The urinary C-peptide excretion in normal healthy children.
The 24 h urinary C-peptide excretion was determined in 137 normal healthy children, 52 girls and 85 boys, 3-15 years of age. No significant difference was found between boys and girls. Median value of urinary C-peptide for boys and girls was 0.24 nmol/kg/24 h with a range of 0.07-0.61 nmol/kg/24 h. Urinary C-peptide correlated positively and significantly with age, weight, height, body surface area and the 24 h urinary creatinine excretion. Since the values of C-peptide excretion were not normally distributed they were log transformed and plotted against body weight. The linear regression and the 95% confidence limits were then calculated. Girls at puberty, 11-15 years of age, had significantly higher C-peptide excretion per kg body weight and per body surface area than younger girls, 3-10 years of age. Boys 13-15 years of age had significantly higher C-peptide excretion per body surface area than younger boys, 5-12 years of age. This indicates that children during the maximal growth spurt have an increased insulin secretion as measured by urinary C-peptide per body surface area.


Reducing CD4 Monitoring in Children on Antiretroviral Therapy With Virologic Suppression.
Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after ≥1 year on ART (time 0)] and (2) ≥1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure. Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone.


Benzylation and nitrosation of 4-amino-2-(methylsulfanyl)pyrimidin-6(1H)-one: two P2(1)/c polymorphs of 4-amino-1-benzyl-2-(methylsulfanyl)pyrimidin-6(1H)-one with Z' = 1 and 2, 4-amino-6-benzyloxy-2-(methylsulfanyl)pyrimidine and 4-amino-1-benzyl-2-(methylsulfanyl)-5-nitrosopyrimidin-6(1H)-one all give different hydrogen-bonded supramolecular structures.
4-Amino-1-benzyl-2-(methylsulfanyl)pyrimidin-6(1H)-one, C(12)H(13)N(3)OS, crystallizes in two polymorphic forms, both having space group P2(1)/c, with Z' = 1 for form (I) and Z' = 2 for form (II). In (I), the molecules are linked by a single N-H.O hydrogen bond into simple C(6) chains, which are themselves linked into sheets by aromatic pi-pi interactions, while in (II), chains of edge-fused R(4)(2)(8) and R(4)(4)(24) rings are generated by four distinct N-H.O hydrogen bonds. In 4-amino-1-benzyl-2-(methylsulfanyl)-5-nitrosopyrimidin-6(1H)-one, C(12)H(12)N(4)O(2)S, (III), where Z' = 2, two independent three-centre N-H.(N,O) hydrogen bonds generate a C(5)C(6)[R(1)(2)(5)] chain of rings. In 4-amino-6-benzyloxy-2-(methylsulfanyl)pyrimidine, C(12)H(13)N(3)OS, (IV), which is isomeric with (I) and (II), a combination of N-H.N and N-H.O hydrogen bonds generates a sheet of alternating R(2)(2)(8) and R(6)(6)(28) rings.


Transient and persistent depolarization-induced changes of protein phosphorylation in a molluscan nervous system.
Phosphoproteins in the CNS of the nudibranch mollusc, Hermissenda crassicornis, were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. After preincubation in artificial sea-water containing 32P, nervous systems were exposed to elevation of external K+ (100 or 300 mM) for a period (e.g., 30 min) approximating a period of depolarization which occurs during classical conditioning. Elevated external K+ was found to change the state of phosphorylation of three distinct proteins (Mr 56,000, 25,000, and 20,000) in three distinct ways without consistently changing that of any other proteins. Phosphorylation of an Mr 56,000 protein was increased by high K+ about twofold only in the presence of external Ca2+ [( Ca2+]o). Phosphorylation of Mr 25,000 protein, on the other hand, was decreased up to 10-fold by high K+, irrespective of the level of [Ca2+]o. The effect of depolarization on Mr 25,000 protein phosphorylation most likely represents dephosphorylation rather than proteolysis. This interpretation is consistent with the observations that (a) reappearance of the Mr 25,000 protein occurred in the presence of the protein synthesis inhibitors cycloheximide, puromycin, or anisomycin, and (b) the Hermissenda nervous system apparently contains a NaF- and EDTA-sensitive protein phosphatase capable of dephosphorylating Mr 25,000 protein. High K+ also reduced Mr 20,000 protein phosphorylation which was dependent on [Ca2+]o even in normal low K+ (10 mM) medium. Removal of [Ca2+]o enhanced reduction of Mr 20,000 phosphorylation due to the high K+ treatment. Interestingly, reduction of the Mr 25,000 protein phosphorylation was long-lasting, i.e., its phosphorylation did not fully recover to a control level for at least 30 min after the high K+ conditions had been removed.(ABSTRACT TRUNCATED AT 250 WORDS)


Duration of Treatment of Carrot Hypocotyl Explants with 2,4-Dichlorophenoxyacetic Acid for Direct Somatic Embryogenesis.
The relationship between the concentration of 2,4-dichlorophe- noxyacetic acid (2,4-D) and the duration of treatment with 2,4-D on direct somatic embryogenesis from carrot hypocotyl explants was examined. Elevated concentrations of 2,4-D (up to 100 mg/ liter) reduced the duration of pretreatment required for successful embryogenesis.


Inositol acylation of a potential glycosyl phosphoinositol anchor precursor from yeast requires acyl coenzyme A.
Glycosyl phosphoinositol (GPI) anchors on proteins can be modified by palmitoylation of their inositol residue, which makes such anchors resistant to cleavage by phosphatidylinositol-specific phospholipase C (PI-PLC) (Roberts, W. L., Myher, J. J., Kuksis, A., Low, M. G., and Rosenberry, T.L. (1988) J. Biol. Chem. 263, 18766-18775). Mannosylated GPI lipids made in trypanosomal and mammalian cells can also be inositol-acylated, indicating that inositol acylation may be a normal step in GPI anchor synthesis. We find that Saccharomyces cerevisiae mutants blocked in dolichyl phosphate mannose synthesis accumulate a lipid that can be radiolabeled in vivo with [3H]myo-inositol, [3H]GlcN, and [3H]palmitic acid. This lipid is resistant to PI-PLC, yet sensitive to mild alkaline hydrolysis, and has been characterized as GlcN-phosphatidylinositol (PI), fatty acylated on its inositol residue. When yeast membranes are incubated with UDP-[14C] GlcNAc, 14C-labeled GlcNAc-PI and GlcN-PI are made. Addition of ATP and CoA, or of palmitoyl-CoA to incubations results in the synthesis of [14C]GlcN-(acyl-inositol)PI. This lipid is also made when membranes are incubated with [1-14C]palmitoyl-CoA and UDP-GlcNAc. We propose that acyl CoA is the donor in inositol acylation of GlcN-PI, and that GlcN-(acyl-inositol)PI is an obligatory intermediate in GPI synthesis.


Ventricular volume and length in hypertensive diastolic heart failure.
Patients with diastolic heart failure are thought to have a normal or small ventricle with impaired ventricular filling that requires increased filling pressure to maintain normal stroke volume. In this study we test the hypothesis that patients with hypertensive diastolic heart failure have increased left ventricular volumes compared with age-, sex-, and body size-matched control subjects. Left ventricular chordal dimensions from 2-dimensional echocardiography and volumes from 3-dimensional echocardiography were obtained in control subjects (n = 96) and patients with hypertensive diastolic heart failure (n = 28) and compared before and after controlling for age, sex, and body size. Volumes by 3-dimensional echocardiography were significantly larger in the heart failure group than in the control group (P < .05). After matching for age, sex, and body size, volumes remained significantly larger in the patients with heart failure (P < .05). Chordal dimensions were not significantly different between the two groups. Stroke volume and centerline length of the ventricle were significantly increased in the heart failure group compared with matched control subjects (P < .05). Our group of patients with hypertensive diastolic heart failure had significantly increased left ventricular volumes and stroke volume compared with control subjects, compatible with volume overload heart failure. Two-dimensional echocardiographic measurement of the ventricular chordal dimension failed to detect this enlargement. Ventricular length appeared to be preferentially increased in the patients with hypertensive diastolic heart failure.


Long term fluctuations of groundwater mine pollution in a sulfide mining district with dry Mediterranean climate: Implications for water resources management and remediation.
Water resources management and restoration strategies, and subsequently ecological and human life quality, are highly influenced by the presence of short and long term cycles affecting the intensity of a targeted pollution. On this respect, a typical acid mine drainage (AMD) groundwater from a sulfide mining district with dry Mediterranean climate (Iberian Pyrite Belt, SW Spain) was studied to unravel the effect of long term weather changes in water flow rate and metal pollutants concentration. Three well differentiated polluting stages were observed and the specific geochemical, mineralogical and hydrological processes involved (pyrite and enclosing rocks dissolution, evaporitic salts precipitation-redisolution and pluviometric long term fluctuations) were discussed. Evidencing the importance of including longer background monitoring stage in AMD management and restoration strategies, the present study strongly advise a minimum 5-years period of AMD continuous monitoring previous to the design of any AMD remediation system in regions with dry Mediterranean climate.


Influence of dietary patterns on contaminants bioaccessibility and intestinal transport by in vitro assays.
Food contaminants are usually studied as isolated molecules, not considering the overall meal components. Notwithstanding, contaminants are not ingested individually, therefore their risks should be assessed in the context of the overall diet. In the present study the influence of three well known dietary patterns, Western (W), Mediterranean (M) and vegetarian (V), on the bioaccessibility and intestinal transport of polycyclic aromatic hydrocarbons (PAHs) (benzo[a]pyrene (BaP) and benzo[b]fluoranthene (BbF)), heterocyclic aromatic amines (HAAs) (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-Amino-9H-pyrido[2,3-b]indole (AAC)) and mycotoxins (MY) (aflatoxin B2 (AB2) and ochratoxin A (OTA)) was evaluated. Whole meals representative of W, M and V patterns were spiked with 100 µg kg-1 of each contaminant and subjected to the Infogest in vitro digestion method. Intestinal transport was performed using Caco-2 cells in apical/basolateral inserts. Contaminants were quantified by QuEChERS/HPLC/Fluorescence analysis. The dietary pattern itself influenced significantly the bioaccessibility of some contaminants, since higher bioaccessibility of HAAs (PhIP and AAC) was observed for V diet, while higher bioaccessibility of PAHs (BBF and BAP) and the MY (OTA) was observed for W diet. Concerning intestinal transport, the effect of the diet matrices was less noticed. Notwithstanding, AAC transport increased with W diet, while AB2s transport increased with the V diet. Regarding PAHs the three patterns either blocked (BbF) or reduced (BaP) the transport. Besides the well known nutritional, protective or deleterious effects of the different dietary patterns, the increased bioaccessibility or intestinal transport of some food contaminants, can have an additional influence on the global health impact.


