[SYTO/EB dyes for detection of skin viability].
the main purpose of this study is to develop an assay for detection of skin viability in situ. Two nucleic acid dyes, SYTO 13 and ethidium bromide (EB), are used to assess the viability of skin tissue. The viability of cells can be determined by different colors under fluorescence microscope. In this study, the recovery of skin restored at 4 degrees C for different periods is measured by SYTO/EB dyes and a type of indirect assessment, WST-1. Then both results are compared. The results measured by two methods showed that the viability of skin tissue was nearly 30% after two weeks storage. At any point of experiment, the data from two methods have not obvious variance. The assessment of skin viability by SYTO/EB is also quick, sensitive and convenient. At the same time the viability of any type of cells can be observed in situ. So it can be considered as an available method for detection of skin viability.


Magic Numbers for the Photoelectron Anisotropy in Li-Doped Dimethyl Ether Clusters.
Photoelectron velocity map imaging of Li(CH3OCH3) n clusters (1 ≤ n ≤ 175) is used to search for magic numbers related to the photoelectron anisotropy. Comparison with density functional calculations reveals magic numbers at n = 4, 5, and 6, resulting from the symmetric charge distribution with high s-character of the highest occupied molecular orbital. Since each of these three cluster sizes correspond to the completion of a first coordination shell, they can be considered as "isomeric motifs of the first coordination shell". Differences in the photoelectron anisotropy, the vertical ionization energies and the enthalpies of vaporization between Li(CH3OCH3) n and Na(CH3OCH3) n can be rationalized in terms of differences in their solvation shells, atomic ionization energies, polarizabilities, metal-oxygen bonds, ligand-ligand interactions and by cooperative effects.


Are parental health habits transmitted to their children? An eight year longitudinal study of physical activity in adolescents and their parents.
Parents are believed to play a role in influencing their children's health behaviours. This longitudinal study of two generations (parents and their children) examined associations between parents' self-reported leisure-time physical activity changes and the self-reported physical activity changes of their offspring in a sample of 557 adolescents over an 8 year period (from 13 to 21 years of age). The results revealed only weak and non-existent associations between changes in parents' physical activity and changes in adolescent physical activity from 13 to 21 years of age. The findings did not support the hypothesis that adolescents' leisure-time physical activity covaried with their parents' leisure-time physical activity over time. This may mean that parental physical activity is not transmitted to their children to the degree that is often believed.


Role of eukaryotic translation initiation factors 3a in hypoxia-induced right ventricular remodeling of rats.
Eukaryotic translation initiation factors 3a (eIF3a) is involved in regulating cell cycle, cell division, growth and differentiation. Previous studies suggest a role of eIF3a on fibrosis disease and cellular proliferation and differentiation of fibroblasts. The present study aims to investigate the role of eIF3a on hypoxia-induced right ventricular (RV) remodeling and underlying mechanism. RV remodeling was induced by hypoxia (10% O2, 3 weeks) in rats. Primary cardiac fibroblasts were cultured in vitro and their proliferation was investigated by MTS and EdU incorporation method. eIF3a knockdown was conducted by eIF3a siRNA. The expression/level of TGF-β1, eIF3a, p27 and α-SMA, collagen-I, collagen-III, ANP and BNP were analyzed by ELISA, real-time PCR or Western blot. The expression of eIF3a was obviously increased in right ventricle of RV remodeling rats accompanied by up-regulation of α-SMA and collagens. In cultured cardiac fibroblasts, application of exogenous TGF-β1-induced cellular proliferation and differentiation concomitantly with up-regulation of eIF3a expression and down-regulation of p27 expression. The effects of TGF-β1-induced proliferation and up-regulation of α-SMA and collagen in cardiac fibroblasts were abolished by eIF3a siRNA. eIF3a siRNA reversed TGF-β1 induced down-regulation of p27 expression. The eIF3a plays a crucial role in hypoxia-induced RV remodeling by regulating TGF-β1-induced proliferation and differentiation of cardiac fibroblasts, which is mediated via eIF3a/p27 pathway.


Racial Disparities in Outcomes After Common Abdominal Surgical Procedures-The Impact of Access to a Minimally Invasive Approach.
It is presently considered the standard of care to perform many routine intra-abdominal operations using a minimally invasive approach. The authors recently identified a racial disparity in access to a laparoscopic approach to inguinal hernia repair, cholecystectomy, appendectomy, and colectomy. The present study further evaluates this patient cohort to assess the relationship between the race and postoperative complications and test the mediating effect of the selected surgical approach. After institutional review board approval, patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent inguinal hernia repair, cholecystectomy, appendectomy, or colectomy in 2016 were identified. Patient demographics, including the self-reported race and ethnicity, as well as clinical, operative, and postoperative variables were recorded. After the exclusion of cases associated with diagnoses of cancer, a 4:1 propensity score matching algorithm generated a clinically balanced cohort of patients of white and black self-reported race. The mediating effect of an open approach to surgery on the relationship between black self-reported race and postoperative complications was evaluated via a series of regressions. There were 41,340 unilateral inguinal hernia repairs, 3182 bilateral inguinal hernia repairs, 60,444 cholecystectomies, 50,523 appendectomies, and 58,012 colectomies included in the database in 2017. Exclusion of cases associated with cancer and subsequent propensity score matching returned 17,540 unilateral hernia repairs, 890 bilateral hernia repairs, 23,865 cholecystectomies, 11,660 appendectomies, and 12,320 colectomies. On mediation analysis, any complication, severe complication, and death were significant when regressed on black self-reported race (any: odds ratio [OR] = 1.210, 95% confidence interval [CI] = 1.132-1.291, P < 0.001; severe: OR = 1.352, 95% CI = 1.245-1.466, P < 0.001; death: OR = 1.358, 95% CI = 1.000-1.818, P = 0.044), and open surgery was a significant mediator in the incidence of any complication and severe complication (any: OR = 1.180, 95% CI = 1.105-1.260, P < 0.001 and severe: OR = 1.307, 95% CI = 1.203-1.418, P < 0.001). These findings underscore the importance of access to a minimally invasive approach to surgery. However, other factors may contribute to racial disparities in postoperative complications after common abdominal operations.


mGluR5 promotes the progression of multiple myeloma in vitro via Ras-MAPK signaling pathway.
Multiple myeloma (MM) is a malignant plasma cancer which remains difficult to be cured. Recently, numerous research studies have appeared, exploring MM from molecular level. However, there is no study about the impact of metabotropic glutamate receptors (mGluRs), especially mGluR5, on MM progression. Thus, the present research was dedicated to the exploration of the influence of mGluR5 on MM. In this research, we used quantitative real-time polymerase chain reaction (qRT-PCR) to check the gene expression in MM, western blot assay to check the protein expression of the gene, MTT assay to quantify the cell viability, and flow cytometry (FCM) apoptosis method to evaluate cell apoptosis in order to acquire the results. The purpose was to assess the role of mGluR5 in MM cells. The qRT-PCR was used and it was found that mGluR5 was overexpressed in MM cell lines and MM tissues compared to normal ones. To better observe the function of mGluR5 in MM, cell viability and apoptosis were checked using MTT and FCM apoptosis assays after the treatment with agonists and antagonists. Agonist-induced mGluR5 upregulation could promote MM cell viability and inhibit apoptosis. The same results were obtained through MTT and FCM apoptosis assays after upregulation and downregulation of mGluR5 by transfection. To further investigate the inner mechanism, the effect of mGluR5 on Ras-MAPK pathway was checked using western blot. It was found that the upregulation of mGluR5 could activate the Ras-MAPK pathway. The mGluR5 might be involved in promoting cell proliferation and inhibiting cell apoptosis in MM. It can be an essential biomarker in the screening for MM and a potential part of future MM therapies.


Correction: The impact of Fosetyl-Aluminium application timing on Karnal bunt suppression and economic returns of bread wheat (Triticum aestivum L.).
[This corrects the article DOI: 10.1371/journal.pone.0244931.].


Systematic strain construction and process development: Xylitol production by Saccharomyces cerevisiae expressing Candida tenuis xylose reductase in wild-type or mutant form.
A novel Saccharomyces cerevisiae whole-cell biocatalyst for xylitol production based on Candida tenuis xylose reductase (CtXR) is presented. Six recombinant strains expressing wild-type CtXR or an NADH-specific mutant were constructed and evaluated regarding effects of expression mode, promoter strength, biocatalyst concentration and medium composition. Intracellular XR activities ranged from 0.09 U mgProt(-1) to 1.05 U mgProt(-1) but did not correlate with the strains' xylitol productivities, indicating that other factors limited xylose conversion in the high-activity strains. The CtXR mutant decreased the biocatalyst's performance, suggesting use of the NADPH-preferring wild-type enzyme when (semi-)aerobic conditions are applied. In a bioreactor process, the best-performing strain converted 40 g L(-1) xylose with an initial productivity of 1.16 g L(-1)h(-1) and a xylitol yield of 100%. The obtained results underline the potential of CtXR wild-type for xylose reduction and point out parameters to improve "green" xylitol production.


Resorbable membrane design: In vitro characterization of silver doped-hydroxyapatite-reinforced XG/PEI semi-IPN composite.
In this study, the production and characterization of silver-doped hydroxyapatite (AgHA) reinforced Xanthan gum (XG) and Polyethyleneimine (PEI) reinforced semi-interpenetrating polymer network (IPN) biocomposite, known to be used as bone cover material for therapeutic purposes in bone tissue, were performed. XG/PEI IPN films containing 2AgHA nanoparticles were produced by simultaneous condensation and ionic gelation. Characteristics of 2AgHA-XG/PEI nanocomposite film were evaluated by structural, morphological (SEM, XRD, FT-IR, TGA, TM, and Raman) and biological activity analysis (degradation, MTT, genotoxicity, and antimicrobial activity) techniques. In the physicochemical characterization, it was determined that 2AgHA nanoparticles were homogeneously dispersed in the XG/PEI-IPN membrane at high concentration and the thermal and mechanical stability of the formed film were high. The nanocomposites showed high antibacterial activity against Acinetobacter Baumannii (A.Baumannii), Staphylococcus aureus (S.aureus), and Streptococcus mutans (S.mutans). L929 exhibited good biocompatibility for fibroblast cells and was determined to support the formation of MCC cells. It was shown that a resorbable 2AgHA-XG/PEI composite material was obtained with a high degradation rate and 64% loss of mass at the end of the 7th day. Physico-chemically developed biocompatible and biodegradable XG-2AgHA/PEI nanocomposite semi-IPN films possessed an important potential for the treatment of defects in bone tissue as an easily applicable bone cover. Besides, it was noted that 2AgHA-XG/PEI biocomposite could increase cell viability, especially in dental-bone treatments for coating, filling, and occlusion.


