Artesunate possesses anti-leukemia properties that can be enhanced by arsenic trioxide.
Artesunate (ART), an effective and safe anti-malaria drug, also exhibits anticancer activity. We studied the effects of ART on proliferation and apoptosis of human K562 and U937 leukemia cell lines. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay demonstrated that ART inhibits cell growth in a dose- and time-dependent manner. Based on the findings obtained from light, fluorescence and transmission electron microscopy and propidium iodide staining, the effect of ART was shown to be mediated through apoptosis. In parallel, ART treatment increased Fas expression, while it decreased the c-Fos level in K562 cells. Furthermore, co-treatment with arsenic trioxide (ATO) significantly facilitated ART-induced K562 cell apoptosis. These findings demonstrated that ART had an antitumor activity against K562 and U937 leukemia cells, largely due to inhibition of proliferation and induction of apoptosis via the intrinsic pathway; and this tumoricidal function could be enhanced by ATO.


Long-term ultrasonographic and venographic study of the development of tarsal vein thrombosis in a cow.
The development of thrombosis of three tarsal veins in a cow was studied by repeated ultrasonographic and venographic examinations for nine months. The venous diameter, the echogenicity of the thrombi and the sequential venographic findings were evaluated. Initially, the thrombosed parts of the ramus cranialis and caudalis of the vena saphena lateralis and the ramus caudalis of the vena saphena medialis had greatly increased diameters and were not compressible. The thrombi appeared as poorly echogenic masses. Within five months, the diameters of the occluded veins had decreased to almost normal dimensions. The echogenicity of the thrombi diminished at their distal and proximal ends. The length of the thrombi was decreased by up to 6.5 cm. However, the thrombosed veins did not re-open. One year after diagnosis, the cow was culled and the persistence of the venous thromboses was confirmed.


[Scientific publication output of Spanish emergency physicians from 2005 to 2014: a comparative study].
To analyze the research output of Spanish emergency physicians between 2005 and 2014 and to compare it to their output in the previous 10-year period (1995-2004) as well as to that of emergency physicians in other countries and Spanish physicians in other specialties. Original articles indexed in the Science Citation Index Expanded of the Web of Science were included. Documents from Spanish emergency physicians were identified by combining the word Spain and any other search term identifying an emergency service or unit in Spain. To identify articles from 7 other Spanish specialties (hematology, endocrinology, cardiology, pneumology, digestive medicine, pediatrics, surgery and orthopedic medicine or traumatology) and emergency physicians in 8 other countries (United States, United Kingdom, Ireland, Italy, France, Germany, Netherlands, Belgium) we used similar strategies. Information about production between 1995 and 2004 was extracted from a prior publication. Spanish emergency physicians signed 1254 articles (mean [SD], 125 [44] articles/y) between 2005 and 2014. That level of productivity was greater than in the 1995-2004 period (mean, 26 [14] articles/y), although the annual growth rate fell from 12.5% in the previous 10-year period to 5.2% in the most recent one. Emergency medicine was among the least productive Spanish specialties we studied, but our discipline's annual growth rate of 5.2% was the highest. Spanish emergency medicine occupies an intermediate position (ranking fifth) among the 9 countries studied, although the population-adjusted rank was higher (fourth). When output was adjusted for gross domestic product, Spain climbed higher in rank, to second position. The annual growth rate was the fourth highest among countries, after Germany (9.9%), the Netherlands (7.3%), and Italy (6.0%). The research output of Spanish emergency physicians continues to be quantitatively lower than that of other Spanish specialties and of emergency physicians in other countries. The annual rate of growth in publications, although good, fell below the growth rate of the previous period.


Rebalancing glucolipid metabolism and gut microbiome dysbiosis by nitrate-dependent alleviation of high-fat diet-induced obesity.
High-fat diet (HFD)-induced obesity is accompanied by compromised nitric oxide (NO) signaling and gut microbiome dysregulation. Inorganic dietary nitrate, which acts as a NO donor, exerts beneficial effects on metabolic disorders. Here, we evaluated the effects of dietary nitrate on HFD-induced obesity and provided insights into the underlying mechanism. To investigate the preventive effect of dietary nitrate on HFD-induced obesity, C57BL/6 mice were randomly assigned into four groups (n=10/group), including normal control diet group (normal water and chow diet), HFD group (normal water and HFD), HFD+NaNO3 group (water containing 2 mM NaNO3 and HFD), and HFD+NaCl group (water containing 2 mM NaCl and HFD). During the experiment, body weight was monitored and glucolipid metabolism was evaluated. The mechanism underlying the effects of nitrate on HFD-induced obesity was investigated by the following: the NO3--NO2--NO pathway; endothelial NO synthase (eNOS) and cyclic guanosine monophosphate (cGMP) levels; gut microbiota via 16SRNA analysis. Dietary nitrate reduced the body weight gain and lipid accumulation in adipose and liver tissues in HFD-fed mice. Hyperlipidemia and insulin resistance caused by HFD were improved in mice supplemented with nitrate. The level of eNOS was upregulated by nitrate in the serum, liver, and inguinal adipose tissue. Nitrate, nitrite, and cGMP levels were decreased in mice fed on HFD but reversed in the HFD+NaNO3 group. Nitrate also rebalanced the colon microbiota and promoted a normal gut microbiome profile by partially attenuating the impacts of HFD. Bacteroidales S24-7, Alistipes, Lactobacillus, and Ruminococcaceae abundances were altered, and Bacteroidales S24-7 and Alistipes abundances were higher in the HFD+NaNO3 group than that in the HFD group. Inorganic dietary nitrate alleviated HFD-induced obesity and ameliorated disrupted glucolipid metabolism via NO3--NO2--NO pathway activation and gut microbiome modulation.


An Airway Network Flow Assignment Approach Based on an Efficient Multiobjective Optimization Framework.
Considering reducing the airspace congestion and the flight delay simultaneously, this paper formulates the airway network flow assignment (ANFA) problem as a multiobjective optimization model and presents a new multiobjective optimization framework to solve it. Firstly, an effective multi-island parallel evolution algorithm with multiple evolution populations is employed to improve the optimization capability. Secondly, the nondominated sorting genetic algorithm II is applied for each population. In addition, a cooperative coevolution algorithm is adapted to divide the ANFA problem into several low-dimensional biobjective optimization problems which are easier to deal with. Finally, in order to maintain the diversity of solutions and to avoid prematurity, a dynamic adjustment operator based on solution congestion degree is specifically designed for the ANFA problem. Simulation results using the real traffic data from China air route network and daily flight plans demonstrate that the proposed approach can improve the solution quality effectively, showing superiority to the existing approaches such as the multiobjective genetic algorithm, the well-known multiobjective evolutionary algorithm based on decomposition, and a cooperative coevolution multiobjective algorithm as well as other parallel evolution algorithms with different migration topology.


Relationship between plasma concentrations and clinical effects of perampanel: A prospective observational study.
The purpose of the study was to investigate the potential correlation between plasma concentration of the newer antiseizure medication (ASM) perampanel (PMP) and both tolerability and seizure control in patients with epilepsy. The study design was multicenter, open, and prospective. Plasma samples were collected in the morning 12 h apart from once-a-day bedtime PMP dose. Perampanel tolerability was assessed on the day of drug monitoring by clinical examination and patients' interview. Response to PMP was defined as ≥50% reduction from baseline seizure frequency (pretreatment). The main outcomes were the comparisons of PMP plasma concentration-to-weight-adjusted dose ratio (C/D) [(μg/mL)/(mg/kg/day)] between patients with and without PMP-related adverse effects (AEs) and between responders and nonresponders. Ninety-seven patients (54% men), mean ± SD age 36 ± 14 years were enrolled in the study. The mean PMP dose was 6.7 ± 2.3 mg, drug treatment averaged 46 ± 34 weeks. The mean plasma concentration was 360 ± 268 ng/mL (range: 37-1213 ng/mL). Forty patients (41%) reported at least one AE, mainly dizziness and behavioral changes. No significant difference was found in median PMP C/Ds between patients with (2.94) and without (2.76) AEs, otherwise comparable for clinical variables. Forty-four patients (45%) were responders, at a median PMP C/D of 3.10, similar to the value of 2.76 found in nonresponders. These two groups also overlapped for clinical characteristics. This is the first prospective real-life study to evaluate the relationship between PMP plasma concentrations, seizure control, and AEs. In line with the few real-world available data, we did not find any significant correlation between PMP plasma concentrations and both tolerability and seizure control.


Quantitative immunohistochemical analysis of islet amyloid polypeptide (IAPP) in normal, impaired glucose tolerant, and diabetic cats.
Islet amyloid polypeptide (IAPP, "amylin") has been proposed as having important roles in the pathogenesis of type 2 diabetes mellitus via its biological activity and by forming islet amyloid. The domestic cat develops a type of diabetes that closely resembles type 2 diabetes in humans, including the frequent formation of islet amyloid deposits in the impaired glucose tolerant (IGT) and diabetic state. With the aid of computerized image analysis and immunohistochemistry, we examined the IAPP and insulin content in pancreatic islets of normal, IGT and diabetic cats. IAPP immunoreactivity in beta cells from IGT cats was significantly stronger (p < 0.01) as compared with cells from normal cats, while the insulin labelling strength was unchanged. Overtly diabetic cats were usually almost devoid of beta cells. As in humans, cellular IAPP but not IAPP in islet amyloid deposits was labelled by the newly developed monoclonal antibody to IAPP 4A5, thus providing further evidence that IAPP is modified by a yet unknown mechanism during the amyloidogenic process. The study provides evidence that an increased beta cell storage of IAPP independent of insulin may be an important factor in the early phase of the development of islet amyloid in this form of diabetes.


KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential.
KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating function of KIR2DL4, and whether it can provide inhibitory signals, is not known. Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane region that is required for the activation signal. The activity of the mutated KIR2DL4 molecules was tested in a redirected lysis assay. The ITIM was not necessary for activation of lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4 inhibited the signal delivered by the activating receptor CD16. In pull-down experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory potential in addition to its activating function.


A characteristic condition of finite nilpotent group.
This paper gives a characteristic condition of finite nilpotent group under the assumption that all minimal subgroups of G are well-suited in G.


Adult stem cells for chronic lung diseases.
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF.


Failure Rate of Retropubic Midurethral Sling With and Without Concomitant Robotic Sacrocolpopexy.
The retropubic midurethral sling (rMUS) and sacrocolpopexy are treatments for stress urinary incontinence (SUI) and pelvic organ prolapse, respectively, which are often performed concomitantly. The purpose of this study was to identify whether a difference exists in the failure rates of rMUS when placed alone or at the time of robotic sacrocolpopexy (RSC). We conducted a single-center retrospective cohort study of patients who underwent rMUS placement between December 2015 and March 2020. The primary outcome was rMUS failure defined as additional treatment for SUI at any point. There were 160 patients who underwent isolated rMUS and 175 patients who underwent rMUS and RSC. Patients who underwent isolated rMUS were more likely to be obese (P < 0.01). Patients who underwent RSC were older (63.3 ± 9.9 vs 57.7 ± 13.7 years, P < 0.0001) and more likely to be White (P = 0.02). Follow-up ranged from 0 to 46 months (median, 3 months; interquartile range, 3 months). Failure was observed in 2.3% of rMUS placed alone and 8.6% of rMUS with RSC. Patients who underwent rMUS and RSC had an odds ratio of 3.63 for rMUS failure (P = 0.03; 95% confidence interval, 1.16-11.38). Hypertension was associated with 4 times higher rMUS failure (odds ratio, 4.18; P = 0.02; 95% confidence interval, 1.29-13.58). We observed a significantly increased rate of rMUS failure from those placed alone to those placed at the time of RSC. Retropubic midurethral sling at the time of RSC was 4 times more likely to result in additional SUI treatment.


CS-SELEX generates high-affinity ssDNA aptamers as molecular probes for hepatitis C virus envelope glycoprotein E2.
Currently, the development of effective diagnostic reagents as well as treatments against Hepatitis C virus (HCV) remains a high priority. In this study, we have described the development of an alive cell surface--Systematic Evolution of Ligands by Exponential Enrichment (CS-SELEX) technique and screened the functional ssDNA aptamers that specifically bound to HCV envelope surface glycoprotein E2. Through 13 rounds of selection, the CS-SELEX generated high-affinity ssDNA aptamers, and the selected ssDNA aptamer ZE2 demonstrated the highest specificity and affinity to E2-positive cells. HCV particles could be specifically captured and diagnosed using the aptamer ZE2. A good correlation was observed in HCV patients between HCV E2 antigen-aptamer assay and assays for HCV RNA quantities or HCV antibody detection. Moreover, the selected aptamers, especially ZE2, could competitively inhibit E2 protein binding to CD81, an important HCV receptor, and significantly block HCV cell culture (HCVcc) infection of human hepatocytes (Huh7.5.1) in vitro. Our data demonstrate that the newly selected ssDNA aptamers, especially aptamer ZE2, hold great promise for developing new molecular probes, as an early diagnostic reagent for HCV surface antigen, or a therapeutic drug specifically for HCV.


The people behind the papers - Mingxi Deng and Yan Yan.
Drosophila wing discs are epithelial sac-like organs and a powerful model for investigating the link between proliferation and patterning. Of particular interest is the question of how single cells in the disc integrate information regarding position and growth control, as morphogens that pattern an axis can also regulate cell division. A new Techniques and Resources article in Development reports the application of single cell sequencing technologies to dissociated discs in an effort to understand these problems. We caught up with first author Mingxi Deng and his supervisor Yan Yan, Assistant Professor at The Hong Kong University of Science and Technology (HKUST), to hear more about the story.


Cell size homeostasis under the circadian regulation of cell division in cyanobacteria.
Bacterial cells maintain their characteristic cell size over many generations. Several rod-shaped bacteria, such as Escherichia coli and the cyanobacteria Synechococcus elongatus, divide after adding a constant length to their length at birth. Through this division control known as the adder mechanism, perturbation in cell length due to physiological fluctuation decays over generations at a rate of 2-1 per cell division. However, previous experiments have shown that the circadian clock in cyanobacteria reduces cell division frequency at a specific time of day under constant light. This circadian gating should modulate the division control by the adder mechanism, but its significance remains unknown. Here we address how the circadian gating affects cell length, doubling time, and cell length stability in cyanobacteria by using mathematical models. We show that a cell subject to circadian gating grows for a long time, and gives birth to elongated daughter cells. These elongated daughter cells grow faster than the previous generation, as elongation speed is proportional to cell length and divide in a short time before the next gating. Hence, the distributions of doubling time and cell length become bimodal, as observed in experimental data. Interestingly, the average doubling time over the population of cells is independent of gating because the extension of doubling time by gating is compensated by its reduction in the subsequent generation. On the other hand, average cell length is increased by gating, suggesting that the circadian clock controls cell length. We then show that the decay rate of perturbation in cell length depends on the ratio of delay in division by the gating τG to the average doubling time τ0 as [Formula: see text] . We estimated τG≈2.5, τ0≈13.6 hours, and τG/τ0≈0.18 from experimental data, indicating that a long doubling time in cyanobacteria maintains the decay rate similar to that of the adder mechanism. Thus, our analysis suggests that the acquisition of the circadian clock during evolution did not impose a constraint on cell size homeostasis in cyanobacteria.


A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects.
Leuprolide acetate microspheres developed by Shanghai Livzon Pharmaceutical Co., Ltd. (T) have been marketed in China for more than 10 years, benefiting a large number of patients, and will continue to play an important role in China. However, as a generic drug, it is unclear whether there is a difference in efficacy between T and the original product Enantone® (R). This study compared the differences in efficacy and safety of two 1-month depot formulations in 48 healthy Chinese male subjects by comparing multiple pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The main research indicators were the PK parameters of leuprolide (Cmax, AUC0-t, AUC0-D7, and AUCD7-t) and the PD parameters of testosterone (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) after 42 days of administration. The Cmax, AUC0-t, AUC0-D7 and AUCD7-t of leuprolide were slightly higher in the T group than in the R group with 90% confidence intervals (CIs) of 94.43-118.53%, 109.13-141.88%, 109.53-139.54%, and 105.17-145.74%, respectively. No significant differences in the PD parameters (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) existed between the T and R groups, and 90% CIs were 62.80-93.57%, 88.17-110.55, 95.72%-118.50%, and 79.77-105.63, respectively. At 672 h (D28), the castration rate of T was 91.30% (21/23) and that of R was 60.87% (14/23). The PK characteristics were consistent and the inhibitory effects on testosterone levels were similar in both T and R groups; further, clinical safety was observed for both T and R formulations, suggesting that these two products can replace each other in clinical practice. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20200641.


Optimization of the quantitative analysis of the major cannabis metabolite (11-nor-9-COOH-delta 9-tetrahydrocannabinol) in urine by gas chromatography/mass spectrometry.
A gas chromatographic/mass spectrometric electron impact method is presented for the detection and quantification of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH) in urine, for use in the confirmation of presumptive results obtained by other techniques. Four extraction procedures, two solid-liquid and two liquid-liquid, have been compared. A comparison of two trimethylsilylating methods demonstrates that the best results are obtained by the use of a mixture containing N-methyl-N-trimethylsilyl-trifluoroacetamide, trimethyliodosilane and dithioerithritol (100:0.2:1) v/v/w. The use of ketoprofen as a new internal standard for the quantification of THC-COOH has proved to be very effective. Both spiked samples and samples from cannabis users have been successfully analysed. It has also been demonstrated that the presence of other drugs of abuse in urine samples do not interfere with cannabis quantification by the method reported here.


Adverse health outcomes of road traffic injuries in Iran after rapid motorization.
Recent studies have made it clear that Iran has too many road traffic injuries (RTI). This paper explains the reasons for high traffic injury rates and points to solutions. It also provides detailed data on the burden of traffic injury in Iran in 2005. Traffic injury rates have rapidly risen out of control because for a variety of possible reasons such as increasing number of non-standard cars and motorcycles, low gas price, decreasing ratio of travels via public transportation than with private vehicles, and problems with safety design. Besides a high need for a system safety approach, Iran needs to deal with the problem of producing a high number of cars and motorcycles. Providing safe mobility for the people of Iran needs to be a top priority of the government.


