Cytokine-induced senescence for cancer surveillance.
The immune response is a first-line systemic defense to curb tumorigenesis and metastasis. Much effort has been invested to design antitumor interventions that would boost the immune system in its fight to defeat or contain cancerous growth. Tumor vaccination protocols, transfer of tumor-associated-antigen-specific T cells, T cell activity-regulating antibodies, and recombinant cytokines are counted among a toolbox filled with immunotherapeutic options. Although the mechanistic underpinnings of tumor immune control remain to be deciphered, these are studied with the goal of cancer cell destruction. In contrast, tumor dormancy is considered as a dangerous equilibrium between cell proliferation and cell death. There is, however, emerging evidence that tumor immune control can be achieved in the absence of overt cancer cell death. Here, we propose cytokine-induced senescence (CIS) by transfer of T helper-1 cells (TH1) or by recombinant cytokines as a novel therapeutic intervention for cancer treatment. Immunity-induced senescence triggers a stable cell cycle arrest of cancer cells. It engages the immune system to construct defensive, isolating barriers around tumors, and prevents tumor growth through the delivery or induction of TH1-cytokines in the tumor microenvironment. Keeping cancer cells in a non-proliferating state is a strategy, which directly copes with the lost homeostasis of aggressive tumors. As most studies show that even after efficient cancer therapies minimal residual disease persists, we suggest that therapies should include immune-mediated senescence for cancer surveillance. CIS has the goal to control the residual tumor and to transform a deadly disease into a state of silent tumor persistence.


Structure and function of neonatal social communication in a genetic mouse model of autism.
A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup-mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.


Modeling of femtosecond pulse propagation inside x-cut and z-cut MgO doped LiNbO3 anisotropic crystals.
A four-dimensional spatiotemporal nonlinear Schrödinger equation coupled with a plasma equation is solved for anisotropic crystal of MgO doped lithium niobate. The modeling is performed for x-cut and z-cut lithium niobate crystals commonly used for waveguide writing by femtosecond lasers. The effect of various parameters such as energy, duration, and polarization of the incident laser pulse on distribution of the plasma density in the vicinity of focus is studied. Our simulations reveal that the maximum plasma density in the vicinity of the focus is higher for longer pulse durations and higher pulse energies. Furthermore, it is observed that for the same peak powers of the incident pulse, the plasma density generated inside the crystal is higher for linear polarization as compared to circular polarization.


Aedes mosquito saliva modulates Rift Valley fever virus pathogenicity.
Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated. Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract. C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays. After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice. Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.


Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production.
Initial alterations in fetal hemoglobin (HbF) production among eight sickle cell anemia subjects treated with hydroxyurea (Hu) are summarized. Four of these subjects had been previously treated with 5-azacytidine (5-aza). All subjects treated with Hu (50 mg/kg/d for three to five days) had suppression of their total reticulocyte counts by seven days, whereas the four subjects previously treated with 5-aza (2 mg/kg/d for three to five days) had increased reticulocyte counts at day 7. The effect of Hu on increasing the number of HbF-containing reticulocytes (F reticulocytes) is extremely variable, ranging from ten-to less than onefold differences in maximal posttherapy v pretherapy levels. Recovery from marrow suppression did not result in greater than twofold increases in F reticulocyte counts. Mean day 7 F reticulocyte levels in the four subjects treated with both Hu and 5-aza were 4.1 X 10/microL and 15.4 X 10(4)/microL, respectively. Among Hu-treated subjects, increased F reticulocyte production was correlated with low serum creatinine levels and rapid removal of Hu from the plasma. Furthermore, suppression of CFU-E colony formation on day 2 of therapy with Hu was inversely correlated with maximal F reticulocyte response. We conclude that where Hu treatment results in marrow toxicity (decreased reticulocyte counts, decreased CFU-E colony formation) HbF production is less likely to increase. Those sickle cell anemia subjects with minimal renal dysfunction (serum creatinine level, greater than 1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu.


Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.
We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.


Feasibility of Social Distancing Practices in US Schools to Reduce Influenza Transmission During a Pandemic.
Schools are socially dense environments, and school-based outbreaks often predate and fuel community-wide transmission of seasonal and pandemic influenza. While preemptive school closures can effectively reduce influenza transmission, they are disruptive and currently recommended only for pandemics. We assessed the feasibility of implementing other social distancing practices in K-12 schools as a first step in seeking an alternative to preemptive school closures. We conducted 36 focus groups with education and public health officials across the United States. We identified and characterized themes and compared feasibility of practices by primary versus secondary school and region of the United States. Participants discussed 29 school practices (25 within-school practices implemented as part of the school day and 4 reduced-schedule practices that impact school hours). Participants reported that elementary schools commonly implement several within-school practices as part of routine operations such as homeroom stay, restriction of hall movement, and staggering of recess times. Because of routine implementation and limited use of individualized schedules within elementary schools, within-school practices were generally felt to be more feasible for elementary schools than secondary schools. Of reduced-schedule practices, shortening the school week and the school day was considered the most feasible; however, reduced-schedule practices were generally perceived to be less feasible than within-school practices for all grade levels. Our findings suggest that schools have many options to increase social distance other than closing. Future research should evaluate which of these seemingly feasible practices are effective in reducing influenza transmission in schools and surrounding communities.


Etiology of chylothorax in 203 patients.
To characterize the etiology of chylothorax in patients encountered at a single tertiary referral center and to compare the findings with those from previous studies. The medical records of all patients with chylothorax seen at the Mayo Clinic in Rochester, Minn, over a 21-year period, from January 1, 1980, to December 31, 2000, were retrospectively reviewed to ascertain the underlying cause of their condition. We identified 203 patients with chylothorax; 92 were females (male-female ratio, 1.21). The median age was 54.5 years (range, 21 weeks' gestation to 93 years). Dyspnea, the most common presenting symptom, occurred in 98 (56.6%) of 173 patients in whom initial symptoms were recorded, whereas 64 (37.0%) had no respiratory symptoms. Median duration of symptoms before diagnosis was 7.5 weeks (range, 1 day to 4.5 years). Causes of chylothorax included surgery or trauma in 101 patients (49.8%), various medical conditions in 89 (43.8%), and unknown in 13 (6.4%). Among surgical procedures, esophagectomy (29 patients) and surgery for congenital heart disease (28 patients) were the most common causes of chylothorax. Among medical conditions, lymphoma (23 patients), lymphatic disorders (19 patients), and chylous ascites (16 patients) were the most common causes. Chylothorax has numerous causes. In contrast to previous studies, surgery or trauma was the most common cause of chylothorax at our institution, accounting for nearly 50% of cases. Lymphoma and other malignancies caused chylothorax in only 16.7% of cases. These numbers are possibly related to the high volume of cardiothoracic surgical procedures performed at our tertiary referral center.


Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models.
Purpose: Estrogen receptor-positive (ER+) breast cancers are typically treated with endocrine agents, and dependence on the ER pathway is often retained even after multiple rounds of antiestrogen therapy. Selective estrogen receptor degraders (SERD) are being developed as a strategy to more effectively target ER and exploit ER dependence in these cancers, which includes inhibiting both wild-type and mutant forms of ER. The purpose of this study was to evaluate the efficacy of a novel orally bioavailable SERD, elacestrant (RAD1901), in preclinical models of ER+ breast cancer.Experimental Design: Elacestrant was evaluated as a single agent and in combination with palbociclib or everolimus in multiple ER+ breast cancer models, including several patient-derived xenograft models.Results: Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo, and significantly inhibits tumor growth of multiple PDX models. Furthermore, we demonstrate that elacestrant in combination with palbociclib or everolimus can lead to greater efficacy in certain contexts. Finally, elacestrant exhibits significant antitumor activity both as a single agent and in combination with palbociclib in two patient-derived breast cancer xenograft models harboring ESR1 mutations.Conclusions: These data underscore the potential clinical utility of elacestrant as a single agent and as a combination therapy, for both early- and late-stage ER+ disease. Clin Cancer Res; 23(16); 4793-804. ©2017 AACR.


