Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.
The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.


Cu-catalyzed debrominative cyanation of gem-dibromoolefins: a facile access to α,β-unsaturated nitriles.
An efficient catalytic route for the synthesis of α,β-unsaturated nitriles from easily accessible gem-dibromoolefins has been developed. The method utilized inexpensive reagents such as Cu2O as a catalyst, L-proline as a ligand and NaCN as a cyanide source to afford α,β-unsaturated nitriles in high yields (62-86%). A deuterium exchange study has shown that one of the bromide atoms of gem-dibromoolefins exchanges with cyanide while the other with a deuterium atom.


Pregnancy outcome in women with cerebral palsy: A nationwide population-based cohort study.
Cerebral palsy (CP) is a lifelong disorder with a high rate of comorbidities and complications. We hypothesized that women with CP are at increased risk of adverse pregnancy outcome. In this nationwide population-based cohort study 1997-2011, we examined the outcome of 770 births in women with CP vs 1 247 408 births in women without a CP diagnosis using the Swedish Medical Birth Register. We used unconditional logistic regression, adjusting for maternal age, smoking, parity, year of birth and epilepsy, to calculate adjusted odds ratios for adverse pregnancy outcome. Main adverse outcome was preterm birth. Secondary outcomes were cesarean section, induction of labor, low 5-min Apgar score, small for gestational age, large for gestational age, and stillbirth. After adjusting for potential confounders, maternal CP was associated with increased risk of preterm birth (12.9% vs 4.9%; adjusted odds ratio [aOR] 2.8, 95% CI 2.3-3.5), cesarean delivery (aOR 1.9, 95% CI 1.6-2.2), induced delivery (aOR 1.4, 95% CI 1.1-1.6), low 5-min Apgar score (aOR 1.8, 95% CI 1.1-2.9) and small of gestational age birth (aOR 1.6, 95% CI 1.2-2.3). We found no increased risk of large for gestational age or stillbirth. Women with CP are at increased risk of preterm birth and other adverse pregnancy outcomes, suggesting that they deserve extra surveillance during antenatal care. Further studies, with information on type of CP and gross motor function, are warranted to better understand the association between CP and pregnancy outcome.


Transient brain responses predict the temporal dynamics of sound detection in humans.
The neural events leading up to the conscious experience of stimulus events have remained elusive. Here we describe stimulation conditions under which activation in human auditory cortex can be used to predict the temporal dynamics of behavioral sound detection. Subjects were presented with auditory stimuli whose energy smoothly increased from a silent to a clearly audible level over either 1, 1.5, or 2 s. Magnetoencephalographic (MEG) recordings were carried out in the passive and active recording conditions. In the active condition, the subjects were instructed to attend to the auditory stimuli and to press a response key when these became audible. In both conditions, the stimuli elicited a prominent transient response whose emergence is unexplainable by changes in stimulus intensity alone. This transient response was larger in amplitude over the right hemisphere and in the active condition. Importantly, behavioral sound detection followed this brain activation with a constant delay of 180 ms, and further the latency variations of the brain response were directly carried over to behavioral reaction times. Thus, noninvasively measured transient events in the human auditory cortex can be used to predict accurately the temporal course of sound detection and may therefore turn out to be useful in clinical settings.


2-(3-Benzoyl-4-hy-droxy-1,1-dioxo-2H-1λ,2-benzothia-zin-2-yl)-1-phenyl-ethanone.
In the title mol-ecule, C(23)H(17)NO(5)S, the heterocyclic thia-zine ring adopts a half-chair conformation, with the S and N atoms displaced by 0.383 (3) and 0.473 (3) Å, respectively, on opposite sides of the mean plane formed by the ring C atoms. The phenyl rings attached to carbonyl groups lie almost parallel to each other at a dihedral angle 7.43 (9)°, the distance between the centroids of the rings being 3.780 (1) Å. The C(thia-zine)-C=O and O=C-CH(2) groups make dihedral angles of 37.56 (16) and 1.93 (18)°, respectively, with the phenyl groups to which they are attached. The crystal structure features O-H⋯O and C-H⋯O hydrogen bonds and further consolidated by C-H⋯π inter-actions; an intra-molecular O-H⋯O hydrogen bond is also present.


The CellSoft computerized semen analysis system. I. Consistency of measurements and stability of results in relation to sample size analyzed.
The CellSoft TM computer-assisted digital image analysis system was evaluated for reproducibility of measurements and for the sample size needed to obtain stable results for seven parameters characterizing human spermatozoa. The parameters were sperm density, velocity, linearity, percent motile cells, maximum and mean amplitude of sperm head's lateral displacement (ALH max and ALH mean) and beat cross frequency. Thirty men were assigned to three equally large groups according to sperm density, and the groups were studied separately. Consistency of measurements was highly acceptable for all parameters (coefficient of variation ranging from 0.9% to 3.7%). The average minimum number of sample size needed for stable results varied between the groups and within each group dependent upon the parameter studied. Velocity and linearity seemed to require the lowest average cell number, while percentage motile cells and ALH max needed the highest sample size. Our current recommendation of sample sizes is outlined in detail and limitations and future utility of CellSoft is discussed.


Structural studies of an immunoenhancing glucan of an ectomycorrhizal fungus Ramaria botrytis.
A water-soluble glucan was isolated from the alkaline extract of an ectomycorrhizal fungus, Ramaria botrytis. On the basis of sugar analysis, methylation analysis, Smith degradation, partial hydrolysis, and 1D/2D NMR studies, the structure of the repeating unit of the glucan was established as: [structure: see text]. This glucan showed immunostimulating activity by NO production on RAW 264.7, a murine macrophage cell line. Splenocyte and thymocyte proliferation were measured using, respectively, single cell suspensions of spleen and thymus obtained from normal mice.


Cystic fibrosis and infantile hypertrophic pyloric stenosis: is there an association?
Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasian populations. The generally accepted incidence of CF in the United States is 1 in 3,200 in the Caucasian population. Intestinal obstructions and atresias have been described among patients with CF. An association of CF with infantile hypertrophic pyloric stenosis (IHPS) has not been previously documented. A review in our clinic of 72 patients with CF revealed IHPS in two. The incidence of 2.7% is greater than the 0.3% incidence expected in the general population. This ninefold increase in IHPS in patients with CF suggests an association between the two and warrants further investigation.


Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir.
Kangri cancer found only in Kashmir (north India) is a unique thermally induced squamous cell carcinoma of the skin that develops because of chronic and persistent irritation due to the use of a kangri (a brazier) by the Kashmiri people to combat the chilling cold temperature during winter. Being unique to this region, the molecular etiology of the invasive kangri cancer is not known fully. The TP53 gene, codon 72 polymorphism (Arg72Pro), has been found to be associated with cancer susceptibility but has not been investigated in kangri cancer risk. A case control study was conducted to find the genotype distribution of TP53 Arg72Pro SNP and to elucidate the possible role of this SNP as risk factor in kangri cancer development. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we tested the genotype distribution of 106 kangri cancer patients in comparison with 200 cancer-free controls from the same geographical region. A significant difference was observed between the control and kangri cancer patients with odds ratio = 2.02 and 95% confidence interval = 1.2-3.3 (p = 0.01). Interestingly, the proline form was abundantly observed in advanced-grade tumors (p < 0.05). We also found a significant association of the variant allele (GC + CC) with male subjects and patients >45 years of age (p < 0.05). Thus, it is evident from our study that Arg72Pro SNP is implicated in kangri cancer and that the rare, proline-related allele is connected with higher susceptibility to kangri cancer.


Combinatorial effects of geopropolis produced by Melipona fasciculata Smith with anticancer drugs against human laryngeal epidermoid carcinoma (HEp-2) cells.
The identification of natural products exerting a combined effect with therapeutic agents could be an alternative for cancer treatment, reducing the concentration of the drugs and side effects. Geopropolis (Geo) is produced by some stingless bees from a mixture of vegetable resins, gland secretions of the bees and soil. It has been used popularly as an antiseptic agent and to treat respiratory diseases and dermatosis. To determine whether Geo enhances the anticancer effect of carboplatin, methotrexate and doxorubicin (DOX), human laryngeal epidermoid carcinoma (HEp-2) cells were treated with Geo alone or in combination with each drug. Cell growth, cytotoxicity and apoptosis were evaluated using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and flow cytometry. Scratch assay was used to analyze cell migration and transmission electron microscopy to observe morphologic alterations. The influence of Geo on drug resistance was also investigated assessing P-glycoprotein (P-gp) action. Geo inhibited cell proliferation and migration. The combination Geo+DOX led to the highest cytotoxic activity and induced apoptosis, leading to loss of membrane integrity. Geo had no effect on P-gp-mediated efflux of DOX. Data indicate that Geo combined with DOX could be a potential clinical chemotherapeutic approach for laryngeal cancer treatment.


On the role of protein synthesis in the response of adrenal tumor cells to ACTH.
Y-1 adrenal tumor cells were incubated with aminoglutethimide with and without ACTH. Greater production of pregnenolone from endogenous cholesterol was observed (after washing to remove aminoglutethimide) in mitochondria from cells incubated with aminoglutethimide and ACTH than in those from cells incubated with aminoglutethimide alone. This response was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. ACTH increased the incorporation of [3H]tyrosine into protein associated with mitochondria but not into total cell protein or protein of postmitochondrial supernatant. This response did not require aminoglutethemide block and was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. Dibutyryl cyclic AMP produced both of these responses (increased production of pregnenolone and synthesis of protein associated with mitochondria). The concentration of cycloheximide required to cause 50% inhibition of the responses to ACTH and dibutyryl cyclic AMP was approximately the same for steroidogenesis by whole cells, for production of pregnenolone by isolated mitochondria, for incorporation of [3H]tyrosine into Y-1 cell protein and for the increase in synthesis of protein associated with mitochondria produced by ACTH (0.08--0.2 microgram/ml). Disc gel electrophoresis revealed that the increased incorporation of [3H]tyrosine involved two proteins corresponding to molecular weight of approximately 27,000 and 13,000 respectively. These observations suggest that ACTH promotes synthesis of protein(s) by cytoplasmic ribosomes on stable messenger RNA, that the protein(s) becomes associated with mitochondria and that the protein(s) includes one or more which are associated with the increase in production of pregnenolone produced in mitochondria by the addition of ACTH to adrenal cells.


