Effects of Modified Dietary Fiber from Fresh Corn Bracts on Obesity and Intestinal Microbiota in High-Fat-Diet Mice.
The effects of insoluble dietary fiber from fresh corn bracts modified by dynamic high-pressure micro-fluidization (DHPM) on the pathological characteristics of obesity, intestinal microflora distribution and production of short-chain fatty acids in high-fat-diet C57BL/6 mice were evaluated. The results show that the DHPM-modified dietary fiber from fresh corn bracts significantly reduces weight gain, insulin resistance and oxidative damage caused by a high-fat diet, and promotes the production of SCFAs, especially acetic acid, propionic acid and butyric acid. These modified dietary fibers also change the proportion of different types of bacteria in the intestinal microflora of mice, reduce the ratio of Firmicutes and Bacteroidota and promote the proliferation of Bifidobacteriales. Therefore, the DHPM-modified dietary fiber from fresh corn bracts can be used as a good intestinal microbiota regulator to promote intestinal health, thereby achieving the role of preventing and treating obesity.


Muscle coordination of support, progression and balance during stair ambulation.
Stair ambulation is more physically demanding than level walking because it requires the lower-limb muscles to generate greater net joint moments. Although lower-limb joint kinematics and kinetics during stair ambulation have been extensively studied, relatively little is known about how the lower-limb muscles accelerate the whole-body center of mass (COM) during stair ascent and descent. The aim of the current study was to evaluate differences in muscle contributions to COM accelerations between level walking and stair ambulation in 15 healthy adults. Three-dimensional quantitative gait analysis and musculoskeletal modeling were used to calculate the contributions of the individual lower-limb muscles to the vertical, fore-aft and mediolateral accelerations of the COM (support, progression, and balance, respectively) during level walking, stair ascent and stair descent. Muscles that contribute most significantly to the acceleration of the COM during level walking (hip, knee, and ankle extensors) also dominate during stair ambulation, but with noticeable differences in coordination. In stair ascent, gluteus maximus accelerates the body forward during the first half of stance and soleus accelerates the body backward during the second half of stance, opposite to the functions displayed by these muscles in level walking. In stair descent, vasti generates backward and medial accelerations of the COM during the second half of stance, whereas it contributes minimally during this period in level walking. Gluteus medius performs similarly in controlling mediolateral balance during level walking and stair ambulation. Differences in lower-limb muscular coordination exist between stair ambulation and level walking, and our results have implications for interventions aimed at preventing stair-related falls.


False memory formation in cannabis users: a field study.
Cannabis use is widespread and has previously been associated with memory impairments. However, the role of cannabis in relation to false memory production, i.e., memories of events that were not experienced, is less well-understood. The aim of the current field study was to examine the impact of cannabis use on false memory production. The Deese/Roediger-McDermott (DRM) paradigm was used to induce false memories. In this paradigm, participants study word lists that are associatively related to a non-presented word, termed the critical lure. In a later memory test, true recognition rates and false alarm rates toward critical lures and unrelated items are assessed. Memory performance was compared between three groups: regular cannabis consumers who were acutely intoxicated (n = 53), regular cannabis consumers who were sober (n = 50), and cannabis-naïve controls (n = 53). The participants were approached in Dutch coffee shops (cannabis outlets) and cafes and asked to participate in our study. After collecting general information on their cannabis use, they were subjected to the DRM procedure. Although false memory rates for critical lures did not statistically differ between groups, both intoxicated and sober cannabis consumers falsely recognized more unrelated items than control participants. Also, individuals without a history of cannabis use demonstrated higher memory accuracy compared with the intoxicated group. It is concluded that cannabis intoxication and history of cannabis use induce a liberal response criterion for newly presented words for which the level of association with previously learned words is low and uncertainty is high.


Quality assurance in radiation therapy: clinical and physical aspects. Radiation protection.
One usually thinks of radiation safety as keeping patient and personnel exposure as low as reasonably achievable; however, radiation protection activities play an important role in quality assurance for both the clinical and physical aspects. Radiation protection has several aspects: The first step is the design of the irradiation device and its shielding. While this step is out of the hands of the user, the location and level of leakage radiation must be verified by the user. Periodic leak testing of sealed sources is required. Room shielding design is based on the leakage levels specified by the manufacturer and on levels of scatter and primary radiation impinging on the radiation barriers. The addition of shielding for photoneutrons should be planned for accelerators producing photons above 10 MeV. Integrity and adequacy of shielding should be verified by survey after unit installation. Installation and periodic testing of interlocks are necessary to assure that nonirradiation conditions can be restored as soon as necessary. Personnel monitoring serves two purposes; to provide a record of personnel exposures and to alert one to unsuspected changes that may have taken place in procedure, shielding integrity, or source location. Area monitoring and survey on a periodic basis also provides knowledge of unsuspected changes in procedure, shielding integrity, or source location. Brachytherapy and the transport of small radiation sources require additional precautionary actions. Protection of patient anatomy not being treated reduces the chance of normal tissue damage and the possibility of carcinogenic effects.


Physical exercise improves cognitive function by enhancing hippocampal neurogenesis and inhibiting apoptosis in male offspring born to obese mother.
Maternal obesity induces hippocampal functional changes and leads to deficits in cognitive functions, such as learning and memory in offspring. We investigated the protective effects of physical exercise against cognitive function deficit in offspring born to obese mothers. Neurotrophic factors, neurogenesis, and apoptosis were analyzed in the hippocampus and dentate gyrus of offspring. Four-week-old female rats were fed a high-fat diet (HFD) for 20 weeks: 12 weeks prior to mating, and 8 weeks during pregnancy and breast-feeding. Male offspring rats were randomly divided into four groups: Control group (CON), exercise and control group (ECON), male offspring born to obese mother group (MOM), and exercise and MOM group (EMOM). In the exercise groups, treadmill exercise was performed 6 times per week for 4 weeks. Male offspring rats were subjected to the Morris water maze tests and step-down avoidance to assess spatial learning and memory, and short-term memory. The result showed that deficits in spatial learning and memory, and short-term memory in male offspring born to obese mothers was associated with decreases in brain-derived neurotrophic factor (BDNF) levels and neurogenesis, and an increase in apoptosis in the hippocampal dentate gyrus. Physical exercise improved spatial learning and memory, and short-term memory by enhancing BDNF levels and neurogenesis, and by inhibiting apoptosis in the hippocampal dentate gyrus of male offspring born to obese mothers. Our results suggest that physical exercise may be a preventive measure against or a treatment for cognitive function impairment.


Experimental evidence reveals the UCP1 genotype changes the oxygen consumption attributed to non-shivering thermogenesis in humans.
Humans have spread out all over the world adapting to many different cold environments. Recent worldwide genome analyses and animal experiments have reported dozens of genes associated with cold adaptation. The uncoupling protein 1 (UCP1) gene enhances thermogenesis reaction in a physiological process by blocking ATP (adenosine triphosphate) synthesis on a mitochondrial membrane in brown adipose tissues. To our knowledge, no previous studies have shown an association between variants of the UCP1 gene and physiological phenotypes concerning non-shivering thermogenesis (NST) under the condition of low temperature in humans. We showed that the degree of NST for healthy subjects in an artificial climate chamber is significantly different among UCP1 genotypes. Defining the haplotypes covering the UCP1 region (39.4 kb), we found that the frequency of the haplotype with the highest NST was significantly correlated with latitudes and ambient temperature. Thus, the data in this study provide the first evidence that the UCP1 genotype alters the efficiency of NST in humans, and likely supports the hypothesis that the UCP1 gene has been related to cold adaptation in human evolutionary history.


Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice.
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.


Evolution of colorectal cancer: change of pace and change of direction.
This review compiles evidence for an alternative to the classical adenoma-carcinoma sequence in the evolution of colorectal cancer. It is suggested that between 30 and 50 of colorectal cancers are not initiated by mutation of the tumor suppressor gene APC, but through the epigenetic silencing of genes implicated in the control of differentiation, cell cycle control and DNA repair proficiency. The precursor polyps are often characterized by a serrated architecture, and include hyperplastic polyps, admixed polyps and serrated adenomas. The alternative pathway is heterogeneous and may culminate in cancers showing low or high level DNA microsatellite instability (MSI-L and MSI-H, respectively), and in cancers that are microsatellite stable (MSS). Cancers showing DNA MSI may be characterized by an accelerated evolution. Cancers in hereditary non-polyposis colorectal cancer show features of both classical (adenoma and APC mutation) and alternative pathways (rapid evolution, MSI-H and lack of chromosomal instability).


Raman spectroscopy study of acid-base and structural properties of 9-[2-(phosphonomethoxy)ethyl]adenine in aqueous solutions.
The acid-base properties of the acyclic antiviral nucleotide analogue 9- [2-(phosphonomethoxy)ethyl] adenine (PMEA) in aqueous solutions are studied by means of Raman spectroscopy in a pH range of 1-11 and compared with the properties of its common adenosine monophosphate counterparts (5'-AMP, 3'-AMP, and 2'-AMP). Factor analysis is used to separate the spectra of pure ionic species (PMEA2-, HPMEA-, H2PMEA, H3PMEA+) in order to determine their abundance, sites of protonation, and corresponding spectroscopic pK(a) values. The characteristic Raman features of the neutral adenine moiety in PMEA2- and HPMEA- species resemble those of neutral adenine in the AMPs, whereas significant differences are observed between the Raman spectra of the N1-protonated adenine of the solute zwitterionic H2PMEA and its N1-protonated AMP counterparts. On the contrary, the spectrum of crystalline H2PMEA, adopting an "anti-like" conformation, is found to be similar to the N1-protonated AMPs in solution. To explain peculiar Raman features a "syn-like" conformation is suggested for N1-protonated PMEA species in aqueous solutions instead of an anti-like one adopted by H2PMEA in crystals or by common AMPs in aqueous solutions. A physical mechanism of the anti-like to syn-like conformational transition of the solute PMEA that is due to adenine protonation and the flexibility of the (phosphonomethoxy)ethyl group is proposed and discussed.


