Current Warm-Up Practices and Contemporary Issues Faced by Elite Swimming Coaches.
McGowan, CJ, Pyne, DB, Raglin, JS, Thompson, KG, and Rattray, B. Current warm-up practices and contemporary issues faced by elite swimming coaches. J Strength Cond Res 30(12): 3471-3480, 2016-A better understanding of current swimming warm-up strategies is needed to improve their effectiveness. The purpose of this study was to describe current precompetition warm-up practices and identify contemporary issues faced by elite swimming coaches during competition. Forty-six state-international level swimming coaches provided information through a questionnaire on their prescription of volume, intensity, and recovery within their pool and dryland-based competition warm-ups, and challenges faced during the final stages of event preparation. Coaches identified four key objectives of the precompetition warm-up: physiological (elevate body temperature and increase muscle activation), kinesthetic (tactile preparation, increase "feel" of the water), tactical (race-pace rehearsal), and mental (improve focus, reduce anxiety). Pool warm-up volume ranged from ∼1300 to 2100 m, beginning with 400-1000 m of continuous, low-intensity (∼50-70% of perceived maximal exertion) swimming, followed by 200-600 m of stroke drills and 1-2 sets (100-400 m in length) of increasing intensity (∼60-90%) swimming, concluding with 3-4 race or near race-pace efforts (25-100 m; ∼90-100%) and 100-400 m easy swimming. Dryland-based warm-up exercises, involving stretch cords and skipping, were also commonly prescribed. Coaches preferred swimmers complete their warm-up 20-30 minutes before race start. Lengthy marshalling periods (15-20+ minutes) and the time required to don racing suits (>10 minutes) were identified as complicating issues. Coaches believed that the pool warm-up affords athletes the opportunity to gain a tactile feel for the water and surrounding pool environment. The combination of dryland-based activation exercises followed by pool-based warm-up routines seems to be the preferred approach taken by elite swimming coaches preparing their athletes for competition.


A Feasible Role of Neuropilin Signaling in Pharyngeal Pouch Formation in Zebrafish.
Pharyngeal pouches are an important epithelial structure controlling facial skeletal development in vertebrates. A series of pouches arise sequentially in the pharyngeal endoderm through collective cell migration followed by rearrangement of pouch-forming cells. While crucial transcription factors and signaling molecules have been identified in pouch formation, a role for Neuropilins (Nrps) in pouch development has not yet been analyzed in any vertebrates. Nrps are cell surface receptors essential for angiogenesis and axon guidance. In all vertebrates, the two Nrp family members, Nrp1 and Nrp2, are conserved in the genome, with two paralogs for Nrp1 (Nrp1a and Nrp1b) and Nrp2 (Nrp2a and Nrp2b) being identified in zebrafish. Here, I report a potential requirement of Nrp signaling in pouch development in zebrafish. nrp1a and nrp2b were expressed in the developing pouches, with sema3d, a ligand for Nrps, being expressed in the pouches. Knocking down Nrps signaling in the pharyngeal endoderm led to severe defects in pouches and facial cartilages. In addition, blocking Mitogen-activated protein kinase (MAPK) activities, a downstream effector of Nrp signaling, in the pharyngeal endoderm caused similar defects in pouches and facial skeleton to those by knocking down Nrps signaling. My results suggest that Nrp signaling acts for pouch formation through MAPK.


Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback.
Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state. The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154.


Copper-catalyzed N-arylation of imidazoles and benzimidazoles.
4,7-Dimethoxy-1,10-phenanthroline (L1c) was found to be an efficient ligand for the copper-catalyzed N-arylation of imidazoles and benzimidazoles with both aryl iodides and bromides under mild conditions. Further optimization of the system has revealed that the addition of poly(ethylene glycol) accelerates this reaction. A variety of hindered and functionalized imidazoles, benzimidazoles, and aryl halides were transformed in good to excellent yields. Heteroaryl halides were also coupled in moderate to good yields. We also present the results obtained from a series of coupling reactions, which directly compare the use of L1c with other recently reported ligands.


The role of cacao extract in reduction of the number of mutans streptococci colonies in the saliva of 12-14 year-old-children.
Cacao bean husk ethanol extract (CBHEE) has polyphenol that acts as an antibacterial agent, specially anti-glucosyltransferase. This study is aimed to see the effectiveness of CBHEE to reduce the number of mutans streptococci colonies in the saliva of children (with young permanent teeth), when CBHE is used as mouth rinse. This study used cross-sectional study design with time-series experimental study and used simple random sampling on 30 subjects. The chosen subjects are those who have middle oral hygiene status (OHI-S). Each subject was given the same intervention; in the first step, saliva was collected from the subjects (prior to intervention), in the second step, the subjects were given 15 mL of CBHEE 0.1% mouth rinse to rinse their mouth for about 30 s. After intervention, their saliva was collected twice in 15 min and 30 min after intervention. Furthermore, the number of mutans streptococci colonies were measured in colony-forming units (CFU) and the data was statistically analyzed using analysis of variance (ANOVA) and paired t-test. The data was analyzed and processed using Statistical Package for the Social Sciences (SPSS) 22.0 for windows versions. The data statistically showed, significantly, the reduction of Streptococcus mutans colonies before and after 30 min of intervention. Before intervention, there were 59.10 CFU/mL of mutans streptococci, and after 15 min of intervention it showed reduction of mutans streptococci to 25.73 CFU/mL and after 30 min of intervention, the counts of mutans streptococci showed a reduction to 9.40 CFU/mL. From the test results, statistical value of this research was P = 0.000 (P < 0.05), which means that the reduction of the mutans streptococci count was significant. Using CBHEE as mouth rinse for children has been proven highly effective in reducing mutans streptococci colony counts in the mouth.


Histochemical and immunohistochemical studies of distribution of acetylcholinesterase-positive fibers and peptidergic terminals in the nasal mucosa of rats.
To further investigate the mechanism of nasal secretion closely related to the innervation patterns in nasal mucosa with emphasis on the acetylcholinesterase (AChE)-positive fibers and peptidergic terminals in nasal mucosa as well as trigeminal ganglion (TG) cells. Histochemical demonstration of AChE-positive fibers, immunohistochemical study of the distribution patterns of multiple peptidergic terminals, double labelling of AChE and substance P (SP) and somatostatin (SOM) mRNA in situ hybridization were carried out in nasal mucosa and trigeminal ganglion (TG) in rats. AChE-positive terminals were mainly distributed in the mid to posterior one third of septal nasal mucosa, with greater staining density on the walls of small vessels and glands. There were fewer such terminals in turbinate mucosa. Tachykinins-ergic terminals, including substance P (SP)-, neurokinin A (NKA)-, neurokinin B (NKB)- and calcitonin gene-related peptide (CGRP)-ergic terminals, had an extensive localizations in nasal mucosa, involving the following areas: between epithelial cells, submucosa, the walls of small vessels, glands and venous sinusoids in both septal and turbinate nasal mucosa. Septal mucosa had the greater density. There were overlaps in the distribution of these peptidergic terminals. There were also vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and galanin (GAL)-ergic terminals in nasal mucosa. But no neurotensin (NT)- and somatostatin (SOM)-ergic terminals were found. In situ hybridization revealed SOMmRNA expression in TG cells. AChE and nine neuropeptides existed in the cytoplasms of TG cells. Besides, AChE and SP could exist simultaneously in cytoplasms of TG cells. AChE-positive (corresponding to parasympathetic nerves) and peptidergic terminals have different distribution patterns in the nasal mucosa of rats, although an overlap does exist, indicative of their different physiological effects on the regulation of nasal secretion and other functions; AChE and multiple neuropeptides in the cytoplasm of TG cells might play a role in modulating the nasal secretion in response to stimuli in the nasal mucosa.


Hereditary Transthyretin Amyloidosis: Clinical Presentation and Management Updates.
Hereditary transthyretin amyloidosis, once a rare progressive neuropathy and/or cardiomyopathy, is now recognized with increasing worldwide frequency, various phenotypes, and over 130 gene mutations identified to date. This inherited disorder develops as a result of mutated transthyretin amyloid aggregation and systematic deposition throughout the body. With increasing knowledge about the pathophysiology of this disease, new disease-modifying therapies are being developed. In addition to slowing progression, these new agents were found to improve quality of life and reduce the severity of neuropathic symptoms. Two new gene-modifying therapies recently received Food and Drug Administration approval following the positive results from phase III trials. These include an antisense oligonucleotide, inotersen, and small interfering RNA, patisiran, which were reported to reduce the production of transthyretin and had promising safety profiles. Additional novel therapies are being explored with hopes to prolong survival. Therefore, early diagnosis of this treatable disorder has become increasingly important in clinical practice.


Relationship between plasma ammonia concentration and beta-N-acetylhexosaminidase isoenzyme activities in liver cirrhosis.
Ammonia is known to increase the secretion of beta-N-acetylhexosaminidase (Hex) to the extracellular medium in cultured human fibroblasts and Hep G2 cells. We examined 35 patients with liver cirrhosis and the results revealed a significant increase for the plasma activities of total Hex and its isoenzymes Hex A and Hex B (p < 0.001). The partial correlations, with other biochemical markers of liver injury constant, between plasma ammonia concentration and the activity (r = 0.658) and the proportion in percentage of the Hex B isoenzyme (r = 0.692) were statistically significant (p < 0.001). The increased concentration of ammonia could explain, at least partially, an increased secretion of Hex B isoforms to the plasma in patients with liver disease.