Incontinentia pigmenti presenting as encephalopathy.
Incontinentia Pigmenti is a rare neurocutaneous disorder that may present with neurological symptoms in early infancy in addition to characteristic skin rashes. We report a two-mo-old girl presenting with a rash and encephalopathy. Magnetic resonance imaging of brain showed hemorrhagic infarcts. First we thought baby was suffering from a skin infection with meningo-encephalitis and later with development of characteristic skin lesions, neuroimaging and skin biopsy changes we reconsidered our diagnosis as Incontinentia pigmenti.


Experimental setup for the identification of mitochondrial protease substrates by shotgun and top-down proteomics.
Mitochondria possess a proteolytic system that contributes to the regulation of mitochondrial dynamics, mitochondrial biogenesis and mitophagy. We aimed at the identification by bottom-up proteomics of altered protein processing due to the activation of mitochondrial proteases in a cellular model of impaired dopamine homeostasis. Moreover, we optimized the conditions for top-down proteomics to identify the cleavage site sequences.


Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest.
Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21(Cip1), p27(Kip1), p15(INK4B), and p16(INK4A)) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors.


Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.
Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). A total of 100 obese women aged 33-51 years with BMI ≥ 28 kg/m² and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n = 50) or identical placebo (n = 50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. At 12 weeks, a total of 92 participants completed this trail. Compared with the placebo group (n = 47), histidine supplementation significantly decreased HOMA-IR (-1.09 [95% CI -1.49, -0.68]), BMI (-0.86 kg/m² [95% CI -1.55, -0.17]), waist circumference (-2.86 cm [95% CI -3.86, -1.86]), fat mass (-2.71 kg [95% CI -3.69, -1.73]), serum NEFA (-173.26 μmol/l [95% CI -208.57, -137.94]), serum inflammatory cytokines (TNF-α, -3.96 pg/ml [95% CI -5.29, -2.62]; IL-6, -2.15 pg/ml [95% CI -2.52, -1.78]), oxidative stress (superoxide dismutase, 17.84 U/ml [95% CI 15.03, 20.65]; glutathione peroxidase, 13.71 nmol/ml [95% CI 9.65, 17.78]) and increased serum histidine and adiponectin by 18.23 μmol/l [95% CI 11.74, 24.71] and 2.02 ng/ml [95% CI 0.60, 3.44] in histidine supplementation group (n = 45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes.


Selective prophylactic solvent-detergent plasma and cryoprecipitate transfusion to prevent intraventricular hemorrhage in extreme preterm infants: A case-historical control.
Contradictory evidence exists whether a prophylactic coagulation factor transfusion in the first hours of life (HOL) prevents intraventricular hemorrhage (IVH) in extreme preterm infants (EPI, <28 weeks gestation). We aimed to determine whether selective prophylactic solvent-detergent plasma and cryoprecipitate transfusion within 12 hours of life (SP-SDP/Cryoprecipitate-T) could prevent IVH in EPI. This is a retrospective analysis, case-historical control, of prospectively collected data from a pre-existing electronic neonatal database at a Saudi tertiary neonatal intensive care unit. We compared the IVH rate in EPI born in the first 4 years (Jan 2010-Dec 2013) of the SP-SDP/Cryoprecipitate-T period with that of EPI born during the last 4 years (Jan 2006-Dec 2009) of the rescue SDP/Cryoprecipitate-T period. The IVH rate was lower in the SP compared to the rescue- SDP/Cryoprecipitate-T period (30.8% versus 51.2%, odds ratio 0.42, 95% confidence interval 0.21, 0.88, p = 0.02). This difference remained significant after controlling for six other IVH risk factors. Early SP-SDP/Cryoprecipitate-T may reduce the IVH rate in EPI. A large multicenter clinical trial is required for confirm the short and long-term benefit and risk of this intervention. Until then, early SP-SDP/Cryoprecipitate-T may be considered by an institution with a persistently high IVH rate.


Barriers to women's disclosure of domestic violence in health services in Palestine: qualitative interview-based study.
Domestic violence (DV) damages health and requires a global public health response and engagement of clinical services. Recent surveys show that 27% of married Palestinian women experienced some form of violence from their husbands over a 12 months' period, but only 5% had sought formal help, and rarely from health services. Across the globe, barriers to disclosure of DV have been recorded, including self-blame, fear of the consequences and lack of knowledge of services. This is the first qualitative study to address barriers to disclosure within health services for Palestinian women. In-depth interviews were carried out with 20 women who had experienced DV. They were recruited from a non-governmental organisation offering social and legal support. Interviews were recorded, transcribed and translated into English and the data were analysed thematically. Women encountered barriers at individual, health care service and societal levels. Lack of knowledge of available services, concern about the health care primary focus on physical issues, lack of privacy in health consultations, lack of trust in confidentiality, fear of being labelled 'mentally ill' and losing access to their children were all highlighted. Women wished for health professionals to take the initiative in enquiring about DV. Wider issues concerned women's social and economic dependency on their husbands which led to fears about transgressing social and cultural norms by speaking out. Women feared being blamed and ostracised by family members and others, or experiencing an escalation of violence. Palestinian women's agency to be proactive in help-seeking for DV is clearly limited. Our findings can inform training of health professionals in Palestine to address these barriers, to increase awareness of the link between DV and many common presentations such as depression, to ask sensitively about DV in private, reassure women about confidentiality, and increase awareness among women of the role that health services can play in DV.


Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.
VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA) coupled with high-performance liquid (HPLC) or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.


Aromatase inhibitors in postmenopausal breast cancer patients.
Aromatase inhibitors (AIs) have greatly enriched the treatment of hormone receptor-positive breast cancer in postmenopausal patients. Before the introduction of the well-tolerated third-generation AIs, tamoxifen was the mainstay of endocrine therapy for hormone receptor-positive breast cancer. Many clinical trials have shown the superiority of AIs compared with tamoxifen in adjuvant breast cancer treatment, as well as their benefit in metastatic breast cancer. NCCN guidelines recommendations for their use are based on the evidence provided by these clinical trials. This discussion reviews the evidence supporting the current guidelines for use of AI therapy in the treatment of hormone receptor-positive postmenopausal breast cancer patients.


Self-scattering effects in femtosecond laser nanoablation.
We experimentally investigate the self-reflectivity of intense strongly focused femtosecond laser pulses used for single-shot femtosecond laser ablation of silicon-on-insulator (SOI). We model the self-reflectivity using 2D finite-difference time-domain simulations of a single femtosecond laser pulse interacting with a submicrometer-sized time- and space-dependent plasma induced by the incident pulse itself and find excellent agreement with our experimental results. The simulation shows that the laser-induced plasma scatters the incident pulse into the guided modes of the device layer of the SOI.


Dystrophin isoforms DP71 and DP427 have distinct roles in myogenic cells.
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene, a complex gene that generates a family of distinct isoforms. In immature muscle cells, two dystrophin isoforms are expressed, Dp427 and Dp71. To characterize the function of Dp71 in myogenesis, we have examined the expression of Dp71 in myogenic cells. The localization of Dp71 in these cells is distinct from the localization of Dp427. Whereas Dp427 localizes to focal adhesions and surface membrane during myogenesis, Dp71 localizes to stress fiberlike structures in myogenic cells. Biochemical fractionation of myogenic cells demonstrates that Dp71 cosediments with the actin bundles thus confirming this interaction. Furthermore, transfection of C2C12 myoblasts with constructs encoding Dp71 fused to green fluorescent protein targeted the protein to the actin microfilament bundles. These results demonstrate involvement of Dp71 with the actin cytoskeleton during myogenesis and suggest a role for Dp71 that is distinct from Dp427.


The antibacterial activity of honey derived from Australian flora.
Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4 °C than at 25 °C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25 °C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted.


