Prolonged naproxen joint residence time after intra-articular injection of lipophilic solutions comprising a naproxen glycolamide ester prodrug in the rat.
Intra-articular injection of oil solutions of lipophilic prodrugs that rapidly degrade to their parent compound in synovial fluid may constitute a feasible approach to increase the joint residence time of non-steroidal anti-inflammatory drugs. In this in vivo study, oil solutions of the N,N-diethyl glycolamide ester prodrug of naproxen (16 mg/ml) were injected into the rat knee joint by dosing 6 μl formulation per 100g body weight. The sustained release properties were compared to those of intra-articularly injected aqueous and oil solutions of naproxen by monitoring the naproxen serum concentrations over time. Two oils, medium-chain triglycerides and castor oil, differing with respect to viscosity were tested. After intra-articular administration of oil prodrug solutions, a significant increase in the time to maximum naproxen serum concentration from around 40 to 245 min, an increase in the MRT(j) from around 0.11 to 3.3h and a 30% reduction in the maximum serum concentration were observed compared to that of the parent naproxen. The similar serum profiles obtained using the two oils indicate that the release was not affected by the oil viscosity. A prolonged naproxen joint residence time in rats was shown by intra-articular injection of an oil prodrug solution.


[Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique].
To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. This is an intervention study, which included 40 preterm infants (≤34 weeks) aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5minutes. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50), the end diastolic flow velocity (p=0.17), the mean flow velocity (p=0.07), the resistance index (p=0.41) and the pulsatility index (p=0.67) over time. The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants.


Comparison of oncologic outcomes after radical prostatectomy in men diagnosed with prostate cancer with PSA levels below and above 4 ng/mL.
To assess whether the PSA level (threshold 4 ng/mL) is a prognostic factor in biochemical recurrence-free survival in men with prostate cancer (PCa) with an initial PSA level <10 ng/mL who underwent robotic-assisted laparoscopic radical prostatectomy (RARLP). We prospectively recruited data for consecutive patients treated by RARLP for PCa with an initial PSA level below 10 ng/mL between 2003 and 2011 at our institution. We divided the population into two groups: patients with a PSA level below 4 ng/mL (G1; n = 53) and patients with a PSA level between 4 and 10 ng/mL (G2; n = 371). Biochemical recurrence was defined as a single increase in PSA greater than 0.2 ng/mL after surgery. Multivariate analysis was used to assess prognostic factors of recurrence-free survival. Overall, 424 patients were included, and the median age was 62 (58-67) years. The median PSA was 5.8 ng/mL (4.8-7.7 ng/mL). Overall, 6 patients from G1 and 34 patients from G2 experienced a biochemical recurrence. Overall, the 5-year recurrence-free survival rate was 86.6 %. The PSA level at diagnosis (under or over 4 ng/mL) was not significantly linked to recurrence-free survival (HR = 0.59, p = 0.25). However, positive margins and a Gleason score >7 on the specimen were significantly linked to recurrence-free survival with respective hazard ratios of 4.30 (p < 0.0001) and 6.18 (p < 0.0001), respectively. A PSA level <4 ng/mL alone appears to be obsolete as a cut-off to define a population of men likely to have indolent disease.


Environmental Triggers for Vasculitis.
Systemic vasculitides are autoimmune diseases characterized by vascular inflammation. Most types of vasculitis are thought to result from antigen exposure in genetically susceptible individuals, suggesting a likely role for environmental triggers in these conditions. Seasonal and geographic variations in incidence provide insight into the potential role of environmental exposures in these diseases. Many data support infectious triggers in some vasculitides, whereas other studies have identified noninfectious triggers, such as airborne pollutants, silica, smoking, and heavy metals. We review the known and suspected environmental triggers in giant cell arteritis, Takayasu arteritis, polyarteritis nodosa, Kawasaki disease, and antineutrophil cytoplasmic antibody-associated vasculitis.


Systemically administered N-methyl-D-aspartate interferes with acquisition of a passive avoidance response in rats.
The effect of several doses of systemically administered N-methyl-D-aspartate (NMDA) was studied on step-through passive avoidance (PA) retention in rats. Retention of single trial PA was significantly reduced by preacquisition (30 minutes) doses of NMDA (3, 10, 30, and 50 mg/kg SC). Preacquisition amnesia was found when NMDA (30 mg/kg SC) was administered between two and 60 minutes. At shorter and longer pretreatment times (0.5 and 180 minutes) NMDA (30 mg/kg SC) did not disrupt retention testing. Across the same dose range and pretreatment times, NMDA failed to interfere with PA retention when given after acquisition or before retention testing. The results suggest that systemic NMDA administration can interfere with the acquisition of a PA response but does not alter consolidation of information or retrieval.


Tetrakis-acridinyl peptide: distance dependence of photoinduced electron transfer in deoxyribonucleic acid assemblies.
The distance dependence of photoinduced electron transfer in deoxyribonucleic acid (DNA) duplex was investigated using the "TAP cassette" systems of the general formula (AT)6A(n)XA(9-n) (X denote guanine (G) or cytosine (C)). The tetrakis-9-acridinyl peptide (TAP) binds tightly with (AT)6 duplex region showing strong fluorescence that was not quenched by the A(n)XA(9-n) single-stranded region. Quenching was observed after duplex formation with the complementary T(9-n)XT(n) strand (G-C pairing), showing clear dependence on the distance between the TAP and a guanine. An extremely low beta value of 0.22 was obtained in our electron transfer (ET) system that suggests exceptional good mediation of ET process. Experiments with G-mismatches showed negligible quenching for systems with guanine separated by more than one AT base pair that indicated rather inefficient ET process for duplexes containing disrupted pi-electronic system.


Assembling the puzzle: Oligomerization of α-pore forming proteins in membranes.
Pore forming proteins (PFPs) share the ability of creating pores that allow the passage of ions, proteins or other constituents through a wide variety of target membranes, ranging from bacteria to humans. They often cause cell death, as pore formation disrupts the membrane permeability barrier required for maintaining cell homeostasis. The organization into supramolecular complexes or oligomers that pierce the membrane is a common feature of PFPs. However, the molecular pathway of self-assembly and pore opening remains unclear. Here, we review the most recent discoveries in the mechanism of membrane oligomerization and pore formation of a subset of PFPs, the α-PFPs, whose pore-forming domains are formed by helical segments. Only now we are starting to grasp the molecular details of their function, mainly thanks to the introduction of single molecule microscopy and nanoscopy techniques. This article is part of a Special Issue entitled: Pore-forming toxins edited by Mauro Dalla Serra and Franco Gambale.


Lignin-ultrasound method: Enhancement of antimicrobial capacity of MoS2-containing films.
To improve the antimicrobial ability of MoS2-containing films, we used lignin and triple-frequency ultrasound for liquid-phase exfoliation (LPE) to obtain MoS2 nanosheets. Photoresponsive antimicrobial films with MoS2 nanosheets, lignin, polyvinyl alcohol and deep eutectic solvents were subsequently prepared. Lignin functionalized the MoS2 nanosheets by chemically linking with S in MoS2 and significantly improved the exfoliation efficiency. Tri-frequency ultrasound produces beneficial effects on the LPE process by creating a more homogeneous sound field and a stronger degree of cavitation. The concentration of MoS2 nanosheets in the exfoliating solution could reach 1.713 mg/mL under the effect of lignin-ultrasound. The antimicrobial ability of the films was analyzed, and the colony-forming units of E. coli and S. aureus could be reduced from 7 × 106 to 1 × 106 cfu/mL under the irradiation of infrared. The lignin in the film undergoes depolymerization and demethoxylation under the irradiation of infrared to have a more phenolic hydroxyl structure, which confers the growth inhibition ability of the films for bacteria that cannot be in close contact with the film. The method we used has some significance for the preparation of MoS2 nanosheets, and composite films prepared from MoS2, and lignin can be used in food packaging, wound antimicrobials, and other fields.


Increased c-kit and stem cell factor expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.
Persistent pulmonary hypertension(PPH) in congenital diaphragmatic hernia (CDH) is caused by increased vascular cell proliferation and endothelial cell (EC) dysfunction, thus leading to obstructive changes in the pulmonary vasculature. C-Kit and its ligand, stem cell factor(SCF), are expressed by ECs in the developing lung mesenchyme, suggesting an important role during lung vascular formation. Conversely, absence of c-Kit expression has been demonstrated in ECs of dysplastic alveolar capillaries. We hypothesized that c-Kit and SCF expression is increased in the pulmonary vasculature of nitrofen-induced CDH. Timed-pregnant rats received nitrofen or vehicle on gestational day 9(D9). Fetuses were sacrificed on D15, D18, and D21, and divided into control and CDH group. Pulmonary gene expression levels of c-Kit and SCF were analyzed by qRT-PCR. Immunofluorescence double staining for c-Kit and SCF was combined with CD34 to evaluate protein expression in ECs of the pulmonary vasculature. Relative mRNA levels of c-Kit and SCF were significantly increased in lungs of CDH fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly increased vascular c-Kit and SCF expression in mesenchymal ECs of CDH lungs on D15, D18, and D21 compared to controls. Increased expression of c-Kit and SCF in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that increased c-Kit signaling during lung vascular formation may contribute to vascular remodeling and thus to PPH.


The social weight of spoken words.
Speech serves a linguistic function, cueing sounds and words, and a social function, cueing talkers and their social attributes. Listeners readily map sound patterns in speech to social representations. This mapping introduces social biases on the recognition and encoding of sound patterns produced by different groups and individuals.


KLF8 transcription factor participates in oncogenic transformation.
Kruppel-like factor 8 (KLF8) is a member of the family of KLF transcription factors. Several KLF members have been shown to play a role in oncogenesis. We have previously demonstrated that KLF8 mediates cell cycle progression downstream of focal adhesion kinase (FAK) by upregulating cyclin D1. FAK plays a critical role in transformation and tumorigenesis and is aberrantly upregulated in many types of human cancer. Little is known about the function of KLF8 in these regards. Here we provide evidence suggesting a novel role of KLF8 in oncogenic transformation. We show that KLF8 expression is elevated in several types of human cancer cells and primary tumor tissues. Induced expression of ectopic KLF8 causes serum-independent growth and morphological transformation in NIH3T3 cells and enhances anchorage-independent growth of v-Src-transformed cells. In contrast, expression of a dominant-negative mutant of KLF8 dramatically suppresses the transformed phenotypes induced by v-Src. In addition, the KLF8-enhanced transformation in the v-Src cells was prevented by ablating cyclin D1 expression. Overall, these results indicate that KLF8 is required for v-Src-induced transformation and may play a role in tumor progression of human cancer.