Fetal MR imaging of atelosteogenesis type II (AO-II).
The diastrophic dysplasia family of osteochondrodysplasias comprises a spectrum of skeletal diseases characterized by abnormal growth and remodelling of cartilage and bone. They are caused by mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene. Different defects in this gene product give rise to the variety of phenotypes based on the level of residual transport capacity. We reported a case of a fetus with this spectrum, evaluated and diagnosed with fetal MRI.


Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.
Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.


Structural, vibrational, and rovibrational analysis of tetrafluoroethylene.
High resolution FTIR spectra of (13)C enriched tetrafluoroethylene (C(2)F(4)) were measured at 150 K at the Australian Synchrotron. Rovibrational transitions were assigned in the a-type symmetric and b-type antisymmetric CF(2) stretches of (12)C(13)CF(4) and (13)C(2)F(4) near 1170 cm(-1) and 1300 cm(-1), respectively. Ground vibrational state spectroscopic constants for both molecules were determined in addition to the upper state constants for ν(11) and ν(9) of (13)C(2)F(4) and ν(11), ν(2)+ν(6), and ν(5) of (12)C(13)CF(4). The ground state constants, along with those determined for the (12)C(2)F(4) isotopologue from previously published data, were used to determine a semi-experimental r(e) structure r(CC) = 132.36 ± 0.37 pm, r(CF) = 131.11 ± 0.23 pm, α(FCC) = 123.3 ± 0.3° in excellent agreement with ab initio structures. Lower resolution FTIR spectra were measured between 100 and 5000 cm(-1) at room temperature and band centres obtained for all modes of the three isotopologues; although only 5 out of 12 modes in (12)C(2)F(4) and (13)C(2)F(4) are infrared (IR) active, the others were inferred from combination and hot-band positions. A number of modes are observed to be infrared active only in the (12)C(13)CF(4) isotopologue due to its lower symmetry. Most notably, decoupling of the antisymmetric CF(2) motions in the two halves of (12)C(13)CF(4) results in 2 strongly IR active modes that involve motion at one carbon or the other.


[Bovine liver glutamate dehydrogenase modified by 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl: enzymatic activity and catalytic properties].
When modified by 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) bovine liver glutamate dehydrogenase (L-glutamate NAD(P) oxidoreductase, E. C. 188.8.131.52) looses its catalytical activity and sensitivity to allosteric inhibitor GTP. The stoicheiometry of the binding of TMPO to glutamate dehydrogenase has been studied--each protomer bound one molecule of TMPO. It is supposed that TMPO reacts with lysine residue located in the enzyme's active center.


Nanoliter liquid metering in microchannels using hydrophobic patterns.
Nanoliter-sized liquid drops can be accurately metered inside hydrophilic microchannels using a combination of hydrophobic surface treatment and air pressure. The technique involves spontaneously filling the microchannels up to a hydrophobic region and splitting a liquid drop by injecting air through a hydrophobic side channel. The hydrophobic regions are fabricated by using a patterned metal mask on a substrate. The patterned substrate is immersed in an isooctane solution containing 1H,1H,2H,2H-per-fluorodecyltrichlorosilane to form hydrophobic patches on the exposed surface. Stripping the metal mask leaves the hydrophobic patches and restores the hydrophilic substrate surface. Precise and accurate liquid volumes, ranging from 0.5 to 125 nanoliters, have been metered using this technique. Theoretical predictions of the pressure needed to meter drops compare well with the experimental values.


Substrate recognition and modification by the nosiheptide resistance methyltransferase.
The proliferation of antibiotic resistant pathogens is an increasing threat to the general public. Resistance may be conferred by a number of mechanisms including covalent or mutational modification of the antibiotic binding site, covalent modification of the drug, or the over-expression of efflux pumps. The nosiheptide resistance methyltransferase (NHR) confers resistance to the thiazole antibiotic nosiheptide in the nosiheptide producer organism Streptomyces actuosus through 2'O-methylation of 23S rRNA at the nucleotide A1067. Although the crystal structures of NHR and the closely related thiostrepton-resistance methyltransferase (TSR) in complex with the cofactor S-Adenosyl-L-methionine (SAM) are available, the principles behind NHR substrate recognition and catalysis remain unclear. We have analyzed the binding interactions between NHR and model 58 and 29 nucleotide substrate RNAs by gel electrophoresis mobility shift assays (EMSA) and fluorescence anisotropy. We show that the enzyme binds to RNA as a dimer. By constructing a hetero-dimer complex composed of one wild-type subunit and one inactive mutant NHR-R135A subunit, we show that only one functional subunit of the NHR homodimer is required for its enzymatic activity. Mutational analysis suggests that the interactions between neighbouring bases (G1068 and U1066) and A1067 have an important role in methyltransfer activity, such that the substitution of a deoxy sugar spacer (5') to the target nucleotide achieved near wild-type levels of methylation. A series of atomic substitutions at specific positions on the substrate adenine show that local base-base interactions between neighbouring bases are important for methylation. Taken together these data suggest that local base-base interactions play an important role in aligning the substrate 2' hydroxyl group of A1067 for methyl group transfer. Methylation of nucleic acids is playing an increasingly important role in fundamental biological processes and we anticipate that the approach outlined in this manuscript may be useful for investigating other classes of nucleic acid methyltransferases.


Expression of cyclin E and p27(KIP1) in cervical carcinoma.
Carcinogenesis is characterized by deregulation of the cell cycle. Although p53 is still the most important cell-cycle regulator in human malignancies, there is an increased body of evidence indicating that the aberrant expression of cyclins and cyclin-dependent kinase (CDK) inhibitors is considered as one of the most important events in malignant transformation of various human cancers. Among these cell-cycle regulators, the role of cyclin E and p27(KIP1) in the tumorigenesis of the uterine cervix has been poorly defined. Using formalin-fixed, paraffin-embedded cervical tissues, we investigated the expression of cyclin E and p27(KIP1) by immunohistochemistry, and human papillomavirus (HPV) types 16 and 18 by nested polymerase chain reaction (PCR) in 22 control cases, 23 cases with cervical intraepithelial neoplasia (CIN), and 45 patients with invasive cervical carcinoma (ICC). The p27 index (P27I) was significantly lower in patients with ICC and CIN compared to those with a normal cervix. Patients with either invasive cancer or CIN were found to have a significantly higher cyclin E index (CEI) than the controls (P<0.05). Our results were consistent with the concept that the deregulated expression of cyclin E and p27(KIP1) may play an important role in the neoplastic transformation of cervical carcinoma.


Comparison of risk factors for four sexually transmitted infections: results from a study of attenders at three genitourinary medicine clinics in England.
To compare the risk factors for four common sexually transmitted infections (STIs) in attenders at three large urban genitourinary medicine (GUM) clinics in England. Clinical, demographic, and behavioural data on attenders at two clinics in London and one in Sheffield were collected. Risk factors associated with first episodes of genital warts and genital herpes simplex virus (HSV), and uncomplicated gonorrhoea and chlamydia were investigated using the presence of each of these STIs as the outcome variable in separate multiple logistic regression analyses. Using data on the first attendance of the 18,238 patients attending the clinics in 1996, the risk of a gonorrhoea or chlamydia diagnosis was strongly associated with teenagers compared with those aged over 34, with black Caribbeans and black Africans compared with whites, and increased with the number of sexual partners. The risk of genital warts or HSV diagnosis was lowest in black Caribbeans and black Africans compared with whites and was not associated with the number of sexual partners. While genital warts were associated with younger age, odds ratios were much lower compared with those for the bacterial infections. Genital HSV diagnoses were not associated with age. This study of GUM clinic attenders suggests a reduction in the incidence of bacterial STIs may be achievable through targeted sexual health promotion focusing particularly on black ethnic minorities, teenagers, and those with multiple sexual partnerships. Viral STIs were less clearly associated with population subgroups and a broader population based approach to sexual health promotion may be more effective in controlling these infections.


Real-time electronic health record mortality prediction during the COVID-19 pandemic: a prospective cohort study.
To rapidly develop, validate, and implement a novel real-time mortality score for the COVID-19 pandemic that improves upon sequential organ failure assessment (SOFA) for decision support for a Crisis Standards of Care team. We developed, verified, and deployed a stacked generalization model to predict mortality using data available in the electronic health record (EHR) by combining 5 previously validated scores and additional novel variables reported to be associated with COVID-19-specific mortality. We verified the model with prospectively collected data from 12 hospitals in Colorado between March 2020 and July 2020. We compared the area under the receiver operator curve (AUROC) for the new model to the SOFA score and the Charlson Comorbidity Index. The prospective cohort included 27 296 encounters, of which 1358 (5.0%) were positive for SARS-CoV-2, 4494 (16.5%) required intensive care unit care, 1480 (5.4%) required mechanical ventilation, and 717 (2.6%) ended in death. The Charlson Comorbidity Index and SOFA scores predicted mortality with an AUROC of 0.72 and 0.90, respectively. Our novel score predicted mortality with AUROC 0.94. In the subset of patients with COVID-19, the stacked model predicted mortality with AUROC 0.90, whereas SOFA had AUROC of 0.85. Stacked regression allows a flexible, updatable, live-implementable, ethically defensible predictive analytics tool for decision support that begins with validated models and includes only novel information that improves prediction. We developed and validated an accurate in-hospital mortality prediction score in a live EHR for automatic and continuous calculation using a novel model that improved upon SOFA.


Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.
The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.


Effects of exceeding stroke frequency of maximal effort on hand kinematics and hand propulsive force in front crawl.
This study aimed to assess kinematic and kinetic changes in front crawl with various stroke frequency (SF) conditions to investigate why swimming velocity (SV) does not increase above a certain SF (SFmax). Eight male swimmers performed 20 m front crawl four times. The first trial involved maximal effort, whereas SF was controlled during the next three trials. The instructed SFs were 100 (T100%), 110 (T110%), and 120% (T120%) of the SFmax. Through pressure measurement and underwater motion analysis, hand propulsive force (calculated by the difference between the palm and dorsal pressure value and the hand area) and the angle of attack of the hand were quantified, and differences between trials were assessed by a repeated-measures ANOVA. There was no difference in SV between the conditions, while the angle of attack during the latter half of the underwater stroke at T120% was smaller by 25.7% compared with T100% (p = 0.007). The lower angle of attack induced a lower pressure value on the palm that consequently caused a smaller hand propulsive force at T120% than T100% (p = 0.026). Therefore, the decrease in the angle of attack must be minimised to maintain the hand propulsive force.


Biopolymer supported electroanalytical methods for the determination of biomolecules and food additives - a comprehensive perspective.
This review aims at highlighting the significant role biopolymers play in a multitude of fields such as medical diagnostics, the cosmetics industry, food toxicity, and environmental sensing applications. The development of biomaterials, their properties, evaluation, and applications have been subjects of interest for researchers in recent years. Biomaterials and nanomaterials increase the sensing platforms' adaptability and may enable the development of sensors by taking advantage of their new and synergistic features. This review includes more than 50 research works since 2010, describing the diverse roles played by various biopolymers in the sensing field. It has been noticed that there is only a limited number of publications reported on biopolymer-supported electrochemical sensors. Hence, we offer a thorough analysis of biopolymer uses in healthcare and food detection, including those that are carbon-based, inorganic, and organic. The latest advancements in the field of biopolymer-supported electrochemical sensors for biomolecules and food additives are discussed in this review and hold tremendous potential for the application of biopolymers in the early screening of diseases and point-of-care testing.


A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat.
We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 μg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 μg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 μg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours.


[Assessing senior high school students' resistance responses to offers of alcohol and tobacco from peers of the same age].
Objectives The purpose of this survey was to clarify the characteristics of adolescents' resistance responses to offers of alcohol and tobacco by conducting a survey of Japanese senior high school students.Methods An anonymous self-administered questionnaire was distributed at five high schools in A prefecture (A total of 2,498 students, comprising 1,713 boys and 785 girls, participated, with a valid response rate of 96.1%.). The contents of the questionnaire included the following: 1) a list of 9 resistance responses, 2) the drinking and smoking behavior of subjects (for the past month); alcohol-resistance self-efficacy and tobacco-resistance self-efficacy, 3) drinking and smoking behavior of close friends; an estimation of peers' alcohol and tobacco use (descriptive norms) as adjustment variables. Factor analysis (likelihood method, promax rotation) was used to clarify the type of resistance responses. In addition, we used multiple logistic regression analysis with current drinking and smoking behavior as dependent variables, and gender, grade, school type, and type of resistance responses as independent variables, simultaneously. Model 1 was not adjusted, model 2 was adjusted for alcohol-resistance self-efficacy and tobacco-resistance self-efficacy, and model 3 was adjusted for the drinking and smoking behavior of close friends, and the estimation of peers' alcohol and tobacco use.Results Of the 9 types of resistance responses, the most common responses among participants were "simply say I don't want" "no," and "provide explanation for refusal." The responses for both drinking and smoking tended to be similar. From factor analysis, 3 factors were identified to explain optimal resistance reponses, namely, "non-responsive/forthright resistance responses," "ambiguous/reversal resistance responses," and "excuse/concise resistance responses." Regarding the relationship with current drinking behavior, only "ambiguous/reversal refusal" showed a significant odds ratio in all models (odds ratio (95%CI); 1.77(1.36-2.30), 1.66(1.27-2.17), 1.59(1.19-2.13)). Regarding the relationship with current smoking behavior, only "excuse/concise refusal" showed a significant odds ratio in all models (odds ratio (95%CI); 0.38(0.22-0.66), 0.47(0.25-0.87), 0.44(0.23-0.82)).Conclusion Senior high school students' resistance responses to alcohol and tobacco offers tended to be similar. However, as a result of analyzing the relationship between current drinking or smoking behavior and resistence responses, only current smoking behavior showed a negative correlation with resistance responses.


Validity of a discharge diagnosis of heart failure: implications of misdiagnosing.
Heart failure (HF) costs are largely due to hospitalization. The validity of a death/discharge diagnosis of HF (DDHF) is largely unknown. The authors assessed the validity of DDHF and the impact of misdiagnosing. The case notes of patients consecutively admitted to a medical department between January and June 2001 were reviewed. Cases with DDHF or cardiovascular diseases, potential precursors of HF (PPHF), were included. The diagnosis of HF (European Society of Cardiology guidelines) was classified as definite, possible, or miscoded. Of the 1038 patients admitted, 234 were enrolled: 157 with DDHF and 77 with PPHF. One hundred eighty patients had a definite diagnosis of HF. Of the 157 diagnoses coded as definite HF, 130 were correct, 21 had possible HF, and 6 were miscoded. Of the 77 patients classified as having PPHF, 38 had definite HF. The accuracy of the DDHF diagnosis was 72.2%: 21.1% were underdiagnosed and 8.3% overdiagnosed. DDHF failed to capture many HF admissions and therefore alone underestimates the prevalence, burden, and costs of the syndrome.


Evolving eyes.
Despite the incredible diversity among extant eyes, laws of physics constrain how light can be collected resulting in only eight known optical systems in animal eyes. Surprisingly, all animal eyes share a common molecular strategy using opsin for catching photons, but there are a diverse collection of mechanisms with proteins unrelated to each other used to focus light for vision. However, opsin is expressed in either one of two types of photoreceptor that differ fundamentally in their structure and tissue of origin. Taken together, this collection of observations strongly suggests that eyes have had multiple origins with remarkable convergence due to physics and molecular conservation of the opsin protein. Yet recent work has shown that a family of conserved genes are involved in eye formation despite substantial differences in their structure and origin, leading to a controversy over whether eyes evolved once or repeatedly. A likely resolution of this discussion is that particular genes and genetic programs have become associated with specific features needed for eyes and such suites of genes have been recruited as new eyes evolve. Since specific genes and their products are used repeatedly, it is somewhat difficult to conceptualize their causal relationships relative to evolutionary processes. However, detailed comparison of developmental programs may offer clues about multiple origins.


Tailoring mechanical properties of aerogels for aerospace applications.
Silica aerogels are highly porous solid materials consisting of three-dimensional networks of silica particles and are typically obtained by removing the liquid in silica gels under supercritical conditions. Several unique attributes such as extremely low thermal conductivity and low density make silica aerogels excellent candidates in the quest for thermal insulation materials used in space missions. However, native silica aerogels are fragile at relatively low stresses. More durable aerogels with higher strength and stiffness are obtained by proper selection of silane precursors and by reinforcement with polymers. This paper first presents a brief review of the literature on methods of silica aerogel reinforcement and then discusses our recent activities in improving not only the strength but also the elastic response of polymer-reinforced silica aerogels. Several alkyl-linked bis-silanes were used in promoting flexibility of the silica networks in conjunction with polymer reinforcement by epoxy.


Peak blood-ethanol concentration and the time of its occurrence after rapid drinking on an empty stomach.
Healthy men, 20 to 60 years old, drank a moderate dose of ethanol in the morning after an overnight fast. They consumed either neat whisky in amounts corresponding to 0.34, 0.51, 0.68, 0.85, or 1.02 g of ethanol per kilogram of body weight or 0.80 g/kg ethanol solvent diluted with orange juice. The peak blood-ethanol concentration (BEC) increased with the dose administered, but the time required to reach the peak was not markedly influenced over the range of doses studied. At a dose of 0.68 g/kg, the peak BEC ranged from 52 to 136 mg/dL (N = 83), and slow absorption (a late-occurring peak) produced a lower peak BEC. The peak BEC was reached between 0 and 45 min for 77% of the subjects (N = 152) and between 0 and 75 min for 97% of them. The time of peaking in venous blood occurred, on average, 10 min later than in capillary (fingertip) blood although the peak BEC was not appreciably different; the mean venous BEC was 97.0 mg/dL (range, 76 to 112 mg/dL), and the mean capillary BEC was 99.6 mg/dL (range, 75 to 123 mg/dL). When subjects drank 0.80 g/kg ethanol diluted with orange juice over 30 min, the average BEC increment between the end of drinking and the peak was 33 mg/dL (range, 0 to 58 mg/dL). The rate of absorption of ethanol was 1.78 mg/dL/min (range, 0.52 to 4.8 mg/dL/min), and the peak BEC occurred within 60 min after the end of drinking in 92% of the trials. The largest BEC increment (mean, 21 mg/dL; range, 0 to 44 mg/dL) was seen during the first 15 min after the drinking period.


