Photochromic dibenzobarrlenes: long-lived triplet biradical intermediates.
Upon exposure to UV light, the disubstituted dibenzobarrelene derivative 1a turns green in the solid phase and reverts back to its original pale-yellow color within several hours in the dark. The lifetime of the colored species in degassed benzene at room temperature is 37 +/- 2 s (Ea for decoloration is 14.5 +/- 0.7 kcal mol-1 and log A is 8.92 +/- 0.5 s-1) and highly sensitive to molecular oxygen; the Stern-Volmer quenching constant is 6.9 +/- 0.2 x 108 M-1 s-1. Similarly, the disubstituted dibenzobarrelenes 1b and 1c exhibited pink coloration when exposed to UV light in the solid phase. On the basis of combined experimental and theoretical evidence, it is proposed that upon photoexcitation the excited singlet state of 1a undergoes rapid intersystem crossing to its triplet state, followed by intramolecular delta-H abstraction, to yield the triplet biradical intermediate (3)2. Upon prolonged irradiation, 2 undergoes cyclization to the alcohol 3, which affords the enone 4 as the final photoproduct. The delta-H abstraction on the triplet-state potential energy surface, calculated at the B3LYP/6-31G* level of density functional theory (DFT), has an activation energy of 18.5 kcal/mol. Further, the absorption spectrum of the triplet biradical (3)2, obtained from time-dependent DFT calculations, displays an intense absorption maximum at 670 nm, which is in good agreement with the observed absorption peak at 700 nm. The molecular-orbital analysis of the triplet diradical (3)2 suggests that its long-wavelength absorption involves the transition of the unpaired electron from the comparatively localized benzyl-type HOMO to the extensively conjugated benzoyl-type LUMO. The present experimental and theoretical results strongly support the intervention of a long-lived triplet biradical (3)2 in the photochromism of appropriately substituted dibenzobarrelenes.


Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review.
Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF-κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor-β, Wnt/β-catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N-acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti-inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.


The holistic effects of medical cannabis compared to opioids on pain experience in Finnish patients with chronic pain.
Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only targeting pain intensity. However, this hypothesis has not been previously systematically tested. A retrospective internet survey was used in a sample of Finnish chronic pain patients (40 MC users and 161 opioid users). The patients evaluated statements describing positive and negative phenomenological effects of the medicine. The two groups were propensity score matched to control for possible confounding factors. Exploratory factor analysis revealed three experience factors: Negative Side Effects, Positive Holistic Effects, and Positive Emotional Effects. The MC group (matched n = 39) received higher scores than the opioid group (matched n = 39) in Positive Emotional Effects with large effect size (Rank-Biserial Correlation RBC = .71, p < .001), and in Holistic Positive Effects with medium effect size (RBC = .47, p < .001), with no difference in Negative Side Effects (p = .13). MC and opioids were perceived as equally efficacious in reducing pain intensity. Ratings of individual statements were exploratively examined in a post hoc analysis. MC and opioids were perceived to be equally efficacious in reducing pain intensity, but MC additionally positively affected broader pain-related factors such as emotion, functionality, and overall sense of wellbeing. This supports the hypothesis that MC alleviates pain through holistically altering the pain experience.


[Spread of tumor tissue and prognosis in stomach cancer].
The report deals with an analysis of a 3-year follow-up of 38 patients of stage III stomach cancer. Tumor tissue disaggregation was investigated in the said patients using methods developed by the authors. The tumor disaggregation rate in patients dead within the first two years after surgery was higher (275 +/- 6.6) than in those dead within three years (237 +/- 10.8) or longer (235 +/- 7.2). High rate of tumor tissue disaggregation proved to be an unfavorable prognostic factor.


Association of PRPS1 Mutations with Disease Phenotypes.
Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I superactivity resulting in purine overproduction. Patients with PRS-I superactivity demonstrate uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. On the other hand, decreased activity leads to X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I. Mild PRS-I deficiency (DFNX-2) results in non-syndromic progressive hearing loss whereas moderate PRS-I deficiency (CMTX5) and severe PRS-I deficiency (Arts syndrome) present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment. Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in patients with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients and open new avenues of therapeutic intervention.


Hemodialysis catheter-associated superior vena cava syndrome and pulmonary embolism: a case report and review of the literature.
Hemodialysis (HD) catheters are frequently inserted into the superior vena cava (SVC), and can lead to thrombotic complications. However, to our knowledge, HD catheter-related thrombosis leading to subsequent SVC syndrome, bacteremia, and pulmonary emboli has not been described. A 28-year-old dialysis-dependent woman with IgA nephropathy developed facial swelling, head pressure, headache, nausea, dizziness and fever 6 weeks after right internal jugular (IJ) HD catheter placement. Chest and neck imaging demonstrated a non-occlusive thrombus surrounding the HD catheter and extending from the SVC to the junction of the right IJ and right subclavian veins, confirming thrombosis-associated SVC syndrome. Intravenous (IV) anticoagulation was initiated, as well as IV vancomycin for Staphylococcus epidermidis bacteremia. Despite prompt intravenous anticoagulation, 9 and 12 days after initial presentation she developed catheter-associated pulmonary embolism (PE) and PE-associated pulmonary infarction, respectively. Hypercoagulable workup was negative. The HD catheter was eventually replaced, HD resumed, and the patient was transitioned from intravenous to oral anticoagulation and discharged. Nine months later, she underwent successful renal transplantation. SVC syndrome and pulmonary embolism are potential consequences of HD catheter-related thrombosis. Given the frequency of HD catheter placement, physicians should be aware of these potential complications in any patient with HD catheter-related thrombosis.


Structure-Stability-Function Mechanistic Links in the Anti-Measles Virus Action of Tocopherol-Derivatized Peptide Nanoparticles.
Measles remains one of the leading causes of child mortality worldwide and is re-emerging in some countries due to poor vaccine coverage, concomitant with importation of measles virus (MV) from endemic areas. The lack of specific chemotherapy contributes to negative outcomes, especially in infants or immunodeficient individuals. Fusion inhibitor peptides derived from the MV Fusion protein C-terminal Heptad Repeat (HRC) targeting MV envelope fusion glycoproteins block infection at the stage of entry into host cells, thus preventing viral multiplication. To improve efficacy of such entry inhibitors, we have modified a HRC peptide inhibitor by introducing properties of self-assembly into nanoparticles (NP) and higher affinity for both viral and cell membranes. Modification of the peptide consisted of covalent grafting with tocopherol to increase amphipathicity and lipophilicity (HRC5). One additional peptide inhibitor consisting of a peptide dimer grafted to tocopherol was also used (HRC6). Spectroscopic, imaging, and simulation techniques were used to characterize the NP and explore the molecular basis for their antiviral efficacy. HRC5 forms micellar stable NP while HRC6 aggregates into amorphous, loose, unstable NP. Interpeptide cluster bridging governs NP assembly into dynamic metastable states. The results are consistent with the conclusion that the improved efficacy of HRC6 relative to HRC5 can be attributed to NP instability, which leads to more extensive partition to target membranes and binding to viral target proteins.


Appetite for vitamin C: its relationship to cellular energy potential.
Appetite for vitamin C varies between individuals who consume it for control of inflammatory respiratory, and central nervous symptoms, all of which may have an allergic etiology. The mechanisms affecting appetite for vitamin C are discussed. Ascorbic acid is involved in the appreciation of taste which is diminished in allergic disease, as is appetite in scorbutic conditions. The actions of some appetite-depressant drugs such as fenfluramine, are reduced by administration of vitamin C. It appears that appetite diminished when brain ascorbic levels are reduced below a critical level. When tissue ascorbic acid concentrations are reduced, cellular electric potential is diminished. Cellular electric potential is diminished in allergic disease concurrently with development of symptoms. It is suggested that patho-physiological changes in the nervous system may occur in consequence of increased utilisation of ascorbic acid resulting from allergic and iatrogenic challenge. Appetite for vitamin C would be then be affected on an idiosyncratic basis. It is possible that this appetite is controlled by a neurological feed-back mechanism, activation of which is determined by reduction in cellular electric potential of tissues depleted by ascorbic acid.


Evaluating the environmental parameters that determine aerobic biodegradation half-lives of pesticides in soil with a multivariable approach.
Aerobic biodegradation half-lives (half-lives) are key parameters used to evaluate pesticide persistence in soil. However, half-life estimates for individual pesticides often span several orders of magnitude, reflecting the impact that various environmental or experimental parameters have on half-lives in soil. In this work, we collected literature-reported half-lives for eleven pesticides along with associated metadata describing the environmental or experimental conditions under which they were derived. We then developed a multivariable framework to discover relationships between the half-lives and associated metadata. We first compared data for the herbicide atrazine collected from 95 laboratory and 65 field studies. We discovered that atrazine application history and soil texture were the parameters that have the largest influence on the observed half-lives in both types of studies. We then extended the analysis to include ten additional pesticides with data collected exclusively from laboratory studies. We found that, when data were available, pesticide application history and biomass concentrations were always positively associated with half-lives. The relevance of other parameters varied among the pesticides, but in some cases the variability could be explained by the physicochemical properties of the pesticides. For example, we found that the relative significance of the organic carbon content of soil for determining half-lives depends on the relative solubility of the pesticide. Altogether, our analyses highlight the reciprocal influence of both environmental parameters and intrinsic physicochemical properties for determining half-lives in soil.