The association between cataract and incidence of cognitive impairment in older adults: A systematic review and meta-analysis.
Cataract has been shown to be associated with an increased risk of cognitive impairment. However, the results of previous studies have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between cataract and the incidence of cognitive impairment in older adults. A comprehensive search of electronic databases from inception to January 2023 was performed to identify relevant studies. Data were extracted from eligible studies and a meta-analysis was performed to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI). We included 13 studies with 25 study arms involving a total of 798,694 participants. Compared with participants without cataract, those with cataract had a higher risk of developing all-cause dementia (pooled HR: 1.22; 95 % CI: 1.08-1.38; I2 =86 %; 9 studies), Alzheimer's disease dementia (pooled HR: 1.18; 95 % CI: 1.07-1.30; I2 =0 %; 9 studies), vascular dementia (pooled HR: 1.21; 95 % CI: 1.02-1.43; I2 =77 %;3 studies) and mild cognitive impairment (pooled HR: 1.30; 95% CI: 1.13-1.50; I2 =0%;2 studies). There was no significant association between cataract and mixed dementia (pooled HR: 1.03; 95 % CI: 0.52-2.04; I2 =78 %;2 studies). We assessed the risk of bias of the included studies using the Newcastle-Ottawa Scale and found that most of them had a low or moderate risk of bias. The number of studies in each meta-analysis ranged from two to nine, with more studies available for all-cause dementia and Alzheimer's disease dementia than for vascular dementia and mixed dementia. The findings suggest that cataract may be associated with cognitive impairment in older adults. However, the causal relationship between cataract and cognition remains unclear and requires further investigation.


Shared antigenicity and immunogenicity of type 4 pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoaea, Dichelobacter nodosus, and Vibrio cholerae.
Immunoblotting with polyclonal rabbit antibodies raised against pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoeae, Dichelobacter nodosus, and Vibrio cholerae was used to demonstrate that these polypeptides display conserved antigenic and, in most cases, immunogenic determinants. These determinants appear to be localized to the highly homologous amino-terminal domains (residues 1 to 25).


Heparin-induced thrombocytopenia: 2008 update.
Unfractionated heparin (UFH) and the low molecular weight heparin (LMWH) preparations are two of the most commonly prescribed medications in the hospital, and indications for their use are increasing. An increasingly recognized untoward effect of either UFH or LMWH is heparin-induced thrombocytopenia (HIT), a transient, prothrombotic condition that may result in venous or arterial thrombosis and amputation or death. This immune-mediated process generally develops within 4 to 14 days of administration, although it may occur more rapidly if there has been a recent exposure; it may even occur days to weeks after UFH or LMWH has been discontinued. Although once considered necessary for the diagnosis of HIT, thrombocytopenia is no longer essential. A 50% reduction in the platelet count from pre-heparin treatment levels is now considered a more specific finding. Prompt recognition, discontinuation of the offending agent, and initiation of an alternative anticoagulant are essential for prevention and/or treatment of these potentially devastating complications.


Evaluation of the Efficacy and Color Stability of Two Different At-Home Bleaching Systems on Teeth of Different Shades: A Randomized Controlled Clinical Trial.
This randomized controlled clinical trial compared the bleaching efficacy of two different at-home bleaching systems on teeth of different shades and their color stability after a 6-month follow-up. Ninety-two patients (777 teeth) were randomly divided into three groups: (a) negative control, (b) patients treated with a custom-made tray containing 10% carbamide peroxide (10% CP/PF) (Opalescence PF), and (c) patients treated with a pre-loaded tray containing 6% hydrogen peroxide (6% HP/Go) (Opalescence Go). Teeth in all groups were divided into three sub-groups according to the VITA Classic Shade Guide: light (A1-C1), medium dark (C2-B3), and dark (A3.5-C4). Bleaching systems were performed in accordance with manufacturers' instructions for 14 days. The color values were measured at the baseline, 10 days and 14 days of bleaching, 2 weeks, and 6 months after bleaching. Three-way ANOVA and Mann-Whitney U tests were used for statistical analysis (α = 0.05). Irrespective of original shade, both bleaching groups showed significantly higher ΔE* values than the control groups, and the ΔE* values were significantly higher in the 10% CP/PF groups than those in the 6% HP/Go groups (p < 0.05). In both bleaching systems, the dark teeth showed higher ΔE* values than the light teeth (p < 0.05). The ΔE* values decreased significantly only in the 10% CP/PF groups after 6 months (p < 0.05). Both bleaching agents produced a bleaching effect, but 10% CP/PF was more effective. A pre-loaded tray system may be used for dental bleaching, but it is still less effective than conventional a 10% carbamide peroxide system, irrespective of the initial shade. (J Esthet Restor Dent 29:325-338, 2017).


Dual spinneret electrospun nanofibrous/gel structure of chitosan-gelatin/chitosan-hyaluronic acid as a wound dressing: In-vitro and in-vivo studies.
Structural and compositional similarity to the natural extracellular matrix (ECM) is a main characteristic of an ideal scaffold for tissue regeneration. In order to resemble the fibrous/gel structure of skin ECM, a multicomponent scaffold was fabricated using biopolymers with structural similarity to ECM and wound healing properties i.e., chitosan (CS), gelatin (Gel) and hyaluronic acid (HA). The CS-Gel and CS-HA nanofibers were simultaneously electrospun on the collector through dual-electrospinning technique. The presence of polymers, possible interactions, and formation of polyelectrolyte complex were proven by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and thermogravimetric analysis (TGA). The noncomplex component of CS-HA fibers formed a gel state when the scaffold was exposed to the aqueous media, while the CS-Gel fibers reserved their fibrous structure, resulting in formation of fibrous/gel structure. The CS-Gel/CS-HA scaffold showed significantly higher cell proliferation (109%) in the first 24 h comparing with CS (90%) and CS-Gel (96%) scaffolds. Additionally, the initial cell adhesion improved by incorporation of HA. The in-vivo wound healing results in rat elucidated more wound healing capability of the CS-Gel/CS-HA scaffold in which new tissue with most similarity to the normal skin was formed.


Influences of health insurance status on clinical treatments and outcomes for 4,714 patients after acute myocardial infarction in 14 Chinese general hospitals.
It is unknown whether insurance status influences care provided and patients' prognosis, in China. This retrospective cohort study included medical records of 4,714 patients with acute myocardial infarction aged 20 and older, discharged consecutively from 14 Chinese hospitals between January 2000 and February 2003. Uni-variate analysis, multivariate logistic regression and linear regression were used to compare differences in patients' characteristics, care provided and prognosis between insured patients and the uninsured. The uninsured were more likely to be older, female, have transfer admissions, and less likely to be hospitalized to institutions with cardiac interventional facilities, intensive care units or coronary care units. The uninsured were also less likely to undergo diagnostic procedures, interventions and to receive medications, and stayed shorter in hospital and consumed less health care resources. In-hospital mortality in the uninsured, the non-government insured and the government insured was 10.5%, 12.2% and 8.4% respectively. After adjusting for potential confounders, odd ratio in hospital mortality was 1.079 (95% CI, 0.836-1.392) and 0.763 (95% CI, 0.559-1.041) for the non-government insured and the government insured, compared to the uninsured. At significant level of 0.05, we could not assert insurance status is a significant factor to in-hospital mortality.


The female athlete triad: a terrible trio implications for primary care.
To describe the components of the female athlete triad, including definitions and clinical criteria for diagnosis, methods of screening, and treatment options. Selected scientific literature; standard diagnostic guidelines. The female athlete triad is a cascading event consisting of disordered eating, amenorrhea, and osteoporosis. This disorder can occur in any sport but is seen most often in events that emphasize thinness and appearance such as gymnastics, ballet, and diving. It can often go unrecognized and result in irreversible bone loss and possible death. Primary care nurse practitioners (NPs) may be the first health care professionals encountering these females; they need to recognize the risk factors and institute a multidisciplinary approach to treatment. The treatment team should be composed of the patient, the NP, a dietitian, a psychologist, psychiatrist, or psychiatric nurse specialist, and the patient's family, coaches, and trainers.


Antipsychotic Medication Use in Nursing Homes: Approaches to Reduce Use and National Trends.
Consensus exists regarding the need to reduce antipsychotic medication use in nursing homes, multiple initiatives have been implemented with the intent to achieve this goal, and progress is being made. While limited high quality research is available documenting the impact of various approaches, resource tool kits and best practice descriptions can help guide efforts.


Optical source apportionment of aqueous brown carbon (BrC) on a daytime and nighttime basis in the eastern Indo-Gangetic Plain (IGP) and insights from 13C and 15N isotopic signatures.
This study reports day-night and seasonal variations of aqueous brown carbon (BrCaq) and constituent humic-like substances (HULIS) (neutral and acidic HULIS: HULIS-n and HULIS-a) from the eastern Indo-Gangetic Plain (IGP) of India during 2019-2020. This is followed by the application of the receptor model positive matrix factorization (PMF) for optical source apportionment of BrCaq and the use of stable isotopic ratios (δ13C and δ15N) to understand atmospheric processing. Nighttime BrCaq absorption and mass absorption efficiencies (MAE) were enhanced by 40-150 % and 50-190 %, respectively, compared to the daytime across seasons, possibly as a combined effect from daytime photobleaching, dark-phase secondary formation, and increased nighttime emissions. MAE250 nm/MAE365 nm (i.e., E2/E3) ratios and Angstrom Exponents revealed that BrCaq and HULIS-n were relatively more aromatic and conjugated during the biomass burning-dominated periods while BrCaq and HULIS-a were comprised mostly of non-conjugated aliphatic structures from secondary processes during the photochemistry-dominated summer. The relative radiative forcing of BrCaq with respect to elemental carbon (EC) was 10-12 % in the post-monsoon and winter in the 300-400 nm range. Optical source apportionment using PMF revealed that BrCaq absorption at 300, 365 and 420 nm wavelengths in the eastern IGP is mostly from biomass burning (60-75 %), followed by combined marine and fossil fuel-derived sources (24-31 %), and secondary processes (up to 10 %). Source-specific MAEs at 365 nm were estimated to be the highest for the combined marine and fossil fuel source (1.34 m2 g-1) followed by biomass burning (0.78 m2 g-1) and secondary processing (0.13 m2 g-1). Finally, δ13C and δ15N isotopic analysis confirmed the importance of summertime photochemistry and wintertime NO3--dominated chemistry in constraining BrC characteristics. Overall, the quantitative apportionment of BrCaq sources and processing reported here can be expected to lead to targeted source-specific measurements and a better understanding of BrC climate forcing in the future.