Serum samples from patients with active psoriasis enhance lymphocyte-induced angiogenesis and modulate endothelial cell proliferation.
In former studies we have shown the increased angiogenic capability of peripheral blood mononuclear cells (MNCs) from patients with the active guttate type of psoriasis vulgaris. The present study tested the effects of serum factors from 67 patients with various forms of psoriasis vulgaris and from 32 healthy individuals on the angiogenic capability of normal human MNCs in an animal system. The angiogenesis-enhancing effect was most marked in the serum samples from patients with plaquelike and peripherally spreading lesions lasting for one to two months, and tended to disappear in patients with long-lasting and/or stationary lesions. Serum samples from patients with psoriasis were also capable of modulating the proliferation of normal human endothelial cells in vitro, and this modulation was correlated with the duration of relapse. The effects of psoriatic sera on normal human MNC function and on endothelial cell growth may be of importance for vascular proliferation in psoriasis.


A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas.
A large number of monoclonal antibodies (MoAbs) against human tumor cells have been generated and it has been shown that these MoAbs are useful tools in the diagnosis and treatment of cancer patients, as well as in the basic investigation of the oncogenesis and characterization of cancer cells. The 22-1-1 MoAb was established by cell fusion between mouse myeloma cells and spleen cells derived from mice immunized with the human uterine cervical adenocarcinoma cell line, SiSo. The tissue distribution and biologic characteristics of the 22-1-1 antigen (Ag) were examined. The 22-1-1 Ag was distinct from the known tumor-associated antigens such as YH 206, GA 733, CA 125, carcinoembryonic antigen, and sialyl Le(x) molecules in an expression pattern in human tumor cell lines. An immunohistochemical study revealed that 22-1-1 Ag was expressed in 87.5% of uterine cervical adenocarcinomas, 66% of uterine endometrial adenocarcinomas, and 58.8% of ovarian carcinomas. Moreover, 22-1-1 Ag was detected in 87.7% of uterine cervical squamous cell carcinomas; however, it was not detected in 87.7% of uterine cervical or ovarian tissues, except in uterine endometrial glands, in which its expression was observed at low levels. The 22-1-1 Ag was secreted into cell culture supernatant fluids and was also detected in the vaginal discharges of uterine cervical carcinoma patients. The antigenic epitope of 22-1-1 Ag was shown to be a protein with a molecular weight of 78 kilodaltons using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.


Magnetic resonance imaging, pacemakers and implantable cardioverter-defibrillators: current situation and clinical perspective.
New developments and expanding indications have resulted in a significant increase in the number of patients with pacemakers and internal cardioverterdefibrillators (ICDs). Because of its unique capabilities, magnetic resonance imaging (MRI) has become one of the most important imaging modalities for evaluation of the central nervous system, tumours, musculoskeletal disorders and some cardiovascular diseases. As a consequence of these developments, an increasing number of patients with implanted devices meet the standard indications for MRI examination. Due to the presence of potential life-threatening risks and interactions, however, pacemakers and ICDs are currently not approved by the Food and Drug Administration (FDA) for use in an MRI scanner. Despite these limitations and restrictions, a limited but still growing number of studies reporting on the effects and safety issues of MRI and implanted devices have been published. Because physicians will be increasingly confronted with the issue of MRI in patients with implanted devices, this overview is given. The effects of MRI on an implanted pacemaker and/or ICDs and vice versa are described and, based on the current literature, a strategy for safe performance of MRI in these patients is proposed. (Neth Heart J 2010;18:31-7.).


False iliac aneurysms.
Of 2,389 aortoiliac, femoral bypasses performed from 1971 to 1983 at our institution, 182 pseudoaneurysms were observed; of these, only 17 were false anastomotic iliac aneurysms (9.4%) among 13 patients. The mode of presentation varied from pain or swelling in the lower quadrant of the abdomen, or a combination of both, to acute rupture of the false aneurysm in the abdomen. The surgical management of patients with false aneurysms was the same for those with true aneurysms. Three patients died because of complications during the early postoperative period. Histologic studies secured during operation provided evidence supporting our belief that the main causes of false iliac aneurysms are primarily a weakened host arterial wall and secondarily the inadequacy of suture material used.


The role of macrophage polarization on bipolar disorder: Identifying new therapeutic targets.
Bipolar disorder is a chronic, severe and disabling disease; however, its pathophysiology remains poorly understood. Recent evidence has suggested that inflammation and immune dysregulation play a significant role in the pathophysiology of bipolar disorder. This review is aimed to highlight the importance of systemic inflammation in modulating the inflammatory response of microglia and hence its potential involvement with bipolar disorder. We also discuss novel therapeutic strategies that emerge from this new research. This article presents a theoretical synthesis of the effects of systemic inflammation on the immune response of the central nervous system in bipolar disorder. The complex relationship between stress, pro-inflammatory cytokines and microglial dysfunction is summarized, emphasizing the role of the kynurenine pathway in this process and, consequently, their effects on neuronal plasticity. Bipolar patients demonstrate increased serum levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α) and lower hypothalamic-pituitary-adrenal axis sensitivity. This imbalance in the immune system promotes a change in blood-brain barrier permeability, leading to an inflammatory signal spread in the central nervous system from the periphery, through macrophages activation (M1 polarization). Chronic microglial activation can result in neuronal apoptosis, neurogenesis inhibition, hippocampal volume reduction, lower neurotransmitters synthesis and cytotoxicity, by increasing glutamate production and kynurenine metabolism. This review provides an overview of the mechanisms involved in the immune system imbalance and its potential involvement in the pathophysiology of bipolar disorder. Consequently, new strategies that normalize the immune-inflammatory pathways may provide a valuable therapeutic target for the treatment of these disorders.


Applications of cell sorting in biotechnology.
Due to its unique capability to analyze a large number of single cells for several parameters simultaneously, flow cytometry has changed our understanding of the behavior of cells in culture and of the population dynamics even of clonal populations. The potential of this method for biotechnological research, which is based on populations of living cells, was soon appreciated. Sorting applications, however, are still less frequent than one would expect with regard to their potential. This review highlights important contributions where flow cytometric cell sorting was used for physiological research, protein engineering, cell engineering, specifically emphasizing selection of overproducing cell lines. Finally conclusions are drawn concerning the impact of cell sorting on inverse metabolic engineering and systems biology.


Ankylosing spondylitis associated with pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a frequent complication of connective tissue diseases, such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. However, the occurrence of PAH in a patient with ankylosing spondylitis (AS) has not been previously reported with a detailed clinical description in the English literature. We herein report the first case of AS associated PAH in a 27-year-old Taiwanese man with a chief complaint of intermittent palpitations lasting for two years. To the best of our knowledge, this is the first reported case of AS associated with PAH with a detailed clinical description and findings of right heart catheterization published in the English literature.


Use of noninvasive methods in evaluation of left ventricular performance in coronary artery disease. II: Change in systolic time intervals after coronary artery bypass in patients with stable angina.
Serial recording of systolic time intervals (STI) was used to assess changes in left ventricular (LV) function in 92 patients with stable angina undergoing coronary angiography and LV cineangiography. On the basis of angiography, patients were placed in the following study groups: mild or absent coronary artery disease group -21 patients with less than 70 per cent occlusion of all coronary arteries, considered to have non-significant coronary artery disease and not needing bypass surgery; surgical bypass group-52 patients with evidence of significant (less than 70%) obstruction of at least one coronary artery who underwent myocardial revascularization; and medical group-19 patients with evidence of significant coronary artery disease not undergoing bypass surgery. Measured STI, corrected for heart rate and sex, were expressed as indices. No significant differences were noted in the mean STI from the time of initial evaluation to second evaluation 3 to 6 months later in either the mold or absent coronary artery disease patients or the medical group. In the surgical bypass group, however, serial studies at initial angiographic evaulation and 3 to 6 months after bypass surgery showed a shortened pre-ejection period (PEP) from 150 +/- 20 to 142 +/- 16 mn (P less than 0-001), prolonged left ventricular ejection time (LVET) from 396 +/- 21 to 409 +/- 14 ms (P less than 0-02), and decreased PEP/LVET from 0-45 +/- 0-11 to 0-04 +/- 0-07 (P less than 0-02). Paired data analysis of the three groups also showed a significant change only within the surgical bypass group from initial to find study, with a shortened PEP (P less than 0-002), prolonged LVET (P less than 0-001), and decreased PEP/LVET (P less than 0-001). These data suggest improvement in LV function in patients with significant coronary artery disease within a few months of myocardial revascularization, without demonstrable change in STI in those patients with coronary artery disease not subjected to revascularization.