An appointment reminder system's effect on reducing the number of hypertension patients who drop out from care.
We evaluated the effects of an appointment reminder system on the appointment-keeping behavior and blood pressure control status of hypertensive patients receiving care in an urban medical clinic. The study population consisted of 973 adult hypertensive patients receiving medical care at a family practice clinic affiliated with the Wayne State University School of Medicine, Detroit, Michigan. Of the 973 patients enrolled in the study, 486 were randomly assigned to a group that received appointment reminder cards and telephone calls to reschedule missed appointments, and 487 were assigned to a nonintervention control group. Patients were followed-up with regard to their appointment-keeping behavior and blood pressure control status, five to eight months after being entered in the study. The study results indicate that patients in the appointment reminder group kept significantly more appointments and were less likely to drop out of treatment than patients in the control group. The dropout rate was 46 percent lower among patients in the appointment reminder group than in the control group. Patients in the appointment reminder group also demonstrated slightly better blood pressure control at the end of the study compared with patients in the control group, although none of the differences in blood pressure levels between groups were statistically significant at the 5 percent level.


Second time a charm? Remobilization of peripheral blood stem cells with plerixafor in patients who previously mobilized poorly despite using plerixafor as a salvage agent.
Plerixafor is a recently introduced agent used to improve peripheral blood stem cell (PBSC) mobilization in patients with hematologic malignancies. However, some patients still cannot mobilize adequately even with plerixafor. We retrospectively reviewed the PBSC collections of 18 consecutive lymphoma and multiple myeloma patients, who had previously mobilized poorly despite the use of plerixafor and received plerixafor again during remobilization. During the first mobilization attempt, all 18 recombinant granulocyte-colony-stimulating factor (G-CSF; two) or G-CSF plus chemotherapy-mobilized patients (16) had poor response to plerixafor, with peripheral blood (PB) CD34+ counts ranging from 0 to 7.48 × 10(6)/L after the first dose. They collected only 0.15 × 10(6) to 1.63 × 10(6) (median, 0.40 × 10(6)) CD34+ cells/kg after one to four collections. The median average daily yield was 0.24 × 10(6) CD34+ cells/kg. Remobilization began 1 to 4 weeks later with G-CSF, plerixafor, and with (three) or without (15) cyclophosphamide. The PB CD34+ cell counts after the first dose of plerixafor were 3.04 × 10(6) to 127.54 × 10(6)/L (median, 14.58 × 10(6)/L). After one to four doses of plerixafor, each patient collected an additional 0.39 × 10(6) to 14.02 × 10(6) (median, 1.89 × 10(6)) CD34+ cells/kg, and the median daily average was 0.78 × 10(6) CD34+ cells/kg. Cumulatively, after two rounds of collections, 15 collected more than 2.0 × 10(6) CD34+ cells/kg. Thirteen have proceeded to autologous stem cell transplantation (ASCT) and successfully engrafted. In patients who had responded poorly to the use of plerixafor as a mobilization salvage agent, response to remobilization with plerixafor for the second time was variable, but most (83.3%) patients were able to collect enough PBSCs to proceed to ASCT.


A simple quantitative assay of vascular plasminogen activator--not only stimulated fibrinolytic activity but also basal fibrinolytic activity are correlated with venous fibrinolytic activity.
A simple method for the quantitative assay of vascular plasminogen activator is described. From 24 chronic renal failure patients who were undergoing surgery for A/V fistular or shunt construction, small pieces of artery (mean 7.8 mg, range 3.0-18.5 mg) and vein (mean 4.5 mg, range 3.0-8.8 mg) were used. The fibrinolytic activity was assayed on a well-controlled fibrin plate by only distilled water immersion and incubation at 37 degrees C. Basal fibrinolytic activity was correlated with venous fibrinolytic activity (r = 0.773, p less than 0.0001) and with arterial fibrinolytic activity (r = 0.55, 0.005 less than p less than 0.01). The increment of fibrinolytic activity by venous occlusion was correlated to venous fibrinolytic activity (r = 0.849, p less than 0.0001) but not to arterial fibrinolytic activity (r = 0.34, 0.1 less than p less than 0.25).


Heat and outpatient visits of skin diseases - A multisite analysis in China, 2014-2018.
Many studies have shown that various kinds of diseases were associated with the variation of ambient temperature. However, there's only a scrap of evidence paying attention to the link between temperature and skin diseases, and no relevant national research was performed in China. This study aimed to quantify the effect of heat on skin diseases and identify the vulnerable populations and areas in China. Daily meteorological data, air pollutant data and outpatient data were collected from in 18 sites of China during 2014-2018. A time-series study with distributed lag nonlinear model and multivariate meta-analysis was applied to analyze the site-specific and pooled associations between daily mean temperature and daily outpatient visits of skin diseases by using the data of warm season (from June to September). Stratified analysis by age, sex and climate zones and subtypes of skin diseases were also conducted. We found a positive linear relationship between the ambient temperature and risk of skin diseases, with a 1.25% (95%CI: 0.34%, 2.16%) increase of risk of outpatient visits for each 1 °C increase in daily mean temperature during the warm season. In general, groups aged 18-44 years, males and people living in temperate climate regions were more susceptible to high temperature. Immune dysfunction including dermatitis and eczema were heat-sensitive skin diseases. Our findings suggested that people should take notice of heat-related skin diseases and also provided some references about related health burden for strategy-makers. Targeted measures for vulnerable populations need to be taken to reduce disease burden, including monitoring and early warning systems, and sun-protection measures.


Nitric oxide effects on Rhodnius prolixus's immune responses, gut microbiota and Trypanosoma cruzi development.
The immune system of Rhodnius prolixus comprehends the synthesis of different effectors that modulate the intestinal microbiota population and the life cycle of the parasite Trypanosoma cruzi inside the vector midgut. One of these immune responses is the production of reactive nitrogen species (RNS) derived by the action of nitric oxide synthase (NOS). Therefore, we investigated the effects of L-arginine, the substrate for nitric oxide (NO) production and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of NOS, added in the insect blood meal. We analyzed the impact of these treatments on the immune responses and development of intestinal bacteria and parasites on R. prolixus nymphs. The L-arginine treatment in R. prolixus nymphs induced a higher NOS gene expression in the fat body and increased NO production, but reduced catalase and antimicrobial activities in the midgut. As expected, L-NAME treatment reduced NOS gene expression in the fat body. In addition, L-NAME treatment diminished catalase activity in the hemolymph and posterior midgut reduced phenoloxidase activity in the anterior midgut and increased the antimicrobial activity in the hemolymph. Both treatments caused a reduction in the cultivatable intestinal microbiota, especially in insects treated with L-NAME. However, T. cruzi development in the insect's digestive tract was suppressed after L-arginine treatment and the opposite was observed with L-NAME, which resulted in higher parasite counts. Therefore, we conclude that induction and inhibition of NOS and NO production are associated with other R. prolixus humoral immune responses, such as catalase, phenoloxidase, and antibacterial activities in different insect organs. These alterations reflect on intestinal microbiota and T. cruzi development.


Changes in cytoplasmic and mitochondrial enzymes in rat liver after ischemia followed by reperfusion.
The behavior of cytoplasmic and mitochondrial enzymes has been studied in rat liver at 1, 5, and 24 hr after 60 min of ischemia using histochemical methods. This period of ischemia resulted 24 h after ischemia in liver cell necrosis in about 15% of the volume of the ischemic liver lobes. As early as after 1 hr reperfusion lactate dehydrogenase (LDH, cytoplasm) activity decreased in a certain proportion of the liver parenchymal cells, whereas glutamate dehydrogenase (GDH, mitochondrial matrix) activity started to decrease after 5 hr reperfusion; the activities of mitochondrial membrane enzymes, monoamine oxidase and succinate dehydrogenase, did not decrease before 24 hr of reperfusion. It has been concluded that the early decrease in LDH activity is caused by leakage into the blood and reflects reversible damage; when this decrease is accompanied by a decrease in GDH activity irreversible liver cell damage is assumed. Diminished activity of mitochondrial membrane enzymes, due to leakage and denaturation, is observed when real necrosis can be assessed.


Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity.
Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity.


Postoperative evaluation of bone bridge after alveolar bone graft with cortical bone lining technique.
For alveolar bone grafting (ABG), we have been performing surgery using a technique in which a cortical bone lining iliac endplate is applied to the anterior nasal aperture inferior margin. Herein, we used conventional and cortical bone lining techniques to examine the postoperative bone-bridge morphology after ABG. Fifty-five unilateral patients who underwent ABG at our clinic from October 2012 to March 2019 were included. We used postoperative CT data to compare the labiolingual width of the grafted bone and anterior-posterior and vertical shapes of the nasal aperture inferior margin with respect to the ungrafted side. The cortical bone lining technique was superior to the conventional method. The cortical bone lining technique showed good results regardless of alveolar cleft width or oral-nasal fistula. Also, tooth movement into the grafted area was involved in maintaining the residual graft bone; however, the cortical bone lining technique had better results. The cortical bone lining technique allows for the physical closure of nasolateral mucosal fistulas when it is technically difficult, and it can apply sufficient pressure to the bone marrow cancellous bone filling over the cortical plate bone. Our results illustrate the effectiveness of the cortical bone lining technique.


Astrocyte physiopathology: At the crossroads of intercellular networking, inflammation and cell death.
Recent breakthroughs in neuroscience have led to the awareness that we should revise our traditional mode of thinking and studying the CNS, i.e. by isolating the privileged network of "intelligent" synaptic contacts. We may instead need to contemplate all the variegate communications occurring between the different neural cell types, and centrally involving the astrocytes. Basically, it appears that a single astrocyte should be considered as a core that receives and integrates information from thousands of synapses, other glial cells and the blood vessels. In turn, it generates complex outputs that control the neural circuitry and coordinate it with the local microcirculation. Astrocytes thus emerge as the possible fulcrum of the functional homeostasis of the healthy CNS. Yet, evidence indicates that the bridging properties of the astrocytes can change in parallel with, or as a result of, the morphological, biochemical and functional alterations these cells undergo upon injury or disease. As a consequence, they have the potential to transform from supportive friends and interactive partners for neurons into noxious foes. In this review, we summarize the currently available knowledge on the contribution of astrocytes to the functioning of the CNS and what goes wrong in various pathological conditions, with a particular focus on Amyotrophic Lateral Sclerosis, Alzheimer's Disease and ischemia. The observations described convincingly demonstrate that the development and progression of several neurological disorders involve the de-regulation of a finely tuned interplay between multiple cell populations. Thus, it seems that a better understanding of the mechanisms governing the integrated communication and detrimental responses of the astrocytes as well as their impact towards the homeostasis and performance of the CNS is fundamental to open novel therapeutic perspectives.