[Remote results of proxopheline therapy of patients with primary open-angle glaucoma].
Effects of an original Russian combined preparation proxofelin, consisting of 1% proxodolol and 0.25% clofelin solutions, on intraocular pressure (IOP), hydrodynamics, ocular function, arterial pressure, and heart rate have been evaluated in 42 patients (59 eyes) with primary open-angle glaucoma for up to 2 years. Examinations were carried out before proxofelin therapy and after 6, 12, 18, and 24 months of regular therapy (twice a day). Pronounced hypotensive effect on IOP (10.0 +/- 0.3-11.2 +/- 0.2 mm Hg) was due to a significant increase (p < 0.01) in the discharge easiness coefficient (by 50-77% in comparison with the initial value) and suppressed production of aqueous humor (by 40-50% of the initial level). Visual acuity did not change, visual field was significantly (p < 0.05) extended during all terms of examinations, changes in arterial pressure and heart rate during long-term therapy were negligible. The hypotensive effect of proxofelin was insufficient in 20% patients; in such cases its combination with pilocarpin was effective. In the rest patients tolerant IOP was attained by instillations of the monopreparation. Hence, proxofelin is an effective drug for treating primary open-angle glaucoma; its efficiency is apparently due to its hypotensive action.


The hydrophobic force: measurements and methods.
The hydrophobic force describes the attraction between water-hating molecules (and surfaces) that draws them together, causing aggregation, phase separation, protein folding and many other inherent physical phenomena. Attempts have been made to isolate the range and magnitude of this interaction between extended surfaces for more than four decades, with wildly varying results. In this perspective, we critically analyse the application of common force-measuring techniques to the hydrophobic force conundrum. In doing so, we highlight possible interferences to these measurements and provide physical rationalisation where possible. By analysing the most recent measurements, new approaches to establishing the form of this force become apparent, and we suggest potential future directions to further refine our understanding of this vital, physical force.


Intensity, polarization, and phase information in optical disk systems.
Digital information in optical data storage systems can be encoded in the intensity, in the polarization state, or in the phase of a carrier laser beam. Intensity modulation is achieved at the surface of the storage medium either through destructive interference from surface-relief features (e.g., CD or DVD pits) or through reflectivity variations (e.g., alteration of optical constants of phase-change media). Magneto-optical materials make use of the polar magneto-optical Kerr effect to produce polarization modulations of the focused beam reflected from the storage medium. Both surface-relief structures and material-property variations can create, at the exit pupil of the objective lens of the optical pickup, a phase modulation (this, in addition to any intensity or polarization modulation or both). Current optical data storage systems do not make use of this phase information, whose recovery could potentially increase the strength of the readout signal. We show how all three mechanisms can be exploited in a scanning optical microscope to reconstruct the recorded (or embedded) data patterns on various types of optical disk.


A pharmacoepidemiological study of the multi-level determinants, predictors, and clinical outcomes of biosimilar epoetin alfa for renal anaemia in haemodialysis patients: background and methodology of the MONITOR-CKD5 study.
Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants.


Participating in a support group: experience lived by women with breast cancer.
The goal of the study was to understand the meaning of support groups in the life of women with breast cancer. It is a qualitative study with 30 mastectomized women who belonged to six support groups in the city of Fortaleza, Ceará. Data were collected with semi-structured interviews, organized and analyzed based on the interactionism concept. The results characterized the support groups as a mechanism to cope with the situation and to overcome the suffering derived from the diagnosis and treatment of the breast carcinoma. The socialization of the experiences facilitated the search for assistance in the support groups, since sharing the problems with mastectomized women was a way to preserve a high self-esteem, have faith and overcome some difficulties. Participating in the group provided well-being and a differentiated care, since it was considered a way to know, accept and understand the disease and its cure, facilitating the socialization of ideas.


Subclavian artery patch angioplasty. Treatment of infants and young children with aorta coarctation.
Repair of thoracic aorta coarctation in infants has had a high recurrence rate in most series. Recurrence is the result of several factors, but the type and growth of anastomosis are of primary importance. Subclavian artery patch angioplasty was used consecutively in eight children under the age of 5 years. There are six long-term survivors who have been observed for an average of 22 months. Body surface area during this time increased from a mean of 0.22 sq m preoperatively to a mean of 0.54 sq m at present. Blood pressure in the arms and legs were recorded at recent examination using an ultrasound pressure recorder. Only one patient had a substantial gradient (30 mm Hg). All survivors are asymptomatic. Use of the subclavian artery appears to allow for growth at the repair site.


Individual neuronal subtypes control initial myelin sheath growth and stabilization.
In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors. To address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes. In the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons. We conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.


Biochemical and cytochemical evidence indicates that coated vesicles in chick embryo myotubes contain newly synthesized acetylcholinesterase.
We have isolated highly purified coated vesicles from 17-d-old chick embryo skeletal muscle. These isolated coated vesicles contain acetylcholinesterase (AChE) in a latent, membrane-protected form as demonstrated enzymatically and morphologically using the Karnovsky and Roots histochemical procedure (J. Histochem. Cytochem., 1964, 12:219-221). By the use of appropriate inhibitors the cholinesterase activity can be shown to be specific for acetylcholine. It also can be concluded that most of the AChE represents soluble enzyme since it is rendered soluble by repeated freeze-thaw cycles. To determine the origin of the coated vesicle-associated AChE, we have isolated coated vesicles from cultured chick embryo myotubes which have been treated with diisopropylfluorophosphate, an essentially irreversible inhibitor of both intra- and extracellular AChE, and have been allowed to recover for 3 h. This time is not enough to allow any newly synthesized AChE to be secreted. These coated vesicles also contain predominantly soluble AChE. These data are compatible with the hypothesis that coated vesicles are important intermediates in the intracellular transport of newly synthesized AChE.


Conditions and extent of volatile loss from the Moon during formation of the Procellarum basin.
Rocks from the lunar interior are depleted in moderately volatile elements (MVEs) compared to terrestrial rocks. Most MVEs are also enriched in their heavier isotopes compared to those in terrestrial rocks. Such elemental depletion and heavy isotope enrichments have been attributed to liquid-vapor exchange and vapor loss from the protolunar disk, incomplete accretion of MVEs during condensation of the Moon, and degassing of MVEs during lunar magma ocean crystallization. New Monte Carlo simulation results suggest that the lunar MVE depletion is consistent with evaporative loss at 1,670 ± 129 K and an oxygen fugacity +2.3 ± 2.1 log units above the fayalite-magnetite-quartz buffer. Here, we propose that these chemical and isotopic features could have resulted from the formation of the putative Procellarum basin early in the Moon's history, during which nearside magma ocean melts would have been exposed at the surface, allowing equilibration with any primitive atmosphere together with MVE loss and isotopic fractionation.


[Serum osteocalcin in insulin-dependent diabetic patients].
Serum osteocalcin (BGP) is the currently most reliable marker of osteoblastic activity and of the bone formation index. To investigate its state in patients with insulin-dependent diabetes mellitus (IDDM) we measured the BGP level in 82 individuals divided in two groups. The control group (CG) consisted of 26 healthy volunteers (16 males and 10 females: mean age 25.6 +/- 2.8 years). The diabetic group (DG) consisted of 56 patients with IDDM (36 males and 20 females; mean age 23.2 +/- 6 years). The DG was, in its turn, subdivided in four subgroups (A, B, C, D) depending on the time from the diagnosis (TE) (less than 2, 2-5, 5-10, and greater than 10 years). The DG had a significantly lower BGP than CG (3.01 +/- 1.5 vs 3.9 +/- 1.7 ng/nl; p = 0.024). BGP levels were also lower in the subgroups C (2.4 +/- 1.0 ng/ml; p = 0.006) and D (1.7 +/- 0.9 ng/ml; p = 0.000) than in CG. When they were compared between them, the subgroups A (3.6 +/- 1.1 ng/ml) and B (4.5 +/- 1.4 ng/ml) had BGP levels significantly higher than subgroups C (2.4 +/- 1.0 ng/ml; p = 0.009 and p = 0.000) and D (1.7 +/- 0.9 ng/ml; p = 0.000 and p = 0.000). There were no differences between subgroups A and B, on the one hand, and C and D, on the other. There was a highly significant lineal correlation between TE and the BGP levels (r = 0.5196; p = 0.000). The patients with IDDM have reduced BGP levels; this reduction becomes apparent after 5 years of clinical evolution and shows a correlation with the time since the diagnosis.


Airway remodelling in asthma: from benchside to clinical practice.
Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.


