Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women.
A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.


[The surgical emergent therapy for massive hemoptysis in 52 cases].
The result of surgical emergent operation in 52 cases with massive hemoptysis failed by medical therapy was reported. Hemoptysis ceased in 51 of the 52 cases. One patient died after operation, giving a mortality rate of 1.9%. Other complications were occurred in two patients, but none was bronchial fistula. The complication rate was 3.8%. The surgical indication of this series would include: (1) The amount of hemoptysis more than 600 ml per 24 h, failed by medical treatment. (2) Massive hemoptysis repeated or a history of suffocation. (3) Irreversible lesion in the lung with the bleeding site identified accurately. (4) The general condition and vital organs of the patient would permit surgical therapy. Various types of pulmonary resection with successful results should be selected.


[Reasons for personnel turnover in a private health facility].
This study was done in a Sao Paulo city hospital with 54 nurses who required for dismissal from January, 1995 to January, 1996. All of them at the dismissal interview provided information on how long they had worked for the hospital, reasons for leaving and their frank opinions about the hospital itself, nurse department directors and personal suggestions. The study goal was to evaluate the reasons for high turnover of institutions nurses in order to draw adequate administrative intervention strategies. An exploratory study of retrospective character with data quantitative qualitative analysis has been used. Data analysis considered that 74% of the nurses had left the institution in 12 months but 35.3% until the third month. The nurses emphasized work conditions specially the staff, benefits and interpersonal communication. The results came towards our perception on the institution nurses turnover causes.


Subperiosteal face lift: a 200-case, 4-year review.
The subperiosteal face lift is a procedure designed to rejuvenate the upper and middle thirds of the face. Herein is reviewed a 4-year series of 200 consecutive patients who have undergone a subperiosteal face lift with a special emphasis on handling of the zygomatic arch. The main operative indication was significant ptosis of the midface soft tissue. Dissection of the maxilla, zygoma, periorbital areas, and the anterior arch was carried out through either a gingivo-buccal sulcus incision (39 cases) or a subciliary incision (161 cases). Dissection of the posterior arch was carried out in a plane superficial to the innominate fascia. A back-cut was made in the superficial musculoaponeurotic system and subcutaneous tissue down to midtragus, and a subperiosteal tunnel was entered by piercing through the posterior arch periosteum. By using a Cottle elevator (sweeping superiorly and inferiorly), the arch dissection was completed in a posterior to anterior direction. All patients underwent a concurrent brow lift (190 endoscopically and 10 by means of coronal incision). The forehead incision was used to dissect the lateral orbital rims. Twelve patients (6 percent) had undergone a previous rhytidectomy. All but four patients were women and ranged in age from 34 to 76 years (mean, 54+/-11). Mean follow-up period was 27 months (1 to 41 months). The postoperative complication rate was 5 percent and included transient frontal branch weakness (n = 2), resolved at 41 and 71 days postoperatively; hematoma (n = 2); transient infraorbital nerve paresthesia (n = 1); asymmetrical smile (n = 3); and facial tics (n = 2). Two patients (1 percent) required a secondary surgery on their brows or midface. An upper blepharoplasty was needed in 26 patients (13 percent). The overall aesthetic results were excellent, with good elevation of the eyebrows, lateral canthus, and the midface soft tissues. In conclusion, the subperiosteal face lift is a procedure designed to rejuvenate the upper and middle thirds of the face. Approaching the arch posteriorly and in a systematic fashion simplifies the procedure and reduces the risk of facial nerve injury.


Grit: perseverance and passion for long-term goals.
The importance of intellectual talent to achievement in all professional domains is well established, but less is known about other individual differences that predict success. The authors tested the importance of 1 noncognitive trait: grit. Defined as perseverance and passion for long-term goals, grit accounted for an average of 4% of the variance in success outcomes, including educational attainment among 2 samples of adults (N=1,545 and N=690), grade point average among Ivy League undergraduates (N=138), retention in 2 classes of United States Military Academy, West Point, cadets (N=1,218 and N=1,308), and ranking in the National Spelling Bee (N=175). Grit did not relate positively to IQ but was highly correlated with Big Five Conscientiousness. Grit nonetheless demonstrated incremental predictive validity of success measures over and beyond IQ and conscientiousness. Collectively, these findings suggest that the achievement of difficult goals entails not only talent but also the sustained and focused application of talent over time.


Functional assessment of four types of disintegrants and their effect on the spironolactone release properties.
Spironolactone is a drug derived from sterols that exhibits an incomplete oral absorption due to its low water solubility and slow dissolution rate. In this study, formulations of spironolactone with four disintegrants named as croscarmellose sodium, crospovidone, sodium starch glycolate and microcrystalline cellulose II (MCCII) were conducted. The effect of those disintegrants on the tensile strength, disintegration time and dissolution rate of spironolactone-based compacts was evaluated using a factorial design with three categorical factors (filler, lubricant, and disintegrant). The swelling values, water uptake and water sorption studies of these disintegrants all suggested that MCCII compacts disintegrate by a wicking mechanism similar to that of crospovidone, whereas a swelling mechanism was dominant for sodium starch glycolate and croscarmellose sodium. The disintegration time of MCCII and sodium starch glycolate remained unchanged with magnesium stearate. However, this lubricant delayed the disintegration time of crospovidone and croscarmellose sodium. MCCII presented the fastest disintegration time independent of the medium and lubricant employed. The water sorption ratio and swelling values determined sodium starch glycolate followed by croscarmellose sodium as the largest swelling materials, whereas crospovidone and MCCII where the least swelling disintegrants. The swelling property of sodium starch glycolate and croscarmellose sodium was strongly affected by the medium pH. The disintegration time of spironolactone compacts was faster when starch was used as a filler due to the formation of soft compacts. In this case, the type of filler employed rather than the disintegrant had a major effect on the disintegration and dissolution times of spironolactone.


Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery.
Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01-1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03-1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.


[Plasma cells in the cerebrospinal fluid of patients with cerebral cysticercosis].
We studied in twenty patients with proven cerebral cysticercosis the presence of plasma cells in the cerebrospinal fluid (CSF). We found plasma cells in 50 per cent of the patients. All of them had subarachnoid cysticercosis or basal arachnoiditis. The presence of plasma cells was significantly associated to higher protein levels, greater number of inflammatory cells, and higher levels of IgG in the CSF. None of the patients had received medical treatment or steroids prior to the test. These findings suggest a role of plasma cells in the pathogenesis of the cysticercotic disease. The presence of plasma cells in the CSF is part of the immune response against the parasite. We also found that plasma cells are more frequently encountered in the CSF (50 per cent) than eosinophils (20 per cent) in patients with cerebral cysticercosis.


Volatile Compound-Mediated Recognition and Inhibition Between Trichoderma Biocontrol Agents and Fusarium oxysporum.
Certain Trichoderma strains protect plants from diverse pathogens using multiple mechanisms. We report a novel mechanism that may potentially play an important role in Trichoderma-based biocontrol. Trichoderma virens and T. viride significantly increased the amount/activity of secreted antifungal metabolites in response to volatile compounds (VCs) produced by 13 strains of Fusarium oxysporum, a soilborne fungus that infects diverse plants. This response suggests that both Trichoderma spp. recognize the presence of F. oxysporum by sensing pathogen VCs and prepare for attacking pathogens. However, T. asperellum did not respond to any, while T. harzianum responded to VCs from only a few strains. Gene expression analysis via qPCR showed up-regulation of several biocontrol-associated genes in T. virens in response to F. oxysporum VCs. Analysis of VCs from seven F. oxysporum strains tentatively identified a total of 28 compounds, including six that were produced by all of them. All four Trichoderma species produced VCs that inhibited F. oxysporum growth. Analysis of VCs produced by T. virens and T. harzianum revealed the production of compounds that had been reported to display antifungal activity. F. oxysporum also recognizes Trichoderma spp. by sensing their VCs and releases VCs that inhibit Trichoderma, suggesting that both types of VC-mediated interaction are common among fungi.


Predictive Mapping of Antimicrobial Resistance for Escherichia coli, Salmonella, and Campylobacter in Food-Producing Animals, Europe, 2000-2021.
In Europe, systematic national surveillance of antimicrobial resistance (AMR) in food-producing animals has been conducted for decades; however, geographic distribution within countries remains unknown. To determine distribution within Europe, we combined 33,802 country-level AMR prevalence estimates with 2,849 local AMR prevalence estimates from 209 point prevalence surveys across 31 countries. We produced geospatial models of AMR prevalence in Escherichia coli, nontyphoidal Salmonella, and Campylobacter for cattle, pigs, and poultry. We summarized AMR trends by using the proportion of tested antimicrobial compounds with resistance >50% and generated predictive maps at 10 × 10 km resolution that disaggregated AMR prevalence. For E. coli, predicted prevalence rates were highest in southern Romania and southern/eastern Italy; for Salmonella, southern Hungary and central Poland; and for Campylobacter, throughout Spain. Our findings suggest that AMR distribution is heterogeneous within countries and that surveillance data from below the country level could help with prioritizing resources to reduce AMR.