The oral glucose tolerance test in men under 55 years of age with intermittent claudication.
Blood glucose at sixty, ninety, and one hundred twenty minutes after a standardized oral glucose load was compared in healthy middle-aged men and patients with intermittent claudication. No difference was found when the authors compared blood glucose at zero and sixty minutes. At both ninety and one hundred twenty minutes, however, they found a relative hypoglycemia in patients with peripheral arteriosclerotic disease in an early stage.


A Study of Stakeholder Views to Shape a Communication Strategy for GMO in Brazil.
This paper analyzes the view of stakeholders on genetically modified organisms (GMOs) and the implications of these views on communication strategies for agricultural biotechnology in Brazil. It identifies and describes common groups of attitudes toward GMOs using multivariate statistical analyses. The study then looks for patterns of association between the common attitude groups and the following variables: socioeconomic characteristics trust in institutions as information sources and familiarity with the Brazilian biosafety authority. The article contributes to the understanding of public awareness by highlighting how information sources, trust in institutions, and socioeconomic characteristics, such as age and occupational qualification, play important roles in defining patterns of attitudes toward GMOs. The paper also discusses the implications of this knowledge for the development of a communication strategy plan that would promote public awareness and stimulate a well-informed Brazilian public debate on biosafety.


Alginate-graphene oxide hybrid gel beads: an efficient copper adsorbent material.
Here we report on the adsorption performance of calcium alginate (Ca-Alg2) and Ca-Alg2 with encapsulated graphene oxide (Ca-Alg2/GO) gel bead adsorbents for the successful removal of Cu(2+) ions from aqueous solution. Different adsorbent doses, Cu(2+) concentrations and contact times were investigated using equilibrium and kinetic studies. The adsorbents were characterized using Fourier transform-infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA) and focussed ion beam scanning electron microscopy (FIB/SEM). The equilibrium adsorption data were fitted to Langmuir isotherms and the maximum adsorption capacities of the Ca-Alg2 and Ca-Alg2/GO gel beads were found to be 42.7 mg g(-1) and 60.2 mg g(-1), respectively. The equilibrium adsorption data were fitted to a pseudo-second-order kinetic equation showing that the Ca-Alg2 gel beads had a higher kinetic adsorption rate at 0.0425 g mg(-1)min(-1) compared to Ca-Alg2/GO at 0.0179 g mg(-1)min(-1).


The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat.
Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasingly, allosteric modulation of ligand-gated receptors is recognized as a potential strategy to obtain desired efficacy in the absence of the putative adverse effects associated with agonist activation. We compared the anti-hyperalgesic and anti-inflammatory effects of the α7 nACh receptor agonist compound B with the positive allosteric modulator (PAM) PNU-120596 and the standard non-steroidal anti-inflammatory drug (NSAID), diclofenac, in rats with hind paw inflammation induced by either formalin, carrageenan or complete Freund's adjuvant (CFA). When administered before carrageenan, both diclofenac (30 mg·kg(-1) ) and PNU-120596 (30 mg·kg(-1) ) significantly reduced mechanical hyperalgesia and weight-bearing deficits for up to 4 h. Compound B (30 mg·kg(-1) ) also attenuated both measures of pain-like behaviour, albeit less robustly. Whereas compound B and PNU-120596 attenuated the carrageenan-induced increase in levels of TNF-α and IL-6 within the hind paw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by carrageenan or CFA was also partially reversed by compound B and PNU-120596. However, diclofenac was considerably more efficacious. Formalin-induced nocifensive behaviours were only reversed by compound B, albeit at doses which disrupted motor performance. α7 nACh receptor PAMs could prove to be useful in the treatment of inflammatory pain conditions, which respond poorly to NSAIDs or in situations where NSAIDs are contra-indicated.


Inflammation associated with left ventricular hypertrophy in bipolar disorder: A cross-sectional study.
Inflammation has received increasing attention as a contributor to the pathophysiology of bipolar disorder (BD) and cardiac hypertrophy into heart failure (HF). Accordingly, we chose BD-related inflammatory markers to investigate their relationships with cardiac left ventricular function and structure in BD. Sixty physically healthy and euthymic patients with bipolar I disorder were recruited to compare with 50 healthy normal controls. The echocardiography was performed to estimate left ventricular mass index (LVMI) as a parameter of LV hypertrophy (LVH) and left ventricle ejection fraction (LVEF) as a parameter of systolic function. An LVEF above the normal range (>70%) was defined as a hyperdynamic heart. Participants' levels of inflammatory and atherosclerosis-related parameters were measured. Compared with normal controls, BD group had significantly higher rates of LVH (63% vs. 42%) and hyperdynamic heart (32% vs. 2%) and higher mean values of LVMI and LVEF. After adjustment for the effects of BMI and age, multiple regression analyses of BD group showed that the peripheral level of interleukin-8 was positively associated with LVMI and the level of soluble tumor necrosis factor receptor 1 (sTNF-R1) was positively associated with LVEF. Patients with BD from young adulthood are likely to have LVH with normal LV function and hyperdynamic heart associated with diastolic dysfunction. Low-grade inflammation may underlie the mechanisms of LV hypertrophy and cardiac dysfunction in BD patients.


A facile synthesis of FePS3@C nanocomposites and their enhanced performance in lithium-ion batteries.
FePS3@C nanocomposites are successfully synthesized by a facile two-step route. The as-synthesized samples show excellent thermal and environmental stability. As a novel anode material for lithium batteries, the FePS3@C nanocomposites exhibit a high capacity of 1000 mA h g-1 at a current density of 0.2 A g-1 and excellent reversibility over 100 cycles, indicating their promising applications in lithium storage.


Single shot multispectral multidimensional imaging using chaotic waves.
Multispectral imaging technology is a valuable scientific tool for various applications in astronomy, remote sensing, molecular fingerprinting, and fluorescence imaging. In this study, we demonstrate a single camera shot, lensless, interferenceless, motionless, non-scanning, space, spectrum, and time resolved five-dimensional incoherent imaging technique using tailored chaotic waves with quasi-random intensity and phase distributions. Chaotic waves can distinctly encode spatial and spectral information of an object in single self-interference intensity distribution. In this study, a tailored chaotic wave with a nearly pure phase function and lowest correlation noise is generated using a quasi-random array of pinholes. A unique sequence of signal processing techniques is applied to extract all possible spatial and spectral channels with the least entropy. The depth-wavelength reciprocity is exploited to see colour from depth and depth from colour and the physics of beam propagation is exploited to see at one depth by calibrating at another.


Low spinal anesthesia for the prevention of autonomic dysreflexia in the spinal cord injury patient.
Twenty-five patients with traumatic spinal cord injuries above T7 have been managed with low spinal anesthesia during endoscopic urologic procedures. The technique has been completely successful in preventing autonomic dysreflexia and has not been associated with hypotension.


Ophthalmological findings in brucellosis.
To evaluate the ophthalmological findings in patients diagnosed with acute, subacute or chronic brucellosis and to determine the effects of this disease on ocular structures. Eighty-seven patients diagnosed with brucellosis and 71 healthy cases (as a control group) were enrolled in this prospective study. All participants underwent a complete ophthalmic evaluation, including slit lamp biomicroscopic examination, Goldman applanation tonometry, specular microscopy, optical coherence tomography and fundoscopy with pupil dilation. Overall, ocular involvement was present in 47 eyes of 27 (31.03%) patients diagnosed with brucellosis and was most common in the chronic brucellosis group. In the acute brucellosis group, papillary conjunctivitis in 8 eyes of 4 patients and anterior uveitis in 10 eyes of 6 patients were noted. In the subacute brucellosis group, papillary conjunctivitis in 4 eyes of 2 patients and sequelae of anterior uveitis in 6 eyes of 3 patients were observed. In the chronic brucellosis group, panuveitis in 4 eyes of 2 patients, choroiditis in 4 eyes of 2 patients, and signs of previous anterior uveitis in 11 eyes of 6 patients were noted. Visual acuity was significantly worse in patients with acute anterior uveitis (AAU) or previous anterior uveitis (PAU) compared with the control cases. Ocular involvement should be kept in mind in patients with brucellosis, especially acute, and brucellosis should be included in the differential diagnosis of patients with anterior uveitis living in endemic areas, since the clinical presentation of the disease may not be overt.


Ultrasensitive SERS detection of antitumor drug methotrexate based on modified Ag substrate.
Methotrexate (MTX) is a drug with broad-spectrum antitumor activity that is of great importance in therapeutic drug monitoring applications. In this essay, the two-step modified concentrated Ag colloid with the assistance of KF and MgSO4 was used as the SERS active substrate for the ultrasensitive detection of MTX and its commercial formulations (tablets). It can be found that the two-step modification of the samples is a crucial procedure to remove the by-products in the synthesis of Ag colloid and further concentrate the Ag colloid. Under the optimal detection conditions, the minimum detection concentration of MTX is 1 × 10-16 mol/L. And, there is a good linear relationship over a wide concentration range of 1 × 10-16-1 × 10-6 mol/L. The labelled amounts of the two manufacturers of MTX commercial tablets are in the range of 96.4-104.3% with the RSDs between 1.8% and 3.5% by this method, which are in accordance with the methodological requirements. These results prove that the proposed SERS method exhibits a good reproducibility and ultra-high sensitivity for the detection of the antitumor drug MTX.