HLA antigens in two siblings with autoimmune Addison's disease.
The diagnosis of autoimmune Addison's disease was established in two siblings by demonstration of serum antibodies against adrenal cortex antigen, elevated P-ACTH combined with a low P-cortisol, and the absence of P-cortisol response to exogenous ACTH. HLA typing in the two siblings and their parents revealed the same HLA phenotype in the two patients. This is compatible with an autosomal recessive mode of inheritance and indicates that a supposed trait for autoimmune Addison's disease may segregate with the HLA complex in the familial form of autoimmune Addison's disease.


Oesophageal squamous cell carcinoma: I. A critical review of surgery.
Authors writing an oesophageal cancer include adenocarcinoma to a variable extent--between 1 and 75 per cent--but the true incidence of this histological type is about 1 per cent. Most adenocarcinomas are gastric in origin, involving the lower oesophagus, have a lower operative mortality than in the middle or upper one-third of the oesophagus and poorer prognosis than squamous cell carcinoma, but there is no alternative treatment to surgery. Squamous cell carcinoma of the oesophagus, separated incompletely but as far as possible, has been analysed by reviewing data on 83 783 patients in 122 paERS. After trying to standardize the data, it appears that of 100 patients with the condition, 58 will be explored and 39 have the tumour resected, of whom 13 will die in hospital. Of the 26 patients leaving hospital with the tumour excised, 18 will survive for 1 year, 9 for 2 years and 4 for 5 years. Oesophageal resection for squamous cell carcinoma has the highest operative mortality of any routinely performed surgical procedure today.


Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation.
To examine the molecular mechanisms by which mechanical stimuli induce cardiac hypertrophy and specific gene expression, we cultured rat neonatal cardiocytes in deformable dishes and imposed an in vitro mechanical load by stretching the adherent cells. Myocyte stretching increased total cell RNA content and mRNA levels of c-fos and skeletal alpha-actin. Nuclear run-off transcription assay revealed that this increase in c-fos mRNA level by stretching at least partially reflects changes in the transcriptional status. The transfected chloramphenicol acetyltransferase gene linked to upstream sequences of the fos gene indicated that sequences containing a serum response element were required for efficient transcription by stretching and that sequences containing a cAMP/calcium response element might not be involved in the c-fos response to myocyte stretching. The accumulation of c-fos mRNA by stretching was suppressed by protein kinase C inhibitors at the transcriptional level and inhibited markedly by down-regulation of protein kinase C. Moreover, myocyte stretching increased inositol phosphate levels, and activation of protein kinase C by phorbol esters stimulated the expression of c-fos and skeletal alpha-actin genes. These findings suggest that mechanical stimuli (myocyte stretching) might directly induce cardiac hypertrophy and specific gene expression possibly via protein kinase C activation.


The histochemical nature of homogeneous amorphous materials in odontogenic epithelial tumors.
The homogeneous acellular materials in the adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and calcifying odontogenic cyst were examined histochemically for specific staining of amino acids and protein groups. These materials gave a positive reaction for periodic acid-Sciff (PAS), alloxan-Schiff, and dinitrofluorobenzene-H-acid and low reaction for alcian blue, dimethylaminobenzaldehyde (method for tryptophan) and the Morel-Sisley diazotization method. They appear to have approximately the same composition as enamel matrix and are not amyloid in nature. The materials may be synthesized products from neoplastic epithelium that may originate from enamel organs.


Relationship between Nonalcoholic Fatty Liver Disease and Vitamin D Nutritional Status in Extreme Obesity.
To evaluate the relationship of nonalcoholic fatty liver disease (NAFLD) with nutritional status of vitamin D in extreme obesity. Descriptive cross-sectional study in individuals with class III obesity (BMI ≥ 40 kg/m2), aged ≥ 20 years to < 60 years. Data were obtained for weight, height, waist circumference (WC), and serum 25-hydroxyvitamin D (25(OH)D) levels. Vitamin D analysis was performed by high performance liquid chromatography (HPLC) and the cutoff points used for its classification were < 20 ng/mL for deficiency and 20-29.9 ng/ml for insufficiency. NAFLD gradation was conducted through histological evaluation by liver biopsy. The sample is comprised of 50 individuals (86% female). BMI and average weight were 44.1 ± 3.8 kg/m2 and 121.4 ± 21.4 kg, respectively. Sample distribution according to serum 25(OH)D levels showed 42% of deficiency and 48% of insufficiency. The diagnosis of NAFLD was confirmed in 100% of the individuals, of which 70% had steatosis and 30% had steatohepatitis. The highest percentage of 25(OH)D insufficiency was seen in individuals with steatosis (66%/n = 21) and steatohepatitis (93%/n = 16). All individuals with steatohepatitis presented VDD (p < 0.01). The results of this study showed high prevalence of serum 25(OH)D inadequacy in individuals with class III obesity, which worsens as the stage of liver disease progresses.


Where do objects become scenes?
Regions tuned to individual visual categories, such as faces and objects, have been discovered in the later stages of the ventral visual pathway in the cortex. But most visual experience is composed of scenes, where multiple objects are interacting. Such interactions are readily described by prepositions or verb forms, for example, a bird perched on a birdhouse. At what stage in the pathway does sensitivity to such interactions arise? Here we report that object pairs shown as interacting, compared with their side-by-side depiction (e.g., a bird besides a birdhouse), elicit greater activity in the lateral occipital complex, the earliest cortical region where shape is distinguished from texture. Novelty of the interactions magnified this gain, an effect that was absent in the side-by-side depictions. Scene-like relations are thus likely achieved simultaneously with the specification of object shape.


Behind-the-Scenes Infection Prevention: Focusing on Clinical Surfaces and Instrument Processing.
All dental healthcare providers need to ensure patient and worker safety by maintaining excellent standards with regard to cleaning and disinfecting treatment rooms and reprocessing critical instruments. Especially in this day and age of heightened infection control concerns, proper cleaning and disinfection protocols are critically important to prevent cross-contamination and maintain hygienic conditions. This article reviews infection prevention strategies in the dental office, beginning with treatment room cleaning and disinfection, which includes maintenance of various types of surfaces and the use of barrier protection, and continuing to the disinfection and sterilization of dental instruments. The article also discusses methods for validating the sterilization process and proper instrument storage.


Descriptive Epidemiology of Non-Time-Loss Injuries in Collegiate and High School Student-Athletes.
Research on non-time-loss (NTL) injuries, which result in less than 24 hours of restriction from participation, is limited. To describe the epidemiology of NTL injuries among collegiate and high school student-athletes. Descriptive epidemiology study. Aggregate injury and exposure data collected from a convenience sample of National College Athletic Association varsity teams and 147 high schools in 26 states. Collegiate and high school student-athletes participating in men's and boys' baseball, basketball, football, lacrosse, soccer, and wrestling and women's and girls' basketball, field hockey, lacrosse, soccer, softball, and volleyball during the 2009-2010 through 2013-2014 and the 2011-2012 through 2013-2014 academic years, respectively, participated. Collegiate student-athletes participating in men's and women's ice hockey were also included. Injury data from the National Collegiate Athletic Association Injury Surveillance Program and the National Athletic Treatment, Injury and Outcomes Network were analyzed. Injury counts, rates per 1000 athlete-exposures (AEs), and rate ratios were reported with 95% confidence intervals (CIs). A total of 11 899 and 30 122 NTL injuries were reported in collegiate and high school student-athletes, respectively. The proportion of NTL injuries in high school student-athletes (80.3%) was 1.61 times greater than that of collegiate student-athletes (49.9%; 95% CI = 1.59, 1.63). The NTL injury rate in high school student-athletes (8.75/1000 athlete-exposures [AEs]) was 2.18 times greater than that of collegiate student-athletes (4.02/1000 AEs; 95% CI = 2.13, 2.22). Men's ice hockey (5.27/1000 AEs) and boys' football (11.94/1000 AEs) had the highest NTL injury rates among collegiate and high school athletes, respectively. Commonly injured body parts in collegiate and high school student-athletes were the hip/thigh/upper leg (17.5%) and hand/wrist (18.2%), respectively. At both levels, contusions, sprains, and strains were the most frequent diagnoses. Contact with another player was the most cited injury mechanism (college = 38.0%, high school = 46.3%). Non-time-loss injuries compose large proportions of collegiate and high school sports injuries. However, the NTL injury rate was higher in high school than in collegiate student-athletes. Tracking NTL injuries will help to better describe the breadth of injuries sustained by athletes and managed by athletic trainers.


Analysis of the dissociated steroid RU24858 does not exclude a role for inducible genes in the anti-inflammatory actions of glucocorticoids.
Although repression of inflammatory gene expression makes glucocorticoids powerful anti-inflammatory agents, side effects limit usage and drive the search for improved glucocorticoid receptor (GR) ligands. In A549 pulmonary cells, dexamethasone and the prototypical dissociated ligand RU24858 (Mol Endocrinol 11:1245-1255, 1997) repress interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8. Although RU24858 is a weaker GR ligand, both glucocorticoids showed similar efficacies on transrepression of nuclear factor kappaB (NF-kappaB)-dependent transcription, whereas RU24858 yielded less than 12% of the response to dexamethasone on a classic glucocorticoid response element (GRE) reporter (transactivation). Modest NF-kappaB-dependent transrepression ( approximately 40%), along with analysis of IL-8 transcription rate and the accumulation of unspliced nuclear RNA, indicates that transrepression does not fully account for the repression of genes such as IL-8. This was confirmed by the finding that mRNA degradation is increased by both dexamethasone and RU24858. Analysis of IL-1beta-induced steady-state mRNA levels for IL-8 and COX-2 show that dexamethasone- and RU24858-dependent repression of these genes is attenuated by inhibitors of transcription and protein synthesis. Because similar effects were observed with respect to COX-2 and IL-8 protein expression, we conclude that glucocorticoid-dependent gene expression is necessary for repression by both glucocorticoids. Despite RU24858 being defective at classic GRE-dependent transactivation, both dexamethasone and RU24858 induced the expression of potentially anti-inflammatory genes and metabolic genes, suggesting the importance of nontraditional glucocorticoid-dependent gene expression. Thus, classic transactivation- and transrepressionbased screens for anti-inflammatory "dissociated" GR ligands may be flawed because they may not reflect the effects on real glucocorticoid-inducible genes.


Proof of concept study: Testing human volatile organic compounds as tools for age classification of films.
Humans emit numerous volatile organic compounds (VOCs) through breath and skin. The nature and rate of these emissions are affected by various factors including emotional state. Previous measurements of VOCs and CO2 in a cinema have shown that certain chemicals are reproducibly emitted by audiences reacting to events in a particular film. Using data from films with various age classifications, we have studied the relationship between the emission of multiple VOCs and CO2 and the age classifier (0, 6, 12, and 16) with a view to developing a new chemically based and objective film classification method. We apply a random forest model built with time independent features extracted from the time series of every measured compound, and test predictive capability on subsets of all data. It was found that most compounds were not able to predict all age classifiers reliably, likely reflecting the fact that current classification is based on perceived sensibilities to many factors (e.g. incidences of violence, sex, antisocial behaviour, drug use, and bad language) rather than the visceral biological responses expressed in the data. However, promising results were found for isoprene which reliably predicted 0, 6 and 12 age classifiers for a variety of film genres and audience age groups. Therefore, isoprene emission per person might in future be a valuable aid to national classification boards, or even offer an alternative, objective, metric for rating films based on the reactions of large groups of people.


Spatial and temporal analysis of Clostridium difficile infection in patients at a pediatric hospital in California.
To examine the usefulness of temporal and spatial analysis in identifying nosocomial transmission of Clostridium difficile among pediatric patients hospitalized on four wards at The Children's Hospital of Central California from September 8, 1998, to January 16, 1999. Stool specimens obtained from the clinical microbiology laboratory during the study period were tested by culture and latex agglutination for C. difficile. Polymerase chain reaction was used to identify toxin genes. Isolates obtained were mapped to a grid for each ward and were analyzed using the Knox test. Results were compared with DNA fingerprints generated by arbitrarily primed polymerase chain reaction. Total occupancy of these 4 wards was 438 during the study period. Stool specimens were available for 256 (58%) of these patients, yielding 67 C. difficile isolates and generating 2,211 case pairs for analysis by the Knox test. After stratification by toxin status, 5 clustered pairs of toxigenic isolates were identified on 1 of the wards by this method. Fingerprint analysis identified 4 clusters with indistinguishable banding patterns on 2 of the 4 wards. Two of the identified clusters were toxigenic and 2 were nontoxigenic. None of these clusters corresponded to clusters identified by the Knox test. The Knox test is an ineffective method for identifying cases resulting from nosocomial transmission of C. difficile in a pediatric setting due to the persistence of C. difficile spores and the unique environment of a pediatric hospital. Molecular analysis remains the most effective method.


Knowledge and attitude of guardians towards eye health of primary school pupils in Ilorin, Nigeria.
To determine guardians' knowledge and attitude towards pupils' eye health and draw implication for designing children-oriented ocular health messages. A survey of 1,393 guardians selected through multistage random sampling in Ilorin, Nigeria. Using structured questionnaire, information sought included guardians' demographic characteristics, relationship to pupils, occupation, awareness of eye specialists, perception of normal vision, pupils' eye complaints, and ways of treating children eye conditions. Data analysis was done with SPSS 12.0.1. The test of significance was performed using Chi square test and significance was taken at p < 0.05. Guardians comprised 689 (49.4%) males and 704 (50.6%) females, mean age 43.61 SD 11.45. Most (88.54%) were pupils' parents and (11.46%) were relations (n=1,318); (55.15%) were in low-paying occupations (n=1,311); (87.92%) were aware of eye specialists, (12.08%) unaware, (n=1192); (97.27%) adjudged normal vision at least important, (2.73%) not important (n=1,174). Pupils' eye complaints (n=914) included pain (26.04%), itching (24.73%), redness (21.12%), discharge (8.53%), blur vision (8.21%), photophobia (7.33%) and lacrimation (4.05%). Guardians (n=1,069) managed pupils' eye diseases using hospital treatment (61.65%), neglect (21.33%), self medication (9.26%) and traditional medication (7.76%). There were no significant associations between guardians' ways of managing pupils' eye diseases and their views on normal vision (p = 0.940); awareness of eye care specialists (p = 0.952); and economic occupational grouping (p = 0.959). The negative implications of neglecting eye diseases and use of self and harmful traditional eye-medications by some of the guardians need to be discouraged by appropriate eye health education.


Furosemide, Patella vulgata beta-glucuronidase and drug analysis: conditions for enhancement of the TLC detection of apomorphine, butorphanol, hydromorphone, nalbuphine, oxymorphone and pentazocine in equine urine.
We have investigated the action of five sources of beta-glucuronidase enzymes on the hydrolysis of glucuronides of apomorphine, butorphanol, hydromorphone, nalbuphine, oxymorphone and pentazocine in equine urine. For all glucuronides tested, Patella vulgata beta-glucuronidase yielded the largest thin layer chromatographic (TLC) spots. For oxymorphone, P. vulgata was the only treatment to yield detectable TLC spots under test parameters. For these six drugs, TLC spot size and chromatographic quality were compared between control horses and horses pretreated with furosemide four hours earlier. Furosemide pretreatment produced a statistically significant increase in spot size and was found to enhance chromatogram quality. These findings support previous suggestions that P. vulgata is a superior drug-glucuronide hydrolyzing enzyme. They also support earlier reports that administration of furosemide at four hours pre-race is unlikely to result in significant interference with routine drug testing procedures.


Live donor liver transplantation in adults.
Live donor liver transplantation (LDLT) was initiated in 1988 for children recipients. Its application to adult recipients was limited by graft size until the first right liver LDLT was performed in Hong Kong in 1996. Since then, right liver graft has become the major graft type. Despite rapid adoption of LDLT by many centers, many controversies on donor selection, indications, techniques, and ethics exist. With the recent known 11 donor deaths around the world, transplant surgeons are even more cautious than the past in the evaluation and selection of donors. The need for routine liver biopsy in donor evaluation is arguable but more and more centers opt for a policy of liberal liver biopsy. Donation of the middle hepatic vein (MHV) in the right liver graft was considered unsafe but now data indicate that the outcome of donors with or without MHV donation is about equal. Right liver LDLT has been shown to improve the overall survival rate of patients with chronic liver disease, acute or acute-on-chronic liver failure and hepatocellular carcinoma waiting for liver transplantation. The outcome of LDLT is equivalent to deceased donor liver transplantation despite a smaller graft size and higher technical complexity.


Evaluation of arm and thigh circumference in screening low birth weight newborns.
The present cross-sectional study collected data regarding birth weight along with arm and thigh circumference of 174 consecutive newborns delivered at Maternity Hospital, Tasgaon during 2003. To compare & evaluate utility of arm & thigh circumferences for the detection of LBW newborns. Assessment of the best suitable measurement for identification of low birth weight newborns was made by comparison of Coefficient of Determinants (R(2)), Sensitivity and Specificity values and Kappa Statistics. The estimated cut off points of arm and thigh circumference for given value of birth weight 2.5 kg. were 9.1 cm and 14.2 cm. respectively. Although both measurements are highly sensitive, present study established supiriority of arm circumference over thigh circumference in predicting low birth weight newborns. Thigh circumference is more reliable. Advantages of these measurements are their simplicity & low cost.


Isolation of Chlamydia trachomatis from the urethra and from prostatic fluid in men with signs and symptoms of acute urethritis.
Chlamydia trachomatis was isolated from the urethra in 71 of 275 men primarily attending the outpatient clinic of the Department of Urology because of symptoms of acute urethritis, and with more than four polymorphonuclear leukocytes in each of at least five fields of the swabbed urethral exudate (x1000). C. trachomatis was isolated from 34 of 48 men below 26 years of age, while only 37 of the 227 men aged 26 years or older harboured chlamydial infection. C. trachomatis was isolated from the prostatic secretion of 26 men with acute urethritis and more than 20 polymorphonuclear leukocytes in 10 or more random fields (x450) in the stripped prostatic fluid, suggesting a positive correlation between chlamydial infection and sub-acute silent prostatitis. Among 70 men with C. trachomatis isolated from the urethra, the organism had disappeared at re-examination within 10 days in 19 (27%). Such a disappearance was found in only one of 26 men (4%) in whom C. trachomatis had been isolated not only from the urethra but also from stripped prostatic fluid. Four weeks after two treatment cycles of lymecycline 300 mg twice daily for 7 days with an interval of 10 days, C. trachomatis was but isolated in any urethral specimen, nor from the expressed prostatic fluid.


Castleman's disease and mesangial proliferative glomerulonephritis: the role of interleukin-6.
Renal complications of Castleman's disease (angiofollicular lymph node hyperplasia) are uncommon. The reported cases are very heterogeneous and their renal pathology ranged from minimal change disease, mesangial proliferative glomerulonephritis, to amyloidosis. We have previously reported two cases of Castleman's disease with renal complications. We now present two more such cases. In contrast to other reports, all our cases are of the plasma cell type and their renal pathology showed remarkable similarities, namely mesangial proliferation, interstitial plasma cell infiltration and negative immunofluorescence. The level of serum interleukin-6 (IL-6) in both patients was elevated at presentation and came down with immunosuppressive therapy.


On the mechanism of acute tolerance to furosemide diuresis.
The renal response to continuous furosemide infusion (8 mg/h) and subsequent ECV changes was studied in 8 healthy volunteers. Furosemide increased urine flow from a basal flow of 4.3 ml/min to a maximum of 15.4 ml/min. During dehydration (-1.8 kg) the diuresis decreased to 8.4 ml/min. The sodium, chloride and potassium excretion likewise decreased. This reduction in diuretic effect (acute tolerance) was accompanied by significantly increased plasma levels of norepinephrine (1.38 to 2.14 nmol/l), PRA (0.52 to 1.13 ng/ml/h) and aldosterone (0.29 to 0.45 nmol/l). After rehydration the urine flow increased to 23.1 ml/min. The changes in diuretic response from initial effect to the dehydrated state and after rehydration were mainly a consequence of changed renal sensitivity to furosemide (urinary excretion of 21 to 14 to 35 mumol Na+ per microgram furosemide excreted). It is proposed that activation of the sympathetic nervous system and/or the renin-angiotensin-aldosterone system may play a role in mediating the acute tolerance to furosemide diuresis. The relative importance of each remains to be clarified.


Nurse-staffing levels and the quality of care in hospitals.
It is uncertain whether lower levels of staffing by nurses at hospitals are associated with an increased risk that patients will have complications or die. We used administrative data from 1997 for 799 hospitals in 11 states (covering 5,075,969 discharges of medical patients and 1,104,659 discharges of surgical patients) to examine the relation between the amount of care provided by nurses at the hospital and patients' outcomes. We conducted regression analyses in which we controlled for patients' risk of adverse outcomes, differences in the nursing care needed for each hospital's patients, and other variables. The mean number of hours of nursing care per patient-day was 11.4, of which 7.8 hours were provided by registered nurses, 1.2 hours by licensed practical nurses, and 2.4 hours by nurses' aides. Among medical patients, a higher proportion of hours of care per day provided by registered nurses and a greater absolute number of hours of care per day provided by registered nurses were associated with a shorter length of stay (P=0.01 and P<0.001, respectively) and lower rates of both urinary tract infections (P<0.001 and P=0.003, respectively) and upper gastrointestinal bleeding (P=0.03 and P=0.007, respectively). A higher proportion of hours of care provided by registered nurses was also associated with lower rates of pneumonia (P=0.001), shock or cardiac arrest (P=0.007), and "failure to rescue," which was defined as death from pneumonia, shock or cardiac arrest, upper gastrointestinal bleeding, sepsis, or deep venous thrombosis (P=0.05). Among surgical patients, a higher proportion of care provided by registered nurses was associated with lower rates of urinary tract infections (P=0.04), and a greater number of hours of care per day provided by registered nurses was associated with lower rates of "failure to rescue" (P=0.008). We found no associations between increased levels of staffing by registered nurses and the rate of in-hospital death or between increased staffing by licensed practical nurses or nurses' aides and the rate of adverse outcomes. A higher proportion of hours of nursing care provided by registered nurses and a greater number of hours of care by registered nurses per day are associated with better care for hospitalized patients.


The metabolism and drug-drug interaction potential of the selective prostacyclin receptor agonist selexipag.
1. The metabolism of selexipag has been studied in vivo in man and the main excreted metabolites were identified. Also, metabolites circulating in human plasma have been structurally identified and quantified. 2. The main metabolic pathway of selexipag in man is the formation of the active metabolite ACT-333679. Other metabolic pathways include oxidation and dealkylation reactions. All primary metabolites undergo subsequent hydrolysis of the sulphonamide moiety to their corresponding acids. ACT-333679 undergoes conjugation with glucuronic acid and aromatic hydroxylation to P10, the main metabolite detected in human faeces. 3. The formation of the active metabolite ACT-333679 is catalysed by carboxylesterases, while the oxidation and dealkylation reactions are metabolized by CYP2C8 and CYP3A4. CYP2C8 is the only P450 isoform catalysing the aromatic hydroxylation to P10. CYP2C8 together with CYP3A4 are also involved in the formation of several minor ACT-333679 metabolites. UGT1A3 and UGT2B7 catalyse the glucuronidation of ACT-333679. 4. The potential of selexipag to inhibit or induce cytochrome P450 enzymes or drug transport proteins was studied in vitro. Selexipag is an inhibitor of CYP2C8 and CYP2C9 and induces CYP3A4 and CYP2C9 in vitro. Also, selexipag inhibits the transporters OATP1B1, OATP1B3, OAT1, OAT3, and BCRP. However, due to its low dose and relatively low unbound exposure, selexipag has a low potential for causing drug-drug interactions.


Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis.
This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment. Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy. A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy. Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.


Pools of ribosomal proteins in Escherichia coli. Studies on the exchange of proteins between pools and ribosomes.
A labelling technique in vivo has been introduced which allows the tritiation of cell components with high specific activity during growth in rich medium. By this technique the pool size of each protein can be measured directly in the supernatant from centrifugation at 150000 times g. A measurable pool was found for the proteins S1, S2, S10, L1, L4, L7, L8/9, L10, L12, L21, and L25. Experiments on migration of ribosomal proteins from the supernatant to ribosomes (i.e. association) and vice versa (dissociation) demonstrate a remarkable constancy in the composition of the ribosome. There is no significant difference between ribosomes engaged or not engaged in poly-(Phe) synthesis.


Characterization of the Methylthioadenosine Phosphorylase Polymorphism rs7023954 - Incidence and Effects on Enzymatic Function in Malignant Melanoma.
Deficiency of methylthioadenosine phosphorylase (MTAP) supports melanoma development and progression through accumulation of its substrate 5'-methylthioadenosine (MTA), which leads amongst others to a constitutive inhibition of protein arginine methyltransferases (PRMTs) and activation of the transcription factor AP-1 via the receptor ADORA2B. Genetic association studies have also suggested that genetic polymorphism in MTAP may modulate the risk of melanoma. Here, we investigated the only globally common non-synonymous single nucleotide polymorphism (SNP) reported to date for MTAP. The SNP rs7023954 is located in exon 3 (c.166G>A), and leads to the conservative substitution of one branched-chain amino acid residue (valine) for another (isoleucine) at position 56 (p.Val56Ile). Whereas genotype frequencies in normal and primary melanoma tissues or cell lines were in Hardy-Weinberg equilibrium based on cDNA amplicon sequencing, a marked (P = 0.00019) deviation was observed in metastatic melanoma tissues and cell lines due to a deficit of heterozygotes. Enzyme assays conducted on the co-dominantly expressed alleles revealed no difference in the conversion rate of MTA to adenine and 5-methylthioribose-1-phosphate, indicating that this known enzymatic activity does not modulate the tumor suppressive function of MTAP.


Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia.
Preeclampsia (PE) remains a major cause of maternal/fetal morbidity-mortality worldwide. The first stage of PE is characterized by placental hypoxia due to a relative reduction in uteroplacental blood flow, resulting from restricted trophoblast invasion. However, hypoxia is also an essential element for the success of invasion. Under hypoxic conditions, 2-methoxyestradiol (2-ME) could induce the differentiation of cytotrophoblast cells into an invasive phenotype in culture. 2-Methoxyestradiol is generated by catechol-O-methyltransferase, an enzyme involved in the metabolic pathway of estrogens. During pregnancy, circulating 2-ME levels increase significantly when compared to the menstrual cycle. Interestingly, plasma levels of 2-ME are lower in women with PE than in controls, and these differences are apparent weeks or even months before the clinical manifestations of the disease. This article reviews the metabolic pathways involved in 2-ME synthesis and discusses the roles of these pathways in normal and abnormal pregnancies, with particular emphasis on PE.


Characterization of [3H]AMP binding to rat adipose plasma membranes and its substrate specificity.
We evaluated the binding of [3H]AMP to rat adipose plasma membranes and studied the substrate specificity of the process. The [3H]AMP binding was investigated by high-speed filtration under conditions of virtually complete inhibition of the 5'-nucleotidase activity by EDTA/Na. The Scatchard plot revealed the existence of a single class of AMP-binding sites on the membrane surface with Kd of 2.14 +/- 0.210 microM and the binding capacity (Bmax) of 26.0 +/- 0.68 pmol per mg protein. Addition of ATP (12.5 microM) or ADP (3.5 microM) to the incubation medium resulted in a two-fold increase of Kd, whereas in the presence of adenosine (400 microM) or its pharmacological antagonist theophylline (200 microM), the number of AMP-binding sites decreased. Therefore, ATP and ADP but not adenosine compete with AMP for the same nucleotide-binding site. It is suggested that the observed [3H]AMP binding may be primarily caused by the interaction of AMP with a specific substrate-binding active centre of the membrane ectoenzyme 5'-nucleotidase.


Dynamics in psoralen-damaged DNA by 1H-detected natural abundance 13C NMR spectroscopy.
The dynamics of the DNA oligomer d(GCGTACGC)2 and the 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen-DNA furanside monoadduct (MAf) of this oligomer have been determined from NMR relaxation parameters. Longitudinal and transverse 13C relaxation rates and heteronuclear NOE relaxation data have been measured at natural abundance and have been analyzed in the context of the Lipari and Szabo model-free formalism. The generalized order parameters for methine carbons in the octamer sequence d(GCGTACGC)2 (UM) are relatively and uniformly high for the entire molecule. The generalized order parameters for methine carbons in the MAf are significantly lower for the deoxyribose bearing the damaged thymidine base and for the bases flanking the lesion on the undamaged strand, indicating additional conformational flexibility due to the lesion. The order parameters for the bases on the damaged strand flanking the lesion remain high. Analysis of the relaxation data indicates substantial chemical exchange for the adenosine residues in the UM TpA site, and this chemical exchange is quenched upon MAf formation. These data are discussed in terms of a model for DNA damage recognition by the nucleotide excision repair system.


Optimized Soft Lithography Method for Polymer Cholesteric Liquid Crystal Flakes Fabrication.
Polymer cholesteric liquid crystal (PCLC) flakes are gaining increasing interest for a wide variety of applications because of their unique optical properties and capabilities. Soft lithography is the most effective way to fabricate regularly shaped PCLC flakes. However, it is not easy to peel the flakes from the mold without breaking them. In order to peel the PCLC flakes from the patterned polydimethylsiloxane (PDMS) mold in a convenient way, in this paper, a method of coating a layer of polyvinyl alcohol (PVA) on a PDMS mold was proposed. The influence of the thickness of the PVA layer on the shape of the PCLC flakes and the release time from the PDMS mold were investigated. The results show that the presence of the PVA layer can speed up the release of the PCLC flakes and help maintain the shape effectively. Notably, the utilization of a PVA layer makes the PDMS mold recyclable. The influence of PCLC flake shape was also studied. This work will promote the development of switchable PCLC flake-based technologies.


Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus.
The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier's plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 +/- 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 +/- 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02-1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01-1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02-1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease were independent predictors of work disability.


Biomarkers intersect with the exposome.
The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment.


Comparisons of physical imaging properties among three kinds of imaging plates used in photostimulable phosphor systems for dental radiography.
The purpose of this study was to compare the physical imaging properties of three kinds of imaging plates (IPs) used with two photostimulable phosphor systems for dental radiography: HR-V, used with the Digora, BAS-SR, and ST-V, used with the DenOptix for intraoral radiography and panoramic radiography, respectively. Sensitivity to X-ray, gradient, modulation transfer function (MTF), noise power spectrum (NPS), noise-equivalent quanta (NEQ), and detective quantum efficiency (DQE) were compared. All imaging plates were read using the DenOptix scanner with inactive automatic range control (ARC). The scanning resolution was set at 300 dpi. Decay of image information by room light was also compared at inactive and active ARC settings. BAS-SR showed the lowest sensitivity, the lowest gradient, the highest MTF, and the highest NPS. ST-V showed the highest sensitivity, the highest gradient, the lowest MTF, and the lowest NPS. HR-V was the second best for all imaging properties examined in this study. NEQ and DQE of BAS-SR were lowest, and those of ST-V were highest at low spatial frequencies. However, BAS-SR showed relatively constant NEQ and DQE while those of ST-V decreased remarkably at high spatial frequencies. NEQ and DQE of HR-V were the second best at low spatial frequencies and the best at high spatial frequencies. Therefore, we concluded that HR-V has the best imaging properties for dental radiography among three kinds of IPs evaluated in this study. However, the light decay speed of image information with HR-V was remarkably faster than with BAS-SR. To adopt HR-V for a system with which IPs are treated in an ordinary room, the light decay should be taken into account.


Role of percutaneous coronary intervention in the treatment of left main coronary artery disease.
Revascularization with coronary artery bypass graft surgery is the choice of therapy in patients with left main (LM) coronary artery stenosis. During the last decade, the introduction of drug-eluting stents, together with antiplatelet and antithrombotic treatments, has improved the outcome of percutaneous coronary interventions (PCIs) by reducing the number of repeat revascularizations and the risk of stent thrombosis. Many institutions inside and outside the United States have adopted stent treatment of unprotected LM coronary artery disease as a more routine strategy. However, coronary bypass surgery has improved as well by using more arterial grafts, better perioperative care, and optimizing medical treatment postoperatively. The advances in stent technique may reduce the gap between coronary surgery and PCIs further, but the results of the Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization study, randomizing patients with LM coronary artery disease between coronary bypass grafting and PCIs, will be needed to test whether PCIs is noninferior to coronary bypass surgery.


Solitary fibrous tumor arising in an intrathoracic goiter.
Solitary fibrous tumor (SFT) is a rare spindle cell tumor most often found in the mediastinal pleura. Nineteen cases of SFT arising in the thyroid gland have been reported. We report a case of SFT of the thyroid gland with immunohistochemical and cytogenetic investigation. A 58-year-old man had pulmonary symptoms, thought to be asthma. Computed tomographic scan revealed a large goiter with a solid hyperechoic nodule. The results of thyroid function tests were normal. Microscopically, the lesion was composed of fibroblast-like spindle cells in a patternless growth. Cellular atypia or necrosis was not seen, and mitotic activity was low. Immunohistochemistry showed positive reaction for CD34, vimentin, bcl-2, and CD99. Fluorescence in situ hybridization analysis of more than 100 cells exhibited no trisomy 21. Complete surgical removal of tumor is the treatment of choice. The histological appearance and immunohistochemical reaction pattern of SFT is characteristic. The entity should be considered when dealing with a spindle cell lesion in the thyroid gland. All cases of this site of origin reported have had a benign clinical course. As only a small number of cases have been described, we recommend long-term follow-up.


[Evaluation of basic laparoscopic training under 5A teaching mode].
Objective: To evaluate the rationality and effectiveness of basic laparoscopic training under 5A teaching mode. Methods: A prospective randomized controlled study was conducted. The teaching records of 70 trainees who received basic laparoscopic traning at the Laparoscopic Surgical Training Base in Chinese PLA General Hospital from July to December 2019 were analyzed. All the trainees participating in the laparoscopy training had obtained the national practicing physician certificates, including 12 junior physicians of our center, 9 intermediate physicians of our center, 19 advanced physicians, 13 postgraduate students, 8 doctoral students, and 9 surgical standardized training physicians. A random number table method was used to divide all the trainees into two groups: the traditional teaching group or the 5A teaching group (35 people in each group). In the traditional teaching group, the training of 4 modules of " precise beans, quincuncial piles, ring positioning and knot-tying suture" modules according to a fixed sequence and schedule was carried out. Each module had a learning time of 8 hours. In the 5A teaching group, the training started from five dimensions of analysis, aim, accomplishment, appraise and advance. Before conducting each stage of training, the actual operation ability of the trainees was tested, each class hour was designed individually, accurate teaching was conducted to the trainees, the ability of the trainees was evaluated dynamically, and the previous steps were cycled periodically based on class hours. The operating time and pass rate of trainees of two groups in the basic operation module of laparoscopy were statistically analyzed, and a hierarchical analysis of related influencing factors was conducted. Results: The time of above modules before training in the 5A teaching group and the traditional teaching group was similar (all P>0.05). After definitive training, the time required for trainees in 5A teaching group and traditional teaching group to complete the 4 modules was shortened to varying degrees. Compared to traditional teaching group, 5A teaching group spent less time in completing each project [precise beans: (63.2±10.1) seconds vs. (83.6±18.7) seconds, quincuncial piles: (56.2±7.3) seconds vs. (101.4±31.7) seconds, ring positioning: (84.2±13.7) seconds vs. (127.3±28.5) seconds, knot-tying suture: (263.2±41.8) seconds vs.(428.8±95.2) seconds, all P<0.05], and had higher pass rates [precise beans: 97.1% (34/35) vs. 80.0% (28/35), quincuncial piles: 91.4% (32/35) vs.71.4% (25/35), ring positioning: 100.0% (35/35) vs. 82.9% (29/35), knot-tying suture: 77.1% (27/35) vs. 60.0% (21/35), all P<0.05]. Among the junior trainees (junior physicians of our center, postgraduate students, doctoral students, and standardized surgical training physicians) and intermediate trainees (intermediate physicians of our center and advanced physicians), the 5A teaching group completed 3 modules (quincuncial piles, ring positioning and knot-tying suture) faster than the traditional teaching group [junior trainees: quincuncial piles (76.4±12.4) seconds vs. (139.8±41.6) seconds, ring positioning (92.2±20.5) seconds vs. (131.3±28.4) seconds, knot-tying suture (293.8±66.7) seconds vs. (444.3±103.3) seconds; intermediate trainees: quincuncial piles (51.4±5.9) seconds vs. (94.7±8.6) seconds, ring positioning (63.9±13.5) seconds vs. (87.5±18.6) seconds, knot-tying suture (210.1±35.6) seconds vs. (367.5±54.9) seconds, all P<0.05]. Conclusion: 5A teaching mode can acheive better training results compared with the traditional teaching mode in basic laparoscopic training, and is worthy of further popularization and application.


Four-year results of a prospective single-arm study on 200 semi-constrained total cervical disc prostheses: clinical and radiographic outcome.
OBJECTIVE Recent studies have described encouraging outcomes after cervical total disc replacement (cTDR), but there are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration. The aim in this paper was to provide 4-year clinical and radiographic outcome results on the activ C disc prosthesis. METHODS A total of 200 subjects underwent single-level activ C (Aesculap AG) implantation between C-3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis. RESULTS Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4° preoperatively to -6.2° at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical treatment. CONCLUSIONS The activ C is a safe and effective device for cervical disc replacement confirming the encouraging results after cTDR. Clinical trial registration no.: NCT02492724 ( clinicaltrials.gov ).


[Construction of beta-hydroxyacyl-acyl carrier protein dehydratase mutant of Toxoplasma gondii by tetracycline inducible expression system].
To construct a beta-hydroxyacyl-acyl carrier protein dehydratase (FABZ) mutant of Toxoplasma gondii with tetracycline inducible expression system. The fabz gene was amplified from T. gondii genomic DNA, and then used to construct the tetracycline inducible expression vector pTetO7-Sag1-FABZ-Ty-DHFR. The vector was transfected into TATi strain by electroporation. The FABZ defective mutant was selected by pyrimethamine and limitting dilution assay. The expression of Ty-tagged mutant was detected by Western blotting. 5 x 10(5) tachyzoites of FABZ defective mutant were cultured in HFF in the presence of anhydrotetracycline (ATc, 1 microg/ml) for 24 h and 48 h, respectively. The expression of Ty-tagged FABZ protein in the mutant was detected by Western blotting. The mutant could express the transit peptide (t-FABZ) and mature FABZ (m-FABZ) with the Ty-epitope tag. After ATc added in culture medium for 24 h and 48 h, the expression of t-FABZ in the mutant decreased significantly (P<0.05). The FABZ mutant is constructed with a tetracycline inducible expression system.


Investigation and control of a suspected nosocomial outbreak of pan-drug resistant Acinetobacter baumannii in an intensive care unit.
Acinetobacter baumannii, a non-fermenting Gram-negative bacterium, is a common pathogen in intensive care units (ICU) that is easily spread through contact and can cause nosocomial outbreaks. This study investigated the risk factors associated with outbreaks of pan-drug resistant Acinetobacter baumannii (PDR-Ab) infection by studying a suspected nosocomial outbreak in a comprehensive ICU in a teaching hospital in China, and discusses the effectiveness of current prevention and control measures. Pathogen detection methods involving pulsed field gel electrophoresis (PFGE) were employed to survey patients infected or colonized with PDR-Ab. An epidemiological investigation was conducted to determine the risk factors for infection or colonization with PDR-Ab between 1 October 2014 and 16 January 2015. The rate of PDR-Ab infection in the ICU was higher during the period from 1 October 2014 to 16 January 2015 than it was between 1 October 2013 and 16 January 2014. Only two cases were confirmed to have the same genotype. Risk factors were explored and the rate of infection was found to be controlled by interventions targeting these risk factors. A decrease in the number of infections was observed after multiple prevention and control measures were implemented, preventing the outbreak of a nosocomial infection.


Giardia lamblia trophozoites in gastric biopsies.
To assess the prevalence of gastric giardiasis in gastric biopsies of patients with carcinoma stomach and in patients taking treatment for duodenal ulcer. Gastric biopsy specimens from 54 patients of carcinoma stomach and 100 antral biopsies from patients taking treatment for duodenal ulcer were included in the study. Sections were stained with haematoxylin and eosin, methylene blue and May Grunwald-Giemsa stains and examined for presence of Giardia lamblia trophozoites. Eight out of 54 (14.9%) biopsies of gastric carcinoma patients harboured trophozoites of Giardia lamblia. Associated H. pylori infection was present in all biopsies (8/8; 100%). Atrophy and intestinal metaplasia was present in 62.5% (5/8) and 25% (2/8) cases respectively. Sections from seven out of 35 patients (20%) taking treatment for duodenal ulcer showed presence of G. lamblia. H. pylori infection, gastritis and atrophy were found in 85.7% (6/7), 71.4% (5/7) and 28.6% (2/7) cases respectively. First gastric biopsy in these patients was negative for G. lamblia but 2nd and 3rd biopsies were positive. A careful search for G. lamblia trophozoites should be made while examining the gastric biopsies, especially in patients with carcinoma stomach, intestinal metaplasia, atrophic gastritis and those taking treatment for duodenal ulcer. This may help in indirect diagnosis of clinically unsuspected cases of intestinal giardiasis and may explain persistence of vague upper gastrointestinal tract (UGIT) symptoms despite clearance of H. pylori in patients on anti-ulcer therapy.


Ochrobactrum quorumnocens sp. nov., a quorum quenching bacterium from the potato rhizosphere, and comparative genome analysis with related type strains.
Ochrobactrum spp. are ubiquitous bacteria attracting growing attention as important members of microbiomes of plants and nematodes and as a source of enzymes for biotechnology. Strain Ochrobactrum sp. A44T was isolated from the rhizosphere of a field-grown potato in Gelderland, the Netherlands. The strain can interfere with quorum sensing (QS) of Gram-negative bacteria through inactivation of N-acyl homoserine lactones (AHLs) and protect plant tissue against soft rot pathogens, the virulence of which is governed by QS. Phylogenetic analysis based on 16S rRNA gene alone and concatenation of 16S rRNA gene and MLSA genes (groEL and gyrB) revealed that the closest relatives of A44T are O. grignonense OgA9aT, O. thiophenivorans DSM 7216T, O. pseudogrignonense CCUG 30717T, O. pituitosum CCUG 50899T, and O. rhizosphaerae PR17T. Genomes of all six type strains were sequenced, significantly expanding the possibility of genome-based analyses in Ochrobactrum spp. Average nucleotide identity (ANIb) and genome-to-genome distance (GGDC) values for A44T and the related strains were below the single species thresholds (95% and 70%, respectively), with the highest scores obtained for O. pituitosum CCUG 50899T (87.31%; 35.6%), O. rhizosphaerae PR17T (86.80%; 34.3%), and O. grignonense OgA9aT (86.30%; 33.6%). Distinction of A44T from the related type strains was supported by chemotaxonomic and biochemical analyses. Comparative genomics revealed that the core genome for the newly sequenced strains comprises 2731 genes, constituting 50-66% of each individual genome. Through phenotype-to-genotype study, we found that the non-motile strain O. thiophenivorans DSM 7216T lacks a cluster of genes related to flagella formation. Moreover, we explored the genetic background of distinct urease activity among the strains. Here, we propose to establish a novel species Ochrobactrum quorumnocens, with A44T as the type strain (= LMG 30544T = PCM 2957T).


Effect of custom-made foot orthoses in female hallux valgus after one-year follow up.
Subtalar joint hyperpronation plays a fundamental role in the development of hallux valgus (HV). Foot orthotics have used to treat this condition and are aimed at preventing progression of the deformity. The aim of this study was to determine if the use of custom-made foot orthotics for 12 months prevented the advancement of HV in women. Prospective trial, using a repeated-measures design. Fifty-four women with mild to moderate HV were divided into two groups: the experimental group used custom-made foot orthoses, and the control group used no treatment. First intermetatarsal (IMA) and hallux abductus (HAA) angles were measured at the beginning of the study and after 12-months follow up. Inter-group comparisons were made of these angles at both times of measurement, and intra-group comparisons between the two times of measurement. The initial HAA was similar in both groups (19.92 ± 4.25 degrees for the control group, 20.55 ± 5.10 degrees for the experimental group; p = 0.392), and also the IMA (10.56 ± 2.45 degrees for the control group, 10.86 ± 2.33 for the experimental group; p = 0.618) There were no significant differences in the follow-up values of these angles (p = 0.395 and p = 0.288, respectively). There were no significant intra-group differences in the comparisons of the initial and follow-up angles. HV did not have a significantly slower evolution in participants of the experimental group compared with controls. Custom-made orthoses appear to have no effect in the evolution of mild and moderate HV during a 12 month period. Clinical relevance Subtalar joint hyperpronation plays a fundamental role in the development of hallux valgus. Conservative management typically involves the use of foot orthotics which is aimed at preventing the progress of the condition. The use of foot orthotics however should be used as a long term management strategy (beyond 12 months).


Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1.
Mitotic centromere-associated kinesin (MCAK) plays an essential role in spindle formation and in correction of improper microtubule-kinetochore attachments. The localization and activity of MCAK at the centromere/kinetochore are controlled by Aurora B kinase. However, MCAK is also abundant in the cytosol and at centrosomes during mitosis, and its regulatory mechanism at these sites is unknown. We show here that cyclin-dependent kinase 1 (Cdk1) phosphorylates T537 in the core domain of MCAK and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of MCAK by Cdk1 promotes the release of MCAK from centrosomes and is required for proper spindle formation. Interfering with the regulation of MCAK by Cdk1 causes dramatic defects in spindle formation and in chromosome positioning. This is the first study demonstrating that Cdk1 regulates the localization and activity of MCAK in mitosis by directly phosphorylating the catalytic core domain of MCAK.


A peroxisomal lon protease and peroxisome degradation by autophagy play key roles in vitality of Hansenula polymorpha cells.
In eukaryote cells various mechanisms exist that are responsible for the removal of non-functional proteins. Here we show that in the yeast Hansenula polymorpha (H. polymorpha) a peroxisomal Lon protease, Pln, plays a role in degradation of unfolded and non-assembled peroxisomal matrix proteins. In addition, we demonstrate that whole peroxisomes are constitutively degraded by autophagy during normal vegetative growth of WT cells. Deletion of both H. polymorpha PLN and ATG1, required for autophagy, resulted in a significant increase in peroxisome numbers, paralleled by a decrease in cell viability relative to WT cells. Also, in these cells and in cells of PLN and ATG1 single deletion strains, the intracellular levels of reactive oxygen species had increased relative to WT controls. The enhanced generation of reactive oxygen species may be related to an uneven distribution of peroxisomal catalase activities in the mutant cells, as demonstrated by cytochemistry. We speculate that in the absence of HpPln or autophagy unfolded and non-assembled peroxisomal matrix proteins accumulate, which can form aggregates and lead to an imbalance in hydrogen peroxide production and degradation in some of the organelles.


Virtual Coordinate System in Unicoronal Synostosis.
We propose a landmark-based, virtual coordinate system, specifically designed for assessment of asymmetrical craniofacial anatomy associated with unicoronal synostosis. CT scans of 33 patients with nonsyndromic unicoronal synostosis were included. Proposed mid-sagittal plane was compared with commonly used sagittal planes: (1) nasion, sella, and basion (N-S-BA); (2) midplane of bilateral frontozygomatic sutures (midFZ); and (3) the skull gravity center plane, to evaluate reliability and validity in the assessments of the anterior and posterior skull base. The proposed midplane is similar to the midFZ plane in describing the direction of the anterior skull base. However, it has less bias than the N-S-BA (P < 0.001), and the gravity center planes (P < 0.001). The proposed midplane measures the direction of the posterior skull base plane, similar to the midFZ and gravity center planes, but it has less measurement deviation than the N-S-BA plane (P < 0.001). The most protrusive point on the frontal bone in unicoronal patients is contralateral to the fused suture and distant from the mid-sagittal plane by 13.93 ± 4.01 mm. In addition, it is more anteriorly positioned, by 5.32 mm (P < 0.001), when compared with the corresponding point on the synostotic side. The uppermost point of the supraorbital rim on the synostotic side is cephalic to that of the contralateral side by 4.09 mm (P < 0.001). Prioritized orientation of an averaged Frankfort horizontal plane, followed by the location of the mid-sagittal and coronal planes, can generate a reliable and valid coordinate framework for the assessment of asymmetric skull shape in unicoronal synostosis.


Incidence and outcomes of lymphoid malignancies in adolescent and young adult patients in the United States.
Lymphoma incidence and survival in adolescent and young adult (AYA, defined as 15-39 years of age) and adult patients (>39 years) were assessed using Surveillance, Epidemiology, and End Results (SEER) data. From 2000 to 2014, 431 721 lymphoma cases were reported to SEER, 9% in AYA patients. In the AYA group, the highest age-adjusted incidence rate was for classical Hodgkin lymphoma [HL; 3·4 per 100 000 person-years; 95% confidence interval (CI), 3·38-3·49] followed by diffuse large B cell lymphoma (DLBCL; 1·56, 95% CI, 1·53-1·60) and for adults, it was plasma cell neoplasms (14·17, 95% CI, 14·07-14·27), DLBCL (13·86, 95% CI, 13·76-13·96) and chronic lymphocytic leukaemia (CLL; 13·19, 95% CI, 13·09-13·29). HL comprised 42% of lymphoma cases for AYAs, but only 4% in adults. The occurrence of DLBCL among AYAs and adults was similar, 18% and 20%, respectively. Twenty-eight percent of AYAs compared with 9% of adults presented with stage II disease, and 21% of AYAs compared with 10% of adults had B-symptoms. Extranodal disease was less common (33%) in AYAs than adults (59%). Overall, AYA patients with lymphoma have better 2- and 5-year relative survival rates (RSRs) compared to adults. When restricted to HL and DLBCL, RSR of AYA patients exceeds adult RSR.


Knockdown of TRPM8 suppresses cancer malignancy and enhances epirubicin-induced apoptosis in human osteosarcoma cells.
As the function of transient receptor potential melastatin member 8 (TRPM8) in osteosarcoma is still unknown, we aim to investigate the possible effects and potential mechanisms of TRPM8 on cell proliferation, metastasis and chemosensitivity in osteosarcoma cells. We find that TRPM8 is aberrantly over-expressed in human osteosarcoma tissues and cell lines. Knockdown of TRPM8 by siRNA in osteosarcoma cells leads to the impaired regulation of intracellular Ca(2+) concentration and then the Akt-GSK-3β pathway and the phosphorylation of p44/p42 and FAK are suppressed. Knockdown of TRPM8 not only negatively influences the cell proliferation and metastasis but also enhances epirubicin-induced cell apoptosis. Such results reveal that TRPM8 is worthy further investigation for its potential as a clinical biomarker and therapeutic target in osteosarcoma.


[Initial Groningen experiences with dynamic cardiomyoplasty].
Four patients, one woman and three men aged 48, 62, 49, en 54 years respectively, were subjected to cardiomyoplasty because of medically refractory heart failure secondary to ischaemic or idiopathic dilating cardiomyopathy. The operation and the training period were uncomplicated. In one patient symptoms of heart failure did not improve; the other patients experienced substantial relief of symptoms. However, all three died suddenly within one year after the operation, probably due to ventricular arrhythmias. Cardiomyoplasty may deserve a place in the treatment of heart failure, provided sudden death can be better prevented. Possibly, treatment with an implantable cardioverter-defibrillator might be useful.


Solvent and solvent isotope effects on the vibrational cooling dynamics of a DNA base derivative.
Vibrational cooling by 9-methyladenine was studied in a series of solvents by femtosecond transient absorption spectroscopy. Signals at UV and near-UV probe wavelengths were assigned to hot ground state population created by ultrafast internal conversion following electronic excitation by a 267 nm pump pulse. A characteristic time for vibrational cooling was determined from bleach recovery signals at 250 nm. This time increases progressively in H2O (2.4 ps), D2O (4.2 ps), methanol (4.5 ps), and acetonitrile (13.1 ps), revealing a pronounced solvent effect on the dissipation of excess vibrational energy. The trend also indicates that the rate of cooling is enhanced in solvents with a dense network of hydrogen bonds. The faster rate of cooling seen in H2O vs D2O is noteworthy in view of the similar hydrogen bonding and macroscopic thermal properties of both liquids. We propose that the solvent isotope effect arises from differences in the rates of solute-solvent vibrational energy transfer. Given the similarities of the vibrational friction spectra of H2O and D2O at low frequencies, the solvent isotope effect may indicate that a considerable portion of the excess energy decays by exciting relatively high frequency (>/=700 cm-1) solvent modes.


Response of Gene Expression and Alternative Splicing to Distinct Growth Environments in Tomato.
Phenotypic plasticity is the phenomenon that one particular genotype produces different phenotypes under different environmental conditions, but its underlying molecular and genetic mechanisms are poorly understood. Plastic traits may be under the control of genes whose expression is modulated by environmental cues. In this study, we investigated phenotypic plasticity in tomato (Solanum lycopersicum) and its ancestral species S. pimpinellifolium by comparing the global gene expression of young seedlings grown under two distinct growth conditions. Our results show that more than 7000 genes exhibited differential expression in response to environmental changes from phytotron to a plastic greenhouse, and 98 environmentally sensitive genes displayed the same patterns of expression response across the two tomato species. We also found that growth conditions had a remarkable impact on transcriptome complexity, attributable to alternative splicing (AS), in which 665 splice variants showed differential expression in response to the environmental changes. Moreover, more splice variants and AS events per gene were detected in plastic greenhouse-grown seedlings than their phytotron counterparts, and these seedlings also had higher percentages of intron retention events. The identification of the conserved environmentally-sensitive genes and the splice variants in this study will be useful for further analysis of gene regulation of environmental response in tomato and other crops.


Enzymatic deglutathionylation to generate interleukin-4 cysteine muteins with free thiol.
Interleukin-4 (IL-4) is a prototypical regulator protein of the immune system that is crucial for the pathogenesis and maintenance of asthma and other atopic diseases. It, together with IL-13, uses the IL-4 receptor α chain (IL-4Rα) to signal into immune and other cells. An IL-4 mutein acting as a dual IL-4/IL-13 receptor antagonist is in clinical development. Here, it is described how IL-4 muteins containing a single engineered cysteine with a free thiol can be prepared and used for site-specific chemical modification. The muteins were initially expressed in E. coli, refolded, and purified, but not in a fully reduced nonconjugated form. Attempts to reduce the cysteine chemically failed because the native disulfide bonds of IL-4 were also reduced under similar conditions. Therefore, an enzymatic procedure was developed to reduce glutathionylated IL-4 cysteine muteins employing glutaredoxin and reduced glutathione. Cysteine muteins engineered at four different positions around the IL-4Rα binding site were enzymatically reduced at different rates. All muteins were prepared with free thiol in reasonable yield and were modified by N-ethylmaleimide (NEM) or maleimido-PEG. The effect on IL-4Rα binding of cysteine substitution and of the site-specific modification by glutathione, N-ethylmaleimide (NEM), or a branched 2.36 kDa poly(ethylene glycol) (PEG) will be discussed.


Allosteric sites of the large subunit of the spinach leaf ADPglucose pyrophosphorylase.
Pyridoxal-P, an analog of 3-phosphoglycerate, activates spinach leaf ADPglucose pyrophosphorylase. Reductive phosphopyridoxylation of the enzyme yields enzyme less dependent on the presence of activator for activity. Labeled pyridoxal-P is incorporated into both the 51- and 54-kDa subunits of the enzyme. The sequence of the single tryptic labeled peptide of the small subunit has been reported (Morell, M., Bloom, M., and Preiss, J. (1988) J. Biol. Chem. 263, 633-637). Three distinct labeled peptides are isolated from the tryptic digest of the large subunit. 3-Phosphoglycerate inhibits incorporation of pyridoxal-P by 80% into all three large subunit tryptic peptides, whereas inorganic phosphate, the allosteric inhibitor, inhibits incorporation into only one of those peptides. Comparison of the sequences of the labeled tryptic peptides with those of large and small subunits of the enzyme from other species indicate their positions in the primary structure of the spinach enzyme large subunit. The conservation in the amino acid sequences surrounding the lysyl residue in the small subunit and of the lysyl residue in the large subunit in higher plant and in cyanobacterial ADPglucose pyrophosphorylases, which are protected from phosphopyridoxylation by both allosteric effectors, suggests that these lysyl residues are involved in activator binding.


Emissions and Occupational Exposure Risk of Halogenated Flame Retardants from Primitive Recycling of E-Waste.
The production and usage of non-polybrominated diphenyl ether (PBDE) halogenated flame retardants (HFRs) have substantially increased after the ban of several PBDEs. This has resulted in widespread environmental occurrence of non-PBDE HFRs, further amplified by emissions from primitive recycling of obsolete electronics (e-waste). The present study conducted chamber experiments to characterize 15 HFRs (∑15HFR) from thermal treatment and open burning of typical e-waste. Emission factors of ∑15HFR from thermal treatment were 2.6 × 104-3.9 × 105 ng g-1, slightly higher than those from open burning (8.8 × 103-1.0 × 105 ng g-1). Greater output over input mass ratios of ∑15HFR were obtained in thermal treatment than in open burning. Particulate and gaseous HFRs dominated the emissions in thermal treatment and open burning, respectively, largely because of the different temperatures used in the two processes. Particulate HFRs were primarily affiliated with fine particles (Dp < 1.8 μm) peaking at 0.56-1.0 or 0.32-0.56 μm in both thermal treatment and open burning. Occupational exposure to most FRs was relatively low, but several PBDEs may pose potential health risk to workers in e-waste home-workshops. Potentially accruing emissions and health risks of non-PBDE HFRs from primitive recycling of e-waste remain a great concern.