Chemical analysis of World Trade Center fine particulate matter for use in toxicologic assessment.
The catastrophic destruction of the World Trade Center (WTC) on 11 September 2001 caused the release of high levels of airborne pollutants into the local environment. To assess the toxicity of fine particulate matter [particulate matter with a mass median aerodynamic diameter < 2.5 microm (PM2.5)], which may adversely affect the health of workers and residents in the area, we collected fallen dust samples on 12 and 13 September 2001 from sites within a half-mile of Ground Zero. Samples of WTC dust were sieved, aerosolized, and size-separated, and the PM2.5 fraction was isolated on filters. Here we report the chemical and physical properties of PM2.5 derived from these samples and compare them with PM2.5 fractions of three reference materials that range in toxicity from relatively inert to acutely toxic (Mt. St. Helens PM; Washington, DC, ambient air PM; and residual oil fly ash). X-ray diffraction of very coarse sieved WTC PM (< 53 microm) identified calcium sulfate (gypsum) and calcium carbonate (calcite) as major components. Scanning electron microscopy confirmed that calcium-sulfur and calcium-carbon particles were also present in the WTC PM2.5 fraction. Analysis of WTC PM2.5 using X-ray fluorescence, neutron activation analysis, and inductively coupled plasma spectrometry showed high levels of calcium (range, 22-33%) and sulfur (37-43% as sulfate) and much lower levels of transition metals and other elements. Aqueous extracts of WTC PM2.5 were basic (pH range, 8.9-10.0) and had no evidence of significant bacterial contamination. Levels of carbon were relatively low, suggesting that combustion-derived particles did not form a significant fraction of these samples recovered in the immediate aftermath of the destruction of the towers. Because gypsum and calcite are known to cause irritation of the mucus membranes of the eyes and respiratory tract, inhalation of high doses of WTC PM2.5 could potentially cause toxic respiratory effects.


Isothermal cavity, blackbody radiation source.
A prototype blackbody radiation source has been developed which incorporates a double cone cavity of extremely uniform surface temperature. This uniformity of surface temperature is the result of a unique method of supplying heat to the cavity. The principle of operation is based on heat pipe techniques which transfer heat by change of phase and mass transfer. The cavity is heated by serving as the condenser section of the heat pipe which is inherently a nearly isothermal device. Optical tests show that the isothermal cavity has a lambertian distribution over an inclusive angle of better than 60 degrees while operating between 419 degrees C and 760 degrees C.


Experimental sepsis impairs humoral memory in mice.
Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.


Electrical Myostimulation (EMS) Improves Glucose Metabolism and Oxygen Uptake in Type 2 Diabetes Mellitus Patients--Results from the EMS Study.
In patients with type 2 diabetes mellitus (T2DM) exercise training is recommended to improve glycemic control. Electrical myostimulation (EMS) of skeletal muscles is a new method to increase exercise capacity in patients with chronic heart failure. The aim of this study was to investigate the effects of EMS in T2DM on glucose metabolism, body composition, and exercise performance using a newly designed stimulation suit that involves trunk, leg, and arm muscles. Fifteen individuals (nine males; 61.7±14.8 years old) were trained for 10 weeks twice weekly for 20 min with EMS. Effects on glucose, glycosylated hemoglobin (HbA(1c)), oxygen consumption, and body composition were evaluated. There was a significant increase of oxygen uptake at the aerobic threshold from 12.3±0.8 to 13.3±0.7 mL/kg/min (P=0.003) and of maximal work capacity from 96.9±6.4 to 101.4±7.9 W (P=0.046), with a concomitant trend for improved maximal oxygen uptake (from 14.5±0.9 to 14.7±0.9 mL/kg/min [P=0.059]). Fasting blood glucose level decreased from 164.0±12.5 to 133.4±9.9 mg/dL (P=0.001), and HbA(1c) level decreased from 7.7±0.3% to 7.2±0.3% (P=0.041), whereas mean total weight (from 101.5±4.0 to 103.1±4.3 kg) and proportion of body fat (from 38.8±3.2% to 40.3±3.4%) remained statistically unchanged. EMS can improve glucose metabolism and functional performance in T2DM patients. These data suggest that EMS might emerge as a novel additional therapeutic mode of exercise training and might help patients to overcome their sedentary lifestyle.


Spinal arteriovenous malformation presenting as spastic monoplegic cerebral palsy in a child.
A case of spinal arterio-venous malformation (AVM) initially diagnosed as unilateral cerebral palsy (CP) is reported. The presentation was of a long-standing spastic monoparesis of the left leg, with initial response to Botulinum toxin injections to the calf and tibialis posterior muscles. This was followed by progressive deterioration occurring over a 3-month period before further investigation and definitive diagnosis at 7 years. Imaging demonstrated a large extra-medullary spinal AVM compressing the mid-thoracic cord. This was successfully managed by embolisation with a non-adhesive polymer: ethylene-vinyl alcohol copolymer injected into the dominant feeding vessel. This case highlights the need to consider alternative diagnoses when a child with a diagnosis of CP presents with atypical clinical features such as monoparesis and has worsening or altered clinical signs. Moreover, a normal magnetic resonance imaging brain scan and the absence of ipsilateral upper limb neurological signs or functional impairment should raise suspicion even in the context of static lower limb signs. A literature review was performed on the management of spinal AVM in children and this will be is discussed.


Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization.
A neuron's dendrites typically do not cross one another. This intrinsic self-avoidance mechanism ensures unambiguous processing of sensory or synaptic inputs. Moreover, some neurons respect the territory of others of the same type, a phenomenon known as tiling. Different types of neurons, however, often have overlapping dendritic fields. We found that Down's syndrome Cell Adhesion Molecule (Dscam) is required for dendritic self-avoidance of all four classes of Drosophila dendritic arborization (da) neurons. However, neighboring mutant class IV da neurons still exhibited tiling, suggesting that self-avoidance and tiling differ in their recognition and repulsion mechanisms. Introducing 1 of the 38,016 Dscam isoforms to da neurons in Dscam mutants was sufficient to significantly restore self-avoidance. Remarkably, expression of a common Dscam isoform in da neurons of different classes prevented their dendrites from sharing the same territory, suggesting that coexistence of dendritic fields of different neuronal classes requires divergent expression of Dscam isoforms.


Occupational contact dermatitis in hairdressers/cosmetologists: retrospective analysis of north american contact dermatitis group data, 1994 to 2010.
European studies document that occupational contact dermatitis (CD) is common in hairdressers, but studies from North America are lacking. The objectives of this study were to estimate the prevalence of occupational CD among North American hairdressers/cosmetologists (HD/CS) and to characterize responsible allergens and irritants as well as their sources. A cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group between 1994 and 2010 was conducted. Of 35,842 patients, 432 (1.2%) were HD/CS. Significantly, most of the HD/CS were female (89.8%) and younger than 40 years (55.6%) as compared with non-hairdressers (P < 0.0001). The rates for allergic and irritant CD in HD/CS were 72.7% and 37.0%, respectively. The most common body site of involvement was the hand, and this was significantly more common than in non-HD/CS (P < 0.0001). The most frequent currently relevant and occupationally related allergens were glyceryl thioglycolate, p-phenylenediamine, nickel sulfate, 2-hydroxyethyl methacrylate, and quaternium-15. Hair dyes, permanent wave solutions, and other hair products were common sources of allergens. The North American Contact Dermatitis Group allergen series missed at least 1 occupationally-related allergen in 26.2% of patients. Contact dermatitis in North American HD/CS is common, and occupationally related allergens are those found in HD/CS products. Supplemental hairdressing/cosmetology antigen series are important in detecting all occupationally related allergens in this population.


A Weighted Sum Validity Function for clustering with a Hybrid Niching Genetic Algorithm.
Clustering is inherently a difficult problem, both with respect to the construction of adequate objective functions as well as to the optimization of the objective functions. In this paper, we suggest an objective function called the Weighted Sum Validity Function (WSVF), which is a weighted sum of the several normalized cluster validity functions. Further, we propose a Hybrid Niching Genetic Algorithm (HNGA), which can be used for the optimization of the WSVF to automatically evolve the proper number of clusters as well as appropriate partitioning of the data set. Within the HNGA, a niching method is developed to preserve both the diversity of the population with respect to the number of clusters encoded in the individuals and the diversity of the subpopulation with the same number of clusters during the search. In addition, we hybridize the niching method with the k-means algorithm. In the experiments, we show the effectiveness of both the HNGA and the WSVF. In comparison with other related genetic clustering algorithms, the HNGA can consistently and efficiently converge to the best known optimum corresponding to the given data in concurrence with the convergence result. The WSVF is found generally able to improve the confidence of clustering solutions and achieve more accurate and robust results.