Persistent activation of the D1R/Shp-2/Erk1/2 pathway in l-DOPA-induced dyskinesia in the 6-hydroxy-dopamine rat model of Parkinson's disease.
Prolonged l-3,4-dihydroxyphenylalanine (l-DOPA) administration, the gold standard therapy for Parkinson's disease (PD) is associated with serious motor complications, known as l-DOPA-induced dyskinesia (LID). One of the major molecular changes associated with LID is the increased activity of the extracellular signal-regulated kinases 1/2 (Erk1/2) signaling in the medium spiny neurons of the striatum induced by malfunctioning in the dopamine D1 receptor (D1R)-mediated transmission. We have previously established that in the striatum, activation of Shp-2, an intracellular tyrosine phosphatase associated with the D1R, is a requisite for the D1R to activate Erk1/2. In this study, we investigated the role of striatal D1R/Shp-2 complex in the molecular event underlying LID in the 6-OHDA-lesioned rat model of PD. We found that in hemiparkinsonian rats experiencing LID, the physiological interaction between D1R and Shp-2 in the striatum was preserved. In these animals, the chronic activation of D1R either by l-DOPA or by the selective D1R agonist SKF 38393 induced both dyskinesia and Shp-2/Erk1/2 activation. These effects were prevented by the selective D1R-antagonist SCH23390 suggesting the involvement of striatal D1R/Shp-2 complex, via Erk1/2 activation, in the molecular events underlying LID. Interestingly, we found that D1R-mediated Shp-2-Erk1/2 activation was persistently detected in the striatum of dyskinetic rats during l-DOPA washout, with a close correlation between LID severity and the extent of long term activation of both Shp-2 and Erk1/2. Taken together, our data show that in hemiparkinsonian rats developing dyskinesia, the aberrant phosphorylation of Shp-2 by D1R activation, represents an upstream molecular event leading to the persistent phosphorylation of Erk1/2 and therefore a novel therapeutic target to counteract LID development and maintenance during l-DOPA therapy.


When liposomes met antibodies: Drug delivery and beyond.
Drug encapsulated liposomes and monoclonal antibodies (Mabs) are two distinctively different classes of therapeutics, but both aim to become the ultimate "magic bullet". While PEGylated liposomes rely on the enhanced permeability and retention (EPR) effect for accumulation in solid tumor tissues, Mabs are designed to bind tightly to specific surface antigens on target cells to exert effector functions. Immunoliposome (IL) refers to the structural combination of liposomes and antibodies, whereas the antibodies are usually decorated on the liposome surface. ILs can therefore take advantage of interactions between antibodies and cancer cells for more efficient endocytosis and intracellular drug delivery. The antibody structure, affinity, density, as well as the liposome surface properties and drug to lipid ratios all contribute to the IL pharmacokinetic(PK) and pharmacodynamic(PD) behaviors. The optimal formulation parameters may vary for different target cells and tissues. Furthermore, besides the delivery of cytotoxic drugs to cancer cells, new ILs are being developed to interact with multiple target receptors, multiple target cells and trigger multiple therapeutic effects. We envision that the IL format can be a great platform for the molecular engineering of multi-valent, multi-specific interactions to achieve complex biological functions for therapeutic benefits, especially in the area of cancer immunotherapy.


The global stability investigation of the mathematical design of a fractional-order HBV infection.
This work presents approximate solutions of a fractional-order design for hepatitis B virus infection. The numerical solution of the system is given by using an implicit fractional linear multi-step method of the second order. Here, Caputo fractional derivative is considered for fractional derivative. Basic theoretical properties are discussed. We prove the global stability analysis of the fractional-order model. Numerical simulations are demonstrated to display our theoretical results. This current study is to reveal that the order of the fractional derivative β does not affect the regular state's stability concerning both theoretical and numerical results. Besides, if the fractional-order β increases, the solutions converge more rapidly to the regular states. Finally, we note that this study can provide beneficial outcomes for understanding and estimating the dissipation of distinct epidemics.


Sodium alginate-based edible coating containing nanoemulsion of Citrus sinensis essential oil eradicates planktonic and sessile cells of food-borne pathogens and increased quality attributes of tomatoes.
There is a growing interest from the worldwide scientific community in formulating edible- biodegradable coatings to replace non-biodegradable and expensive commercial wax-based coatings for preserving postharvest quality attributes of vegetables including tomatoes. Postharvest tomatoes are a suspected vehicle for both Salmonella and Listeria in food poisoning incidents. In this work, the effectiveness of edible nano-emulsion coatings containing sweet orange essential oil and sodium alginate were prepared and characterized, then evaluated antibacterial and antibiofilm activity against Salmonella and Listeria and simultaneously, examined its coating effect on various quality characteristics of tomatoes at 22 ± 2 °C over a 15 days storage period. DLS (Dynamic light scattering) study revealed stable nanoemulsion formulation with 43.23 nm particle size. The high whiteness index of nanoemulsion has a positive impact on product marketability and desirability. Antibacterial and antibiofilm studies revealed nanoemulsion effectively eradicate both sessile and planktonic forms of Salmonella and Listeria in both single and multi-species culture conditions. Tomatoes coated with edible coating significantly enhanced firmness up to 33%, decreased total mesophilic bacteria including Salmonella and Listeria, and reduced weight loss up to 3 fold lower than uncoated one. Sensory analysis revealed that the use of the edible coating increased the total acceptance scores of tomatoes.


Effect of electrical stimulation of "rewarding" areas of the hypothalamus on habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.
Four groups of 12-month-old C57BL/6J male mice had chronic electrodes implanted in the median forebrain bundle. In three groups the "rewarding" property of electrical stimulation was determined during a single 30-min session of self-stimulation (ISS) before the beginning of the experiment. In the fourth group this test was postponed until the end of experiment. Every two weeks for 12 weeks all animals were subjected to repeated 3-hr cold stress tests consisting of partial physical restraint at an ambient temperature of 10 degrees C. The time interval between tests No. 3 and No. 4 was intentionally delayed up to four weeks. During the 4-week interval, animals of one of the groups tested for ISS remained in their home cages; mice of the second ISS-tested group received daily 30-min sessions of brain stimulation; and animals of the third ISS-tested group were placed daily for 30 min in the experimental chamber where they had been tested for ISS previously but received no brain stimulation. Animals of the fourth group, which were not tested for ISS prior to the experiment, also were placed daily in the experimental chamber without brain stimulation. Repeated cold testing resulted in improvement of cold tolerance (decrease of the rate of decline of colonic temperature during cold exposure) in the second and third tests relative to the first cold test in all groups (cold habituation).(ABSTRACT TRUNCATED AT 250 WORDS)


The Protective Role of Resilience in Emotional Exhaustion Among Dental Students at Clinical Levels.
The epidemic of burnout among dental students has been repeatedly documented. This study aimed to assess burnout, specifically emotional exhaustion (EE), and examined the impact of protective and risk psychological factors for EE among clinical-level dental students in Saudi Arabia (SA). A cross-sectional study was conducted, using a convenience sample of undergraduate dental students who were recruited from five separate dental schools. A self-administered questionnaire was distributed to 500 students to obtain socio-demographic data and to assess the students' psychological characteristics (Maslach Burnout Inventory EE subscale, Dental Environment Stress Scale [DES] and Brief Resilience Scale [BRS]). Descriptive, bivariate and multivariable logistic regression analyses were performed. Of 272 respondents, 53% reported high EE. Adjusted multivariable logistic regression modelling demonstrated that students who reported higher BRS scores were significantly less likely to report high EE (adjusted odds ratio [AOR]=0.79, 95% CI=0.70-0.89, p<0.001). However, females were more than twice as likely as males to report high EE (AOR=2.27, 95% CI=1.14-4.61, p=0.024). In addition, students who reported higher DES scores also reported high EE (AOR=1.10, 95% CI=1.07-1.12, p<0.001). The findings suggest that resilience is a protective factor against high EE, after adjusting for key characteristics. There is a need for a preventive programme that addresses EE, taking into consideration other unexplored underlying factors.


Peripartum hysterectomy: an economic analysis of direct healthcare costs using routinely collected data.
To estimate resource use and costs associated with peripartum hysterectomy for the English National Health Service. Analysis of linked Clinical Practice Research Datalink and Hospital Episodes Statistics (CPRD-HES) data. Women undergoing peripartum hysterectomy between 1997 and 2013 and matched controls. Inverse probability weighted generalised estimating equations were used to model the non-linear trend in healthcare service use and costs over time, accounting for missing data, adjusting for maternal age, body mass index, delivery year, smoking and socio-economic indicators. Primary care, hospital outpatient and inpatient attendances and costs (UK 2015 prices). The study sample included 1362 women (192 cases and 1170 controls) who gave birth between 1997 and 2013; 1088 (153 cases and 935 controls) of these were deliveries between 2003 and 2013 when all categories of hospital resource use were available. Based on the 2003-2013 delivery cohort, peripartum hysterectomy was associated with a mean adjusted additional total cost of £5380 (95% CI £4436-6687) and a cost ratio of 1.76 (95% CI 1.61-1.98) over 5 years of follow up compared with controls. Inpatient costs, mostly incurred during the first year following surgery, accounted for 78% excluding or 92% including delivery-related costs. Peripartum hysterectomy is associated with increased healthcare costs driven largely by increased post-surgery hospitalisation rates. To reduce healthcare costs and improve outcomes for women who undergo hysterectomy, interventions that reduce avoidable repeat hospitalisations following surgery such as providing active follow up, treatment and support in the community should be considered. A large amount of NHS data on peripartum hysterectomy suggests active community follow up could reduce costs, #HealthEconomics.