Dual roles of progesterone in embryo implantation in mouse.
Progesterone (P4) is essential for the development of endometrial receptivity for blastocyst implantation and pregnancy maintenance. Many studies have demonstrated that P4 restrains endometrial tissue breakdown by inhibiting the stimulation of matrix metalloproteinases (MMPs), which implies that P4 impedes the invasion of trophoblast cells into endometrial tissue. To investigate the role of P4 on the attachment and invasion of the trophoblast cells in the entire process of embryo implantation, we used two in vitro coculture systems of blastocysts on a monolayer of uterine epithelial cells and ectoplacental cone (EPC) on uterine decidual cells. The results indicated that all doses of P4 significantly promoted blastocyst attachment, and that except for a concentration of 3.18 x 10-8 mol/L, P4 markedly increased the percentage of blastocysts with outgrowth. However, all concentrations of RU486 clearly prevented blastocyst attachment, and except for a concentration of 10-8 mol/L, all doses of RU486 significantly inhibited the outgrowth of blastocysts. The effect of 3.18 x 10-6 mol/L of P4 on the attachment and outgrowth of blastocysts was significantly blocked by all concentrations of RU486. All concentrations of P4 retarded the attachment of EPC on uterine decidual cells and decreased the outgrowth area of EPC. Except for a concentration of 3.18 x 10-8 mol/L, all concentrations of P4 had a significant inhibitory effect on the percentage of EPC outgrowth. Conversely, except for a concentration of 10-8 mol/L, all doses of RU486 had a significant stimulatory effect on the attachment of EPC. All concentrations of RU486 clearly promoted the outgrowth and outgrowth area of EPC. The inhibitory effect of P4 on EPC was clearly blocked by all doses of RU486. In addition, P4 promoted the activity of MMP-2 on blastocysts and EPC, but P4 inhibited the activity of MMP-9 on EPC. In summary, P4 played dual roles at the early and late stages of embryo implantation in mouse. When blastocysts interacted with the uterine epithelial cells, P4 promoted the attachment and invasion of the primary trophoblast giant cells. When EPC was in contact with uterine decidual cells, P4 inhibited the attachment and invasion of the secondary trophoblast giant cells. Furthermore, the role of P4 was transduced through the classic nuclear receptor.


In vitro activity studies of doripenem and two other carbapenems tested against Pseudomonas aeruginosa and other non-fermentative bacilli.
Over the past decade, an increasing prevalence of infections caused by non-fermenting Gram-negative bacteria has been reported in many countries. Among these bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with high mortality and treatment failures. Treatment options for multidrug-resistant P. aeruginosa and A. baumannii infections are limited to carbapenems in most cases. The mechanisms of carbapenem resistance have been identified in P. aeruginosa and other Gram-negative non-fermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target- site alterations. This article reviews the in vitro activity of doripenem and compares it with that of imipenem and meropenem against a large collection of non-fermenting Gram-negative bacilli, obtained in worldwide surveillance studies between 2000 and 2010. A detailed examination of the available data demonstrate that doripenem has more potent in vitro antibacterial activity against P. aeruginosa and Acinetobacter species compared to other carbapenems. Furthermore, doripenem has a limited ability to select for carbapenem-resistant mutants in vitro.


[Endogenous and exogenous estrogens].
Before menopause, women are protected from the risk of hypertension and atherosclerosis by endogenous estrogens. Estrogens have a vasoprotective role, while progesterone seems to have a neutral effect. Exogenous estrogens used in menopausal treatment have vascular effects. These effects depend of type, dose and administration type, and with age and atherosclerosis stages. Synthetic progestins have varying clinical effects. Each drug must be evaluated separately.


Immune gains through brain drains.
In a mouse model of pneumococcal meningitis, skull channels provide extravascular signaling to the skull marrow capable of initiating local marrow hematopoiesis.


Human papillomavirus (HPV) infection, HIV infection and cervical cancer in Tanzania, east Africa.
The presence of HPV-DNA was determined in tumor biopsies of cervical-cancer patients and in cervical swabs of non-cancer patients from Tanzania, East Africa, by Southern blot hybridization and/or PCR. HPV types 16 and 18 were detected in 38% and 32%, respectively, of 50 cervical-carcinoma biopsies. A consensus primer PCR capable of detecting a broad spectrum of HPV types revealed the presence of HPV-DNA in 59% of 359 cervical swabs of non-cancer patients. Type-specific PCR showed that types 16 and 18 accounted for 13.2% and 17.5%, respectively, of all HPV infections. Therefore we concluded that HPV 18 is more prevalent in Tanzania than in any other geographical location so far reported. The strongest risk factors for the presence of any HPV-DNA in the 359 female non-cancer patients were young age and HIV infection. The epidemiology of HPV types 16 and 18 was found to differ from that of other HPV types, being associated in univariate analysis with trichomonas vaginalis infection, martial status (single/divorced), age at first intercourse, and young age at menarche. However, young age at menarche accounted for most of the effects of all other, variables in multivariate analysis. Of the non-cancer patients, 12.8% had antibodies against HIV I (no patient being severely symptomatic), and HIV infection was highly correlated with the presence of HPV-DNA, especially types 16 and 18. While HPV-DNA of any type was detectable 1.4-fold more often in HIV-positive patients than in HIV-negative patients, evidence of an infection with HPV types 16 or 18 was found 2.2-fold more often in the HIV-positive patients. The HIV-positive women did not show an increased rate of cervical cytological abnormalities as assessed by PAP staining of a single cervical smear, the overall rate of abnormalities being 2.8%. Furthermore, the age-adjusted prevalence of HIV antibodies was found to be considerably lower in 270 cervical-carcinoma patients (3% HIV-positive) in comparison with non-cancer patients. Thus there was no association observable between the prevalence of HIV infections and the frequency of cervical cytological abnormalities or cervical cancer in the setting of this cross-sectional study.


Imaging of cerebral metastases.
MR imaging with intravenous gadolinium has greatly enhanced our ability to detect and delineate intracranial metastases as well as to differentiate them from other disease processes. Techniques such as magnetization transfer and triple dose gadolinium imaging have further improved lesion detection. Consideration of these radiologic techniques, including the issues and controversies of screening and cost effectiveness, suggests a reasonable approach to imaging patients with possible intracranial metastases. Newer modalities such as echo planar imaging, spectroscopy, PET, and SPECT, may in the future, prove to be very useful in the evaluation of patients with intracranial metastases. Proper imaging is also critical to appropriate diagnosis and management of meningeal metastases, calvarial metastases, and paraneoplastic disease.


Open prostatectomy is still a valid option for large prostates: a high-volume, single-center experience.
To evaluate, in a retrospective, single-center trial, our open prostatectomy outcomes and complications in the past 12 years to emphasize the feasibility of open prostatectomy for large prostates. A total of 1193 patients underwent open prostatectomy from 1995 to 2007. We retrospectively analyzed the data from 664 patients who had preoperative, operative, and postoperative data available. The mean patient age was 67.5 years (range 52-86). The mean preoperative prostate-specific antigen value was 9.6 ng/mL (range 1.65-45.6). The mean prostatic weight was 88.7 g (range 45-324) and was significantly different for the 1995-2001 and 2002-2007 groups (73.6 vs 98.2 g, respectively). Of the 664 patients, 208 (31%) had had an indwelling catheter before surgery. The average International Prostate Symptom Score was 21.7 (range 13-32) preoperatively and 10.6 (range 8-18) postoperatively (P <.005). The average hospitalization was 6.74 days (range 4-14). Blood transfusion was required in 12.7% of the patients either intraoperatively or postoperatively. Postoperatively, 82 patients (12.3%) had urinary tract infections, 22 (3.2%) had bladder neck obstruction, 5 (0.7%) had urinary incontinence, and 15 (2.3%) had a ureteral meatus stricture. Open prostatectomy is a feasible treatment option for patients with a large prostate and also for patients with additional bladder pathologic findings such as bladder calculi or diverticula for whom endoscopic treatment modalities are not appropriate. Consequently, open prostatectomy is still the primary option for patients with a prostate greater than 100 cm(3) and preserves its importance in urology practice, even in the presence of endoscopic innovations.


Clinician decisions and computers.
The clinician's decisions are subject to numerous distorting influences. Computer decision aids can help avoid these distortions by placing the clinician's limited personal experience into broader perspective through comparison with a larger repository of clinically relevant information; by making explicit the assumptions implied by his or her decisions; and by alerting the clinician whenever the decisions made do not appear consistent with these assumptions, with the available information or with the conventional rules of logic. Practical standards of performance with respect to the development, validation and clinical application of these decision aids are still in evolution, however, and a variety of ethical and legal issues have yet to be addressed. Despite the promise of computer decision aids, it remains to be seen whether their diffusion into medical practice will improve the quality and cost of health care.


Biological characterization of a new silicon based coating developed for dental implants.
Taking into account the influence of Si in osteoblast cell proliferation, a series of sol-gel derived silicon based coating was prepared by controlling the process parameters and varying the different Si-alkoxide precursors molar rate in order to obtain materials able to release Si compounds. For this purpose, methyltrimethoxysilane (MTMOS) and tetraethyl orthosilicate (TEOS) were hydrolysed together and the sol obtained was used to dip-coat the different substrates. The silicon release ability of the coatings was tested finding that it was dependent on the TEOS precursor content, reaching a Si amount value around ninefolds higher for coatings with TEOS than for the pure MTMOS material. To test the effect of this released Si, the in vitro performance of developed coatings was tested with human adipose mesenchymal stem cells finding a significantly higher proliferation and mineralization on the coating with the higher TEOS content. For in vivo evaluation of the biocompatibility, coated implants were placed in the tibia of the rabbit and a histological analysis was performed. The evaluation of parameters such as the bone marrow state, the presence of giant cells and the fibrous capsule proved the biocompatibility of the developed coatings. Furthermore, coated implants seemed to produce a qualitatively higher osteoblastic activity and a higher number of bone spicules than the control (uncoated commercial SLA titanium dental implant).