Use of multimedia in patient and caregiver education for cancer pain management: a literature review.
Pain is one of the most prominent symptoms faced by cancer patients. It is known that patient and caregiver-targeted educational interventions addressing the proper use of pain management may provide significant clinical value. This review examines the literature surrounding the use of multimedia interventions for patient and caregiver education (PCE) on pain management compared to traditional educational interventions. A literature search was conducted in Ovid MEDLINE (1946-July Week 2, 2016), Ovid Embase (1947-2016 Week 29), and Ovid Cochrane Central Register of Controlled Trials (up to June 2016). Paired reviewers conducted title and abstract screening and full-text screening to identify experimental, quasi-experimental and cohort studies evaluating one or more multimedia-based PCE interventions focused on cancer pain and pain management and targeting patients and/or caregivers. Findings were extracted by paired reviewers and synthesized qualitatively. Of the 68 full-text papers assessed, 7 were deemed relevant, of which 5 were RCTs and 2 were observational studies. We found limited but convincing quantitative data to suggest that the use of multimedia use in pain management education for patients/caregivers has greater value-added benefit compared to standard education. While there is evidence suggesting a positive effect on pain-related outcomes with the use of multimedia-based patient and caregiver-targeted interventions, it is limited to a small number of lower-quality studies. More robust and large-scale studies are needed to supplement existing evidence and provide more insight regarding the usability and user-friendliness of these tools in practice.


The Role of Uric Acid for Predicting Future Metabolic Syndrome and Type 2 Diabetes in Older People.
Although it is known that high uric acid (UA) level is associated with type 2 diabetes (T2DM) and metabolic syndrome (MetS), most of the previous studies were focused on adults. Since aging becomes a major problem for many societies, in this longitudinal study, we investigated the role of UA in future T2DM and MetS in a large cohort of people who were older than 65 years. A cross-sectional and longitudinal study. 18,907 elderly (9,732 men, 9,175 women) aged above 65 years, enrolled from health check-up centers, were classified into three subgroups by 10-year intervals (young old 65-74 years, YO; old old 75-84 years, OO; and oldest old 85-94 years, ODO), with the average follow-up period of 4.3 years. The optimal cut-off values (CoVs) of baseline UA to predict future MetS and T2DM were determined by receiving operating characteristic (ROC) curve analysis. Using these CoVs of UA, the participants were divided into normal- and high-level groups of UA. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of UA for the risk of future MetS and T2DM. In addition, Kaplan-Meier plots and log rank test were used to evaluate the time effect on the incidence of developing MetS and T2DM between the two groups. In ROC curve analysis, the optimal CoVs of baseline UA were 6.0, 6.3 and 6.7 mg/dl in YO, OO, and ODO men, respectively; 5.5 and 4.9 mg/dl in YO and OO women, respectively (all p < 0.05). However, the CoVs of UA in ODO women (6.1 mg/dl) failed to show its discriminant power (p = 0.13). The Cox regression analysis showed the YO subjects with a higher baseline level of UA had a higher risk of developing MetS (HRs 1.56 and 1.58 for men and women, respectively, both p < 0.001); as for T2DM the HRs were 1.39 and 1.57. In OO men, the HRs was 1.89 for developing future MetS. However, no significant findings could be noted in the ODO group. Kaplan-Meier plots and log rank test also showed the same findings. Our study showed that old subjects with high levels of UA will have a higher chance to have MetS and T2DM, particularly in the YO group (6.0 mg/dl for men and 5.5 mg/dl for women, respectively). Using UA as one of the metabolic biomarkers may help clinicians to early detect and prevent MetS and diabetes.


The current status of molecular diagnosis of inherited retinal dystrophies.
We are witnessing lightning-fast advances in the molecular diagnosis of inherited retinal dystrophies, mainly due to the widespread use of next-generation sequencing technologies. The purpose of this review is to highlight the breadth of findings from this in-depth testing approach, and to propose changes to our traditional testing and diagnostic paradigms. Lessons learned from modern molecular testing suggest that the previous concept of inherited retinal dystrophies as a group of 'single gene diseases' may require a significant update. All of the known retinal dystrophies genes can now be sequenced. In many cases, this nonhypothesis driven testing strategy is uncovering mutations in unsuspected genes, generating data that challenges established concepts of genetic mechanisms and provides insights regarding genes previously thought to be exclusively related to syndromic disease. Recent advances in testing have improved not only the breadth, but also the depth of genetic data. For example, deep intronic sequencing has uncovered many novel intronic mutations/variations in the ABCA4 gene. Currently, in approximately 50-60% of patients with nonsyndromic retinal dystrophy, the disease mechanism can be identified. The presence of pathogenic alleles in more than one gene is not uncommon. Retinal dystrophy, with relatively defined clinical presentations and a large but limited number of genes involved, is becoming a model for the next-generation study of molecular disease mechanisms.


Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity.
Despite the enormous success of second generation antihistamines, in the mid-1980s, about 10 years after their introduction in the market, several reports appeared in the literature indicating the rare occurrence of a form of polymorphic ventricular dysrhythmia, the 'torsade de pointes', after the administration of astemizole or terfenadine. This cardiac side-effect has been interpreted as a consequence of the interference of these drugs with cardiac K+ channels involved in action potential repolarization, and in particular with the IKr component of the cardiac repolarizing current. As the K+ channels encoded by the human ether-a-gogo-related gene (HERG) seem to represent the molecular basis of IKr, this cardiac K+ channel was soon recognized as a primary target for second generation antihistamine-induced proarrhythmic effects. In fact, both terfenadine and astemizole have been shown to block HERG K+ channels in a concentration range similar to that found in the plasma of subjects with cardiotoxic manifestations. However, no correlation can be found between the ability to prolong the cardiac action potential duration and the H1-antagonistic activity by several antihistamines, suggesting that HERG blockade and cardiotoxic potential are not class properties of second generation antihistamines. In fact, other molecules such as cetirizine, loratadine, acrivastine, and fexofenadine seem to lack both cardiotoxic potential and HERG-blocking ability at therapeutically relevant concentrations. The marked heterogeneity displayed by second generation antihistamines in their ability to prolong the cardiac action potential duration and to block HERG K+ channels might be of considerable therapeutical significance for those patients at risk of developing cardiac dysrhythmias and in need of therapy with H1-receptor blockers; it also emphasizes the importance of an evaluation of the possible blockade of HERG K+ channels during the early developmental phases of novel compounds belonging to this therapeutical class.


Evaluation of antiangiogenic and antiproliferative potential of ethanolic extracts of Andrographis echioides using in vitro and in ovo assays.
Andrographis echioides is a prevalently used medicinal herb in South Asian countries. Scientific researches with the extracts of A. echioides revealed its antipyretic, anti-inflammatory, antimicrobial, ulceroprotective, and hepatoprotective properties. This study was done to elucidate antiproliferative and antiangiogenic potential of ethanolic extracts of A. echioides (EEAE) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and chorioallantoic membrane (CAM) assay. EEAE was prepared using Soxhlet apparatus with ethanol after being sun-dried and powdered. MCF 7 (human invasive breast ductal carcinoma) cell lines retaining attributes of differentiated mammary epithelium with both estrogen and progesterone receptors were treated with EEAE, and antiproliferative effect was seen using Mosmann method of MTT assay using 5-fluorouracil (5-FU) as a comparator. The evaluation of antiangiogenic potential of EEAE was done by comparing mean vessel density (MVD) in chick CAM after treatment with EEAE, thalidomide, and vascular endothelial growth factor (VEGF) using CAM assay, an in ovo assay. EEAE displayed antiproliferative activity from low to high concentrations with MTT assay. The IC50 of EEAE and 5-FU was 62.5 and 15.6 μg/ml, respectively (P < 0.05). The exhibition of its antiangiogenic activity increased proportionately with increasing concentration. VEGF increased MVD by 45.94%; thalidomide decreased it by 53.76%. There was a decrease of MVD by 5.91%, 20.46%, and 35.95% at concentrations of 25, 50, and 100 μg of EEAE, respectively. EEAE possessed significant antiangiogenic and antiproliferative activity, making them a promising substrate in the development of a novel anticancer drug and can be successfully used in the therapy of various cancers after establishment of the anticancer effects in animal models and subsequently in clinical trials.