Molecular forms and localization of acetylcholinesterase and nonspecific cholinesterase in regenerating skeletal muscles.
Molecular forms and histochemical localization of acetylcholinesterase and nonspecific cholinesterase were analysed in muscle regenerates obtained from rat EDL and soleus muscles after ischaemic-toxic degeneration and irreversible inhibition of preexistent enzymes. Regenerating myotubes and myofibres produce the 16S AChE form in the absence of innervation. The 10S AChE form prevails over 4S form with maturation into striated fibres. Although the patterns of AChE molecular forms in normal EDL and soleus muscles differ significantly no such differences were observed in noninnervated regenerates from both muscles. Two types of focal accumulation of AChE appear on the sarcolemma of regenerating muscles: first, in places of former motor endplates and, second, in extra-junctional regions. The 4S form of nonspecific cholinesterase is prevailing in regenerating myotubes whereas its asymmetric forms or focal accumulations could not be identified reliably. The satellite cells which survive after muscle degeneration probably originate from some type of late myoblasts and transmit the information concerning the ability to synthesize the asymmetric AChE forms and to focally accumulate AChE to regenerating muscle cells. Synaptic basal lamina from former motor endplates may locally induce AChE accumulations in regenerating muscles.


Atmospheric pressure chemical ionization mass spectrometry of retro-carotenoids.
The single and double bonds of the polyene chain of the studied retro-carotenoids are located at the neighboring positions compared to those of regular carotenoids. Our mass spectrometry approach targeted at facilitating the characterization of retro-carotenoids as their structural diversity in nature is not yet fully elucidated. Moreover, extended π-electron systems endow several retro-carotenoids with exceptional colors from golden-orange to vibrant red that stimulate the food industry's interest. Atmospheric pressure chemical ionization-quadrupole time-of-flight-high-resolution mass spectrometry (APCI-QTOF-HRMS) experiments of the three structurally related retro-carotenoids rhodoxanthin, eschscholtzxanthone, and eschscholtzxanthin were performed to elucidate the formation of specific ion species compared to those of the common carotenoids lutein and zeaxanthin. Mass fragmentations of the aforementioned retro-carotenoids were unraveled using APCI-tandem mass spectrometry (MS/MS) in the negative and positive ion modes. Abundant in-source fragment ions [M + H - H2 O]+ of eschscholtzxanthin and eschscholtzxanthone were formed in the positive ion mode owing to the loss of water at the hydroxylated ε-rings. Eliminations of the ε-rings at the characteristic exocyclic double bonds at C-6,7 and C-6',7' were observed after the resonance-stabilized loss of water. Distinct product ions were yielded for all retro-carotenoids assessed because of the cleavage at their typical central single bond at C-15,15'. Detailed APCI-QTOF-HRMS analyses enabled a highly accurate detection of the most abundant ion species and respective signal intensity ratios of retro-carotenoids, facilitating their further screening and reliable identification in natural sources. Mass fragmentations of the studied retro-carotenoids were found to be substantially impacted by the extraordinary configuration of their polyene backbone.


Chymotryptic and tryptic peptides of fragment alpha 1-CB3 from bovine corneal collagen. Pinpointing the sites of hexose attachment.
Tryptic peptides of citraconylated fragment alpha1-CB3 and chymotryptic peptides of fragment alpha1-CB3 of bovine corneal collagen were prepared, isolated and characterized. Their amino acid compositions were consistent with the amino acid sequence of fragment alpha1-CB3 from calf skin collagen. Two glycoside sites were identified in bovine corneal fragment alpha1-CB3, one of them being the first located in the overlap region of collagen. The results are related to the uniformly narrow collagen fibres found in cornea and essential for its transparency.


Harnessing the antigenic fingerprint of each individual cancer for immunotherapy of human cancer: genomics shows a new way and its challenges.
The idea that individual tumors are antigenically unique has been around since the very dawn of our recognition of adaptive immune response to tumors. That idea has inspired a small number of attempts at individualized immunotherapy of human cancers. Such previous attempts for solid tumors have been hobbled by an inability to define the individually unique antigenic repertoire of tumors because of technological difficulties. The new availability of rapid and cheap high throughput DNA sequencing promises to overcome that hurdle. Using this new ability, coupled with bio-informatic tools, it is now possible to define the immunogenic repertoire of any tumor to a high degree of granularity within a practical time frame and an acceptable cost. The development of these ideas, and a small number of such studies that underscore this promise, is discussed. This new way--of characterizing the tumor immunome through characterization of the tumor genome--has distinct challenges, including selection of the appropriate peptides, choosing methods of immunizations that can incorporate tens of epitopes, and addressing issues of antigenic heterogeneity of tumors. However, tools for meeting these challenges exist and are emergent.


Establishment of monoclonal antibody and scFv immuno-based assay for Cry2Aa toxin in spiked grain samples.
Bacillus thuringiensis (Bt) Cry toxins have been widely used in the development of genetically modified organisms (GMOs) for pest control. This work aimed to establish more cost effective methods for used Cry2Aa toxins. Three immunoassay methods (IC-ELISA, DAS-ELISA, and CLEIA) were successfully developed in this work. The mAb was used as the detecting antibody, for the IC-ELISA, the range of IC20 to IC80 was 1.11 μg/mL - 60.70 μg/mL, and an IC50 of 10.65 μg/mL. For the DAS-ELISA, the limit of detection (LOD) and limit of quantitation (LOQ) were 10.76 ng/mL and 20.70 ng/mL, respectively. For the CLEIA, the LOD and LOQ were 6.17 ng/mL and 7.40 ng/mL, respectively. The scFv-based detections were the most sensitive for detecting Cry2Aa. The LOD and LOQ for the DAS-ELISA were 118.75 ng/mL and 633.48 ng/mL, respectively. The LOD and LOQ for the CLEIA, read as 37.47 ng/mL and 70.23 ng/mL, respectively. The fact that Cry2Aa toxin was recovered in spiked grain samples further demonstrated that the approaches might be used to identify field samples. These methods provided good sensitivity, stability, and applicability for detecting Cry2Aa toxin, promising ultrasensitive monitoring and references for Cry toxins risk assessment.


Expression of non-classical islet hormone-like peptides during the embryonic development of the pancreas.
Understanding of islet embryogenesis may prove to be key in the design of future therapies for diabetes directed at re-initiating islet growth, with the goal to replace and/or replenish the impaired beta-cell mass in the disease. In this context, studies of islet neurohormonal peptides, known to play a role in the local regulation of islet function, and their expression during islet embryogenesis are important. Here we review our studies on the embryonic islet expression of islet amyloid polypeptide (IAPP) and the PP-fold peptides pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY). IAPP, which is constitutively expressed in beta- and delta-cells in the adult rat, was found to occur in the assumed pluripotent islet progenitor cell, together with PYY, glucagon, and to a lesser extent with insulin. As development proceeds, the insulin/IAPP phenotype is segregated from that of PYY/glucagon; with the formation of islet-like structures, insulin/IAPP-expressing cells primarily occupy their central portions, while PYY/glucagon-expressing cells are found in their periphery. At the time of formation of islet-like structures, expression of NPY is induced in the insulin/IAPP-containing cells. Whereas NPY-expression ceases at birth, PYY is constitutively expressed in non-beta-cells in the mature rat. Expression of PP is induced just prior to birth in a separate population of islet cells, occasionally co-expressed with PYY. Although a clear role for these peptides during embryogenesis has not been identified, they conceivably could play a role in the control of insulin secretion, islet growth and islet blood flow.


Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment.
Human ovarian carcinoma cells (MDAH 2774) were treated with sodium ascorbate (VC), menadione (VK3), or with a VC:VK3 combination for 1 h and then studied using light microscopy (LM) and scanning (SEM) and transmission electron (TEM) microscopy. Plasma membrane damage (blisters and blebs, hairy aspect) results from vitamin C (VC) treatment, while cytoskeletal damage and self-morsellation are caused by vitamin K3 (VK3) treatment. VC:VK3-treated cells exhibit exacerbated injuries characteristic of both VC and VK3 treatment as well as a significant decrease in cell diameters from 20-35 microm for control cells to 7-12 microm for VC:VK3 treatment. Moreover, after a 1-h exposure to the vitamin combination, autoschizis (43%), apoptosis (3%), and oncosis (1.9%) are observed at the percentages indicated. All cellular changes associated with autoschizis observed with SEM were confirmed by LM and TEM observations and are consistent with cell death by autoschizis: decrease in cell size, cytoplasmic self-excisions, degradation of the nucleus and nucleolus without formation of apoptotic bodies and, ultimately, karyorrhexis and karyolysis. These results also suggest that the vitamin combination may find clinical use in the treatment of ovarian cancer.


Hyaluronate in articular cartilage: age-related changes.
Articular cartilage of fetal calves, calves, and steers together with normal and osteoarthrotic human cartilage was analyzed for hyaluronate. The hyaluronate content increased with maturation in healthy tissue, particularly in regions of maximum contact, but was low in diseased cartilage.


Racial/ethnic discrimination and alcohol use disorder severity among United States adults.
Racism, and resultant racial/ethnic discrimination is a ubiquitous social determinant of health that is linked to adverse alcohol-related outcomes. To our knowledge, no studies have examined whether manifestations of racial/ethnic discrimination increase risk of DSM-5 alcohol use disorder (AUD) severity levels. Analyses were conducted among 17,115 racial/ethnic minority respondents of the National Epidemiologic Survey on Alcohol-Related Conditions III (NESARC-III), a cross-sectional survey fielded in 2012-2013. We used multinomial logistic regression to examine the associations between measures of racial/ethnic discrimination and past-year AUD severity levels following the DSM-5 definition, while adjusting for poverty thresholds set by the U.S. Census Bureau, and race/ethnicity (American Indian or Alaskan Native; Asian, Native Hawaiian, or Other Pacific Islander; Black or African American; Hispanic or Latino). We also evaluated whether associations between discrimination and AUD severity varied by poverty status and race/ethnicity. Covariate-adjusted multinomial logistic regressions suggested that in comparison to those who did not experience discrimination, those who experienced discrimination had a 1.5-fold greater risk of mild AUD, a 1.6-fold greater risk of moderate AUD, and a 2.3-fold greater risk of severe AUD. We found no evidence to suggest that the strength of the association between racial/ethnic discrimination and AUD severity varied across race/ethnic group or poverty status. Experience of racial/ethnic discrimination is associated with greater AUD severity in the U.S. regardless of one's specific racial/ethnic group membership or poverty status. Strategies to reduce risk for severe AUD should include efforts to minimize the occurrence and impact of interpersonal and institutional racism.