Brief version of the coping health inventory for parents (CHIP) among family caregivers of children with chronic diseases.
The Coping Health Inventory for Parents (CHIP) has demonstrated good psychometric properties in several language forms and has been used to assess the coping behaviors of families facing disease. However, the CHIP has not been validated in Mexico among families of children with chronic conditions, where it could be useful for research and intervention. The objectives of this instrumental study were to obtain a version of the CHIP for the Spanish language in Mexico, establish the factor structure of the Mexican version of the CHIP, probe its internal consistency reliability, and assess its concurrent construct validity. A nonprobability sample of 405 family caregivers of children with chronic diseases responded to a battery of measurement instruments that included the CHIP, the Beck Anxiety Inventory, and the Beck Depression Inventory. The sample was randomly divided into two parts. In one subsample (190 participants), an exploratory factor analysis was performed using a principal component analysis and oblique rotation. In the second subsample (215 participants), a confirmatory factor analysis was performed using maximum likelihood estimation. The scale was reduced to 16 items (CHIP-16) with factorial loads greater than .50. The empirical criteria used to determine the number of factors converged on the following five factors: belief and trust (McDonald ω = .85), spouse/partner relationship (ω = .79), home care (ω = .77), family involvement (ω = .75), and security/stability (ω = .79). The overall internal consistency was good (ω = .88). The five-factor model showed acceptable fit indices and high parsimony. The mean CHIP-16 scores and the Spouse/partner relationship scores among the caregivers with anxiety were greater than those among the caregivers without anxiety. The mean home-care scores among the women were greater than those among men. The 16-item version of the CHIP showed good internal consistency and construct validity; thus, the CHIP-16 is a useful instrument for measuring and assessing coping in family caregivers of children with chronic diseases.


A common mechanism underlies vertebrate calcium signaling and Drosophila phototransduction.
Drosophila phototransduction is an important model system for studies of inositol lipid signaling. Light excitation in Drosophila photoreceptors depends on phospholipase C, because null mutants of this enzyme do not respond to light. Surprisingly, genetic elimination of the apparently single inositol trisphosphate receptor (InsP(3)R) of Drosophila has no effect on phototransduction. This led to the proposal that Drosophila photoreceptors do not use the InsP(3) branch of phospholipase C (PLC)-mediated signaling for phototransduction, unlike most other inositol lipid-signaling systems. To examine this hypothesis we applied the membrane-permeant InsP(3)R antagonist 2-aminoethoxydiphenyl borate (2-APB), which has proved to be an important probe for assessing InsP(3)R involvement in various signaling systems. We first examined the effects of 2-APB on Xenopus oocytes. We found that 2-APB is efficient at reversibly blocking the robust InsP(3)-mediated Ca(2+) release and store-operated Ca(2+) entry in Xenopus oocytes at a stage operating after production of InsP(3) but before the opening of the surface membrane Cl(-) channels by Ca(2+). We next demonstrated that 2-APB is effective at reversibly blocking the response to light of Drosophila photoreceptors in a light-dependent manner at a concentration range similar to that effective in Xenopus oocytes and other cells. We show furthermore that 2-APB does not directly block the light-sensitive channels, indicating that it operates upstream in the activation of these channels. The results indicate an important link in the coupling mechanism of vertebrate store-operated channels and Drosophila TRP channels, which involves the InsP(3) branch of the inositol lipid-signaling pathway.


Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood.
Klebsiella pneumoniae is a prominent cause of nosocomial infections worldwide. Bloodstream infections caused by carbapenem-resistant K. pneumoniae, including the epidemic lineage known as multilocus sequence type 258 (ST258), are difficult to treat, and the rate of mortality from such infections is high. Thus, it is imperative that we gain a better understanding of host defense against this pathogen as a step toward developing novel therapies. Here we tested the hypothesis that the resistance of ST258 to bactericidal components of human blood, such as serum complement, is linked to virulence capacity in the context of bacteremia. There was significant variance in the survival of ST258 clinical isolates in heparinized human blood or normal human serum. The rate of survival of ST258 isolates in human blood was, in general, similar to that in normal human serum, suggesting a prominent role for complement (rather than leukocytes) in the healthy host defense against ST258 isolates and related organisms. Indeed, deposition of serum complement-the C5b to C9 (C5b-C9) membrane attack complex-onto the surface of ST258 isolates accompanied serum bactericidal activity. Human serum treated with pharmacological inhibitors of complement, depleted of antibody, or heated at 56°C for 30 min had significantly reduced or absent bactericidal activity. In contrast to heparinized blood from humans, that from BALB/c mice lacked bactericidal activity toward the ST258 isolates tested, but the virulence of these ST258 isolates in a mouse bacteremia model was inexplicably limited. Our data highlight the importance of the complement system in host defense against ST258 bacteremia, and we propose that there is the potential to enhance complement-mediated bactericidal activity using an antibody-based approach.


Single-Step Printable Hydrogel Microarray Integrating Long-Chain DNA for the Discriminative and Size-Specific Sensing of Nucleic Acids.
A simple approach to fabricating hydrogel-based DNA microarrays is reported by physically entrapping the rolling circle amplification (RCA) product inside printable in situ gelling hydrazone cross-linked poly(oligoethylene glycol methacrylate) hydrogels. The hydrogel-printed RCA microarray facilitates improved RCA immobilization (>65% even after vigorous washing) and resistance to denaturation relative to RCA-only printed microarrays in addition to size-discriminative sensing of DNA probes (herein, 27 or fewer nucleotides) depending on the internal porosity of the hydrogel. Furthermore, the high number of sequence repeats in the concatemeric RCA product enables high-sensitivity detection of complementary DNA probes without the need for signal amplification, with signal/noise ratios of 10 or more achieved over a short 30 min assay time followed by minimal washing. The inherent antifouling properties of the hydrogel enable discriminative hybridization in complex biological samples, particularly for short (∼10 nt) oligonucleotides whose hybridization in other assays tends to be transient and of low affinity. The scalable manufacturability and efficient performance of these hydrogel-printed RCA microarrays thus offer potential for rapid, parallel, and inexpensive sensing of short DNA/RNA biomarkers and ligands, a critical current challenge in diagnostic and affinity screening assays.


Phenotypic integration in response to incubation environment adaptively influences habitat choice in a tropical lizard.
Phenotypic integration, in which a suite of traits change in a correlated or covarying response to shifts in environmental conditions, may enhance an organism's fitness. In skinks, rocky environments select for longer limbs and rapid running and climbing. We examined whether differences in nest temperature coincident with specific habitats caused phenotypically integrated effects on morphology, locomotor performance, and behavior in the skink Carlia longipes. Specifically, we determined whether microhabitat choices were integrated with adaptive morphology for each habitat. Using a split-clutch design, we incubated eggs at thermal regimes that mimicked the thermal environments of nests from two habitat types (forest = warm; rocky = cool). Hatchlings from cool incubation environments had longer limbs and greater running and climbing speeds, which are likely to be beneficial for rocky habitats. In addition, individuals from cool incubation environments selected rocky microhabitats more frequently than did hatchlings from warm incubation environments. We demonstrate phenotypic integration in response to nest temperature that affected morphology, performance, and ultimately habitat selection in a way that should increase hatchling fitness.


Neurological impairment in a surviving twin following intrauterine fetal demise of the co-twin: a case study.
It has been established that twin pregnancies are at an increased risk for complications, including the risk of morbidity or mortality for one or both of the infants. Cerebral palsy and other associated neurological deficits also occur at higher rates in twin pregnancies. This report examines two cases of intrauterine demise of one twin with subsequent survival of the co-twin. In both cases, the surviving infant suffered significant neurological sequelae. Impairments observed in these two cases include multicystic encephalomalacia and periventricular leukomalacia as well as the subsequent development of cerebral palsy. This case study explores the predisposing factors, incidence, pathophysiology, consequences, and future research implications of these findings.


Osteosarcomas of the mandible: are they different from other tumor sites?
Osteosarcomas of the mandible (MOS) affect 1/10 million persons/year, mostly the young adult. Due to lack of specific data, the treatment of MOS is extrapolated from that of extragnathic OS but varies widely between institutions. We aimed at providing a focused description of MOS histologies and grades through the English literature, at determining the evidence-based role of chemotherapy, of adjuvant radiation therapy and the potential of reconstructive surgery tailored through modern pre-operative multi-modal imaging. The estimated proportion of high grade MOS was 58%. However, low-grade MOS may be underestimated as they are mostly reported as case reports. The intermediate grade was hardly found in the literature. Estimated weighted-mean proportions of chondroblastic and osteoblastic MOS were 37% and 46%, respectively. Multimodal imaging modalities including MRI has a great potential for accurate pre-operative assessment of tumor extensions into bone and soft tissues. Surgery is the mainstay of treatment and margins the most important factor. The role of neoadjuvant chemotherapy in treating occult systemic metastases and in increasing the probability of clear margins is controversial, as well as the histology-dependent response to chemotherapy. The role of adjuvant radiotherapy (mostly proposed for positive margins) and/or adjuvant chemotherapy is still controversial. Crude survival is around 77% and local control around 67%. Local failure is the main cause of death in MOS compared to extragnathic sites.


Cutaneous draining sinus tract of odontogenic origin: unusual presentation of a challenging diagnosis.
A 44-year-old woman presented with a chronically draining lesion on her cheek just lateral to the nasofacial sulcus. The lesion was refractory to treatment with oral antibiotics. Physical examination revealed poor dentition, and a panoramic radiograph demonstrated periapical abscesses in the maxillary right lateral incisor and canine. A diagnosis of cutaneous fistula of odontogenic origin was made, and the patient was treated with tooth extraction. The cutaneous fistula subsequently resolved. Intraoral examinations and radiographs are critical for making the diagnosis of cutaneous draining sinus tract of odontogenic origin. Many patients undergo unnecessary surgical therapies before having the correct diagnosis made, but root canal therapy or surgical extraction is the treatment of choice. A dental origin must be considered for any chronically draining sinus of the face or neck.