Substrate Directed Asymmetric Reactions.
Historically, reagent controlled reactions (mechanism controlled reactions) have played a significant role in the asymmetric synthesis of complex structures. In contrast, today's asymmetric synthesis is greatly dependent on substrate directed approaches. In this approach, a polar functional group, namely, a "directing group", in the vicinity of the reactive site inside the substrate has been documented to preassociate with the chiral catalyst, which exerts stereodirecting influence by directing the reacting partner toward one of the enantiotopic faces of the reaction center. Those reactions usually proceed through exceptionally ordered transition states and result in extraordinary levels of stereoselection. Within the last four decades, the substrate directed approach has become an indispensible tool for the preparation of complex chiral frameworks starting directly from relatively simple achiral substrate molecules via asymmetric induction or various resolution techniques or both. Likewise, the substrate directed approach has been applied to functionalize enantiopure substrates bearing pre-exisiting stereocenters into complex structures as a single diastereomer. A classical example is Sharpless asymmetric epoxidation of allylic alcohols in which the free hydroxy function acts as an active anchor to a dimeric Ti-catalyst that controls the stereochemical outcome of the epoxidation process by transferring the oxidant enantioselectively. The principal aim of the present review is to give a general overview of substrate directed asymmetric transformations, a topic that has not yet been documented in the form of a concise review of recently developed approaches. Due to the large number of related applications, only recent advances that have been documented within the last two decades have been reviewed. Furthermore, in the current review, we have mainly highlighted asymmetric reactions that are controlled by abundant and frequently used directing groups such as hydroxy, amide, and sulfonamide groups. In addition, selected examples of a few important substrate-directed chemo-, regio-, and diastereoselective reactions have also been included in this review.


How prenatal environmental factors affect rat molar enamel formation?
Amelogenin (AMELX) and ameloblastin (AMBN) are crucial for enamel formation, and interruptions in the production of these proteins may cause enamel defects. We investigated how prenatal environmental factors (chronic stress, bisphenol A (BPA), amoxicillin, and lipopolysaccharide (LPS)) affect AMELX and AMBN production of ameloblasts. Fifteen pregnant Sprague-Dawley rats were divided into four experimental groups and a control group. Chronic-stress group rats were exposed to a 12:12 light/light cycle (LL) from day E18 until delivery. BPA group rats were orally administered 5 μg/kg BPA daily from day E1 until delivery. Amoxicillin group rats were injected 100 mg/kg amoxicillin daily from day E18 until delivery. LPS-infection group rats were injected 125 μg/kg bacterial LPS once on day E18. Seven pups from the control group and ten pups from the experimental groups were euthanized on P10. Sections were stained with hematoxylin and eosin (H&E) and Gomori's one-step trichrome staining (GT) and incubated with rabbit polyclonal antibodies to AMELX and AMBN, to evaluate staining intensity at ameloblast stages. The surface morphology was evaluated with a stereomicroscope. AMELX (p = 0.008, p = 0.0001, p = 0.009) and AMBN (p = 0.002, p = 0.001, p = 0.0001) staining of all groups were significantly lower than that of the control group in the secretory, transitional, and maturation stages. Abnormal enamel matrix formation was observed in the H&E and GT staining sections of all experimental groups. Yellowish coloration of the amoxicillin group was observed in morphologic evaluation.


Minas Artisanal Cheese As Potential Source of Multidrug-Resistant Escherichia coli.
Bacteria develop resistance to antibiotics naturally, but the inappropriate and widespread use of antibiotics in humans and animals has made antimicrobial resistance one of the biggest threats to modern medicine. Raw milk cheese can represent an important source of antimicrobial resistance. Thus, the objective of this study was to evaluate the prevalence and sensitivity of Escherichia coli isolated from artisanal cheese made from raw milk produced in Minas Gerais, Brazil. E. coli counts were determined using the most probable number method. An antibiogram was performed using the disk diffusion method, following the protocol described by the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) for 14 antibiotics of nine classes. E. coli was detected in 35 (71.4%) of the samples, with populations between 0.56 to 4.87 log (NMP/g) of cheese. The presence of E. coli resistant to multiple antimicrobials was more frequent in cheeses, with an E. coli population below the levels established by regulatory limits. Only four samples (11.4%) had all E. coli isolates susceptible to the 14 antimicrobials evaluated. The results showed the heterogeneity of antimicrobial resistance in E. coli between the producing regions of Minas artisanal cheese. Multidrug resistance was detected in 29% of the E. coli isolates and in almost 40% (38.8%) of the cheese samples. The frequency of multidrug-resistant (MDR) isolates was different between the production regions (p < 0.05). The presence of MDR E. coli in cheese from region D was 14, 4, and 20 times more likely than in cheese from regions A, B, and C, respectively. A multiple antibiotic resistance index of 0.200 predicted the presence of MDR E. coli in raw milk artisanal cheese with 99% probability. In conclusion, artisanal cheese can act as sources of MDR E. coli to colonize the human gastrointestinal tract.


Identification of proteins that associate with integrin α2 by proteomic analysis in human fibrosarcoma HT-1080 cells.
Integrins are adhesion receptors for components of the extracellular matrix (ECMs) that regulate multiple cellular functions, such as migration, invasion, proliferation, and survival by mediating bidirectional signal transmission. Even though many proteins have been reported to associate with integrins both on and in cells, systemic analyses of the adhesome have not been carried out. In previous studies, we identified proteins associating with a membrane-type protease, MT1-MMP, using nano-flow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) of associated proteins prepared by optimized conditions for cell lysis and purification. Since integrins were identified as MT1-MMP-associated proteins, we next applied this method to analyze integrin-associated proteins. In this study, we expressed integrin α2 fused at the C terminus to a FLAG peptide in HT1080 cells. Cells stably expressing the chimeric protein were lysed with 1% Brij-98 and affinity purified using anti-FLAG antibody. Integrin β1 co-purified with integrin α2 confirming the specificity of the purification procedure. Analysis of the purified mixture by nano-LC/MS/MS identified 70 proteins. Nineteen of these were membrane proteins, including adhesion proteins, receptors, transporters, proteinases, and ion-channel receptors, and the balance were cytoplasmic. Interestingly, eight of the proteins had previously been shown to associate with MT1-MMP. We believe the present study provides a platform to facilitate the study of the mechanisms of cell adhesion, migration, and invasion.


[Combined cataract and vitreoretinal surgery].
Both cataract and many vitreoretinal diseases occur more frequently and often at the same time in the elderly population. Therefore, one has to consider whether to combine cataract surgery and vitrectomy or to plan a sequential approach. The aim of the present survey - based on a thorough review of the current literature - is to point out the advantages and disadvantages of a combined versus a sequential approach. Furthermore, practically oriented guidelines have been compiled for finding the right indication for a combined procedure with regard to the underlying vitreoretinal disease.


Smartphone-Enabled Health Coaching Intervention (iMOVE) to Promote Long-Term Maintenance of Physical Activity in Breast Cancer Survivors: Protocol for a Feasibility Pilot Randomized Controlled Trial.
Although physical activity has been shown to contribute to long-term disease control and health in breast cancer survivors, a majority of breast cancer survivors do not meet physical activity guidelines. Past research has focused on promoting physical activity components for short-term breast cancer survivor benefits, but insufficient attention has been devoted to long-term outcomes and sustained exercise adherence. We are assessing a health coach intervention (iMOVE) that uses mobile technology to increase and sustain physical activity maintenance in initially inactive breast cancer survivors. This pilot randomized controlled trial (RCT) is an initial step in evaluating the iMOVE intervention and will inform development of a full-scale pragmatic RCT. We will enroll 107 physically inactive breast cancer survivors and randomly assign them to intervention or control groups at the University Health Network, a tertiary cancer care center in Toronto, Canada. Participants will be women (age 18 to 74 years) stratified by age (55 years and older/younger than 55 years) and adjuvant hormone therapy (AHT) exposure (AHT vs no AHT) following breast cancer treatment with no metastases or recurrence who report less than 60 minutes of preplanned physical activity per week. Both intervention and control groups receive the 12-week physical activity program with weekly group sessions and an individualized, progressive, home-based exercise program. The intervention group will additionally receive (1) 10 telephone-based health coaching sessions, (2) smartphone with data plan, if needed, (3) supportive health tracking software (Connected Wellness, NexJ Health Inc), and (4) a wearable step-counting device linked to a smartphone program. We will be assessing recruitment rates; acceptability reflected in selective, semistructured interviews; and enrollment, retention, and adherence quantitative intervention markers as pilot outcome measures. The primary clinical outcome will be directly measured peak oxygen consumption. Secondary clinical outcomes include health-related quality of life and anthropometric measures. All outcome measures are administered at baseline, after exercise program (month 3), and 6 months after program (month 9). This pilot RCT will inform full-scale RCT planning. We will assess pilot procedures and interventions and collect preliminary effect estimates. ClinicalTrials.gov NCT02620735; https://clinicaltrials.gov/ct2/show/NCT02620735 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT02620735).


[Metronidazole content of normal and tumor tissues in the combined treatment of patients with osteogenic sarcoma].
A study was made of the time course of the level of metronidazole in the blood and tissues of 97 patients with localized osteogenic sarcoma in several modes of the drug administration (per os, using an enema and their combinations). The maximum drug concentration in the blood was achieved with the combined mode of the drug administration at a dose of 8 g/m2, enhancing local and general effects on a tumor, manifesting themselves in the reduction of sizes of a tumor, its morphological changes and an increase in the average period of metastasis detection. The 3-year survival rates showed no significant differences between groups of patients receiving and not receiving metronidazole.


Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore.
Dengue illness causes 50-100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings. We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%-59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9-14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively. Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.


Does the Back Plate Position Influence Swimming Start Temporal Characteristics?
The current study examined the back plate position impact on the block phase movement pattern and total starting performance with a distinction for sex. Thirty-eight swimmers performed starts changing the back plate position (preferred position, one position forward and one position backward), with the data being assessed using a 3D dynamometric central and a video camera. In males, the 15 m start time was 0.1 s shorter for the preferred position compared with the backward position (p < 0.05). Regardless of the back plate positioning, the swimmers spent a similar time on the block. A more forward position of the back plate postponed the rear foot take-off and consequently reduced the front foot stand duration. A back plate position effect was revealed for those variables with a larger effect size in males whereas in females, a change of about two positions was needed to reach a significance level. Probably due to the specification of physical domains, a greater impact on the changes introduced was noted for males. Therefore, whilst searching for the optimal starting position, adjustments to the back plate placement might affect a greater number of males than females. To reinforce the starting optimization during the training process and its monitoring, the effect of personal preference toward the starting block setting was also considered.


Dorsal mesoderm has a dual origin and forms by a novel mechanism in Hymenochirus, a relative of Xenopus.
The dorsal mesoderm in the frog Hymenochirus forms by a mechanism not previously described in any other vertebrate. Unlike its close relative, Xenopus laevis, in which the mesoderm derives entirely from the deep mesenchymal cells of the marginal zone, Hymenochirus has "surface mesoderm" originating in the involuting marginal zone epithelium. Fluorescently labeled grafts show stage-specific invasion of deep axial tissue by cells originally located in the surface layer. These cells participate in normal mesoderm development. In video recordings, the labeled surface area shrinks as surface cells invade the deep layer. Furthermore, the mechanism of surface mesoderm morphogenesis differs from that described in other amphibians. Scanning electron microscopy at several neurula stages indicates that prospective somite cells do not individually detach from their epithelial neighbors to ingress into the deep layer, as seen in other amphibians; instead, their basal ends adhere to the somitic mesoderm as a coherent layer, taking on somitic morphology while still a part of the archenteron lining. This novel morphogenetic process we dub "relamination." Prospective notochord cells individually spread on the ventral surface of the notochord, gradually ingressing from their epithelial neighbors, but by a mechansism involving active pulling and spreading by their invasive basal ends rather than depending on apical constriction as do the corresponding "bottle cells" in other amphibians. Lateral endoderm migrates dorsally, replacing the relaminating surface mesoderm and fusing at the dorsal midline of the archenteron. These processes demonstrate the diversity of morphogenesis at the cellular, and presumably the molecular, level and shed light on the evolution of morphogenetic mechanisms.


The effect of paraoxon on GABA uptake in rat cerebellar synaptosomes.
The compounds used to treat organophosphate (OP) poisoning are not able to fully alleviate long-lasting effects. They are mainly used to antagonize the cholinergic effects of OPs; however, non-cholinergic effects such as interference with different neurotransmitter systems, especially GABA release and uptake, are now attracting more attention. Cerebellar synaptosomes were used to investigate any potential interaction between paraoxon and GABA uptake. The cerebella of 250- to 280-g Wistar rats were rapidly dissected out, homogenized, centrifuged, and incubated with 0.004 microM [(3)H]GABA in the presence of different doses of paraoxon for 15 minutes at 37 degrees C. At the end of the incubation period, the synaptosomes were layered in chambers of a superfusion system (UGO). To assay the amount of [(3)H]GABA uptake, radioactivity was measured using a beta-counter (Winspectrul). Mean GABA uptake was 111, 95, 71, 73, and 75 percent of the control values in the presence of paraoxon concentrations of 0.01, 0.1, 1, 10, and 100 microM, respectively. Accordingly, GABA uptake was significantly reduced at doses 1, 10, and 100 microM of paraoxon (P<0.05). Paraoxon may interfere with GABA uptake by cerebellar synaptosomes at micromolar concentrations or higher.


Glycaemic index of some commercial gluten-free foods.
Gluten-free products present major challenges for the food industry in terms of organoleptic, technological and nutritional characteristics. The absence of gluten has been shown to affect starch digestibility, thus increasing the postprandial glycaemic response. However, in recent years, gluten-free technologies have been improved, thus possibly modifying this quality parameter. We investigated the glycaemic index (GI) of 10 commercial foods aiming to update the GI values of the most common gluten-free products consumed in Italy. The in vivo GI was evaluated for six bakery products and four types of pasta. The postprandial glucose response was obtained in two groups with 10 healthy volunteers each. The overall GI values ranged from 37.5 for breakfast biscuits to 66.7 for puffed multigrain cake. Breads and pasta had GI values consistently lower than those previously reported in the literature. The present study showed that several commercial GF products exhibited low and medium GI values, not confirming the previous observations on the high GI of GF. However, considering the multiple formulations and processes for preparation of these products, further studies are recommended.


Simple Theory for the Dynamics of Mean-Field-Like Models of Glass-Forming Fluids.
We propose a simple theory for the dynamics of model glass-forming fluids, which should be solvable using a mean-field-like approach. The theory is based on transparent physical assumptions, which can be tested in computer simulations. The theory predicts an ergodicity-breaking transition that is identical to the so-called dynamic transition predicted within the replica approach. Thus, it can provide the missing dynamic component of the random first order transition framework. In the large-dimensional limit the theory reproduces the result of a recent exact calculation of Maimbourg et al. [Phys. Rev. Lett. 116, 015902 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.015902]. Our approach provides an alternative, physically motivated derivation of this result.


Diels⁻Alder-Crosslinked Polymers Derived from Jatropha Oil.
Methyl oleate, methyl linoleate, and jatropha oil were fully epoxidized using in situ-generated performic acid. The epoxidized compounds were further reacted with furfurylamine in a solvent-free reaction to obtain furan-functionalized fatty esters which, then, functioned as oligomers for a network preparation. Thermoreversible crosslinking was obtained through a (retro) Diels⁻Alder reaction with bismaleimide, resulting in the formation of a brittle network for furan-functionalized methyl linoleate and jatropha oil. The furan-functionalized fatty esters were mixed with alternating (1,4)-polyketone reacted with furfurylamine (PK-Furan) for testing the mechanical and self-healing properties with DMTA and DSC, respectively. Full self-healing properties were found, and faster thermoreversibility kinetics were observed, compared to PK-Furan.


Expression of Lymphangiogenic Markers in Rejected Human Corneal Buttons after Penetrating Keratoplasty.
To investigate the extent and distribution of lymphangiogenesis in the rejected corneal graft, we determined the expression of several lymphangiogenic markers in rejected human corneal buttons. Thirty-four corneal buttons were obtained from patients who underwent re-keratoplasty for graft rejection after penetrating keratoplasty. All corneas showed signs of rejection, such as, sudden mutton-fat keratic precipitates (KPs) or lines before re-keratoplasty. The corneas were halved, and one half was used for immunostaining and the other half was used for RT-PCR. Expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3, LYVE-1 and podoplanin were measured as lymphangiogenic markers. Four non-operated normal corneas were used as controls. Numerous podoplanin positive cells were found in the anterior and posterior stroma. However, LYVE-1 positive mature lymphatics were found only in herpetic keratitis (HK)-induced graft rejection, and not in pseudophakic bullous keratopathy (PBK). RT-PCR showed that levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 mRNAs were elevated in rejected corneal buttons versus the non-operated control corneas. Based upon the pre-keratoplasty pathologic conditions, HK cases showed higher levels of VEGF-A and VEGFR-2 than PBK. The mRNA ratios (keratoplastic cornea/normal cornea) for VEGF-A and VEGFR-2 were 8.9 and 5.8, respectively. The results suggested that the VEGF-A and the VEGFR-2 may be a more important pathway for lymphangiogenesis in rejected corneal grafts than the VEGFR-3. In addition, organized lymphangiogenesis is more prominent in HK than PBK.


Early Outcomes Of Decentralized Care for Rifampicin-Resistant Tuberculosis in Johannesburg, South Africa: An Observational Cohort Study.
We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6-21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27-218). Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.


Prevalence of type 2 diabetes mellitus in Iran and its relationship with gender, urbanisation, education, marital status and occupation.
We investigated the prevalence of type 2 diabetes mellitus and its relationship between gender, urbanisation, education, marital status and occupation in the Iranian population. A total of 3,778 men and women aged between 15 and 64 years were recruited by using a cluster-stratified sampling method from Khorasan province, northeast Iran. Using an interviewer-administrated questionnaire, demographical data including gender, urbanisation, education, marital status and occupation was collected. Anthropometrical and biochemical measurements were taken for each subject. Associations of type 2 diabetes mellitus and other variables were tested for significance. The prevalence of diabetes mellitus (defined as fasting blood sugar equal to or more than 126 mg/dL) was 5.5 percent, and the prevalence in men and women was 5.1 percent and 5.8 percent, respectively, with a significantly higher prevalence among urban dwellers (seven percent) compared to that of the rural subgroup (three percent, p-value is less than 0.001). Diabetes mellitus was found to be most prevalent among the older age group (age more than 60 years, 10.9 percent), those who were retired (14.4 percent), and illiterate (6.1 percent, p-value is less than 0.001). Marital status was not significantly related to diabetes mellitus (p-value equals 0.09). The prevalence of diabetes mellitus is related to some sociodemographical factors within the Iranian population. Thus the preventive strategies should be based on the affective factors. The urbanisation of the population with the migration of people from rural to urban areas may account in part for the increasing prevalence of type 2 diabetes mellitus in Iran.


Potential Effects of Romanian Propolis Extracts against Pathogen Strains.
The impact of globalization on beekeeping brings new economic, scientific, ecological and social dimensions to this field The present study aimed to evaluate the chemical compositions of eight propolis extracts from Romania, and their antioxidant action and antimicrobial activity against seven species of bacteria, including pathogenic ones: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The phenolic compounds, flavonoids and antioxidant activity of propolis extracts were quantified; the presence of flavones and aromatic acids was determined. Quercetin and rutin were identified by HPLC analysis and characterized using molecular descriptors. All propolis samples exhibited antibacterial effects, especially against P. aeruginosa and L. monocytogenes. A two-way analysis of variance was used to evaluate correlations among the diameters of the inhibition zones, the bacteria used and propolis extracts used. Statistical analysis demonstrated that the diameter of the inhibition zone was influenced by the strain type, but no association between the propolis origin and the microbial activity was found.


Potassium/proton antiport system of Escherichia coli.
The intracellular level of potassium (K(+)) in Escherichia coli is regulated through multiple K(+) transport systems. Recent data indicate that not all K(+) extrusion system(s) have been identified (15). Here we report that the E. coli Na(+) (Ca(2+))/H(+) antiporter ChaA functions as a K(+) extrusion system. Cells expressing ChaA mediated K(+) efflux against a K(+) concentration gradient. E. coli strains lacking the chaA gene were unable to extrude K(+) under conditions in which wild-type cells extruded K(+). The K(+)/H(+) antiporter activity of ChaA was detected by using inverted membrane vesicles produced using a French press. Physiological growth studies indicated that E. coli uses ChaA to discard excessive K(+), which is toxic for these cells. These results suggest that ChaA K(+)/H(+) antiporter activity enables E. coli to adapt to K(+) salinity stress and to maintain K(+) homeostasis.


Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells.
Population-based studies suggest a reduced incidence of morbidity and mortality from coronary heart disease caused by moderate and regular consumption of red wine. Endothelial nitric oxide (NO) is a pivotal vasoprotective molecule. This study examines the influence of red wine polyphenols on the regulation of endothelial nitric oxide synthase (eNOS) expression and subsequent NO synthesis, focusing on the putative long-lasting antiatherosclerotic effects of red wine. Treatment (20 hours) of human umbilical vein endothelial cells (HUVECs) and of the HUVEC-derived cell line EA.hy926 with a alcohol-free red wine polyphenol extract (RWPE) led to a concentration-dependent (100 to 600 microg/mL), significant increase in NO release (up to 3.0-fold/HUVEC and 2.0-fold/EA.hy926) as shown by use of the fluorescent probe DAF-2. This effect was corroborated by the [14C]L-arginine/L-citrulline conversion assay in intact EA.hy926 cells. RWPE (20 hours, 100 to 600 microg/mL) also significantly increased eNOS protein levels up to 2.1-fold. Furthermore, we found an increased human eNOS promotor activity (up to 2-fold) in response to red wine polyphenols (18 hours, 100 to 600 microg/mL), as demonstrated by a luciferase reporter gene assay. We provide conclusive data showing for the first time that a RWPE increases eNOS expression and subsequent endothelial NO release. Increased active eNOS levels may antagonize the development of endothelial dysfunction and atherosclerosis, a hypothesis that supports the view that red wine indeed may have long-term protective cardiovascular properties mediated by its polyphenols.


A review of health-related quality-of-life measures in stroke.
The objective of this review was to evaluate health-related quality of life (HR-QOL) measures for use with patients with stroke. HR-QOL measures are increasingly used for assessment in many health conditions; these measures may serve an important role in evaluating the impact of stroke and of stroke interventions. HR-QOL measures used in patients with stroke should: (i) cover the domains of HR-QOL that may be affected by stroke; (ii) have administration characteristics suitable for use in patients with stroke; and (iii) have undergone reliability and validity assessment in patients with stroke. The present study evaluates HR-QOL measures with reference to these requirements. A systematic literature review was conducted to identify and evaluate HR-QOL measures of potential use in studies of patients with stroke. Identified measures were assessed with regard to stroke-relevant domains covered, measure characteristics (e.g. self-administration versus administration by an interviewer, interviewer time to complete) and psychometric properties of reliability and validity. The measures evaluated vary widely on domains covered, and limited assessment of the performance of HR-QOL measures has been conducted in patients with stroke. No existing measure comprehensively covers all relevant domains or addresses fully the issues of obtaining and combining HR-QOL assessments in patients and proxies in many stroke populations. Additional psychometric testing in stroke populations is needed for existing HR-QOL measures. In addition, stroke-targeted HR-QOL measures need to be developed and evaluated with patients with stroke.


A typhoid fever outbreak in a slum of South Dumdum municipality, West Bengal, India, 2007: evidence for foodborne and waterborne transmission.
In April 2007, a slum of South Dumdum municipality, West Bengal reported an increase in fever cases. We investigated to identify the agent, the source and to propose recommendations. We defined a suspected case of typhoid fever as occurrence of fever for > or = one week among residents of ward 1 of South Dumdum during February - May 2007. We searched for suspected cases in health care facilities and collected blood specimens. We described the outbreak by time, place and person. We compared probable cases (Widal positive > or = 1:80) with neighbourhood-matched controls. We assessed the environment and collected water specimens. We identified 103 suspected cases (Attack rate: 74/10,000, highest among 5-14 years old group, no deaths). Salmonella (enterica) Typhi was isolated from one of four blood specimens and 65 of 103 sera were > or = 1:80 Widal positive. The outbreak started on 13 February, peaked twice during the last week of March and second week of April and lasted till 27 April. Suspected cases clustered around three public taps. Among 65 probable cases and 65 controls, eating milk products from a sweet shop (Matched odds ratio [MOR]: 6.2, 95% confidence interval [CI]: 2.4-16, population attributable fraction [PAF]: 53%) and drinking piped water (MOR: 7.3, 95% CI: 2.5-21, PAF-52%) were associated with illness. The sweet shop food handler suffered from typhoid in January. The pipelines of intermittent non-chlorinated water supply ran next to an open drain connected with sewerage system and water specimens showed faecal contamination. The investigation suggested that an initial foodborne outbreak of typhoid led to the contamination of the water supply resulting in a secondary, waterborne wave. We educated the food handler, repaired the pipelines and ensured chlorination of the water.


The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy.
Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic disease in which degeneration of the retina occurs as a remote effect of cancer in a distant part of the body. Immunoreactivity of sera from CAR patients and controls have been analyzed. Immunostaining of human retinal proteins showed that a soluble protein of Mr approximately 46 kDa (p46) is labeled by antibodies from several CAR patients with various types of cancer (lung, breast, bladder, prostate, salivary gland, and gastrointestinal tract cancer and chronic lymphocytic leukemia). These sera did not show reactivity with the 23-kDa protein previously associated with CAR. To identify and further characterize p46, the retinal protein was purified to homogeneity by anion-exchange chromatography and preparative gel electrophoresis. Protein sequence analysis of the peptides from p46 revealed a high homology with human enolase, an important glycolytic enzyme. Although enolase has been previously identified as a product of several types of tumors, and enolase activity has been detected in the sera of some cancer patients, the existence of autoantibodies directed to enolase has not been described. This is the first report of the presence of serum antibodies to retinal enolase in the patients with cancer and the CAR syndrome. When antibodies of specific isotypes (IgG, IgM, and IgA) were measured, IgG1 isotype was dominant. The significance of these antibodies for the disease process is under investigation.


In-silico investigation of some recent natural compounds for their potential use against SARS-CoV-2: a DFT, molecular docking and molecular dynamics study.
Since its first appearance in December 2019, SARS-CoV-2 has infected many people all over the world, causing serious health problems in many people and causing many deaths, but no specific drug has been developed yet. SARS-CoV-2 main protease (SARS-CoV-2 Mpro) has an important role in viral replication and transcription, so inhibition of this enzyme is proposed to be an attractive route for the treatment of COVID-19. Natural compounds have been used in the treatment of many diseases throughout the history. In this study, it was aimed to investigate SARS-CoV-2 Mpro inhibition abilities, thus the therapeutic potentials of some novel phytochemicals which have recently been entered the literature. For this purpose, eleven novel phytochemicals obtained from various natural resources have been investigated for their potential antiviral activity against SARS-CoV-2 with the use of in silico methods. In the first part of the study, DFT (density functional theory) calculations were performed on the investigated compounds. In this part, geometry optimizations, vibrational analyses, and MEP (molecular electrostatic potential) map calculations were performed. In the second part, molecular docking calculations and then molecular dynamics (MD) simulations were performed to investigate how these natural compounds interact with SARS-CoV-2 Mpro which is a promising target for COVID-19 treatments. In this part, MM-PBSA (molecular mechanics with Poisson-Boltzmann surface area) calculations were also performed to determine the binding free energies of the investigated compounds. Results showed that most of the investigated compounds interacted with SARS-CoV-2 Mpro effectively and can be promising structures for drug development studies for COVID-19.Communicated by Ramaswamy H. Sarma.


The microbiome-metabolome crosstalk in the pathogenesis of respiratory fungal diseases.
Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and pathogen exposure. There is increasing evidence that the individual microbiome supervises the outcome of the host-fungus interaction by influencing mechanisms of immune regulation, inflammation, metabolism, and other physiological processes. Microbiome-mediated mechanisms of resistance allow therefore the control of fungal colonization, preventing the onset of overt disease, particularly in patients with underlying immune dysfunction. Here, we review this emerging area of research and discuss the contribution of the microbiota (and its dysbiosis), including its immunoregulatory properties and relationship with the metabolic activity of commensals, to respiratory fungal diseases. Finally, we highlight possible strategies aimed at decoding the microbiome-metabolome dialog and at its exploitation toward personalized medical interventions in patients at high risk of infection.


[Retrospective analysis of primary parapharyngeal space tumors].
Objective:To explore the clinical feature and surgical treatment of patients with parapharyngeal space tumors. Method:A retrospective review of 214 cases with parapharygeal space tumors treated. The data on clinical manifestations, imaging examinations, pathological types, surgical approach, and postoperative complications were reviewed. Result:Of the 214 cases, the tumor was benign in nature in 135 cases(63.1%) and malignant in 79 cases(36.9%). There was no gender difference in the incidence of benign tumors, and the ratio of male to female was 1:1. The incidence of malignant tumors was higher in males than in females, and the ratio was 3.3:1. Regardless of benign and malignant tumors, the high incidence age is 40-59. Two-thirds of cases of parapharyngeal space tumors had different degrees of peripheral structural invasion. The most common cases involving the skull base were 76 cases(35.5%), followed by blood vessels and nerves, 24 cases(11.2%) and 16 cases(7.5%),respectively. Complications occurred in 65 patients(31.4%), the most common complications were hoarseness caused by X-cranial nerve palsy. Conclusion:There are various pathological types of parapharyngeal space tumors, and surgery is the first choice for parapharyngeal space tumors. The surgical plan should be made according to the imaging examinations, lesions, and the pathology et al. The risk of complications should be fully informed before the operation, and the cooperation of the patients should be obtained.


Rapid epidemiologic assessment of breastfeeding practices: probit analysis of current status data.
We describe the use of probit analysis to estimate breastfeeding indicators from current status epidemiological data. A health centre-based sample of 2411 children aged 0-1 year was investigated in Santo Andre, a large town in the Metropolitan Area of Sao Paulo, southeastern Brazil. Mothers were interviewed during routine pediatric consultations and asked about their current infant feeding practices. Probit regressions were calculated by a public-domain microcomputer programme written by one of us. The median duration of total (i.e. exclusive plus partial) breastfeeding in this children's sample, estimated as 108.8 days (95 per cent confidence interval: 95.5-123.2 days), is close to that recently reported in the city of Sao Paulo and nearby towns. However, the median duration of exclusive breastfeeding (28.9 days, 95 per cent CI: 17.9-38.3 days) is rather short when compared to recent estimates from this same region. Despite the nationwide efforts for promotion of exclusive breastfeeding, only 14 per cent (95 per cent CI: 12.3-17 per cent) of the infants were still being exclusively breastfed by 120 days of age. Therefore, a key feature of breastfeeding practices in this population sample, namely, the early introduction of supplementary foods, was identified by using simplified methods of data collection and analysis. This communication suggests that probit analysis of current status data may be further explored as a method for rapid epidemiologic assessment of breastfeeding practices.


An overview of buprenorphine prescribing for the advanced practice psychiatric nurse.
Rates of at-risk opioid use, opioid use disorder, and opioid overdose remain alarmingly high. There are medications that can be used to treat opioid use disorder, including methadone, buprenorphine, and naltrexone, although access to care remains difficult. This review seeks to provide advanced practice psychiatric nurses (APPNs) with an overview of buprenorphine prescribing, with an emphasis on novel, long-acting delivery systems. APPNs should be familiar with best practices regarding buprenorphine prescribing. Some patients may benefit from long-acting delivery methods, such as subdermal implants, or subcutaneous injections. APPNs can reduce barriers to buprenorphine access and should be familiar with best practices related to buprenorphine prescribing.


Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system.
The family of metastasis-associated (MTA) genes is a small group of transcriptional co-regulators which are involved in various physiological functions, ranging from lymphopoietic cell differentiation to the development and maintenance of epithelial cell adhesions. By recruiting histone-modifying enzymes to specific promoter sequences, MTA proteins can function both as transcriptional repressors and activators of a number of cancer-relevant proteins, including Snail, E-cadherin, signal transducer and activator of transcriptions (STATs), and the estrogen receptor. Their involvement in the epithelial-mesenchymal transition process and regulatory interactions with estrogen receptor activity has made MTA proteins highly interesting research candidates, especially in the field of hormone-sensitive breast cancer and malignancies of the female reproductive tract. This review focuses on the current knowledge about the function and regulation of MTA1 and MTA3 proteins in gynecological cancer, including ovarian, endometrial, and cervical tumors.


Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis.
This study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN). We studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy. Elevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage. Our study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.


Does triage to critical care during a pandemic necessarily result in more survivors?
The 2009 H1N1 pandemic reinforced the need for a planned response to increased demand for critical care. Triage protocols have been proposed incorporating the exclusion of specified subgroups of patients from critical care. There have been no studies that explore the theoretical underpinning of triage at referral, and it is not clear under what circumstances triage would confer the intended benefits. We sought to explore the mechanisms whereby triage could lead to fewer deaths across a critical care population in the context of a pandemic. We constructed a mathematical model based on queuing theory to compare the estimated short-term survival achieved by using a critical care service with and without triage at referral. Illustrative scenarios concerning a hypothetical critical care population were constructed to explore the roles of length of stay and critical care survival in determining the impact of triage and to identify "tipping points" of demand at which triage would result in more survivors. Not applicable as this was a data-free mathematical modeling exercise. We identified circumstances in which triage would be expected to result in more survivors and circumstances in which it would not. In some scenarios, excluding patient groups solely on the basis of anticipated length of stay could be effective due to a more efficient use of critical care bed days. The impact of triage is dependent on the level of demand and on the scale of achievable differences between included and excluded groups in terms of anticipated length of stay and critical care survival. It cannot be assumed that triage can or will result in fewer deaths. It should be remembered that there are considerations other than population-level short-term survival when determining the objectives of triage and its ethical implementation.


Ross procedure. Inserting the autograft using a fully supported root replacement method; techniques and results.
The root replacement (RR) method for insertion of the pulmonary autograft (PA) has resulted in improved immediate aortic valve competence. However, the unsupported pulmonary artery wall is thinner, more elastic, and thus more prone to dilatation than the normal aortic root. This might predispose to late aortic regurgitation (AR) due to splaying of the aortic commissures, similar to the mechanism of AR in Marfan's syndrome. A fully supported root replacement (FSRR) method was designed and implemented in 78 patients, with preservation of the aortic root and proximal ascending aortic remnant fully to surround and support the PA root. Additional aortic annulus reduction was performed in 29 patients, and adjustment of the sinotubular diameter in 27. Seventy-eight patients were analyzed with sequential Doppler echocardiography. The maximal neoaortic sinus diameter remained constant for up to three years after surgery (mean 34.3 +/- 4.0 mm) compared with before surgery (35.2 +/- 4.0 mm). There was one early death, no late deaths or reoperations, and at last follow up AR was nil/trivial in 72% of patients, mild in 27% and moderate in 1%. There was no progression of AR over four years' follow up. By comparison, four patients previously underwent unsupported RR for insertion of the PA; in these patients, mean neoaortic sinus diameter increased significantly from 31 +/- 6 mm to 41 +/- 3 mm at three years after surgery (p = 0.005). Insertion of the PA using a FSRR method prevents dilatation of the neoaortic sinuses and sinotubular junction without need for prosthetic material, and provides similar results to conventional RR with regard to aortic valve competence. Retaining the advantages of RR in this manner and maintaining aortic root size may prove valuable in the longer term.


A strict experimental test of macroscopic realism in a superconducting flux qubit.
Macroscopic realism is the name for a class of modifications to quantum theory that allow macroscopic objects to be described in a measurement-independent manner, while largely preserving a fully quantum mechanical description of the microscopic world. Objective collapse theories are examples which aim to solve the quantum measurement problem through modified dynamical laws. Whether such theories describe nature, however, is not known. Here we describe and implement an experimental protocol capable of constraining theories of this class, that is more noise tolerant and conceptually transparent than the original Leggett-Garg test. We implement the protocol in a superconducting flux qubit, and rule out (by ∼84 s.d.) those theories which would deny coherent superpositions of 170 nA currents over a ∼10 ns timescale. Further, we address the 'clumsiness loophole' by determining classical disturbance with control experiments. Our results constitute strong evidence for the superposition of states of nontrivial macroscopic distinctness.


Vancomycin as an Antibacterial Agent Capped with Silver Nanoparticles: An Experimental Potential Analysis.
For the treatment of various infections, a variety of antimicrobial drugs are formulated. Nevertheless, many bacterial infections now exhibit antibiotic resistance due to the widespread utilization antibiotics. Methicillin-resistant among the most dangerous multidrug-resistant bacteria is Staphylococcus aureus (MRSA). Vancomycin became a viable therapy option due to MRSA resistance to methicillin medicines. One of the well-informed antibacterial compounds with wideband antibacterial activity is silver nanoparticles (AgNPs). AgNPs are thus suitable candidates for usage in conjunction alongside vancomycin to increase its antibacterial effect. The goal of the present research work is to boost the antibacterial potency of the glycopeptide antibiotic vancomycin towards Gram-positive (Staphylococcus aureus) but also Gram-negative (Escherichia coli) bacteria. The chemical reduction approach is used to create a colloidal solution of silver nanoparticles utilizing silver nitrate as a precursor in the environment of the ionic surfactant trisodium citrate that serves as covering including reducing reagent. Vancomycin was used to functionalize the synthesized nanoparticles and create the nanodrug complex (Van@AgNPs). The synergistic antibacterial potential of silver nanoparticles coated with vancomycin on both test pathogens was investigated using the agar well diffusion technique. The antibacterial potency for both classes of bacteria has significantly increased, according to the well diffusion test. It has been noted that this improvement is synergistic instead of additive.


A holistic approach to managing palm oil mill effluent (POME): biotechnological advances in the sustainable reuse of POME.
During the last century, a great deal of research and development as well as applications has been devoted to waste. These include waste minimization and treatment, the environmental assessment of waste, minimization of environmental impact, life cycle assessment and others. The major reason for such huge efforts is that waste generation constitutes one of the major environmental problems where production industries are concerned. Until now, an increasing pressure has been put on finding methods of reusing waste, for instance through cleaner production, thus mirroring rapid changes in environmental policies. The palm oil industry is one of the leading industries in Malaysia with a yearly production of more than 13 million tons of crude palm oil and plantations covering 11% of the Malaysian land area. However, the production of such amounts of crude palm oil result in even larger amounts of palm oil mill effluent (POME), estimated at nearly three times the quantity of crude palm oil. Normally, POME is treated using end-of-pipe processes, but it is worth considering the potential value of POME prior to its treatment through introduction of a cleaner production. It is envisaged that POME can be sustainably reused as a fermentation substrate in the production of various metabolites, fertilizers and animal feeds through biotechnological advances. The present paper thus discusses various technically feasible and economically beneficial means of transforming the POME into low or preferably high value added products.


Vital status in the National Panel Survey of Black Americans: a test of the National Death Index among African Americans.
To test the specificity of the National Death Index (NDI), information was submitted on 157 randomly selected respondents from the National Panel Survey of Black Americans (NPSBA) who were known to be living as of 1992. Information also was submitted for 153 known deceased respondents from the panel survey to test the sensitivity of the NDI. The NDI was very sensitive; however, specificity was somewhat less impressive. Although we found the NDI/NPSBA match to be highly accurate, there was a nontrivial number of false positives.


Electronic Predissociation in the Dichloromethane Cation CH2Cl2+ Electronic State 2A1.
The loss of a Cl atom from metastable CH2Cl2+ in the mass-analyzed ion kinetic energy experiment is characterized by a borderline zero kinetic energy release and large kinetic isotope effects on chlorine and hydrogen. Ab initio calculations are employed to assist the interpretation in terms of a nonadiabatic reaction involving electronic predissociation of the electronically excited state 2A1 and two-dimensional reaction dynamics. Strong curvature in the reaction coordinate leads to a bobsled effect that accounts for the low kinetic energy release. The kinetic isotope effects enter via the predissociation rate and are interpreted in terms of vibrational overlap integrals.


Refractory epilepsy associated with microglial activation.
Experimental and clinical studies support a pathogenic role of microglial activation and proliferation (MAP) in epileptogenesis. From a consecutive series of 319 surgically treated epilepsy cases, we retrospectively reviewed the histopathological sections of 92 cases to define the prevalence and severity of MAP after excluding the other 227 because of coexisting disorders that might contribute to MAP. Severity of MAP was compared with underlying abnormalities. We assessed the response to intravenous immunoglobulin and plasmapheresis in one patient with severe MAP who had failed multiple antiepileptic drugs and epilepsy surgery. MAP was detected with routine (hematoxylin and eosin) stain in 46 of 92 cases (50%). MAP was mild in 32 cases (69.6%), moderate in 12 (26.1%), and severe in 2 (4.3%). The prevalence and severity of MAP were independent of underlying abnormalities. Immunomodulatory therapy was followed by a greater than 90% reduction in seizure activity in the treated patient. MAP is prevalent in resected human epilepsy tissue. Failure to down-regulate MAP contributes to chronic neuronal hyperexcitability. We hypothesize that MAP initiates a cycle of inflammation-induced seizures and seizure-induced inflammation. Microglia-driven epilepsy may be a primary pathogenic process in a small number of cases, as suggested by the pathology and therapeutic response in our patient, but may contribute to epileptogenesis in many more.


Autonomic and antihypertensive activity of oral amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent in conscious rats.
The autonomic and antihypertensive activities of amosulalol (YM-09538) were studied in conscious rats. Single oral administration of amosulalol antagonized the phenylephrine-induced pressor and isoproterenol-induced positive chronotropic responses with DR10 values of 11.5 and 13.6 mg/kg in pithed rats, respectively, indicating that the compound inhibits both alpha 1- and beta 1-adrenoceptors to almost the same extent in agreement with previously reported results in vitro. Amosulalol was approximately 50 times less potent than prazosin and 12 times more potent than labetalol at alpha 1-adrenoceptors, and it was approximately as effective as labetalol and 2 times more potent than propranolol at beta 1-adrenoceptors. In spontaneously hypertensive rats (SHR), renal hypertensive rats and DOCA/salt hypertensive rats, a single oral administration of amosulalol (3-30 mg/kg) lowered acutely systolic blood pressure with a duration of over 6 hr and was found to be approximately 50 times less potent than prazosin and 3 times more potent than labetalol in lowering blood pressure. Propranolol did not cause such an immediate hypotensive effect. Amosulalol and labetalol did not increase heart rate, whereas prazosin induced a tachycardia in the hypertensive rats. Repeated oral administrations of amosulalol and labetalol (50 mg/kg/day, b.i.d., for 12 weeks) produced not only an antihypertensive effect without evidence of tolerance, but also reductions in plasma renin activity (PRA) and heart rate in SHR with established hypertension. We conclude that alpha-adrenoceptor blockade by amosulalol might account for its antihypertensive activity and that its beta-adrenoceptor blockade might inhibit reflexogenic increases in heart rate and PRA due to the reduction in blood pressure.


Coagulation protein function VII: diametric effects of acetaldehyde on factor VII and factor IX function.
The first metabolite of ethanol, acetaldehyde, has the ability to form adducts with proteins and alter their function. It has been shown that acetaldehyde reacts with various proteins of the blood coagulation pathway and, subsequently, produces a prolongation of the clotting time. This study evaluated the function of clotting proteins from the extrinsic coagulation pathway (factor VII) and the intrinsic coagulation pathway (factor IX) when preincubated with acetaldehyde as compared to a control and compared to preincubation with ethanol. Prior to use in a clotting assay, incubation times with acetaldehyde, ethanol, and the control were the same for both factors VII and IX. An automatic fibrometer measured the clotting times. Factor VII preincubated with acetaldehyde prolonged the clotting time. However, factor IX preincubated with acetaldehyde actually decreased the clotting time. Of interest, both factors VII and IX preincubated with acetaldehyde produced statistically significant results when compared to the control and ethanol. This experiment indicates that acetaldehyde, in forming an adduct with proteins of the blood coagulation pathway, may induce a conformational change of factors VII and IX so as to either increase or decrease the clotting time. Therefore, it is possible that some of the deranged coagulation in alcohol abusers may be a final net result of the interaction of acetaldehyde and proteins of the coagulation pathway.


Does intervention in utero preserve the obstructed kidneys of fetal lambs? A histological, cytological, and molecular study.
Ureteropelvic junction obstruction is a common cause of end-stage nephropathy in children. Our aim was to investigate whether relief of obstruction in utero can alleviate the development of nephropathy. A silastic tube was tied around the left superior segment ureter to induce unilateral partial ureteral obstruction in 22 fetal sheep at 75- 85 d of gestation. Three weeks later, the tubes were removed to relieve the obstruction in 10 of the 22 lambs. A sham operation was performed on four fetuses (the control). At birth, the lambs were killed, and their kidneys were removed to study the changes in histology, podocytes, and expression of paired-box 2 (PAX2) and VEGF. In the obstructed kidneys, we observed cysts of various sizes in the cortex, fibrosis in the interstitial tissue, much decreased number of glomeruli, severe podocyte foot process fusion, and markedly increased PAX2 and decreased VEGF expressions. However, relief of obstruction preserved the number of glomeruli, significantly increased VEGF expression, reduced fusion of the podocyte foot processes, andrestored expression of PAX2 to some extent. Thus, relief ofobstruction in utero may prevent or attenuate the development ofnephropathy in lambs.


Time reversal communication in a time-varying sparse channel.
Recently time reversal (TR) communications has been extended to time-varying channels. The basic idea is to implement it on a block-by-block basis such that within each block the channel remains time-invariant and subsequently is updated using detected symbols (decision-directed mode). Using experimental data (12-20 kHz) collected in shallow water, this letter investigates three different block-based TR approaches: (1) without explicit phase tracking, (2) with phase tracking, and (3) exploiting channel sparsity. The TR approaches then are compared to a conventional adaptive multichannel equalizer. It is found that approach (3) generally provides the best performance and robustness.


Radiological Analysis of Gentamicin Eluting Synthetic Bone Graft Substitute Used in the Management of Patients With Traumatic Bone Voids.
Background Management of traumatic bone voids has always been challenging. Gentamicin eluting synthetic bone graft substitute (Cerament-G) showed encouraging results in achieving good bone healing with a satisfactory degree of resorption when utilised as a void filler. This study aims to assess the radiological signs of Cerament-G remodelling when used for patients with traumatic bone voids. Methods Retrospective data analysis of all patients admitted to our unit between 2015 and 2021 with traumatic bone voids who had Cerament-G applied intraoperatively as a void filler. Postoperative radiographic images of the fracture site at six weeks, three months, six months, and at the final follow-up were reviewed. The radiological signs of Cerament-G integration, percent of void healing at the final follow-up were assessed. Results A total of 51 patients (52 fractures) were included in the study. Among them 10 were female and 41 were male with a mean age of 42.7 (11 - 90) years. The mean void size was 6.58 cm3. Mean follow-up duration was 9.73 months. Primary fracture union was achieved in 44 (86.3%) patients. Delayed union was reported in six (11.7%) patients, while one (1.9%) patient had non-union. Twenty-seven (52%) patients had >90% of void healing with normal trabecular bone. Twenty (38.5%) patients had 50-90% void healing with normal bone. Whereas only five (9.5%) patients had less than 50% of void healing. Conclusion Cerament-G used as a void filler for patients with traumatic bone void has resulted 98% fracture union rate with good signs of radiological remodelling into a trabecular bone. More than 50% void filling with new trabecular bone was reported in more than 90% of patients. Non-union was reported in only one patient.


Effects of yogurt ingestion on mucosal and systemic cytokine gene expression in the mouse.
To assess the potential for ingestion of yogurt to modulate immunity, its effects on basal gene expression of cytokines in systemic and mucosal sites were determined in mice. Yogurts were manufactured from pasteurized nonfat dry milk using five commercial starter cultures with or without Bifidobacterium sp. and Lactobacillus acidophilus. Treatment mice were fed the AIN-93G diet mixed 1:1 with unheated yogurt or heat-treated yogurt (wt/wt) for 2 and 4 weeks, and control mice were fed the AIN-93G diet mixed 1:1 (wt/wt) with nonfat dry milk. The viability of the various bacterial groups in unheated yogurts was maintained above 10(6) CFU/g throughout the feeding period. The yogurt-feeding regimens did not significantly affect weight gain. Relative mRNA levels in spleen, mesenteric lymph nodes, or Peyer's patches for the cytokines interferon-gamma, tumor necrosis factor-alpha, interleukin-2, -4, and -6, and the "housekeeping gene" beta2-microglobulin were determined by reverse transcriptase-polymerase chain reaction in conjunction with hybridization analysis. Prolonged feeding of some yogurts decreased expression of several cytokine mRNAs, the depression of tumor necrosis factor-alpha mRNA in the spleen being the most prominent effect. Heat-treated yogurts were more effective in altering cytokine mRNA expression than were unheated yogurts containing viable organisms. Generally, yogurts either had no effect or decreased specific cytokine mRNA in the test organs, regardless of whether they contained Bifidobacterium sp. and L. acidophilus. These results suggest that, in contrast with previous studies in vitro, some yogurt formulations may reduce rather than stimulate basal cytokine expression and that these effects are most prominent in the systemic compartment.


Substance abuse and maternity: the United States as a case study.
Two themes pervade the issue of women and addiction in the United States: anger and blame directed at women who use alcohol and other drugs; and neglect and a consequent lack of appropriate treatment. Often the focus is on the addicted pregnant woman and the debate posits a woman's right to autonomy and privacy in opposition to the future child's right to be born free from harm. Others emphasize the tension between blaming individuals and holding the state accountable for provision of services. These conflicts have impeded the diagnosis of women with substance abuse problems, the availability of services and women's access to appropriate care.


Prospects and perspectives in primate aging research.
As improvements in standard of living and advances in medicine have resulted in greater life expectancy, the relative proportion of elderly has continued to increase in human populations across the globe. The primary goal of aging research is to gain a better understanding of the series of events that lead to increased frailty and disease vulnerability with age. The direct study of human aging is an active area of research; however, the opportunity to conduct mechanistic studies and gain insights into the underlying biology is limited. In this special forum issue of Antioxidant & Redox Signaling, we present a selection of articles and reviews that illustrate some of the recent advances in primate aging research. The overarching goal of this work is to underscore the potential for mechanistic discovery that is presented by nonhuman primate models, and to promote studies that validate novel approaches and techniques in nonhuman primates before their adaptation for human health care.


The Role of Neutrophil to Lymphocyte Count Ratio in the Differential Diagnosis of Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia: a Cross-Sectional Study at Ayder and Mekelle Hospitals, Ethiopia.
The differential diagnosis of pulmonary tuberculosis and bacterial community-acquired pneumonia is often a challenging phenomenon. The neutrophil to lymphocyte count ratio, a suitable indicator of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. The main aim this study is to evaluate the role of neutrophil to lymphocyte count ratio in the differential diagnosis of pulmonary tuberculosis and bacterial Community-Acquired Pneumonia at Ayder and Mekelle hospitals, Mekelle, Ethiopia. A hospital based cross-sectional study was conducted from February to May 2017 on a total of 146 patients at Ayder and Mekelle hospitals. After taking written informed consent, study participants were interviewed for a detailed history and 5 mL of blood was collected for hematological analysis. Pulmonary tuberculosis was diagnosed by using Ziehl-Neelsen and Gene X-pert. Community acquired pneumonia was diagnosed using sputum culture. Student's t-test, Pearson's chi-square test, and receiver operating characteristics curve analysis were used. A p-value < 0.05 was considered statistically significant. The neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate were significantly higher in pulmonary tuberculosis patients than bacterial community-acquired pneumonia patients. Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate with cutoff values of ≥ 2.72 and ≥ 39, respectively, showed the highest area under the curve (AUC = 0.69; 95% CI: 0.62, 0.77). Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate together at a time with their respective cutoff values gave a 69% accuracy in differentiating pulmonary tuberculosis from bacterial community-acquired pneumonia. Therefore, neutrophil to lymphocyte count ratio and erythrocyte sedimentation rate can be used in differentiating pulmonary tuberculosis from PTB patients from bacterial Community-acquired pneumonia, especially in resource-limited settings.


Ergosterol as a measure of living fungal biomass: persistence in environmental samples after fungal death.
The membrane lipid ergosterol is found almost exclusively in fungi, and is frequently used by environmental microbiologists as an indicator of living fungal biomass, based on the assumption that ergosterol is labile, and therefore rapidly degraded after the death of fungal hyphae. We studied the degradation of ergosterol in environmental samples without living fungi. Under the conditions used in this study, ergosterol was very stable both when added as a pure compound and when associated with dead fungi. The decrease of ergosterol was at most 34% during 2 months when protected from sunlight. Presence of a natural bacterial assemblage did not enhance degradation over this time period, as compared to sterile controls. However, photochemical degradation was significant, and led to a 43% decrease of in ergosterol content during 24 h. These results suggest that ergosterol should be used cautiously as a biomarker for living fungi.


The RNA replication enhancer element of tombusviruses contains two interchangeable hairpins that are functional during plus-strand synthesis.
Replication of the RNA genomes of tombusviruses, which are small plus-sense RNA viruses of plants, may be regulated by cis-acting elements, including promoters and replication enhancers that are present in the RNA templates. Using a partially purified RNA-dependent RNA polymerase (RdRp) preparation (P. D. Nagy and J. Pogany, Virology 276:279-288, 2000), we demonstrate that the minus-strand templates of tombusviruses contain a replication enhancer, which can upregulate RNA synthesis initiating from the minimal plus-strand initiation promoter by 10- to 20-fold in an in vitro assay. Dissection of the sequence of the replication enhancer element revealed that the two stem-loop structures present within the approximately 80-nucleotide-long enhancer region have interchangeable roles in upregulating RNA synthesis. The single-stranded sequence located between the two stem-loops also plays an important role in stimulation of RNA synthesis. We also demonstrate that one of the two hairpins, both of which are similar to the hairpin of the minus-strand initiation promoter, can function as a promoter in vitro in the presence of short cytidylate-containing initiation sites. Overall, the in vitro data presented are consistent with previous in vivo results (D. Ray and K. A. White, Virology 256:162-171, 1999) and they firmly establish the presence of a replication enhancer on the minus-stranded RNA of tombusviruses.


Predisposing Factors for Sexual Dysfunction in Multiple Sclerosis.
Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) has a detrimental impact on individual health-related quality of life (HRQoL). It is not clear whether SD in multiple sclerosis (MS) is an independent symptom or merely a byproduct of other symptoms such as depression or anxiety. This cross-sectional study of 93 pwMS determines risk factors for SD in MS based on prevalence, HRQoL, and associated disease outcomes. Diagnosis of SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (measured by Expanded Disability Status scale, EDSS), depression and anxiety [Hospital Anxiety and Depression Scale (HADS)], and HRQoL [Multiple Sclerosis Quality of Life-54 (MSQoL-54)]. Multivariate regression models were performed to determine independent risk factors for SD in pwMS. Almost half of the participants in this study (46%) reported SD. HRQoL was significantly poorer in patients with MS suffering from SD (median [IQR] MSQoL-54 scores: physical subscale 52 [41-68] vs. 81 [69-89], p < 0.001; mental subscale 50 [38-82] vs. 86 [70-89], p < 0.001). In the multivariate model, EDSS was the only independent risk factor for SD (OR 18.1 for EDSS ≥4 [95% CI 3.3-31.4, p < 0.001]), while depression and anxiety were not. We conclude that the risk for SD is growing with increasing EDSS and is independent of depression or anxiety. Screening for SD becomes particularly relevant in patients with growing disability.