Primary benign liver lesions.
Benign focal liver lesions can origin from all kind of liver cells: hepatocytes, mesenchymal and cholangiocellular line. Their features at imaging may sometimes pose difficulties in differential diagnosis with malignant primary and secondary lesions. In particular, the use of MDCT and MRI with extracellular and hepatobiliary Contrast Agents may non invasively help in correct interpretation and definition of hepatocellular or mesenchymal and inflammatory nature, allowing to choose the best treatment option. The peculiarities of main benign liver lesions at US, CT and MRI are described, with special attention to differential diagnosis and diagnostic clues.


A predictive model for survival of gallbladder adenocarcinoma.
Gallbladder cancer (GBC) is a life-threatening disease with a poor prognosis worldwide. Although several risk factors for survival have been identified, an ideal model for predicting prognosis has still not been developed due to the low incidence of GBC. This study aims to solve this dilemma by attempting to develop an efficient survival prediction model for GBC. This is a retrospective study. From January 2009 to June 2016, 164 patients with a confirmed histological diagnosis of gallbladder adenocarcinoma were enrolled in this study. The cohort was randomly divided into two cohorts, the development cohort (n = 110) and validation cohort (n = 54). On the basis of the risk factors identified in the development cohort, a nomogram-based predictive model (P-risk Plus), composed of carbohydrate antigen 199 and pathological characteristics, was established for prognosis. In this model, the calibration curves for the 1-, 2-, and 3-year survival probabilities were well-matched with the actual survival rates. In addition, the highest C-index and best decision curve analysis were able to be obviously determined. Meanwhile, the P-risk Plus model result yielded a better fit for survival between the development and validation groups. Compared with conventional tumor stages, our nomogram-based P-risk Plus model for gallbladder adenocarcinoma has a better predictive capacity and thereby has a better potential to facilitate decision-making clinically.


The ecological significance of nickel hyperaccumulation: a plant chemical defense.
Nickel hyperaccumulating plants have more than 1000 mg Ni kg-1 dry weight when grown on nickel-bearing soils. We hypothesized that Ni hyperaccumulation could serve as a chemical defense against herbivores In feeding experiments with potential insect herbivores and Ni hyperaccumulating plants, only those inseets fed leaves from plants grown on non-nickel-bearing soil survived or showed a weight gain. Among chemical parameters measured, only Ni content of plants was sufficient to explain this result. When subjected to herbivory by lepidopteran larvae, plants grown on Ni-amended soil showed greater survival and yield than plants on unamended soil. Ni hyperaccumulation may be an effective plant chemical defense against herbivores because of its high lethality, apparent low cost, and broad spectrum of toxicity.


Impact of Frailty on Outcomes in Patients Undergoing Open Abdominal Aortic Aneurysm Repair.
Frailty is a global state that does not relate directly to comorbidities and is prevalent among patients with vascular disease. The Clinical Frailty Scale (CFS) is a rapid assessment tool to identify vulnerable and frail patients. In this study, we sought to evaluate whether the preoperative CFS score could be used to independently predict mortality and morbidity after elective open abdominal aortic aneurysm (AAA) repair. We retrospectively reviewed our institutional National Vascular Registry (NVR) data to identify all patients who underwent an elective open juxta or infrarenal AAA repair between January 2014 and December 2018. The NVR data set included preoperative risk factors, imaging findings, intraprocedural variables, and postprocedural outcomes. A total of 184 patients were assessed using the CFS before they underwent elective open AAA repair. Among 26 (14%) individuals categorized as vulnerable using the CFS, there was no significant difference in age or preoperative cardiac and respiratory testing compared with nonfrail patients. However, vulnerable patients were significantly more likely to have a longer length of stay (12.2 days vs. 8.8 days, P-value 0.044), suffer from respiratory complications (35% vs. 15%, P-value 0.022) and renal failure (23% vs. 6%, P-value 0.013), or die (23% vs. 2%, P-value 0.0003). The regression analysis identified a vulnerable frailty score to be the only significant predictor of mortality (odds ratio = 36.7, P < 0.001), all other factors were not shown to be independent predictors. The CFS is a practical tool for assessing preoperative frailty among patients undergoing elective open AAA repair and can be used to predict mortality and morbidity after surgery.


Effects of rising atmospheric CO2 levels on physiological response of cyanobacteria and cyanobacterial bloom development: A review.
Increasing atmospheric CO2 concentration negatively impacts aquatic ecosystems and may exacerbate the problem of undesirable cyanobacterial bloom development in freshwater ecosystems. Elevated levels of atmospheric CO2 may increase the levels of dissolved CO2 in freshwater systems, via air-water exchanges, enhancing primary production in the water and catchments. Although high CO2 levels improve cyanobacterial growth and increase cyanobacterial biomass, the impacts on their internal physiological processes can be more complex. Here, we have reviewed previous studies to evaluate the physiological responses of cyanobacteria to high concentrations of CO2. In response to high CO2 concentrations, the pressures of inorganic carbon absorption are reduced, and carbon concentration mechanisms are downregulated, affecting the intracellular metabolic processes and competitiveness of the cyanobacteria. Nitrogen and phosphorus metabolism and light utilization are closely related to CO2 assimilation, and these processes are likely to be affected by resource and energy reallocation when CO2 levels are high. Additionally, the responses of diazotrophic and toxic cyanobacteria to elevated CO2 levels were specifically reviewed. The responses of diazotrophic cyanobacteria to elevated CO2 concentrations were found to be inconsistent, probably because of differences in other factors in experimental designs. Toxic cyanobacteria tended to be superior to non-toxic strains at low levels of CO2; however, the specific effects of microcystin on the regulation require further investigation. Furthermore, the effects of increasing CO2 levels on cyanobacterial competitiveness in phytoplankton communities and nutrient cycling in aquatic ecosystems were reviewed. High CO2 concentrations may make cyanobacteria less competitive relative to other algal taxa; however, due to the complexity of natural systems and the specificity of algal species, the dominant positions of the cyanobacteria do not seems to be changed. To better understand cyanobacterial responses to elevated CO2 levels and help control cyanobacterial bloom developments, this review has identified key areas for future research.


Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma.
Cholangiocarcinomas (CCAs) are rare but aggressive tumors of the bile ducts. CCAs are often diagnosed at an advanced stage and respond poorly to current conventional radiotherapy and chemotherapy. High mobility group A1 (HMGA1) is an architectural transcription factor that is overexpressed in multiple malignant tumors. In this study, we showed that the expression of HMGA1 is frequently elevated in CCAs and that the high expression of this gene is associated with a poor prognosis. Functionally, HMGA1 promotes CCA cell proliferation/invasion and xenograft tumor growth. Furthermore, HMGA1 transcriptionally activates RAD51 by binding to its promoter through two HMGA1 response elements. Notably, overexpression of HMGA1 promotes radioresistance whereas its knockdown causes radiosensitivity of CCA cells to X-ray irradiation. Moreover, rescue experiments reveal that inhibition of RAD51 reverses the effect of HMGA1 on radioresistance and proliferation/invasion. These findings suggest that HMGA1 functions as a novel regulator of RAD51 and confers radioresistance in cholangiocarcinoma.


DNA damage response impacts macrophage functions.
In this issue of Blood, Pereira-Lopes et al demonstrate that a defect in a DNA damage response (DDR) component alters homeostasis of macrophages and their inflammatory responses.


Social deprivation and adult blunt chest trauma: A retrospective study.
The relationship between socioeconomic status and various components of health is well established. Research has also highlighted that social deprivation can affect patterns of injury and outcome after trauma. The interaction between outcomes following blunt chest trauma and socioeconomic status has received limited attention in trauma research. The aim of this study was to investigate the relationship between socioeconomic factors, mechanisms of injury and outcomes following blunt chest trauma using deprivation measures calculated on the basis of domicile postcodes. A retrospective study design was used in order to examine the medical notes of all blunt chest wall trauma patients who presented to the ED of a large regional trauma centre in South West Wales in 2012 and 2013. Baseline characteristics were presented as median and interquartile range or numbers and percentages. Differences between the baseline characteristics were analysed using Mann-Whitney U test and Fisher's exact test. Odds ratios and 95% confidence intervals were presented from the univariable analysis. Multivariable logistic regression analysis was used to identify significant predictors for the development of complications. Patients in the 'more deprived' group were more likely to be the victims of assault (p < 0.001) and were more likely to have an unplanned re-attendance at the Emergency Department than the patients in the 'less deprived' group (p < 0.001). On multivariable analysis, social deprivation was not a risk factor for the development of complications, but it was a significant risk factor for prolonged length of stay (p < 0.05). This is the first study in which social deprivation has been investigated as a risk factor for complications following isolated blunt chest wall trauma. Residing in a 'more deprived' area in South West Wales is not associated with the development of complications following isolated blunt chest wall trauma.


ICD-10: from assessment to remediation to strategic opportunity.
Healthcare finance teams should perform an enterprisewide assessment to determine what ICD-10 means to their organization, strategically, operationally, and financially. CFOs should strategically evaluate the impact of ICD-10 on the organization's entire financial operation. Organizations should have a contingency plan in place across all processes.


Changes in succinate dehydrogenase activity in various parts of the brain during combined exposure to vibration and licorice root.
Data obtained in the studies reported here provide evidence that during exposure to vibration for 30 days, feeding with licorice root significantly increases the activity of the anaerobic respiration enzyme succinate dehydrogenase (SDH) in the cerebral cortex, while activity in the subcortex, conversely, decreases. Combined treatment for 30 days with licorice root and vibration after a preliminary 30-day period of feeding with licorice root resulted in high SDH activity in all the structures studied, improving brain energy supply and metabolism and ameliorating the effect of vibration.


Eucaryotic codes.
This article is a review of the rules used by eucaryotic cells to translate a nuclear messenger RNA into a polypeptide chain. The recent observation that these rules are not identical in two species of a same phylum indicates that they have changed during the course of evolution. Possible scenarios for such changes are presented.