Schinus terebinthifolius Raddi (Brazilian pepper) leaves extract: in vitro and in vivo evidence of anti-inflammatory and antioxidant properties.
The aim of this work was to evaluate the anti-inflammatory and antioxidant effects of ethyl acetate extract obtained from the leaves of Brazilian peppertree Schinus terebinthifolius Raddi (EAELSt). Total phenols and flavonoids, chemical constituents, in vitro antioxidant activity (DPPH and lipoperoxidation assays), and cytotoxicity in L929 fibroblasts were determined. In vivo anti-inflammatory and antioxidant properties were evaluated using TPA-induced ear inflammation model in mice. Phenol and flavonoid contents were 19.2 ± 0.4 and 93.8 ± 5.2 of gallic acid or quercetin equivalents/g, respectively. LC-MS analysis identified 43 compounds, of which myricetin-O-pentoside and quercetin-O-rhamnoside were major peaks of chromatogram. Incubation with EAELSt decreased the amount of DPPH radical (EC50 of 54.5 ± 2.4 µg/mL) and lipoperoxidation at 200-500 µg/mL. The incubation with EAELSt did not change fibroblast viability up to 100 µg/mL. Topical treatment with EAELSt significantly reduced edema and myeloperoxidase activity at 0.3, 1, and 3 mg/ear when compared to the vehicle-treated group. In addition, EAELSt decreased IL-6 and TNF-α levels and increased IL-10 levels. Besides, it modulated markers of oxidative stress (reduced total hydroperoxides and increased sulfhydryl contents and ferrium reduction potential) and increased the activity of catalase and superoxide dismutase, without altering GPx activity.


Predictors of Adverse Events Among Chronic Total Occlusion Patients Undergoing Successful Percutaneous Coronary Intervention and Medical Therapy.
Limited data are available on the predictors of major adverse cardiac events (MACE) after a successful coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and medical therapy. This study aimed to identify predictors of MACE in CTO patients undergoing successful recanalization and medical therapy. A total of 2015 patients with CTOs were enrolled. About 718 patients underwent successful CTO recanalization, and 1297 patients received medical therapy. The primary outcome was the frequency of MACE, defined as a composite of cardiac death, myocardial infarction, and target-vessel revascularization. Multivariate models were used to determine predictors of MACE. In successful CTO recanalization group, MACE occurred in 123 (17.1%) patients. In multivariate analysis, heart failure (hazard ratio [HR] 1.77, 95% confidence interval [CI]: 1.04-3.04, p = 0.036) was identified as independent predictors for MACE in successful CTO recanalization. Additionally, in medical therapy group, the significant predictors of MACE were male gender (HR 1.53, 95% CI: 1.13-2.05, p = 0.005), diabetes mellitus (HR 1.39, 95% CI: 1.11-1.74, p = 0.003), heart failure (HR 1.44, 95% CI: 1.10-1.87, p = 0.007), J-CTO score (HR 1.17, 95% CI: 1.07-1.28, p = 0.001) and multivessel disease (HR 2.20, 95% CI: 1.42-3.39, p < 0.001). Heart failure was predictor for composite cardiovascular events in patients with CTO after successful recanalization. Male gender, diabetes mellitus, heart failure, J-CTO score and multivessel disease were predictors of MACE in CTO patients with medical therapy.


The time-distance recorder as a means of improving the accuracy of fetal blood flow measurements.
The influence of pulsatile diameter changes on calculation of volume flow has been studied. In vitro studies and an animal study were carried out with a real-time imaging and pulsed Doppler velocity measurement system. For precise pulsatile diameter information a wall motion tracking device was incorporated. Whereas in vitro a high degree of accuracy was found for the measurements of volume flow, this could not be substantiated in the descending aorta of the fetal lamb, in which Doppler volume flow differed between -7.5 and 17% from magnetic volume flow. In a clinical study the relative influence of various diameter approximations on calculated fetal aortic volume flow was assessed in 16 normal third trimester pregnancies. Depending on the selected diameter approximation method it appeared that differences from 19% underestimation to 9% overestimation in calculated volume flow could be obtained when reference was made to volume flow derived from diameter and velocity information.


Vaccines, Politics and Mandates: Can We See the Forest for the Trees? Comment on "Convergence on Coercion: Functional and Political Pressures as Drivers of Global Childhood Vaccine Mandates".
Under-vaccination is a complex problem that is not simple to address whether this is for routine childhood immunization or for coronavirus disease 2019 (COVID-19) vaccination. Vaccination mandates has been one policy instrument used to try to increase vaccine uptake. While the concept may appear straight forward there is no standard approach. The decision to shift to a more coercive mandated program may be influenced by both functional and/or political needs. With mandates there may be patient and/or public push back. Anti-mandate protests and increased public polarization has been seen with COVID-19 vaccine mandates. This may negatively impact on vaccine acceptance ie, be counterproductive, causing more harm than overall good in the longer term. We need a better understanding of the political and functional needs that drive policy change towards mandates as well as cases studies of the shorter- and longer-term outcomes of mandates in both routine and pandemic settings.


Evidence for chemotaxis during sexual development in Dictyostelium discoideum.
Amoebae in mated cultures of Dictyostelium discoideum show oriented movement towards young aggregates, suggesting that cemotaxis is involved in macrocyst development. Amoebae also show directional movement towards midendocyte stages, indicating that as the macrocyst develops it continues to be a source of chemoattractant. These data are discussed in terms of our current knowledge about mating in the cellular slime moulds.


Increased lactic acid content associated with extracellular matrix depletion in a porcine disc degeneration induced by superficial annular lesion.
Degenerative intervertebral disc (IVD) disease can cause lower back pain. However, the change of lactic acid content during disc degeneration process still unclear. The objective of this study was to investigate whether the change of the content of lactic acid is associated with depletion of degenerative intervertebral disc extracellular matrix. A total of 18 miniature pigs were equally divided into annular lesion surgery (AL) and sham group. The lateral superficial annulus fibrosus (AF) of T12-L4 discs in AL group were penetrated by 3.5 mm trepan with the depth of 3 mm, the same IVD were only exposed without any injury in the sham group. At 4, 8 and 12 weeks after surgery, the degree of intervertebral disc degeneration was evaluated by magnetic resonance, histological and biochemical analysis. No obvious degeneration was found in sham group. However, disc degeneration was found and gradually worsened in AL group after surgery. Histological analysis showed that the AF was rupture and disorder, the number of cells in nucleus pulposus (NP) was decreased in AL group. Compared with the sham group, the extent of type II collagen (Col-II) and aggrecan in NP tissue was dramatically decreased in AL group, consistent with the results of Col -II immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Besides, the gene expression of matrix metallopeptidase 3 and 13 also continuous increased in AL group. The amount of lactic acid and nerve growth factor in NP tissue was gradually increased after operation in AL group. The content of lactic acid gradually increased after annular lesion, associated with the damage of AF structural and the decrease of Col -II and aggrecan in NP tissue, which leading to the disc degeneration. Depletion of extracellular matrix is consistent with lactic acid accumulation inside of IVD.


A method for scoring the cell type-specific impacts of noncoding variants in personal genomes.
A person's genome typically contains millions of variants which represent the differences between this personal genome and the reference human genome. The interpretation of these variants, i.e., the assessment of their potential impact on a person's phenotype, is currently of great interest in human genetics and medicine. We have developed a prioritization tool called OpenCausal which takes as inputs 1) a personal genome and 2) a reference context-specific TF expression profile and returns a list of noncoding variants prioritized according to their impact on chromatin accessibility for any given genomic region of interest. We applied OpenCausal to 6,430 samples across 18 tissues derived from the GTEx project and found that the variants prioritized by OpenCausal are highly enriched for eQTLs and caQTLs. We further propose a strategy to integrate the predicted open scores with genome-wide association studies (GWAS) data to prioritize putative causal variants and regulatory elements for a given risk locus (i.e., fine-mapping analysis). As an initial example, we applied this method to a GWAS dataset of human height and found that the prioritized putative variants and elements are correlated with the phenotype (i.e., heights of individuals) better than others.


Age and prostate volume are risk factors for transient urinary incontinence after transurethral enucleation with bipolar for benign prostatic hyperplasia.
To investigate the predictive factors for transient urinary incontinence after transurethral enucleation with bipolar. We retrospectively analyzed the data of 584 patients who underwent transurethral enucleation with bipolar between December 2011 and September 2016 operated by a single surgeon. Urinary incontinence after transurethral enucleation with bipolar was defined as involuntary leakage of urine that required the use of pads. It was evaluated at 1 week, and 1, 3, 6, 12 and 24 months after transurethral enucleation with bipolar. We defined transient urinary incontinence as urinary incontinence persisting up to 1 month after transurethral enucleation with bipolar. Based on independent risk factors identified by a multivariate stepwise logistic regression analysis, a nomogram to predict transient urinary incontinence was developed. Of the 584 patients, 17.3%, 13.5%, 3.1%, 0.41%, and 0% patients had urinary incontinence at 1 week, 1, 3, 6 and 12 months after transurethral enucleation with bipolar, respectively. The mean (±standard error) age was 69.6 ± 0.26 years, estimated prostate volume was 54.7 ± 0.91 cm3 , operative time was 58.0 ± 1.1 min and the prostate specimen weight was 30.6 ± 0.69 g. On univariate analysis, age, prostate volume estimated by transrectal ultrasonography, prostate-specific antigen, prostate specimen weight, operative time, prostate specimen weight/prostate volume and prostate specimen weight/operative time were significant predictive factors for transient urinary incontinence after transurethral enucleation with bipolar. On multivariate analysis, age (hazard ratio 1.07, P-value = 0.0034) and prostate volume (hazard ratio 1.03, P-value < 0.0001) were independent risk factors for transient urinary incontinence after transurethral enucleation with bipolar. Age and prostate volume estimated by transrectal ultrasonography seem to represent significant independent risk factors for transient urinary incontinence after transurethral enucleation with bipolar. This should be well discussed with the patient before surgery.