Normal amniotic fluid volume changes throughout pregnancy.
The purpose of this study was to provide a quantitative characterization of the changes in amniotic fluid volume that occur throughout gestation. From 705 published amniotic volumes for normal pregnancies, we found that after log transformation, amniotic fluid volume had a uniform variability over 8 to 43 weeks' gestation. Thus the 95% confidence interval covered the range of 1/2.57 to 2.57 times the mean volume at any given gestational age. Contrary to expected trends, mean amniotic fluid volume did not change significantly between 22 and 39 weeks and averaged 777 ml, with the 95% confidence interval ranging from 302 to 1997 ml. The data are summarized in nomograms covering 8 to 43 weeks' gestation.


Bezafibrate confers neuroprotection in the 5xFAD mouse model of Alzheimer's disease.
Mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD), the most common neurodegenerative disease. Prior studies suggested impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD. Bezafibrate, a peroxisome proliferator-activated receptor (PPAR) pan-agonist, has been shown to enhance mitochondrial biogenesis and increase oxidative phosphorylation capacity. In the present study, we investigated whether bezafibrate could rescue mitochondrial dysfunction and other AD-related deficits in 5xFAD mice. Bezafibrate was well tolerated by 5xFAD mice. Indeed, it rescued the expression of key mitochondrial proteins as well as mitochondrial dynamics and function in the brain of 5xFAD mice. Importantly, bezafibrate treatment led to significant improvement of cognitive/memory function in 5xFAD mice accompanied by alleviation of amyloid pathology and neuronal loss as well as reduced oxidative stress and neuroinflammation. Overall, this study suggests that bezafibrate improves mitochondrial function, mitigates neuroinflammation and improves cognitive functions in 5xFAD mice, thus supporting the notion that enhancing mitochondrial biogenesis/function is a promising therapeutic strategy for AD.


The Timing, the Treatment, the Question: Comparison of Epidemiologic Approaches to Minimize Immortal Time Bias in Real-World Data Using a Surgical Oncology Example.
Studies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are. To demonstrate the impact of immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013-2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the "true" relationship between surgical resection and mortality was known. 24,329 women (median age 61, IQR 51-71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure [HR, 0.54; 95% confidence interval (CI), 0.51-0.57], followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59-0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67-0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias -0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, -0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, -0.074) produced meaningfully biased estimates. Researchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present. Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data.


Penetration of the brain by nonionic water soluble tri- and hexaiodinated contrast media. Experimental autoradiographic study of two contrast media: Iotrol and Iopamidol labelled with iodine 125.
After suboccipital injection of Iotrol and Iopamidol labelled with iodine 125 in rabbits, we measured residual radioactivity in the whole brain and optical density on autoradiographs of brain sections obtained 2, 8 and 24 h after injection. Residual radioactivity is higher with Iotrol than with Iopamidol after 8 h and 24 h. At densitometry, while the penetration of the cortex is the same with both media at 2 h (although subcortical passage of Iotrol is greater), by 8 h the concentration of Iopamidol is twice that of Iotrol, and at 24 h it is three times as high. A similar pattern was seen in the subcortical region. These densitometric findings are in agreement with previous electrophysiological studies, in which changes were less severe and more transient with Iotrol than with Iohexol. There is nevertheless an apparent lack of agreement between the studies of radioactivity and the electrical findings. The lower neurotoxicity of Iotrol may be explained by: a longer half-life in the subarachnoid space; its larger molecules, which inhibit diffusion in the extracellular fluid, and its more hydrophilic nature, which reduces intracellular penetration.


Technique of mesenteric lengthening in ileal reservoir-anal anastomosis.
Construction of a satisfactory ileal reservoir-anal anastomosis is dependent on the ability of the reservoir to reach the anus without tension. A technique has been developed for the generation of satisfactory mesenteric length in 159 consecutive J-reservoir procedures. By careful attention to technical details with particular reliance on the division of branches between the primary and secondary arcade vessels within the mesentery, sufficient length can be achieved in each case with an acceptable complication rate. When combined with the ease of construction of the J-reservoir, this technique of mesenteric lengthening has made the double-loop reservoir the procedure of choice.


S-acylation-dependent association of the calcium sensor CBL2 with the vacuolar membrane is essential for proper abscisic acid responses.
Calcineurin B-like (CBL) proteins contribute to decoding calcium signals by interacting with CBL-interacting protein kinases (CIPKs). Currently, there is still very little information about the function and specific targeting mechanisms of CBL proteins that are localized at the vacuolar membrane. In this study, we focus on CBL2, an abundant vacuolar membrane-localized calcium sensor of unknown function from Arabidopsis thaliana. We show that vacuolar targeting of CBL2 is specifically brought about by S-acylation of three cysteine residues in its N-terminus and that CBL2 S-acylation and targeting occur by a Brefeldin A-insensitive pathway. Loss of CBL2 function renders plants hypersensitive to the phytohormone abscisic acid (ABA) during seed germination and only fully S-acylated and properly vacuolar-targeted CBL2 proteins can complement this mutant phenotype. These findings define an S-acylation-dependent vacuolar membrane targeting pathway for proteins and uncover a crucial role of vacuolar calcium sensors in ABA responses.


Crystallography relevant to Mars and Galilean icy moons: crystal behavior of kieserite-type monohydrate sulfates at extraterrestrial conditions down to 15 K.
Monohydrate sulfate kieserites (M 2+SO4·H2O) and their solid solutions are essential constituents on the surface of Mars and most likely also on Galilean icy moons in our solar system. Phase stabilities of end-member representatives (M 2+ = Mg, Fe, Co, Ni) have been examined crystallographically using single-crystal X-ray diffraction at 1 bar and temperatures down to 15 K, by means of applying open He cryojet techniques at in-house laboratory instrumentation. All four representative phases show a comparable, highly anisotropic thermal expansion behavior with a remarkable negative thermal expansion along the monoclinic b axis and a pronounced anisotropic expansion perpendicular to it. The lattice changes down to 15 K correspond to an 'inverse thermal pressure' of approximately 0.7 GPa, which is far below the critical pressures of transition under hydro-static compression (Pc ≥ 2.40 GPa). Consequently, no equivalent structural phase transition was observed for any compound, and neither dehydration nor rearrangements of the hydrogen bonding schemes have been observed. The M 2+SO4·H2O (M 2+ = Mg, Fe, Co, Ni) end-member phases preserve the kieserite-type C2/c symmetry; hydrogen bonds and other structural details were found to vary smoothly down to the lowest experimental temperature. These findings serve as an important basis for the assignment of sulfate-related signals in remote-sensing data obtained from orbiters at celestial bodies, as well as for thermodynamic considerations and modeling of properties of kieserite-type sulfate monohydrates relevant to extraterrestrial sulfate associations at very low temperatures.


[Telemedicine in Otorhinolaryngology and Head and Neck Surgery - An universal remedy?]
Digitalization in healthcare has gained considerable importance in recent years and especially during the Covid19 pandemic. The pandemic has undeniably severely limited human interactions. In light of the risk of infection, and also in light of the decreasing number of physician consultations by patients due to fear of infection, the medical community has had to seek new platforms for physician-patient interaction and -communication and achieved these goals predominantly by accelerating the development of digitization processes and telemedicine. In otolaryngology, the term telemedicine usually refers to video consultation (VS) or teleconsultations. In principle, ENT physicians belong to the group of specialists who are allowed to perform and invoice video consultations. Data protection and legal aspects pose challenges with regard to offering telemedical services. From an ethical point of view, any telemedical consultation would also have to be preceded by a mandatory explanation of the risks and disadvantages of using these procedures, and the basis for liability would also have to be clarified here in principle. Telemedicine will also have to assert itself in view of the evidence. Thus, at least from the medical university side, accompanying studies should be initiated when new telemedical procedures are offered, in order to evaluate the corresponding advantages and disadvantages on the basis of evidence. In terms of professional policy, care should always be taken to ensure that telemedicine is only offered by players in the healthcare sector who can also guarantee personal treatment of the patient assessed by telemedicine.


Evaluating child maltreatment and family violence risk during the COVID-19 Pandemic: Using a telehealth home visiting program as a conduit to families.
The COVID-19 pandemic has affected many child maltreatment risk factors and may have affected maltreatment among vulnerable families. We surveyed 258 certified providers of an evidence-based home visiting program, SafeCare, about their perception of the impact of the pandemic on the families they serve. We examined if the providers perceived an overall change in child maltreatment and family violence risk among the families with young children they served and factors that may have contributed to changes. Regressions estimated the relationship between providers' assessment of families' ability to social distance, emotional struggles, and access to public resources/services with providers' perception of child maltreatment and family violence risk in the home. Findings indicate that 87% of providers believed maltreatment risk had increased during the pandemic. Providers serving families who were unable to social distance due to employment were more likely to report increased supervisory neglect and material neglect among the families they serve. Providers reporting that families were struggling with elevated frustration levels also reported more family conflict and material neglect among the families they serve. Results from this research can inform strategic decision-making for policies and programs that address the challenges low-income families with young children face in emergency situations.