A new species of the genus Disogmus Förster (Hymenoptera, Proctotrupoidea, Proctotrupidae) from the Eocene Rovno amber.
Disogmus rasnitsyni Kolyada & Perkovsky, sp. n. is described from a fossil inclusion of Late Eocene amber (Ukraine). The new species is most similar to Disogmus basalis (Thomson, 1857), in particular, in the shape of the tyloids and the general shortening of the segments of antennae, but distinctly differs from it and the other species of the genus by having tyloids on flagellar segments 2-4 compared to 3-6 and 4-7 in other species.


Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease.
Single nucleotide polymorphisms in PICALM, a key component of clathrin-mediated endocytosis machinery, have been identified as genetic susceptibility loci for late onset Alzheimer's disease (LOAD). We previously reported that PICALM protein levels were decreased in AD brains and that PICALM was co-localised with neurofibrillary tangles in LOAD, familial AD with PSEN1 mutations and Down syndrome. In the present study, we analysed PICALM expression, cell localisation and association with pathological cellular inclusions in other tauopathies and in non-tau related neurodegenerative diseases. We observed that PICALM was associated with neuronal tau pathology in Pick disease and in progressive supranuclear palsy (PSP) and co-localised with both 3R and 4R tau positive inclusions unlike in corticobasal degeneration (CBD) or in frontotemporal lobar degeneration (FTLD)-MAPT P301L. PICALM immunoreactivities were not detected in tau-positive tufted astrocytes in PSP, astrocytic plaques in CBD, Lewy bodies in Lewy body disease, diffuse type (LBD) and in TDP-43-positive inclusions in FTLD. In the frontal cortex in tauopathies, the ratio of insoluble to soluble PICALM was increased while the level of soluble PICALM was decreased and was inversely correlated with the level of phosphotau. PICALM decrease was also significantly correlated with increased LC3-II and decreased Beclin-1 levels in tauopathies and in non-tau related neurodegenerative diseases. These results suggest that there is a close relationship between abnormal PICALM processing, tau pathology and impairment of autophagy in human neurodegenerative diseases.


Melatonin, sleep, and shift work adaptation.
Night work is associated with disrupted circadian rhythms, fatigue, accidents, and chronic disease. Melatonin secretion helps regulate sleep and circadian rhythms. Melatonin, sleep disturbances, and symptoms (sleep, fatigue, mental) were compared among workers on permanent day, swing, and night shifts. Urinary 6-hydroxymelatonin sulfate (6-OHMS) was measured in postwork and postsleep samples. Disrupted circadian melatonin production was evaluated using the sleep:work 6-OHMS ratio. Wrist actigraphy characterized light exposures and sleep characteristics. Night workers had altered melatonin, disrupted sleep, and elevated symptom prevalence. Subjects grouped by their sleep:work 6-OHMS ratio rather than shift had even greater symptom prevalence. Risks for two or more symptoms were 3.5 to 8 times greater among workers with sleep:work ratios < or =1 compared to those with ratios >1. This ratio may help identify workers at increased risk for accidents or injuries.


The effect of crossword puzzles on nursing students' learning of concepts related to pain management course: A randomized controlled trial.
Nursing students encounter various terms and concepts during their undergraduate education. Repeating and reinforcing these terms and concepts is challenging. Active learning strategies are recommended to enhance students' effectiveness, productivity and interest in the learning process in undergraduate education. This study aims to investigate the effect of crossword puzzles on nursing students' learning success and knowledge retention of the concepts related to the pain management course. The study was conducted as a randomized controlled trial. The study was conducted in the nursing department of a state university in the southern region of Turkey. The study involved 72 s-year nursing students who were enrolled in the Pain Management course. Data were collected using a "Personal Information Form" and three different "Pain Management Knowledge Tests." While the control group received only the standard lecture technique as a traditional method, the experimental group was exposed to crossword puzzles as an active learning method for three lesson hours following the standard lecture technique. Research data were collected between November and December 2022 in the classroom. Descriptive statistics, the Independent Samples t-test, Repeated Measures ANOVA test and Pearson's chi-squared test were employed for data analysis. There was no significant difference between the pre-test and first post-test mean scores of both groups (p ˃ 0.05). However, the second post-test scores of the experimental group were significantly higher than those of the control group (p < 0.05). The use of crossword puzzles positively affected nursing students' knowledge levels regarding concepts related to the pain management course. NCT05424770.


Synthesis, biological evaluation, and molecular modelling of novel quinoxaline-isoxazole hybrid as anti-hyperglycemic.
In our effort to develop potent anti-hyperglycemic compounds with inhibitory activity against α-amylase and α-glucosidase, a series of novel quinoxaline-isoxazole moieties were synthesized. The novel quinoxaline-isoxazole derivatives were assessed in vitro for their anti-hyperglycemic activities on α-amylase and α-glucosidase inhibitions. The results revealed promising IC50 values compared to acarbose as a positive control for α-amylase and α-glucosidase. Among them, N-Ethyl-7-chloro-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5b showed dual inhibitory with IC50 of 24.0 µM for α-amylase and 41.7 µM for α-glucosidase. In addition, N-Ethyl-7-methoxy-3-((3-(2-chlorophenyl)isoxazol-5-yl)methoxy)quinoxalin-2-amine 5j also had dual bioactivities against α-amylase and α-glucosidase with IC50 of 17.0 and 40.1 µM, respectively. Nevertheless, two more compounds N-Ethyl-7-cyano-3-((3-phenylisoxazol-5-yl)methoxy)quinoxaline-2-amine 5e showed strong mono-inhibition for α-glucosidase with IC50 of 16.6 µM followed by N-Ethyl-7-methoxy-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5 f with IC50 of 18.6 µM. The molecular docking study for α-glucosidase inhibitor provided the binding energy ranging from 8.3 to 9.1 kcal/mol and α-amylase inhibitor showed the binding energy score at 8.4 and 8.5 kcal/mol. The dual inhibitions nature of 5b and 5j were further analyzed and confirmed via molecular dynamics including the stability of the compound, interaction energy, binding free energy, and the interaction residue analysis using the MM-GBSA approach. The results showed that compound 5j was the most potent compound. Lastly, the drug-likeness properties were also evaluated with all synthesized compounds 5a-5j and the results reveal that all potent compounds meet Lipinski's rules of five.


Intraoperative detection of methemoglobinemia in a patient given benzocaine spray to relieve discomfort from a nasogastric tube: a case report.
A 27-year-old man who had 2 admissions 1 month apart for abdominal surgery had a high methemoglobin (MHb) level secondary to liberal use of benzocaine oral spray. A co-oximetry level for MHb of greater than 0.30 proportion of total hemoglobin (30.1%) was detected intraoperatively. The patient was successfully treated with methylene blue intravenously and recovered uneventfully. When the arterial blood gas with a normal partial pressure of oxygen is inconsistent with a low pulse oximeter reading and with the physical appearance of the patient, methemoglobinemia should be considered as a differential diagnosis. This case illustrates the acquired form of methemoglobinemia. Adequate oxygen delivery to the tissues in the body is compromised when MHb overwhelms the capacity of the red blood cells to carry oxygen. If methemoglobinemia is left untreated, it may be fatal.


Preliminary Findings of Focus Group Analysis to Support the Needs of Adolescent and Young Adult Patients and Survivors of Cancer: Steps Toward a National Adolescent and Young Adult Supportive Care Program.
Adolescents and young adult (AYA) oncology care has evolved to address their unique supportive care needs, yet deficiencies remain. We planned a multiphase sequential mixed methods study beginning with focus groups (FGs) with AYAs receiving care at the Princess Margaret Cancer Centre, to improve supportive care delivery. Herewith, we report on the preliminary findings from first phase of project and outline future expected goals. Our findings suggest four major themes identified from FG discussion with AYAs: (1) having peer-driven support, (2) incorporating hybrid approach to information delivery, (3) integrating general practitioners in AYAs care, and (4) providing AYAs-specific supportive care programs.


Topical steroids under wet-wrap dressings in atopic dermatitis--a vehicle-controlled trial.
The wet-wrap dressing technique has proved to be beneficial in cases of exacerbated atopic dermatitis (AD) skin lesions. The effect of wet-wrap dressings was investigated in a controlled trial comparing a steroid (mometasone furoate 0.1%)-containing and a steroid-free (vehicle) preparation in an in-patient comparison study. 20 children aged 2-17 years with exacerbated AD were treated twice daily with wet-wrap dressings over a 5-day period. AD in treated areas significantly improved in both study arms; however, the effect was significantly better in the mometasone-treated group (p < 0.01). Transepidermal water loss improved in both arms without any significant differences. Staphylococcus aureus colonization decreased during the first 3 days of active treatment independently of the therapeutic modalities chosen. At day 5, colony counts further dropped on the steroid-treated lesions. Application of the wet-wrap dressing technique for exacerbated AD lesions is effective, combination with a topical steroid being superior to a steroid-free application without bearing the risk of a bacterial superinfection.


Diverse cell junctions with unique molecular composition in tissues of a sponge (Porifera).
The integrity and organization of animal tissues depend upon specialized protein complexes that mediate adhesion between cells with each other (cadherin-based adherens junctions), and with the extracellular matrix (integrin-based focal adhesions). Reconstructing how and when these cell junctions evolved is central to understanding early tissue evolution in animals. We examined focal adhesion protein homologs in tissues of the freshwater sponge, Ephydatia muelleri (phylum Porifera; class Demospongiae). Our principal findings are that (1) sponge focal adhesion homologs (integrin, talin, focal adhesion kinase, etc.) co-precipitate as a complex, separate from adherens junction proteins; (2) that actin-based structures resembling focal adhesions form at the cell-substrate interface, and their abundance is dynamically regulated in response to fluid shear; (3) focal adhesion proteins localize to both cell-cell and cell-extracellular matrix adhesions, and; (4) the adherens junction protein β-catenin is co-distributed with focal adhesion proteins at cell-cell junctions everywhere except the choanoderm, and at novel junctions between cells with spicules, and between cells with environmental bacteria. These results clarify the diversity, distribution and molecular composition of cell junctions in tissues of E. muelleri, but raise new questions about their functional properties and ancestry.