Perceptions of gender-based discrimination during surgical training and practice.
Women represent 15% of practicing general surgeons. Gender-based discrimination has been implicated as discouraging women from surgery. We sought to determine women's perceptions of gender-based discrimination in the surgical training and working environment. Following IRB approval, we fielded a pilot survey measuring perceptions and impact of gender-based discrimination in medical school, residency training, and surgical practice. It was sent electronically to 1,065 individual members of the Association of Women Surgeons. We received 334 responses from medical students, residents, and practicing physicians with a response rate of 31%. Eighty-seven percent experienced gender-based discrimination in medical school, 88% in residency, and 91% in practice. Perceived sources of gender-based discrimination included superiors, physician peers, clinical support staff, and patients, with 40% emanating from women and 60% from men. The majority of responses indicated perceived gender-based discrimination during medical school, residency, and practice. Gender-based discrimination comes from both sexes and has a significant impact on women surgeons.


Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives.
Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.


A Boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells.
Reduction in cholesterol blood levels represents one of the therapeutic goals to achieve in order to reduce the occurrence of cardiovascular diseases. Commonly, this goal is attempted by promoting healthy lifestyle behaviors and low-fat diets. Recently, several nutraceuticals have been shown to possess cholesterol-lowering properties and are becoming common over the counter products. Among others, apple polyphenols efficiently lower total cholesterol levels in humans and impact overall lipid metabolism. Malus Pumila Miller cv Annurca is an apple native to Southern Italy presenting one of the highest content of procyanidin B2, a dimeric procyanidin. Tested in clinical trials, the oral consumption of an Annurca polyphenolic extract (AAE) exerted a cholesterol-lowering effect similar to the statins Atorvastatin and Simvastatin. Despite AAE activity, the analysis of the molecular mechanism behind its cholesterol-lowering effect is unclear. Using isotope labeling and high-resolution mass spectrometry approaches we here performed a metabolic profiling of in vitro cultured human hepatocytes treated with AAE to reveal its mechanism of action. The results show that AAE acts differently than statins. The extract reprograms hepatic cell metabolism and promotes mitochondrial respiration, lipolysis and fatty acid β-oxidation. Citrate and acetyl-CoA, both necessary for the production of cholesterol, are diverted to the Krebs Cycle by AAE, that, ultimately, lowers cholesterogenesis and fatty acid synthesis.


Cryopreservation of canine spermatozoa: theoretical prediction of optimal cooling rates in the presence and absence of cryoprotective agents.
In the present study a shape independent differential scanning calorimeter (DSC) technique was used to measure the dehydration response during freezing of ejaculated canine sperm cells. Volumetric shrinkage during freezing of canine sperm cell suspensions was obtained at cooling rates of 5 and 10 degrees C/min in the presence of extracellular ice and CPAs (6 different combinations of freezing media were used, ranging from a media with no CPAs, and those with 0.5%, 3%, and 6% glycerol and with 0.5% and 3% Me(2)SO). Using previously published data, the canine sperm cell was modeled as a cylinder of length 105.7mum and a radius of 0.32mum with an osmotically inactive cell volume, V(b), of 0.6 V(o), where V(o) is the isotonic cell volume. By fitting a model of water transport to the experimentally obtained volumetric shrinkage data the best fit membrane permeability parameters (L(pg) and E(Lp)) were determined. The "combined best fit" membrane permeability parameters at 5 and 10 degrees C/min for canine sperm cells in the absence of CPAs are: L(pg)=0.52x10(-15)m(3)/Ns (0.0029mum/min-atm) and E(Lp)=64.0kJ/mol (15.3kcal/mol) (R(2)=0.99); and the corresponding parameters in the presence of CPAs ranged from L(pg)[cpa]=0.46 to 0.53x10(-15) m(3)/Ns (0.0027-0.0031mum/min-atm) and E(Lp)[cpa]=46.4-56.0kJ/mol (11.1-13.4kcal/mol). These parameters are significantly different than previously published parameters for canine and other mammalian sperm obtained at suprazero temperatures and at subzero temperatures in the absence of extracellular ice. The parameters obtained in this study also suggest that optimal rates of freezing canine sperm cells ranges from 10 to 30 degrees C/min; these theoretical cooling rates are found to be in close conformity with previously published but empirically determined optimal cooling rates.


Longitudinal association of serum 25-hydroxyvitamin D levels with metabolically healthy body size transition in children and adolescents: A prospective cohort study with 2 years of follow-up.
Although the associations of vitamin D with obesity and metabolic abnormalities have been reported, the role of vitamin D in the transition of obesity phenotype remains unclear but is highly desired since it is crucial to identify potential methods for obesity management. Therefore, we aimed to investigate the relationship between vitamin D and the risk for metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO) in metabolically healthy children with 2 years of follow-up. Data were collected from a population-based cohort consisting of 6424 metabolically healthy children aged 6-16 years at baseline. Metabolic abnormalities including hypertension, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), hyperglycemia, and hyperuricemia were assessed both at baseline and follow-up. Baseline serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured as exposure. The obesity phenotype transition was evaluated by weight status with the combination of metabolic health status from baseline to follow-up. During a 2-year follow-up, 889 (13.8 %) incident MUO cases occurred. For participants with obesity, each 10 nmol/L increment in 25(OH)D concentrations was associated with a 21 % (95%CI: 13 %∼43 %) and a 7 % (95%CI: 1 %∼14 %) decreased risk in high TG and hyperuricemia, respectively. A 51 % (95%CI: 22 %∼69 %) lower risk of MUO was observed in participants with sufficient vitamin D levels (≥50 nmol/L) compared to those with vitamin D deficiency (<30 nmol/L). Besides, among children who were MHO at baseline, those with sufficient vitamin D levels (≥50 nmol/L) were more likely to transition to metabolically healthy normal weight (MHNW) than vitamin D deficient individuals (<30 nmol/L). Vitamin D may prevent the development of MUO and help increase the transition from MHO to MHNW. The findings highlight that vitamin D might be an effective nutrient for obesity management.


Quantitative analysis of visually reviewed normal scalp EEG predicts seizure freedom following anterior temporal lobectomy.
Anterior temporal lobectomy (ATL) is a widely performed and successful intervention for drug-resistant temporal lobe epilepsy (TLE). However, up to one third of patients experience seizure recurrence within 1 year after ATL. Despite the extensive literature on presurgical electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities to prognosticate seizure freedom following ATL, the value of quantitative analysis of visually reviewed normal interictal EEG in such prognostication remains unclear. In this retrospective multicenter study, we investigate whether machine learning analysis of normal interictal scalp EEG studies can inform the prediction of postoperative seizure freedom outcomes in patients who have undergone ATL. We analyzed normal presurgical scalp EEG recordings from 41 Mayo Clinic (MC) and 23 Cleveland Clinic (CC) patients. We used an unbiased automated algorithm to extract eyes closed awake epochs from scalp EEG studies that were free of any epileptiform activity and then extracted spectral EEG features representing (a) spectral power and (b) interhemispheric spectral coherence in frequencies between 1 and 25 Hz across several brain regions. We analyzed the differences between the seizure-free and non-seizure-free patients and employed a Naïve Bayes classifier using multiple spectral features to predict surgery outcomes. We trained the classifier using a leave-one-patient-out cross-validation scheme within the MC data set and then tested using the out-of-sample CC data set. Finally, we compared the predictive performance of normal scalp EEG-derived features against MRI abnormalities. We found that several spectral power and coherence features showed significant differences correlated with surgical outcomes and that they were most pronounced in the 10-25 Hz range. The Naïve Bayes classification based on those features predicted 1-year seizure freedom following ATL with area under the curve (AUC) values of 0.78 and 0.76 for the MC and CC data sets, respectively. Subsequent analyses revealed that (a) interhemispheric spectral coherence features in the 10-25 Hz range provided better predictability than other combinations and (b) normal scalp EEG-derived features provided superior and potentially distinct predictive value when compared with MRI abnormalities (>10% higher F1 score). These results support that quantitative analysis of even a normal presurgical scalp EEG may help prognosticate seizure freedom following ATL in patients with drug-resistant TLE. Although the mechanism for this result is not known, the scalp EEG spectral and coherence properties predicting seizure freedom may represent activity arising from the neocortex or the networks responsible for temporal lobe seizure generation within vs outside the margins of an ATL.


Distribution and sampling of the whiteflies Aleurothrixus floccosus, Dialeurodes citri, and Parabemisia myricae (Homoptera: Aleyrodidae) in citrus in Spain.
From 1993 to 1995 data sets were collected from four citrus groves in Valencia, Spain, to determine the distribution patterns of eggs and nymphs of Aleurothrixus floccosus (Maskell), Dialeurodes citri (Ashmead), and Parabemisia myricae (Kuwana) on leaves, and to develop reliable sampling plans for estimating densities of immature whiteflies. A. floccosus showed higher aggregation than the other two species. The dispersion index b from the Taylor power law did not vary between different developing stages for A. floccosus and D. citri, reaching overall values of 1.70 and 1.53, respectively. In P. myricae, b was 1.60 for eggs and N1, and 1.46 for the remaining nymphs. The minimum number of leaves to estimate the population density with a coefficient of variation of 0.25 for densities above 10 immature whiteflies per leaf was 40 for D. citri and P. myricae, and 250 for A. floccosus. Binomial sampling programs for the three species were rejected for pest management purposes due to the high sample sizes required. The enumerative procedure of counting the number of insects per leaf appears to be the most suitable method for D. citri and P. myricae. For A. floccosus an index of occupation (from 0 to 10) linearly related to the proportion of the leaf undersurface occupied by this insect was found to be reliable and time-saving. Examining 150 leaves with this index achieves the desired relative variation level of 0.25 for most population densities usually found in commercial groves.