A challenging diagnosis: Lesson from case series of sacral Ewing sarcoma.
Ewing's sarcoma is an aggressive bone and the surrounding soft tissue cancer primarily found in children and young adults. It is mostly observed in the trunk and long bones while unusually seen in the sacrum. Sacral Ewing sarcoma has a unique anatomic limitation due to neurological structures, vertebral column, and pelvic involvement. Hence, identifying sacral Ewing's sarcoma remains a challenge. This is a case series including three patients diagnosed with Sacral Ewing's sarcoma. These three cases have been diagnosed based on clinical and radiographic examination, MRI, histopathology, and immunohistochemistry examination. Sacral Ewing's sarcoma remains a challenge to diagnose due to its unique anatomy site. MRI examination is sensitive to detect lesions but nonspecific. Thus, require histopathological confirmation. Early diagnosis of Ewing's sarcoma is essential and we need to perform further examinations, such as immunohistochemistry examination, to confirm the diagnosis of Ewing's sarcoma.


Facial lymph node involvement as a prognostic factor for patient survival in oral cavity squamous cell carcinoma.
To investigate the incidence of metastasis to facial lymph nodes (FLNs) and to determine its impact on the prognosis and survival of patients at onset of oral cavity squamous cell carcinoma (OSCC). A retrospective review of 641 patients with OSCC treated with curative surgery (CS) alone or CS + postoperative radiotherapy (PORT) was performed. Based on FLN status, an analysis of clinicopathologic parameters, prognosis, and survival was conducted. By classifying patients according to FLN status, a reasonable treatment modality was identified in the low-risk group, which was defined as those who had N0-1 disease, negative margin, and no extracapsular nodal spread (ENS). FLN involvement was identified in 103 patients (16 %), which showed statistically significant associations with several established risk factors and negatively affected local controls (P < 0.001), neck controls (P < 0.001), and disease-specific survival (P < 0.001). Compared to CS alone, CS + PORT increased the 5-year neck control rate (76.8 vs. 30.7 %, P = 0.006) and disease-specific survival rate (67.8 vs. 30.7 %, P = 0.037) of the OSCC patients with FLN metastasis in the low-risk group. Metastasis to FLNs is strongly associated with poor disease control and lower survival rate of OSCC patients. PORT minimized the residual risk of involved FLN in the low-risk group.


Discernibility of the Interdigitation Zone (IZ), a Potential Optical Coherence Tomography (OCT) Biomarker for Visual Dysfunction in Aging.
Photoreceptor (PR) outer segments, retinal pigment epithelium apical processes, and inter-PR matrix contribute to the interdigitation zone (IZ) of optical coherence tomography (OCT). We hypothesize that this interface degrades over adulthood, in concert with a delay of rod mediated dark adaptation (RMDA). To explore this idea, we determined IZ discernibility and RMDA in younger and older adults. For this cross-sectional study, eyes of 20 young (20-30 years) and 40 older (≥60 years) participants with normal maculas according to the AREDS 9-step grading system underwent OCT imaging and RMDA testing at 5° superior to the fovea. Custom FIJI plugins enabled analysis for IZ discernibility at 9 eccentricities in 0.5 mm steps on one single horizontal B-scan through the fovea. Locations with discernible IZ met two criteria: visibility on B-scans and a distinct peak on a longitudinal reflectivity profile. The frequency of sites meeting both criteria was compared between both age groups and correlated with rod intercept time (RIT). The median number of locations with discernible IZ was significantly higher (foveal, 4 vs. 0, p = 0.0099; extra-foveal 6 vs. 0, p < 0.001) in eyes of young (26 ± 3 years) compared to older (73 ± 5 years) participants. For the combined young and older sample, the higher frequency of discernible IZ was correlated with shorter RIT (faster dark adaptation) (rs = -0.56, p < 0.0001). This association was significant within young eyes (rs = -0.54; p = 0.0134) and not within older eyes (rs = -0.29, p = 0.706). Results suggest that the interface between outer segments and apical processes degrades in normal aging, potentially contributing to delayed rod-mediated dark adaptation. More research is needed to verify an age-related association between IZ discernibility and rod-mediated dark adaptation. If confirmed in a large sample, IZ discernibility might prove to be a valuable biomarker and predictor for visual function in aging.


Variations in the central corneal thickness during the menstrual cycle in Indian women.
To determine the changes in central corneal thickness (CCT) during the menstrual cycle in Indian women. A prospective observational clinical study at a tertiary care center between December 2015 and December 2018. One hundred and twenty sixty women between 18 and 45 years were included. The CCT was measured using an ultrasound pachymeter at three specific timelines of the menstrual cycle: at the beginning (1st to 3rd day), during ovulation time (14th to 16th day), and at the end of the cycle (28th to 33rd day). Phases of the cycle were confirmed by the urine luteinizing hormone level. The mean CCT of both eyes was 541.76 ± 4.21 μm, 559.21 ± 4.50 μm, and 544.52 ± 8.06 μm at the beginning, mid, and end of cycle, respectively. The mean CCT of the right eye was 541.68 ± 4.15 μm, 559.08 ± 4.50 μm, and 544.44 ± 8.06 μm and of the left eye was 541.84 ± 4.27 μm, 559.35 ± 4.50 μm, and 544.61 ± 8.06 μm at the beginning, mid, and end of cycle, respectively. The CCT value was significantly (P < 0.001) higher during ovulation compared to the beginning and end of the menstrual cycle. Our study recommends adding menstrual history in the workup of women undergoing refractive surgery as physiological variations in the CCT may result in unexpected surgical outcomes.


Towards a definition of Ancient Rare Diseases (ARD): Presenting a complex case of probable Legg-Calvé-Perthes Disease from the North Caucasian Bronze Age (2200-1650 cal BCE).
This study discusses the challenges and possibilities of establishing a definition for Ancient Rare Diseases (ARD) in a probable case of Legg-Calvé-Perthes Disease (LCPD) from the Bronze Age cemetery Kudachurt 14, situated in the Northern Caucasus. We investigated the skeletal remains of a male aged 35-45 years at death. For comparison we examined other males buried at Kudachurt 14 (n = 24) and reviewed 22 LCPD cases from the paleopathological literature. We use macroscopic as well as osteometric examination methods and imaging techniques. The morphology of the left hip joint corresponds to skeletal characteristics for LCPD. Co-occurring osteochondrosis dissecans, femoral anteversion, and atrophy of the left femoral shaft suggest a complex disease course. Modern criteria of rare diseases applied on ancient skeletal remains are either non-transferable or require completion. We conclude that rarity is dynamic, etiological uncertainty has to be accepted, and the respective socioeconomic context is crucial. Degree of disability and level of sociomedical investment are not defining criteria for ARD. Dating 2200-1650 cal BCE, this study currently presents the earliest case of probable LCPD. This is the first attempt to transform modern characteristics of rare diseases for establishing a paleopathological concept of ARD. As this study is limited to LCPD, our conclusions are not directly applicable to other ARD in question. More focused paleopathological research on skeletal populations from different cultures and time periods is needed, enabling an evolutionary perspective on the comparability of ancient, modern and future rare diseases.


Ice-Inspired Superlubricated Electrospun Nanofibrous Membrane for Preventing Tissue Adhesion.
Inspired by the superlubricated surface (SLS) of ice, which consists of an ultrathin and contiguous layer of surface-bound water, we built a SLS on the polycaprolactone (PCL)/poly(2-methacryloxyethylphosphorylcholine) (PMPC) composite nanofibrous membrane via electrospinning under controlled relative humidity (RH). The zwitterionic PMPC on the nanofiber provided a surface layer of bound water, thus generating a hydration lubrication surface. Prepared under 20% RH, electrospun PCL/PMPC nanofibers reached a minimum coefficient of friction (COF) of about 0.12 when the weight ratio of PMPC to PCL was 0.1. At a higher RH, a SLS with an ultralow COF of less than 0.05 was formed on the composite nanofibers. The high stability of the SLS hydration layer on the engineered nanofibrous membrane effectively inhibited fibroblast adhesion and markedly reduced tissue adhesion during tendon repair in vivo. This work demonstrates the great potential of this ice-inspired SLS approach in tissue adhesion-prevention applications.


Protocol for the MobiMD trial: A randomized controlled trial to evaluate the effect of a self-monitoring mobile app on hospital readmissions for complex surgical patients.
Hospital readmissions are estimated to cost $17.4 billion per year in the Medicare population alone, with readmission rates as high as 30% for patients undergoing complex abdominal surgery. Improved transitional care and self-monitoring may reduce preventable readmissions for such high-risk populations. In this study, we will conduct a single-institution randomized controlled trial (RCT) to assess the effect of a novel transitional care mobile app, MobiMD, on hospital readmission in complex abdominal surgery patients. Three hundred patients will be randomized 1:1 to standard of care (SOC) versus SOC plus MobiMD app in a parallel, single-blinded, two-arm RCT. Eligible patients are those who undergo complex abdominal surgery in the division of Surgical Oncology, Colorectal Surgery or Transplant Surgery. The MobiMD app provides push notification reminders directly to the patient's smart device, prompting them to enter clinical data and patient-reported outcomes. Clinical data collected via the MobiMD app include vital signs, red flag symptoms, daily wound and surgical drain images, ostomy output, drain output, medication compliance, and wound care compliance. These data are reviewed daily by a physician. The primary outcome is the proportion of participants readmitted to the hospital within 30 days of surgery. Secondary outcomes are 90-day hospital readmission, emergency department and urgent care visits, complication severity, and total readmission cost. If effective, mobile health apps such as MobiMD could be routinely integrated into surgical transitional care programs to minimize unnecessary hospital readmissions, emergency department visits and healthcare resource utilization. Clinical trials identifier: NCT04540315.


The green and blue crop water requirement WATNEEDS model and its global gridded outputs.
Accurately assessing green and blue water requirements from croplands is fundamental to promote sustainable water management. In the last decade, global hydrological models have provided important insights into global patterns of water requirements for crop production. As important as these models are, they do not provide monthly crop-specific and year-specific data of green and blue water requirements. Gridded crop-specific products are therefore needed to better understand the spatial and temporal evolution of water demand. Here, we present a global gridded database of monthly crop-specific green (rain-fed) and blue (irrigated) water requirements for 23 main crops and 3 crop groups obtained using our WATNEEDS model. For the time periods in which our dataset matched, these estimates are validated against existing global products and satellite based datasets of evapotranspiration. The data are publicly available and can be used by practitioners in the water-energy-food nexus to assess the water sustainability of our food and energy systems at multiple spatial (local to global) and temporal (seasonal to multi-year) scales.