Interspecific differences in root exudation for three tropical seagrasses and sediment pore-water dissolved organic carbon beneath them.
Seagrass beds act as blue carbon sinks globally; however, little attention has been given to carbon dynamics in the seagrass rhizosphere. Hence, in this study, the quantity and characteristics of dissolved organic carbon (DOC) from root exudation of the three dominant tropical seagrasses (Thalassia hemprichii, Enhalus acoroides, and Cymodocea rotundata) and sediment pore water beneath them were compared, to examine their interspecific differences, and to establish a connection between seagrass root exudation and sediment carbon. The rate of root-exuded DOC from T. hemprichii (2.15 ± 1.06 mg g DW root-1 h-1) was significantly higher (p < 0.05) than that from E. acoroides (0.72 ± 0.39 mg g DW root-1 h-1) and C. rotundata (0.46 ± 0.25 mg g DW root-1 h-1). Root exudation rates were more affected by root hair density and root hair length than by root carbon, nitrogen, and soluble sugar content. Simultaneously, DOC concentrations of the sediment pore water beneath T. hemprichii, E. acoroides and C. rotundata were 22.05 ± 11.61 mg l-1, 15.55 ± 2. 66 mg l-1, and 14.32 ± 1.82 mg l-1, respectively. The corresponding absorption coefficients at 254 nm (a254) were 30.53 ± 18.00, 17.31 ± 2.24, and 14.07 ± 2.03, respectively, while the relevant specific ultraviolet absorbances at 254 nm (SUVA254) were 1.38 ± 0.29, 1.19 ± 0.26 and 1.03 ± 0.28, respectively. Therefore, the roots of T. hemprichii exuded DOC at a higher rate, leading to a higher pore-water DOC pool in the sediment. This suggests that T. hemprichii played a greater role in the sediment carbon pool through root exudation. Thus, it can be considered as the priority species for transplantation to promote the carbon sink function of seagrass beds.


Interactions between Dpr11 and DIP-γ control selection of amacrine neurons in Drosophila color vision circuits.
Drosophila R7 UV photoreceptors (PRs) are divided into yellow (y) and pale (p) subtypes. yR7 PRs express the Dpr11 cell surface protein and are presynaptic to Dm8 amacrine neurons (yDm8) that express Dpr11's binding partner DIP-γ, while pR7 PRs synapse onto DIP-γ-negative pDm8. Dpr11 and DIP-γ expression patterns define 'yellow' and 'pale' color vision circuits. We examined Dm8 neurons in these circuits by electron microscopic reconstruction and expansion microscopy. DIP-γ and dpr11 mutations affect the morphologies of yDm8 distal ('home column') dendrites. yDm8 neurons are generated in excess during development and compete for presynaptic yR7 PRs, and interactions between Dpr11 and DIP-γ are required for yDm8 survival. These interactions also allow yDm8 neurons to select yR7 PRs as their appropriate home column partners. yDm8 and pDm8 neurons do not normally compete for survival signals or R7 partners, but can be forced to do so by manipulation of R7 subtype fate.


Semi-automatic method for determination of different isoforms of carbohydrate-deficient transferrin.
Carbohydrate deficient transferrin (CDT) has been reported to be one of the best biochemical markers of alcohol abuse. However, a need still exists for a simple and practical method for widespread laboratory use. A semi-automatic (SA) isoelectric focusing (IEF) assay for CDT (SA-IEF-CDT) by a Phast System is introduced here. Different isoforms of transferrin were separated by IEF on polyacrylamide gels (pI 4.0-6.5) and located by immunofixation with an anti-transferrin serum. The precipitation bands were stained with Coomassie Brilliant Blue and quantitated densitometrically. The present method gave a picture of the relative amounts of 10 different transferrin isoforms. The percentage of CDT with pI > or = 5.7 (representing di-, mono- and asialotransferrin) was calculated. For comparisons transferrin bands with pI > or = 5.6 (tri-, di-, mono-, and asialotransferrin), pI > or = 5.8 (mono- and asialotransferrin) and pI > or = 5.9 (asialotransferrin) as well as GGT, ASAT and ALAT were calculated. The method showed good linearity and it identified different isoforms in concentrations of < 10 mg/l of transferrin. The correlation of the present method with a commercially available method employing anion exchange followed by double antibody RIA (AE-RIA-CDT) was good (n = 38, r = 0.924). In 19/20 (95%) of healthy controls, the CDT value was below 4.4% (mean + 2 S.D.) of total transferrin, while higher values were observed in all 20 (100%) alcoholics. In conclusion, the developed semi-automatic method is a practical and reliable alternative for determination of different transferrin isoforms.


[Emergency departments--2016 update].
Acute medical care in hospital emergency departments has experienced rapid development in recent years and gained increasing importance not only from a professional medical point of view but also from an economic and health policy perspective. The present article therefore provides an update on the situation of emergency departments in Germany. Care in emergency departments is provided with an increasing tendency to patients of all ages presenting with varying primary symptoms, complaints, illnesses and injury patterns. In the process, patients reach the emergency department by various routes and structural provision. Cross-sectional communication and cooperation, prioritization and organization of emergency management and especially medical staff qualifications increasingly play a decisive role in this process. The range of necessary knowledge and skills far exceeds the scope of prehospital medical emergency care and the working environment differs substantially. In addition to existing structural and economic problems, the latest developments, as well as future proposals for the design of in-hospital emergency medical care in interdisciplinary emergency departments are described.


Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients.
SARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Previous studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited. We addressed the gap of existing knowledge with regard to a differentiated understanding of disease dynamics in SARS-CoV-2 infection while specifically considering disease stage and severity. We biomedically characterized quantitative proteomics in a hospitalized cohort of COVID-19 patients with mild to severe symptoms suffering from different (co)-morbidities in comparison to both healthy individuals and patients with non-COVID related inflammation. Deep clinical phenotyping enabled the identification of individual disease trajectories in COVID-19 patients. By the use of the individualized disease phase assignment, proteome analysis revealed a severity dependent general type-2-centered host response side-by-side with a disease specific antiviral immune reaction in early disease. The identification of phenomena such as neutrophil extracellular trap (NET) formation and a pro-coagulatory response characterizing severe disease was successfully validated in a second cohort. Together with the regulation of proteins related to SARS-CoV-2-specific symptoms identified by proteome screening, we not only confirmed results from previous studies but provide novel information for biomarker and therapy development.


Caspase inhibition switches the mode of cell death induced by cyanide by enhancing reactive oxygen species generation and PARP-1 activation.
Execution of apoptosis can involve activation of the caspase family of proteases. Recent studies show that caspase inhibition can switch the morphology of cell death from apoptotic to necrotic without altering the level of death among cell populations. In the present study, the effect of caspase inhibition on cortical (CX) cell death induced by cyanide was investigated. In primary cultured CX cells exposed to cyanide (400 microM), death was primarily apoptotic as indicated by positive TUNEL staining. Reactive oxygen species (ROS) generation and subsequent caspase activation mediated the apoptosis. Inhibition of the caspase cascade with zVAD-fmk switched the apoptotic response to necrotic cell death, as assessed by increased cellular efflux of LDH and propidium iodide uptake by the cells. The change in death mode was accompanied by a marked increase in poly (ADP-ribose) polymerase-1 (PARP-1) activity, reactive oxygen species (ROS) generation, a reduction in the mitochondrial membrane potential (Delta psi(m)), and reduced cellular ATP. Prior treatment of cells with 3-aminobenzamide (3-AB), a PARP-1 inhibitor, prevented the cells from undergoing necrosis and preserved intracellular ATP levels. These findings indicate that apoptosis and necrosis share common initiation pathways and caspase inhibition can switch the apoptotic response to necrosis. Inhibition of PARP-1 preserves cellular ATP levels and in turn blocks execution of the necrotic death pathway.


Average chest wall thickness at two anatomic locations in trauma patients.
Needle thoracostomy is the emergent treatment for tension pneumothorax. This procedure is commonly done using a 4.5cm catheter, and the optimal site for chest wall puncture is controversial. We hypothesize that needle thoracostomy cannot be performed using this catheter length irrespective of the site chosen in either gender. A retrospective review of all chest computed tomography (CT) scans obtained on trauma patients from January 1, 2011 to December 31, 2011 was performed. Patients aged 18 and 80 years were included and patients whose chest wall thickness exceeded the boundary of the images acquired were excluded. Chest wall thickness was measured at the 2nd intercostal (ICS), midclavicular line (MCL) and the 5th ICS, anterior axillary line (AAL). Injury severity score (ISS), chest wall thickness, and body mass index (BMI) were analyzed. 201 patients were included, 54% male. Average (SD) BMI was 26 (7)kg/m(2). The average chest wall thickness in the overall cohort was 4.08 (1.4)cm at the 2nd ICS/MCL and 4.55 (1.7)cm at the 5th ICS/AAL. 29% of the overall cohort (27 male and 32 female) had a chest wall thickness greater than 4.5cm at the 2nd ICS/MCL and 45% (54 male and 36 female) had a chest wall thickness greater than 4.5cm at the 5th ICS/AAL. There was no significant interaction between gender and chest wall thickness at either site. BMI was positively associated with chest wall thickness at both the 2nd and 5th ICS/AAL. A 4.5cm catheter is inadequate for needle thoracostomy in most patients regardless of puncture site or gender.


Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011-2012 influenza vaccine season.
We have previously reported an age-related impairment in the serum antibody response to pandemic (p)2009 H1N1, measured by hemagglutination inhibition assay and ELISA. The present study extends these observations and evaluates IgG subclass distribution in healthy individuals of different ages vaccinated during the 2011-2012 season. The 2011-2012 vaccination season was characterized by a vaccine containing the pandemic (p)2009 H1N1 strain for the third consecutive year. All of our subjects were previously immunized, and therefore seroprotected at t0. Nevertheless, aging impaired the serum antibody response to H1N1, as antibody titers increased after vaccination in young and less in elderly individuals. The peak of the response was at day 7 (t7), in contrast with what is usually seen at day 21-28, suggesting a memory response characterized by the induction of an IgG subclass with a shorter half-life. We hypothesized that the IgG3 response, with its much shorter half-life, might be more represented. Antibodies were predominantly of the IgG1 subclass in both age groups, although a robust IgG3 response was also induced and accounted for a significant proportion of the overall response. IgG2 and IgG4 antibodies were at indiscernible levels. We showed a much higher percentage of IgG3 (40-50%) than previously in the literature (less than 10%). To explain if this was associated with a particular cytokine profile, we measured H1N1-induced T cell cytokines in vitro and found that IgG3 levels were positively correlated with TNF-α and IL-6. Moreover, activation-induced cytidine deaminase (AID) mRNA expression, a predictive biomarker of optimal in vivo vaccine response, was found to significantly correlate with IgG3 and also with IgG1 similar to what we have shown previously for total IgG. In the 2011-2012 season, the pandemic (p)2009 H1N1 strain was present in the vaccine for the third consecutive year and therefore each individual was seroprotected at t0. The peak of the response was at t7, suggesting a memory response characterized by a robust induction of IgG3, which was associated with TNF-α and IL-6 production. Both IgG1 and IgG3 responses were decreased by age. AID was confirmed to be a predictive biomarker of optimal vaccine responses.