Biomonitoring of atmospheric pollution with heavy metals in the copper mine vicinity located near Radovis, Republic of Macedonia.
This investigation was undertaken to determine the atmospheric pollution with heavy metals due to copper mining Bucim near Radovis, the Republic of Macedonia. Moss samples (Hyloconium splendens and Pleurozium schrebery) were used for biomonitoring the possible atmospheric pollution with heavy metals in mine vicinity. Sixteen elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mn, Na, Ni, Pb, Sr, and Zn) were analysed by application of flame and electrothermal atomic absorption spectrometry (FAAS and ETAAS) and atomic emission spectrometry with inductively coupled plasma (ICP-AES). The obtained values were statistically processed using nonparametric and parametric analysis. The median value for copper obtained from moss samples (10 mg kg(-1)) was much lower compared with the same values for the whole territory of the Republic of Macedonia (22 mg kg(-1)). The range of values (2.1-198 mg kg(-1)) shows much higher content of this element in the samples taken from the study area compared to the appropriate values for the whole territory of Macedonia. The association of elements As, Cd, Cu, Fe, Pb, and Zn was singled out by factor analysis as a characteristic anthropogenic group of elements. Maps of area deposition were made for this group of elements, wherefrom correlation of these anthropogenic born elements was confirmed.


Enhancing partner support to improve smoking cessation.
While many cessation programmes are available to assist smokers in quitting, research suggests that support from individual partners, family members, or 'buddies' may encourage abstinence. To determine if an intervention to enhance one-to-one partner support for smokers attempting to quit improves smoking cessation outcomes, compared with cessation interventions lacking a partner-support component. We limited the search to the Cochrane Tobacco Addiction Group Specialised Register, which was updated in April 2018. This includes the results of searches of the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (via OVID); Embase (via OVID); and PsycINFO (via OVID). The search terms used were smoking (prevention, control, therapy), smoking cessation and support (family, marriage, spouse, partner, sexual partner, buddy, friend, cohabitant and co-worker). We also reviewed the bibliographies of all included articles for additional trials. We included randomised controlled trials recruiting people who smoked. Trials were eligible if they had at least one treatment arm that included a smoking cessation intervention with a partner-support component, compared to a control condition providing behavioural support of similar intensity, without a partner-support component. Trials were also required to report smoking cessation at six months follow-up or more. Two review authors independently identified the included studies from the search results, and extracted data using a structured form. A third review author helped resolve discrepancies, in line with standard methodological procedures expected by Cochrane. Smoking abstinence, biochemically verified where possible, was the primary outcome measure and was extracted at two post-treatment intervals where possible: at six to nine months and at 12 months or longer. We used a random-effects model to pool risk ratios from each study and estimate a summary effect. Our update search identified 465 citations, which we assessed for eligibility. Three new studies met the criteria for inclusion, giving a total of 14 included studies (n = 3370). The definition of partner varied among the studies. We compared partner support versus control interventions at six- to nine-month follow-up and at 12 or more months follow-up. We also examined outcomes among three subgroups: interventions targeting relatives, friends or coworkers; interventions targeting spouses or cohabiting partners; and interventions targeting fellow cessation programme participants. All studies gave self-reported smoking cessation rates, with limited biochemical verification of abstinence. The pooled risk ratio (RR) for abstinence was 0.97 (95% confidence interval (CI) 0.83 to 1.14; 12 studies; 2818 participants) at six to nine months, and 1.04 (95% CI 0.88 to 1.22; 7 studies; 2573 participants) at 12 months or more post-treatment. Of the 11 studies that measured partner support at follow-up, only two reported a significant increase in partner support in the intervention groups. One of these studies reported a significant increase in partner support in the intervention group, but smokers' reports of partner support received did not differ significantly. We judged one of the included studies to be at high risk of selection bias, but a sensitivity analysis suggests that this did not have an impact on the results. There were also potential issues with detection bias due to a lack of validation of abstinence in five of the 14 studies; however, this is not apparent in the statistically homogeneous results across studies. Using the GRADE system we rated the overall quality of the evidence for the two primary outcomes as low. We downgraded due to the risk of bias, as we judged studies with a high weighting in analyses to be at a high risk of detection bias. In addition, a study in both analyses was insufficiently randomised. We also downgraded the quality of the evidence for indirectness, as very few studies provided any evidence that the interventions tested actually increased the amount of partner support received by participants in the relevant intervention group. Interventions that aim to enhance partner support appear to have no impact on increasing long-term abstinence from smoking. However, most interventions that assessed partner support showed no evidence that the interventions actually achieved their aim and increased support from partners for smoking cessation. Future research should therefore focus on developing behavioural interventions that actually increase partner support, and test this in small-scale studies, before large trials assessing the impact on smoking cessation can be justified.


Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants with birth weights of 500-1,499 g.
Bronchopulmonary dysplasia (BPD) continues to be a major pulmonary complication in very low birth weight (VLBW) and extremely low birth weight (ELBW) survivors of neonatal intensive care units (NICUs). Many factors including partial pressures of carbon dioxide (PaCO: (2)) have been implicated as possible causes. Permissive hypercapnia has become a more common practice in ventilated infants, but its effect on BPD is unclear. The hypothesis of this study was that hypercarbia is associated with increased BPD in infants with birth weights of 500-1,499 g. Nine hospitals were involved in this observational cohort study. Maternal and infant information including socio-demographics, antenatal steroids, gender, race, gestational age, birth weight, intubation and ventilator status, physiologic variables and data on therapies were collected by chart abstraction. SNAP scores were assigned. Candidate BPD risk factors, including cumulative exposures derived from blood gas and ventilation data in the first 6 days of life, were identified. Risk models were developed for 425 preterm infants who survived to 36 weeks post-menstrual age. BPD occurrence was associated with the cumulative burden of MAP >0 cm H(2)O in the first 6 days of life (P < 0.0001). After adjustment for the burden of MAP, the occurrence of hypercarbia (PaCO: (2) >50 torr) was associated with a greater incidence of BPD (P = 0.024). Among 293 intubated, mechanically ventilated infants, those with hypercarbia occurring only when MAP ≤ 8 cm H(2)O, a scenario more comparable to permissive hypercapnia, also had increased BPD incidence compared to infants without hypercarbia (P = 0.0003). Hypercarbia during the first 6 days of life was associated with increased incidence of BPD in these infants. Mechanically ventilated infants with hypercarbia during low MAP also had a significant increase in BPD. Permissive hypercapnia in ventilated infants needs further close review before the practice becomes even more widespread.


The surgical treatment of Chiari I malformation.
A retrospective study was undertaken on 133 patients with a Chiari I malformation treated within the last 16 years at the Departments of Neurosurgery at the Nordstadt Hospital Hannover, Germany, and the University of California, Los Angeles, U.S.A. Ninety-seven patients presented with symptoms related to accompanying syringomyelia and 4 with associated syringobulbia. They underwent 149 surgical procedures and were followed for a mean of 39 +/- 52 months. A decompression at the foramen magnum was performed in 124 patients, while 22 of those with syringomyelia were treated by shunting (7 syringosubarachnoid shunts, 15 syringoperitoneal or -pleural shunts), and 3 by ventriculoperitoneal shunts for hydrocephalus. Except for ventriculoperitoneal shunting, at least a short-term decrease in size of an associated syrinx was observed for all procedures in the majority of cases. However, no long-term benefit was observed for syrinx shunting operations. The best clinical long-term results were obtained with decompression of the foramen magnum in patients with (86% free of a clinical recurrence) and without syringomyelia (77% free of a clinical recurrence). We advise against syrinx shunting, a large craniectomy, and obex plugging which are associated with higher recurrence rates. Instead, surgery should consist of a small craniectomy, opening of the dura, archnoid dissection to establish normal cerebrospinal fluid (CSF) outflow from the 4th ventricle, and a fascia lata dural graft.


Investigations concerning the changes in serum proteins during immunization; the cause of hypoalbuminemia with high gamma globulin values.
On hyperimmunization of rabbits with pneumococcal vaccine, increase in the content of gamma globulin and fall of albumin in the serum are produced. In such hyperimmunized rabbits, investigations of the plasma volume, albumin degradation, and the distribution of the albumin intra- and extravascularly were undertaken by Sterling's method employing rabbit albumin labelled with I(131). The investigations do not suggest any significant alteration in the albumin degradation nor in the distribution between the intra- and extravascular albumin. It was demonstrated that the plasma volume increases simultaneously with increase in the gamma globulin and fall in albumin. It is concluded that the fall in serum albumin observed is due to a regulative mechanism which attempts to maintain the colloid-osmotic pressure by increasing the plasma volume.