Synthetic lethal approaches to target cancers with loss of PTEN function.
Phosphatase and tensin homolog (PTEN) is a tumour suppressor gene and has a role in inhibiting the oncogenic AKT signalling pathway by dephosphorylating phosphatidylinositol 3,4,5-triphosphate (PIP3) into phosphatidylinositol 4,5-bisphosphate (PIP2). The function of PTEN is regulated by different mechanisms and inactive PTEN results in aggressive tumour phenotype and tumorigenesis. Identifying targeted therapies for inactive tumour suppressor genes such as PTEN has been challenging as it is difficult to restore the tumour suppressor functions. Therefore, focusing on the downstream signalling pathways to discover a targeted therapy for inactive tumour suppressor genes has highlighted the importance of synthetic lethality studies. This review focuses on the potential synthetic lethality genes discovered in PTEN-inactive cancer types. These discovered genes could be potential targeted therapies for PTEN-inactive cancer types and may improve the treatment response rates for aggressive types of cancer.


Pretreatment with granulocyte colony-stimulating factor attenuated renal ischaemia and reperfusion injury via activation of PI3/Akt signal pathway.
Granulocyte colony-stimulating factor (G-CSF) has been shown to exert protective effects in various tissues and experimental models of ischaemia-induced injury. However, the mechanism of renoprotective action in ischaemia/reperfusion (I/R) renal injury of G-CSF was unknown. Male C57BL/6J mice, subjected to renal ischaemia for 45 min, 48 h and 7 days reperfusion, were administered either saline, wortmannin, G-CSF, and G-CSF plus wortmannin 3 days prior to I/R. Saline-treated group served as the control. At 48 h and 7 days of reperfusion, the mice were killed. Significantly, renal dysfunction and morphological injury were identified at 48 h and 7 days after I/R. Wortmannin pretreatment worsened the renal injury significantly. However, G-CSF pretreatment significantly attenuated renal injury, reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive ratio of renal tubular epithelial cells and inflammation cytokine expression in the kidney. Moreover, G-CSF pretreatment inhibited the expression of Bax and increased the expression of bcl-2 and p-Akt in the kidney. Wortmannin blunted the beneficial effects of G-CSF. The cytoprotective action of G-CSF against I/R injury seems to be associated with its anti-apoptotic action mediated by upregulation of p-Akt signal pathway.


Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients.
Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients' survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4−20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.


Evidence for a role of protein phosphorylation in the maintenance of the cnidarian-algal symbiosis.
The endosymbiotic relationship between cnidarians and photosynthetic dinoflagellate algae provides the foundation of coral reef ecosystems. This essential interaction is globally threatened by anthropogenic disturbance. As such, it is important to understand the molecular mechanisms underpinning the cnidarian-algal association. Here we investigated phosphorylation-mediated protein signalling as a mechanism of regulation of the cnidarian-algal interaction, and we report on the generation of the first phosphoproteome for the coral model system Aiptasia. Mass spectrometry-based phosphoproteomics using data-independent acquisition allowed consistent quantification of over 3,000 phosphopeptides totalling more than 1,600 phosphoproteins across aposymbiotic (symbiont-free) and symbiotic anemones. Comparison of the symbiotic states showed distinct phosphoproteomic profiles attributable to the differential phosphorylation of 539 proteins that cover a broad range of functions, from receptors to structural and signal transduction proteins. A subsequent pathway enrichment analysis identified the processes of "protein digestion and absorption," "carbohydrate metabolism," and "protein folding, sorting and degradation," and highlighted differential phosphorylation of the "phospholipase D signalling pathway" and "protein processing in the endoplasmic reticulum." Targeted phosphorylation of the phospholipase D signalling pathway suggests control of glutamate vesicle trafficking across symbiotic compartments, and phosphorylation of the endoplasmic reticulum machinery suggests recycling of symbiosome-associated proteins. Our study shows for the first time that changes in the phosphorylation status of proteins between aposymbiotic and symbiotic Aiptasia anemones may play a role in the regulation of the cnidarian-algal symbiosis. This is the first phosphoproteomic study of a cnidarian-algal symbiotic association as well as the first application of quantification by data-independent acquisition in the coral field.


Concurrent Interstitial Granulomatous Dermatitis and TNF-α Antagonist-Induced Lupus Syndrome Secondary to Adalimumab for Crohn's Disease.
Tumor necrosis factor (TNF) antagonists have revolutionized management for various autoimmune and inflammatory conditions, including rheumatoid arthritis (RA), inflammatory bowel disease, hidradenitis suppurativa, psoriatic arthritis, and plaque psoriasis. However, adverse effects may necessitate switching to another biologic with a different mechanism of action. Here we report TNF-α antagonist-induced lupus syndrome (TAILS) revealed by interstitial granulomatous dermatitis (IGD), in the atypical context of Crohn's disease (CD).


Opioid and Cannabis Use During Pregnancy and Breastfeeding in Relation to Sociodemographics and Mental Health Status: A Descriptive Study.
This study of Canadian women estimates the prevalence of opioid and cannabis use during pregnancy and cannabis use during the breastfeeding period and explores the sociodemographic and mental health characteristics associated with use. A total of 13 000 women who gave birth between January and June 2018 were invited to participate in the Survey on Maternal Health by Statistics Canada; 7111 women participated for a response rate of 54.7%. Participants were asked about their mental health, supports during pregnancy, and substance use. Multivariable logistic regression was used to describe the relationship between sociodemographic and mental health characteristics and substance use during pregnancy and while breastfeeding. The prevalence of self-reported opioid use during pregnancy was 1.4% (95% confidence interval [CI] 1.1%-1.8%). A higher proportion of women reported using cannabis during pregnancy and while breastfeeding, at 3.1% (95% CI 2.5%-3.6%) and 2.6% (95% CI 2.1%-3.1%), respectively. Younger age, not being in a relationship, lower level of education, and thoughts of self-harm were significantly associated with cannabis use during pregnancy. Lower level of education and thoughts of self-harm were also significantly associated with cannabis use while breastfeeding, as were symptoms of postpartum depression and/or generalized anxiety. Lower level of education and symptoms of postpartum depression and/or generalized anxiety were also significantly associated with opioid use during pregnancy. The results of this survey show relatively low levels of opioid and cannabis use during pregnancy and cannabis use while breastfeeding in Canada. Different sociodemographic and mental health characteristics are associated with the use of these substances, and public health interventions and policies should take into account these factors.


Influence of a freshman-year panel presentation on medical students' attitudes toward homosexuality.
To explore medical students' changes in group attitude toward homosexuality following mid-year exposure as freshmen to a panel presentation on the topic and, later, following clinical experiences. At the beginning, middle, and end of 1991-92 and during the psychiatry clerkship in 1993-94, all 186 students in the class of 1995 at the Louisiana State University School of Medicine in New Orleans were asked to complete anonymously the Index of Attitudes toward Homosexuals. The two subsequent entering classes were also surveyed, at the beginning and in the middle of their freshman year. Group attitudes among the three consecutive classes were remarkably consistent. The original cohort displayed a decrease in group homophobic attitude over time, with the reduced mean score at mid-year continuing its downward trend at year's end, though rebounding somewhat by the junior year. However, the group mean score remained in the low-grade homophobic category throughout the three-year study. That the mean scores of the three classes remained at the low-grade homophobic level suggests the desirability of establishing an ongoing forum to enable students to examine all deeply held beliefs that may affect patient care.


Biodynamic responses of adolescent idiopathic scoliosis exposed to vibration.
Patients with adolescent idiopathic scoliosis suffer severe health issues. The unclear dynamic biomechanical characteristics of scoliosis were needed to be explored to improve the prevention and treatment in clinics. Validated 3D finite element (FE) models of thoracolumbosacral spine (T1-S1) both with and without scoliosis were developed from computed tomography (CT) images. Modal and harmonic analyses were performed to investigate the biomechanical responses of the spinal models to vibration. Resonant frequencies of the scoliotic model were lower than those of the model without scoliosis. Peak amplitudes occurred at vibrational frequencies close to the modal resonant frequencies, which caused the deformed thoracic segment in scoliosis suffered the maximum amplitude. The stresses on vertebrae and intervertebral discs in the scoliotic model derived from vibrations were significantly larger than those in the non-scoliosis model, and heterogeneously concentrated on the scoliotic thoracic segment. In conclusion, the scoliotic spine in the patients with Lenke 1BN scoliosis is more prone to injuries than the non-scoliotic spine while vibrating. Scoliotic thoracic segments in patients with Lenke 1BN scoliosis were the more vulnerable and sensitive component of the T1-S1 spine to vibration than lumbar spines. This study suggested that vibration would impair the scoliotic spines, and patients with Lenke 1BN scoliosis should avoid exposure to vibration, especially the low-frequency vibration.


Pain, health perception and sleep: impact on the quality of life of firefighters/rescue professionals.
To evaluate the quality of life of firefighters and rescue professionals, and characterize their socio-demographic, health, work and lifestyle profile. Cross-sectional study that used a socio-demographic, lifestyle, health, work data questionnaire and the WHOQOL-BREF quality of life aspects, in Fire Department bases, Civil Air Patrol Group of the Military Police and Rescue Group of Emergency Services. Ninety professionals participated in this study - 71 firefighters, 9 nurses, 7 doctors and 3 flight crew members. The average age of the group was 36.4 ± 7.8 years; they worked about 63.7 hours per week; 20.2% reported pain in the last week and 72.7% had body mass index above 25 kg/m2. The average of the WHOQOL-BREF domains was: physical (74.6), psychological (75.2), social (76.5) and environmental (58.7). Significant association was found (Mann-Whitney test and Spearman correlation) between the WHOQOL-BREF domains and pain in the past six months, in the last week, health perception, job satisfaction, hours of sleep, domestic tasks and study. The main factors related to quality of life were presence of pain, health perception, sleep and domestic activity.