Biochemical monitoring of the treatment in paediatric patients with mitochondrial disease.
Treatment strategies in mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. In this study we evaluated the monitoring of tocopherol, carnitine and ubiquinone concentrations in a group of paediatric patients during a follow-up period of 18 months and the response to treatment of these patients by means of the determination of blood lactate, plasma alanine and oxygen consumption by lymphocytes in relation to the clinical status of the patients. Tocopherol, carnitine and ubiquinone concentrations were easily corrected with therapy. Blood lactate proved the best biochemical tool to assess the response to treatment in paediatric patients. According to our results, improvement or stabilization of the clinical course seems to be more related to the biochemical or molecular defect than to the effectiveness of the treatment.


Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation.
Gene fusions and point mutations of RET kinase are crucial for driving thoracic cancers, including thyroid cancer and non-small cell lung cancer. Various scaffolds based on different heterocycles have been synthesized and evaluated as RET inhibitors. In this work, we investigate pyrrolo[2,3-d]pyrimidine derivatives for inhibition of RET-wt, drug resistant mutant RET V804M and RET gene fusion driven cell lines. Several compounds were synthesized and the structure activity relationship was extensively studied to optimize the scaffold. Thieno[2,3-d]pyrimidine, a bioisostere of pyrrolo[2,3-d]pyrimidine, was also explored for the effect on RET inhibition. We identified a lead compound, 59, which shows low nanomolar potency against RET-wt and RET V804M. Further 59 shows growth inhibition of LC-2/ad cells which RET-CCDC6 driven. We also determined that 59 is a type 2 inhibitor of RET and demonstrated its ability to inhibit migration of tumor cells. Based on computational studies, we proposed a binding pose of 59 in RET pocket and have quantified the contributions of individual residues for its binding. Together, 59 is an important lead compound which needs further evaluation in biological studies.


Genome-wide identification and evolutionary analyses of the PP2C gene family with their expression profiling in response to multiple stresses in Brachypodium distachyon.
The type-2C protein phosphatases (PP2Cs), negatively regulating ABA responses and MAPK cascade pathways, play important roles in stress signal transduction in plants. Brachypodium distachyon is a new model plant for exploring the functional genomics of temperate grasses, cereals and biofuel crops. To date, genome-wide identification and analysis of the PP2C gene family in B. distachyon have not been investigated. In this study, 86 PP2C genes in B. distachyon were identified. Domain-based analyses of PP2C proteins showed that they all contained the phosphatase domains featured as 11 conserved signature motifs. Although not all phosphatase domains of BdPP2C members included all 11 motifs, tertiary structure analysis showed that four residues contributing to magnesium/manganese ions (Mg(2+)/Mn(2+)) coordination were conserved, except for two noncanonical members. The analysis of their chromosomal localizations showed that most of the BdPP2C genes were located within the low CpG density region. Phylogenetic tree and synteny blocks analyses among B. distachyon, Arabidopsis thaliana and Oryza sativa revealed that all PP2C members from the three species can be phylogenetically categorized into 13 subgroups (A-M) and BdPP2Cs were evolutionarily more closely related to OsPP2Cs than to AtPP2Cs. Segmental duplications contributed particularly to the expansion of the BdPP2C gene family and all duplicated BdPP2Cs evolved mainly from purifying selection. Real-time quantitative reverse transcription PCR (qRT-PCR) analysis showed that BdPP2Cs were broadly expressed in disparate tissues. We also found that almost all members displayed up-regulation in response to abiotic stresses such as cold, heat, PEG and NaCl treatments, but down-regulation to biotic stresses such as Ph14, Guy11 and F0968 infection. In the present study, a comprehensive analysis of genome-wide identification and characterization of protein domains, phylogenetic relationship, gene and protein structure, chromosome location and expression pattern of the PP2C gene family was carried out for the first time in a new model monocot, i.e., B. distachyon. Our results provide a reference for genome-wide identification of the PP2C gene family of other species and also provide a foundation for future functional research on PP2C genes in B. distachyon.


Open Reduction of Closed Pediatric Tibial Shaft Fractures Treated With Intramedullary Stabilization Does Not Increase Risk of Postoperative Complications.
To compare union and complication rates in pediatric patients presenting with tibial shaft fractures treated with closed or open reduction before intramedullary stabilization. Retrospective review. Multiple pediatric trauma centers. Pediatric patients presenting with tibial shaft fractures treated with intramedullary stabilization. Intramedullary stabilization after closed or open reduction (percutaneous and open approach). Union rates, infection rate (superficial and deep), and unplanned return to the operating room (OR). One hundred sixty-six patients were included in this study. One hundred thirty-six patients presented with closed fractures, and 30 patients presented with open tibial shaft fractures. Thirty-seven of the 136 patients (27%) with closed fractures had their fracture specifically opened during surgical fixation. There was no statistical difference in radiographic union at 6 months between fractures electively opened and those treated with closed reduction alone 97% versus 98% (P = 0.9). No patient who underwent an open reduction developed infections or wound-healing concerns, whereas 2 of the 99 (2%) patients treated closed had superficial surgical site infections requiring additional treatment (P = 0.999). There was no difference in unplanned return to OR between those who underwent open reduction at the time of intramedullary stabilization (P = 0.568). Performing an open reduction in a closed pediatric tibial shaft fracture before intramedullary fixation does not increase the risk of surgical site infections or wound issues, delayed union, or unplanned return to the OR. An open reduction of a closed tibial shaft fracture for purposes of improving a reduction before intramedullary stabilization may be a safe and effective clinical practice. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Halothane and temperature interact to increase succinylcholine-induced jaw contracture in the rat.
The agonist actions of succinylcholine (SCh) have recently come under study because of their involvement in the clinical problem of masseter muscle rigidity, and their possible involvement in malignant hyperthermia. The authors investigated factors affecting SCh-induced contractures in an animal preparation. Rats were anesthetized with either halothane (1-2%) or pentobarbital. Resting and twitch isometric tension were measured from the jaw muscles. Succinylcholine (500 or 750 micrograms/kg) was administered intravenously, producing increases in resting tension (i.e., contractures). Jaw muscle temperature was controlled by radiant heat. Succinylcholine increased jaw muscle tension for several seconds. These contractures exhibited tachyphylaxis, and were antagonized by vecuronium (0.8-1.5 mg/kg), indicating mediation by acetylcholine receptors (AChR). In the presence of 2% halothane, contractures were tenfold greater at a rectal temperature of 41 degrees C than at 37 degrees C. In contrast, under 50 mg/kg intraperitoneal pentobarbital anesthesia, contractures were not affected by rectal temperature. Neither the half-decay time of contracture nor twitch tension (0.2 Hz, preceding SCh) were increased in the presence of halothane at 41 degrees C. In a set of experiments in which rectal temperature was maintained at 37 degrees C but jaw temperature was varied between 36-41 degrees C, there was a significant regression of SCh-induced jaw contracture on temperature in the presence of halothane. In contrast, there was no significant relationship between jaw temperature and contracture in the presence of pentobarbital. These results in the rat demonstrate a temperature-dependent interaction between halothane and SCh that has not previously been described.


Fundus autofluorescence imaging using red excitation light.
Retinal disease accounts significantly for visual impairment and blindness. An important role in the pathophysiology of retinal disease and aging is attributed to lipofuscin, a complex of fluorescent metabolites. Fundus autofluorescence (AF) imaging allows non-invasive mapping of lipofuscin and is a key technology to diagnose and monitor retinal disease. However, currently used short-wavelength (SW) excitation light has several limitations, including glare and discomfort during image acquisition, reduced image quality in case of lens opacities, limited visualization of the central retina, and potential retinal light toxicity. Here, we establish a novel imaging modality which uses red excitation light (R-AF) and overcomes these drawbacks. R-AF images are high-quality, high-contrast fundus images and image interpretation may build on clinical experience due to similar appearance of pathology as on SW-AF images. Additionally, R-AF images may uncover disease features that previously remained undetected. The R-AF signal increases with higher abundance of lipofuscin and does not depend on photopigment bleaching or on the amount of macular pigment. Improved patient comfort, limited effect of cataract on image quality, and lack of safety concerns qualify R-AF for routine clinical monitoring, e.g. for patients with age-related macular degeneration, Stargardt disease, or for quantitative analysis of AF signal intensity.


Phase II assessment of recombinant leukocyte A interferon with difluoromethylornithine in disseminated malignant melanoma.
Sixteen patients with advanced melanoma received IFN-alpha 2A, 36 X 10(6) U/m2 i.m., on days 3-7 with 2.25 g/m2 DFMO p.o. on days 1-7. We observed no objective regressions. Median time to progression was 1.2 months with a median survival of 5.2 months. A flu-type syndrome was the predominant sequela. From the dose and schedule that we utilized, this regimen holds little promise against disseminated malignant melanoma.


Simultaneous production of 2,3-butanediol, ethanol and hydrogen with a Klebsiella sp. strain isolated from sewage sludge.
A Klebsiella sp. HE1 strain isolated from hydrogen-producing sewage sludge was examined for its ability to produce H2 and other valuable soluble metabolites (e.g., ethanol and 2,3-butanediol) from sucrose-based medium. The effect of pH and carbon substrate concentration on the production of soluble and gaseous products was investigated. The major soluble metabolite produced from Klebsiella sp. HE1 was 2,3-butanediol, accounting for over 42-58% of soluble microbial products (SMP) and its production efficiency enhanced after increasing the initial culture pH to 7.3 (without pH control). The HE1 strain also produced ethanol (contributing to 29-42% of total SMP) and a small amount of lactic acid and acetic acid. The gaseous products consisted of H2 (25-36%) and CO2 (64-75%). The optimal cumulative hydrogen production (2.7 l) and hydrogen yield (0.92mol H2 mol sucrose(-1)) were obtained at an initial sucrose concentration of 30g CODl(-1) (i.e., 26.7gl(-1)), which also led to the highest production rate for H2 (3.26mmol h(-1)l(-1)), ethanol (6.75mmol h(-1)l(-1)) and 2,3-butanediol (7.14mmol h(-1)l(-1)). The highest yield for H2, ethanol and 2,3-butanediol was 0.92, 0.81 and 0.59molmol-sucrose(-1), respectively. As for the overall energy production performance, the highest energy generation rate was 27.7kJ h(-1)l(-1) and the best energy yield was 2.45kJmolsucrose(-1), which was obtained at a sucrose concentration of 30 and 20g CODl(-1), respectively.