BCG immunization at birth and atopic diseases in a homogeneous population of Spanish schoolchildren.
The role of immunization with bacillus Calmette-Guérin (BCG) in the prevalence of asthma, hay fever and atopic dermatitis is not definitely established and seems to be influenced by ethnic background. The aim of this study was to analyze the relationship between this immunization and the prevalence of those diseases in a homogeneous population of Spanish schoolchildren. The International Study of Asthma and Allergies in Childhood (ISAAC) core and environmental questionnaires were used in four different centers of the Spanish North Atlantic coast. Bilbao, San Sebastián and Asturias have a universal BCG immunization policy during the first days of life, whereas La Coruña discontinued this practice in 1989. Except for this center, immunization coverage was above 90%. A random sample of schools of Asturias or all schools in the city district (rest of centers) with children 6 and 7 years old was surveyed. The participation rate was above 70%. After excluding those children born outside Spain, the numbers were 6,762 immunized and 2,828 nonimmunized. After adjusting for gender, age, smoking habits of the father and mother, truck traffic near the household, older and younger siblings and having a cat or a dog during the first year of the child's life, the adjusted ORs of the BCG-immunized children suffering from asthma, hay fever and atopic dermatitis were respectively 0.87 (95% CI 0.76-1.00), 0.87 (0.75-1.01) and 0.89 (0.76-1.05). BCG immunization offers a weak but significant protection against asthma and hay fever in Spanish schoolchildren.


Uniform Atomic Layer Deposition of Al2O3 on Graphene by Reversible Hydrogen Plasma Functionalization.
A novel method to form ultrathin, uniform Al2O3 layers on graphene using reversible hydrogen plasma functionalization followed by atomic layer deposition (ALD) is presented. ALD on pristine graphene is known to be a challenge due to the absence of dangling bonds, leading to nonuniform film coverage. We show that hydrogen plasma functionalization of graphene leads to uniform ALD of closed Al2O3 films down to 8 nm in thickness. Hall measurements and Raman spectroscopy reveal that the hydrogen plasma functionalization is reversible upon Al2O3 ALD and subsequent annealing at 400 °C and in this way does not deteriorate the graphene's charge carrier mobility. This is in contrast with oxygen plasma functionalization, which can lead to a uniform 5 nm thick closed film, but which is not reversible and leads to a reduction of the charge carrier mobility. Density functional theory (DFT) calculations attribute the uniform growth on both H2 and O2 plasma functionalized graphene to the enhanced adsorption of trimethylaluminum (TMA) on these surfaces. A DFT analysis of the possible reaction pathways for TMA precursor adsorption on hydrogenated graphene predicts a binding mechanism that cleans off the hydrogen functionalities from the surface, which explains the observed reversibility of the hydrogen plasma functionalization upon Al2O3 ALD.


Carcinoid tumor arising in a tailgut cyst of the anorectal junction with distant metastasis: a case report and review of the literature.
Tailgut cyst is a rare congenital presacral lesion and is believed to arise from the persistent remnants of the postanal gut. Malignancy occurring in a tailgut cyst is extremely rare, and to our knowledge only 5 cases of carcinoid tumor arising in a tailgut cyst have been reported in the literature to date. We report a sixth case of carcinoid tumor arising in a tailgut cyst. The patient was a 41-year-old woman who presented with perianal pain. Sigmoidoscopy showed a 2-cm submucosal mass located 4 cm above the anal verge. The mass was a multilocular cyst with gray-tan solid portions. The cyst was lined by ciliated columnar, squamous, and transitional epithelia with small foci of carcinoid tumor in the cystic wall. The carcinoid tumor showed a trabecular growth pattern with uniform oval or round cells containing fine chromatin and positive immunoreactivity for chromogranin, synaptophysin, and cytokeratin. This case was unique because the tumor occurred at the anorectal junction, not in the retrorectal space, and unlike previously reported cases showed aggressive behavior and distant metastases.


Depressive symptomatology and grief in Spanish women who have suffered a perinatal loss.
Perinatal grief differs from other types of mourning. Two goals were set: to describe the progression of the process of grief and the symptoms of depression throughout the year following perinatal loss, and to study its association with socio-economic and obstetric factors. The study involved the participation of 70 women who had suffered a medical termination of pregnancy or a prenatal/postnatal death. Three assessments were made after the loss (after 1 month, 6 months and 1 year) with the Perinatal Grief Scale (PGS) to assess grief and the Beck Depression Inventory (BDI) for depressive symptomatology. Symptoms pertaining to grief and depression were observed in the first month after the loss, and a significant decrease in scores over the two follow-ups. No significant differences were observed in grief and depression depending on the type of loss, no significant associations were found with the age of the mother, her socioeconomic level, or obstetric factors (week of gestation of the loss, having a child or having suffered a previous miscarriage). Perinatal grief is a complex construct, with multiple variables involved, and one which involves significant emotional discomfort.


Relationship of genetic variation in the serotonin transporter gene (SLC6A4) and congenital and acquired cardiovascular diseases.
Recent reports have suggested an association between variation in the serotonin transporter and primary pulmonary hypertension and myocardial infarction. We set out to determine whether these associations were present in a population of patients who underwent SLC6A4 genotyping and to explore whether genetic variation in the serotonin transporter might be also associated with other cardiovascular functional and structural abnormalities. Included were 3473 patients who were genotyped for the SLC6A4 5HTTLPR polymorphism and a subset for rs25531 (n=816) and STin2 (n=819). An association was observed between 5HTTLPR and primary pulmonary hypertension (p=0.0130), anomalies of the cerebrovascular system (p<0.0001), and other anomalies of great veins (p=0.0359). The combined 5HTTLPR and rs25531 genotype was associated with tachycardia (p=0.0123). There was an association of the STin2 genotype with abnormal electrocardiogram (ECG) (p=0.0366) and abnormal cardiac study (0.0311). Overall, these results represent a step toward the understanding of the impact of SLC6A4 variation on cardiovascular pathology.


12-month prevalence of panic disorder with or without agoraphobia in the Swedish general population.
The present study examined the prevalence of panic disorder with or without agoraphobia according to DSM-IV criteria in the Swedish general population. Data were obtained by means of a postal survey administrated to 1000 randomly selected adults. The panic disorder module of the World Health Organization's Composite International Diagnostic Interview (CIDI) was included in the survey. 12-month prevalence was estimated at 2.2 % (CI 95 % 1.02 % - 3.38 %). There was a significant sex difference, with a greater prevalence for women (5.6 %) compared to men (1 %). The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world.


[Clinical randomized study of bee-sting therapy for rheumatoid arthritis].
To observe the clinical effect of bee-sting (venom) therapy in the treatment of rheumatoid arthritis (RA). One hundred RA patients were randomly divided into medication (control) group and bee-venom group, with 50 cases in each. Patients of control group were treated with oral administration of Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7. 5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi-points and the above-mentioned Western medicines. Ashi-points were selected according to the position of RA and used as the main acupoints, supplemented with other acupoints according to syndrome differentiation. The treatment was given once every other day and all the treatments lasted for 3 months. Compared with pre-treatment, scores of joint swelling degree, joint activity, pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking duration, morning stiff duration in bee-venom group and medication group were improved significantly (P<0.05, 0.01). Comparison between two groups showed that after the therapy, scores of joint swelling, pain and pressing pain, joint-swelling number and morning stiff duration, and the doses of the administered MTX and Mobic in bee-venom group were all significantly lower than those in medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was markedly higher than that in medication group (P<0.05). In addition, the relapse rate of bee-venom group was obviously lower than that of medication group (P<0.05; 12% vs 32%). Combined application of bee-venom therapy and medication is superior to simple use of medication in relieving RA, and when bee-sting therapy used, the commonly-taken doses of western medicines may be reduced, and the relapse rate gets lower.


Ocular manifestations of cat-scratch disease.
Bartonella henselae has only recently been isolated, characterized, and found to be the principal cause of cat-scratch disease (CSD). The availability of specific serologic investigations has allowed the recognition of a spectrum of ocular CSD syndromes that previously were ill defined and considered idiopathic. The primary inoculation complex causing regional lymphadenopathy is represented in the eye by Parinaud's oculoglandular syndrome; B. henselae is the most common cause. Leber's neuroretinitis has been identified for 80 years, and new data suggest that it is commonly a manifestation of CSD; the extent of the association remains to be determined. CSD optic neuritis is also described. The vitreoretinal manifestations include anterior uveitis, vitritis, pars planitis, focal retinal vasculitis, a characteristic retinal white spot syndrome, Bartonella retinitis, branch retinal arteriolar or venular occlusions, focal choroiditis, serous retinal detachments, and peripapillary angiomatous lesions. The pattern of ocular disease in AIDS-associated B. henselae infections is poorly delineated; unusual manifestations include conjunctival and retinal bacillary angiomatosis. The benefit of antimicrobial therapy for CSD in immunocompetent individuals has been difficult to establish, partly because most infections are self limited. Empirically, azithromycin, ciprofloxacin, rifampin, parenteral gentamicin, or trimethoprim-sulfamethoxazole provide the best therapeutic choices to minimize damage to the eye.


Substrate Specificity and Inhibitor Sensitivity of Plant UDP-Sugar Producing Pyrophosphorylases.
UDP-sugars are essential precursors for glycosylation reactions producing cell wall polysaccharides, sucrose, glycoproteins, glycolipids, etc. Primary mechanisms of UDP sugar formation involve the action of at least three distinct pyrophosphorylases using UTP and sugar-1-P as substrates. Here, substrate specificities of barley and Arabidopsis (two isozymes) UDP-glucose pyrophosphorylases (UGPase), Arabidopsis UDP-sugar pyrophosphorylase (USPase) and Arabidopsis UDP-N-acetyl glucosamine pyrophosphorylase2 (UAGPase2) were investigated using a range of sugar-1-phosphates and nucleoside-triphosphates as substrates. Whereas all the enzymes preferentially used UTP as nucleotide donor, they differed in their specificity for sugar-1-P. UGPases had high activity with D-Glc-1-P, but could also react with Fru-1-P and Fru-2-P (Km values over 10 mM). Contrary to an earlier report, their activity with Gal-1-P was extremely low. USPase reacted with a range of sugar-1-phosphates, including D-Glc-1-P, D-Gal-1-P, D-GalA-1-P (Km of 1.3 mM), β-L-Ara-1-P and α-D-Fuc-1-P (Km of 3.4 mM), but not β-L-Fuc-1-P. In contrast, UAGPase2 reacted only with D-GlcNAc-1-P, D-GalNAc-1-P (Km of 1 mM) and, to some extent, D-Glc-1-P (Km of 3.2 mM). Generally, different conformations/substituents at C2, C4, and C5 of the pyranose ring of a sugar were crucial determinants of substrate specificity of a given pyrophosphorylase. Homology models of UDP-sugar binding to UGPase, USPase and UAGPase2 revealed more common amino acids for UDP binding than for sugar binding, reflecting differences in substrate specificity of these proteins. UAGPase2 was inhibited by a salicylate derivative that was earlier shown to affect UGPase and USPase activities, consistent with a common structural architecture of the three pyrophosphorylases. The results are discussed with respect to the role of the pyrophosphorylases in sugar activation for glycosylated end-products.


Seborrheic keratosis evolution into squamous cell carcinoma: A truly modified sun-related tumor? A case report and review of the literature.
The incidence of seborrheic keratosis (SK) generally increases with age and are mostly localized on the trunk, face and neck, especially on sun-exposed areas. The association between SK and skin malignancies appears to be accidental, but in situ transformation occurs more frequently in sun-exposed areas. Histopathological examination of all SK cases should be considered, especially when SK lesions exhibit atypical clinical manifestations, such as ulceration and cresting, as they may herald malignant transformation. In addition, other features associated with malignant transformation include excoriations or hemorrhages identified on the lesion, modification and evolution of the macroscopic characteristics, and the presence of local erythema or pruritus. Immunocompromised patients exhibit an increased risk of malignant transformation, even when radiation is involved.


Lessons from genetically engineered animal models. IV. Nitric oxide synthase gene knockout mice.
Nitric oxide is a ubiquitous molecule implicated in a variety of biological processes. The specific action of nitric oxide depends on its enzymatic sources, namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), each having distinct tissue localization. Conventional pharmacological antagonists could not distinguish these enzymes or provide models of chronic nitric oxide depletion in whole animals. Several lines of knockout mice have been generated to distinguish the roles of nitric oxide from each enzyme: nitric oxide from nNOS is a major inhibitory neurotransmitter, nitric oxide from eNOS regulates blood flow under physiological conditions, and nitric oxide from iNOS causes hypotension during severe inflammatory conditions. Moreover, the nitric oxides from each isoform have different roles in tissue injury and inflammation. Studies of NOS-deficient animals have also identified redundant and compensatory pathways and revealed the consequences of life-long deficiency of these enzymes. The nNOS-deficient mice develop gastric dilation and stasis, the eNOS-deficient mice develop hypotension and lack vasodilatory responses to injury, and iNOS-deficient mice are more susceptible to inflammatory damage but more resistant to septic shock.


Clinical characteristics, risk factors, and outcomes of usual and unusual site venous thromboembolism.
: The primary objective was to demonstrate the different risk factors among patients presenting with usual and unusual site venous thromboembolism (VTE). The secondary objectives were to compare clinical characteristics and outcomes in each group. This was a retrospective observational cohort study. Patients admitted in Chiang Mai University Hospital who were diagnosed with VTE during January 2010 through December 2012 were included and classified into two groups: the usual and unusual site VTE. The usual sites of VTE included pulmonary embolism and lower extremity deep vein thrombosis. Clinical characteristics, risk factors, treatment, recurrence, bleeding rates, and deaths were collected. There were 165 patients included in the study, 82 in usual site group and 83 in unusual site group. Patients in usual site group were older than unusual site group (mean 58 vs. 50 years, P = 0.003) and were more symptomatic (89 vs. 49.4%, P < 0.001). The higher proportion of patients in usual site group had prolonged immobilization (22.0 vs. 2.4%, P < 0.001), prior surgery (12.2 vs. 1.2%, P = 0.005), and a history of chemotherapy (25.6 vs. 3.6%, P < 0.001). Local inflammation was significantly more common in unusual site group (0 vs. 8.5%, P < 0.001). The recurrent VTE and major bleeding rates were not statistically different between groups. The 3-year mortality rate was significantly higher in usual site VTE group (73.1 vs. 57.8%, P = 0.049). The study revealed the different risk factors and clinical characteristics between usual and unusual VTE sites.


[Endarterectomy and carotid angioplasty: surgical perspective].
Carotid endarterectomy (CE) is a well-established operation, although recently it has been challenged by newer, less invasive procedures such as carotid angioplasty with or without insertion of a stent. In this article the author gives his views on the use of CE in patients with carotid stenosis, both those with and those without symptoms, and also those in whom no definite indication has yet been established. In symptomatic carotid stenosis it had been clearly shown that CE is an effective procedure for the prevention of strokes and death from strokes in patients with carotid stenosis of over 70%, provided that the patients have reasonable general health and life expectation. There is only minor benefit from surgery in patients with asymptomatic disease of the carotid arteries and much less than in those with symptomatic carotid disease. Therefore endarterectomy is recommended when there is obvious progression of the degree of stenosis, especially when the stenosis has reached 70% or the patient begins to complain of symptoms. One of the most serious complications of CE is acute myocardial infarction. It is a good time to design careful randomised studies to compare endarterectomy with angioplasty, probably with stenting, in a selected group of patients at greater risk than those accepted for endarterectomy.


[Maternal morbidity after abdominal cesarean section in relation to bacterial amniotic fluid colonization and premature rupture of fetal membranes].
At the time of Caesarean section, amniotic fluid was collected transabdominally from 1025 patients. In 990 patients cultures were performed on the amniotic fluid. The incidence of Caesarean section of all patients was 16.1%, the perinatal mortality in all patients 0.61%, in cases of Caesarean section 1.93%. The influence of bacterial colonisation in the amniotic cavity was analyzed with respect to premature ruptured membranes and frequency of vaginal examinations on the maternal post-operative morbidity (wound-seroma and abscess 2.4%, febrile morbidity 17%, urinary tract infection 19%). Bacterial contamination was present in 33.3% of the amniotic fluid or uterine cavity, after ruptured membranes in 44.3%, without ruptured membranes in 23.35%. There is a significant influence of the positive cultured amniotic fluid on the wound healing and on the febrile morbidity, while the urinary tract infection has been not influenced. The bacterial contamination of the amniotic fluid is correlated to the frequency of vaginal examination and the presence of ruptured membranes. The following microbiologic isolates were found in the amniotic fluids: Staphylococcus epidermidis 36.38%, Streptococcus B 12.23%, Streptococcus D 10.3%, Escherichia coli 8.42%, Staphylococcus aureus 7.88%, Peptococci 3.26%, Streptococcus salivarius 2.99%, Bacteroides 2.4%. According to these data, patients with ruptured membranes of an interval of more than 12 hrs and with more than 7 vaginal examinations could be selected for antibiotic prophylaxis to achieve a reduction in febrile morbidity and in wound infection.


[Vibrio vulnificus septicemia in Spain].
Vibrio vulnificus is a virulent marine organism, able to contaminate sea-food. It usually produces bacteremia associated with secondary skin lesions in patients with underlying conditions, such as hepatic cirrhosis. We report a case of septic shock and characteristic skin lesions, due to Vibrio vulnificus in a patient with cirrhosis, who had eaten raw oysters. The patient survived in spite of the severity of the clinical picture. We conclude that Vibrio vulnificus infection must be considered in the differential diagnosis of sepsis and skin lesions.


Synaptic transfer from outer hair cells to type II afferent fibers in the rat cochlea.
Type II cochlear afferents receive glutamatergic synaptic excitation from outer hair cells (OHCs) in the rat cochlea. However, it remains uncertain whether this connection is capable of providing auditory information to the brain. The functional efficacy of this connection depends in part on the number of presynaptic OHCs, their probability of transmitter release, and the effective electrical distance for spatial summation in the type II fiber. The present work addresses these questions using whole-cell recordings from the spiral process of type II afferents that run below OHCs in the apical turn of young (5-9 d postnatal) rat cochlea. A "high potassium puffer" was used to elicit calcium action potentials from individual OHCs and thereby show that the average probability of transmitter release was 0.26 (range 0.02-0.73). Electron microscopy showed relatively few vesicles tethered to ribbons in equivalent OHCs. A "receptive field" map for individual type II fibers was constructed by successively puffing onto OHCs along the cochlear spiral, up to 180 μm from the recording pipette. These revealed a conservative estimate of 7 presynaptic OHCs per type II fiber (range 1-11). EPSCs evoked from presynaptic OHCs separated by >100 μm did not differ in amplitude or waveform, implying that the type II fiber's length constant exceeded the length of the synaptic input zone. Together these data suggest that type II fibers could communicate centrally by maximal activation of their entire pool of presynaptic OHCs.