Putting genome analysis to good use: lessons from C-reactive protein and cardiovascular disease.
New methods of studying the human genome offer novel ways to examine the relationship between biomarkers and common, chronic human diseases. As an example, we will review a large genomics study (Elliott et al, JAMA 2009; 302:37-48) that concluded that C-reactive protein (CRP) is likely not a cause of coronary heart disease, although it is a marker for it.


Treatment toxicity reduction: breast cancer.
Since curative treatment of advanced breast cancer is still beyond our reach, the importance of reducing overall toxicity of systemic treatment must be stressed. This seems to be possible by adapting the form and intensity of therapy to the prognosis and stage of disease and by using drugs exhibiting high antitumoral efficacy combined with low systemic toxicity. In 475 patients with metastatic breast cancer, we initiated a prognosis-oriented therapeutic strategy. We developed a prognostic score so as to classify patients into 'high' and 'low' risk groups. In this way we were able to separate patients into two groups with statistically different survival times. In addition, we found that the impact of the first polychemotherapy on survival is different when comparing patient with favourable and unfavourable prognostic scores. Patients with favourable prognostic factors had exactly the same survival time independent of tumour progression, stable disease or even partial remission. Only patients achieving a complete remission survived longer. In contrast, patients with unfavourable prognostic factors apparently benefited from chemotherapy. Patients achieving stable disease or objective tumour remission had a significantly longer survival time than those patients with immediate tumour progression. Additionally, for most of the patients in this group, chemotherapy induced a transient stabilization or improvement of tumour induced symptoms. Therefore, we conclude that chemotherapy of advanced breast cancer is necessary. However, to reduce overall toxicity, it must be planned and administered according to the prognostic picture of the individual patient.


Knowledge and attitudes about acquired immunodeficiency syndrome in nursing and nonnursing groups.
A study was undertaken to determine the difference in knowledge and attitudes about acquired immunodeficiency syndrome (AIDS) in nursing and nonnursing groups, and to determine the effect that knowledge acquisition would have on attitudes about AIDS. The total study population consisted of 60 registered nurses, 50 baccalaureate nursing students, 42 liberal arts college students, and 30 nonnurse adults. An AIDS knowledge and attitude assess test was developed and used in the study. Univariate descriptive methodology, descriptive correlational analysis, and a pretest-posttest design were used. Phase I showed that professional nurses with graduate degrees have the highest knowledge base and the most positive attitudes about AIDS; and that nursing students' attitudes are more similar to the attitudes of nonnursing students than of professional nurses. Phase II showed that people's attitudes about AIDS could be changed by increasing their knowledge levels, and nursing students showed more increase in knowledge and more significant changes in attitudes following education than liberal arts college students.


Integrating cullin2-RING E3 ligase as a potential biomarker for glioblastoma multiforme prognosis and radiosensitivity profiling.
Positive epidermal growth factor receptor (EGFR) immunoreactivity in glioblastoma multiforme (GBM) often predicts poor radiation response. Meanwhile, all attempts to target EGFR pharmaceutically have been unsuccessful, mainly due to molecular heterogeneity of EGFR expression in GBM. A molecular biology-based and efficient way to access cellular protein levels of EGFR is urgently needed. EGFR, together with HIF-1α and Cyclin B1, is degraded via cullin2-RING E3 ligase (CRL2). It is worthwhile to investigate the possible involvement of CRL2 on GBM survival and radiosensitivity. Clinicopathological features, radiographic images, survival data, RNA-Seq, copy number variations (CNVs), and other genetic changes were studied on over 3800 glioma and GBM cases, which are derived from 5 independent cohorts. These datasets include the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, Ivy Glioblastoma Atlas Project, Clinical Proteomic Tumor Analysis Consortium, and the 2008 Parson's GBM dataset. Expression of CUL2, which encodes the scaffold protein cullin2 in the CRL2 E3 ligase, can predict GBM progression and survival rate. Cullin2 protein levels are inversely related to those of HIF-1α, VEGF-A, Cyclin B1, and EGFR. Elevated CUL2 expression predicts increased radiosensitivity and dampened signal intensities in perfusion imaging. CUL2 expression are regulated via CNVs, which are inheritable structural DNA variations. CUL2 expression levels and CNVs can be integrated as potential biomarkers in facilitating GBM and prognosis and radiosensitivity profiling.


Assessment of the Role of 2,2,2-Trifluoroethanol Solvent Dynamics in Inducing Conformational Transitions in Melittin: An Approach with Solvent 19F Low-Field NMR Relaxation and Overhauser Dynamic Nuclear Polarization Studies.
2,2,2-Trifluoroethanol (TFE) is one of the fluoroalcohols that have been known to induce and stabilize an open helical structure in many proteins and peptides. The current study has benchmarked low-field 19F NMR relaxation and 19F Overhauser dynamic nuclear polarization (ODNP) by providing a brief account of TFE solvent dynamics in a model melittin (MLT, an antimicrobial peptide) solution with a TFE-D2O cosolvent mixture at pH 7.4. Further, this approach has been employed to reveal the solvation of MLT by TFE in a nonbuffered solution with pH 2.8 for the first time. The structural transition of MLT has been elucidated via solvent dynamics by measuring the 19F TFE relaxation rates at 0.34 T for various TFE-D2O compositions in the absence (bulk TFE) and in the presence of MLT at both the pH values. A complementary initial record of circular dichroism experiments on these aqueous MLT solutions with TFE as the cosolvent at two different pH conditions demonstrated the structural transition from a random coil to a helical or from a folded helical to an open helical structure. The molecular correlation time derived from the corresponding relaxation rates shows that TFE resides on the MLT surface in both pH conditions. However, the trends in the variation of molecular correlation time ratio as a function of TFE concentration represent that the mechanism and the extent to which TFE affects the MLT structural integrity are different at different pH values. The extraction of the DNP coupling parameter from steady-state 19F ODNP experiments performed in the presence of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl at 0.34 T revealed changes in the solvation dynamics of TFE concomitant with the MLT structural transition. In summary, 19F relaxation and ODNP measurements made at a low field have allowed direct monitoring of TFE dynamics during the MLT structural transition in terms of preferential solvation. The choice of experiments performed at a moderately low field (0.34 T) enabled us to exploit on the one hand almost 1200-fold mitigation of the strong contribution of 19F chemical shift anisotropy at 11.76 T, whereas on the other hand, the ODNP experiment offered a window for probing molecular dynamics on timescales of the order of 10-1000 ps.


Isolation of a substance activating foot formation in hydra.
We have developed an assay for a substance from hydra that accelerates foot regeneration in the animal. This substance is specific for the foot as evidenced by the following findings: (1) It is present in the animal as a steep gradient descending from foot to head, paralleling the foot-forming potential of the tissue (2) It does not accelerate head regeneration, nor do the head factors of hydra discovered by Schaller (1973) and Berking (1977) accelerate foot regeneration. We propose that the foot-activating substance is a morphogen responsible for foot formation in hydra. The foot activator can be extracted from hydra tissue with methanol and separated from other known morphogens of hydra by gel filtration and ion-exchange chromatography. A substance with similar biological and physicochemical properties can be isolated from sea anemones.


The effect of sealants on dental caries: a review.
Many dentists are concerned that caries may progress if inadvertently sealed within a tooth by a pit and fissure sealant. Several research studies have been performed to determine whether this is an important concern. This report reviews the methods and results of those studies.


Carbon dots based fluorescent sensor for sensitive determination of hydroquinone.
In this paper, a novel biosensor based on Carbon dots (C-dots) for sensitive detection of hydroquinone (H2Q) is reported. It is interesting to find that the fluorescence of the C-dots could be quenched by H2Q directly. The possible quenching mechanism is proposed, which shows that the quenching effect may be caused by the electron transfer from C-dots to oxidized H2Q-quinone. Based on the above principle, a novel C-dots based fluorescent probe has been successfully applied to detect H2Q. Under the optimal condition, detection limit down to 0.1 μM is obtained, which is far below U.S. Environmental Protection Agency estimated wastewater discharge limit of 0.5 mg/L. Moreover, the proposed method shows high selectivity for H2Q over a number of potential interfering species. Finally, several water samples spiked with H2Q are analyzed utilizing the sensing method with satisfactory recovery. The proposed method is simple with high sensitivity and excellent selectivity, which provides a new approach for the detection of various analytes that can be transformed into quinone.