[New classification of enteroviruses of pigs: serological and molecular genetic aspects].
Due to changes in modern classification and nomenclature family Picornaviridae made by the International Committee of Taxonomy of Viruses, conducted genetic and serological reclassification of 36 industrial, typical and laboratory strains porcine enteroviruses isolated in Ukraine. The results of molecular genetic studies of 34 strains assigned to the family Picornaviridae, genus Teschovirus, species Porcine teschovirus, 2 strains of virus did not engage in polymerase chain reaction with species specific primer. In the neutralization reaction of the virus revealed that 23 strains belonging to 1 serotype Porcine teschovirus, 4 strain--PTV-3, 1--to PTV-6, 1 strain--to Porcine sapelovirus, three strains have between typical antigenic properties, and 4 strains--antigenically different from reference strains Porcine teschovirus, Enterovirus G and Porcine sapelovirus.


Negative association between trunk fat, insulin resistance and skeleton in obese women.
To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m(2)) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD; at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005).Multivariate analysis demonstrated that only vitamin D was independent of TF variable. In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.


Genomic analysis of Eimeria spp. populations in relation to performance levels of broiler chicken farms in Arkansas and North Carolina.
The impact of coccidiosis outbreaks on the productivity of broiler chicken farms can be substantial, depending on the severity of disease caused by particular species and strains of Eimeria. We examined the genetic diversity of Eimeria species present in commercial broiler farms in relation to their performance level. Four groups of broiler chicken farms in Arkansas (AR) and North Carolina (NC), having either high or low performance levels, were sampled for Eimeria spp. oocysts. We amplified gDNA from oocysts by using genus-specific primers targeting 18S ribosomal RNA, the first and second internal transcribed spacer regions, and cytochrome c oxidase subunit I as the established species-specific primers. Eimeria spp. diversity was not homogenous among the 4 farm groups, with less-pathogenic species (E. mitis and E. mivati-like) associated with AR and NC high-performance farms, respectively, and a pathogenic species (E. brunetti) associated with AR low-performance farms. Sequence analyses identified multiple E. maxima and E. mitis genetic variants, from which 2 E. maxima variants were unique to low-performance farms. Distinct populations of sequences at the NC high-performance farms were identified as E. mivati-like, based on homology searches. Our study demonstrated the utility of analyzing multiple genomic loci to assess composition and polymorphisms of Eimeria spp. populations.


Building a virtual cancer research organization.
The Cancer Research Network (CRN) comprises the National Cancer Institute and 11 nonprofit research centers affiliated with integrated health care delivery systems. The CRN, a public/private partnership, fosters multisite collaborative research on cancer prevention, screening, treatment, survival, and palliation in diverse populations. The CRN's success hinges on producing innovative cancer research that likely would not have been developed by scientists working individually, and then translating those findings into clinical practice within multiple population laboratories. The CRN is a collaborative virtual research organization characterized by user-defined sharing among scientists and health care providers of data files as well as direct access to researchers, computers, software, data, research participants, and other resources. The CRN's research management Web site fosters a high-functioning virtual scientific community by publishing standardized data definitions, file specifications, and computer programs to support merging and analyzing data from multiple health care systems. Seven major types of standardized data files developed to date include demographics, health plan eligibility, tumor registry, inpatient and ambulatory utilization, medication dispensing, laboratory tests, and imaging procedures; more will follow. Data standardization avoids rework, increases multisite data integrity, increases data security, generates shorter times from initial proposal concept to submission, and stimulates more frequent collaborations among scientists across multiple institutions. The CRN research management Web site and associated standardized data files and procedures represent a quasi-public resource, and the CRN stands ready to collaborate with researchers from outside institutions in developing and conducting innovative public domain research.


Induction of kranz anatomy and C4-like biochemical characteristics in a submerged amphibious plant by abscisic acid
The amphibious leafless sedge Eleocharis vivipara develops C4-like traits as well as Kranz anatomy under terrestrial conditions, but it develops C3-like traits without Kranz anatomy under submerged conditions. When submerged plants are exposed to aerial conditions, they rapidly produce new photosynthetic tissues with C4-like traits. In this study, experiments were performed to determine whether abscisic acid (ABA), a plant stress hormone, could induce the formation of photosynthetic tissues with Kranz anatomy and C4-like biochemical traits under water in the submerged form. When the submerged plants were grown in water containing 5 &mgr;M ABA, they developed new photosynthetic tissues with Kranz anatomy, forming well-developed Kranz (bundle sheath) cells that contained many organelles. The ABA-induced tissues accumulated large amounts of phosphoenolpyruvate carboxylase, pyruvate orthophosphate dikinase, and NAD-malic enzyme at the appropriate cellular sites. The tissues had 3.4 to 3.8 times more C4 enzyme activity than did tissues of the untreated submerged plants. Carbon-14 pulse and carbon-12 chase experiments revealed that the ABA-induced tissues fixed higher amounts of carbon-14 into C4 compounds and lower amounts of carbon-14 into C3 compounds as initial products than did the submerged plants and that they exhibited a C4-like pattern of carbon fixation under aqueous conditions of low carbon, indicating enhanced C4 capacity in the tissues. This report provides an example of the hormonal control of the differentiation of the structural and functional traits required for the C4 pathway.


Erratum to: Endophthalmitis in Boston keratoprosthesis: case series and review of literature.
To report the clinical and microbiological characteristics of infectious endophthalmitis after Boston type I keratoprosthesis (B-K-Pro) implantation. Retrospective analysis of 45 eyes that received a B-K-Pro type 1 between 2009 and 2012 was performed. Five eyes with a diagnosis of exogenous endophthalmitis after B-K-pro type 1 were identified and information about demographic data, indication for K-Pro, post-operative bandage contact lens use, post-operative prophylactic antibiotic use, timing and clinical presentation of endophthalmitis, gram stain and culture results of intraocular fluid and preoperative and post-operative visual acuity were collected. The incidence of endophthalmitis was 11.1 % (5 of 45 eyes) and average time to develop endophthalmitis was 5.62 months (range 2 days to 8 months). Mean patient age was 31.4 years (5 to 65 years). The surgical indications included corneal injury due to chemical burns (n = 2), multiple failed grafts secondary to microbial keratitis (n = 2) and congenital glaucoma with congenital herpetic keratitis (n = 1). Post-Boston K-Pro, the visual acuity ranged from light perception (LP) to 20/50. K-pro was explanted in 4 patients. There was bacterial and fungal growth in two patients each and one vitreous did not grow anything. All the eyes were phthisical at last visit. Infectious endophthalmitis after K-Pro implantation in our study had a higher incidence, early onset and extremely poor visual outcome compared with post-cataract surgery endophthalmitis, as reported in literature. Not only bacterial but also fungal infections are an important etiology for infectious endophthalmitis in these cases.


The accuracy and reliability of estimation of lateral pillar height in determining the herring grade in Legg-Calvé-Perthes disease.
The amount of the preserved lateral pillar height (LPH) for assigning Herring grades is estimated during daily practice in Perthes disease. Despite this estimation, Herring classification has been reported to have a good interobserver agreement. The purpose of this study was to investigate whether the amount of preserved LPH has an effect on interobserver agreement. The results of surgeons' estimates were compared with objective measurement results. Good agreement was found among three experienced pediatric orthopaedic surgeons in 50 patients (1 vs. 2, kappa=0.527; 2 vs. 3, kappa=0.526; 1 vs. 3, kappa=0.539). Twenty of these cases had a ratio of the LPH scattered between 0.45 and 0.60 and 0.90 and 0.99 (transition between group B and C, and group A and B). When the borderline cases were evaluated separately, the interobserver reliability was poor (1 vs. 2, kappa=0.194; 2 vs. 3, kappa=0.256; 1 vs. 3, kappa=0.154), which may be explained by misperception of the preserved LPH. If the Herring classification is to be used as the prognostic indicator for deciding among the treatment alternatives, and LPH is the major determinant of the management, measurements should be used instead of estimates, especially in borderline cases.