Impact of the COVID-19 Pandemic on Unhealthy Eating in Populations with Obesity.
This study aimed to examine the impact of the coronavirus disease (COVID-19) pandemic on patronage to unhealthy eating establishments in populations with obesity. Anonymized movement data accounting for roughly 10% of devices in the United States at 138,989 unhealthy eating locations from December 1, 2019, through April 2020 and the percentage of adults with obesity, the poverty rate, and the food environment index in 65% of United States counties were collected and merged. A cluster corrected Poisson spline regression was performed predicting patronage by day, the percentage of adults with obesity in the establishment's county, the county's poverty rate, and its food environment index, as well as their interactions. Patronage to unhealthy eating establishments was higher where there was a higher percentage of the adult population with obesity. A similar pattern was observed for counties with a lower food environment index. These disparities appear to have increased as the COVID-19 pandemic spread. These results suggest unhealthy eating patterns during the COVID-19 pandemic are higher in already at-risk populations. Policy makers can use these findings to motivate interventions and programs aimed at increasing healthy food intake in at-risk communities during crises.


The GLP-1 receptor agonists exenatide and liraglutide activate Glucose transport by an AMPK-dependent mechanism.
Potentiation of glucose-induced insulin secretion is the main mechanism of exenatide (EXE) antidiabetic action, however, increased glucose utilization by peripheral tissues has been also reported. We here studied the effect of EXE on glucose uptake by skeletal muscle cells. 2-deoxy-glucose (2DG) uptake and intracellular signal pathways were measured in rat L6 skeletal muscle myotubes exposed to 100 nmol/l EXE for up to 48 h. Mechanisms of EXE action were explored by inhibiting AMPK activity with compound C (CC, 40 μmol/l) or siRNAs (2 μmol/l). Time course experiments show that EXE increases glucose uptake up to 48 h achieving its maximal effect, similar to that induced by insulin, after 20 min (2- vs 2.5-fold-increase, respectively). Differently from insulin, EXE does not stimulate: (i) IR β-subunit- and IRS1 tyrosine phosphorylation and binding to p85 regulatory subunit of PI-3kinase; (ii) AKT activation; and (iii) ERK1/2 and JNK1/2 phosphorylation. Conversely, EXE increases phosphorylation of α-subunit of AMPK at Thr172 by 2.5-fold (p < 0.01). Co-incubation of EXE and insulin does not induce additive effects on 2DG-uptake. Inhibition of AMPK with CC, and reduction of AMPK protein expression by siRNA, completely abolish EXE-induced 2DG-uptake. Liraglutide, another GLP-1 receptor agonist, also stimulates AMPK phosphorylation and 2DG-uptake. Moreover, EXE stimulates 2DG-uptake also by L6 myotubes rendered insulin-resistant with methylglyoxal. Finally, EXE also induces glucose transporter Glut-4 translocation to the plasma membrane. In L6 myotubes, EXE and liraglutide increase glucose uptake in an insulin-independent manner by activating AMPK.


Behavioral, electroencephalographic, and biochemical changes in porta-cava shunted rats.
Behavioral, electroencephalographic, and biochemical alterations have been studied in rats with porta-caval shunt, up to 45--50 days after the operation. No behavioral or electroencephalographic changes have been observed, while modifications of various amino acids both in plasma and brain have been found. Among all the amino acids considered of particular significance are the plasma and brain increases of tyrosine, phenylalanine, and tryptophan, since they are the precursors of biogenic amines. In fact, the increase of 5-HIAA found in regions of CNS which are richest in serotoninergic synapsis could indicate an increased turnover of 5-HT. On the other hand no significant alterations of turnover of catecholamines have been found.


Tick subolesin is an ortholog of the akirins described in insects and vertebrates.
The tick protective antigen, subolesin, is a regulatory protein involved in the control of multiple cellular pathways. Subolesin is evolutionary conserved in invertebrates and vertebrates with sequence homology to akirins, a recently renamed group of proteins that were proposed to function as transcription factors in Drosophila and mice. The objective of this research was to provide evidence of the sequence and functional homology between tick subolesin and akirins. The phylogenetic analysis of subolesin and akirins showed that they are evolutionary conserved. The effect of subolesin and akirin2 knockdown was compared in adult ticks and mice, respectively. The results demonstrated that tick subolesin is an ortholog of insect and vertebrate akirins and suggested that these proteins function in the regulation of NF-kappaB-dependent and independent expression of signal transduction and innate immune response genes. These results suggest that these proteins have an important role in host-pathogen interactions.


Palladium-catalyzed allylic transposition of (allyloxy) iminodiazaphospholidines: a formal [3,3]-aza-phospha-oxa-Cope sigmatropic rearrangement for the stereoselective synthesis of allylic amines.
The synthesis of N-protected allylic amines has been achieved utilizing a palladium(II)-catalyzed, [3,3]-rearrangement of (allyloxy) iminodiazaphospholidines. This [3,3]-aza-phospha-oxa-Cope sigmatropic rearrangement reaction is thermodynamically driven by a P=N to P=O interconversion and is an alternative to the Overman rearrangement. The overall process involves the nucleophilic displacement of an allylic alcohol onto a P(III) precursor, followed by a Staudinger reaction to generate the (allyloxy) iminodiazaphospholidine precursors. Pd(II)-catalyzed [3,3]-aza-phospha-oxa-Cope rearrangement then gives a phosphoramide, which is readily hydrolyzed under acidic conditions to yield allylic amine derivatives. Pd(II) catalysis is believed to occur in a fashion analogous to that of the rearrangement of allylic imidates. The scope of racemic, diastereoselective, and enantioselective variants of this rearrangement is described. The use of chiral diamine auxiliaries in diastereoselective rearrangements is reported. Rearrangement of chiral N,N'-dimethyl cyclohexanediamine derived diazaphospholidines gives rise to phosphoramides with moderate diastereoselectivities (up to 3.5:1 dr). The same major diastereomeric product in these rearrangements was prepared irrespective of the starting allylic alcohol geometry. An enantioselective variant of the reaction was demonstrated for the rearrangement of cis-(allyloxy) iminodiazaphospholidines with cobalt oxazoline palladacycle (COP-X) catalysts (5 mol %) in high yield and enantioselectivity (up to 96% ee).


Unsymmetric Twofold Scholl Cyclization of a 5,11-Dinaphthyltetracene: Selective Formation of Pentagonal and Hexagonal Rings via Dicationic Intermediates.
Even though the Scholl reaction is one of the most powerful processes for the synthesis of polycyclic aromatic hydrocarbons (PAHs), its mechanism still remains a subject of discussion. Herein, we report a unique twofold Scholl cyclization of a 5,11-dinaphthyltetracene. Single-crystal X-ray diffraction analysis of the cyclization product revealed that unsymmetric cyclizations of the two naphthyl groups resulted in the formation of fully unsaturated pentagonal and hexagonal rings. The thus obtained product exhibits a twisted π-surface and an absorption band that reaches up to 950 nm. A combined experimental and theoretical study showed that such unsymmetric Scholl cyclizations can be rationalized in terms of a mechanism that involves dicationic intermediates, which stands in contrast to previously reported pathways based on radical cations and arenium ions.


Optimization of Heart Failure Treatment by Heart Rate Reduction.
Heart failure (HF) treatment should be optimized in addition to guideline-directed and recommended drugs to achieve an appropriate heart rate (i.e. 50-60 bpm) by ivabradine in patients with a heart rate >70 bpm in sinus rhythm and with an ejection fraction ≤35%. Heart rate reduction was to reduce cardiovascular death and HF hospitalization dependent on baseline resting heart rate. In particular in patients at a heart rate >75 bpm, a reduction in cardiovascular death, all-cause death, HF death, HF hospitalization and all-cause hospitalization has been observed. The optimal heart rate achieved appears to be between 50-60 bpm, if well tolerated as in these patients the lowest event rate is observed on treatment. Heart rate reduction is, therefore, a treatable risk factor in chronic HF. Observational studies support the concept that it is a risk indicator in other cardiovascular and non-cardiovascular conditions. Whether heart rate reduction is also modifying risk in other conditions than chronic HF should be explored in prospective clinical trials.


IgAs against acetaldehyde-modified red cell protein as a marker of ethanol consumption in male alcoholic subjects, moderate drinkers, and abstainers.
Alcohol abuse has been shown to result in the production of antibodies against acetaldehyde-modified epitopes in proteins. However, as yet, only limited information has been available on the clinical usefulness of such responses as markers of hazardous drinking. We developed an ELISA to measure specific IgAs against acetaldehyde-protein adducts. This method was evaluated in cross-sectional and follow-up studies on male heavy drinkers with a current ethanol consumption of 40 to 540 g/d (n=40), moderate drinkers consuming 1 to 40 g/d (n=25), and abstainers (n=16). The clinical assessments included detailed interviews on the amounts and patterns of ethanol consumption and various biochemical markers of alcohol abuse and liver function. The mean antiadduct IgAs (198+/-28 U/L) in the alcohol abusers were significantly higher than those in the moderate drinkers (58+/-11 U/L, p<0.001) or abstainers (28+/-8 U/L, p<0.001). The values of moderate drinkers were also higher than those in abstainers (p<0.05). The amount of ethanol consumed during the period of 1 month preceding blood sampling correlated strongly with antiadduct IgAs (r=0.67, p<0.001). The sensitivity (73%) and specificity (94%) of this marker were found to exceed those of the conventional laboratory markers of alcohol abuse in comparisons contrasting heavy drinkers with abstainers although not in comparisons contrasting heavy drinkers with moderate drinkers. During abstinence, antiadduct IgAs disappeared with a mean rate of 3% per day. In additional analyses of possible marker combinations, antiadduct IgAs, together with CDT, were found to provide the highest sensitivity and specificity. Measurements of antiadduct IgAs may provide a new clinically useful marker of alcohol abuse, providing a close relationship between marker levels and the actual amounts of recent ethanol ingestion.