Young age at first intercourse and risk-taking behaviours--a study of nearly 65 000 women in four Nordic countries.
Risk-taking behaviours such as early initiation of smoking, alcohol drinking and sexual activity often cluster within individuals and could be characteristics of adolescents who in general are risk takers. In the present study, using a large population-based sample of 64 659 women aged 18-45 years in four Nordic countries, we investigate whether young age at first sexual intercourse is associated with subsequent risk-taking behaviours. We examined the association between young age at first sexual intercourse (age ≤14 years) and subsequent risk-taking behaviours by using multivariate logistic regression by which odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were estimated. The OR of reporting more than 10 lifetime sexual partners was almost four times higher among women who reported a young age at first intercourse (OR = 3.79; 95% CI: 3.60-4.00) in comparison with women >14 years at first intercourse. Furthermore, women who were young at first intercourse were more likely to report two or more recent partners (OR = 1.67; 95% CI: 1.54-1.82) and to have a history of STIs (OR = 2.03; 95% CI: 1.93-2.13). In addition, young age at first intercourse was associated with current smoking (OR = 2.31; 95% CI: 2.20-2.43) and binge drinking (OR = 1.36; 95% CI: 1.28-1.44). All ORs were adjusted for age, years of education and country of residence. Young age at first intercourse is associated with subsequent risk-taking behaviours. Our study emphasizes the importance of targeting prevention efforts towards the complexity of risk-taking behaviours.


Continued improvement of cardiovascular mortality in Hungary--impact of increased cardio-metabolic prescriptions.
During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior. Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered. We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI). The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome. These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.


[The notochord proteins of true sturgeons carrying the At1 epitope].
Previously we reported the production of monoclonal antibodies against chordin, an acidic glycoprotein from true sturgeon notochord, carrying glycans terminating with 3-sulfoglucuronic acid. In addition, monoclonal antibodies At1, not reacting with chordin, were produced. Here we describe At1 epitope expression in sturgeon tissues and target proteins for At1 antibodies, and test interaction of these proteins with chordin and other molecules carrying glycan with 3-sulfoglucuronic acid. The expression of the antigens carrying At1 epitope during sturgeon development has also been studied.


[Repair of ventricular septal defects with pericardial xenografts in infants].
The article deals with the experience in the clinical use of pericardial xenografts in surgical correction of large ventricular septal defects in babies. Primary closure of the VSD under conditions of hypothermic perfusion at a low volume rate was carried out in 202 children whose ages ranged from 6 weeks to 12 months and body weight from 3.5 to 10 kg. The aorta was not clamped. In 142 patients the defect was closed with xenogenous pericardium treated with 0.6% glutaraldehyde solution on HEPE buffer and 1% sodium dodecyl sulfate solution. A pericardial xenograft treated by Carpantje's method was used before 1985 (59 patients). The hospital mortality rate was 6.4% (13 patients). The mortality rate was 5.1% among patients over 6 months of age and 11% among those under 6 months of age, which is explained by their initially extremely grave condition. The long-term results were studied in 133 patients by bidimensional and Doppler echocardiography. The pressure in the right ventricle was found to be normal (26 +/- 4.3 mm Hg) in all patients. The right- and left-ventricular end-diastolic volumes were normal, just like the ejection fractions (55.4 +/- 6.6 and 57.3 +/- 6.8%, respectively). A small escape of blood at the level of the graft was found in only 5% of patients. Mild incompetence of the tricuspid valve without clinical manifestations was revealed in 18% of patients. In none of the cases, signs of calcinosis or aneurysm of the graft were found, fatal outcomes in the long-term postoperative periods were not encountered.(ABSTRACT TRUNCATED AT 250 WORDS)


Association Between Substance Use Behaviors, Developmental Assets and Mental Health: A Glance at Latin American Young College Students.
Positive Youth Development (PYD) is an approach that promotes resilience and focuses on youth strengths rather than their weaknesses as done by the traditional deficit-based perspective. Research in Europe and North America show that developmental assets are associated with school success, psychological well-being, and lower health risks among youth and young adults. However, not much research has been done on these associations in Latin American contexts. The purpose of this research study is to assess the association between substance use behaviors, such as drunkenness and the use of illicit drugs, and mental health, together with the mediating role of developmental assets representing youth strengths (e.g., social competence) and contextual resources (e.g., social support at home or school). Cross-national data was collected from Colombian (n = 210; 70.4% females) and Peruvian (n = 349; 66.5% females) 1st year university students. Results shed light on the protective role of developmental assets regarding substance use behaviors and mental well-being. Specifically, the results showed direct negative associations between developmental assets and substance use behaviors and positive associations of developmental assets with mental health indicators. Internal assets appear to be a stronger predictor of social, emotional, and psychological well-being compared to external assets. We did not find any statistical significance in the association of substance use behavior and mental health. We discuss implications regarding research, policy, and practice.


[Transperitoneal and transvaginal hysterectomy using devices of the dosed high-frequency electrical current].
The experience of application of apparatuses of the dosed high-frequency electric influence EK300M-1 "Patonmed" and energetic platform "Forcetriad", manufactured by Valleylab firm, during hysterectomy performance, using various surgical accesses, was presented. The variants of the applied regimens, depending on the vessels diameter and coexistant diseases, were proposed.


Antenatal administration of hepatitis B immunoglobulin and hepatitis B vaccine to prevent mother to child transmission in hepatitis B virus surface antigen positive pregnant women: A systematic review and meta-analysis.
This study aims at evaluating the benefits and harms of hepatitis B immune globulin (HBIG) and hepatitis B vaccine (HBVac) in preventing mother to child transmission in HBV surface antigen (HBsAg) positive pregnant women during antenatal period. Seven electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Database, Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), and 3 clinical trial registry platforms were searched from inception date to December 2017. Only randomized controlled trials (RCTs) were included in this study. The Cochrane risk of bias tool was applied to assessing the risk of bias. The outcomes were analyzed by Review Manager 5.3 software. Sixteen RCTs involving 2440 HBsAg positive pregnant women were included in the meta-analysis. Compared with placebo group, HBIG and HBVac group had a significant decrease in the number of newborns who were HBsAg positive (relative risks [RR]: 0.2, 95% confidence interval [CI] [0.18, 0.40], P < .00001) and HBV-DNA positive (RR: 0.25, 95% CI [0.09, 0.71], P = .010), and had a significant increase in the number of anti-HBs positive newborns (RR: 3.95, 95% CI [3.11, 5.00], P < .00001). After 1-year follow up, the number of HBsAg positive newborns continued to decline (RR: 0.09, 95% CI [0.04, 0.20], P < .00001) and the number of anti-HBs positive newborns continued to increase in HBIG and HBVac group (RR: 1.30, 95% CI [1.22, 1.38], P < .00001). Compared with HBIG group, HBIG and HBVac group had no significant difference in the number of HBsAg positive newborns (RR: 1.68, 95% CI [0.66, 4.30], P = .28), and had a significant decrease in the number of HBsAg positive newborns (RR: 0.31, 95% CI [0.12, 0.84], P = .02). Additionally, only 1 study reported 2 swelling cases, 4 studies were reported no adverse events, and 11 studies were not report adverse reaction. HBIG and HBVac could be an effective alternative for HBsAg positive pregnant women to prevent mother to child transmission. However, due to the limitations of the study, the long-term efficacy and safety of HBIG and HBVac still need long-term and high-quality research to confirm.


Complications following liver resection for colorectal metastases do not impact on longterm outcome.
It has been suggested that adverse postoperative outcomes may have a negative impact on longterm survival in patients with colorectal liver metastases. This study was conducted to evaluate the prognostic impact of postoperative complications in patients submitted to a potentially curative resection of colorectal liver metastases. A retrospective analysis of outcomes in 199 patients submitted to hepatic resection with curative intent for metastatic colorectal cancer during 1999-2008 was conducted. The overall complication rate was 38% (n = 75). Of all complications, 79% were minor (Grades I or II). There were five deaths (3%). The median length of follow-up was 39 months. Rates of 5-year overall and disease-free survival were 44% and 27%, respectively. Univariate analysis demonstrated that an elevated preoperative level of carcinoembryonic antigen (CEA), intraoperative blood loss of > 300 ml, multiple metastases, large (≥ 35 mm) metastases and resection margins of < 1 mm were associated with poor overall and disease-free survival. In addition, male sex and synchronous metastases were associated with poor disease-free survival. Postoperative complications did not have an impact on either survival measure. The multivariate model did not include complications as a predictive factor. Postoperative complications were not found to influence overall or disease-free survival in the present series. The number and size of liver metastases were confirmed as significant prognostic factors.


Safety and efficacy of epidural analgesia.
Epidural analgesia remains a widely used analgesic technique. This article aims to assess the safety of epidural analgesia by balancing efficacy and complications, of epidural analgesia for acute, labor and chronic pain. Main indications for epidural analgesia include major open abdominal surgery, thoracotomy and labor analgesia. Past and current literature show that epidural analgesia leads to statistically significant, but possibly clinically less meaningful, reductions in pain scores compared with intravenous analgesia. The debate continues whether epidural analgesia leads to decreased complications and improved outcome. Noninferiority of alternative regional analgesic approaches, that is continuous-wound-infiltration, peripheral nerve blocks or surgical site infiltration, appears to be present and is promising for the future. Serious adverse events after epidural analgesia seem to occur more often than was previously thought and clinicians must realize that incidence rates differ in specific perioperative patient populations. Epidural analgesia for obstetric analgesic purposes is considered to be well tolerated in young, healthy women, since efficacy has been proven and complications leading to permanent neurological damage seldomly occur. Safety of epidural analgesia for perioperative and chronic pain treatment is more difficult to balance; careful selection of appropriate patients cannot be over-emphasized.