Nitrative DNA damage in cultured macrophages exposed to indium oxide.
Indium compounds are used in manufacturing displays of mobile phones and televisions. However, these materials cause interstitial pneumonia in exposed workers. Animal experiments demonstrated that indium compounds caused lung cancer. Chronic inflammation is considered to play a role in lung carcinogenesis and fibrosis induced by particulate matters. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation and may participate in carcinogenesis. To clarify the mechanism of carcinogenesis, we examined 8-nitroG formation in indium-exposed cultured cells. We treated RAW 264.7 mouse macrophages with indium oxide (In2O3) nanoparticles (primary diameter: 30-50 nm), and performed fluorescent immunocytochemistry to detect 8-nitroG. The extent of 8-nitroG formation was evaluated by quantitative image analysis. We measured the amount of nitric oxide (NO) in the culture supernatant of In2O3-treated cells by the Griess method. We also examined the effects of inhibitors of inducible NO synthase (iNOS) and endocytosis on In2O3-induced 8-nitroG formation. In2O3 significantly increased the intensity of 8-nitroG formation in RAW 264.7 cells in a dose-dependent manner. In2O3-induced 8-nitroG formation was observed at 2 h and further increased at 4 h, and the amount of NO released from In2O3-exposed cells was significantly increased at 2-4 h compared with the control. 8-NitroG formation was suppressed by 1400W (an iNOS inhibitor), methyl-β-cyclodextrin and monodansylcadaverine (inhibitors of caveolae- and clathrin-mediated endocytosis, respectively). These results suggest that endocytosis and NO generation participate in indium-induced 8-nitroG formation. NO released from indium-exposed inflammatory cells may induce DNA damage in adjacent lung epithelial cells and contribute to carcinogenesis.


Are portable ankle brachial pressure index measurement devices suitable for hypertension screening?
In a large-scale population cardiovascular screening programme, peripheral artery disease (PAD) and hypertension would ideally be rapidly assessed using a single device. The ankle-brachial pressure index (ABPI) is calculated by comparing the ankle and brachial blood pressure (BP). However, it is currently unclear whether brachial BP measurements provided by automated PAD screening systems are sufficiently accurate for simultaneous hypertension screening. Two portable PAD screening devices, the MESI ABPI MD and Huntleigh's Dopplex ABIlity, were evaluated following the European Society of Hypertension International Protocol (ESH-IP) Revision 2010 using a mercury-free sphygmomanometer as a reference device. On average, the MESI slightly underestimated brachial systolic blood pressure (BP) with a bias and standard deviation (SD) of -3.5 (SD: 3.3) mmHg and diastolic BP with a bias of -1.5 (SD: 2.3) mmHg. For systolic BP estimates, the Dopplex was more accurate than the MESI with a lower bias of -0.5 (SD: 4.2) mmHg but less precise. The MESI successfully fulfilled all the requirements of the ESH-IP for hypertension screening. The Dopplex device failed the ESH-IP due to the absence of DBP measurements. The MESI device appears to be suitable for simultaneous PAD and hypertension screening as part of a preventative care programme. Huntleigh's Dopplex ABIlity failed to pass the ESH-IP validation test. Further clinical trials are underway to assess the use of the MESI for simultaneous screening for hypertension and PAD in a population screening setting.


[Preservation of vitamin C in vitamin-enriched apple products].
The content of vitamin C (the total of ascorbic and dehydroascorbic acids) in preserved apple products vitaminized with ascorbic acid was assayed once a month over a year. It was found that the products retained vitamin C sufficiently well, though the content of ascorbic acid decreased considerably, as the most amount of ascorbic acid was oxidized to form dehydroascorbic acid. The study conducted indicates the expediency of making vitaminized apple products.


Stepwise kinetic equilibrium models of quantitative polymerase chain reaction.
Numerous models for use in interpreting quantitative PCR (qPCR) data are present in recent literature. The most commonly used models assume the amplification in qPCR is exponential and fit an exponential model with a constant rate of increase to a select part of the curve. Kinetic theory may be used to model the annealing phase and does not assume constant efficiency of amplification. Mechanistic models describing the annealing phase with kinetic theory offer the most potential for accurate interpretation of qPCR data. Even so, they have not been thoroughly investigated and are rarely used for interpretation of qPCR data. New results for kinetic modeling of qPCR are presented. Two models are presented in which the efficiency of amplification is based on equilibrium solutions for the annealing phase of the qPCR process. Model 1 assumes annealing of complementary targets strands and annealing of target and primers are both reversible reactions and reach a dynamic equilibrium. Model 2 assumes all annealing reactions are nonreversible and equilibrium is static. Both models include the effect of primer concentration during the annealing phase. Analytic formulae are given for the equilibrium values of all single and double stranded molecules at the end of the annealing step. The equilibrium values are then used in a stepwise method to describe the whole qPCR process. Rate constants of kinetic models are the same for solutions that are identical except for possibly having different initial target concentrations. Analysis of qPCR curves from such solutions are thus analyzed by simultaneous non-linear curve fitting with the same rate constant values applying to all curves and each curve having a unique value for initial target concentration. The models were fit to two data sets for which the true initial target concentrations are known. Both models give better fit to observed qPCR data than other kinetic models present in the literature. They also give better estimates of initial target concentration. Model 1 was found to be slightly more robust than model 2 giving better estimates of initial target concentration when estimation of parameters was done for qPCR curves with very different initial target concentration. Both models may be used to estimate the initial absolute concentration of target sequence when a standard curve is not available. It is argued that the kinetic approach to modeling and interpreting quantitative PCR data has the potential to give more precise estimates of the true initial target concentrations than other methods currently used for analysis of qPCR data. The two models presented here give a unified model of the qPCR process in that they explain the shape of the qPCR curve for a wide variety of initial target concentrations.


Treatment and outcomes in patients with myocardial infarction treated with acute β-blocker therapy: results from the American College of Cardiology's NCDR(®).
Although β-blockers (BBs) reduce long-term mortality in patients after myocardial infarction (MI), data regarding acute usage are conflicting. We examined acute (≤24 hours) BB use in 34,661 patients with ST-elevation MI (STEMI) and non-ST-segment MI (NSTEMI) included in the NCDR(®) ACTION Registry(®)-GWTG™ (291 US hospitals) between January 2007 and June 2008. Patients with contraindications or did not receive BBs or with missing data were excluded. We analyzed the use and impact of BB stratified by variables associated with increased risk for shock specified in the recent guidelines: age >70 years, symptoms >12 hours (STEMI patients), systolic blood pressure <120 mm Hg, and heart rate >110 beat/min on presentation. Among patients without contraindications, at least 1 high-risk variable was found in 45% of STEMI and 63% of NSTEMI patients. In-hospital complications including cardiogenic shock, mortality, and the composite outcome of shock or mortality were significantly increased with more shock risk factors in both STEMI and NSTEMI patients. Very early use in the emergency department was associated with a significantly increased risk of shock for both STEMI and NSTEMI patients compared to patients treated later but within 24 hours. Risk factors for shock are common in STEMI and NSTEMI patients treated with early BBs. Increasing numbers of risk factors were associated with increased risk for shock or death in patients treated with BBs. These results are consistent with current recommendations for avoiding early BB treatment for patients with acute MI.


True antisense oligonucleotides with modified nucleotides restricted in the N-conformation.
As first-generation antisense oligonucleotides, more than a dozen phosphorothioate oligodeoxynucleotides (PS ODNs) have been clinically developed, but only one has reached the market. To improve the drawbacks of PS ODNs, such as low affinity to target mRNA and non-specific binding to proteins, modified oligonucleotides with 2'-modified sugars such as 2'-O-(2-methoxy)ethyl and 2'-F modification or with bridged sugars such as oxyalkylene linkages between 2'-oxygen and 4'-carbon, have been synthesized as 2'-MOE, 2'-F RNA, 2',4'-BNA/LNA and ENA oligonucleotides. They have shown properties of higher affinity to complementary single-stranded RNA and DNA than those of PS ODNs due to their preorganized N-conformation. On the basis of the properties of these newly designed oligonucleotides, their in vitro and in vivo applications for gene silencing as true antisense oligonucleotides have been reported. In this review, antisense applications with these modified oligonucleotides are focused on.


Intraindividual variability in nifedipine pharmacokinetics and effects in healthy subjects.
The intraindividual variability in pharmacokinetics and effects of oral nifedipine (10 mg), administered with 1 week intervals, was investigated in twelve young healthy subjects. The population estimate of the coefficient of intraindividual variability (CVw) in AUC of nifedipine (13%) was much smaller than the pure between-subject variability (CVb 54%). The long-term (1 1/2 year) intraindividual variability was much larger than the short-term variability. Maximum changes from baseline-values of mean blood pressure (SBP -5%, DBP -4%) and mean heart rate (HR +21%) were small. Individual maximum changes in systolic blood pressure, diastolic blood pressure, and heart rate (SBP, DBP, and HR) and areas under effect curves were highly variable (CVw 34-250%, CVb 8-88%). For most subjects a significant positive linear relation was observed between nifedipine plasma concentration and the change in HR (mean r = 0.63). The CVw in slope (106%) and intercept (685%) were even larger than the high CVb in these parameters (38% and 252%). Changes in blood pressure were not significantly related to nifedipine plasma concentrations within these healthy subjects. The small intraindividual variability in nifedipine pharmacokinetics allows crossover studies to detect pharmacokinetic relationships between nifedipine and other dihydropyridine calcium entry blockers.