Multi-vehicle interaction safety of connected automated vehicles in merging area: A real-time risk assessment approach.
The risky lane-changing manoeuvre of vehicles often occurs at expressway entrances, which would result in a high crash risk in the freeway system and significantly impact its safety. The highly anticipated environment of connected and autonomous vehicles (CAVs) is expected to reduce the associated crash risk of lane changing by offering various types of driving support, which utilise surrounding traffic information. The modelling crash risk under the environment of CAV driving during mandatory lane changing in merging areas faces new challenges due to the novelty of CAVs and subsequent shortage of data. To explore such risk situation of multi-vehicle interaction at expressway entrances, this study proposed a supervised learning algorithm and a Bayesian hierarchical model to assess risk levels and predict the probability of risk occurrence at different risk levels of interactive vehicles in real time of mandatory driving behaviour during the merging process. The learning algorithm, based on XGBoost, was exploited to classify risk levels. The Bayesian hierarchical model was used to analyse the probability of real-time risk comprising vehicle physical state layer, multi-vehicle interaction layer and risk probability layer. The probabilistic model parameters were calibrated using Markov Chain Monte Carlo (MCMC) Gibbs sampling method. The K-fold cross validation method was used to validate the proposed model of risk level. The probabilistic model validity was tested through posterior prediction of P-value. The quantitative risk estimation of CAVs through a few merging cases was conducted. Results show that the identification accuracy of slight, low, moderate and high risk is 94.24%, 85.82%, 84.16% and 79.69%, respectively. The P-value of Durbin-Watson's posterior, normal hypothesis, test distribution symmetry and kurtosis are all close to 0.5. Therefore, the method of real-time risk assessment is convergent and has good fitting. This research can promote cautious driving behaviours and provide reference for driver's decision making in the long term under the environment of CAVs.


[Prevention of childhood bronchial asthma--needs, abilities, limitations].
Through lack of effective primary prevention of childhood asthma, good secondary prevention program by early detection of the disease, is needed. Therefore we sought to estimate sensitivity, specificity and predictive values of asthma symptoms questionnaire. In Mikołów District 899 school children, aged 8-9 years were screened using respiratory symptoms questionnaire (80% of all in that age group). Question on "attacks of dyspnea" had the best positive predictive value (28%), high specificity (61%) and sensitivity (92%). Positive predictive values for other single symptoms were lower, but comparable values had "attacks of dyspnea with wheezing" (25%), with lower specificity (35%) and high sensitivity (95%). These findings confirm that standard questionnaire is a useful instrument for the childhood asthma screening. Until design and validation of more advanced screening tools, early identification children with asthma by questionnaire should be basic in prevention programs of the disease.


Suicide Communication on Social Media and Its Psychological Mechanisms: An Examination of Chinese Microblog Users.
This study aims to examine the characteristics of people who talk about suicide on Chinese microblogs (referred to as Weibo suicide communication (WSC)), and the psychological antecedents of such behaviors. An online survey was conducted on Weibo users. Differences in psychological and social demographic characteristics between those who exhibited WSC and those who did not were examined. Three theoretical models were proposed to explain the psychological mechanisms of WSC and their fitness was examined by Structural Equation Modeling (SEM). 12.03% of our respondents exhibited WSC in the past 12 months. The WSC group was significantly younger and less educated, preferred using blogs and online forums for expressing themselves, and reported significantly greater suicide ideation, negative affectivity, and vulnerable personality compared to non-WSC users. SEM examinations found that Weibo users with higher negative affectivity or/and suicidal ideation, who were also using blogs and forums more, exhibited a significantly higher possibility of WSC. Weibo users who are at greater suicide risk are more likely to talk about suicide on Weibo. WSC is a sign of negative affectivity or suicide ideation, and should be responded to with emotional support and suicide prevention services.


Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters.
The prototype mammalian proprotein processing enzyme furin is shown to be encoded by three distinct FUR mRNA isoforms which differ only in their 5'-untranslated regions. By primer extension analysis, the transcription start sites of the three mRNA isoforms were defined. The genomic regions located immediately upstream of the three alternative transcriptional start sites were shown to possess promoter activity in transfection experiments using the luciferase encoding gene as reporter. In a liver cell line, the P1 promoter appeared to be the strongest; in a lung cell line, the P1A promoter. Human FUR promoter P1 but not P1A or P1B was transactivated by transcription factor C/EBP beta. Other members of this family of bZIP transcription factors, C/EBP alpha and C/EBP delta, were not able to transactivate the P1 promoter. Promoter P1A and P1B have characteristics of promoters of housekeeping genes. They lack TATA or CAAT boxes upstream of the transcription start site but are very GC-rich and contain several SP1 sites. Promoter P1, on the other hand, has a TATA box in the proximal promoter region. In electromobility shift assays and DNase I footprinting analysis, transcription factor SP1 was found to bind to the proximal region of the P1 promoter. Altogether, our results indicate that expression of the human FUR gene is directed by alternative promoters, housekeeping (GC-rich) as well as regulated (TATA-containing) promoters, suggesting that their differential use may be a mechanism to modulate levels of the furin enzyme.


Direct continuous supercritical fluid extraction as a novel method of wine analysis. Comparison with conventional indirect extraction and implications for wine variety identification.
Direct supercritical fluid extraction (SFE) of wines with carbon dioxide was compared to SFE of the sorbent used for solid-phase extraction of the same wine samples (SPE-SFE). Compared to SPE-SFE, the direct SFE results in amore specific and representative gas chromatographic fingerprint of the wine sample. The multivariate statistical processing of the direct SFE-GC data provides a clear-cut and sharp discrimination among the individual wine varieties while the discrimination based on the SPE-SFE-GC data is relatively poor. This finding reflects the adverse effects of additional analyte-sorbent interactions and sorption/desorption steps involved in SPE-SFE.


Association of MTHFR 677C>T polymorphism with IUGR and placental abruption risk: A systematic review and meta-analysis.
The effects of the MTHFR 677C > T polymorphism on the intrauterine growth restriction (IUGR) and placental abruption risk have been evaluated in some studies. However, those studies results were conflicting and ambiguous. Therefore, we carried out the current meta-analysis to evaluate the association of MTHFR 677C > T polymorphism with risk of IUGR and placental abruption from all eligible studies. An electronic search of the PubMed, Embase, Scopus and CNKI databases was performed up to February 25, 2020. A total of 25 case-control studies including eight studies with 687 cases and 2336 controls for IUGR and 17 studies with 1574 cases and 5758 controls for placental abruption were selected. The analysis results indicated that MTHFR 677C > T polymorphism was associated with an increased risk of IUGR and placental abruption in global population. When stratified by ethnicity a significant association between the MTHFR 677C > T polymorphism and IUGR risk was found in Caucasians and Africans. However, there was no a significant association between the MTHFR 677C > T polymorphism and placental abruption risk by ethnicity. Our pooled data indicated that the MTHFR 677C > T polymorphism might play a role in development of IUGR and placental abruption.


Comparison of the response of diaphragm and upper airway dilating muscle activity in sleeping cats.
The steady state and transient effects of hyperoxic hypercapnia on the electromyographic activities of the genioglossus (GG), posterior cricoarytenoid (PCA), and diaphragm (D) were studied in cats instrumented with chronically implanted electrodes during non-rapid eye movement sleep. Hypercapnia (inhalation of 3.4 and 7.4% CO2 in O2) increased the phasic electrical activity occurring during inspiration of all three muscles. Activities of the PCA and D increased in a parallel fashion with increasing CO2. The GG responded to steady state CO2 inhalation alinearly, with larger increases in activity occurring when CO2 was raised from 3.4 to 7.4% than when CO2 was increased from 0 to 3.4%. When gas mixtures containing CO2 were given, the GG reached its new steady state level more slowly than the D or PCA, and when CO2 was rapidly removed from the inspired gas mixture, the GG attained its steady state sooner than the D. These results suggest that in sleeping cats, hypercapnia does not affect either transient or steady state responses of the GG in the same way as the D or the PCA. These differences seem to be explained largely by different threshold characteristics of hypoglossal and phrenic neurons.


Evaluation of matrix effect and chromatography efficiency: new parameters for validation of method development.
From the viewpoint of regulatory guidelines, validation of LC-UV and LC-MS based methods have the same requirements. Matrix effects are not considered for most method validations if they do not influence reproducibility or assay linearity. Since matrix effects can strongly suppress ionizaton efficiency and therefore reduce sensitivity, they must be evaluated (and discussed in the context of method development)--prior to method qualification. The severity of matrix effects is directly dependent upon chromatographic performance. We suggest that evaluation of matrix effects and LC efficiency is essential information for method assessment, optimization and transfer to other mass spectrometers, and should be a mandatory part of routine LC/MS method validation.


Comparison between bloodstream and procyclic form trypanosomes for serological diagnosis of African human trypanosomiasis.
Trypanosoma brucei brucei MiTat 1.2 bloodstream and corresponding procyclic forms, as well as procyclics of T. b. gambiense and T. b. rhodesiense, were fixed, in suspension, using a mixture of 80% acetone and 0.25% (v/v) formalin in saline and used as antigens for diagnosis of African human trypanosomiasis by the indirect immunofluorescent antibody test. T. b. brucei bloodstream forms detected 41/42 and 37/41 parasitologically diagnosed cases of T. b. rhodesiense and T. b. gambiense trypanosomiasis, respectively, while the procyclic stages detected the same number (41/42) of T. b. rhodesiense, but fewer (29/41) T. b. gambiense infections.


Machine learning to analyze the factors influencing myopia in students of different school periods.
We aim to develop myopia classification models based on machine learning algorithms for each schooling period, and further analyze the similarities and differences in the factors influencing myopia in each school period based on each model. Retrospective cross-sectional study. We collected visual acuity, behavioral, environmental, and genetic data from 7,472 students in 21 primary and secondary schools (grades 1-12) in Jiamusi, Heilongjiang Province, using visual acuity screening and questionnaires. Machine learning algorithms were used to construct myopia classification models for students at the whole schooling period, primary school, junior high school, and senior high school period, and to rank the importance of features in each model. The main influencing factors for students differ by school section, The optimal machine learning model for the whole schooling period was Random Forest (AUC = 0.752), with the top three influencing factors being age, myopic grade of the mother, and Whether myopia requires glasses. The optimal model for the primary school period was a Random Forest (AUC = 0.710), with the top three influences being the myopic grade of the mother, age, and extracurricular tutorials weekly. The Junior high school period was an Support Vector Machine (SVM; AUC = 0.672), and the top three influencing factors were gender, extracurricular tutorial subjects weekly, and whether can you do the "three ones" when reading and writing. The senior high school period was an XGboost (AUC = 0.722), and the top three influencing factors were the need for spectacles for myopia, average daily time spent outdoors, and the myopic grade of the mother. Factors such as genetics and eye use behavior all play an essential role in students' myopia, but there are differences between school periods, with those in the lower levels focusing on genetics and those in the higher levels focusing on behavior, but both play an essential role in myopia.