Host ranges of Listeria-specific bacteriophages from the turkey processing plant environment in the United States.
Even though at least 400 Listeria phages have been isolated from various sources, limited information is available on phages from the food processing plant environment. Phages in the processing plant environment may play critical roles in determining the Listeria population that becomes established in the plant. In this study, we pursued the isolation of Listeria-specific phages from environmental samples from four turkey processing plants in the United States. These environmental samples were also utilized to isolate Listeria spp. Twelve phages were isolated and classified into three groups in terms of their host range. Of these, nine (group 1) showed a wide host range, including multiple serotypes of Listeria monocytogenes, as well as other Listeria spp. (L. innocua, L. welshimeri, L. seeligeri, and L. ivanovii). The remaining phages mostly infected L. monocytogenes serotype 4b as well as L. innocua, L. ivanovii, and/or L. welshimeri. All but one of the strains of the serotype 4b complex (4b, 4d, 4e) from the processing plant environment could be readily infected by the wide-host-range phages isolated from the environment of the processing plants. However, many strains of other serotypes (1/2a [or 3a] and 1/2b [or 3b]), which represented the majority of L. monocytogenes strains isolated from the environmental samples, were resistant to infection by these phages. Experiments with two phage-resistant strains showed reduced phage adsorption onto the host cells. These findings suggest that phage resistance may be an important component of the ecology of L. monocytogenes in the turkey processing plants.


From Traditional to Targeted Immunotherapy in Myasthenia Gravis: Prospects for Research.
Treatment of Myasthenia Gravis (MG) is still based on non-specific immunosuppression. Long-term high dose corticosteroids is still a major cause of side effects, in young as well as in elderly patients in whom comorbidities further increase the burden of chronic immunosuppression. Moreover, awareness of the limits of traditional therapies has led to the concept of "refractory MG." The therapeutic approach to MG is therefore progressively evolving from the classic combination of corticosteroids and immunosuppressive drugs to new biological compounds targeting different immunopathological steps. Killing of B cells with Rituximab has been proposed and tested with positive results, particularly in patients with MuSK-associated MG. Therapeutic monoclonals against B cells at different stages of their maturation, or against molecules involved in B cell activation and function, represent a new area for further investigation. A differently targeted approach involved Eculizumab, a monoclonal antibody preventing the formation of C59b-induced MAC causing destruction of the neuromuscular junction. Data from clinical trials led to the approval of Eculizumab in the United States and Europe for MG. Since Eculizumab is a complement-targeted therapy, its use is limited to anti-acetylcholine receptor-associated MG, since anti-MuSK antibodies belong to IgG4 subclass and do not fix complement. Several anti-complement compounds are under investigation. An even more recent approach is the interference with the neonatal Fc receptor leading to a rapid reduction of circulating IgGs and hence of specific autoantibodies, an approach suitable for both anti-acetylcholine- and MuSK-associated MG. The investigation of compounds that selectively target the immune system will stimulate the search for specific biomarkers of disease activity and response to treatment, setting the basis for personalized medicine in MG.


An eQTL-based method identifies CTTN and ZMAT3 as pemetrexed susceptibility markers.
Pemetrexed, approved for the treatment of non-small cell lung cancer and malignant mesothelioma, has adverse effects including neutropenia, leucopenia, thrombocytopenia, anemia, fatigue and nausea. The results we report here represent the first genome-wide study aimed at identifying genetic predictors of pemetrexed response. We utilized expression quantitative trait loci (eQTLs) mapping combined with drug-induced cytotoxicity data to gain mechanistic insights into the observed genetic associations with pemetrexed susceptibility. We found that CTTN and ZMAT3 expression signature explained >30% of the pemetrexed susceptibility phenotype variation for pemetrexed in the discovery population. Replication using PCR and a semi-high-throughput, scalable assay system confirmed the initial discovery results in an independent set of samples derived from the same ancestry. Furthermore, functional validation in both germline and tumor cells demonstrates a decrease in cell survival following knockdown of CTTN or ZMAT3. In addition to our particular findings on genetic and gene expression predictors of susceptibility phenotype for pemetrexed, the work presented here will be valuable to the robust discovery and validation of genetic determinants and gene expression signatures of various chemotherapeutic susceptibilities.


2D Arrays of Organic Qubit Candidates Embedded into a Pillared-Paddlewheel Metal-Organic Framework.
The creation of ordered arrays of qubits that can be interfaced from the macroscopic world is an essential challenge for the development of quantum information science (QIS) currently being explored by chemists and physicists. Recently, porous metal-organic frameworks (MOFs) have arisen as a promising solution to this challenge as they allow for atomic-level spatial control of the molecular subunits that comprise their structures. To date, no organic qubit candidates have been installed in MOFs despite their structural variability and promise for creating systems with adjustable properties. With this in mind, we report the development of a pillared-paddlewheel-type MOF structure that contains 4,7-bis(2-(4-pyridyl)-ethynyl) isoindoline N-oxide and 1,4-bis(2-(4-pyridyl)-ethynyl)-benzene pillars that connect 2D sheets of 9,10-dicarboxytriptycene struts and Zn2(CO2)4 secondary binding units. The design allows for the formation of ordered arrays of reorienting isoindoline nitroxide spin centers with variable concentrations through the use of mixed crystals containing the secondary 1,4-phenylene pillar. While solvent removal causes decomposition of the MOF, magnetometry measurements of the MOF containing only N-oxide pillars demonstrated magnetic interactions with changes in magnetic moment as a function of temperature between 150 and 5 K. Variable-temperature electron paramagnetic resonance (EPR) experiments show that the nitroxides couple to one another at distances as long as 2 nm, but act independently at distances of 10 nm or more. We also use a specially designed resonance microwave cavity to measure the face-dependent EPR spectra of the crystal, demonstrating that it has anisotropic interactions with impingent electromagnetic radiation.


Reconstruction of three-dimensional anisotropic structure from small-angle scattering experiments.
When subjected to flow, the structures of many soft-matter systems become anisotropic due to the symmetry breaking of the spatial arrangements of constituent particles at the microscopic level. At present, it is common practice to use various small-angle scattering techniques to explore flow-induced microstructural distortion. However, there has not been a thorough discussion in the literature on how a three-dimensional anisotropic structure can be faithfully reconstructed from two-dimensional small-angle scattering spectra. In this work, we address this issue rigorously from a mathematical perspective by using real spherical harmonic expansion analysis. We first show that, except for cases in which mechanical perturbation is sufficiently small, the existing small-angle scattering techniques generally do not provide complete information on structural distortion. This limitation is caused by the linear dependence of certain real spherical harmonic basis vectors on the flow-vorticity and flow-velocity gradient planes in the Couette shear cell. To circumvent the constraint imposed by this geometry, an alternative approach is proposed in which a parallel sliding plate shear cell is used with a central rotary axis along the flow direction. From the calculation of rotation of the reference frame, we demonstrate the feasibility of this experimental implementation for a fully resolved three-dimensional anisotropic structure via a case study of sheared polymers.


Pre-dialysis care trajectory and post-dialysis survival and transplantation access in patients with end-stage kidney disease.
The pre-dialysis care trajectory impact on post-dialysis outcomes is poorly known. This study assessed survival, access to kidney transplant waiting list and to transplantation after dialysis initiation by taking into account the patients' pre-dialysis care consumption (inpatient and outpatient) and the conditions of dialysis start: initiation context (emergency or planned) and vascular access type (catheter or fistula). Adults who started dialysis in France in 2015 were included. Clinical data came from the French REIN registry and data on the care trajectory from the French National Health Data system (SNDS). The Cox model was used to assess survival and access to kidney transplantation. We included 8856 patients with a mean age of 68 years. Survival was shorter in patients with emergency or planned dialysis initiation with a catheter compared to patients with planned dialysis with a fistula. The risk of death was lower in patients who were seen by a nephrologist more than once in the 6 months before dialysis than in those who were seen only once. The rate of kidney transplant at 1 year post-dialysis was lower for patients with emergency or planned dialysis initiation with a catheter (respectively, HR = 0.5 [0.4; 0.8] and HR = 0.7 [0.5; 0.9]) compared to patients with planned dialysis start with a fistula. Patients who were seen by a nephrologist more than three times between 0 and 6 months before dialysis start were more likely to access the waiting list 1 and 3 years after dialysis start (respectively, HR = 1.3 [1.1; 1.5] and HR = 1.2 [1.1; 1.4]). Nephrological follow-up in the year before dialysis initiation is associated with better survival and higher probability of access to kidney transplantation. These results emphasize the importance of early patient referral to nephrologists by general practitioners.


Sputter-depth profiling for thin-film analysis.
Following a brief historical background, the concepts and the present state of sputter-depth profiling for thin-film analysis are outlined. There are two main branches: either the removed matter (as in mass- or optical-spectroscopy-based secondary-ion mass spectrometry or glow-discharge optical emission spectroscopy), or the remaining surface (as in Auger electron spectroscopy and X-ray photoelectron spectroscopy) is characterized. These complementary methods show the same result if there is no preferential sputtering of a component. The common root of both is the fundamental ion-solid interaction. Understanding of how the latter influences the depth resolution has led to important improvements in experimental profiling conditions such as sample rotation and the use of low-energy ions at glancing incidence. Modern surface-analysis instruments can provide high-resolution depth profiles on the nanometre scale. Mathematical models of different sophistication were developed to allow deconvolution of the measured profile or quantification by reconstruction of the in-depth distribution of composition. For the latter purpose, the usefulness of the so-called mixing-roughness-information (MRI) depth model is outlined on several thin-film structures (e.g. AlAs/GaAs and Si/Ge), including its extension to quantification of sputter-depth profiles in layer structures with preferential sputtering of one component (Ta/Si). Using the MRI model, diffusion coefficients at interfaces as low as 10(-22) m(2) s(-1) can be determined. Fundamental limitations of sputter-depth profiling are mainly traced back to the stochastic nature of primary-particle energy transfer to the sputtered particle, promoting atomic mixing and the development of surface roughness. Owing to more sophisticated experimental methods, such as low-energy cluster ion bombardment, glancing ion incidence or 'backside' sputtering, these ultimate limitations can be reduced to the atomic monolayer scale.


A Window of Opportunity: Targeting Cancer Endothelium to Enhance Immunotherapy.
Vascular abnormalities in tumors have a major impact on the immune microenvironment in tumors. The consequences of abnormal vasculature include increased hypoxia, acidosis, high intra-tumoral fluid pressure, and angiogenesis. This introduces an immunosuppressive microenvironment that alters immune cell maturation, activation, and trafficking, which supports tumor immune evasion and dissemination of tumor cells. Increasing data suggests that cancer endothelium is a major barrier for traveling leukocytes, ranging from a partial blockade resulting in a selective endothelial barrier, to a complete immune infiltration blockade associated with immune exclusion and immune desert cancer phenotypes. Failed immune cell trafficking as well as immunosuppression within the tumor microenvironment limits the efficacy of immunotherapeutic approaches. As such, targeting proteins with key roles in angiogenesis may potentially reduce immunosuppression and might restore infiltration of anti-tumor immune cells, creating a therapeutic window for successful immunotherapy. In this review, we provide a comprehensive overview of established as well as more controversial endothelial pathways that govern selective immune cell trafficking across cancer endothelium. Additionally, we discuss recent insights and strategies that target tumor vasculature in order to increase infiltration of cytotoxic immune cells during the therapeutic window of vascular normalization hereby improving the efficacy of immunotherapy.


Lactic acid bacteria used in inoculants for silage as probiotics for ruminants.
Many studies have shown the beneficial effects on ruminant performance of feeding them with silages inoculated with lactic acid bacteria (LAB). These benefits might derive from probiotic effects. The purpose of the current study was to determine whether LAB included in inoculants for silage can survive in rumen fluid (RF), as the first step in studying their probiotic effects. Experiments were conducted in the United States and Israel with clarified (CRF) and strained RF (SRF) that were inoculated at 10(6)-10(8) microorganisms/mL with and without glucose at 5 g/L. RF with no inoculants served as control. Ten commercial inoculants were used. The RF was incubated at 39 degrees C and sampled in duplicates at 6, 12, 24, 48, 72, and 96 h for pH and LAB counts. The results indicate that with glucose the pH of the RF decreased during the incubation period. In the SRF, the pH of the inoculated samples was higher than that of the controls in most cases. This might be a clue to the mechanism by which LAB elicit the enhancement in animal performance. LAB counts revealed that the inoculants survived in the RF during the incubation period. The addition of glucose resulted in higher LAB counts.


The association between motor capacity and mobility performance: frailty as a moderator.
In older adults, the linkage between laboratory-assessed 'motor capacity' and 'mobility performance' during daily routine is controversial. Understanding factors moderating this relationship could help developing more valid assessment as well as intervention approaches. We investigated whether the association between capacity and performance becomes evident with transition into frailty, that is, whether frailty status moderates their association. We conducted a cross-sectional analysis of the observational (blinded for review) study in a community-dwelling cohort in (blinded for review). Participants were N = 112 older adults aged 65 years or older who were categorized as non-frail (n = 40), pre-frail (n = 53) or frail (n = 19) based on the Fried frailty index.Motor capacity was quantified as normal (NWS) and fast walking speed (FWS). Mobility performance was quantified as 1) cumulated physical activity (PA) time and 2) everyday walking performance (average steps per walking bout; maximal number of steps in one walking bout), measured by a motion sensor over a 48 h period. Hierarchical linear regression analyses were performed to evaluate moderation effects. Unlike in non-frail persons, the relationship between motor capacity and mobility performance was evident in pre-frail and frail persons, confirming our hypothesis. A moderating effect of frailty status was found for 1) the relationship between both NWS and FWS and maximal number of steps in one bout and 2) NWS and the average steps per bout. No moderation was found for the association between NWS and FWS with cumulated PA. In pre-frail and frail persons, motor capacity is associated with everyday walking performance, indicating that functional capacity seems to better represent mobility performance in this impaired population. The limited relationship found in non-frail persons suggests that other factors account for their mobility performance. Our findings may help to inform tailored assessment approaches and interventions taking into consideration a person's frailty status.


Non-AIDS defining cancers in the D:A:D Study--time trends and predictors of survival: a cohort study.
Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these. Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression. Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort. The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.


Lymphoblastic lymphoma in adult patients: clinicopathological features and response to intensive multiagent chemotherapy analogous to that used in acute lymphoblastic leukemia.
This paper analyzes the clinicopathological features of 31 consecutive adult patients with lymphoblastic lymphoma (LBL) and reports on our experience in treating them with two successive multidrug programs analogous to those used in acute lymphoblastic leukemia (ALL) in adults. Protocol 1 (18 patients) consisted of an intensive four-drug induction therapy (daunorubicin, cyclophosphamide, vincristine, prednisone), CNS prophylaxis (cranial irradiation and intrathecal methotrexate), and continuous maintenance with methotrexate and mercaptopurine for three years, with periodical reinductions with vincristine and prednisone. Protocol 2 (13 patients) included a similar induction regimen (doxorubicin instead of daunorubicin, dexamethasone instead of prednisone), followed by post-remission intensification with alternating courses of non-cross-resistant agents (amsacrine and high dose cytarabine; vincristine, cyclophosphamide and doxorubicin; etoposide and conventional dose cytarabine) given in a cyclical eight-month program. CNS prophylaxis consisted of intrathecal methotrexate and systemic high-dose cytarabine. The patient characteristics of the two therapy groups were comparable. The complete remission (CR) rate for both groups was 77%, with a median overall and relapse-free survival of 18 and 29 months, respectively. The three-year overall survival of complete remitters was 59%. No correlation was found between CR rate and age, mediastinal, or bone marrow involvement. Stage I disease had a significantly higher CR rate (100%) than did stages II-IV (64%). Leukemic evolution occurred in 32% of cases, within a median time of 11 months from diagnosis; meningeal disease developed in six cases (19%); in four of them leukemia was concomitant. No significant differences were found between the two successive treatments for CR rate, survival, CNS relapses or toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)


Gbetagamma-copurified lipid kinase impurity from Sf9 cells.
G-protein betagamma dimers are prime regulators transmitting extracellular signals to wide-ranging cellular effectors including phosphoinositide 3-kinase (PI3K) isoforms beta and gamma. Recombinant Gbetagamma purified from Sf9 cells via metal-affinity and anion exchange chromatography exhibited a wortmannin-insensitive phospholipid kinase activity that copurified from the insect cells. To exclude false-positive results of Gbetagamma-dependent lipid kinase activity, the elimination of insect phospholipid kinase from Gbetagamma protein samples is necessary to avoid interference with the intrinsic lipid kinase activity of PI3K isoforms in reconstitution experiments. Here we describe an improved procedure of Gbeta(1)gamma(2) purification from cell membranes that separates the contaminating phospholipid kinase.


Structural Modification and Bioavailability of Starch Components As Related to the Extent of Maillard Reaction: An Enzymatic Degradation and a Solid-State (13)C CPMAS NMR Study.
Starch and starch components, amylose and amylopectin, from potato, have been studied in order to understand the modifications, induced by different levels of the Maillard reaction occurring in the presence of amino acids (L-lysine in this study), in the macromolecular structure and digestibility. Structural characterization was performed by (13)C CPMAS NMR, and differences in the bioavailability of these polymers were studied by enzymatic degradation kinetics. Results obtained reveal that changes are induced by the Maillard reaction, whose occurrence has been verified and measured by the furosine (epsilon-N-2-furoylmethyl-L-lysine) evaluation, on the macromolecular structure of starchy materials and on their enzymatic susceptibility. Lysine seems to act as a disordering agent; a loss of crystallinity is evident for starch and amylopectin and, in particular, for amylose. Finally, within the same sample, as the lysine concentration increases, the polymer digestibility decreases, confirming that structural organization is not the only determinant of starch digestibility.


A probabilistic metric for the validation of computational models.
A new validation metric is proposed that combines the use of a threshold based on the uncertainty in the measurement data with a normalized relative error, and that is robust in the presence of large variations in the data. The outcome from the metric is the probability that a model's predictions are representative of the real world based on the specific conditions and confidence level pertaining to the experiment from which the measurements were acquired. Relative error metrics are traditionally designed for use with a series of data values, but orthogonal decomposition has been employed to reduce the dimensionality of data matrices to feature vectors so that the metric can be applied to fields of data. Three previously published case studies are employed to demonstrate the efficacy of this quantitative approach to the validation process in the discipline of structural analysis, for which historical data were available; however, the concept could be applied to a wide range of disciplines and sectors where modelling and simulation play a pivotal role.


Using microwaves to prepare gastropods for DNA barcoding.
Extracting DNA from gastropods presents particular difficulties due to the capacity of the living animal to retract into the shell, resulting in poor penetration of the ethanol into the tissues. Because the shell is essential to establish the link between sequences and traditional taxonomic identity, cracking the shell to facilitate fixation is not ideal. Several methods are currently in routine use to overcome this difficulty, including chemical relaxation, drilling the shell and boiling. Most of these methods are time-consuming, may be safety hazards and constitute a bottleneck in the preparation of large numbers of specimens in the field. We have experimented with a method traditionally used to clean shells that involves placing the living gastropods in a microwave (MW) oven; the electromagnetic radiation very quickly heats both the animal and the water trapped inside the shell, resulting in separation of the muscles that anchor the animal to the shell. Done properly, the body can be removed intact from the shell and the shell voucher is preserved undamaged. To test the method, the bodies of live-collected specimens from two gastropod species were separated from their shell by microwaving and by anesthetizing/drilling. After identical extraction and PCR procedures, the gels showed no difference in DNA quantity or quality, and the resulting sequences are identical within species. The method was then implemented on a large scale during expeditions, resulting in higher percentage of DNA extraction success. The MWs are also effective for quickly and easily removing other molluscs from their shells, that is, bivalves and scaphopods. Workflows implementing the MW technique show a three- to fivefold increase in productivity compared with other methods.


Management of children with aseptic meningitis in the emergency department.
To review the emergency department management of children with aseptic meningitis and compare the clinical features, laboratory findings, and short-term follow-up of those who were hospitalized or discharged to determine guidelines for discharge. Retrospective chart review study. Emergency department of an inner-city teaching, level III, children's hospital during an outbreak of aseptic meningitis from, March through December 1993. The medical records of children < or = 18 years of age diagnosed in the emergency department with aseptic meningitis after lumbar puncture were retrospectively reviewed and analyzed. Thirty-four parameters were recorded for each child including demographic (2), epidemiologic (5), clinical (2), laboratory (10), and short-term follow-up data (5). Of the 158 eligible patients, 99 (62.7%) were hospitalized, and 59 (37.3%) were discharged. Compared to the hospitalized group, children who were discharged were significantly older (5.7 years vs. 4.7 years, P < 0.05) and experienced a more benign course, with lower rates of headache (54.7 vs. 85.7%, P < 0.05), vomiting (38.2 vs. 69.7%, P < 0.05), and irritability (1.8 vs. 8.1%, P < 0.05). They also had significantly (P < 0.05) lower mean peripheral and cerebrospinal fluid leukocyte counts (13,233 vs. 11,498/mm3 and 293.91 vs. 105.29/mm3, respectively). Interestingly, 30 (50.8%) of children in the discharged group had over 50% polymorphonuclears in their cerebrospinal fluid (CSF) cell count. The hospitalization rate during the day was significantly (P < 0.05) lower than that for the evening and night shifts (51.5 vs. 66.7%, respectively). In the discharged group, symptoms of headache, fever, and vomiting resolved after an average of 3.05 days, 2.25 days, and 1.3 days, respectively. The average hospitalization time was 3.5 days. There were no significant complications in either group. More important, in neither group were there any misdiagnoses of bacterial meningitis as aseptic meningitis. During the study period, the ambulatory management of the 59 patients cost $51,625 less than the hospitalization of an equal number of children. It is feasible, clinically safe and less costly to treat a subgroup of children with aseptic meningitis in an ambulatory setting. Although absolute criteria for ambulatory follow-up could not be defined, age >1 year, a nontoxic clinical appearance, normal white blood cell count, mild cerebrospinal fluid pleocytosis (even with a high percentage of polymorphonuclear cells), negative CSF Gram stain, and a reliable family setting could serve as guidelines for decision-making regarding emergency department discharge. Further prospective research is needed to better specify these criteria.


Adjuvant intravesical bacillus calmette-guérin therapy and survival among elderly patients with non-muscle-invasive bladder cancer.
National guidelines recommend adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy for higher-risk non-muscle-invasive bladder cancer (NMIBC). Although a survival benefit has not been demonstrated, randomized trials have shown reduced recurrence and delayed progression after its use. We investigated predictors of BCG receipt and its association with survival for older patients with NMIBC. We identified individuals with NMIBC registered in the Surveillance, Epidemiology, and End Results-Medicare database from 1991 to 2003. We used logistic regression to compare those treated with BCG within 6 months of initial diagnosis with those not treated, adjusting for demographic and clinical factors. Cox proportional hazards modeling was used to analyze the association between BCG and overall survival (OS) and bladder cancer-specific survival (BCSS) for the entire cohort and within tumor grades. Of 23,932 patients with NMIBC identified, 22% received adjuvant intravesical BCG. Predictors of receipt were stages Tis and T1, higher grade, and urban residence. Age > 80 years, fewer than two comorbidities, and not being married were associated with decreased use. In the survival analysis, BCG use was associated with better OS (hazard ratio [HR], 0.87; 95% CI, 0.83 to 0.92) in the entire cohort and BCSS among higher-grade cancers (poorly differentiated: HR, 0.78; 95% CI, 0.72 to 0.85; undifferentiated: HR, 0.66; 95% CI, 0.56 to 0.77). Despite guidelines recommending its use, BCG is administered to less than one quarter of eligible patients. This large population-based study found improved OS and BCSS were associated with use of adjuvant intravesical BCG among older patients with NMIBC. Better-designed clinical trials focusing on higher-grade cancers are needed to confirm these findings.


Dietary energy restriction modulates the activity of AMP-activated protein kinase, Akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver.
Dietary energy restriction (DER) inhibits mammary carcinogenesis, yet mechanisms accounting for its protective activity have not been fully elucidated. In this study, we tested the hypothesis that DER exerts effects on intracellular energy sensing pathways, resulting in alterations of phosphorylated proteins that play a key role in the regulation of cancer. Experiments were conducted using the 1-methyl-1-nitrosourea-induced mammary cancer model in which rats were 0%, 20%, or 40% energy restricted during the postinitiation stage of carcinogenesis. Parallel experiments were done in non-carcinogen-treated rats in which effects of DER at 0%, 5%, 10%, 20%, or 40% in liver were investigated. In a DER dose-dependent manner, levels of Thr(172) phosphorylated AMP-activated protein kinase (AMPK) increased in mammary carcinomas with a concomitant increase in phosphorylated acetyl-CoA-carboxylase, a direct target of AMPK, the phosphorylation of which is regarded as an indicator of AMPK activity. Levels of phosphorylated mammalian target of rapamycin (mTOR) decreased with increasing DER, and down-regulation of mTOR activity was verified by a decrease in the phosphorylation state of two mTOR targets, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryote initiation factor 4E binding protein 1 (4E-BP1). Coincident with changes in mTOR phosphorylation, levels of activated protein kinase B (Akt) were also reduced. Similar patterns were observed in mammary glands and livers of non-carcinogen-treated rats. This work identifies components of intracellular energy sensing pathways, specifically mTOR, its principal upstream regulators, AMPK and Akt, and its downstream targets, p70S6K and 4E-BP1, as candidate molecules on which to center mechanistic studies of DER.


Genetic analysis of growth patterns of black and white dairy heifers.
Monthly BW to 600 d of age along with BW at first calving of 743 heifers were analyzed to estimate the genetic relationship between BW at first calving and other growth variables. The Von Bertalanffy function and a two-phase logistic function were used to fit growth patterns of individual heifers. The two-phase logistic function fitted the data more adequately than did the Von Bertalanffy function. Calves from first parity dams were born at a lower degree of maturity than calves from third parity dams. Calves with a high proportion of Holstein genes had a higher BW both at first calving and at maturity. Heritabilities of the variables of the Von Bertalanffy and the two-phase logistic function ranged from 0.02 to 0.31 and 0.15 to 0.26, respectively. Estimated mature BW had a highly negative correlation with rate of maturation (-0.56 to -0.82); BW at first calving had a high genetic correlation (0.74 to 0.90) with estimated mature BW and a negative correlation with maturation rate (-0.18 to -0.40). Results of this study indicated that BW at first calving can be used as an indirect trait when mature BW is included in the breeding goal.