The Validity of Training Endoscopic Sinus and Skull Base Surgery Techniques on the Experimental Head Model.
The aim of this study was to better understand the usual learning curve in acquiring endonasal endoscopic sinus and skull base surgery (ESSBS) techniques during the novice training on the lamb's head model. Ten novices were asked to perform 10 bilateral dissections on the particular lamb's head each. The dissections were uniform, consisted of 10 well-defined steps, beginning from the simple removal of the inferior turbinate, and ending with more complicated procedures like cerebrospinal fluid leak repair, Draf 3 procedure for the frontal sinus and elevation of the nasal septal flap. The dissections have been supervised by experienced surgeons. A set of standard ESSBS instruments and 0° and 45° endoscopes have been used under the navigational system. The time required to complete each step has been measured in minutes. In general and quite expectedly, time rates have been obviously lowering as the number of the dissections performed has been growing in each of the participants. Training of the endonasal ESSBS techniques on the lamb's head proved to be useful for novices in getting basic surgical skills in the field. Because of the high degree of anatomic similarity and high level of the anatomic dimensions congruency between the lamb's head and human head (sheep's head has bigger dimensions!) it proved to be an essential preparation for the human cadaveric dissection. The median values of the time rates having been needed to complete the particular of the 10 steps in the last novices' dissections could be accepted as an orientation, just suggesting that once the time needed to complete 1 of the 10 steps has been and achieved by the particular novice, this could be an approximate sign of the maturity for the exercises on human cadaver head.


Hyperexcitability and Hyperplasticity Disrupt Cerebellar Signal Transfer in the IB2 KO Mouse Model of Autism.
Autism spectrum disorders (ASDs) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASDs has been suggested, but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 (Islet Brain-2) KO mice of either sex. The IB2 gene (chr22q13.3 terminal region) deletion occurs in virtually all cases of Phelan-McDermid syndrome, causing autistic symptoms and a severe delay in motor skill acquisition. IB2 KO granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability, raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from a "Mexican hat" to a "stovepipe hat" profile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity were remarkably increased. These results show for the first time that hyperexcitability and hyperplasticity disrupt signal transfer in the granular layer of IB2 KO mice, supporting cerebellar involvement in the pathogenesis of ASD.SIGNIFICANCE STATEMENT This article shows for the first time a complex set of alterations in the cerebellum granular layer of a mouse model [IB2 (Islet Brain-2) KO] of autism spectrum disorders. The IB2 KO in mice mimics the deletion of the corresponding gene in the Phelan-McDermid syndrome in humans. The changes reported here are centered on NMDA receptor hyperactivity, hyperplasticity, and hyperexcitability. These, in turn, increase the excitatory/inhibitory balance and alter the shape of center/surround structures that emerge in the granular layer in response to mossy fiber activity. These results support recent theories suggesting the involvement of cerebellum in autism spectrum disorders.


Protease nexin-1 is expressed at the mouse met-/mesencephalic junction and FGF signaling regulates its promoter activity in primary met-/mesencephalic cells.
The expression pattern of the serine protease inhibitor gene Protease nexin-1 (PN-1) has been analyzed by in situ hybridization during embryonic nervous system development. PN-1 was found to be specifically expressed at the junction between the mes- and metencephalon (mid- and hindbrain). Transgenic embryos expressing the bacterial lacZ gene under the control of different fragments of the PN-1 upstream regulatory region were used to demarcate an enhancer sufficient for expression at this putative segmental border. Primary cell cultures derived from the embryonic neural tube at the level of the met-/mesencephalic junction were used to demonstrate a specific effect on transcriptional activity by basic fibroblast growth factor and Engrailed transcription factors, providing evidence that PN-1 is a target gene of these factors. The results of this study place PN-1 into the signaling cascade(s) considered to be important for the development of this junction and suggest a role for PN-1 in the establishment or maintenance of the differences between these adjacent neuromeres.


Nanoscopy reveals the layered organization of the sarcomeric H-zone and I-band complexes.
Sarcomeres are extremely highly ordered macromolecular assemblies where structural organization is intimately linked to their functionality as contractile units. Although the structural basis of actin and Myosin interaction is revealed at a quasiatomic resolution, much less is known about the molecular organization of the I-band and H-zone. We report the development of a powerful nanoscopic approach, combined with a structure-averaging algorithm, that allowed us to determine the position of 27 sarcomeric proteins in Drosophila melanogaster flight muscles with a quasimolecular, ∼5- to 10-nm localization precision. With this protein localization atlas and template-based protein structure modeling, we have assembled refined I-band and H-zone models with unparalleled scope and resolution. In addition, we found that actin regulatory proteins of the H-zone are organized into two distinct layers, suggesting that the major place of thin filament assembly is an M-line-centered narrow domain where short actin oligomers can form and subsequently anneal to the pointed end.


User perspectives on issues that influence the quality of daily life of ventilator-assisted individuals with neuromuscular disorders.
To identify user perspectives on the issues that impact the quality of the daily lives of ventilator-assisted individuals living in the community. Semistructured interviews were held with 26 Canadian ventilator-assisted individuals (mean age 44+/-14 [SD] years, range 23 to 60 years; mean ventilator experience 18+/-13 years, range three to 53 years) whose disability from neuromuscular conditions necessitated assistance with activities of daily living. Participants described their daily life experiences and perceptions of the factors that limited or enhanced their quality. Interviews were tape-recorded, transcribed and analyzed for emergent codes and themes. Ventilator users characterized important issues in terms of personal successes and limitations, as well as dependencies on others for daily living. Personal support services, income security, health care and transportation were important positive contributors to their quality of life. Dependency on others was clearly a negative contributor. The ventilator was regarded as a form of assistive technology, similar to a wheelchair. Ventilator users perceived that ventilation was associated with a stigma and negative assumptions about disability, particularly if suctioning was required. The majority of participants considered home mechanical ventilation to be a positive benefit for independent living, enhancing their overall health. They were clear as to the issues of importance to them, and formulated recommendations for health care providers and policy makers that could improve the quality of their daily lives. Many of the issues identified in the present report are faced by the growing community of ventilator users.


Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin.
The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin-mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N-acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3-fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo-substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly-N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3-fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.


Postcircumcision necrosis of the glans penis: gray-scale and color Doppler sonographic findings.
We report the case of a 2-week-old male infant who developed necrosis of the glans penis as a result of circumcision. Based on the clinical absence of impairment of micturition on gray-scale and color Doppler sonographic findings, which showed the relatively superficial necrosis of the skin layers without underlying damage to the corpora cavernosa or urethra, a conservative approach was chosen with a good prognosis. A 4-month follow-up sonograpic examination revealed evidence of glans healing with superficial skin epithelization. These findings may lead to mild cosmetic damage, but no future functional complications are expected. To our knowledge, this is the first report of gray-scale and color Doppler sonographic evaluation of the ischemic process of the glans in a neonate with this rare complication of circumcision.


Health insurance coverage during the years preceding medicare eligibility.
Adults in late middle age who lack health insurance are more likely to die or experience a decline in their overall health. Because most estimates of the uninsured are cross-sectional, the true number of individuals whose health is at risk from being uninsured is unclear. We analyzed a nationally representative sample of 6065 US adults 51 to 57 years old who were interviewed in 1992, 1994, 1996, 1998, and 2000 as part of the Health and Retirement Study. Insurance coverage was determined at the time of each interview and classified as private, public, or uninsured. Longitudinal data were used to determine the proportion of individuals who were uninsured at any interview during the 8-year study period. The proportion of participants who were uninsured at the time of the 1992, 1994, 1996, 1998, and 2000 interviews was 14.3%, 10.8%, 9.7%, 8.8%, and 8.2%, respectively. People frequently transitioned between having insurance and being uninsured. As a result, despite the declining prevalence of being uninsured, the percentage who were uninsured at least once during the 8-year period rose to 23.3% by 2000; few participants (2.6%) were continuously uninsured. Only 60.1% of participants were continuously enrolled in private insurance across all 5 interviews. The proportion of US adults in late middle age at risk from being uninsured over a 10-year follow-up period was 2 to 3 times higher than cross-sectional estimates. At least one quarter of older adults will be uninsured at some point during the years preceding eligibility for Medicare.


Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review.
The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD. Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity criteria were reported in French or English. Overall, the mean number of items on the modified version of STARD was 12.4 (range: 2 to 18). This systematic review provides a critical appraisal and repository of instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. More research is needed to pursue the validation of the existing instruments and the development of patient versions. This will help researchers capture the complexity of the decision-making process within specific clinical encounters.


Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review.
Gastric cancer, a common malignant disease, seriously endangers human health and life. The high mortality rate due to gastric cancer can be attributed to a lack of effective therapeutic drugs. Cancer cells utilize the glycolytic pathway to produce energy even under aerobic conditions, commonly referred to as the Warburg effect, which is a characteristic of gastric cancer. The identification of new targets based on the glycolytic pathway for the treatment of gastric cancer is a viable option, and accumulating evidence has shown that phytochemicals have extensive anti-glycolytic properties. We reviewed the effects and mechanisms of action of phytochemicals on aerobic glycolysis in gastric cancer cells. Phytochemicals can effectively inhibit aerobic glycolysis in gastric cancer cells, suppress cell proliferation and migration, and promote apoptosis, via the PI3K/Akt, c-Myc, p53, and other signaling pathways. These pathways affect the expressions of HIF-1α, HK2, LDH, and other glycolysis-related proteins. This review further assesses the potential of using plant-derived compounds for the treatment of gastric cancer and sheds insight into the development of new drugs.


[Pulse therapy with methylprednisolone and cyclophosphamide in systemic juvenile rheumatoid arthritis: the results of an open, parallel, controlled, randomized, 12-month study].
The treatment for systemic JRA is among actual problems of pediatric rheumatology. To evaluate the effectiveness of pulse therapy (PT) with methylprednisolone 25-30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4-0.5 g/sq. m body surface area (BSA) on the 3rd day, repeated quarterly for 12 months, 30 patients with systemic JRA were randomized into 3 groups: 1--those with disease duration (DD) less than 2 years receiving PT (n = 13), 2--with DD 2 years and more (n = 8) receiving PT, and 3--with DD less than 2 years receiving no PT. Children in all 3 groups received concomitant medication (one of nonsteroidal anti-inflammatory drugs, methotrexate 10 mg/sq. m BSA/week and oral steroids). A rapid and significant improvement, according to systemic and articular manifestations as well as laboratory indices occurred in the 1st group, in most of the measured parameters exceeded effects in the other two groups and gave the opportunity to avoid the administration of oral steroids or to give the lesser initial dose. Side effects were minor and completely reversible.


Impact of Prolonged Ischemia on the Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1).
Antibodies targeting programmed death receptor 1 or programmed death ligand 1 (PD-L1) have become a standard of care to treat different cancers; for some of these tumors, there is a correlation between tissue expression of PD-L1 and response rates in patients. Although most of the analytical challenges in the evaluation of PD-L1 expression have been standardized, preanalytical issues have been less explored. The objective of this study was to evaluate the impact of time of ischemia on the performance of 2 commonly used antibodies against PD-L1. Sixteen tonsillectomy samples were kept in ischemia for <30 minutes from sample obtention (control) and 1, 3, 6, 12, and 24 hours at room temperature before formalin fixation and paraffin embedding. Selected areas were inserted into TMA paraffin recipient blocks stained with SP142 and SP263 antibodies and evaluated by 2 blind observers. The proportion of suboptimally stained samples was significantly higher for samples with cold ischemia times 6 hours or over ( P <0.0001). False-negative results were 25% in samples exposed to 6 hours of ischemia and raised to 34% for samples remaining in ischemia for 12 or 24 hours. When all observations were pooled, SP142 provided suboptimal results in 24% of observations and SP263 in 12.5%; this is a statistically significant difference ( P =0.042). In conclusion, the quality of staining for PD-L1 in tonsil samples varies with the time of cold ischemia. The SP142 antibody presented a significantly lower tolerance to prolonged cold ischemia than SP263. These results reveal the relevance of controlled preanalytical processing of samples.


The Longitudinal Impact of Hearing Impairment on Cognition Differs According to Cognitive Domain.
Identification and modification of the risk factors for cognitive decline throughout the adult life span are priority subjects in a progressively aging society; however, much remains to be learned. The aim of this study was to understand whether changes in cognitive function can be affected by hearing impairment (HI) and whether the impact of HI differs depending on the cognitive domain. A total of 1109 individuals aged 60-79 years at baseline who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences (NILS-LSA) was followed up for a maximum of 13.3 years. Cognitive function was evaluated using four subtests of the Japanese Wechsler Adult Intelligence Scale-Revised Short Forms (JWAIS-R-SF): namely, Information, Similarities, Picture Completion, and the Digit Symbol Substitution subtests. The HI was defined as a pure-tone average of the better ear >25 dB. A longitudinal analysis of 4437 observations obtained during a follow-up period of approximately 12 years was performed. We estimated linear changes in subtest scores by HI status, using the time-varying mixed-effects regression model, which included fixed terms for the intercept, HI status at baseline, time (years elapsed since baseline) and an HI × time interaction term adjusted for age at baseline, sex, education, and other possible confounders. There were significant main effects of HI on the scores of the four subtests after adjustment. The HI × time interaction was significant for the scores of the Information (p = 0.001) and Digit Symbol Substitution subtests (p = 0.001). The scores of the HI group declined faster in the Information and Digit Symbol Substitution subtests compared to those in the no-HI group. The model-predicted 12-year slope using a mean baseline age (68.7 years) indicated no significant decline in the individuals without HI at baseline for the Information and Similarities subtests, however, this tolerance was lost in the individuals with HI. In conclusion, the present observation showed that the impact of HI on cognition was longitudinally significant and implied that the effect differs according to cognitive domain.


[Tobacco smoking and cancer risk].
Smoking tobacco is the most important and potentially modifiable risk factor for cancer in Germany. Combining tobacco with alcohol can multiply cancer risks. Up to 30 % of cancer deaths are due to tobacco smoking. 23,3 % of 18-64 year-old Germans are current smokers; in addition, 11 % of the population are regularly exposed to secondhand tobacco smoke. Tobacco smoking is causally associated with oropharyngeal, laryngeal, nose, paranasal sinus, lung, esophageal, gastric, pancreatic, hepatocellular, biliary, colorectal, kidney, ureter, urinary bladder, uterine cervix and ovary cancers and leukemia. Smokers should be supported to stop smoking and join programmes of cancer screening. Smoking cessation effectively reduces tobacco-associated cancer risk.


Microsomal epoxide hydrolase genotype and risk of myocardial infarction.
DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). Microsomal epoxide hydrolase (EPHX1) is involved in the metabolism of tobacco smoke mutagens and an amino acid substitution (H139R) in exon 4 of the EPHX1 gene is associated with increased enzyme activity. The objective of this study was to investigate the effect of EPHX1 genotype on risk of myocardial infarction (MI) and to determine whether smoking interacts with genotype to modify risk. Cases (n = 2,022) with a first acute non-fatal MI and population-based controls (n = 2,022) living in Costa Rica, matched for age, sex and area of residence were genotyped by RFLP-PCR. Smoking status was determined by questionnaire. The frequency of the R139 allele was 17% for both cases and controls. EPHX1 genotype was not associated with risk of MI, regardless of smoking status. Compared to individuals with the HH genotype, the multivariate adjusted odds ratio (95% confidence interval) for risk of MI was 0.95 (0.81-1.11) for individuals with the HR genotype and 1.18 (0.79-1.76) for those with the RR genotype. These results suggest that EPHX1 does not play a significant role in the development of CHD.


Hb Grove City [β38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G]: a new low oxygen affinity β chain variant.
A previously unreported β chain hemoglobin (Hb) variant, Hb Grove City [β38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G], was discovered in a woman who presented with hypoxia and mild anemia. Her young daughter also tested positive for the variant and displayed similar symptoms. Hemoglobin-oxygen dissociation testing confirmed right-shifted oxygen dissociation curves. A corresponding Hb variant was detected by high performance liquid chromatography (HPLC) and intact mass spectrometry (MS) but was not detected by capillary electrophoresis (CE), isoelectrofocusing (IEF) or alkaline or acid electrophoresis. DNA sequencing analysis confirmed a β-globin gene mutation. All three previous mutations at this locus affect oxygen affinity, as does this new variant. This newly described variant showed variable stability results and therefore may be mildly unstable but is not associated with microcytosis, significant hemolysis or clinically evident cyanosis. It is important to consider hemoglobinopathies in patients who are anemic and have unexplained hypoxia. Arterial blood gas and p50 evaluations may prevent unnecessary diagnostic interventions. Additionally, Hb variants with altered oxygen affinity can be electrophoretically silent; therefore, multiple methods including MS and/or DNA sequencing are warranted when clinical suspicion is high.


Soil respiration in Tibetan alpine grasslands: belowground biomass and soil moisture, but not soil temperature, best explain the large-scale patterns.
The Tibetan Plateau is an essential area to study the potential feedback effects of soils to climate change due to the rapid rise in its air temperature in the past several decades and the large amounts of soil organic carbon (SOC) stocks, particularly in the permafrost. Yet it is one of the most under-investigated regions in soil respiration (Rs) studies. Here, Rs rates were measured at 42 sites in alpine grasslands (including alpine steppes and meadows) along a transect across the Tibetan Plateau during the peak growing season of 2006 and 2007 in order to test whether: (1) belowground biomass (BGB) is most closely related to spatial variation in Rs due to high root biomass density, and (2) soil temperature significantly influences spatial pattern of Rs owing to metabolic limitation from the low temperature in cold, high-altitude ecosystems. The average daily mean Rs of the alpine grasslands at peak growing season was 3.92 µmol CO(2) m(-2) s(-1), ranging from 0.39 to 12.88 µmol CO(2) m(-2) s(-1), with average daily mean Rs of 2.01 and 5.49 µmol CO(2) m(-2) s(-1) for steppes and meadows, respectively. By regression tree analysis, BGB, aboveground biomass (AGB), SOC, soil moisture (SM), and vegetation type were selected out of 15 variables examined, as the factors influencing large-scale variation in Rs. With a structural equation modelling approach, we found only BGB and SM had direct effects on Rs, while other factors indirectly affecting Rs through BGB or SM. Most (80%) of the variation in Rs could be attributed to the difference in BGB among sites. BGB and SM together accounted for the majority (82%) of spatial patterns of Rs. Our results only support the first hypothesis, suggesting that models incorporating BGB and SM can improve Rs estimation at regional scale.


Birth weight and gestational age in children with cerebral palsy or seizure disorders.
Birth weight and gestational age of single-born children with cerebral palsy (CP) and those with seizure disorders were compared with norms for 40,000 single-born children in the same prospectively identified population. Low birth-weight and short gestation were important risk factors for CP, but these characteristics were uncommon, and the majority of children with CP were of normal birth weight and term gestational age. Preterm children with CP by age 7 years tended to have been even smaller at birth than was appropriate for their short gestions. Among term infants with later CP, the birth weights of the majority were appropriate for dates, but a subgroup were noticeably small for dates at term. Low birth weight, preterm birth, and smallness for dates at term were not significantly related to the risk of seizure disorders in children free of CP.


Working in the Electronic Garden: The Visual Rhetoric of Herman Miller's Action Office.
The image on the cover of this journal represents the intersection of two important architectural and technological changes to American offices in the 1970s: the growth of the open-plan office and the transformation of corporate computing. This advertising image shows how manufacturer Herman Miller promoted its Action Office furniture system as a means of facilitating and supporting these twin developments, portraying the modern office as a verdant electronic garden. Through a close reading of the imagery, the author argues that the representation of people, plants, computers, and furniture is designed to convey both the humanizing qualities of the open-plan concept and the system's technical and aesthetic aspects. The image is a rich primary source that reveals important aspects of the rhetoric of Herman Miller.


DECIPHER, a search-based approach to chimera identification for 16S rRNA sequences.
DECIPHER is a new method for finding 16S rRNA chimeric sequences by the use of a search-based approach. The method is based upon detecting short fragments that are uncommon in the phylogenetic group where a query sequence is classified but frequently found in another phylogenetic group. The algorithm was calibrated for full sequences (fs_DECIPHER) and short sequences (ss_DECIPHER) and benchmarked against WigeoN (Pintail), ChimeraSlayer, and Uchime using artificially generated chimeras. Overall, ss_DECIPHER and Uchime provided the highest chimera detection for sequences 100 to 600 nucleotides long (79% and 81%, respectively), but Uchime's performance deteriorated for longer sequences, while ss_DECIPHER maintained a high detection rate (89%). Both methods had low false-positive rates (1.3% and 1.6%). The more conservative fs_DECIPHER, benchmarked only for sequences longer than 600 nucleotides, had an overall detection rate lower than that of ss_DECIPHER (75%) but higher than those of the other programs. In addition, fs_DECIPHER had the lowest false-positive rate among all the benchmarked programs (<0.20%). DECIPHER was outperformed only by ChimeraSlayer and Uchime when chimeras were formed from closely related parents (less than 10% divergence). Given the differences in the programs, it was possible to detect over 89% of all chimeras with just the combination of ss_DECIPHER and Uchime. Using fs_DECIPHER, we detected between 1% and 2% additional chimeras in the RDP, SILVA, and Greengenes databases from which chimeras had already been removed with Pintail or Bellerophon. DECIPHER was implemented in the R programming language and is directly accessible through a webpage or by downloading the program as an R package (http://DECIPHER.cee.wisc.edu).


Molecular characterization of aspergillus fumigatus allergens.
Aspergillus fumigatus (Af) is ubiquitous saprophytic fungus associated with a broad spectrum of diseases in humans. These diseases range from benign colonization of the lung to life threatening diseases such as allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis. Af is the etiologic agent identified in most of the Aspergillus related human diseases and is therefore of particular clinical importance. Af induced obstructive airway diseases may be due to transient exposure to fungal spores resulting in a T helper 2 response. The IgE mediated inflammatory reaction could be due to colonization of bronchial airway epithelium by Af. Early and precise diagnosis of Aspergillus induced respiratory allergy is essential for preventing irreversible lung damages. The major problems in the diagnosis of A. fumigatus induced diseases are due to the lack of standardized and well characterized fungal extracts. The advent of molecular cloning technology and the development of phage surface display technology for cloning genes have facilitated the isolation of more relevant recombinant allergens. Using these techniques, a panel of different Af allergens having distinct IgE binding with various groups of Af sensitized patients have been cloned and characterized. These allergens can be categorized functionally as secreted and cytoplasmic proteins. The distinct IgE binding property of these purified and well characterized recombinant Af allergens may be useful for the differential diagnosis of Af related pulmonary complications.


Regulation of recombination and genomic maintenance.
Recombination is a central process to stably maintain and transmit a genome through somatic cell divisions and to new generations. Hence, recombination needs to be coordinated with other events occurring on the DNA template, such as DNA replication, transcription, and the specialized chromosomal functions at centromeres and telomeres. Moreover, regulation with respect to the cell-cycle stage is required as much as spatiotemporal coordination within the nuclear volume. These regulatory mechanisms impinge on the DNA substrate through modifications of the chromatin and directly on recombination proteins through a myriad of posttranslational modifications (PTMs) and additional mechanisms. Although recombination is primarily appreciated to maintain genomic stability, the process also contributes to gross chromosomal arrangements and copy-number changes. Hence, the recombination process itself requires quality control to ensure high fidelity and avoid genomic instability. Evidently, recombination and its regulatory processes have significant impact on human disease, specifically cancer and, possibly, neurodegenerative diseases.


Lack of correlation between an assay used to determine early marrow allograft rejection and long-term chimerism after murine allogeneic bone marrow transplantation: effects of marrow dose.
The acute rejection of bone marrow (BM) allografts by host effectors can occur within a short period after BM transplantation (BMT) in lethally irradiated mice. Common assays used to ascertain engraftment/resistance involve measuring the growth of granulocyte/monocyte progenitors (colony-forming unit-granulocyte-macrophage) in vitro or splenocyte proliferation assessed by radioisotope incorporation in vivo 5 to 8 days after BMT. However, the correlation of the long-term outcome of BMT with the kinetics of recovery by using the dose of allogeneic BM cells (BMCs) that leads to early rejection as determined by the in vitro assessment has not been extensively studied. Thus, to investigate whether the early rejection of donor BMCs is an indication of a long-term engraftment failure, C57BL/6 (H2b) mice were lethally irradiated and transplanted with various doses of BALB/c (H2d) BMCs. The short-term engraftment of donor precursors (colony-forming unit-granulocyte-macrophage), the kinetics of hematopoietic cell recovery, the extent of donor chimerism, and the proportion of the recipients with long-term survival were determined. The results show that the kinetics and extent of hematopoietic cell recovery were significantly delayed in mice receiving limiting doses of BMCs that were rejected or severely resisted at day 8 after BMT. However, a proportion of these mice survived up to 98 days after BMT with mixed chimerism or donor chimerism. This study demonstrates that early rejection of BM precursors, as assessed by measurement of myeloid progenitors in the spleen after BMT, does not always correlate with the long-term outcome of the marrow allograft and that significant variability is inherent in the extent of chimerism when threshold amounts of BMCs are used.


Hepatocellular carcinoma: Review of disease and tumor biomarkers.
Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest.


Helium Flux from the Earth's Mantle as Estimated from Hawaiian Fumarolic Degassing.
Averaged helium to carbon dioxide ratios measured from systematic collections of gases from Sulphur Bank fumarole. Kilauea, Hawaii, when coupled with estimates of carbon in the earth's crust, give a helium flux of 1 x 105 atoms per square centimeter per second. This is within the lower range of other estimates, and may represent the flux from deep-seated sources in the upper mantle.


Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention.
Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.


Gut Microbiota during Dietary Restrictions: New Insights in Non-Communicable Diseases.
In recent decades, there has been a growing interest in dietary restrictions for their promising effects on longevity and health span. Indeed, these strategies are supposed to delay the onset and burden of non-communicable diseases (NCDs) such as obesity, diabetes, cancer and neurological and gastrointestinal inflammatory diseases. At the same time, the gut microbiota has been shown to play a crucial role in NCDs since it is actively involved in maintaining gut homeostasis through its impact on nutrients metabolism, gut barrier, and immune system. There is evidence that dietary restrictions could slow down age-related changes in the types and numbers of gut bacteria, which may counteract gut dysbiosis. The beneficial effects on gut microbiota may positively influence host metabolism, gut barrier permeability, and brain functions, and subsequently, postpone the onset of NCDs prolonging the health span. These new insights could lead to the development of novel strategies for modulating gut microbiota with the end goal of treating/preventing NCDs. This review provides an overview of animal and human studies focusing on gut microbiota variations during different types of dietary restriction, in order to highlight the close relationship between gut microbiota balance and the host's health benefits induced by these nutritional regimens.


[Effects of ethmozine and ethacizin on the central hemodynamics, peripheral vascular tonus and tissue oxygenation in patients with ventricular rhythm disorders and cardiac insufficiency].
Daily monitoring of the ECG, catheterization of the pulmonary artery, tetrapolar chest rheography, occlusion plethysmography and polarography were employed to study the antiarrhythmic efficacy and the effects on the central and peripheral circulation of the new antiarrhythmic etmozine and etacyzine. Twenty-two patients with a frequent chronic ventricular premature heart beat (PHB) and clinically marked circulatory failure (CF) were entered into the study. Intake of etmozine (600 to 800 mg daily) and etacyzine (100 to 300 mg daily) over 5 to 6 days exerted a positive antiarrhythmic effect in 52.6 and 83.3% of the patients, respectively. Etmozine did not produce any adverse hemodynamic action, whereas etacyzine brought about an insignificant increase in the stroke and minute volumes of the heart (12.3 and 9.8%, respectively). However, the lack of an increase in the heart rate (HR), diastolic pressure in the pulmonary artery and regional vascular resistance (RVR), and no significant rise of the preload (systolic pressure in the right atrium) and afterload (elevation of the mean arterial blood pressure and RVR) attest to the fact that etacyzine has a negligible adverse hemodynamic action in CF patients. Intravenous injection of etmozine does not elicit any changes in the RVR or in the venous tone. Meanwhile intravenous injection of etacyzine leads to a significant reduction in the RVR (23.3%). The treatment with both etmozine and etacyzine given in courses promotes the improvement of the microcirculation and tissue oxygen metabolism in patients presenting with CF. More pronounced positive shifts in the microcirculation were achieved with etacyzine. Apparently, this bears on a more demonstrable arteriolodilatation effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Developing the anemone Aiptasia as a tractable model for cnidarian-dinoflagellate symbiosis: the transcriptome of aposymbiotic A. pallida.
Coral reefs are hotspots of oceanic biodiversity, forming the foundation of ecosystems that are important both ecologically and for their direct practical impacts on humans. Corals are declining globally due to a number of stressors, including rising sea-surface temperatures and pollution; such stresses can lead to a breakdown of the essential symbiotic relationship between the coral host and its endosymbiotic dinoflagellates, a process known as coral bleaching. Although the environmental stresses causing this breakdown are largely known, the cellular mechanisms of symbiosis establishment, maintenance, and breakdown are still largely obscure. Investigating the symbiosis using an experimentally tractable model organism, such as the small sea anemone Aiptasia, should improve our understanding of exactly how the environmental stressors affect coral survival and growth. We assembled the transcriptome of a clonal population of adult, aposymbiotic (dinoflagellate-free) Aiptasia pallida from ~208 million reads, yielding 58,018 contigs. We demonstrated that many of these contigs represent full-length or near-full-length transcripts that encode proteins similar to those from a diverse array of pathways in other organisms, including various metabolic enzymes, cytoskeletal proteins, and neuropeptide precursors. The contigs were annotated by sequence similarity, assigned GO terms, and scanned for conserved protein domains. We analyzed the frequency and types of single-nucleotide variants and estimated the size of the Aiptasia genome to be ~421 Mb. The contigs and annotations are available through NCBI (Transcription Shotgun Assembly database, accession numbers JV077153-JV134524) and at http://pringlelab.stanford.edu/projects.html. The availability of an extensive transcriptome assembly for A. pallida will facilitate analyses of gene-expression changes, identification of proteins of interest, and other studies in this important emerging model system.


Understanding Echinocandin Resistance in the Emerging Pathogen Candida auris.
Candida auris has simultaneously emerged on five continents as a fungal pathogen causing nosocomial outbreaks. The challenges in the treatment of C. auris infections are the variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, the in vitro susceptibility to echinocandin antifungal drugs was determined and FKS1 sequencing was performed on 106 C. auris clinical isolates. Four isolates were identified to be resistant to all tested echinocandins (MIC ≥ 4 mg/liter) and harbored an S639F mutation in FKS1 hot spot region 1. All remaining isolates were FKS1 wild type (WT) and echinocandin susceptible, with micafungin being the most potent echinocandin (MIC50 = 0.125 mg/liter). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all FKS1 WT isolates exhibited an Eagle effect (also known as the paradoxical growth effect), which occurred at various intensities. To assess whether the Eagle effect resulted in pharmacodynamic resistance, 8 representative isolates were evaluated for their in vivo drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in FKS1 are echinocandin resistant and that routine in vitro testing of C. auris isolates for susceptibility to caspofungin by the broth microdilution method should be viewed cautiously or avoided.


Descemet Membrane Endothelial Keratoplasty with Irregular-Edged Graft: A Salvage Method for Large Radial Graft Tears.
Large radial tears of donor Descemet membrane (DM) during the preparation of Descemet membrane endothelial keratoplasty (DMEK) grafts can make the trephination stage impossible because of small graft diameter. This results in irregular-edged grafts. In this study, we report two pseudophakic bullous keratopathy patients who underwent DMEK surgery with irregular-edged Descemet membrane (DM) grafts. Main outcome measures were preoperative and postoperative 1-, 3-, and 6-month best corrected visual acuity (BCVA), endothelial cell density (ECD) and central corneal thickness (CCT). Intraoperative and early postoperative complications were also evaluated. Both irregular-edged grafts were successfully implanted into the anterior chamber, unfolded, and attached to the posterior corneal stroma. Patients' BCVA at 6 months was 1.0 (Snellen equivalent: 20/20) and 0.6 (Snellen equivalent: 20/32) respectively. Decrease in ECD at the last visit was 27% and 25%. CCT decreased from 723 μm and 850 μm to 530 μm and 523 μm, respectively. No intraoperative complications occurred except for the large radial Descemet membrane graft tears that developed during donor DM stripping. None of the cases needed a rebubbling procedure postoperatively. We have demonstrated that irregular-edged DM grafts can be successfully implanted for DMEK surgery with good clinical outcomes.


Alcohol consumption and n-3 polyunsaturated fatty acids in healthy men and women from 3 European populations.
Because high dietary and blood n-3 (omega-3) fatty acids (FAs) are protective against coronary heart disease and sudden cardiac death, the alcohol-associated increase in blood n-3 FAs could be considered an original mechanism of alcohol's cardioprotective effect. Our objective was to assess whether alcohol consumption is associated with concentrations of very-long-chain "marine" (eg, fish oil) n-3 FAs both in plasma and in red blood cell membranes. In the framework of the IMMIDIET (Dietary Habit Profile in European Communities with Different Risk of Myocardial Infarction: the Impact of Migration as a Model of Gene-Environment Interaction) Project, 1604 subjects (802 women-men pairs), aged 26-65 y, were enrolled in Italy, Belgium, and England. A 1-y-recall food-frequency questionnaire was used to evaluate dietary intake. In fully adjusted multivariate analyses, alcohol intake was positively associated with plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA + DHA concentrations (P < 0.0001, P = 0.036, and P = 0.002, respectively) in women and with EPA and the EPA + DHA index in red blood cells (P < 0.0001 and P = 0.037, respectively). In men, only plasma and red blood cell EPA concentrations were associated with alcohol intake (P = 0.003 and P = 0.004, respectively). Stratified analyses showed an association between alcohol and both plasma and red cell EPA (P = 0.008 and P = 0.002, respectively), DHA (P = 0.014 and P = 0.008, respectively), and the EPA + DHA index (P = 0.010 and P = 0.006, respectively) in wine drinkers, whereas no association was found in those who drink beer and spirits. Alcohol intake was associated with higher plasma and red blood cell concentrations of marine n-3 FAs. Components of wine other than alcohol (polyphenols) might exert these effects. Part of the alcohol-induced cardioprotection may be mediated through increased marine n-3 FAs.


Identification and verification of lysine propionylation and butyrylation in yeast core histones using PTMap software.
Ten types of post-translational modifications (PTMs) known to be critical to diverse cellular functions have been described in core histone proteins. However, it remains unclear whether additional PTMs exist in histones, and if so, what roles these undiscovered signals play in epigenetic phenomena. Here, we report a systematic analysis of yeast histone PTMs by mass spectrometry in combination with protein sequence alignment using PTMap, a computer program we recently developed. We have identified, for the first time, multiple sites of lysine propionylation and butyrylation in yeast histones H2B, H3, and H4. We confirmed these modifications by Western blotting using modification-specific antibodies, MS/MS of synthetic peptides, and coelution of synthetic and in vivo-derived peptides from an HPLC column. The presence of multiple modification sites in several yeast histones suggests that these two PTMs are histone marks that are evolutionarily conserved among eukaryotes. In addition, we identified 14 novel mass shifts that do not match any known PTM, suggesting the presence of previously undescribed histone modifications. The chemical natures of these modifications remain to be determined. Our studies therefore expand current knowledge of the "histone code".


Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer.
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 107, which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 103-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism.


Why Does Bi2WO6 Visible-Light Photocatalyst Always Form as Nanoplatelets?
Bi2WO6 nanocrystals exhibit excellent photocatalytic properties in the visible range of the solar spectrum, and intense efforts are directed at designing effective synthesis processes with control of size, morphology, and hierarchical structure. All known hydrothermal syntheses produce either nanoplatelet morphology or hierarchical structures based on such primary entities. Here we investigate the nucleation and growth of Bi2WO6 nanocrystals under hydrothermal conditions using in situ X-ray total scattering (TS) and powder X-ray diffraction (PXRD) measurements. It is shown that the preferential growth of Bi2WO6 nanoplates is due to the presence of disordered layers of Bi2O22+ molecular complexes in the precursor solution with an approximate length of 13 Å. These layers interact with tetrahedral WO42- molecular units and eventually form the disordered cubic (Bi0.933W0.067)O1.6) crystalline phase. When enough tungsten units are intertwined between Bi2O22+ layers formation of Bi2WO6 pristine nanoplates takes place by necessary sideways addition of units in the ac plane. The experimentally observed formation mechanism suggests that the Bi/W atomic ratio must play a central role in the nucleation (assembly of initial crystal layers). Indeed, it is observed in separate continuous flow supercritical synthesis that for a stoichiometric (Bi/W = 2:1) precursor, a (Bi0.933W0.067)O1.6) impurity phase is always observed together with the main Bi2WO6 product. Excess tungsten is required in the precursor to form phase-pure Bi2WO6 material. Thus, the present study also reports a fast, scalable, and green method for production of this highly attractive photocatalyst.


Effects of captopril and propranolol on cognitive function and cerebral blood flow in aged hypertensive rats.
Chronic hypertension has been reported to produce adverse cognitive effects in elderly individuals, perhaps by altering central nervous system hemodynamics. The beneficial or adverse effects of antihypertensive drugs on these processes are not well understood. We examined the effects of captopril (90 mg/kg/day) and propranolol (80 mg/kg/day) on cognitive function and brain blood flow in hypertensive and normotensive rats. Cognitive function was assessed by the Morris water maze, and regional brain blood flow was measured by the [14C]iodoantipyrine method. Nineteen-month-old propranolol-treated hypertensive rats exhibited poorer performance (p < .05) than control rats and had lower brain blood flows, particularly in white matter regions (p < .01). Captopril-treated hypertensive rats did not differ significantly from control rats with regard to either cognitive performance or brain blood flow. In the normotensive rats, there were no effects of either drug on cognitive performance or brain blood flow. Thus, blood pressure reduction by propranolol but not captopril has an adverse effect on cognitive function and brain blood flow in hypertensive rats.


[Value of correcting microcirculatory disorders of inflammatory foci in the treatment of infection].
Experience in the treatment of 94 patients with sepsis is discussed. Studies showed that microcirculatory disorders occurring around the inflammatory focus are among the main causes of insufficient efficacy of antibiotic therapy. For correction of the microcirculatory changes, the authors suggest (in addition to vasodilators, inhibitors of proteases and heparin used earlier for this purpose) transfusion of chilled plasma which is a antithrombin-III donator. As the result of such treatment mortality reduced from 45.8 to 16.7%.


Ecological drivers of marine debris ingestion in Procellariiform Seabirds.
Procellariiform seabirds are both the most threatened bird group globally, and the group with the highest incidence of marine debris ingestion. We examined the incidence and ecological factors associated with marine debris ingestion in Procellariiformes by examining seabirds collected at a global seabird hotspot, the Australasian - Southern Ocean boundary. We examined marine debris ingestion trends in 1734 individuals of 51 Procellariform species, finding significant variation in the incidence of marine debris abundance among species. Variation in the incidence of marine debris ingestion between species was influenced by the taxonomy, foraging ecology, diet, and foraging range overlaps with oceanic regions polluted with marine debris. Among the ecological drivers of marine debris ingestion variability in Procellariiformes, we demonstrate that the combination of taxonomy, foraging method, diet, and exposure to marine debris are the most important determinants of incidence of ingestion. We use these results to develop a global forecast for Procellariiform taxa at the risk of highest incidence of marine debris ingestion. We find seabirds that forage at the surface; especially by surface seizing, diving and filtering, those with a crustacean dominant diet, and those that forage in or near marine debris hotspots are at highest risk of debris ingestion. We predict that family with the highest risk are the storm petrels (Hydrobatidae and Oceanitidae). We demonstrate that the greater the exposure of high-risk groups to marine debris while foraging, the greater the incidence and number of marine debris items will be ingested.


Synthesis of Graphene Oxide-Fe3O4 Based Nanocomposites Using the Mechanochemical Method and in Vitro Magnetic Hyperthermia.
The study presented in this work consists of two parts: The first part is the synthesis of Graphene oxide-Fe3O4 nanocomposites by a mechanochemical method which, is a mechanical process that is likely to yield extremely heterogeneous particles. The second part includes a study on the efficacy of these Graphene oxide-Fe3O4 nanocomposites to kill cancerous cells. Iron powder, ball milled along with graphene oxide in a toluene medium, underwent a controlled oxidation process. Different phases of GO-Fe3O4 nanocomposites were obtained based on the composition used for milling. As synthesized nanocomposites were characterized by x-ray diffraction (XRD), alternating magnetic field (AFM), Raman spectroscopy, and a vibrating sample magnetometer (VSM). Additionally, the magnetic properties required to obtain high SAR values (Specific Absorption Rate-Power absorbed per unit mass of the magnetic nanocomposite in the presence of an applied magnetic field) for the composite were optimized by varying the milling time. Nanocomposites milled for different extents of time have shown differential behavior for magneto thermic heating. The magnetic composites synthesized by the ball milled method were able to retain the functional groups of graphene oxide. The efficacy of the magnetic nanocomposites for killing of cancerous cells is studied in vitro using HeLa cells in the presence of an AC (Alternating Current) magnetic field. The morphology of the HeLa cells subjected to 10 min of AC magnetic field changed considerably, indicating the death of the cells.


Practical aspects of sentinel node biopsy in oral cavity cancer: all nodes that emit a signal are important.
Sentinel node biopsy (SNB) is a safe and effective way to examine an N0 neck in early-stage oral cavity cancer (OCC). In this study, we evaluated the variables of SNB detection, surgery, and outcome. Ninety-two patients with N0 OCC examined with SNB were included. Number and brightness of nodes detected on preoperative imaging and during surgery were analyzed and compared with histological findings. Patients with recurrent disease were evaluated separately and the effect of smoking and alcohol consumption was analyzed. Eighteen patients had at least malignant cells in the sentinel lymph node (SLN); 18 patients had recurrent disease and nine patients died from the cancer. The negative predictive value of SNB was 95%. Six patients did not have metastases in the node with the strongest signal, but metastases were found in an SLN with a weaker signal. Smoking and alcohol consumption did not affect disease-specific or overall survival. SNB has been confirmed to be safe and effective in early stage N0 OCC. However, it is important to carefully harvest up to four hottest SLNs that emit a signal. Treatment of patients with only isolated tumor cells (ITC) in the SLN appears to be necessary.