Production of Gentisyl Alcohol from Phoma herbarum Endophytic in Curcuma longa L. and Its Antagonistic Activity Towards Leaf Spot Pathogen Colletotrichum gloeosporioides.
Endophytes from medicinal plants represent a potential source of bioactive compounds. During the present investigation, fungal endophytes were isolated from turmeric (Curcuma longa), an important medicinal plant. A total of 207 endophytic fungal isolates were obtained from the rhizome of C. longa L. They were grouped into seven genera based on morphological and molecular data. The fungal endophytes of C. longa were evaluated for antifungal activity against Colletotrichum gloeosporioides, the causal organism of leaf spot of turmeric. The disease is a major cause for economic loss in turmeric cultivation. Endophytic Phoma herbarum showed significant activity against C. gloeosporioides and was therefore selected for further studies. A compound gentisyl alcohol was isolated from P. herbarum which showed effective antagonism against C. gloeosporioides. The organism could therefore be used as a biocontrol agent against C. gloeosporioides.


Correlates of physical activity guideline compliance for adolescents in 100 U.S. Cities.
This study assessed the rates and correlates of adolescents' compliance with national guidelines for physical activity. A cross-sectional phone survey of adolescents and their parents was conducted in the 100 largest cities in the United States in 2005. Adolescents ages 14-17 years (n = 6125) were asked how many days during the previous week and during a typical week they were physically active for at least 60 minutes. Compliance was defined as 5+ days per week. Parents provided data on teen's age and race/ethnicity, parental education level, annual household income, and region of residence. Associations among these variables and compliance with physical activity guidelines were examined. Approximately 40% of the females and 57% of the males complied with the national physical activity guidelines. Logistic regression indicated that for both genders, compliance was significantly associated with having higher household income and that, for females only, compliance declined significantly with age. Region of residence did not predict compliance for either gender. A majority of the girls and a large portion of the boys failed to meet the current guidelines, thereby increasing their risks of multiple health problems. Targeting intervention resources for low income teens and older adolescent teen girls is recommended.


High-performance liquid chromatography-inductively coupled plasma profiles of cadmium, zinc, sulphur, and other elements in rat liver supernatants after cadmium injection.
The distribution of cadmium, zinc, sulphur and other elements in the liver supernatants of rats and their variation with time following a single intraperitoneal injection of cadmium chloride were characterized by high-performance liquid chromatography (HPLC) coupled with an inductively coupled plasma. Cadmium that was bound to high-molecular-weight-proteins before the induction of metallothionein was analysed more easily using an Asahipak GS-520 column, whereas the distributions of other elements and of cadmium bound to metallothionein were better characterized on a TSK G3000SW column. Cadmium bound primarily to a distinct high-molecular-weight protein before the induction of metallothionein. After the injection its distribution shifted with time to metallothionein. An atomic emission spectrometer, employing an inductively coupled argon plasma and a vacuum UV monochromator was effectively used as a multi-element specific detector for HPLC.


The characteristics of the positivity to the lactulose breath test in patients with abdominal bloating.
The clinical utility in patients with bloating is still conflicting. We aimed to evaluate the positivity to lactulose breath test (LBT) in patients with bloating, and to assess the clinical characteristics according to the positivity or subtypes of LBT. The patients with abdominal bloating undergoing LBT were investigated. Rome III positive irritable bowel syndrome (IBS) and bowel symptoms were surveyed according to the positivity or subtypes of LBT. The prevalence of IBS and the positivity to LBT was 23.8% (86 of 358) and 29.6% (106 of 358), respectively. The positivity to LBT and the prevalence in subtypes of LBT were not different according to the presence of IBS. The subtypes of LBT positive (+) patients were LBT (H₂) with 61 (57.5%), (CH₄)+ with 30 (28.3%), and (both) positive with 15 (14.2%). The LBT (H₂)+ group was younger, and had higher symptomatic score for the bloating than that in the LBT negative (-) group. The LBT (CH₄)+ group was older, and had higher scores of hard stool and strain than those of the LBT (-) group. In the fasting LBT (H₂)+ group (n=37) diagnosed by increased baseline H₂, the scores for abdominal discomfort, bloating, and flatus were higher than those for the LBT (H₂)+ or LBT(-) groups. The subtypes of the positivity to LBT according to the gas produced or the fasting H₂ may contribute to specificity or severity of abdominal symptoms regardless of the presence of IBS.


Methotrexate therapy in asthma increases T cell susceptibility to corticosteroid inhibition.
Concomitant methotrexate (MTX) therapy of severe, oral corticosteroid-dependent asthmatics has been shown to be corticosteroid sparing, but the mechanism is unknown. We hypothesized that MTX therapy of these patients increases the susceptibility of their T cells to corticosteroid inhibition. To measure prednisolone inhibition of lectin-induced proliferation of peripheral blood T cells from a group of these patients before, during and following MTX therapy. Eighteen severe asthmatics (median (range) age 56 (33-68) years, FEV1 61 (38-69)% predicted, dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high-dose, inhaled corticosteroids) were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. After 12 weeks of MTX, oral prednisolone dosages were reduced systematically over 16 weeks, provided that asthma control did not deteriorate. Patients were followed for a further 12 weeks after MTX withdrawal. Concentration-dependent, prednisolone inhibition of lectin-induced proliferation of peripheral blood T cells was measured just prior to MTX therapy (week 1) and at weeks 12, 28 and 40, and IC50 concentrations were interpolated. By week 28 of MTX therapy, patients were able to reduce oral prednisolone dosages from (median, SIQR) 15 (10-20.5) to 5.9 (1.4-9.4) mg/day (P<0.01) without alteration of lung function and symptoms, while median IC50 values for prednisolone inhibition of peripheral blood T cell proliferation were reduced from 49 (21-144) to 4 (1-9) nm (P<0.0001). These increased again to 15 (9.4-25.7) mg/day and 36 (18-67) nm, respectively, following MTX withdrawal. A correlation (P<0.01) was observed between percentage reductions in prednisolone dosages in vivo and fold changes in prednisolone IC50in vitro between weeks 12 and 28. This effect of MTX may at least partly account for its oral corticosteroid-sparing effect in severe asthma.


Notes on the Stenus cirrus group, with description of two new species from China (Coleoptera, Staphylinidae).
Two new species, Stenus zhangdinghengisp. n., Stenus maoershanussp. n.,of the Stenus cirrus group are described from South China, Guangxi Province. The male of Stenus fellowesi Puthz, 2003 and the female of Stenus huanghaoi Tang & Li, 2008 were discovered for the first time. Their diagnostic characters are illustrated and a key to the Chinese species of the Stenus cirrus group is provided.


Molecular properties of the glutamate receptor mediating synaptic excitation in rat hypothalamic neurons.
AMPA-type glutamate receptors (GluRs) mediate synaptic excitation in networks of cultured rat hypothalamic neurons [18, 25]. Under voltage clamp the agonists quisqualate and AMPA induce current responses which consist of a maintained and/or transient component depending on the concentrations applied. The current-voltage relationship for both components is linear. The biphasic response patterns are due to receptor desensitization which is fast and does not require intracellular second messengers for its activation. Several GluR-subtype-encoding transcripts were found in these neurons using polymerase chain reaction (PCR) methods. While mRNAs encoding the GluR2 and 3 flip forms are expressed early, mRNAs encoding the GluR1, 2 and 3 flop forms and the GluR4 flip form appear only in cultures older than 3 weeks. By comparison to recombinant receptors, the properties of the native receptor can be accommodated by a heteromeric receptor containing GluR2 as one of the subunits.


Indomethacin increases abortifacient effect of PGE2 in man.
Results of this study indicate that pretreatment with indomethacin significantly increases the abortifacient effect of an intravenous infusion of PGE2 in patients admitted for abortion as a result of fetal death in utero. Indomethacin pretreatment shortened the duration of PGE2-induced abortion in primigravid and multigravid groups of patients by about 4 and 2 hours respectively. When primigravid and multigravid groups were combined, the dose of PGE2 needed for complete delivery decreases in the indomethacin-treated group by 39.9%.


Treatment strategies for thymic carcinoma in a real-life setting. Insights from the RYTHMIC network.
Thymic carcinomas are aggressive and difficult to treat a subset of thymic epithelial tumours that represent a heterogeneous group of rare intrathoracic malignancies. The treatment strategy of thymic carcinomas is based on whether surgical resection may be achieved, which represents the most significant favourable prognostic factor on survival. For this study, we took advantage of the unique prospective Réseau tumeurs THYMiques et Cancer (RYTHMIC) database to describe baseline characteristics, analyse treatment strategies in light of existing guidelines and provide landmark patient outcomes data with regards to response and survival of patients in a real-life clinical practice setting. Inclusion criteria for this analysis were the following: (1) histologically-confirmed thymic carcinomas - excluding neuroendocrine tumours-after pathological review by the RYTHMIC pathology panel, (2) discussion of the case at the RYTHMIC multidisciplinary tumour board, (3) at least one active treatment modality. A total of 213 patients were analysed. Overall, 60 (28%) patients were considered as surgical candidates upfront, 91 (43%) patients received primary chemotherapy, and 62 (29%) patients received exclusive chemotherapy. Median overall survival (OS) was 49.2 months (IC95%: 34.8-63.6); OS was significantly longer in patients with a lower stage at diagnosis (p < 0.001), who were operated on upfront, as opposed to patients who received primary or exclusive chemotherapy (p < 0.001). Surgery, conducted upfront or after primary chemotherapy, was significantly associated with more prolonged OS (p < 0.001); complete resection and postoperative radiotherapy were also predictors of better outcome (p = 0.018 and p = 0.051, respectively). Our cohort is the first to analyse in-depth outcomes and treatment strategies in a prospective cohort of consecutive patients with thymic carcinoma. While we confirm the major prognostic impact of surgery, our data highlight the need for optimised multidisciplinary management and innovative therapies as the survival of patients remains limited.


A new species of Anchistrotos Brian, 1906 (Copepoda: Cyclopoida: Taeniacanthidae) from the filamentous shrimpgoby Myersina filifer (Valenciennes) (Perciformes: Gobiidae) in Korean waters.
A new species of Anchistrotos Brian, 1906 (Copepoda: Cyclopoida: Taeniacanthidae), parasitic in the branchial cavities of the filamentous shrimpgoby Myersina filifer (Valenciennes) (Perciformes: Gobiidae) from Korea is described. The new species is most closely related to A. tangi Venmathi Maran, Moon & Adday, 2014, but differs from it by the following combination of characters in the adult female: the U-shaped rostrum, the distal margin of the anal somite lacks patches of spinules, the proximal segment of the maxilliped is without seta, and the maxilliped claw is armed with long and small naked setae. This is the tenth species of the genus and a key is provided to distinguish all nominal species.