Formation of a novel arenium ion from the radical cation of a twisted triphenylene fully annelated with bicyclo[2.2.2]octene units.
[reaction: see text]. Triphenylene 1 was synthesized by palladium-catalyzed cyclotrimerization of a benzyne annelated with two bicyclo[2.2.2]octene (BCO) units. Theoretical calculations indicated that 1 is constrained to a twisted conformation with a C2 symmetry as a result of steric repulsion between the BCO units. The one-electron oxidation of 1 with SbCl5 gave the corresponding radical cation 1*+, which abstracted a chlorine atom in the medium with the concomitant rearrangement to form novel arenium ion 2+.


Adsorption of Transition Metals on Black Phosphorene: a First-Principles Study.
Black phosphorene is a novel two-dimensional material which has unique properties and wide applications. Using first-principles calculations, we investigated the adsorption behavior of 12 different transition metals (TMs; Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Os, Ir, Pt, and Au) on phosphorene. Our results showed that all of the adsorption systems have a large binding energy. The Fe-, Co-, and Au-phosphorene systems display magnetic states with magnetic moments of 2, 1, and 0.96 μB, respectively, which means that these systems are magnetic semiconductors. Adsorption of oxygen molecules on TM-phosphorene was also investigated. Interestingly, all the O2-(TM-phosphorene) systems, except O2-(Pd-phosphorene), can elongate the O-O bond, which is critical to their application as catalysts in the oxidation of CO. We also found that the adsorption of O2 molecules enables the O2-(Fe-, Ni-, Cu-, Ir-, Rh-, Ag-, and Au-phosphorene) systems to become magnetic semiconductors, and it allows O2-(Co-phosphorene) to display half-metallic state. Our results are expected to have important implications for phosphorene-based catalysis and spintronics.


Processing of Spanish Preterite regular and irregular verbs: the role of neighborhood density.
Research into lexical processes shows that frequency and phonological similarity (neighborhood density) affect word processing and retrieval. Previous studies on inflectional morphology have examined the influence of frequency of occurrence in speech production on the inflectional verb paradigm in English. Limited work has been done to examine the influence of phonological similarity in languages with a more complex morphological system than English. The present study examined the influence of neighborhood density on the processing of Spanish Preterite regular and irregular verbs as produced by thirty native speakers of Spanish. The results of a naming task showed that regular verbs were processed faster and more accurately than irregular ones. Similar to what has been observed in English, a facilitative effect of neighborhood density for -ir verbs was observed in both regular and irregular verbs, such that -ir verbs with dense neighborhoods were produced faster and more accurately than -ir verbs with sparse neighborhoods. However, no neighborhood density effects were observed for -ar verbs (regular and irregular) in reaction times and accuracy rates. Thus, the activation of a specific -ir verb was facilitated by similar sounding verbs regardless of being regular and irregular. Implications for models of morphology language processing are discussed.


Cardiac magnetic resonance assessment of left ventricular mass in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is associated with a substantial cardiovascular disease burden including early onset hypertension, intracranial aneurysms, and left ventricular hypertrophy (LVH). A 41% prevalence of LVH has been reported in ADPKD, using echocardiographic assessment of LV mass (LVM). The HALT PKD study was designed to assess the effect of intensive angiotensin blockade on progression of total kidney volume and LVM. Measurements of LVM were performed using cardiac magnetic resonance (MR). Five hundred forty-three hypertensive patients with GFR >60 ml/min per 1.73 m(2) underwent MR assessment of LVM at baseline. LVM was adjusted for body surface area and expressed as LVM index (LVMI; g/m(2)). Baseline BP was 125.1 ± 14.5/79.3 ± 11.6 mmHg. Average duration of hypertension was 5.79 years. Prior use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was present in 59.5% of patients. The prevalence of LVH assessed using nonindexed LVM (g) was 3.9% (n = 21, eight men and 13 women) and 0.93% (n = 5, one man and four women) using LVMI (g/m(2)). In exploratory analyses, the prevalence of LVH using LVM indexed to H(2.7), and the allometric index ppLVmass(HW), ranged from 0.74% to 2.23% (n = 4 to 12). Multivariate regression showed significant direct associations of LVMI with systolic BP, serum creatinine, and albuminuria; significant inverse associations with LVMI were found with age and female gender. The prevalence of LVH in hypertensive ADPKD patients <50 years of age with short duration of hypertension, and prior use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers is low. Early BP intervention in ADPKD may have decreased LVH and may potentially decrease cardiovascular mortality.


Effects of influenza vaccine and sun exposure time against laboratory-confirmed influenza hospitalizations among young children during the 2012-13 to 2015-16 influenza seasons.
Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses. We conducted a matched-pair case-control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012-2013, 2013-2014, 2014-2015, and 2015-2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients' guardians to complete questionnaires. Data were analyzed using conditional logistic regression. We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p < 0.05; OR, 0.667; 95% CI, 0.491-0.906). Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children.


The therapeutic and neuroprotective effects of an antiepileptic drug valproic acid in glioma patients.
Glioma is the most common primary malignant brain tumor in adults and the patients have poor prognosis despite treatment with surgery, radiotherapy and chemotherapy. The anti-epileptic drug, valproic acid (VPA) as a HDAC inhibitors is often used in glioma patients even if the patients don't have brain tumors associated epilepsy (BAE). Some previous studies have found that VPA not only has anti-epileptic effect, but also has anti-glioma growth effect through enhance radiotherapy sensitivity or other mechanism. Then VPA is reported to improve the survival of glioma patients receiving chemoradiation therapy. In addition, there are limited researches have shown that VPA has a neuroprotective effect in protect normal cells and tissues from the deleterious effects of treatment of glioma, especially radiotherapy. We'll give a brief overview of these effects of VPA in glioma patients.


The central nervous system cytokine response to global ischemia following resuscitation from ventricular fibrillation in a porcine model.
Pro-inflammatory cytokines have been implicated as culprits in neurotoxicity following ischemia in small animal models of stroke. The aim of this study was to measure the central nervous system (CNS) cytokine response following resuscitation from ventricular fibrillation (VF) in a porcine model of cardiac arrest and global hypoxic ischemia. VF was induced electrically in 11 anesthetized swine. Following 7 min of untreated VF, animals were resuscitated. Cerebrospinal fluid (CSF) and serum was sampled prior to VF and at 60, 120, and 180 min post-resuscitation from which levels of TNF-alpha, IL-1 beta, and IL-6 were measured. Levels were also drawn in three sham pigs, instrumented but not fibrillated. CSF levels of TNF-alpha rose following resuscitation and were associated with CSF levels of IL-1 beta (p=0.0002). CSF levels of all cytokines except TNF-alpha were associated with their serum counterparts. Measurable increases in pro-inflammatory cytokines in the CSF follow resuscitation from cardiac arrest in this porcine model. The CNS response TNF-alpha and IL-1 beta are associated. However, serum levels of TNF-alpha did not seem to predict CSF levels in this study, consistent with the concept of immune privilege of the CNS.


Estimated growth of lung volume reduction surgery among Medicare enrollees: 1994 to 1996.
To estimate the number of lung volume reduction surgery procedures performed on Medicare enrollees from 1994 to 1996. Statistical analysis of national Medicare claims data. All Medicare enrollees with emphysema hating claims records for pulmonary resection procedures from January 1, 1993, through December 31, 1996. Estimated number of lung volume reduction procedures performed per month from July 1994 through December 1996. An estimated 1,212 lung volume reduction procedures were performed on Medicare enrollees between July 1994 and December 1995 (95% confidence interval, 1,012 to 1,408). Nearly one half of these procedures were performed in the last 3 months of 1995. At the time Health Care Financing Administration announced that it would suspend reimbursement for the procedure (December 1995), lung volume reduction surgery was being performed in 37 states. The number of claims per month decreased from a peak of 169 in December 1995, to 11 in March 1996. Average Medicare reimbursement per procedure was $31,398. Lung volume reduction surgery for patients increased rapidly following its reintroduction in 1994. The growth of lung volume reduction surgery demonstrates that widespread adoption and utilization of a surgical procedure can occur in the absence of data from controlled clinical trials. Medicare expenditures for lung volume reduction surgery were an estimated $30 million to $50 million. Performing the surgery for all current Medicare patients who meet the appropriate clinical criteria would cost an estimated $1 billion.


Absorption and biotransformation of L(+)-tartaric acid in rats.
Oral or parenteral doses of monosodium 14C-L(+)-tartrate (400 mg/kg) are rapidly excreted by rats and a proportion completely metabolized to CO2. The oral dose was well-absorbed.


Novel deep learning-based computer-aided diagnosis system for predicting inflammatory activity in ulcerative colitis.
Endoscopy is increasingly performed for evaluating patients with ulcerative colitis (UC). However, its diagnostic accuracy is largely affected by the subjectivity of endoscopists' experience and scoring methods, and scoring of selected endoscopic images cannot reflect the inflammation of the entire intestine. We aimed to develop an automatic scoring system using deep-learning technology for consistent and objective scoring of endoscopic images and full-length endoscopic videos of patients with UC. We collected 5875 endoscopic images and 20 full-length videos from 332 patients with UC who underwent colonoscopy between January 2017 and March 2021. We trained the artificial intelligence (AI) scoring system using these images, which was then used for full-length video scoring. To more accurately assess and visualize the full-length intestinal inflammation, we divided the large intestine into a fixed number of "areas" (cecum, 20; transverse colon, 20; descending colon, 20; sigmoid colon, 15; rectum, 10). The scoring system automatically scored inflammatory severity of 85 areas from every video and generated a visualized result of full-length intestinal inflammatory activity. Compared with endoscopist scoring, the trained convolutional neural network achieved 86.54% accuracy in the Mayo-scored task, whereas the kappa coefficient was .813 (95% confidence interval [CI], .782-.844). The metrics of the Ulcerative Colitis Endoscopic Index of Severity-scored task were encouraging, with accuracies of 90.7%, 84.6%, and 77.7% and kappa coefficients of .822 (95% CI, .788-.855), .784 (95% CI, .744-.823), and .702 (95% CI, .612-.793) for vascular pattern, erosions and ulcers, and bleeding, respectively. The AI scoring system predicted each bowel segment's score and displayed distribution of inflammatory activity in the entire large intestine using a 2-dimensional colorized image. We established a novel deep learning-based scoring system to evaluate endoscopic images from patients with UC, which can also accurately describe the severity and distribution of inflammatory activity through full-length intestinal endoscopic videos.


HepG2 as promising cell-based model for biosynthesis of long-term metabolites: Exemplified for metandienone.
In order to detect the abuse of substances in sports, the knowledge of their metabolism is of undisputable importance. As in vivo administration of compounds faces ethical problems and might even not be applicable for nonapproved compounds, cell-based models might be a versatile tool for biotransformation studies. We coincubated HepG2 cells with metandienone and D3 -epitestosterone for 14 days. Phase I and II metabolites were analyzed by high-performance liquid chromatography (HPLC)-tandem mass spectrometry and confirmed by gas chromatography-mass spectrometry (GC-MS). The metandienone metabolites formed by HepG2 cells were comparable with those renally excreted by humans. HepG2 cells also generated the two long-term metabolites 17β-hydroxymethyl-17α-methyl-18-nor-androst-1,4,13-trien-3-one and 17α-hydroxymethyl-17β-methyl-18-nor-androst-1,4,13-trien-3-one used in doping analyses, though in an inverse ratio compared with that observed in human urine. In conclusion, we showed that HepG2 cells are suitable as model for the investigation of biotransformation of androgens, especially for the anabolic androgenic steroid metandienone. They further proved to cover phase I and II metabolic pathways, which combined with a prolonged incubation time with metandienone resulted in the generation of its respective long-term metabolites known from in vivo metabolism. Moreover, we showed the usability of D3 -epitestosterone as internal standard for the incubation. The method used herein appears to be suitable and advantageous compared with other models for the investigation of doping-relevant compounds, probably enabling the discovery of candidate metabolites for doping analyses.


Astragalin alleviates cognitive deficits and neuronal damage in SAMP8 mice through upregulating estrogen receptor expression.
Senile plaques composed of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) composed of intracellular hyper-phosphorylated tau are major causes of cognitive impairment and neuronal damage in Alzheimer disease (AD). Astragalin (AST), a naturally-occurring flavonoid compound, was reported to have neuroprotective effects in the brain, but its effects in AD remain unknown. Herein, the learning and memory deficits were alleviated and neuronal damage in the hippocampus were inhibited after the senescence-accelerated mouse prone 8 (SAMP8) mouse were given AST (5 mg/kg or 10 mg/kg) daily by gavage for 2 months. Furthermore, AST reduced Aβ1-40 and Aβ1-42 deposition, decreased β-carboxyl-terminal fragment (β-CTF) protein level and tau hyper-phosphorylation, but increased α-CTF protein level and glycogen synthase kinase-3beta (GSK-3β) phosphorylation in hippocampus of SAMP8 mice. Meanwhile, the effects of AST on AD were also explored in vitro by treating primary neurons with amyloid-β1-42 oligomers (Aβ1-42O). Consistently, AST also alleviated amyloid-β1-42 oligomers (Aβ1-42O)-induced neuronal damage, amyloid plaques, and tau phosphorylation in vitro model. Of note, estrogen receptor (ER)α and ERβ expression in the hippocampus of SAMP8 mice and Aβ1-42O-treated neurons was significantly decreased but their levels were increased by AST. Moreover, in vivo and in vitro experiments revealed that ER antagonist, Fulvestrant, reversed the effects caused by AST. Altogether, our investigation indicates that AST may ameliorate cognitive deficits and AD-type pathologies in SAMP8 mice and Aβ1-42O-treated neurons through upregulating ERα and ERβ expression. Our findings indicate the value of AST as a potential reagent for AD treatment.


Redoxins in peripheral neurons after sciatic nerve injury.
Peripheral nerve injury causes redox stress in injured neurons by upregulations of pro-oxidative enzymes, but most neurons survive suggesting an activation of endogenous defense against the imbalance. As potential candidates we assessed thioredoxin-fold proteins, called redoxins, which maintain redox homeostasis by reduction of hydrogen peroxide or protein dithiol-disulfide exchange. Using a histologic approach, we show that the peroxiredoxins (Prdx1-6), the glutaredoxins (Glrx1, 2, 3 and 5), thioredoxin (Txn1 and 2) and their reductases (Txnrd1 and 2) are expressed in neurons, glial and/or vascular cells of the dorsal root ganglia (DRGs) and in the spinal cord. They show distinct cellular and subcellular locations in agreement with the GO terms for "cellular component". The expression and localization of Glrx, Txn and Txnrd proteins was not affected by sciatic nerve injury but peroxiredoxins were upregulated in the DRGs, Prdx1 and Prdx6 mainly in non-neuronal cells and Prdx4 and Prdx5 in DRG neurons, the latter associated with an increase of respective mRNAs and protein accumulation in peripheral and/or central fibers. The upregulation of Prdx4 and Prdx5 in DRG neurons was reduced in mice with a cre-loxP mediated deficiency of hypoxia inducible factor 1 alpha (HIF1α) in these neurons. The results identify Prdx4 and Prdx5 as endogenous HIF1α-dependent, transcriptionally regulated defenders of nerve injury evoked redox stress that may be important for neuronal survival and regeneration.


Determination of the analgesic 3-phenoxy-N-methylmorphinan in plasma by gas chromatography using either positive chemical ionization mass spectrometric or nitrogen-phosphorus-specific detection analysis.
The compound 3-phenoxy-N-methylmorphinan (I) is under development as an analgesic agent. Studies on the biotransformation of the drug in the rat and in the dog have shown that I is extensively metabolized by N-demethylation to yield the nor-analogue (I-A), by para-hydroxylation of the 3-phenoxy ring to yield the phenolic analogue (I-B), cleavage of the ether linkage to yield levorphanol (I-C), and its N-demethylation to yield nor-levorphanol (I-D). The presence of these four metabolites (two of which, I-B and I-C, have analgesic potential) in addition to the parent drug, necessitated the development of sensitive and specific assays for their quantitation in plasma. This was accomplished by the development of (a) a high-performance liquid chromatographic assay using UV detection to obtain a qualitative/semi-quantitative profile of the metabolites present in plasma; (b) a gas chromatographic--nitrogen--phosphorus-specific detection method for the determination of the parent drug (I) for pre-clinical drug evaluation; and (c) a sensitive and specific gas chromatographic--positive chemical ionization mass spectrometric assay for eventual clinical evaluation for the determination of I and a key metabolite levorphanol (I-C). This report presents some preliminary pharmacokinetic data on I and I-C in the dog obtained during pre-clinical development.


X-ray detectors at the Linac Coherent Light Source.
Free-electron lasers (FELs) present new challenges for camera development compared with conventional light sources. At SLAC a variety of technologies are being used to match the demands of the Linac Coherent Light Source (LCLS) and to support a wide range of scientific applications. In this paper an overview of X-ray detector design requirements at FELs is presented and the various cameras in use at SLAC are described for the benefit of users planning experiments or analysts looking at data. Features and operation of the CSPAD camera, which is currently deployed at LCLS, are discussed, and the ePix family, a new generation of cameras under development at SLAC, is introduced.


A stimulus-control account of regulated drug intake in rats.
Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not. This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement. Rats' nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments. Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration. This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing.


Effects of maternal exposure to di-n-butyl phthalate during pregnancy and breastfeeding on ovarian development and function of F1 female rats.
This study aimed to investigate the effects of maternal exposure to di-n-butyl phthalate (DBP) during pregnancy and breastfeeding on F1 ovarian development and function. A rat model of maternal exposure to DBP during pregnancy and breastfeeding was established by gavage feeding female Sprague Dawley rats with 0, 10, 100, or 600mg/kg/day DBP from gestational day (GD) 12 to postnatal day (PND) 21. F1 offspring were weaned on PND21 and were not exposed to DBP afterward. The age of vaginal opening and estrus onset, estrous cyclicity, c-Kit-ligand expression on ovarian granulosa cells, and the weight of ovaries and uterus of F1 female offspring were not affected, whereas serum levels of estradiol and progesterone were increased significantly by maternal exposure to 10mg/kg/day DBP from GD12 to PND21. Although F1 ovarian function may not be adversely affected by maternal exposure to DBP, the increased reproductive hormone levels may interfere in F1 rat fertility.


Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis.
The factors underlying cardiovascular risk in patients with diabetes have not been clearly elucidated. Efforts to study this in mice have been hindered because the usual atherogenic diets that contain fat and cholesterol also lead to obesity and insulin resistance. We compared plasma glucose, insulin, and atherosclerotic lesion formation in LDL receptor knockout (Ldlr(-/-)) mice fed diets with varying fat and cholesterol content that induced similar lipoprotein profiles. Ldlr(-/-) mice fed a high-fat diet developed obesity, mild hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Quantitative and qualitative assessments of atherosclerosis were unchanged in diabetic Ldlr(-/-) mice fed a high-fat diet compared with lean nondiabetic control mice after 20 weeks of diet. Although one group of mice fed diets for 40 weeks had larger lesions at the aortic root, this was associated with a more atherogenic lipoprotein profile. The presence of a human aldose reductase transgene had no effect on atherosclerosis in fat-fed Ldlr(-/-) mice with mild diabetes. Our data suggest that when lipoprotein profiles are similar, addition of fat to a cholesterol-rich diet does not increase atherosclerotic lesion formation in Ldlr(-/-) mice.


Comparative immunohistochemistry of synaptic markers in the rodent hippocampus in pilocarpine epilepsy.
Pilocarpine-induced epileptic state (Status epilepticus) generates an aberrant sprouting of hippocampal mossy fibers, which alter the intrahippocampal circuits. The mechanisms of the synaptic plasticity remain to be determined. In our studies in mice and rats, pilocarpine-induced seizures were done in order to gain information on the process of synaptogenesis. After a 2-month survival period, changes in the levels of synaptic markers (GAP-43 and Syn-I) were examined in the hippocampus by means of semi-quantitative immunohistochemistry. Mossy fiber sprouting (MFS) was examined in each brain using Timm's sulphide-silver method. Despite the marked behavioral manifestations caused by pilocarpine treatment, only 40% of the rats and 56% of the mice showed MFS. Pilocarpine treatment significantly reduced the GAP-43 immunoreactivity in the inner molecular layer in both species, with some minor differences in the staining pattern. Syn-I immunohistochemistry revealed species differences in the sprouting process. The strong immunoreactive band of the inner molecular layer in rats corresponded to the Timm-positive ectopic mossy fibers. The staining intensity in this layer, representing the ectopic mossy fibers, was weak in the mouse. The Syn-I immunoreactivity decreased significantly in the hilum, where Timm's method also demonstrated enhanced sprouting. This proved that, while sprouted axons displayed strong Syn-I staining in rats, ectopic mossy fibers in mice did not express this synaptic marker. The species variability in the expression of synaptic markers in sprouted axons following pilocarpine treatment indicated different synaptic mechanisms of epileptogenesis.


Distinct roles of CpcG1 and CpcG2 in phycobilisome assembly in the cyanobacterium Synechocystis sp. PCC 6803.
Structural role of the second copy of the rod-core linker CpcG, which was found by genome analysis, was studied in Synechocystis sp. PCC 6803 by gene disruption and fractionation of phycobilisome (sub)complexes. Disruption of cpcG2 (sll1471) resulted in a marked decrease in phycocyanin content both in the background of wild-type and cpcG1 (slr2051)-disruptant. The unique phycocyanin rod-CpcG2 complex without the major allophycocyanin components was isolated from the cpcG1-disruptant. By fluorescence analysis, it was proposed that CpcG2 protein connects the rods with a minor allophycocyanin component, to support energy transfer to Photosystem I.


Ultrahistochemical investigations of dog lung surfactant with ruthenium red and iodoplatinate reactions.
Dog lungs have been fixed by immersion and submitted to two histochemical procedures. An iodoplatinate reaction technique to demontrate choline phospholipids stains cell membranes, inclusion bodies of type II alveolar epithelial cells and tubular myelin figures of pulmonary surfactant, the latter as electron-dense lines measuring 5 nm. The ruthenium red procedure gives rise to an intense contrast of the free surface of alveolar epithelium. The 5 nm-lines of the pulmonary surfactant are seen as electron-lucent lines, but bordered by electron-dense rims. Though both techniques have limitations in their interpretation, which are discussed in this paper, they demonstrate the tubular myelin figures to be a highly organized mixture of phospholipids and glycoproteins.


Isolation and characterization of a sulfated glyceroglucolipid from alveolar lavage of rabbit.
A major acidic glycolipid of the rabbit alveolar lavage has been isolated and characterized. The isolation procedure involved extraction of lipids, column fractionation on DEAE-Sephadex and silicic acid, and thin-layer chromatography. Chemical analysis of the glycolipid revealed the presence of glucose, fatty acids, glycerol mono-ethers and sulfate. By partial acid and alkaline methanolysis, oxidation with periodate and chromium trioxide, and methylation analysis of the native and desulfated compound, the structure of this glycolipid is proposed to be: SO3H-6Glc alpha 1 leads to 6Glc alpha 1 leads to 6Glc alpha 1 leads to 6Glc alpha 1 leads to 3-1,(3)-O-alkyl-2-0-acylglycerol.


Syndromes, disorders and maternal risk factors associated with neural tube defects (VI).
Neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.


Application of cognitive Internet of Medical Things for COVID-19 pandemic.
In the age of advanced digital technology, smart healthcare based on the Internet of Things (IoT) is gaining importance to deal with the current COVID-19 pandemic. In this paper, the novel application of cognitive radio (CR) based IoT specific for the medical domain referred to as Cognitive Internet of Medical Things (CIoMT) is explored to tackle the global challenge. This concept of CIoT is best suited to this pandemic as every person is to be connected and monitored through a massive network that requires efficient spectrum management. An extensive literature survey is conducted in the Google Scholar, Scopus, PubMed, Research Gate, and IEEE Xplore databases using the terms "COVID-19" and "Cognitive IoT" or "Corona virus" and "IoMT". The latest data and inputs from official websites and reports are used for further investigation and analysis of the application areas. This review encompasses different novel applications of CIoMT for fighting the ongoing COVID-19 health crisis. The CR based dynamic spectrum allocation technique is the solution for accommodating a massive number of devices and a wide number of applications. The CIoMT platform enables real-time tracking, remote health monitoring, rapid diagnosis of the cases, contact tracking, clustering, screening, and surveillance thus, reducing the workload on the medical industry for prevention and control of the infection. The challenges and future research directions are also identified. CIoMT is a promising technology for rapid diagnosis, dynamic monitoring and tracking, better treatment and control without spreading the virus to others.


Foliar quality influences tree-herbivore-parasitoid interactions: effects of elevated CO2, O3, and plant genotype.
This study examined the effects of carbon dioxide (CO2)-, ozone (O3)-, and genotype-mediated changes in quaking aspen (Populus tremuloides) chemistry on performance of the forest tent caterpillar (Malacosoma disstria) and its dipteran parasitoid (Compsilura concinnata) at the Aspen Free-Air CO2 Enrichment (FACE) site. Parasitized and non-parasitized forest tent caterpillars were reared on two aspen genotypes under elevated levels of CO2 and O3, alone and in combination. Foliage was collected for determination of the chemical composition of leaves fed upon by forest tent caterpillars during the period of endoparasitoid larval development. Elevated CO2 decreased nitrogen levels but had no effect on concentrations of carbon-based compounds. In contrast, elevated O3 decreased nitrogen and phenolic glycoside levels, but increased concentrations of starch and condensed tannins. Foliar chemistry also differed between aspen genotypes. CO2, O3, genotype, and their interactions altered forest tent caterpillar performance, and differentially so between sexes. In general, enriched CO2 had little effect on forest tent caterpillar performance under ambient O3, but reduced performance (for insects on one aspen genotype) under elevated O3. Conversely, elevated O3 improved forest tent caterpillar performance under ambient, but not elevated, CO2. Parasitoid larval survivorship decreased under elevated O3, depending upon levels of CO2 and aspen genotype. Additionally, larval performance and masses of mature female parasitoids differed between aspen genotypes. These results suggest that host-parasitoid interactions in forest systems may be altered by atmospheric conditions anticipated for the future, and that the degree of change may be influenced by plant genotype.


Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1α, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy.
To determine the vitreous levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α) and angiopoietin-like protein 2 (ANGPTL2) in patients with active proliferative diabetic retinopathy (PDR), and to ascertain their contribution on different clinical presentation of active PDR. This case-control study included 31 eyes with active PDR and 10 eyes with idiopathic macular hole (MH) (control group). Eyes with active PDR were divided into three subgroups: vitreous hemorrhage (VH), tractional retinal detachment (TRD) caused by active fibrovascular membrane (FVM), and coexistence of VH and TRD with FVM. Vitreous samples obtained during vitrectomy were analyzed for concentrations of VEGF, SDF-1α, and ANGPTL2. Vitreous level of VEGF (2021 (168-6550) pg/ml vs 110.1 (74.5-236) pg/ml), SDF-1α (517 (194-1044) pg/ml vs 388 (320-535) pg/ml), and ANGPTL2 (725 (131-1590) ng/ml vs 196 (75.9-437) ng/ml) were significantly higher in eyes with active PDR than in control group (p < 0.001, p = 0.002, and p < 0.001, respectively). The concentrations of these meaditors in each active PDR subgroups were also significantly higher than control group (p < 0.05). The vitreous level of ANGPTL2 was significantly higher in eyes with TRD caused by FVM (1033 ± 401 ng/ml) than in eyes with VH (561 ± 237 ng/ml; p = 0.008). High levels of SDF-1α, ANGPTL2 and particularly VEGF seem to be associated with PDR. Since the vitreous levels of ANGPTL2 tend to be higher in eyes with active fibrovascular tractional detachment, vitreous levels of this chemokine seem to be affected by the clinical presentation of vascularly active PDR eyes.