Heterogeneous intergrowth xLi1.5Ni0.25Mn0.75O2.5·(1 - x)Li0.5Ni0.25Mn0.75O2 (0 ≤ x ≤ 1) composites: synergistic effect on electrochemical performance.
A series of xLi1.5Ni0.25Mn0.75O2.5·(1 - x)Li0.5Ni0.25Mn0.75O2 (0 ≤ x ≤ 1) cathode materials have been synthesized. These compounds exhibit dramatic differences in structure, morphology and charge/discharge characteristics. As the x increases, the morphology shows an amazing trend: starting with an octahedral shape (x = 0), transforming to an octahedral/plate shape (0.1 ≤ x ≤ 0.9) in which both the spinel phase and the layered phase can be indexed in the XRD patterns, and ending up with a plate shape (x = 1.0). The particular layered-spinel composites xLi1.5Ni0.25Mn0.75O2.5·(1 - x)Li0.5Ni0.25Mn0.75O2 (0.1 ≤ x ≤ 0.9) exhibit better cycling stability than that of pristine spinel Li0.5Ni0.25Mn0.75O2 (x = 0) and layered Li1.5Ni0.25Mn0.75O2.5 (x = 1.0) materials. This improved cycling performance of these layered-spinel composites can be ascribed to the heterogeneous intergrowth of some layered phases and spinel phases in the parent structure as detected by TEM. Among these materials, Li0.5Ni0.25Mn0.75O2 and Li1.5Ni0.25Mn0.75O2.5 barely deliver the specific capacities of 90 mA h g(-1) and 117 mA h g(-1) at 5 C and show the capacity retentions of about 83% and 86% at 0.2 C after 50 cycles, respectively, while the layered-spinel 0.8Li1.5Ni0.25Mn0.75O2.5·0.2Li0.5Ni0.25Mn0.75O2 cathode shows the best rate capability of 162 mA h g(-1) at 5 C and the best cycling stability of 98% after 50 cycles at 0.2 C.


Experimental evidence that stripes do not cool zebras.
There are as many as 18 theories for the possible functions of the stripes of zebras, one of which is to cool the animal. We performed field experiments and thermographic measurements to investigate whether thermoregulation might work for zebra-striped bodies. A zebra body was modelled by water-filled metal barrels covered with horse, cattle and zebra hides and with various black, white, grey and striped patterns. The barrels were installed in the open air for four months while their core temperature was measured continuously. Using thermography, the temperature distributions of the barrel surfaces were compared to those of living zebras. The sunlit zebra-striped barrels reproduced well the surface temperature characteristics of sunlit zebras. We found that there were no significant core temperature differences between the striped and grey barrels, even on many hot days, independent of the air temperature and wind speed. The average core temperature of the barrels increased as follows: white cattle, grey cattle, real zebra, artificial zebra, grey horse, black cattle. Consequently, we demonstrate that zebra-striped coats do not keep the body cooler than grey coats challenging the hypothesis of a thermoregulatory role of zebra stripes.


[Effect of antioxidant on hepatic stellate cell proliferation and apoptosis during recovery from liver fibrosis].
Effects of dietary supplementation of vitamin E and selenium on proliferation and apoptosis of activated hepatic stellate cell(HSC) were investigated in the rat model of liver fibrosis induced by intraperitoneal injection with CCl4. Activated HSC was determined by alpha-smooth muscle actin immunohistochemistry staining and apoptotic HSC determined by dual staining both of the terminal deoxynucleotidyl transferase UTP nick end labeling(TUNEL) and of alpha-smooth muscle actin immunohistochemistry. During fibrosis recovery, the number of activated HSCs both in pathological group and in intervention group went down gradually,meanwhile, both the number of apoptotic HSCs and the collagen liver also descend little by little. These data confirmed that HSCs had the core effect on liver fibrogenesis and apoptosis may be a major factor regulating HSCs numbers during the injury-fibrosis-recovery sequence. At each time point, the number of activated HSCs in pathological group is more than intervention group, while apoptotic HSCs are less, which suggested dietary supplement with antioxidative nutrients had effect on HSC apoptosis but more studies are necessary to make the mechanism clearer. Dietary supplement with proper vitamin E and selenium can effectively lighten the hepatic fibrosis and promote the recovery of hepatocyte and the degradation of the existing collagens, ie, it is beneficial to the recovery of hepatic fibrosis.


Optical modeling of wide-bandgap perovskite and perovskite/silicon tandem solar cells using complex refractive indices for arbitrary-bandgap perovskite absorbers.
Wide-bandgap perovskites are attractive top-cell materials for tandem photovoltaic applications. Comprehensive optical modeling is essential to minimize the optical losses of state-of-the-art perovskite/perovskite, perovskite/CIGS, and perovskite/silicon tandems. Such models require accurate optical constants of wide-bandgap perovskites. Here, we report optical constants determined with ellipsometry and spectrophotometry for two new wide-bandgap, cesium-formamidinium-based perovskites. We validate the optical constants by comparing simulated quantum efficiency and reflectance spectra with measured cell results for semi-transparent single-junction perovskite cells and find less than 0.3 mA/cm2 error in the short-circuit current densities. Such simulations further reveal that reflection and parasitic absorption in the front ITO layer and electron contact are responsible for the biggest optical losses. We also show that the complex refractive index of methylammonium lead triiodide, the most common perovskite absorber for solar cells, can be used to generate approximate optical constants for an arbitrary wide-bandgap perovskite by translating the data along the wavelength axis. Finally, these optical constants are used to map the short-circuit current density of a textured two-terminal perovskite/silicon tandem solar cell as a function of the perovskite thickness and bandgap, providing a guide to nearly 20 mA/cm2 matched current density with any perovskite bandgap between 1.56 and 1.68 eV.


A single amino acid change in the E2 glycoprotein of Venezuelan equine encephalitis virus affects replication and dissemination in Aedes aegypti mosquitoes.
Four monoclonal antibody-resistant variants (MARVs) of Venezuelan equine encephalitis (VEE) virus were used to study mosquito-virus interactions. In vitro experiments using an Aedes albopictus cell line, C6/36, demonstrated that an amino acid change in the glycoprotein E2h epitope (MARV 1A3B-7) decreased virus growth when compared with the wild-type, Trinidad donkey virus, and its vaccine derivative, TC-83. The MARVs replicated as efficiently as the parent virus when inoculated into Aedes aegypti mosquitoes, but MARV 1A3B-7 was restricted in its ability to infect and disseminate from the midgut following oral infection. These results demonstrate that a single amino acid change in the E2 glycoprotein can affect the ability of VEE virus to replicate and disseminate in Ae. aegypti mosquitoes.


Arabidopsis J-protein J20 delivers the first enzyme of the plastidial isoprenoid pathway to protein quality control.
Plastids provide plants with metabolic pathways that are unique among eukaryotes, including the methylerythritol 4-phosphate pathway for the production of isoprenoids essential for photosynthesis and plant growth. Here, we show that the first enzyme of the pathway, deoxyxylulose 5-phosphate synthase (DXS), interacts with the J-protein J20 in Arabidopsis thaliana. J-proteins typically act as adaptors that provide substrate specificity to heat shock protein 70 (Hsp70), a molecular chaperone. Immunoprecipitation experiments showed that J20 and DXS are found together in vivo and confirmed the presence of Hsp70 chaperones in DXS complexes. Mutants defective in J20 activity accumulated significantly increased levels of DXS protein (but no transcripts) and displayed reduced levels of DXS enzyme activity, indicating that loss of J20 function causes posttranscriptional accumulation of DXS in an inactive form. Furthermore, J20 promotes degradation of DXS following a heat shock. Together, our data indicate that J20 might identify unfolded or misfolded (damaged) forms of DXS and target them to the Hsp70 system for proper folding under normal conditions or degradation upon stress.


A Phase I Study of Tomotherapy in Patients With Primary Benign and Low-grade Brain Tumors: Late Toxicity and Quality of Life.
To evaluate longitudinal quality of life and late neurotoxicity (>12 mo) of tomotherapy in patients with primary benign and low-grade brain tumors. Between January 2006 and October 2009, 49 patients with brain tumors were treated with tomotherapy at 2 radiotherapy centers in Canada. The median age of the patients was 51.0 years (range, 21 to 74 y); there were 21 men (42.86%) and 28 women (57.14%). All 49 patients had an initial Karnofsky performance score ≥70. One patient (2.04%) received 45 Gy in 25 fractions, 27 patients (55.10%) received 50.4 Gy in 28 fractions, 15 patients (30.6%) received 54 Gy in 30 fractions, and 5 patients (10.2%) received 60 Gy in 30 fractions. A total of 47 patients were analyzed for late toxicity and outcomes. Changes in the Karnofsky Performance Status of the patients did not reach statistical significance (P>0.05). The majority of the quality of life parameters that reached a statistically significant level (P<0.05) of change at 2 years were changes toward improvement (drowsiness, itchy skin, emotional functioning, fatigue, nausea, and appetite). Statistically significant (P<0.05) interval deterioration in physical, role, and social functioning was observed. Actuarial overall survival at 5 years was 91.6%; disease-free survival at 5 years was 86.6%. IMRT helical tomotherapy is well tolerated, without statistically significant constitutional and late neurotoxicity up to the 2-year mark.


Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons.
The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.