The effect of anxiety on heart rate variability, depression, and sleep in chronic obstructive pulmonary disease.
The current study investigates heart rate variability (HRV) responses to a psychosocial stressor in chronic obstructive pulmonary disease (COPD) patients, and the potential role of anxiety as a confounding factor in this relationship. Additionally, this study also investigates the influence of anxiety on sleep and depressive symptoms among COPD patients. The study utilized a 2 (disease status)×2 (anxiety group) factorial design examining HRV associated with anxiety symptoms and COPD during a standardized acute social stress task. Participants (mean age 59.1±11.2 years; 50% female) completed pulmonary function testing, HRV monitoring, and self-report questionnaires assessing psychological factors. 30 COPD patients were age- and gender-matched with 30 healthy controls. HRV response to a psychosocial stressor among participants with higher anxiety (both COPD and healthy) reflected autonomic dysregulation in both time and frequency domains that was not evident among non-anxious participants. COPD participants with higher anxiety reported greater symptoms of depression and poorer sleep quality than did COPD participants with low anxiety. Anxiety is associated with dysregulated HRV response to a psychosocial stressor, but the negative influence of anxiety and COPD on autonomic function did not appear to be additive. Comorbid anxiety in patients with COPD is associated with increased behavioral and psychological symptoms of distress.


Gametocyte development of Plasmodium chabaudi in mice and rats: evidence for host induction of gametocytogenesis.
Gametocytogenesis in Plasmodium chabaudi was studied in intact and splenectomized mice and rats. Blood forms inoculated into mice entered a new asexual cycle, resulting in high parasitaemias 4 days after inoculation. Blood forms inoculated into intact rats were almost eliminated by day 4 after injection. In splenectomized rats, however, the parasitaemia remained constant over this period. With an immunofluorescence test (IFA), using an antiserum to mouse erythrocytes, it was found that the majority of parasites invaded rat erythrocytes, but were unable to enter a new asexual cycle. It was found that up to 50% of the parasites in splenectomized rats developed into gametocytes. The IFA showed that the proportion of gametocytes to asexual forms was very high in splenectomized animals, irrespective of the origin of the host cells-mouse or rat.


Adoption of colonoscopy surveillance intervals in subjects who received polypectomy in southern China: A cost-effectiveness analysis.
We aimed to evaluate the cost-effectiveness of different colonoscopy intervals among average-risk (5 vs 10 years) and high-risk (1 vs 3 years) southern Chinese populations. We constructed a Markov model with a hypothetical population of 100 000 individuals aged 50-85 years. Average risk was defined as 1-2 non-advanced adenomas (tubular adenoma sized < 10 mm without high-grade dysplasia). High risk was defined as ≥ 3 non-advanced adenomas or any advanced adenoma (adenoma sized ≥ 10 mm, with high-grade dysplasia, or with villous/tubulovillous histology). Three strategies were compared: a 5/1 strategy (average-risk subjects: 5-year interval; high-risk subjects: 1-year interval), a 10/3 strategy, and a control strategy (a 10/10 strategy). Costs (US dollar), quality-adjusted-life-years, incremental cost-effectiveness ratio, and net health benefit were calculated. If the incremental cost-effectiveness ratio of one strategy against another was less than willingness-to-pay ($24 302 US/quality-adjusted-life-years), the strategy was more cost-effective than another. Compared with the 10/3 strategy, the 5/1 strategy involved more costs and effects (incremental cost-effectiveness ratio = $40 044 US/quality-adjusted life-years). When the 10/10 strategy was regarded as the control, the 5/1 strategy had a higher incremental cost-effectiveness ratio than the 10/3 strategy ($26 056 vs $10 344 US/quality-adjusted life-years). Furthermore, the 10/3 strategy had the highest net health benefit. A 10/3 interval was more cost-effective than a 5/1 interval. From an economic perspective, our findings supported a 10-year interval for average-risk individuals and a 3-year interval for high-risk subjects. The findings could help form the optimal colonoscopy interval for average-risk and high-risk patients.


Translation of the geriatric emergency department intervention into other emergency departments: a post implementation evaluation of outcomes for older adults.
Increasing numbers of older adults with complex health deficits presenting to emergency departments has prompted the development of innovative models of care. One such model designed to reduce poor outcomes associated with acute healthcare, is the Geriatric Emergency Department Intervention. This intervention is a nurse-led, physician-championed, Emergency Department intervention that improves the health outcomes for frail older adults in the emergency department. This quantitative cohort study aimed to evaluate the healthcare outcomes and costs associated with the implementation of the Geriatric Emergency Department Intervention (GEDI) for adults aged 70 years and over at two hospital sites that implemented the model using the integrated-Promoting Action on Research Implementation in Health Services (i-PARHIS) framework. Hospital A was large teaching hospital located in the tropical north of Australia. Hospital B was a medium sized teaching hospital near Brisbane, Queensland Australia. The effect of the intervention was examined in two ways. Outcomes were compared between: 1) all patients in the pre- and post- implementation periods, and 2) patients seen or not seen by the Geriatric Emergency Department Intervention team in the post-implementation period. The outcomes measured were disposition (discharged home, admitted); emergency department length of stay; hospital length of stay; all cause in-hospital mortality within 28 days; time to re-presentation up to 28 days post-discharge; emergency department and in-hospital costs. Survival analyses were used for the primary and secondary outcome variables and a Cox survival model was used to estimate the associations between variables and outcomes. Multiple regression models were used to examine other secondary outcomes whilst controlling for a range of confounders. The Geriatric Emergency Department Intervention was successfully translated into two different emergency departments. Both demonstrated an increased likelihood of discharge, decreased emergency department length of stay, decreased hospital costs for those who were admitted, with an associated reduction in risk of mortality, for adults aged 70 years and over. The Geriatric Emergency Department Intervention was successfully translated into new sites that adapted the model design. Improvement in healthcare outcomes for older adults presenting to the emergency department was demonstrated, although this was more subtle than in the original model setting.


Current state of clinical end-points assessment in transplant: Key points.
Solid organ transplantation is the treatment of choice for patients with end-stage organ disease. However, organ transplantation can stress the cardiovascular system and decrease immune surveillance, leading to early mortality and graft loss due to multiple underlying comorbidities. Clinical end-points in transplant include death and graft failure. Thus, generating accurate predictive models through regression models is crucial to test for definitive clinical post-transplantation end-points. Survival predictive models should assemble efficient surrogate markers or prognostic factors to generate a minimal set of variables derived from a proper modeling strategy through regression models. However, a few critical points should be considered when reporting survival analyses and regression models to achieve proper discrimination and calibration of the predictive models. Additionally, population-based risk scores may underestimate risk prediction in transplant. The application of predictive models in these patients should therefore incorporate both classical and non-classical risk factors, as well as community-based health indicators and transplant-specific factors to quantify the outcomes in terms of survival properly. This review focuses on assessment of clinical end-points in transplant through regression models by combining predictive and surrogate variables, and considering key points in these analyses to accurately predict definitive end-points, which could aid clinicians in decision making.


Reproducibility and relative validity of a food frequency questionnaire to assess intake of dietary flavonol and flavone in Chinese university campus population.
Epidemiologic studies have shown that populations that consume more fruits and vegetables have lower incidences of some diseases. These health effects have largely been attributed to flavonoid intake and bioavailability. However, no published data on the estimated flavonol and flavone intake of Chinese adults are currently available. Considering reports that food frequency questionnaires (FFQs) have been shown to provide good measurements of energy, macronutrient, and micronutrient intakes, we hypothesized that FFQ may be used to estimate intake of dietary flavonol and flavone. The two 7-day 24-hour dietary recalls (24-HDRs) and plasma levels were used as reference criteria. A total of 128 subjects each completed two 7-day 24-HDR and 2 FFQs, and 92 subjects donated 2 plasma samples. Pearson correlation coefficients and the agreement of quartile categorization between the FFQ and each reference instrument were conducted. Pearson correlation coefficients between 2 FFQs were 0.62 for flavonol and 0.65 for flavone and ranged from 0.48 (quercetin) to 0.63 (luteolin) (all P < .05). Pearson correlation coefficients between FFQ and 24-HDR were 0.62 for flavonol and 0.68 for flavone and ranged from 0.36 (quercetin) to 0.63 (luteolin) (all P < .05). Between the FFQ and plasma samples, Pearson correlation coefficients were 0.52 for flavonol and 0.41 for flavone and ranged from 0.32 (quercetin) to 0.44 (kaempferol) (all P < .05). The complete and partial agreement by quartiles ranged from 70% to 89%. The findings indicate that administering FFQ is a reliable and accurate method of assessing dietary intake of flavonol and flavone.


CT-findings in haemorrhages from aneurysms of the anterior communicating artery: correlation with angiography and clinical course.
CT findings, angiography and clinical course were analyzed in a series of 31 patients with a recent subarachnoid haemorrhage (SAH) from an aneurysm of the anterior communicating artery (ACoAA). It is shown that 3 types of bleedings can be distinguished according to the CT findings. In the first group (52%), suffering a mild or moderate bleeding into the basal cisterns and/or the cisterna lamina terminalis, the aneurysm mostly points downwards and is orientated straight in the midline, the Hunt and Hess Grade at admission is I or II and the prognosis following early surgery is good. In the second group (29%), the aneurysm mostly is orientated towards one side, additional bleeding occurs into the gyrus rectus and the mediobasal frontal lobe, they are in HH Grade II and III and the prognosis following surgery also is relatively good. In group three (19%) however, the aneurysm points upwards, they present with severe bleeding into the cisterna lamina terminalis, the cavum septum pellucidum and rupture into the putamen, hypothalamus and the ventricle. In this group, the HH grade at admission is IV or V and the prognosis is extremely unfavourable. It is concluded, that this classification may be used for decision on early surgery.