Healthcare Information Systems to Assess Influenza Outbreaks: An analysis of the 2009 H1N1 Epidemic in Buenos Aires.
To determine whether a private HIS could have detected the influenza epidemic outbreaks earlier through changes in morbidity and mortality patterns. Data Source included a health information system (HIS) from an academic tertiary health care center integrating administrative and clinical applications. It used a local interface terminology server which provides support through data autocoding of clinical documentation. Specific data subsets were created to compare the burden of influenza during the epidemiological week (EW) 21 to 26 for years 2007 to 2009 among 150,000 Health Maintenance Organization members in Argentina. The threshold for identifying an epidemic was considered met when the weekly influenza-like illness (ILI) rate exceeded 200 per 100,000 visits. Case fatality rates and mortality rates of severe acute respiratory infection (SARI) from 2007 to 2009 were retrospectively compared. Case fatality rates and mortality rates for A/H1N1 influenza 2009 also were estimated. The HIS detected the outbreak in EW 23 while the government Ministry of Health (MoH) gave a national epidemic alert during EW 25. The number of visits for ILI increased more than fourfold when comparing 2009 to the period 2007-2008. The SARI mortality rate in 2009 was higher than in 2008 (RR 2.8; 95%CI 1.18-6.63) and similar to that of 2007 (RR 1.05; 95%CI 0.56-1.49). 2009 was the first year with mortalities younger than 65 years attributable to SARI. The estimated A/H1N1 case fatality rate for SARI was 6.2% (95%CI 2.5 to 15.5) and A/H1N1 mortality rate was 6 per 100,000 (95%CI 0 to 11.6). Our HIS detected the outbreak two weeks before than the MoH gave a national alert. The information system was useful in assessing morbidity and mortality during the 2009 influenza epidemic H1N1 outbreak suggesting that with a private-public integration a more real-time outbreak and disease surveillance system could be implemented.


The impact of CDIO's dimensions and values on IT Learner's attitude and behavior: A regression model using Partial Least Squares.
CDIO (Conceiving-Designing-Implementing-Operating), crowdsourcing and gamification are gaining more popularity in IT education. However, factors that influence learners' attitude toward this method are yet to be discovered. Therefore, this study aims to develop and test a conceptual model of implementing CDIO-based curriculum in IT education. For this purpose, CDIO dimensions were conceptualized and developed into questionnaire items. Then 141 students who experienced the CDIO method in information security course and lab, were sampled through action-research approach to investigate their perceptions and experiences about the learning stages, dimensions and values of this teaching method. Data gathered were analyzed by multiple regression algorithm using Partial Least Squares-Structural Equation Modeling (PLS-SEM) statistical approach. The results reveal that the 'mastery of the concept', 'implement and operate', 'perceived values', 'demonstration and resources', and 'admin' could significantly (in direct and indirect paths) affect learner's intention to accept the CDIO method and adopt it in IT classes. Finally, implications to theory and practice were indicated, and future research directions were suggested.


Autoparathyroidectomy: a case report.
This report describes a patient with primary hyperparathyroidism who became spontaneously normocalcaemic preoperatively. This was due to infarction in a parathyroid adenoma. Plasma parathormone (PTH) levels were monitored pre- and postoperatively.


Carotid stenting versus endarterectomy in patients undergoing reintervention after prior carotid endarterectomy.
Outcomes for patients undergoing intervention for restenosis after prior ipsilateral carotid endarterectomy (CEA) in the era of carotid angioplasty and stenting (CAS) are unclear. We compared perioperative results and durability of CAS vs CEA in patients with symptomatic or asymptomatic restenosis after prior CEA and investigated the risk of reintervention compared with primary procedures. Patients undergoing CAS and CEA for restenosis between January 2003 and March 2012 were identified within the Vascular Study Group of New England (VSGNE) database. End points included any stroke, death or myocardial infarction (MI) within 30 days, cranial nerve injury at discharge, and restenosis ≥ 70% at 1-year follow-up. Multivariable logistic regression was done to identify whether prior ipsilateral CEA was an independent predictor for adverse outcome. Out of 9305 CEA procedures, 212 patients (2.3%) underwent redo CEA (36% symptomatic). Of 663 CAS procedures, 220 patients (33%) underwent CAS after prior ipsilateral CEA (31% symptomatic). Demographics of patients undergoing redo CEA were comparable to patients undergoing CAS after prior CEA. Stroke/death/MI rates were statistically similar between redo CEA vs CAS after prior CEA in both asymptomatic (4.4% vs 3.3%; P = .8) and symptomatic patients (6.6% vs 5.8%; P = 1.0). No significant difference in restenosis ≥ 70% was identified between redo CEA and CAS after prior CEA (5.2% vs 3.0%; P = .5). Redo CEA vs primary CEA had increased stroke/death/MI rate in both symptomatic (6.6% vs 2.3%; P = .05) and asymptomatic patients 4.4% vs 1.7%; P = .03). Prior ipsilateral CEA was an independent predictor for stroke/death/MI among all patients undergoing CEA (odds ratio, 2.1; 95% confidence interval, 1.3-3.5). No difference in cranial nerve injury was identified between redo CEA and primary CEA (5.2% vs 4.7%; P = .8). In the VSGNE, CEA and CAS showed statistically equivalent outcomes in asymptomatic and symptomatic patients treated for restenosis after prior ipsilateral CEA. However, regardless of symptom status, the risk of reintervention was increased compared with patients undergoing primary CEA.


BD ProEx C immunostaining in extramammary Paget's disease and perineal melanoma.
The differential diagnosis of perineal biopsies can include squamous intraepithelial lesions, extramammary Paget's disease, and melanoma. Less frequently two of these lesions coexist. BD ProEx C is a recently developed immunoassay that targets expression of two genes shown to be associated with cervical cancer. Immunostaining for ProEx C has been validated in cervical cytology and positive staining has also been shown to be strongly associated with human papilloma virus (HPV)-induced cervical and anal intraepithelial neoplasia in biopsies. We observed positive staining for ProEx C in Paget cells in all of 26 cases of Paget's disease irrespective of tissue site (extramammary, mammary) and in melanoma cells in all of 12 cases of primary perineal melanoma with immunostaining in >50% of malignant cells in 73% of Paget disease cases and 43% of perineal melanoma cases. Positive staining was heterogeneous and exclusively nuclear in all cases. In situ hybridization was negative for low-risk and high-risk HPV subtypes in all Paget and melanoma cases that were tested. Currently neither of these lesions is known to be HPV related although according to the literature the possibility of a role for HPV in melanoma is still unsettled. Relevant literature is reviewed.


Quantification of active infliximab in human serum with liquid chromatography-tandem mass spectrometry using a tumor necrosis factor alpha -based pre-analytical sample purification and a stable isotopic labeled infliximab bio-similar as internal standard: A target-based, sensitive and cost-effective method.
The therapeutic monoclonal antibody Infliximab (IFX) is a widely used drug for the treatment of several inflammatory autoimmune diseases. However, approximately 10% of patients develop anti-infliximab antibodies (ATIs) rendering the treatment ineffective. Early detection of underexposure to unbound IFX would result in a timely switch of therapy which could aid in the treatment of this disease. Streptavidin coated 96 well plates were used to capture biotinylated-tumor necrosis factor -alpha (b-TNF-α), which in turn was used to selectively extract the active form of IFX in human serum. After elution, IFX was digested using trypsin and one signature peptide was selected for subsequent analysis on liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard used was a stable isotopic labeled IFX bio-similar. The assay was successfully validated according to European Medicines Agency (EMA) guidelines and was found to be linear in a range of 0.5-20μg/mL (r(2)=0.994). Lower limit of quantification for the assay (<20% CV) was 0.5μg/mL, requiring only 2μL of sample. Cross-validation against enzyme-linked immunosorbent assay (ELISA) resulted in a high correlation between methods (r(2)=0.95 with a ρc=0.83) and the accuracy was in line with previously published results. In conclusion, a sensitive, robust and cost-effective method was developed for the bio-analysis of IFX with LC-MS/MS by means of a target-based pre-analytical sample purification. Moreover, low volume and costs of consumables per sample promote its feasibility in (pre)clinical studies and in therapeutic drug monitoring. This method should be considered as first choice due to its accuracy and multiple degree of selectivity.


Potassium channels and regulation of proliferation of human melanoma cells.
1. Ion channels and their possible relation to cell proliferation have been studied in a human melanoma cell line (IGR 1). Membrane currents were recorded by the patch-clamp technique using the cell-attached, cell-free and whole-cell mode. Cell growth was monitored by counting the number of cells at different days after seeding and [3H]thymidine incorporation. 2. A voltage-dependent 10 pS non-inactivating potassium channel (delayed rectifier) is the most commonly observed ion channel in this type of human cell. The channel is active at the normal resting potential and can be blocked by tetraethylammonium chloride (TEA) and also by a membrane-permeable cyclic adenosine monophosphate (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, cyclic AMP). A second type of potassium channel shows properties similar to voltage-dependent A-type potassium channels with complete inactivation. 3. A voltage-independent, non-selective cation channel with a single-channel conductance of approximately 20 pS could be seen in only 8% of the patches. Its properties of modulation are still unknown. 4. The incidence of the 10 pS, non-inactivated potassium channel was maximal at the fourth day after seeding (in 89% of the patches) and was significantly reduced at the seventh day (in 35% of the patches). 5. [3H]thymidine incorporation is maximal at the third day after seeding and is reduced when cells are grown in the presence of TEA or cyclic AMP. This peak of maximal [3H]thymidine incorporation correlated with the incidence of non-inactivated potassium channels. 6. In the presence of TEA or cyclic AMP, growth of the cells is inhibited. We suppose that due to block of potassium channels, most of the melanoma cells are not able to enter the S-phase in the cell division cycle. 7. It is concluded that delayed rectifier potassium channels are involved in the control of melanoma cell proliferation. A similar finding has been reported for K+ channels in T-lymphocytes and human breast carcinoma cells. It is suggested that potassium channels may be involved in controlling the driving force for a calcium influx thereby interacting with Ca(2+)-dependent cell cycle control proteins.