C-Type Natriuretic Peptide in Essential Hypertension: Old Ways for a New Time.
Multiple mechanisms are involved in essential hypertension. Antihypertensive drugs mainly target increased activity of the sympathetic nervous system, altered production of vasoactive mediators, vascular inflammation, fibrosis, and increased peripheral resistance. C-type natriuretic peptide (CNP) is an endothelium-derived peptide that exerts vascular signaling through two receptors: natriuretic peptide receptor-B (NPR-B) and natriuretic peptide receptor-C (NPR-C). This perspective recapitulates the effects of CNP on the vasculature in relation to essential hypertension. Notably, the risk of hypotension when used as therapy is minimal for the CNP system as compared to its related natriuretic peptides, atrial natriuretic peptide, and B-type natriuretic peptide. As modified CNP is currently being introduced as therapy in congenital growth disorders, we propose that targeting the CNP system either by administering exogenous CNP or altering the endogenous concentrations via inhibition of its degradation may represent an important tool in the pharmacological armory for managing long-term essential hypertension.


Blockade of the BLT1-LTB4 axis does not affect mast cell migration towards advanced atherosclerotic lesions in LDLr-/- mice.
Mast cells have been associated with the progression and destabilization of advanced atherosclerotic plaques. Reducing intraplaque mast cell accumulation upon atherosclerosis progression could be a potent therapeutic strategy to limit plaque destabilization. Leukotriene B4 (LTB4) has been reported to induce mast cell chemotaxis in vitro. Here, we examined whether antagonism of the LTB4-receptor BLT1 could inhibit mast cell accumulation in advanced atherosclerosis. Expression of genes involved in LTB4 biosynthesis was determined by single-cell RNA sequencing of human atherosclerotic plaques. Subsequently, Western-type diet fed LDLr-/- mice with pre-existing atherosclerosis were treated with the BLT1-antagonist CP105,696 or vehicle control three times per week by oral gavage. In the spleen, a significant reduction in CD11b+ myeloid cells was observed, including Ly6Clo and Ly6Chi monocytes as well as dendritic cells. However, atherosclerotic plaque size, collagen and macrophage content in the aortic root remained unaltered upon treatment. Finally, BLT1 antagonism did not affect mast cell numbers in the aortic root. Here, we show that human intraplaque leukocytes may be a source of locally produced LTB4. However, BLT1-antagonism during atherosclerosis progression does not affect either local mast cell accumulation or plaque size, suggesting that other mechanisms participate in mast cell accumulation during atherosclerosis progression.


Association between social support and mutual-support needs among the rural adults in China: a cross-sectional study.
In rural China, there is now a huge gap between the supply and demand for old-age care. To close the gap, developing rural mutual old-age services is extremely important. The purpose of this study is to clarify the relationship among social support, mutual support need, and mutual support willingness. We conducted an online questionnaire survey using a Chinese Internet research company; 2,102 valid responses were received. The measures comprised the Social Support Rating Scale, the Mutual Support Willingness Questionnaire, and the Mutual Support Needs Scale. We calculated Pearson correlations to explore the association of social support with mutual-support need and mutual-support-need willingness. Multivariate analyses were also conducted using these factors as dependent variables. The total score for the mutual support need for the adults in rural areas was 58.0 ± 12.1 and 36.96 ± 6.40 for social support, approximately 86.8% of the participants were willing to participate in mutual support. Furthermore, mutual support needs were positively correlated with subjective support (p < 0.01) and support utilization (p < 0.01), but negatively correlated with willingness to support each other (p < 0.05). The need for mutual support was also associated with age, sex, education level, dissatisfaction with the current economic situation, health status, and so on. It is necessary for government and health care providers to assess the different needs of rural older people and encourage individuals and organizations to provide mutual support for older people, especially to enhance emotional care for older people and improve their use of support. This is of great significance for developing mutual support services in rural China.


Daily life blood pressure changes are steeper in hypertensive than in normotensive subjects.
Target organ damage in hypertensive patients is related to their increased average blood pressure and greater 24-hour blood pressure variability. Whether the rate of blood pressure changes is also greater in hypertension, producing a greater stress on arterial walls, is not known, however. Our study aimed at addressing this issue by computer analysis of 24-hour ambulatory intra-arterial blood pressure recordings in 34 subjects (29 males), 13 normotensive subjects and 21 uncomplicated hypertensive subjects (mean age+/-SD, 40.4+/-11.8 years). The number, slope (mm Hg/s), and length (beats) of systolic blood pressure ramps of 3 or more consecutive beats characterized by a progressive increase (+) or reduction (-) in systolic blood pressure of at least 1 mm Hg per beat were computed for each hour and for the whole 24-hour period. Twenty-four-hour average systolic blood pressure was 112.9+/-2.1 and 159.4+/-5.7 mm Hg in normotensive and hypertensive subjects, respectively. Over the 24 hours, the number and length of systolic blood pressure ramps were similar in both groups, whereas the slope was markedly different (24-hour mean+/-SE slope, 4.80+/-0.30 in normotensives and 6.50+/-0.40 mm Hg/s in hypertensives, P<0.05). Ramp slope was not influenced by age or reflex pulse interval changes, but it was greater for higher ramp initial systolic blood pressure values. Thus, in daily life, hypertensive subjects are characterized by steeper blood pressure changes than normotensives, and this, regardless of the mechanisms, may have clinical implications, because it may be associated with greater traumatic effect on the vessel walls of hypertensive patients.


Facial swelling: an atypical presentation of cutaneous lymphoma.
Cutaneous lymphomas (primary and secondary lymphomas involving the skin) are a heterogeneous group with various clinical manifestations, histological features, and prognoses. We describe eight cases of cutaneous lymphoma presenting with facial swelling. Our case series included three cases of primary cutaneous extranodal natural killer/T-cell lymphoma, one case of secondary cutaneous extranodal natural killer/T-cell lymphoma, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of cutaneous CD4+ small/medium pleomorphic T-cell lymphoma, and two cases of peripheral T-cell lymphoma (unspecified). This collection of cases and literature review emphasizes the need for clinical suspicion of cutaneous lymphoma in the differential diagnosis of patients with refractory facial swelling.


An elegant route to overcome fundamentally-limited light extraction in AlGaN deep-ultraviolet light-emitting diodes: Preferential outcoupling of strong in-plane emission.
While there is an urgent need for semiconductor-based efficient deep ultraviolet (DUV) sources, the efficiency of AlGaN DUV light-emitting diodes (LEDs) remains very low because the extraction of DUV photons is significantly limited by intrinsic material properties of AlGaN. Here, we present an elegant approach based on a DUV LED having multiple mesa stripes whose inclined sidewalls are covered by a MgF2/Al omni-directional mirror to take advantage of the strongly anisotropic transverse-magnetic polarized emission pattern of AlGaN quantum wells. The sidewall-emission-enhanced DUV LED breaks through the fundamental limitations caused by the intrinsic properties of AlGaN, thus shows a remarkable improvement in light extraction as well as operating voltage. Furthermore, an analytic model is developed to understand and precisely estimate the extraction of DUV photons from AlGaN DUV LEDs, and hence to provide promising routes for maximizing the power conversion efficiency.


In-vivo effects of ivermectin on Rhipicephalus appendiculatus: the influence of tick feeding patterns and drug pharmacokinetics.
Sublethal effects seen amongst Rhipicephalus appendiculatus feeding on ivermectin-treated rabbits were diverse and dependent both on drug dose, pharmacokinetics and tick feeding patterns: changes in drug formulation, the time of infestation relative to treatment, and the tick instar used, profoundly influenced acaricidal activity. Death was a sequel to paralysis only if tick feeding was interrupted for sufficient time to produce irreversible dehydration. Concurrent pharmacokinetic investigations revealed that, for the larvae of R. appendiculatus, the mean critical lethal dose of ivermectin imbibed over a 5-day engorgement period was 3500 micrograms/kg. This quantity of ivermectin was achieved in the blood-meals of larvae feeding on rabbits treated subcutaneously with a single dose of Ivomec injection (MSD)* greater than or equal to 800 micrograms/kg, provided infestation took place within 24 h of treatment. At lower drug doses, or if larval infestations were delayed for greater than 24 h post-treatment, the quantity of circulating ivermectin (and thus imbibed by the tick larvae) fell below 3500 micrograms/kg and an increasing percentage of larvae successfully engorged and detached. More than 90% of such larvae moulted to the nymphal stage. Nymphae and larvae exhibited similar susceptibility to ivermectin on treated rabbits which could be explained by similar feeding patterns. However, adult female and male ticks were markedly less susceptible and interpretation of ivermectin-induced effects was more complex.


Mechanism of silver staining of histones: evidence for involvement of clustered lysine residues.
Pretreatment of histones with formaldehyde markedly enhances the formation of metalic silver from ammoniacal silver ion. The rate of silver reduction was determined with different histones by spectrophotometric measurement of colloidal silver stabilized in solution, and the apparent reactivity thus determined was found to be in the decreasing order of H1 greater than H2B greater than H2A greater than H3 greater than H4. Involvement of lysine residues was suggested since this order coincides with that of lysine content of these histones. However, the exceptionally high reactivity of histone H1 can be explained only when greater contribution of clustered lysine residues is assumed. Amino group modification and tryptic digestion studies of H1 corroborated this assumption.


The purine nucleotide cycle. Studies of ammonia production by skeletal muscle in situ and in perfused preparations.
Ammonia production by hind limbs of rat was studied in perfused preparations during rest, exercise, and hypoxia, and while the perfusate contained epinephrine or cyanide. Ammonia production by hind limbs was also studied in situ during rest and exercise. Strong correlations were observed between ammonia, IMP, and lactate formation. Adenylosuccinate was not present in detectable amounts in resting muscle (less than 1 nmol/g dry weight) but it appeared and rose sharply in exercising muscle, and then declined during recovery. The maximum found was about 18 nmol/g dry weight. When IMP accumulation exceeded 2.8 mumol/g dry weight, the formation of adenylosuccinate diminished, presumably because of an inhibition of adenylosuccinate synthetase by excess substrate. Exercise resulted in a greatly increased output of ammonia and a decreased output of alanine and glutamine. The tissue contents of aspartate and glutamate were decreased, while that of alanine was increased. The content of malate increased 3-fold during exercise. Epinephrine, hypoxia, and cyanide each caused an increased output of ammonia at the expense of the amino acid content of the tissue. These results provide evidence for the operation of the purine nucleotide cycle in skeletal muscle under various conditions that are associated with an increased rate of glycolysis.