Probing the metabolism of γ-glutamyl peptides in cyanobacteria via metabolite profiling and 13 C labeling.
Cyanobacteria are attractive model organisms for the study of photosynthesis and diurnal metabolism and as hosts for photoautotrophic production of chemicals. Exposure to bright light or environmental pollutants and a diurnal lifestyle of these prokaryotes may result in significant oxidative stress. Glutathione is a widely studied γ-glutamyl peptide that plays a key role in managing oxidative stress and detoxification of xenobiotics in cyanobacteria. The functional role and biosynthesis pathways of this tripeptide have been studied in detail in various phyla, including cyanobacteria. However, other γ-glutamyl peptides remain largely unexplored. We use an integrated approach to identify a number of γ-glutamyl peptides based on signature mass fragments and mass shifts in them in 13 C and 15 N enriched metabolite extracts. The newly identified compounds include γ-glutamyl dipeptides and derivatives of glutathione. Carbon backbones of the former turn over much faster than that of glutathione, suggesting that they follow a distinct biosynthesis pathway. Further, transients of isotopic 13 C enrichment show positional labeling in these peptides, which allows us to delineate the alternative biosynthesis pathways. Importantly, the amino acid of γ-glutamyl dipeptides shows much faster turnover compared to the glutamate moiety. The significant accumulation of γ-glutamyl dipeptides under slow-growth conditions combined with the results from dynamic 13 C labeling suggests that these compounds may act as reservoirs of amino acids in cyanobacteria.


Increasing the human menopausal gonadotropin dose--does the response really improve?
This study assesses the effects of attempts to optimize human menopausal gonadotropin (hMG) dosage in 271 patients who had at least two hyperstimulation cycles for in vitro fertilization or gamete intrafallopian transfer. In the first cycle, all patients received clomiphene citrate and hMG 150 IU/d. In the second cycle, the hMG dose was increased in 45% of patients to try to increase the egg yield. In spite of the increase, the population response was practically identical in both cycles. Median numbers of eggs retrieved (6 versus 6), no eggs retrieved (0.4% versus 1%), only one or two eggs retrieved (10% versus 10%), and canceled cycles (10% versus 10.7%). This suggests that increasing the hMG dosage above 150 IU does not increase the number of eggs retrieved. A poor response may be due to inherent differences in follicular development that cannot be overcome by increases in hMG dosage.


Analysis of post-traumatic growth status and its influencing factors in patients with facial palsy.
Facial nerve paralysis in patients occurs in varying degrees of self-image disorders, both physically and mentally, resulting in low self-esteem, anxiety, depression, and even suicide; however, there were few researches on psychological problems in facial palsy patients at home and abroad. This study's objective was to investigate post-traumatic growth (PTG) in facial nerve palsy patients and analyze its influencing factors. Using the convenience sampling method, a total of 47 patients with facial nerve paralysis were enrolled in the current study between June 1, 2016, and May 31, 2017. Post-traumatic growth rating scale was utilized to investigate the post-traumatic growth of these patients, and factors influencing patients' post-traumatic growth were analyzed through collecting the general sociological information, disease-related information, simple coping style questionnaire, and social support rating scale. The total score of post-traumatic growth in patients with facial nerve paralysis was mean (M) = 63.1, standard deviation (SD) = 19.14. The ranking of five dimensional scores from high to low was as follows: new possibilities, personal strength enhancement, appreciation of life, mental changes, and improvement of relationships with others. Multiple linear regression analysis showed that six variables, namely, the personality type, duration with facial nerve paralysis, and four coping styles, consisting of three types of positive coping styles and one negative coping style, could explain 71.6% of the total post-traumatic growth score. Post-traumatic growth in facial nerve palsy patients is moderate. The personality type of patients, the disease duration, and the coping style are the primary influencing factors. Therefore, clinical staffs should perform personalized nursing protocol and psychological intervention for facial nerve palsy patients to reduce their negative mood, improve their compliance with treatment, and help them recover more rapidly.


An examination of the distinction between nouns and verbs: associations with two different kinds of motion.
Four experiments provide evidence that people are biased to associate particular types of motion with nouns and different types of motion with verbs. Novel nouns and verbs were related to two types of motion: (1) path, or the direction of motion of one character with respect to the other character, and (2) movement orientation, or the direction a character was facing as it moved. Subjects associated verbs more strongly with path than with movement orientation. In contrast, they associated nouns more strongly with movement orientation than with path. Movement orientation was associated with both object categories and verbs, inconsistent with a complete division of labor between these two types of categories. These results are consistent, however, with the notion that people are biased to associate verbs with relations between objects, whereas they are biased to associate object categories with motions defined with respect to the object carrying out those motions.


Stimuli-responsive polyelectrolyte multilayer films and microcapsules.
Polyelectrolyte multilayer (PEM) films and particularly hollow capsules composed of PEM shells have gained significant interest since their introduction. Their compositional versatility and easiness of preparation via so-called layer-by-layer assembly led to the development of numerous systems containing also stimuli-responsive components. This paper reviews the achievements related to the formation, determination of structure, and properties of PEM films and capsules responding to major physical, chemical, and biological stimuli. Their applications as e.g., microcarriers for controlled delivery release of active components, substrates for controlled cells' growth, coatings for enhanced surface adhesion, or self-healing anticorrosive systems are shown and discussed. The influence of various stimuli on integrity, permeability of the films or capsules shell are presented together with related applications in biomedicine for controlled drug release as well as in biotechnology and industrial protective coatings.


Generation & characterization of expandable human liver sinusoidal endothelial cells and their application to assess hepatotoxicity in an advanced in vitro liver model.
Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells forming the hepatic sinusoidal wall. Besides their high endocytic potential, LSECs have been demonstrated to markedly contribute to liver homeostasis and immunity, and may partially explain unexpected hepatotoxicity of drug candidates. However, their use for in vitro investigations is compromised by poor cell yields and a limited proliferation capacity. Here, we report the transient expansion of primary human LSECs from three donors by lentiviral transduction. Transduced ("upcyte®") LSECs were able to undergo at least 25 additional population doublings (PDs) before growth arrest due to senescence. Expanded upcyte® LSECs maintained several characteristics of primary LSECs, including expression of surface markers such as MMR and LYVE-1 as well as rapid uptake of acetylated LDL and ovalbumin. We further investigated the suitability of expanded upcyte® LSECs and proliferating upcyte® hepatocytes for detecting acetaminophen toxicity at millimolar concentrations (0, 0.5, 1, 2, 5, 10 mM) in static 2D cultures and a microphysiological 3D model. upcyte® LSECs exhibited a higher sensitivity to acetaminophen-induced toxicity compared to upcyte® hepatocytes in 2D culture, however, culturing upcyte® LSECs together with upcyte® hepatocytes in a co-culture reduced APAP-induced toxicity compared to 2D monocultures. A perfused Dynamic42 3D model was more sensitive to acetaminophen than the 2D co-culture model. Cytotoxicity in the 3D model was evident by decreased cellular viability, elevated LDH release, reduced nuclei counts and impaired cell morphology. Taken together, our data demonstrate that transient expansion of LSECs represents a suitable method for generation of large quantities of cells while maintaining many characteristics of primary cells and responsiveness to acetaminophen.


The effect of synthetic polymers on the electrical and permeability properties of lipid membranes.
1. The effect of two series of hydrophilic and hydrophobic polymers on the stability, conductivity and permeability towards water and leucine of black lipid membranes and liposomes is reported. 2. The changes in properties of these membrane preparations is related to bulk phase viscosity and dielectric measurements together with monolayer studies. 3. The hydrophobic polymers dramatically increase membrane stability, had no effect on conductivity, but increased the permeability coefficient of leucine. 4. The hydrophilic polymers produced minor, but significant changes to membrane properties. 5. It is concluded that not only basic polymers but also neutral and acidic macromolecules can interact strongly with lipid membranes.


Autologous pericardial patch without infarctectomy for the treatment of acute cardiac rupture.
Acute cardiac rupture is a complication of acute myocardial infarction and is often a lethal condition. The successful management of a case of left ventricular rupture by patch repair with concomitant myocardial revascularization is reported. Pre- and postoperative hemodynamic stabilization was achieved with the aid of intra-aortic balloon pump counterpulsation.


Heterologous expression and biochemical comparison of two homologous SoxX proteins of endosymbiotic Candidatus Vesicomyosocius okutanii and free-living Hydrogenovibrio crunogenus from deep-sea environments.
Candidatus Vesicomyosocius okutanii is a currently uncultured endosymbiotic bacterium of Phreagena okutanii, a clam that inhabits deep-sea vent environments. The genome of Ca. V. okutanii encodes a sulfur-oxidizing (Sox) enzyme complex, presumably generating biological energy for the host from inorganic sulfur compounds. Here, Ca. V. okutanii SoxX (VoSoxX), a mono-heme cytochrome c component of the Sox complex, was shown to be phylogenetically related to its homologous counterpart (HcSoxX) from a free-living deep-sea bacterium, Hydrogenovibrio crunogenus. Both proteins were heterologously expressed in Escherichia coli co-expressing cytochrome c maturation genes for comparative biochemical analysis. The VoSoxX recombinant had significantly lower thermal stability than HcSoxX, reflecting the difference in growth conditions of the source bacteria. The endosymbiont inhabits a mild intracellular environment, whereas the free-living bacterium dwells in a harsh environment. This study represents the first successful case of heterologous expression of genes from Ca. V. okutanii, allowing further biochemical studies of the molecular mechanism of sulfur oxidation in deep-sea environments.


Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication.
The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found.


A wall of information? Exploring the public health component of maternity care in England.
midwives have traditionally had an important role in providing public health messages to women. The range and diversity of the public health remit within maternity services has expanded rapidly over the past decade and maternity support workers as well as midwives are now engaged in public health work in many areas. Given these changes a review of current practice was indicated. to identify student midwives׳, midwives׳ and midwifery support workers׳ current knowledge of and involvement in the public health agenda in England. descriptive qualitative study using online discussion forums. England, United Kingdom undergraduate student midwives, midwives and maternity support workers employed by the National Health Service in England and University employed Leads for Midwifery Education. key themes identified were: the scope of the midwives׳ public health role, training and support for public health role, barriers and facilitators, specific client groups, specialist referral services. Student midwives, midwives and maternity support workers view engagement with, and delivery of, public health initiatives as an integral component of their roles, but are on occasions frustrated by constraints of time, training and public engagement. the National Health Service in England aims to engage pregnant women and new mothers in a diverse range of population based and individualised, public health initiatives. Currently, there are high levels of involvement in the public health agenda from the maternity workforce across a wide range of activities. However, midwives and maternity support workers are restricted by barriers of time, training and resources. These barriers will need addressing for optimal maternity care engagement in public health to be realised. policy makers, commissioners and National Health Service providers need to provide clear guidance on the expectations of the public health remit of midwives and maternity support workers and ensure that such expectations are appropriately resourced to provide effective delivery.


Low rectal toxicity after dose escalated IMRT treatment of prostate cancer using an absorbable hydrogel for increasing and maintaining space between the rectum and prostate: results of a multi-institutional phase II trial.
To evaluate the safety and efficacy of an absorbable hydrogel when injected between the rectum and prostate to reduce rectal radiation toxicity in adult men undergoing Intensity Modulated Radiotherapy (IMRT) for treatment of low and intermediate risk prostate cancer. This prospective, non-randomized, multi-center, single arm, open-label study included 52 men with a confirmed diagnosis of prostate cancer. They received transperineal injection of the hydrogel and 3-5 days after injection the simulation scans. All patients received IMRT (78Gy delivered, 2 Gy per fraction). Space stability was evaluated by using MRI or CT. Gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using RTOG/EORTC scoring system and proctoscopy after 12 months. The median follow up time was 12 months. Hydrogel application was straight forward using brachytherapy equipment and techniques, with minimal patient discomfort. Six patients (12%) experienced acute GI Grade 2 toxicity, with no patients experiencing Grade 3 or 4 toxicity. In addition, no patients had early late GI toxicity ≥ Grade 2 after 12 months. The gel was stable during the course of radiotherapy and was not detectable in MRI after 9-12 months due to absorption in 42 of 43 patients. These data demonstrated that the hydrogel is a safe method to displace the rectal wall away from the prostate therefore substantially reducing toxicity to the rectum.


Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenic.
Long-term exposure to arsenic in drinking water has been linked to cancer and other health effects, including cardiovascular disease. Arsenic in the environment is found in combination with a range of metals that could influence its toxicity. Manganese, in particular, is a metal that is typically found in conjunction with arsenic in contaminated groundwater. Peroxynitrite is a powerful oxidant formed from the reaction between nitric oxide and superoxide anion. Arsenic has been shown to increase the formation of peroxynitrite in bovine aortic endothelial cells (BAECs) and promote the formation of 3-nitrotyrosine (3-NY) in the atherosclerotic plaque of ApoE-/-/LDLr-/- mice. Arsenic exposure also increases leukotriene E4 (LTE4) formation in both the mice and BAECs, an effect that is partially reversed by the addition of Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. In the present study, we investigated the effect of adding nontoxic concentrations of manganese along with arsenic to BAEC cultures. Manganese increased arsenic toxicity and enhanced peroxynitrite, 3-NY, and LTE4 formation in BAECs. Addition of LNAME reduced 3-NY formation induced by arsenic/manganese mixtures, but in contrast to its effect on arsenic alone, L-NAME actually increased LTE4 synthesis in BAECs treated with the arsenic/manganese combination. Overall, these data suggest that manganese may exacerbate the toxic effects of arsenic on the vascular system.


The involvement of parents and nurses in the care of acutely-ill children in a non-specialist paediatric setting.
The examination of both parents' and nurses' expectations and attitudes towards parental participation in the care of ill children in a community hospital, non-specialty setting was undertaken in this exploratory, qualitative research study within Australia. First, in this triangulated research study, 14 in-depth interviews with parents were carried out about their participation in the care of their ill children. Content analysis revealed that the four main themes were to do with parental factors including control, expectations, support and emotion; communication; the importance of being with your child; and the fact that mothers do the mothering and nurses do the nursing. Two focus group sessions were held with paediatric nursing staff. Content analysis confirmed real communication problems between nurses and parents. Implications that arose for nursing practice were for in-service workshops to improve communication between nurses and families as well as workshops to prepare students of university nursing programmes offering paediatric electives.


Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1.
In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population. The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients' survival time was partitioned into three health states - toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations. Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time. Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1-positive mTNBC.


Cesarean section and subsequent fertility: results from the 1982 National Survey of Family Growth.
The purpose of this article was to examine the question of fertility after a cesarean section. The study design is that of a retrospective cohort study with matched pairs, using the cross-sectional interview data of the 1982 National Survey of Family Growth. The subsequent fertility of 406 women who had had their first delivery by cesarean section is compared with that of 406 matched control women. Using any of several measures, women who had had a cesarean section had lower fertility. The difference in fertility seemed to result largely from difficulties in having children after a cesarean section, rather than lessened desire for children. Sterilizations were more frequent and performed earlier among women who had had a cesarean section than among the control women.


[Malnutrition screening in hospitalized children: influence of the hospital unit on its management].
The aims of this study were to assess the prevalence of malnutrition in a pediatric population hospitalized in a French regional hospital and to evaluate the influence of type of hospital unit (pediatric or not) in the screening and the management of malnutrition. This one-day cross-sectional survey was performed in three different seasons during 2003. Every child aged 2 months to 16 years old, hospitalized for more than 48 hours was included. Weight for height, Z-score and Body Mass Index Z-score were used for nutritional assessment. Type of hospitalisation unit, date of admission, associated diagnosis, screening and treatment of malnutrition were also taken into account. Two hundred and eighty hospitalized children were undernourished (11%) and thirty-one children were obese (11%) with no difference in prevalence of malnutrition between pediatric and non-pediatric units. At the time of the study, malnutrition was recognized in one third of the children, at a similar rate whatever the type of hospitalized unit. The children hospitalized in pediatrics wards benefited more frequently from nutritional intervention, i.e. dietician care (43 vs. 16% P < 0.01). Prevalence of malnutrition in hospitalized children is low and the same in pediatric or non-pediatric units. Screening of malnutrition remains unsatisfactory in hospital. However, malnutrition is more frequently treated in pediatric unit compared with non-pediatric unit.


Compositional Variability and Toxic Activity of Mugwort (Artemisia vulgaris) Essential Oils.
The compositional variability of the essential oils of aerial parts of mugwort (Artemisia vulgaris L.), collected from fifteen wild populations in Lithuania is detailed. The most predominant components were davanones (13.8-45.5%, six oils), germacrene D (9.1-30.5%, four oils), 1,8-cineole (16.4%, one oil), camphor (18.9%, one oil), trans-thujone (8.9 and 10.9%, two oils) and cis-chrysanthenyl acetate (10.4%, one oil). To the best of our knowledge, the davanone chemotype for A. vulgaris oils is described for the first time. The toxicity of the mugwort essential oils was determined using brine shrimp (Anemia sp.) assay. LC0 values (10.3-23.1 μg/mL) obtained for the oils after 24 h of exposure revealed that the oils containing appreciable amounts of germacrene D, 1,8-cineole, camphor and davanone were notably toxic.


Hypovitaminosis D in developing countries-prevalence, risk factors and outcomes.
Hypovitaminosis D is a prevalent disorder in developing countries. Clinical manifestations of hypovitaminosis D include musculoskeletal disorders, such as nonspecific muscle pain, poor muscle strength and low BMD, as well as nonmusculoskeletal disorders, such as an increased risk of respiratory infections, diabetes mellitus and possibly cardiovascular diseases. In developing countries, the prevalence of hypovitaminosis D varies widely by and within regions; prevalence ranges between 30-90%, according to the cut-off value used within specific regions, and is independent of latitude. A high prevalence of the disorder exists in China and Mongolia, especially in children, of whom up to 50% are reported to have serum 25-hydroxyvitamin D levels <12.5 nmol/l. Despite ample sunshine throughout the year, one-third to one-half of individuals living in Sub-Saharan Africa and the Middle East have serum 25-hydroxyvitamin D levels <25 nmol/l, according to studies published in the past decade. Hypovitaminosis D is also prevalent in children and the elderly living in Latin America. Risk factors for hypovitaminosis D in developing countries are similar to those reported in Western countries and include extremes of age, female sex, winter season, dark skin pigmentation, malnutrition, lack of sun exposure, a covered clothing style and obesity. Clinical trials to assess the effect of vitamin D supplementation on classical and nonclassical clinical outcomes in developing countries are needed.


Multi modal imaging in corneal edema after corneal collagen cross-linking (CXL); a case-based literature review.
Keratoconus (KCN) is a common ectatic disorder of the cornea. Corneal collagen cross-linking (CXL) is used as an effective option to slowdown the disease progression. Although CXL is considered a safe procedure, corneal endothelial damage, especially in corneal thickness of less than 400 μm, has been reported. A 25-year-old man known case of KCN was referred with complaints about blurred vision and discomfort of the right eye 3 days after performing CXL. The preoperative thinnest point was 461 μm. His presenting BCVA was CF at 1 m. Examination showed central corneal edema and stromal haziness. ASOCT demonstrated increased central corneal thickness and very deep CXL line. In the confocal scan, anterior stroma showed hyper-reflective lines without recognizable cells and nerves, the middle stroma showed rare active and edematous keratocytes and a hyper-reflective reticular pattern with elongated keratocytes and needle-like structures involving the posterior stroma indicated increased depth of CXL. To manage the patient, debridement of loosened epithelium was done. Non-preservative steroid 1% eye drop was prescribed frequently. The corneal edema was completely resolved during 2 months with no need for surgical procedure and BCVA of 20/30 in his right eye. The corneal thickness of more than 400 μm cannot guarantee the absence of corneal edema after corneal collagen cross-linking, which can pertain to several factors such as inadvertently using of higher energy as well as the incorrect observance of all guidelines, instructions, and other precautions, even by a trained surgeon.