D-Lactate associated encephalopathy in short bowel syndrome: management with long-term non-absorbable oral antimicrobials.
We describe a child with short bowel syndrome consequent upon jejunal atresia who developed recurrent episodes of D-Lactate associated encephalopathy. Three species of lactobacillus were isolated from the stool, each sensitive to neomycin. Oral neomycin administration resulted in rapid relief of all symptoms. Cessation of the neomycin on two occasions led to recurrent encephalopathic episodes which quickly resolved with recommencement of treatment. We discuss the possible aetiologies of this encephalopathy syndrome and the therapeutic options.


The impact of COVID-19 pandemic on mental health & wellbeing among home-quarantined Bangladeshi students: A cross-sectional pilot study.
COVID-19 is imposing threat both on physical and mental health since its outbreak. Bangladesh adopted lockdown strategy with potential consequences on day to day life, mental and physical health and this study aims to explore the impact of COVID-19 on mental health and wellbeing among Bangladeshi students. A cross-sectional study was conducted between 9th and 23rd April 2020 among 505 college and university students. Data was collected by using online questionnaire including DASS 21 and IES. Descriptive analysis and bivariate linear regression were performed to examine the association of variables. 28.5 % of the respondents had stress, 33.3% anxiety, 46.92% depression from mild to extremely severe, according to DASS 21 and 69.31% had event-specific distress from mild to severe in terms of severity according to IES. Perceiving physical symptoms as COVID-19 was significantly associated with DASS stress subscale (B = 3.71, 95% CI: 1.01 to 6.40), DASS anxiety subscale (B = 3.95, 95% CI: 1.95 to 5.96), DASS depression subscale (B = 3.82, 95% CI: 0.97 to 6.67) and IES scale (B = 7.52, 95% CI: 3.58 to 11.45). Additionally, fear of infection, financial uncertainty, inadequate food supply, absence of physical exercise and limited or no recreational activity had significant association with stress, anxiety, depression and post-traumatic symptoms. This COVID-19 outbreak imposes psychological consequences on people to a great extent which requires attention from the concerned authorities to cope with this situation mentally. The perception about the outbreak can also play a big role in psychological impact.


A Primary Human Liver Cell Culture Model for Hemorrhagic Fever Viruses.
Viral hemorrhagic fevers affect liver functions such as important metabolic processes and the replacement of new blood cells, coagulation factors, and growth factors. Typically, multi-organ diseases such as viral hemorrhagic fevers are studied in an organism, but it is also possible to derive information about the molecular events involved in disease processes by focusing on liver cell culture. Here we describe a multi-cell culture system that is capable of replicating the arenavirus LCMV-WE, a virus that can cause hemorrhagic fever in primates, as a model for liver infection by a hemorrhagic fever virus.


Synthesis and Host-Guest Chemistry of Chiral Spirobifluorene-Based Macrocycles Soluble in Basic Aqueous Solution.
Synthesis and host-guest chemistry of water-soluble (pH 12.5) chiral spirobifluorene-based macrocycles 2-[n] were carried out. Cationic guests, such as quaternary ammonium salts, were accommodated well in the hosts. Cp2Co+ was especially strongly bound in 2-[4] (Ka of up to 3.0 × 105 M-1). Enantioselective recognition with (l)-carnitine was also achieved.


Point-of-care bedside gas analyzer: limited use of venous pCO2 in emergency patients.
Because arterial punctures are more painful, venous blood gas analysis has been proposed as an alternative. To determine if venous pCO(2) can replace arterial pCO(2) in emergency patients using a bedside blood gas analyzer. This is a cross-sectional study. We recruited patients who were deemed by the attending Emergency Physicians to require arterial blood gas analysis to determine their ventilation or acid-base status. A venous and an arterial blood gas sample were drawn from the patient, temporally as close to each other as possible. Both samples were then analyzed using the same bedside blood gas analyzer immediately after collection. There were 122 paired samples obtained. The strength of the association between arterial and venous pCO(2) is r = 0.838 (p = 0.001). The Bland-Altman bias plot methods for agreement show a mean difference of 3.3 mm Hg with two standard deviation limits of agreement being -17.4 to 23.9; 93.4% of the pCO(2) values fell within two standard deviation limits. Venous pCO(2) below 30 mm Hg had a 100% (95% confidence interval [CI] 90.5-100) sensitivity and 100% (95% CI 80.7-100) Negative predictive value to rule out hypercarbia, defined as arterial pCO(2) > 45 mm Hg. There is significant variability in the arteriovenous difference of pCO(2) readings, hence, arterial punctures are still needed to specifically determine the arterial pCO(2).


Variability in activity of hepatic CYP3A4 in patients infected with HIV.
To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in patients infected with the human immunodeficiency virus (HIV) using the erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to plasma concentrations of indinavir and nelfinavir. Prospective observational study. University infectious diseases clinic. Thirty-nine HIV-positive patients and 47 healthy controls. After the ERMBT in patients and controls, 25 patients received indinavir or nelfinavir. Compared with controls, ERMBT variability was significantly greater in HIV-positive patients, including a subset of 19 patients receiving no concurrent drugs reported to alter CYP3A4 activity. Correlation between the ERMBT and first-dose plasma indinavir concentrations nearly reached statistical significance (p=0.07). Variability in hepatic activity of CYP3A4 in HIV-positive patients may be greater than in controls and may explain some between-subject variability in plasma concentrations of indinavir. However, clearance mechanisms for protease inhibitors are complex, and if it is important to assess systemic exposure, the ERMBT is not a substitute for direct measurement of plasma concentrations.


Polyphosphinoborane Block Copolymer Synthesis Using Catalytic Reversible Chain-Transfer Dehydropolymerization.
An amphiphilic block copolymer of polyphosphinoborane has been prepared by a mechanism-led strategy of the sequential catalytic dehydropolymerization of precursor monomers, H3 B ⋅ PRH2 (R=Ph, n-hexyl), using the simple pre-catalyst [Rh(Ph2 PCH2 CH2 PPh2 )2 ]Cl. Speciation, mechanism and polymer chain growth studies support a step-growth process where reversible chain transfer occurs, i.e. H3 B ⋅ PRH2 /oligomer/polymer can all coordinate with, and be activated by, the catalyst. Block copolymer [H2 BPPhH]110 -b-[H2 BP(n-hexyl)H]11 can be synthesized and self-assembles in solution to form either rod-like micelles or vesicles depending on solvent polarity.


Upregulation of cytidine deaminase in NAT1 knockout breast cancer cells.
Arylamine N-acetyltransferase 1 (NAT1), a phase II metabolic enzyme, is frequently upregulated in breast cancer. Inhibition or depletion of NAT1 leads to growth retardation in breast cancer cells in vitro and in vivo. A previous metabolomics study of MDA-MB-231 breast cancer cells suggests that NAT1 deletion leads to a defect in de novo pyrimidine biosynthesis. In the present study, we observed that NAT1 deletion results in upregulation of cytidine deaminase (CDA), which is involved in the pyrimidine salvage pathway, in multiple breast cancer cell lines (MDA-MB-231, MCF-7 and ZR-75-1). We hypothesized that NAT1 KO MDA-MB-231 cells show differential sensitivity to drugs that either inhibit cellular pyrimidine homeostasis or are metabolized by CDA. The cells were treated with (1) inhibitors of dihydroorotate dehydrogenase or CDA (e.g., teriflunomide and tetrahydrouridine); (2) pyrimidine/nucleoside analogs (e.g., gemcitabine and 5-azacytidine); and (3) naturally occurring, modified cytidines (e.g., 5-formyl-2'-deoxycytidine; 5fdC). Although NAT1 KO cells failed to show differential sensitivity to nucleoside analogs that are metabolized by CDA, they were markedly more sensitive to 5fdC which induces DNA damage in the presence of high CDA activity. Co-treatment with 5fdC and a CDA inhibitor, tetrahydrouridine, abrogated the increase in 5fdC cytotoxicity in NAT1 KO cells, suggesting that the increased sensitivity of NAT1 KO cells to 5fdC is dependent on their increased CDA activity. The present findings suggest a novel therapeutic strategy to treat breast cancer with elevated NAT1 expression. For instance, NAT1 inhibition may be combined with cytotoxic nucleosides (e.g., 5fdC) for breast cancer treatment.


Genotoxic effects of vinclozolin on the aquatic insect Chironomus riparius (Diptera, Chironomidae).
Vinclozolin (Vz) is a pollutant found in aquatic environments whose antiandrogenic effects in reproduction are well known in mammals. Although its reproductive effects have been less studied in invertebrates, other effects, including genotoxicity, have been described. Therefore, in this work, we studied the genotoxic effects of Vz in the freshwater benthic invertebrate Chironomus riparius. DNA damage was evaluated with the comet assay (tail area, olive moment, tail moment and % DNA in tail), and the transcriptional levels of different genes involved in DNA repair (ATM, NLK and XRCC1) and apoptosis (DECAY) were measured by RT-PCR. Fourth instar larvae of C. riparius, were exposed to Vz for 24 h at 20 and 200 μg/L. The Vz exposures affected the DNA integrity in this organism, since a dose-response relationship occurred, with DNA strand breaks significantly increased with increased dose for tail area, olive moment and tail moment parameters. Additionally, the lower concentration of Vz produced a significant induction of the transcripts of three genes under study (ATM, NLK and XRCC1) showing the activation of the cellular repair mechanism. In contrast, the expression of these genes with the highest concentration were downregulated, indicating failure of the cellular repair mechanism, which would explain the higher DNA damage. These data report for the first time the alterations of Vz on gene transcription of an insect and confirm the potential genotoxicity of this compound on freshwater invertebrates.


A comparative study of Chinese and American preservice teachers' intention to teach online based on the Theory of Planned Behavior.
Online learning emerged as a solution to continue with teaching and learning during the Coronavirus (COVID-19) pandemic. Nonetheless, teaching online consumes considerable time and put pressure on teachers' daily lives. Thus, the internal mechanism of preservice teachers' intention to teach online is analyzed in this study. Specifically, this study analyzed preservice teachers' intention to teach online in China and America to illuminate the internal mechanism of teachers' intention to teach online in different cultural backgrounds. One hundred seventy-six Chinese preservice teachers and two hundred forty-one American preservice teachers participated in this study. The confirmatory factor analysis supported that the Intention to Teach Online Scale was reliable in three constructs: online teaching attitude, perceived control, and subjective norm. The result demonstrates that there is a significant difference between Chinese and American preservice teachers' intention to teach online in the online teaching attitude and perceived control. In addition, it is supported that there is a significant difference between the effects of Chinese and American preservice teachers' teaching attitude, perceived control, and subjective norm on their intention to teach online. Moreover, there is a difference in the relationships among Chinese and American teachers' online teaching attitudes, perceived control, and subjective norm. The preservice teachers' demographic features can be factors that caused this difference. Research and practice implications of this study are proposed.