Influence of the chirality of short peptide supramolecular hydrogels in protein crystallogenesis.
For the first time the influence of the chirality of the gel fibers in protein crystallogenesis has been studied. Enantiomeric hydrogels 1 and 2 were tested with model proteins lysozyme and glucose isomerase and a formamidase extracted from B. cereus. Crystallization behaviour and crystal quality of these proteins in both hydrogels are presented and compared.


Multi-scale strain-stiffening of semiflexible bundle networks.
Bundles of polymer filaments are responsible for the rich and unique mechanical behaviors of many biomaterials, including cells and extracellular matrices. In fibrin biopolymers, whose nonlinear elastic properties are crucial for normal blood clotting, protofibrils self-assemble and bundle to form networks of semiflexible fibers. Here we show that the extraordinary strain-stiffening response of fibrin networks is a direct reflection of the hierarchical architecture of the fibrin fibers. We measure the rheology of networks of unbundled protofibrils and find excellent agreement with an affine model of extensible wormlike polymers. By direct comparison with these data, we show that physiological fibrin networks composed of thick fibers can be modeled as networks of tight protofibril bundles. We demonstrate that the tightness of coupling between protofibrils in the fibers can be tuned by the degree of enzymatic intermolecular crosslinking by the coagulation factor XIII. Furthermore, at high stress, the protofibrils contribute independently to the network elasticity, which may reflect a decoupling of the tight bundle structure. The hierarchical architecture of fibrin fibers can thus account for the nonlinearity and enormous elastic resilience characteristic of blood clots.


Cooperative upconversion and optical gain in ion-beam sputter-deposited Er(x)Y(2-x)SiO(5) waveguides.
Single-phase, polycrystalline Er(x)Y(2-x)SiO(5) thin films were deposited by reactive ion-beam sputter deposition and rapid thermal annealing. Due to the crystalline nature, the silicate thin films provide peak Er(3+) emission cross-section of 0.9 +/- 0.02 x 10(-20) cm(2) that is higher than that in silica. Optical gain, with near 60% inversion, is achieved via optical pumping of a single-mode, ridge-type waveguide with the silicate core with an Er concentration of 1.7 x 10(20) cm(-3). Analysis of pump-power dependence of the optical gain and spontaneous emission intensity of Er(3+) indicate that the gain is limited by cooperative upconversion process, whose coefficient is determined to be (8 +/- 3) x 10(-17) cm(3)/sec.


Ventilation or dignified death for patients with high tetraplegia.
The case histories of the 37 patients of the Mersey Regional Spinal Injuries Centre who were artificially ventilated between 1968 and 1984 were reviewed. The patients and caring relatives were interviewed separately to determine their views. Of 21 patients who were still alive, 18 said that they would wish to be temporarily ventilated again if the need arose, two were undecided, and one said that she would wish to be allowed to die. Sixteen caring relatives said that they were glad that the decision to ventilate had been taken. Those who were not glad were all young mothers. The outcome from any combination of factors that existed before injury could not be predicted except that most patients over age 59 fared badly. Patients with spinal cord damage should be artificially ventilated if required, provided that this can be carried out well and that total emotional, educational, and physical support can be provided and maintained. Whether or not scarce resources should be deployed in this manner requires discussion.


Tubular adenoma of the choroid plexus: evidence for glandular differentiation of the neuroepithelium.
A case of tubular adenoma arising in the right ventricular choroid plexus of a 4-month-old boy is described. A basic pattern of neoplastic glandular epithelium and lack of papillary architecture distinguished this tumor from a papilloma. Coexpression of S -100 protein, transthyretin and cytokeratin identified the neoplastic cells as being of choroid plexus origin. Immunohistochemical detection of MIB-1 showed a proliferation rate (16%) similar to adenomas in more conventional locations, but not encountered in benign brain tumors. In situ detection of DNA-derived oligonucleosomal fragments by TUNEL analysis, on the other hand, detected apoptotic activity in 5-8% of tumor cells. The indolent course of the disease in the present case, thus, might suggest a compensatory elimination of proliferating cells by apoptosis. This possibly points to mechanisms of neoplastic transformation different from those involved in choroid plexus papillomas.


Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents.
DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity (30- to 90-fold). Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks that were revealed by proteinase treatment. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Repair kinetics of DNA interstrand cross-link production and removal was measured by alkaline elution for AA8 and mutants UV4 and UV5 after exposure to diepoxybutane. Although the initial number of cross-links was similar for the three cell lines, during 24-h incubation, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity of the five complementation groups to bifunctional alkylation damage are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes.


Positive and negative factors that influence concussion reporting among secondary-school athletes.
Concussions are one of the most common sport-related injuries affecting athletes participating at all levels across a variety of sports. It has been reported that up to 3.8 million concussive events occur per year that are sports-related. One significant issue with identifying concussions is that a clinical diagnosis is based on the presence of signs and symptoms, which are self-reported by the patient. In the adolescent population, injury to the brain is possible with even the slightest insult, which can affect recovery and predispose them to subsequent concussions. Recent legislative efforts have included athlete education as a means to improve concussion reporting. More specifically, all 50 US states and the District of Columbia have implemented concussion legislation that includes some type of concussion education protocol, but there is still little evidence to suggest that enhanced knowledge levels result in behavior changes, including improved concussion-reporting practices. It is unclear what factors make an adolescent athlete more or less likely to report the symptoms of a concussion. What factors positively or negatively influence secondary school athletes' likelihood of reporting symptoms of sport-related concussions?


Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle.
Smooth muscle cells respond to InsP(3)-generating (sarcolemma-acting) neurotransmitters and hormones by releasing Ca(2+) from the internal store. However, the release of Ca(2+) does not occur uniformly throughout the cytoplasm but often into a localized area before being transmitted to other regions of the cell in the form of Ca(2+) waves and oscillations to actively spread information within and between cells. Yet, despite their significance, our understanding of the generation of oscillations to waves is incomplete. A major aspect of controversy centres on whether or not Ca(2+) released from the InsP(3) receptor activates RyRs (ryanodine receptors) to generate further release by Ca(2+)-induced Ca(2+) release and propagate waves or whether the entire process arises from InsP(3) receptor activity alone. Under normal physiological conditions the [Ca(2+)] required to activate RyR (approx. 15 microM) exceeds the bulk average [Ca(2+)](c) (cytoplasmic Ca(2+) concentration) generated by InsP(3) receptor activity (<1 microM). Progression of waves and oscillations by RyR activity would require a loss of control of RyR activity and an unrestrained positive feedback on Ca(2+) release. Under store-overload conditions, RyR Ca(2+) sensitivity is increased and this enables waves to be induced by RyR activity. However, the relevance of these Ca(2+)-release events to normal physiological functioning is unclear. The InsP(3) receptor, on the other hand, is activated by Ca(2+) over the physiological range (up to 300 nM) and deactivated by higher [Ca(2+)](c) (>300 nM), features that favour intermittent activity of the receptor as occurs in waves and oscillations. Experimental evidence for the involvement of RyR relies mainly on pharmacological approaches in the intact cell where poor drug specificity could have led to ambiguous results. In this brief review the possible interactions between InsP(3) receptors and RyR in the generation of oscillations and waves will be discussed. Evidence is presented that RyRs are not required for InsP(3)-mediated Ca(2+) transients. Notwithstanding, ryanodine can inhibit InsP(3)-mediated Ca(2+) responses after RyR activity has been induced by caffeine or by steady depolarization which evokes spontaneous transient outward currents (a sarcolemmal manifestation of RyR activity). Ryanodine inhibits InsP(3)-mediated Ca(2+) transients by depleting the store of Ca(2+) rather than by RyR involvement in the InsP(3)-mediated Ca(2+) increase.


Pneumococcal capsular switching: a historical perspective.
Changes in serotype prevalence among pneumococcal populations result from both serotype replacement and serotype (capsular) switching. Temporal changes in serotype distributions are well documented, but the contribution of capsular switching to such changes is unknown. Furthermore, it is unclear to what extent vaccine-induced selective pressures drive capsular switching. Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937 through 2007 were analyzed. Whole-genome sequence data for a subset of isolates were used to investigate capsular switching events. We identified 36 independent capsular switch events, 18 of which were explored in detail with whole-genome sequence data. Recombination fragment lengths were estimated for 11 events and ranged from approximately 19.0 kb to ≥ 58.2 kb. Two events took place no later than 1960, and the imported DNA included the capsular locus and the nearby penicillin-binding protein genes pbp2x and pbp1a. Capsular switching has been a regular occurrence among pneumococcal populations throughout the past 7 decades. Recombination of large DNA fragments (>30 kb), sometimes including the capsular locus and penicillin-binding protein genes, predated both vaccine introduction and widespread antibiotic use. This type of recombination has likely been an intrinsic feature throughout the history of pneumococcal evolution.


Realizing transformational change through quality improvement in public health.
This article discusses the specific components necessary to achieve transformational change within public health departments as a means for creating sustained performance improvement and better outcomes in the health of the community. This article provides a review of transformation change concepts and application to public health departments. Transformational change for public health departments must be intentionally designed to achieve high performance. While all improvement requires change, not all change results in improvement. The successful transformational change effort always occurs from the top-down, while the process improvement occurs from the bottom-up. Transformational change is possible in public health departments when small incremental improvements are linked with large-scale management changes to continually improve public health performance resulting in better population outcomes.


Repressive coping style and anxiety in stressful dental surgery.
Elevated state-anxiety prior to oral surgery is common and is associated with increased post-operative pain. This paper presents a psychological model of predicting elevated anxiety prior to dental surgery. Elevated anxiety and intraoperative stress can be predicted by measuring trait-anxiety. However, prediction may be improved by using a situationally specific measure of trait-anxiety, and by taking the patient's coping style into account. Thirty-nine patients undergoing wisdom-tooth extraction took part in the study. The Corah Dental Anxiety Scale was a better predictor of pre-operative anxiety than the STAI trait-anxiety scale. Coping style was measured by means of the Marlowe-Crowne Social Desirability Scale in conjunction with scores on trait-anxiety to define three coping style groups: sensitizers (high-anxious), truly low-anxious, and repressors who verbally deny anxiety. Two oral surgeons rated patient intra-operative state on 100 mm visual analogue scales. These ratings indicate that 'repressors' exhibit significantly more stress responses than the truly low-anxious group, in spite of similar (low) trait-anxiety scores. It is concluded that a situationally specific measure of trait-anxiety is the most appropriate predictor of differential state-anxiety elevations prior to oral surgery. Repressive coping style may be a confounding factor, in terms of predicting elevated anxiety, since some people verbally deny being anxious but express it behaviourally.


Functional consequences of genetic diversity in Strongyloides ratti infections.
Parasitic nematodes show levels of genetic diversity comparable to other taxa, but the functional consequences of this are not understood. Thus, a large body of theoretical work highlights the potential consequences of parasite genetic diversity for the epidemiology of parasite infections and its possible implications for the evolution of host and parasite populations. However, few relevant empirical data are available from parasites in general and none from parasitic nematodes in particular. Here, we test two hypotheses. First, that different parasitic nematode genotypes vary in life-history traits, such as survivorship and fecundity, which may cause variation in infection dynamics. Second, that different parasitic nematode genotypes interact within the host (either directly or via the host immune system) to increase the mean reproductive output of mixed-genotype infections compared with single-genotype infections. We test these hypotheses in laboratory infections using genetically homogeneous lines of Strongyloides ratti. We find that nematode genotypes do vary in their survivorship and fecundity and, consequently, in their dynamics of infection. However, we find little evidence of interactions between genotypes within hosts under a variety of trickle- and single-infected infection regimes.


Predictors of Functional Decline in Nursing Home Residents: The Shelter Project.
The aim of our study was to identify independent predictors of functional decline in older nursing home (NH) residents, taking into account both resident and facility characteristics. Longitudinal observational study involving 1,760 older (≥65 y) residents of NH participating in the SHELTER* study (57 NH in eight countries). All residents underwent a comprehensive geriatric assessment using the interRAI LTCF. Functional decline was defined as an increase of at least one point in the MDS Long Form ADL scale during a 1 year follow-up. Facility and country effects were taken into account. During the study period 891 (50.6%), NH residents experienced ADL decline. Residents experiencing ADL decline were older, had lower disability at baseline, were more frequently affected by severe dementia and by urinary incontinence, and used more antipsychotics. In the mixed-effect logistic regression model, factors independently associated with a higher risk of functional decline were dementia and urinary incontinence, whereas the presence of a geriatrician was a protective factor. Both resident and facility characteristics are associated with the risk of functional decline in NH residents. Increasing the quality of healthcare by involving a geriatrician in residents' care might be an important strategy to improve the outcome of this vulnerable population.


Pervasive and strong effects of plants on soil chemistry: a meta-analysis of individual plant 'Zinke' effects.
Plant species leave a chemical signature in the soils below them, generating fine-scale spatial variation that drives ecological processes. Since the publication of a seminal paper on plant-mediated soil heterogeneity by Paul Zinke in 1962, a robust literature has developed examining effects of individual plants on their local environments (individual plant effects). Here, we synthesize this work using meta-analysis to show that plant effects are strong and pervasive across ecosystems on six continents. Overall, soil properties beneath individual plants differ from those of neighbours by an average of 41%. Although the magnitudes of individual plant effects exhibit weak relationships with climate and latitude, they are significantly stronger in deserts and tundra than forests, and weaker in intensively managed ecosystems. The ubiquitous effects of plant individuals and species on local soil properties imply that individual plant effects have a role in plant-soil feedbacks, linking individual plants with biogeochemical processes at the ecosystem scale.


Trypanosoma cruzi infection inhibited by peptides modeled from a fibronectin cell attachment domain.
The mechanism by which Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, becomes attached to mammalian cells is not well understood. Fibronectin is thought to participate in the attachment, and in this study the region of fibronectin that interacts with the surface receptors of T. cruzi trypomastigotes was investigated by testing the binding of the amino acid sequence Arg-Gly-Asp-Ser, corresponding to the cell attachment site of fibronectin to T. cruzi trypomastigotes. Peptides with the sequence Arg-Gly-Asp-Ser, but not Arg-Phe-Asp-Ser, Arg-Phe-Asp-Ser-Ala-Ala-Arg-Phe-Asp, Ser-Lys-Pro, Glu-Ser-Gly, or Ala-Lys-Thr-Lys-Pro, bound to the parasite surface and inhibited cell invasion by the pathogen. Monoclonal antibodies to the cell attachment domain of fibronectin also inhibited cell infection by the parasite. The immunization of BALB/c mice with tetanus toxoid-conjugated peptide induced a significant protection against T. cruzi. The data support the notion that the sequence Arg-Gly-Asp-Ser of cell surface fibronectin acts as a recognition site for attachment of the parasites.


TAZ stimulates exercise-induced muscle satellite cell activation via Pard3-p38 MAPK-TAZ signalling axis.
Exercise stimulates the activation of muscle satellite cells, which facilitate the maintenance of stem cells and their myogenic conversion during muscle regeneration. However, the underlying mechanism is not yet fully understood. This study shows that the transcriptional co-activator with PDZ-binding motif (TAZ) stimulates muscle regeneration via satellite cell activation. Tazf/f mice were crossed with the paired box gene 7 (Pax7)creERT2 mice to generate muscle satellite cell-specific TAZ knockout (sKO) mice. Mice were trained in an endurance exercise programme for 4 weeks. Regenerated muscles were harvested and analysed by haematoxylin and eosin staining. Muscle tissues were also analysed by immunofluorescence staining, immunoblot analysis and quantitative reverse transcription PCR (qRT-PCR). For the in vitro study, muscle satellite cells from wild-type and sKO mice were isolated and analysed. Mitochondrial DNA was quantified by qRT-PCR using primers that amplify the cyclooxygenase-2 region of mitochondrial DNA. Quiescent and activated satellite cells were stained with MitoTracker Red CMXRos to analyse mitochondria. To study the p38 mitogen-activated protein kinase (MAPK)-TAZ signalling axis, p38 MAPK was activated by introducing the MAPK kinase 6 plasmid into satellite cells and also inhibited by treatment with the p38 MAPK inhibitor, SB203580. TAZ interacts with Pax7 to induce Myf5 expression and stimulates mammalian target of rapamycin signalling for satellite cell activation. In sKO mice, TAZ depletion reduces muscle satellite cell number by 38% (0.29 ± 0.073 vs. 0.18 ± 0.034, P = 0.0082) and muscle regeneration. After muscle injury, TAZ levels (2.59-fold, P < 0.0001) increase in committed cells compared to self-renewing cells during asymmetric satellite cell division. Mechanistically, the polarity protein Pard3 induces TAZ (2.01-fold, P = 0.008) through p38 MAPK, demonstrating that the p38 MAPK-TAZ axis is important for muscle regeneration. Physiologically, endurance exercise training induces muscle satellite cell activation and increases muscle fibre diameter (1.33-fold, 43.21 ± 23.59 vs. 57.68 ± 23.26 μm, P = 0.0004) with increased TAZ levels (1.76-fold, P = 0.017). However, sKO mice had a 39% reduction in muscle satellite cell number (0.20 ± 0.03 vs. 0.12 ± 0.02, P = 0.0013) and 24% reduction in muscle fibre diameter compared to wild-type mice (61.07 ± 23.33 vs. 46.60 ± 24.29 μm, P = 0.0006). Our results demonstrate a novel mechanism of TAZ-induced satellite cell activation after muscle injury and exercise, suggesting that activation of TAZ in satellite cells may ameliorate the muscle ageing phenotype and may be an important target protein for the drug development in sarcopenia.


Cardiac output measurement by pulse dye densitometry in cardiac surgery.
Summary The aim of this study was to compare the accuracy of pulse dye densitometry with that of bolus thermodilution cardiac output measurement in patients before and after elective coronary artery bypass grafting. Twenty-eight patients were studied. Agreement between mean thermodilution and pulse dye densitometry cardiac output values was assessed by Bland-Altman analysis. Preoperative median [range] cardiac output was 3.87 [2.37-6.0] l.min(-1) by thermodilution, and 3.11 [1.7-5.45] l.min(-1) by pulse dye densitometry using indocyanine green 5 mg. Pulse dye densitometry underestimated cardiac output (mean bias - 0.42 l.min(-1)); the limits of agreement were +/- 1.91 l.min(-1), and mean error was 50.3%, indicating low precision. Preoperative median [range] cardiac output was 3.85 [2.2-6.0] l.min(-1) for bolus thermodilution cardiac output and 4.2 [2.0-7.2] l.min(-1) for pulse dye densitometry using indocyanine green 20 mg. Mean bias was + 0.566 l.min(-1), the limits of agreement were +/- 2.51 l.min(-1) and mean error was 60.9%. Postoperative cardiac output data were not analysed because pulse dye densitometry signals were low or absent in > 50% of the patients. We conclude that pulse dye densitometry using indocyanine green 5 mg or 20 mg is inaccurate in anaesthetised patients before coronary artery bypass surgery and cannot be used after surgery because of a high incidence of low pulse dye densitometry signal amplitudes.


Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses.
Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children.


The International/Canadian Hereditary Angioedema Guideline.
This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.


Evaluating the reliability of media reports for gathering information about illegal wildlife trade seizures.
Illegal wildlife trade (IWT) is threatening many species across the world. It is important to better understand the scale and characteristics of IWT to inform conservation priorities and actions. However, IWT usually takes place covertly, meaning that the data on species, trade routes and volumes is limited. This means that conservationists often have to rely on publicly available law enforcement reports of seizures as potential indicators of the magnitude and characteristics of IWT. Still, even these data may be difficult to access, leading conservationists to use media reports of seizures instead. This is the case in countries like Nepal, which have limited capacity in data keeping and reporting, and no centralized data management system. Yet reliance on media reports risks introducing further biases, which are rarely acknowledged or discussed. Here we characterize IWT in Nepal by comparing data from three sources of information on IWT between January 2005 and July 2017: seizure reports from three Nepali national daily newspapers, official seizure records for Kathmandu district, and data on additional enforcement efforts against IWT in Nepal. We found a strong positive correlation between the number of official and media-reported seizures over time, but media under-reported seizure numbers, with 78% of seizures going unreported. Seizures of charismatic, protected species were reported more often and seizure reports involving tigers were most likely to be reported (57%). Media reports appeared to be a good indicator of trends and the species being seized but not overall seizure number, with the media largely underestimating total seizure numbers. Therefore, media reports cannot be solely relied upon when it comes to informing conservation decision-making. We recommend that conservationists triangulate different data sources when using seizure data reported in the media to more rigorously characterise IWT.


Hospital and Patient Factors Affecting Veterans' Hospital Choice.
Veterans enrolled in the Veterans Affairs (VA) health care system gained greater access to non-VA care beginning in 2014. We examined hospital and Veteran characteristics associated with hospital choice. We conducted a longitudinal study of elective hospitalizations 2011 to 2017 in 11 states and modeled patients' choice of VA hospital, large non-VA hospital, or small non-VA hospital in conditional logit models. Patients had higher odds of choosing a hospital with an academic affiliation, better patient experience rating, location closer to them, and a more common hospital type. Patients who were male, racial/ethnic minorities, had higher VA enrollment priority, and had a mental health comorbidity were more likely than other patients to choose a VA hospital than a non-VA hospital. Our findings suggest that patients respond to certain hospital attributes. VA hospitals may need to maintain or achieve high levels of quality and patient experience to attract or retain patients in the future.


TNF receptor-activated factor 2 mediates cardiac protection through noncanonical NF-κB signaling.
To elucidate the mechanisms responsible for cytoprotective effects of TNF receptor-activated factor 2 (TRAF2) in the heart, we employed genetic gain- and loss-of-function studies ex vivo and in vivo in mice with cardiac-restricted overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice lacking canonical signaling (Myh6-TRAF2LC/Myh6-IκBαΔN) abrogated the cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional profiling of WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts suggested that the noncanonical NF-κB signaling pathway was upregulated in the Myh6-TRAF2LC mouse hearts. Western blotting and ELISA for the NF-κB family proteins p50, p65, p52, and RelB on nuclear and cytoplasmic extracts from naive 12-week-old WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts showed increased expression levels and increased DNA binding of p52 and RelB, whereas there was no increase in expression or DNA binding of the p50 and p65 subunits. Crossing Myh6-TRAF2LC mice with RelB-/+ mice (Myh6-TRAF2LC/RelB-/+) attenuated the cytoprotective effects of TRAF2 ex vivo and in vivo. Viewed together, these results suggest that crosstalk between the canonical and noncanonical NF-κB signaling pathways is required for mediating the cytoprotective effects of TRAF2.


Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion.
Since pancreatobiliary diversion probably stimulates pancreatic growth by increasing cholecystokinin secretion, the effect of the cholecystokinin antagonist CR-1409 on this adaptive response was tested. Male Wistar rats (n = 108) weighing 220-250g were randomised to receive either pancreatobiliary diversion (n = 60) or sham diversion (n = 48) and thereafter to receive either saline injections or CR-1409 (10 mg/kg/day, subcutaneously). Rats were killed at four, seven, and 14 days postoperatively, when blood was obtained for cholecystokinin assay and the pancreas was assessed for proliferative activity by three techniques: nucleic acid and protein assay, bromodeoxyuridine labelling, and metaphase arrest after vincristine administration (1 mg/kg, intraperitoneally). Pancreatobiliary diversion increased plasma cholecystokinin concentrations by 91% at seven days and 137% at 14 days, irrespective of CR-1409 treatment. Total pancreatic RNA content was doubled by pancreatobiliary diversion at four days (2.15 v 1.07 mg/100 g body weight: p less than 0.001) and at seven days (3.43 v 1.76 mg/100 g: p less than 0.001), and trebled at 14 days (4.27 v 1.32 mg/100 g: p less than 0.001). Pancreatobiliary diversion increased bromodeoxyuridine labelling index from 1.1 to 3.7% at seven days and the cell birth rate from 0.09 to 0.06%. CR-1409 completely abolished this proliferative response and partly prevented the rise in RNA. The results confirm pancreatic hypertrophy and increased acinar cell proliferation after pancreatobiliary diversion. CR-1409 prevents this adaptive growth, probably by blocking cholecystokinin receptors. Bromodeoxyuridine labelling and the metaphase arrest technique may be used to assess pancreatic cell kinetics.


The primary structure of the duck alpha D-globin gene: an unusual 5' splice junction sequence.
The complete nucleotide sequence of the duck minor alpha D-globin gene including the flanking regions has been determined. A unique structural feature of the alpha D-globin gene is a GC instead of the invariant GT dinucleotide at the 5' end of the second intervening sequence. The 1013 base pair long gene has otherwise all the characteristics normally attributed to a functional globin gene. Indirect evidence suggests that the alpha D-globin gene is expressed in vivo.


Accelerometry and salivary cortisol response during Air Force Special Tactics Officer selection.
Special Tactics Officer (STO) selection is conducted to select officers to enter the combat controller training pipeline. The aims were to determine physical activity patterns, estimate energy expenditure, and identify whether return and/or unsuccessful candidates demonstrated differences in cortisol responses compared to non-selected and/or first-time attendees. Participants completed the STO selection, consisting of 5 days of physical and mental challenges. Participants were equipped with ActiCals®, and saliva samples were collected throughout the STO selection. Average activity counts were 684 ± 200 counts∙min-1, with no group differences. Estimated energy expenditure was 4,105 ± 451 kcal∙day-1. Cortisol was elevated following extended physical training but returned to baseline during rest. Return candidates had significantly lower cortisol responses compared to first-timers, 0.43 ± 0.06 μg∙dl-1 versus 0.76 ± 0.18 μg∙dl-1, respectively, p < 0.05. An individual's salivary cortisol response to the stresses incurred during the STO selection has the potential to be incorporated into the entire picture of a candidate's performance and ability to handle stress.


Interpretation of intraluminal manometric measurements in terms of swallowing mechanics.
A unified discussion of the mechanics of the swallowing process, and its interpretation through manometric measurements of intraluminal pressure, are presented in this paper. The goals of the discussions are to provide the reader with basic knowledge of pharyngeal, esophageal, and sphincter mechanics; to relate the mechanical processes to intraluminal pressure recordings; and to clarify the relationship between intraluminal pressure and esophageal muscle contractile behavior. The esophageal phase of bolus transport, in particular, is discussed in some detail due to the relatively simple geometry and the straightforward description of peristalsis and muscle mechanics in this region. Several important issues are emphasized in the discussion. For example, pressure variation within a static bolus is fundamentally different from that within a moving bolus. Manometric recordings must be interpreted accordingly. The importance of differentiating between "hydrodynamic pressure," which is pressure measured within a fluid bolus, and "contact pressure," which is the direct squeeze of the luminal wall on the manometric port in a region devoid of bolus fluid, is discussed in some detail. We argue that pressure "amplitude" does not, in principle, give any indication of the forces required to drive the fluid bolus forward. What should be sought is the variation of intrabolus pressure relative to the contact pressure, particularly during periods in which the contractile segment fails to obliterate the esophageal lumen. Examples of intraluminal pressure recording in the esophagus, using manometry and mathematical models, are presented to demonstrate both the possibilities and the difficulties of interpreting manometric recordings in the absence of concurrent radiographic imaging. We discover that in regions of nearly complete luminal closure, the pressure signature and bolus geometry are strongly coupled during peristaltic transport, providing the possibility that in these regions quantitative measures of muscle performance might be developed without the need for radiographic imaging. On the other hand, the ambiguity in the interpretation of manometric recordings that often accompanies dysphagic conditions suggests that as more sophisticated interpretations are sought, manometry concurrent with radiography will play a more prominent role in patient evaluation.


Phase space representation of spatially partially coherent imaging.
The phase space representation of imaging with optical fields in any state of spatial coherence is developed by using spatial coherence wavelets. It leads to new functions for describing the optical transfer and response of imaging systems when the field is represented by Wigner distribution functions. Specific imaging cases are analyzed in this context, and special attention is devoted to the imaging of two point sources.


Redistribution of energy flow in a material due to damping.
The field lines of energy flow of the radiation emitted by a linear dipole in free space are straight lines, running radially outward from the source. When the dipole is embedded in a medium, the field lines are curves when the imaginary part of the relative permittivity is finite. It is shown that due to the damping in the material all radiation is emitted in directions perpendicular to the dipole axis, whereas for a dipole in free space the radiation is emitted in all directions except along the dipole axis. It is also shown that some field lines in the near field form semiloops. Energy flowing along these semiloops is absorbed by the material and does not contribute to the radiative power in the far field.


Estimating Identification Disclosure Risk Using Mixed Membership Models.
Statistical agencies and other organizations that disseminate data are obligated to protect data subjects' confidentiality. For example, ill-intentioned individuals might link data subjects to records in other databases by matching on common characteristics (keys). Successful links are particularly problematic for data subjects with combinations of keys that are unique in the population. Hence, as part of their assessments of disclosure risks, many data stewards estimate the probabilities that sample uniques on sets of discrete keys are also population uniques on those keys. This is typically done using log-linear modeling on the keys. However, log-linear models can yield biased estimates of cell probabilities for sparse contingency tables with many zero counts, which often occurs in databases with many keys. This bias can result in unreliable estimates of probabilities of uniqueness and, hence, misrepresentations of disclosure risks. We propose an alternative to log-linear models for datasets with sparse keys based on a Bayesian version of grade of membership (GoM) models. We present a Bayesian GoM model for multinomial variables and offer an MCMC algorithm for fitting the model. We evaluate the approach by treating data from a recent US Census Bureau public use microdata sample as a population, taking simple random samples from that population, and benchmarking estimated probabilities of uniqueness against population values. Compared to log-linear models, GoM models provide more accurate estimates of the total number of uniques in the samples. Additionally, they offer record-level predictions of uniqueness that dominate those based on log-linear models.


Bilateral percutaneous ulnar artery approach for retrograde chronic total occlusion intervention.
The transradial approach for coronary diagnostic and therapeutic interventions is a well-established, safe, and effective technique that has shown a success rate comparable to that of the transfemoral approach for chronic total occlusion (CTO) with less access site complications. Recently, the transulnar approach was also found to be a safe and feasible alternative for diagnostic and percutaneous coronary intervention (PCI). There is limited data on the efficacy and safety of the transulnar approach for CTO PCI. Here, we report the case of a patient who underwent coronary intervention for CTO via the bilateral ulnar approach.


Quantifying the accessibility of the metagenome by random expression cloning techniques.
The exploitation of the metagenome for novel biocatalysts by functional screening is determined by the ability to express the respective genes in a surrogate host. The probability of recovering a certain gene thereby depends on its abundance in the environmental DNA used for library construction, the chosen insert size, the length of the target gene, and the presence of expression signals that are functional in the host organism. In this paper, we present a set of formulas that describe the chance of isolating a gene by random expression cloning, taking into account the three different modes of heterologous gene expression: independent expression, expression as a transcriptional fusion and expression as a translational fusion. Genes of the last category are shown to be virtually inaccessible by shotgun cloning because of the low frequency of functional constructs. To evaluate which part of the metagenome might in this way evade exploitation, 32 complete genome sequences of prokaryotic organisms were analysed for the presence of expression signals functional in E. coli hosts, using bioinformatics tools. Our study reveals significant differences in the predicted expression modes between distinct taxonomic groups of organisms and suggests that about 40% of the enzymatic activities may be readily recovered by random cloning in E. coli.