Deoxynivalenol in commercial beer - screening for the toxin with an indirect competitive ELISA.
Antibodies specific for deoxynivalenol (DON) were prepared by immunizing rabbits with a deoxynivalenol-hemiglutaryl-HSA conjugate. The antibody showed cross-reactivity with DON, 15a-acetyl-DON (15-Ac DON), and 3a-acotyl-DON (3-Ac DON) of 100%, 216%, and 260%, respectively. No cross-reactivity was observed against 20 further trichothecenes of the A-, B-, and C-type. An indirect competitive ELISA procedure was set up for the detection of DON in liquid matrices occurring in the brewing process, Including beer. ELISA was sensitive down to 3.8 ng/mL. Detection limit for DON in tenfold diluted beer was 50 ppb. Recovery of the toxin in spiked beer was 45%, 77%, and 83% at toxin levels of 50; 500; and 1,000 ppb, respectively. ELISA results corresponded quite well with HPLC data. 196 commercial beers from several German breweries, including 36 gushing-positive samples, were assayed for DON. Screening revealed toxin levels from not detectable to 569 ppb. 69% of the gushing beers had marked levels of DON. 37% of the gushing-negative beer samples contained DON in detectable amounts with a maximum content of 172 ppb. Wheat beers had significantly higher DON-contents than beers derived from barley. Concentration of the toxin was significantly higher in gushing beers than in nongushing beers from both cereal sources.


Field assessment of Bt cry1Ah corn pollen on the survival, development and behavior of Apis mellifera ligustica.
Honeybees may be exposed to insecticidal proteins from transgenic plants via pollen. An assessment of the impact of such exposures on the honeybee is an essential part of the risk assessment process for transgenic Bacillus thuringiensis corn. A field trial was conducted to evaluate the effect of transgenic Bt cry1Ah corn on the honeybee Apis mellifera ligustica. Colonies of honeybees were moved to Bt or non-Bt corn fields during anthesis and then sampled to record their survival, development and behavior. No differences in immature stages, worker survival, bee body weight, hypopharyngeal gland weight, colony performance, foraging activity or olfactory learning abilities were detected between colonies that were placed in non-Bt corn fields and those placed in Bt corn fields. We conclude that cry1Ah corn carries no risk for the survival, development, colony performance or behavior of the honeybee A. mellifera ligustica.


Should minimal residual disease monitoring in acute lymphoblastic leukemia be standard of care?
In acute lymphoblastic leukemia (ALL), the advent of methods to measure disease not detectable by morphology, ie, minimal residual disease (MRD), has set a new standard to define remission. The clinical importance of MRD has been demonstrated by numerous studies using either flow cytometry or polymerase chain reaction and involving thousands of patients. Results are in remarkable agreement on the association between MRD persistence and risk of subsequent relapse, regardless of the MRD detection method used. More recent data indicate that MRD can also be informative in specific subgroups of ALL patients, such as infants or those with T-lineage ALL. Hence, MRD is now being used in clinical trials to inform treatment decisions and guide patients' clinical management. This article reviews MRD methodologies and clinical applications with emphasis on recently reported technical advances and prognostic associations, and the practical issues related to the implementation of MRD monitoring in the clinic.


Analytical modeling of contaminant transport along sloping coastal beaches in presence of tidal waves and exponential rainfall infiltration.
Coastal beaches are the most important part of the marine environment and are highly influenced by the interactions taking place between groundwater and surface water of any form. Generally, the purity index of the groundwater is based on the concentration of Total Dissolved Solids (TDS) in it. Analytical solutions are the best tools for groundwater flow and transport modeling. However, contaminant transport along the sloping coastal beaches with complex boundaries cannot be addressed with available analytical solutions. In the present study, new analytical models are developed for groundwater flow and contaminant transport for sloping coastal beaches with continuity and tidal boundary conditions. To assess the performance of the new analytical solution and to validate the range of aquifer parameters, numerical simulation is performed using Du-Fort Frankel (DFF) Scheme. Numerical experimentation is carried out using the Tchebycheff and L2 norms. It is observed that the new analytical solution for the contaminant transport gives acceptable results over the wide range of the aquifer parameters. To show the effectiveness of the developed models, two case studies from Indian coastal aquifers namely, Kalpakkam, Tamil Nadu, and Bhavnagar, Gujarat are considered. The profiles of the contaminant concentration are obtained to study the TDS behavior along these complex coastal beaches in the spatiotemporal directions. The results are compared with numerical model results and found to be satisfactory. The combined effect of the initial rainfall and rainfall decay constants showed a significant impact on the concentration of TDS. TDS concentrations are observed to be varying highly with the variation in the tidal constituents and bed slope.


Enrichment of cell populations in metaphase, anaphase, and telophase by synchronization using nocodazole and blebbistatin: a novel method suitable for examining dynamic changes in proteins during mitotic progression.
Mitosis is a continuous process to separate replicated chromosomes into two daughter cells through prophase, metaphase, anaphase, and telophase. Although a number of methods have been established to synchronize cells at different phases of the cell cycle, it is difficult to synchronize cells at the specific phases, anaphase and telophase, during mitosis because of the short duration of anaphase. Here, we show that HeLa S3 cells in anaphase and in telophase are successfully enriched by treatment with a combination of low concentrations of the microtubule-depolymerizing agent nocodazole and the myosin II inhibitor blebbistatin. After 9-h release from thymidine block at G1/S phase, addition of nocodazole at 20 ng/ml but not 40 ng/ml ensures rapid release from the nocodazole arrest. Subsequently, the cells are cultured in the presence of 50 μM blebbistatin for 20 and 50 min to enrich cells in anaphase and telophase, respectively. Western blot analysis verifies down-regulation of phospho-histone H3-Ser10, phospho-Aurora A/B/C, and cyclin B1 during M-phase progression. Furthermore, we show how the electrophoretic mobility shifts of the Src-family kinases c-Yes and c-Src can change in each phase of mitosis. These results provide a useful synchronization method for biochemically examining protein dynamics during M-phase progression.


Investigations of the molecular basis for the temperature-dependent insolubility of cryoglobulins. VI. Quenching by acrylamide of the intrinsic tryptophan fluorescence of cryoglobulin and non-cryoglobulin IgM proteins.
The acrylamide-quenching patterns of the intrinsic tryptophan fluorescence of six cold-soluble monoclonal immunoglobulin M (IgM) and two monoclonal IgM proteins possessing cryoglobulin properties (abnormal cold insolubility) have been compared. Static and dynamic components of quenching have been resolved by a modified form of the Stern-Volmer relationship. The unusual observation of static quenching seen with the multitryptophan containing IgM is determined to be a consequence of essentially homogeneous indole fluorescence arising from conserved tryptophan residues within each homologous immunoglobulin domain. Although the static component of the quenching of the two IgM cryoimmunoglobulins examined is similar to that of the non-cryoimmunoglobulin, IgM, some of the cryoglobulin's tryptophan residues appear to be more kinetically exposed to acrylamide than the tryptophans in the non-cryoglobulin IgM. An unusually large negative entropy of activation observed for the quenching process of both cryoimmunoglobulins suggests some abnormality in the dynamic (flexibility) properties of these proteins.


Repair replication and sister chromatid exchanges as indicators of excisable and nonexcisable damage in human (xeroderma pigmentosum) cells.
Alkylating agents cause damage to DNA which can be repaired by exicsion repair (repair replication) and which induces sister chromatid exhcanges (SCEs). During early times after exposure (within 5 hr) normal and xeroderma pigmentosum (XP) cells perform similar amounts of repair replication. At later times (after 20 hr) normal cells have completed repair replication but XP cells continue at a lower rate. This slowly repaired component of alkylation damage appears to be related to the higher frequencies of SCEs induced by alkylating agents in XP cells compared to normal cells. Therefore, whereas repair replication is an indicator of exicsed damage, SCEs may be indicators of unexcised damage and may show better correlations with the potentially mutagenic and carcinogenic effects of exposure to enbironmental agents.


Quantum catalysis in enzymes: beyond the transition state theory paradigm. A Discussion Meeting held at the Royal Society on 14 and 15 November 2005.
How do enzymes work? What is the physical basis of the phenomenal rate enhancements achieved by enzymes? Do we have a theoretical framework that accounts for observed catalytic rates? These are the foremost questions-with particular emphasis on tunnelling phenomena-debated at this Discussion Meeting by the leading practitioners in the field.


Gastrointestinal protective efficacy of Kolaviron (a bi-flavonoid from Garcinia kola) following a single administration of sodium arsenite in rats: Biochemical and histopathological studies.
Arsenic intoxication is known to produce symptoms including diarrhea and vomiting, which are indications of gastrointestinal dysfunction. We investigated whether Kolaviron (KV) administration protected against sodium arsenite (NaAsO2)-induced damage to gastric and intestinal epithelium in rats. Control rats (Group I) were given a daily oral dose of corn oil. Rats in other groups were given a single dose of NaAsO2 (100 mg/kg; intraperitoneal) alone (Group II) or after pretreatment for 7 days with KV at 100 mg/kg (Group III) and 200 mg/kg (Group IV). Rats were sacrificed afterward and portions of the stomach, small intestine and colon were processed for histopathological examination. Hydrogen peroxide, reduced glutathione, malondialdehyde (MDA) concentrations as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST) and myeloperoxidase (MPO) were measured in the remaining portions of the different gastrointestinal tract (GIT) segments. NaAsO2 caused significant increases (P < 0.05) in MDA levels and MPO activity, with significant reductions (P < 0.05) in GST, GPX, CAT and SOD activities in the stomach and intestines. KV significantly reversed the changes (P < 0.05) in a largely dose-dependent manner. The different segments had marked inflammatory cellular infiltration, with hyperplasia of the crypts, which occurred to much lesser degrees with KV administration. The present findings showed that KV might be a potent product for mitigating NaAsO2 toxicity in the GIT.


A case of acute ischemic duodenal ulcer associated with superior mesenteric artery dissection after transarterial chemoembolization for hepatocellular carcinoma.
We report a case of transarterial chemoembolization (TACE)-related acute ischemic duodenal ulcer that developed in association with dissection of the superior mesenteric artery. We conclude that the acute duodenal ulcer was developed by ischemia related to superior mesenteric artery dissection during TACE. TACE should be conducted carefully with continuous observation of abdominal arteries.