Deoxynortrichoharzin, a new polyketide from the saltwater culture of a sponge-derived Paecilomyces fungus.
The saltwater culture of a Paecilomyces cf. javanica isolated from the marine sponge Jaspis cf. coriacea has yielded a new polyketide, deoxynortrichoharzin (1), and two known diketopiperazines (2 and 3).


Effects of T-2 toxin on induction of petite mutants and mitochondrial function in Saccharomyces cerevisiae.
The influence of the trichothecene mycotoxin T-2 on the mitochondria of Saccharomyces cerevisiae was studied. T-2 is a cytotoxic molecule inhibiting growth and macromolecular synthesis in S. cerevisiae. At low concentrations, T-2 toxin arrested yeast growth on glycerol medium and at higher concentrations, it arrested growth on glucose medium. The toxin was not capable itself of inducing petite mutations. Its inhibitory effect on the growth of petite strains, of both chromosomally isogenic and non-isogenic strains was less than that of grande strains. One exception to this was equally low susceptibility of psi+ SUP4-3 strain in both rho+ and rho- state. T-2 toxin was also capable of retarding the petite inducing activity of the mutagen, ethidium bromide. T-2 toxin inhibited the polymerization of P-ribo-sylaminoimidazole in an ade2 strain of S. cerevisiae. These results show that T-2 toxin is capable of interfering with the activity of the mitochondria in addition to its well studied effects on cytoplasmic protein synthesis.


Pediatric Chronic Kidney Disease.
Chronic kidney disease (CKD) in children has a significant impact on morbidity, mortality, and quality of life. The degree of renal dysfunction should be calculated using pediatric-specific formulas and the degree of CKD staged; this allows for appropriate dosing of medications based on renal function and monitoring for progression and comorbid conditions including metabolic acidosis, bone disease, anemia, cardiovascular complications, malnutrition and electrolyte abnormalities, growth failure, and psychosocial issues. Treatment strategies include treating the underlying disease and using general renal protective measures. Effective management of these complex issues requires a specialized multidisciplinary team approach.


MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts.
The purpose of this study was to identify novel abnormally expressed microRNAs (miRNAs) and their downstream target in diabetic cataract (DC). General feature, fasting blood glucose, glycosylated hemoglobin, and type A1c (HbA1c) expression level of patients were collected. DC capsular tissues were obtained from patients and the lens cells (HLE-B3) exposed to different concentrations of glucose were used to simulate the model in vitro. Both mimic and inhibitor of miR-22-3p were transferred into HLE-B3 to up- and downregulate miR-22-3p expression, respectively. The cellular apoptosis was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence. The downstream target gene of miR-22-3p was identified by dual luciferase reporter. In DC capsules and HLE-B3 under hyperglycemia, miR-22-3p showed a significant downward trend. The expression of BAX was upregulated and the BCL-2 was downregulated following high glucose. The expression of BAX was significantly down- or upregulated in HLE-B3 cells following transfection of mimic or inhibitor of miR-22-3p, respectively. Conversely, BCL-2 was significantly increased or decreased. Dual luciferase reporter assay showed that miR-22-3p directly targeted Krüppel Like Factor 6 (KLF6) to regulate cell apoptosis. In addition, the expression of KLF6 were significantly up- or downregulated following transfection of inhibitor or mimic of miR-22-3p. This study suggested that miR-22-3p could inhibit lens apoptosis by targeting KLF6 directly under high glucose condition. The miR-22-3p/KLF6 signal axis may provide novel insights into the pathogenesis of DC. Differential expression of miR-22-3p may account for the pathogenesis of DC and lead to a new therapeutic strategy for DC.


Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model.
A series of naphthyridine and naphthyridinone allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been optimized to have potent dual activity against the activated kinase as well as the activation of Akt in cells. One molecule in particular, compound 17, has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model.


Activity of the hypothalamo-pituitary ovarian axis in hypothyroid rats with or without triiodothyronine replacement.
The hypothalamic pituitary ovarian axis in adult female rats with 131-I induced hypothyroidism was studied before and after triiodothyronine (T3) replacement. Forty days after 131-I, hypothyroid (H) rats showed irregular cycles with predominantly diestrous vaginal smears, atrophied and underweight ovaries, and decreased serum T3, T4, LH and estradiol (E2). T3 replacement restored normal cycles and ovary weight and increased serum E2 levels above control values, while LH levels remained below the limit of detection of the RIA. The GnRH stimulation test performed on the day that the rats exhibited diestrous vaginal smears elicited a greater increase in FSH than in LH in H rats and a greater increase in LH than in FSH in both H-T3 treated and control rats. The data suggest that the lack of thyroid hormones in adult female rats seems to produce a reversion of sexual hormones to a prepubertal pattern, while T3 treatment restored normal estrous cycles and ovarian function.


Combined penetrating keratoplasty and keratolimbal allograft transplantation in comparison with corneoscleral transplantation in the treatment of severe eye burns.
The aim of this study is to compare the therapeutic outcomes between penetrating keratoplasty (PK) combined with keratolimbal allograft (KLAL) transplantation and corneoscleral transplantation in patients with severe corneal burns. Thirty-eight patients (39 eyes) diagnosed severe corneal burns in stable status with vascularization and corneal opacity were included. We performed combined PK with KLAL transplantation in 23 eyes (group A) and corneoscleral transplantation in 16 eyes (group B). The main outcome measures were postoperative complications and long-term visual acuity and rejection. The incidence of postoperative complications (corneal epithelium defect, hyphaema and hypotony) in group A were obviously less than those in group B. Fifteen eyes (65%) in group A and four eyes (25%) in group B had best-corrected visual acuity of >0.05 at 24 months (P = 0.022). Limbal stem cell rejection occurred in eleven grafts (48%) in group A and eight grafts (50%) in group B (P = 1.000). Nine grafts (39%) in group A and 12 grafts (54%) in group B had endothelial rejection (P = 0.049). PK combined with KLAL transplantation may reduce the risk of postoperative complications. Long-term prognosis appears better than corneoscleral transplantation in the treatment of severe eye burns.


Synthesis of oligosaccharide substrates for N-linked glycoprotein processing enzymes.
The stereoselective syntheses of one pentasaccharide and one tetrasaccharide containing the Glc-alpha-(1-->3)-Man-alpha moiety as their terminal unit, as well as one tetrasaccharide and one trisaccharide containing the Man-alpha-(1-->2)-Man-alpha terminal unit were accomplished through the utilization of two key glycosyl donors, namely, 4-pentenyl 3-O-acetyl-2,4,6-tri-O-benzyl-alpha-D-mannopyranoside and ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-alpha-D-mannopyranoside.


Reversal by tolazoline hydrochloride of xylazine hydrochloride-ketamine hydrochloride immobilizations in free-ranging desert mule deer.
We captured 10 free-ranging desert mule deer (Odocoileus hemionus crooki) (five males and five females) by net-gun from a helicopter and immobilized them with xylazine hydrochloride (HCl) (100 mg) and ketamine HCl (300 to 400 mg) injected intramuscularly. Arousal and ambulation times were 13.9 +/- 4.2 and 14.3 +/- 4.2 min in eight deer injected intravenously with tolazoline HCl (3.0 mg/kg). We observed a curvilinear relationship (R = 0.50, P less than 0.01) between rectal temperature and time after induction of anesthesia. Mean peak temperature (41.4 C) occurred at 23.7 +/- 3.2 min postinduction and was greater (P less than 0.01) than the mean temperature measured initially (40.8 C). Heart and respiratory rates (108 beats/min and 75 breaths/min) were elevated prior to immobilization. Mean heart rate increased (P less than 0.05) from 90 +/- 9 beats/min in anesthetized deer to 120 +/- 13 beats/min after tolazoline HCl injection. A 20% capture-related mortality rate suggests this combination of physical and chemical capture has serious limitations. Captive deer permitted to recover from xylazine HCl-ketamine HCl immobilization without a reversal agent were able to walk in 290 +/- 79 min.


Drug utilisation profile in the Italian paediatric population.
In order to evaluate the prescribing pattern in the Italian paediatric population, prescriptions involving 923,353 children under 14 years old and dispensed during 2006 by the retail pharmacies of 22 Italian local health units were analysed. A total of 561,237 children (61%) received at least one drug prescription. The prescription prevalence rate was highest in children 3 years of age (78%), decreased with increasing age and was higher in boys than in girls (chi(2)=655; p<<0.001). Each treated child received an average of 3.2 prescriptions and 4.8 boxes. Antibiotics and anti-asthmatics were the more prescribed therapeutic classes and represented 80% of prescriptions. Amoxicillin+clavulanic acid was the most prescribed drug (24% of the overall population; 17% of all boxes), followed by inhaled beclometasone and amoxicillin. A total of 620 different drugs were prescribed and the ten leading drugs represented 64% of the prescribed boxes. Six of the ten most prescribed drugs were the same in all age groups. Wide differences were found in the prevalence rate between the different local health units; these ranged between 50.1 and 68.4% (p<<0.001). The prescription prevalence increased in the 2000-2002 period (from 62.2 to 68.3%) and slightly decreased afterwards. Despite some limitations, the systematic monitoring of prescriptions is a valuable tool for evaluating the appropriateness of the care.


A Review on Green Synthesis of Silver Nanoparticles and its Role against Cancer.
Cancer is a fatal disease with a collection of related diseases in various body parts. The conventional therapies cannot show the desired results of treatment due to their imprecise targeting, deprived drug delivery, and side effects. Therefore, it is required to make the drug engineered so that it can target only cancerous cells and inhibit its growth and proliferation. Nanotechnology is a technology that can target and differentiate between cancerous cells and the body's normal cells. Silver itself is a good anticancer and antibacterial agent and employing it with phytochemicals with anticancer properties, and nanotechnology can give the best approach for the treatment. The synthesis of silver nanoparticles using plant extracts is an economical, energy-efficient, low-cost approach, and it doesn't need any hazardous chemicals. In the present review, we discussed different methods of synthesis of silver nanoparticles using herbal extracts and their role against cancer therapy along with the synergistic role of silver and plant extracts against cancer in the formulation.


Glucokinase intrinsically regulates glucose sensing and glucagon secretion in pancreatic alpha cells.
The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells.