A double-blind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery.
Ropivacaine is a long-acting local anesthetic agent with similar potency to that of bupivacaine when administered for epidural anesthesia. Ropivacaine, however, may be less cardiotoxic than bupivacaine. Epidural bupivacaine and ropivacaine have been shown to be equally effective in providing sensory block for lower extremity surgery, but they have not been compared for their ability to produce abdominal wall relaxation. Sixty-six American Society of Anesthesiologists I-III women, 18-70 years old undergoing elective gynecologic surgery were studied in a randomized, double-blind manner after giving informed consent in an institutionally approved protocol. Thirty-four patients received a single epidural injection of 20 ml 0.75% bupivacaine at the L2-L3-L4 interspace and 32 patients received 20 ml 0.75% ropivacaine in a similar manner. Sensory block was tested with pinprick; motor block with a modified Bromage scale, rectus abdominis muscle (RAM) test and surgeon satisfaction. Statistical analysis was performed using the SigmaStat for Windows computer software. Parametric data were analyzed with Student's t-test, while nonparametric data was analyzed using the Mann-Whitney rank sum test. Results are expressed as mean +/- SD. Times to maximal sensory block and peak sensory level achieved were similar in both groups. However, time to complete sensory regression was significantly longer with bupivacaine than ropivacaine (458 +/- 77 vs. 404 +/- 62 minutes, P < .03). Bupivacaine lower extremity motor block onset was significantly faster than ropivacaine (9 +/- 3 vs. 12 +/- 3 minutes, P < .0013). Time to maximum lower extremity motor block was significantly shorter with bupivacaine than ropivacaine (28 +/- 12 vs. 40 +/- 15 minutes, P < .0234). Duration of lower extremity motor block was significantly longer with bupivacaine than ropivacaine (371 +/- 97 vs. 310 +/- 65 minutes P < .069). There was no significant difference between the two groups for changes in RAM scores or the time to achieve those changes. Maximum motor block scores using the modified Bromage score and surgeon satisfaction with operating conditions also did not demonstrate a significant difference between the two groups. In one instance (with ropivacaine), anesthesia was judged clinically inadequate despite evidence of bilateral epidural anesthesia. Both 0.75% ropivacaine and 0.75% bupivacaine provide adequate surgical anesthesia for lower abdominal surgery when administered epidurally. However, lower extremity motor block with ropivacaine is significantly shorter and of slower onset and sensory block shorter at these concentrations.


Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA.
Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a better understanding of the link between epigenetics (DNA methylation) and AS/PH, we examined the relationship of eight measures of AS/PH with CpG sites and co-methylated regions using multi-ancestry participants from Trans-Omics for Precision Medicine (TOPMed) Multi-Ethnic Study of Atherosclerosis (MESA) with sample sizes ranging from 438 to 874. Epigenome-wide association analysis identified one genome-wide significant CpG (cg20711926-CYP1B1) associated with aortic augmentation index (AIx). Follow-up analyses, including gene set enrichment analysis, expression quantitative trait methylation analysis, and functional enrichment analysis on differentially methylated positions and regions, further prioritized three CpGs and their annotated genes (cg23800023-ETS1, cg08426368-TGFB3, and cg17350632-HLA-DPB1) for AIx. Among these, ETS1 and TGFB3 have been previously prioritized as candidate genes. Furthermore, both ETS1 and HLA-DPB1 have significant tissue correlations between Whole Blood and Aorta in GTEx, which suggests ETS1 and HLA-DPB1 could be potential biomarkers in understanding pathophysiology of AS/PH. Overall, our findings support the possible role of epigenetic regulation via DNA methylation of specific genes associated with AIx as well as identifying potential targets for regulation of AS/PH.


Six domains of research ethics. A heuristic framework for the responsible conduct of research.
The purpose of this paper is to provide a simple yet comprehensive organizing scheme for the responsible conduct of research (RCR). The heuristic offered here should prove helpful in research ethics education, where the many and heterogeneous elements of RCR can be bewildering, as well as research into research integrity and efforts to form RCR policy and regulations. The six domains are scientific integrity, collegiality, protection of human subjects, animal welfare, institutional integrity, and social responsibility.


Maturation of the intracellular parasite and antigenicity.
The protein antigens synthesized by the malarial parasite change as the parasite matures, with a number of proteins showing strict stage-specificity. A detailed correlation between the stage-specificity of protein synthesis and parasite structure has yet to be established, but a number of proteins synthesized in the cycle are lost selectively during merozoite escape and reinvasion. These antigens are presumably associated with structures utilized and ultimately lost during this process. Particular interest has focused on some greater than 200K proteins identified as being on the surface of infected erythrocytes and internally and on the surface of merozoites. Smaller parasite proteins have also been identified in the erythrocyte membrane. The erythrocyte itself, including its membrane, is much modified by parasite growth. Changes include the presence of new cytoplasmic structures and differences in the surface labelling and isoantigenic characteristics of the surface membrane. An appreciation of the variability and specificity of exposed parasite antigens, and their relationship to newly exposed isoantigens, is central to our understanding of protective immunity to malaria.


Dynamics of an inhomogeneously coarse grained multiscale system.
To study material phenomena simultaneously at various length scales, descriptions in which matter can be coarse grained to arbitrary levels are necessary. Attempts to do this in the static regime (i.e., zero temperature) have already been developed. We present an approach that leads to a dynamics for such coarse grained models. This allows us to obtain temperature-dependent and transport properties. Renormalization group theory is used to create new local potential models between nodes, within the approximation of local thermodynamical equilibrium. Assuming that these potentials give an average description of node dynamics, we calculate thermal and mechanical properties. If this method can be sufficiently generalized it may form the basis of a multiscale molecular dynamics method with time and spatial coarse graining.


Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals.
Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26-48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a "gene discovery zone". To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.


Coherent Fourier transform electrical pulse shaping.
Fourier synthesis pulse shaping methods allowing generation of programmable, user defined femtosecond optical waveforms have been widely applied in ultrafast optical science and technology. In the electrical domain, arbitrary waveform generation is well established at frequencies below approximately 1 GHz, but is difficult at higher frequencies due to limitations in digital-to-analog converter technology. In this paper we demonstrate a method for electrical waveform synthesis at substantially higher frequencies (approximately 20 GHz electrical bandwidth) by combining Fourier optical pulse shaping (extended to hyperfine frequency resolution) and heterodyne optical to electrical conversion. Our scheme relies on coherent manipulation of fields and phases at all stages, both for processing in the optical domain and for conversion from the optical to the electrical domain. We illustrate this technique through a number of examples, including programmable retardation or advancement of short electrical pulses in time over a range exceeding ten pulse durations. Such optically implemented, coherent Fourier transform electrical pulse shaping should open new prospects in ultrawideband electromagnetics.


Complex evolutionary processes maintain an ancient chromosomal inversion.
Genome re-arrangements such as chromosomal inversions are often involved in adaptation. As such, they experience natural selection, which can erode genetic variation. Thus, whether and how inversions can remain polymorphic for extended periods of time remains debated. Here we combine genomics, experiments, and evolutionary modeling to elucidate the processes maintaining an inversion polymorphism associated with the use of a challenging host plant (Redwood trees) in Timema stick insects. We show that the inversion is maintained by a combination of processes, finding roles for life-history trade-offs, heterozygote advantage, local adaptation to different hosts, and gene flow. We use models to show how such multi-layered regimes of balancing selection and gene flow provide resilience to help buffer populations against the loss of genetic variation, maintaining the potential for future evolution. We further show that the inversion polymorphism has persisted for millions of years and is not a result of recent introgression. We thus find that rather than being a nuisance, the complex interplay of evolutionary processes provides a mechanism for the long-term maintenance of genetic variation.


Update on the Role of High-Flow Nasal Cannula in Infants with Bronchiolitis.
Bronchiolitis (BR), a lower respiratory tract infection mainly caused by respiratory syncytial virus (RSV), can be very severe. Presently, adequate nutritional support and oxygen therapy remain the only interventions recommended to treat patients with BR. For years, mild BR cases were treated with noninvasive standard oxygen therapy (SOT), i.e., with cold and poorly or totally non-humidified oxygen delivered by an ambient headbox or low-flow nasal cannula. Children with severe disease were intubated and treated with invasive mechanical ventilation (IMV). To improve SOT and overcome the disadvantages of IMV, new measures of noninvasive and more efficient oxygen administration have been studied. Bi-level positive air way pressure (BiPAP), continuous positive airway pressure (CPAP), and high-flow nasal cannula (HFNC) are among them. For its simplicity, good tolerability and safety, and the good results reported in clinical studies, HFNC has become increasingly popular and is now widely used. However, consistent guidelines for initiation and discontinuation of HFNC are lacking. In this narrative review, the role of HFNC to treat infants with BR is discussed. An analysis of the literature showed that, despite its widespread use, the role of HFNC in preventing respiratory failure in children with BR is not precisely defined. It is not established whether it can offer greater benefits compared to SOT and when and in which infants it can replace CPAP or BiPAP. The analysis of the results clearly indicates the need for multicenter studies and official guidelines. In the meantime, HFNC can be considered a safe and effective method to treat children with mild to moderate BR who do not respond to SOT.


Improvement in disease severity and pruritus outcomes with crisaborole ointment, 2%, by baseline atopic dermatitis severity in children and adolescents with mild-to-moderate atopic dermatitis.
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). This pooled post hoc analysis of two phase 3 trials (NCT02118766, NCT02118792) assessed improvement and time to improvement in Investigator's Static Global Assessment (ISGA) and Severity of Pruritus Scale (SPS) outcomes in pediatric patients with mild-to-moderate AD. Patients aged ≥2 years were randomly assigned 2:1 to receive twice-daily crisaborole or vehicle for 28 days. Patients aged 2-17 years were pooled for this analysis. Proportions of patients and time to achieving ISGA success (clear [0] or almost clear [1] with ≥2-grade improvement from baseline), ISGA clear/almost clear, ≥1-grade improvement in ISGA, SPS success (SPS score ≤1 with ≥1-grade improvement), or ≥1-grade improvement in SPS score were analyzed and stratified by baseline ISGA. At first postbaseline assessment (day 8), significantly higher proportions of crisaborole- than vehicle-treated patients achieved ISGA success, ISGA clear/almost clear, ≥1-grade ISGA improvement, SPS success, or ≥1-grade improvement in SPS regardless of baseline ISGA. Differences were significantly greater over time for all outcomes for patients with moderate baseline ISGA and numerically greater for those with mild baseline ISGA. Median times to ISGA and SPS outcomes were shorter for crisaborole versus vehicle. Improvement in ISGA and SPS outcomes were observed with crisaborole in pediatric patients with mild-to-moderate baseline AD.


Population genetic structure and post-establishment dispersal patterns of the red swamp crayfish Procambarus clarkii in China.
The red swamp crayfish (Procambarus clarkii) was introduced to China in the early 20(th) century. It has been spread to almost all forms of fresh water bodies including lakes, rivers and even paddyfields in most provinces of China. To clarify issues such as the initial entry point(s), dispersal pattern, genetic diversity and genetic structure of Procambarus clarkii in China, the genetic structure and diversity of P. clarkii populations at 37 sampling sites (35 from China, one from the USA and one from Japan) were analyzed using both mitochondrial gene sequences (COI and 16S rRNA) and 12 nuclear microsatellites. Multiple tests including phylogenetic analyses, Bayesian assignment and analysis of isolation by distance showed that (i) the population from Japan and those collected from China, particularly from NanJing (BGt and XG) and its some neighboring sites (CJr, NT and NB), have similar genetic composition, (ii) relatively high genetic diversity was detected in Chinese populations, (iii) the P. clarkii populations in China did not experience significant population expansions. Taken together, Nanjing, Jiangsu province is the presumed initial entry point, and human-mediated dispersal and adaptive variation are likely responsible for the observed genetic pattern of P. clarkii in China.


Perinatal infections by group B beta-haemolytic streptococci.
Since 1970 there has been an increase in isolations of Group B beta-haemolytic streptococci from infants and mothers at the National Women's Hospital and the organism has become the major cause of fatal perinatal infection. Forty-three of 60 stillborn and liveborn infants with postmortem isolations of Group B streptococci had pneumonia and of these a minority also had meningitis and/or septicaemia. Amnionitis was found in 15 of 20 placentae examined from these patients and an ascending infection from the maternal genital tract, often through intact membranes, was considered likely in the majority. However, a review of the prenatal histories of 33 infants showed that only a minority had premonitory features such as prolonged rupture of membranes, prolonged labour or maternal fever. Thirteen of 26 liveborn infants had a birth weight less than 2500 g. The majority presented within one hour of birth with respiratory distress or apnoea and died within 48 hours of birth. Early diagnosis of Group B infection is possible if bacteriological and radiological evidence is sought in infants of low birth weight, with low Apgar scores and with early onset of respiratory distress syndrome or apnoea in addition to those having the more usual indications of intrauterine infection. Group B streptococci were carried vaginally in 9 per cent of women attending an antenatal clinic and this high carrier rate is considered to preclude prophylactic treatment.


Thermodynamic parameters of end-plate channel blockade.
The reaction kinetics for drug blockade of postsynaptic channels at the mouse neuromuscular junction were studied. The activation energies associated with the onward and off-rate constants, from a sequential model, were measured for procaine, scopolamine, octanol, and heptanol, and from these the transition state thermodynamic parameters of free energy (delta G++), enthalpy (delta H++), and entropy (delta S++) of activation were determined. All agents showed positive entropies of activation for the channel blocking rate constant kappa 2, with the values for the alcohols significantly greater than those for the two positively charged local anesthetics. No significant differences in the activation energies for the off-rate constant kappa-2 were observed between any of the agents. The magnitude of kappa-2 decreased as the hydrophobicity of the agent increased. The large activation energies measured for kappa 2 and kappa-2 (in excess of 10 kcal/mol) are higher than expected for simple rate-limiting diffusion, and the possibility exists that channel blockade involves conformational changes in a protein segment, induced by a hydrophobic interaction between agent and intrachannel site or sites. The large entropy increase observed in the blocking step is indicative of the agent replacing structured waters of hydration near a hydrophobic region of a protein.


Wavelet: a new trend in chemistry.
Since 1989, wavelet transform (WT) has attracted much interest of chemists working on signal and image processing, and the WT-based techniques have been successfully applied to the chemical signal processing. This approach has been demonstrated as fast in computation with localization and having quick decay properties, in contrast to the popular methods existing, especially to the fast Fourier transform. More than 370 papers have been published up to the year 2002 which covered applications of WT in various fields of chemistry, including analytical chemistry, chemical physics, and quantum chemistry. In this paper, we report on applications of WT to data compression, data smoothing and denoising, baseline and background correction, resolution of multicomponent overlapping signals, regression and classification, and analytical images processing in analytical chemistry. Through this report we wish to induce greater interest of chemists in WT and to obtain greater benefits from using the WT-based techniques.


Protecting the fair trial rights of mentally disordered defendants in criminal proceedings: Exploring the need for further EU action.
Using the new legal basis provided by the Lisbon Treaty, the Council of the European Union has endorsed the 2009 Procedural Roadmap for strengthening the procedural rights of suspected or accused persons in criminal proceedings. This Roadmap has so far resulted in six measures from which specific procedural minimum standards have been and will be adopted or negotiated. So far, only Measure E directly touches on the specific issue of vulnerable persons. This Measure has recently produced a tentative result through a Commission Recommendation on procedural safeguards for vulnerable persons in criminal proceedings. This contribution aims to discuss the need for the introduction of binding minimum standards throughout Europe to provide additional protection for mentally disordered defendants. The paper will examine whether or not the member states adhere to existing fundamental norms and standards in this context, and whether the application of these norms and standards should be made more uniform. For this purpose, the procedural situation of mentally disordered defendants in Belgium and England and Wales will be thoroughly explored. The research establishes that Belgian law is unsatisfactory in the light of the Strasbourg case law, and that the situation in practice in England and Wales indicates not only that there is justifiable doubt about whether fundamental principles are always adhered to, but also that these principles should become more anchored in everyday practice. It will therefore be argued that there is a need for putting Measure E into practice. The Commission Recommendation, though only suggestive, may serve as a necessary and inspirational vehicle to improve the procedural rights of mentally disordered defendants and to ensure that member states are able to cooperate within the mutual recognition framework without being challenged on the grounds that they are collaborating with peers who do not respect defendants' fundamental fair trial rights. Throughout this contribution the term 'defendant' will be used, and no difference will be made in terminology between suspected and accused persons. This contribution only covers the situation of mentally disordered adult defendants.


[Noninvasive magnetic resonance myelography in patients with lumbosacral intervertebral disk herniation].
For many decades X-ray myelography has remained one of the major diagnostic methods for spinal pathology. With the advent of computed tomography (CT), CT myelography using water-soluble contrast agents has been developed. Visualization of the subarachnoidal spaces of the spinal cord and dural sac without an intrathecal contrast agent has become possible with the emergence of magnetic resonance imaging (MRI). Its further development and improvement has brought to existence the new noninvasive technique MR myelography based on the suppression of a signal from the medulla and its enhancement from the cerebrospinal fluid-containing spaces. This paper compares routine X-ray myelography, CT myelography, and MR myelography used in the diagnosis of lumbosacral intervertebral disk herniation and assesses the informative value and benefits of MR myelography as a noninvasive diagnostic method for this pathology.


Isolable oxysulfuranes in organic chemistry.
The development of synthetic methods for oxysulfuranes has made a wide range of isolable compounds of hypervalent sulfur available for study. Structure-reactivity correlations are now becoming evident as a result of such study. The fact that oxygen is dicoordinate makes it possible to synthesize cyclic oxysulfuranes and to use the pronounced changes of reactivity which accompany cyclization to design new, potentially useful sulfurane reagents stable enough to allow isolation.


Changes in lung function in adolescents with substance use disorders: an exploratory study.
To compare lung function between adolescents with and without substance use disorder (SUD). This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation. We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%. This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.


A radioimmunoassay for chemically modified grass pollen allergen.
Because of the physicochemical properties of tyrosine adsorbed chemically modified grass pollen allergens neither the human skin test in atopic volunteers nor the inhibition of the radioallergosorbent test are suitable assay procedures. Radioimmunoassays involving a labelled IgG fraction of rabbit antisera to the modified materials can be developed. The dilution inherent in the solubilisation procedure for the tyrosine does not, in most cases, take the antigen concentration below the level of sensitivity of the assay. Assay of different batches of Pollinex with an inhibition assay shows that discernment of different dose levels is possible. The results are compared with a method of assaying total protein.


Arginine vasotocin, steroid hormones and social behavior in the green anole lizard (Anolis carolinensis).
Arginine vasotocin (AVT) is a potent regulator of social behavior in many species, but little is known about its role in reptilian behavior. Here we examine the effect of exogenous AVT on aggressive responding and courtship behavior in the green anole lizard (Anolis carolinensis). Aggressive behavior was stimulated in two ways: (1) mirror presentation (no relative status formed) and (2) size-matched pairs (where a social status is achieved). To elicit courtship behavior, a novel female was introduced into the home cage of a male. Regardless of the behavior condition, male anoles were injected i.p. with either reptile Ringer solution (vehicle) or AVT prior to testing. Animals treated with AVT performed fewer aggressive display bouts during mirror presentation but AVT treatment did not affect the overall number of aggressive display bouts within size-matched pairs. Male courtship behavior was not affected by AVT; however, untreated females displayed more frequently when paired with an AVT-treated male than a vehicle-injected control, suggesting that AVT-treated males were more attractive to females. Regardless of behavior condition, AVT injections led to increases in circulating corticosterone. Overall, we found that AVT tended to reduce aggressive behavior as has been reported for other territorial species. AVT did not perceptibly alter male courtship but did increase the display behavior of untreated females paired with treated males. Our study supports a role for AVT in the regulation of reptile social behavior.


[Effects of land cover change on soil organic carbon and light fraction organic carbon at river banks of Fuzhou urban area].
By using Vario EL III element analyzer, the vertical distribution characteristics of soil organic carbon (SOC) and light-fraction organic carbon (LFOC) in the lawn, patch plantation, and reed wetland at river banks of Fuzhou urban area were studied in July 2007. For all the three land cover types, the SOC and LFOC contents were the highest in surface soil layer, and declined gradually with soil depth. Compared with reed wetland, the lawn and patch plantation had higher SOC and LFOC contents in each layer of the soil profile (0-60 cm), and the lawn had significantly higher contents of SOC and LFOC in 0-20 cm soil layer, compared with the patch plantation. After the reed wetland was converted into lawn and patch plantation, the SOC stock in the soil profile was increased by 94.8% and 72.0%, and the LFOC stock was increased by 225% and 93%, respectively. Due to the changes of plant species, plant density, and management measure, the conversion from natural wetland into human-manipulated green spaces increased the SOC and LFOC stocks in the soil profile, and improved the soil quality. Compared with the SOC, soil LFOC was more sensitive to land use/cover change, especially for those in 0-20 cm soil layer.


How useful are complete blood count and reticulocyte reports to clinicians in Addis Ababa hospitals, Ethiopia?
Complete blood count (CBC) and reticulocyte (Retics) are routine hematology tests useful for the differential diagnosis of anemia and other medical conditions. However, it has been presumed that they are not used as regular as they should be in medical practice in Addis Ababa hospitals. A hospital-based cross-sectional questionnaire survey was conducted during November-December 2010, in which 408 clinicians participated and their response on the use of CBC and Retics was assessed. The always/frequently (A/F) response was considered to reflect routine use of the CBC/Retics parameters by the clinicians. The Chi square test was used to study statistical associations among different variables. Only four of 13 parameters in CBC were frequently or always used by more than 85% of the clinicians. Health Officers were observed to use 12 of the 13 CBC parameters less than the other professional group; interns and residents demonstrated highest use of CBC results. More than a third of clinicians' preferred white blood cell (WBC) differential report in percentages than the more useful absolute number report. Reticulocyte parameters were not being used by majority of clinicians in patient management. Clinicians rated 'average' regarding the adequacy of clinical laboratory methods course they took during medical education. As service users, clinicians indicated mm3 as unit of preference in cell count on the laboratory report form. Overall, most clinicians do not use much of the data provided on routine CBC report. Additional research is needed to understand the issue further. Responsible bodies should promote the appropriate use of CBC/Retics reports by clinicians.


Outbreak of human anthrax in Ramabhadrapuram village of Chittoor district in Andhra Pradesh.
Thirty human anthrax cases were reported from Ramabhadrapuram village of Chittoor district in Andhra Pradesh during November-December, 1989. These cases occurred following an epizootic of anthrax among cattle and sheep of the village and ingestion of contaminated meat by the villagers. The overall attack rate was 24.39 per cent with a case fatality of 16.67 per cent. All age groups and both sexes were affected. Ten cases were of cutaneous form with typical black eschar formation which were confirmed bacteriologically. Fever and headache were common systemic manifestations. They responded well to penicillins and there was no mortality. The possibility of human to human spread is suggested. The twenty cases of internal anthrax comprised intestinal, septicemic, peritonitis, meningeal and pulmonary forms. Sub-clinical forms also occurred. Fever, abdominal pain, ascites, anorexia and vomiting were notable features. Diagnosis was made clinically and also on epidemiological basis. All deaths during this outbreak occurred in women with internal anthrax, the case fatality rate for the latter being 25 per cent. Prophylactic administration of penicillin was done for individuals at risk.


Incidence and trends of cardiac complications in major abdominal surgery.
Cardiovascular complications are the leading cause of death after noncardiac surgery. Major abdominal operations represent the largest category of procedures considered to have an increased risk of cardiovascular complications. The current aim was to examine trends in the incidence of mortality, perioperative myocardial infarction, and cardiac arrest to determine the presence of potential volume-outcome relationships. We performed a retrospective analysis of the Nationwide Inpatient Sample for patients undergoing elective, open abdominal esophagectomy, gastrectomy, pancreatectomy, nephrectomy, hepatectomy, splenectomy, and colectomy (major abdominal surgery) during 2008-2014. Univariate and multivariate analyses were performed to determine the impact of operative volume on rates of myocardial infarction, cardiac arrest, and mortality. Of the 962,754 elective admissions for major abdominal surgery, 1.4% experienced in-hospital mortality, 0.7% myocardial infarction, and 0.35% cardiac arrest. Myocardial infarction and cardiac arrest were associated with a 24-fold increase in risk of perioperative mortality. Compared with institutions that have a very low volume of operations, those hospitals with larger volumes of operations had a decreased risk of cardiac arrest and incident mortality after cardiovascular complications, but the odds of myocardial infarction were greatest at higher operative-volume hospitals. The annual all-cause mortality and myocardial infarction rates decreased over time, but the incidence of cardiac arrest increased. Myocardial infarction or cardiac arrest after major abdominal surgery increased the odds of mortality with superior rescue after cardiovascular complications at higher volume institutions. Across all US hospitals performing major abdominal surgery, the rate of cardiac arrest increased without a concomitant increase in myocardial infarction or mortality. Novel targets for risk modification of myocardial infarction and cardiac arrest as well as investigation of processes that facilitate rescue after these complications at higher operative-volume hospitals are needed to delineate quality improvement opportunities.


Do Older Adults with Overactive Bladder Demonstrate Impaired Executive Function Compared to Their Peers Without OAB?
Maintaining urinary continence is not an automatic process, but relies on continuous processing of sensory signals from the bladder and suppression of the desire to void. Urinary incontinence (UI) and lower urinary tract symptoms (LUTS), including urinary urgency, frequency, and nocturia are highly prevalent among the general population. This prevalence rises in association with increasing age, and this may be in part due to changes in the central nervous system rather than the urinary tract. The aim of this study was to assess if older adults with overactive bladder (OAB) had demonstrable impairment in executive function. This was a cross-sectional study comparing the performance of adults aged 65 and over with and without OAB on two cognitive tests, the Trail Making Test B (TMT-B) and simple reaction time (SRT). OAB was defined as urgency, with at least weekly urgency incontinence and a daytime urinary frequency of 8 or more. The control group were defined as a Bladder control Self-Assessment Questionnaire (B-SAQ) score of ≤4. 56 participants were recruited, of whom 35 met criteria for OAB. The OAB group took significantly longer to complete the TMT-B than the control group (103s vs. 77s, p = .003). There was no difference in the SRT. In this sample of older adults, OAB was associated with measurable slower performance on the TMT-B, suggesting that impaired executive function is associated with OAB.


Epstein-Barr virus (EBV) EB1/Zta protein provided in trans and competent for the activation of productive cycle genes does not activate the BZLF1 gene in the EBV genome.
The Epstein-Barr Virus (EBV) gene BZLF1 encodes the transcription fact or EB1 (also known as Zta) which is essential for the switch from latency to the lytic cycle: EB1 expressed from a plasmid transfected into B cell lines carrying latent EBV episomes, induces a productive viral cycle. Furthermore, EB1-specific DNA-binding sequences (ZREs) have been found in the promoters of many EBV early genes, including the BZLF1 promoter PZ and the PR promoter. At promoter PR, bicistronic mRNAs are initiated which contain, from 5' to 3', the BRLF1 and the BZLF1 open reading frames (ORFs) encoding respectively the R and EB1 proteins. The current model for the activation of the EBV lytic cycle implies that downregulation of the PZ promoter activity is a key element for latency and that a limiting step in the activation of the productive cycle is the translation of EB1. Once made, EB1 autoactivates promoter PZ, activates the PR promoter at which an mRNA coding for the EBV transcription factor R is initiated and activates the EBV early genes and the ORIlyt, due to unrestricted accessibility of the EB1-responsive elements in the viral genome. We show here that EB1 expressed from a plasmid activated most if not all of the EBV early genes in the viral genome but not its own gene, BZLF1. Moreover, transfected EB1 induced the transcription of the bicistronic mRNAs from which R is efficiently translated but not EB1. Our results demonstrate that EB1 provided in trans, although competent to activate the productive cycle genes, was not sufficient to overcome the downregulation of the PZ promoter.


Male psychological adaptation to unsuccessful medically assisted reproduction treatments: a systematic review.
Similarly to women, men suffer from engaging in fertility treatments, both physically and psychologically. Although there is a vast body of evidence on the emotional adjustment of women to infertility, there are no systematic reviews focusing on men's psychological adaptation to infertility and related treatments. The main research questions addressed in this review were 'Does male psychological adaptation to unsuccessful medically assisted reproduction (MAR) treatment vary over time?' and 'Which psychosocial variables act as protective or risk factors for psychological maladaptation?' A literature search was conducted from inception to September 2015 on five databases using combinations of MeSH terms and keywords. Eligible studies had to present quantitative prospective designs and samples including men who did not achieve pregnancy or parenthood at follow-up. A narrative synthesis approach was used to conduct the review. Twelve studies from three continents were eligible from 2534 records identified in the search. The results revealed that psychological symptoms of maladjustment significantly increased in men 1 year after the first fertility evaluation. No significant differences were found two or more years after the initial consultation. Evidence was found for anxiety, depression, active-avoidance coping, catastrophizing, difficulties in partner communication and the use of avoidance or religious coping from the wife as risk factors for psychological maladjustment. Protective factors were related to the use of coping strategies that involve seeking information and attribution of a positive meaning to infertility, having the support of others and of one's spouse, and engaging in open communication about the infertility problem. Our findings recommend an active involvement of men during the treatment process by health care professionals, and the inclusion of coping skills training and couple communication enhancement interventions in counselling. Further prospective large studies with high-quality design and power are warranted.


Women's perceptions of their involvement in treatment decision making for early stage breast cancer.
This study aimed to describe the perceptions of women with early stage breast cancer regarding their involvement in treatment decision making (TDM). Eligible women with early stage breast cancer were recruited immediately after their first consultation with a specialist. Semistructured personal interviews were held prior to treatment. Interviews were audiotaped, transcribed, and analyzed. Nineteen women with early stage breast cancer considering surgery (n = 6) or adjuvant therapy (n = 13) participated. Women described being involved in various stages of TDM and interacting with informal networks and specialists. Women's descriptions suggest that (1) the concept of involvement in TDM may have a broader meaning for patients than strictly their decisional role and (2) inclusion of significant others in TDM contributes to the patient's sense of involvement. Conceptualization and measurement of patient involvement in TDM have often been framed within the context of the medical encounter and the patient's perceived or actual role in this process. Our findings raise questions about what involvement means to patients with early stage breast cancer and suggest that the focus on patient involvement in TDM within the medical encounter may be too narrow to capture the meaning of involvement from the patient's perspective.


Factors related to in-hospital heart failure are very different for unstable angina and non-ST elevation myocardial infarction.
Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) resulted in different degrees of damage to the heart muscle, and yet, when factors related to in-hospital outcomes were examined, these two subsets were often lumped together as non-STelevation acute coronary syndrome. Therefore, we investigated predictors of in-hospital heart failure (HF) in UA and NSTEMI separately. Factors related to HF (Killip > or = 2) were analyzed for NSTEMI and UA in a Thai Acute Coronary Syndrome (ACS) registry conducted in 17 institutions between 2002 and 2005. The registry comprised of 9373 single admissions age 65.1 +/- 12.3 years, 40.2% women, and 45.1% with HF. There were 3548 NSTEMI and 1989 UA with HF prevalence of 56.2% and 27.4%, respectively. Heart failure patients were older, more were women, sicker (as shown by more of those with shock, postcardiac arrest, and breathless on admission), more with diabetes mellitus (DM), received less intervention and medication, and showed higher total death (19.3% vs 5.3% for NSTEMI with and without HF; and correspondingly, 5.9% and 1.9% for UA). Independent predictors (at presentation) for the development of HF following NSTEMI or UA were age (not sex), breathlessness, and less prevalence of chest pain. However, shock and DM were risks only for NSTEMI but not UA. Heart failure was found to be a factor for in-hospital death for NSTEMI only, with odds ratio of 2.84 (confidence interval 2.11-3.82) and 3.23 (2.25-4.64) for total and cardiac deaths, respectively. Non-ST-elevation myocardial infarction and UA showed substantial differences in factors related to predictors for in-hospital outcome such that these should be examined separately.


Comparison of Preschooler Verbal and Graphic Symbol Production Across Different Syntactic Structures.
The present study focuses on the impact of graphic symbols used in Augmentative and Alternative Communication (AAC) on clause construction. It is not yet well-understood to what extent communication produced via graphic symbols differs from verbal production. This study attempts shed light on the impact of the graphic symbol modality on message construction beyond individual differences, language knowledge, and language-specific patterns by providing a direct comparison between children's verbal and graphic symbol production. Nineteen typically developing Hebrew-speaking children aged 4-5 years were presented with 16 short videos of actions and were asked to express what they saw verbally and by choosing among graphic symbols displayed on an iPad communication board. The 570 clauses produced by the children were coded and analyzed. A significant difference was found in favor of verbal speech across different syntactic structures in terms of utilization of the target lexicon, syntactic complexity, and expected target word order. These results are consistent with the existing literature for English. Implications for AAC practices are discussed, highlighting the notion that using graphic symbols to represent spoken language may not reflect actual linguistic knowledge and that adequate, explicit instruction is necessary for graphic representation of more complex linguistic structures.


Light-induced carotenogenesis in Myxococcus xanthus: functional characterization of the ECF sigma factor CarQ and antisigma factor CarR.
Illumination of dark-grown Myxococcus xanthus with blue light leads to the induction of carotenoid synthesis. Central to this response is the activation of the light-inducible promoter, PcarQRS, and the transcription of three downstream genes, carQ, carR and carS. Sequence analysis predicted that CarQ is a member of the ECF (extracytoplasmic function) subfamily of RNA polymerase sigma factors, and that CarR is an inner membrane protein. Genetic analysis strongly implied that CarR is an antisigma factor that sequesters CarQ in a transcriptionally inactive complex. Using in vitro transcription run-off assays, we present biochemical evidence that CarQ functions as a bacterial sigma factor and is responsible for transcription initiation at PcarQRS. Similar experiments using the crtI promoter failed to implicate CarQ in direct transcription of the crtI gene. Experiments using the yeast two-hybrid system demonstrated a protein-protein interaction between CarQ and CarR, providing evidence of a CarQ-CarR complex. The yeast two-hybrid system data also indicated that CarR is capable of oligomerization. Fractionation of M. xanthus membranes with the detergent sarkosyl showed that CarR was associated with the inner membrane. Furthermore, CarR was found to be unstable in illuminated stationary phase cells, providing a possible mechanism by which the CarR-CarQ complex is disrupted.


Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells.
It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0.1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 muM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk.


8-Oxo-7,8-dihydro-2'-deoxyguanosine and abasic site tandem lesions are oxidation prone yielding hydantoin products that strongly destabilize duplex DNA.
In DNA, 2'-deoxyguanosine (dG) is susceptible to oxidative modification by reactive oxygen species (ROS) yielding many products, one of which is 8-oxo-7,8-dihydro-2'-deoxyguanosine (dOG). Interestingly, dOG is stable but much more labile toward oxidation than dG, furnishing 5-guanidinohydantoin-2'-deoxyribose (dGh) that is favored in the duplex context or spiroiminodihydantoin-2'-deoxyribose (dSp) that is favored in the oxidation of single-stranded contexts. Previously, exposure of DNA to ionizing radiation found ∼50% of the dOG exists as a tandem lesion with an adjacent formamide site. The present work explored oxidation of dOG in a tandem lesion with a THF abasic site analog (F) that models the formamide on either the 5' or 3' side. When dOG was in a tandem lesion, both dGh and dSp were observed as oxidation products. The 5' versus 3' side in which F resided influenced the stereochemistry of the dSp formed. Further, tandem lesions with dOG were found to be up to two orders of magnitude more reactive to oxidation than dOG in an intact duplex. When dOG is in a tandem lesion it is up to fivefold more prone to formation of spermine cross-links during oxidation compared to dOG in an intact duplex. Lastly, dOG, dGh, and each dSp diastereomer were synthesized as part of a tandem lesion in a duplex DNA to establish that dOG tandem lesions decrease the thermal stability by 12-13 °C, while dGh or either dSp diastereomer in a tandem lesion decrease the stability by >20 °C. The biological consequences of these results are discussed.


[Treatment of renal anemia with darbepoetin alfa administered once every other week in predialysis patients with chronic kidney disease and previously treated with epoetin alfa].
Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein with up to 3 times longer half-life than recombinant human erythropoietin (rHuEPO) in humans. The aim of this study was to assess the efficacy and safety of darbepoetin alfa given once every other week as treatment of anemia in predialysis patients with chronic renal failure (CRF) previously treated with once-weekly epoetin alfa. A total of 42 CRF patients were included, all of whom had previously been treated with epoetin alfa and showed stable hemoglobin (Hb) levels without dose changes during the last 8 weeks prior to enrolment in this study. All patients received s.c. darbepoetin alfa once every other week at doses calculated from the protein mass equivalence between rHuEPO and darbepoetin alfa. Follow-up lasted for 24 weeks. Dose adjustments were conducted to preserve target Hb levels between 11 and 13 g/dl. Thirty-nine patients completed the 24 weeks of study. Hb levels increased during follow-up [mean values of 0.39 (p < 0.002), 0.58) (p < 0.001), and 0.83 g/dl (p < 0.001) at 8, 16 and 24 weeks, respectively] despite reducing the darbepoetin alfa dose up to 15% at 24 weeks [from 0.192 microg/kg body weight to 0.185, 0.178 and 0.163 at 8, 16, and 24 weeks, respectively (p < 0.001)]. No adverse events related to darbepoetin alfa were reported. In conclusion, these results show s.c. administration of darbepoetin alfa once every other week was superior to weekly epoetin alfa as a maintenance treatment for anemia in predialysis CRF patients, since the former provided higher Hb levels. Moreover, darbepoetin alfa administration was safe in these patients.


NMR 1H-Shielding Constants of Hydrogen-Bond Donor Reflect Manifestation of the Pauli Principle.
NMR spectroscopy is one of the most useful methods for detection and characterization of hydrogen bond (H-bond) interactions in biological systems. For H bonds X-H···Y, where X and Y are O or N, it is generally believed that a decrease in 1H-shielding constants relates to a shortening of H-bond donor-acceptor distance. Here we investigated computationally the trend of 1H-shielding constants for hydrogen-bonded protons in a series of guanine C8-substituted GC pair model compounds as a function of the molecular structure. Furthermore, the electron density distribution around the hydrogen atom was analyzed with the Voronoi deformation density (VDD) method. Our findings demonstrate that 1H-shielding values of the hydrogen bond are determined by the depletion of charge around the hydrogen atom, which stems from the fact that electrons obey the Pauli exclusion principle.


Endovascular treatment of posterior circulation aneurysms.
The objective of this paper was to analyse the technical and clinical outcome in patients receiving endovascular treatment for posterior circulation intracranial aneurysms at Royal Perth Hospital. The case notes and angiograms of 35 patients with ruptured and unruptured posterior circulation aneurysms treated by endovascular coil occlusion between 1992 and 1998 were included in the study. The degree of angiographic occlusion achieved, and periprocedural, short and long-term clinical outcome were retrospectively analysed. Total aneurysm occlusion was achieved at initial treatment in 46% of cases, with 90% or greater occlusion achieved in 97% of cases. For aneurysms 12 mm or less in diameter, 100% of patients treated electively, and 100% of patients with grade I or II subarachnoid haemorrhage treated in the acute postictal phase had a good clinical outcome (Rankin Disability Score 1 and 2), with no serious morbidity or associated mortality. Excluding patients with grade V subarachnoid haemorrhage, the treatment-related serious morbidity rate was 3.4% and procedure-related mortality rate was 0%. We conclude that endovascular management provides an effective means of treatment for selected cases of posterior circulation aneurysms.


Training models and status of clinical neuropsychologists in Europe: Results of a survey on 30 countries.
The aims of the study were to analyze the current European situation of specialist education and training within clinical neuropsychology, and the legal and professional status of clinical neuropsychologists in different European countries. An online survey was prepared in 2016 by a Task Force established by the European Federation of Psychological Associations, and representatives of 30 countries gave their responses. Response rate was 76%. Only three countries were reported to regulate the title of clinical neuropsychologist as well as the education and practice of clinical neuropsychologists by law. The most common university degree required to practice clinical neuropsychology was the master's degree; a doctoral degree was required in two countries. The length of the specialist education after the master's degree varied between 12 and 60 months. In one third of the countries, no commonly agreed upon model for specialist education existed. A more systematic training model and a longer duration of training were associated with independence in the work of clinical neuropsychologists. As legal regulation is mostly absent and training models differ, those actively practicing clinical neuropsychology in Europe have a very heterogeneous educational background and skill level. There is a need for a European standardization of specialist training in clinical neuropsychology. Guiding principles for establishing the common core requirements are presented.


Impaired Mind-Body Connections in Psychosomatic Patients: A Contemporary Neuropsychodynamic Model.
In alexithymia-type psychosomatic patients who do not have the capacity to mentalize, arousal is experienced non-symbolically within the body. These people also often have significant histories of attachment trauma and other adverse childhood experiences. This article extends a previous neuropsychodynamic formulation that takes into account recent work on how attachment trauma is internalized in developing brain circuits. Specifically, it considers the possibility that early attachment trauma impairs thalamo-amygdala-striatal-thalamic circuits, resulting in disconnect of subcortical arousal to the prefrontal cortex where the arousal can be mentalized. These impaired subcortical circuits perpetuate stress deep within these patients' implicit procedural circuitry, making them very resistant to psychotherapy. Knowledge of this interaction deepens our understanding of these patients, who suffer greatly, and suggests guidelines for treatment approaches with which they are more likely to engage.


Association between changes in predicted body composition and occurrence of heart failure: a nationwide population study.
Large population-based studies on the association between changes in body composition and the occurrence of heart failure (HF) are rare. We aimed to determine the association between changes in body composition, including the predicted body fat mass index (pBFMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted lean body mass index (pLBMI), and the occurrence of HF. For present study, 2,036,940 people who consecutively underwent national health examinations from 2010~2011 (baseline period) to 2012~2013 (follow-up period) were included. The pBFMI, pASMI, and pLBMI were indirectly investigated using validated anthropometric prediction equations from the Korean National Health and Nutrition Examination Survey cohort. The outcome was defined as at least two or more claims of HF. During a median of 7.59 years of follow-up, 22,172 participants (event rate, 1.09%) with HF were observed. Decreased changes in the pASMI and pLBMI were associated with the occurrence of HF among males (hazard ratio [HR] 0.966, 95% confidence interval (CI) [0.944-0.988]; HR 0.939, 95%CI [0.923-0.955], respectively) and females (HR 0.924, 95%CI [0.900-0.947]; HR 0.951, 95%CI [0.939-0.963], respectively). An increased change in the pBFMI was associated with the occurrence of HF in males (HR 1.017, 95%CI [1.001-1.034]). However, paradoxically, a change in the pBFMI was associated with the occurrence of HF in females (HR 0.925, 95%CI [0.909-0.942]). Decreased skeletal muscle mass was related to the occurrence of HF. However, the relationship between a change in fat mass and the occurrence of HF was different and even paradoxical depending on sex.


A rational strategy based on experimental designs to optimize parameters of a liquid chromatography-mass spectrometry analysis of complex matrices.
A high number of factors controlled by the experimenter has to be optimized to successfully separate, ionize and detect compounds when analyzing complex matrices by liquid chromatography hyphenated to high resolution mass spectrometry (LC-UV/MS). Key steps to manage such hyphenation are focused on desolvation and ionization processes. In this study, a design of experiments approach was used to optimize decisive parameters (i.e. nebulising, drying and sweep gas flow rates, ion transfer capillary voltage and temperature) for electrospray ionization and atmospheric pressure chemical ionization sources both in positive and negative modes. Central composite designs including 131 experiments each were built to cover rationally a sufficiently wide range of operating conditions. Each run was repeated three times to insure stable conditions of ionization and thus a satisfactory repeatability. Extracted ion chromatograms of twelve model oxygenated compounds were integrated and used as responses for experiment designs. Quadratic models for each standard allowed to take into account interactions between factors. Then responses were simultaneously maximized to achieve optimized factors. To illustrate the methodology relevance, optimal conditions were applied to a lignocellulosic biomass fast pyrolysis oil. Thanks to our high sensitivity method, a large number of molecular formulae was identified, as for instance in negative-ion mode electrospray with more than 5500 identified molecular formulae whereas analysis of the same sample by mass spectrometry without any prior chromatographic separation provided less than 2000 molecular formulae. In short, this study proposed a rational methodology to optimize ionization efficiency for LC-UV/MS analysis of complex mixtures.


Spreading a water droplet through filter paper on the metal substrate for surface-enhanced laser-induced breakdown spectroscopy.
To improve the quantitative analysis accuracy of an aqueous solution using surface-enhanced laser-induced breakdown spectroscopy (SENLIBS), the filter paper was used as a transmission medium by placing it onto the surface of a metallic substrate to make the microdroplet spreading more uniform in a fixed region of the substrate surface. The trace elements (Cu, Pb, Cd, and Cr) in an aqueous solution were detected successfully using this method. The results showed that the sample preparation repeatability of SENLIBS was noticeably improved with the aid of filter paper. Moreover, the limit of detection (LoD) values was similar to those without filter paper. Furthermore, the R2 values were improved from 0.6192~0.9321 to 0.9481~0.9766, the RMSECV values were decreased from 0.53~1.95 μg/mL to 0.33~1.06 μg/mL, and the average relative error (ARE) values were decreased from 8.96~22.31% to 4.28~14.37% with the aid of filter paper. This demonstrated that the use of filter paper could improve the quantitative analysis accuracy of SENLIBS by increasing the sample preparation repeatability.


[Spatial and temporal heterogeneity of pH values in lysosomes from different types of cells cultured in situ].
Distinct variety of the pH value, at the ranges of pH 4.5-7.0, was found in lysosomes. Small lysosomes exhibited lower pH values as compared with large organelles. These lysosomes were measured in cultures of normal cells (hamster fibroblasts, pig embryonal kidney cells, primary culture of chicken embryonal fibroblasts) and of tumoral cells (neurinoma of rat trigeminal ganglion). Studies of individual lysosomes demonstrated that temporal alterations in the pH value reached up to 1.5 un of the pH period 15-45 min. Distinct space-temporal heterogeneity of the cellular lysosomal apparatus in the pH value enabled to create optimal conditions for enzymatic systems catalyzing hydrolysis of various macromolecules. The mean values of pH were very similar in all the cultivated cells studied, within ranges of pH 5.5-5.8, which appears to depend on the similarity of functions of the lysosomal apparatus in the cells of various classes.


Efficacy of nonviral gene transfer in the canine brain.
The purpose of this study was to evaluate the gene transfer capability and tolerability of plasmid DNA/polyethylenimine (PEI) complexes in comparison with adenovirus and naked plasmid DNA in the canine brain. Plasmid or adenoviral vectors encoding firefly luciferase were injected directly into the cerebral parenchyma of five adult dogs at varying doses and volumes. Serial physical and neurological examinations, as well as blood and cerebrospinal fluid (CSF) analyses, were conducted before and after the surgery for 3 days. Three days after gene delivery, a luciferase activity assay and immunofluorescence analysis were used to test the brain tissue for gene expression. Injection into the brain parenchyma resulted in gene transfer throughout the cerebrum with every vector tested. Luciferase expression was highest when adenovirus vectors were used. Injection of plasmid DNA/PEI complexes and naked DNA resulted in similar levels of luciferase expression, which were on average 0.5 to 1.5% of the expression achieved with adenovirus vectors. Immunofluorescent microscopy analysis revealed that plasmid DNA/PEI complexes transduced mainly neurons, whereas adenovirus transduced mainly astrocytes. No significant acute side effects or neurological complications were observed in any of the dogs. Mononuclear cell counts significantly increased in the CSF after adenovirus injection and modestly increased after injection of plasmid DNA/PEI complexes, suggesting that a mild, acute inflammatory response occurred in the central nervous system (CNS). Compared with rodent models that are limited by very small brains, the dog is an excellent preclinical model in which to assess the distribution and safety of emerging gene transfer technologies. In this study, short-term gene transfer was evaluated as a prelude to long-term expression and safety studies. The authors conclude that the viral and nonviral vectors tested were well tolerated and effective at mediating gene transfer throughout a large portion of the canine brain. The nonviral plasmid vectors were less effective than adenovirus, yet they still achieved appreciable gene expression levels. Due to reduced gene transfer efficiency relative to viral vectors, nonviral vectors may be most useful when the expressed protein is secreted or exerts a bystander effect. Nonviral vectors offer an alternative means to genetically modify cells within the CNS of large mammals.


Long-Term Health-Related Quality of Life after Breast Reconstruction: Comparing 4 Different Methods of Reconstruction.
Studies have confirmed that breast reconstruction is beneficial to improve health-related quality of life (HR-QoL) in breast cancer patients. Our aim was to compare 4 different methods of breast reconstruction on patient satisfaction and HR-QoL using both general and specific patient-reported outcome instruments. Retrospectively, 459 patients who underwent breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap, latissimus dorsi flap, lateral thoracodorsal flap, or expander with secondary implant and who had responded to the questionnaires were enrolled. Questionnaire answers, together with demographic and follow-up data, were statistically analyzed and compared between groups. Short-Form 36 Health Survey (SF-36) results were also compared with those from a sample of 930 age-matched women from the Swedish population. There were slight differences in the SF-36 results but no significant differences in Psychological General Well-Being Index and EuroQoL-5 Dimension Questionnaire results between groups. Analysis of Breast-Q showed that the DIEP group had significantly higher score on the scale satisfaction with breast, significantly higher score in satisfaction with outcome than the lateral thoracodorsal flap (P = 0.014) and EXP groups (P = 0.024). There were no significant differences in most of the domains of the HR-QoL instruments. The higher satisfaction with breasts and outcome in the DIEP group is interesting, considering the higher complication rates associated with this reconstruction method. Patients who underwent breast reconstruction with a DIEP flap were more satisfied with their reconstructed breast and outcome than the other 3 groups. Breast reconstruction centers should make DIEP reconstruction widely available to patients after mastectomy.


Pakicetus inachus and the origin of whales and dolphins (Mammalia: Cetacea).
The present paper is concerned with the comparative morphology of the archeocete and odontocete skull. Among the archeocetes, the recently described lower Eocene Pakicetus inachus obviously represents an early stage of adaptation to aquatic life. The morphology of the incomplete cranial remains, however, gives no evidence that Pakicetus was an amphibious intermediate stage. The evolution of advanced archeocetes and odontocetes is characterized by the successive acquirement of new morphological devices related to the emission and perception of ultrasound under water. The formation of a sonar system in odontocetes obviously not only helped to compensate for the loss of the peripheral olfactory system but moreover was a substantial factor in the evolution of the exceptional dolphin brain.


Clinical and molecular features of spinocerebellar ataxia type 6.
The mutation involved in spinocerebellar ataxia type 6 (SCA6) is a small CAG expansion in the alpha-1A subunit of the voltage-dependent calcium channel gene. We looked for this mutation in 91 families with autosomal-dominant cerebellar ataxias and found that SCA6 is a minor locus in our series (2%) and is rare in France (1%). Furthermore, we did not detect the SCA6 mutation on 146 sporadic cases with isolated cerebellar ataxia or olivopontocerebellar atrophy. The normal and expanded alleles ranged from 4 to 15 and 22 to 28 CAG repeats, respectively, and age at onset was correlated to CAG repeat length (r = -0.87). In contrast with other SCA, the expanded allele was stable during transmission. Clinically, SCA6 patients (n = 12) presented with moderate to severe cerebellar ataxia with a lower frequency of associated signs compared with other SCA and a mean age at onset of 45 +/- 14 years (range, 24 to 67). MRI showed extensive cerebellar atrophy but not of the brainstem or cerebral cortex.


Mesoporous Poly(melamine-co-formaldehyde) Particles for Efficient and Selective Phosphate and Sulfate Removal.
Due to the existence-threatening risk to aquatic life and entire ecosystems, the removal of oxyanions such as sulfate and phosphate from anthropogenic wastewaters, such as municipal effluents and acid mine drainage, is inevitable. Furthermore, phosphorus is an indispensable resource for worldwide plant fertilization, which cannot be replaced by any other substance. This raises phosphate to one of the most important mineral resources worldwide. Thus, efficient recovery of phosphate is essential for ecosystems and the economy. To face the harsh acidic conditions, such as for acid mine drainage, an adsorber material with a high chemical resistivity is beneficial. Poly(melamine-co-formaldehyde) (PMF) sustains these conditions whilst its very high amount of nitrogen functionalities (up to 53.7 wt.%) act as efficient adsorption sides. To increase adsorption capacities, PMF was synthesized in the form of mesoporous particles using a hard-templating approach yielding specific surface areas up to 409 m2/g. Different amounts of silica nanospheres were utilized as template and evaluated for the adsorption of sulfate and phosphate ions. The adsorption isotherms were validated by the Langmuir model. Due to their properties, the PMF particles possessed outperforming maximum adsorption capacities of 341 and 251 mg/g for phosphate and sulfate, respectively. Furthermore, selective adsorption of sulfate from mixed solutions of phosphate and sulfate was found for silica/PMF hybrid particles.


Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes.
In this study, we performed high-resolution array comparative genomic hybridization with an array of 4153 bacterial artificial chromosome clones to assess copy number changes in 44 archival breast cancers. The tumors were flow sorted to exclude non-tumor DNA and increase our ability to detect gene copy number changes. In these tumors, losses were more frequent than gains, and gains in 1q and loss in 16q were the most frequent alterations. We compared gene copy number changes in the tumors based on histologic subtype and estrogen receptor (ER) status, i.e., ER-negative infiltrating ductal carcinoma, ER-positive infiltrating ductal carcinoma, and ER-positive infiltrating lobular carcinoma. We observed a consistent association between loss in regions of 5q and ER-negative infiltrating ductal carcinoma, as well as more frequent loss in 4p16, 8p23, 8p21, 10q25, and 17p11.2 in ER-negative infiltrating ductal carcinoma compared with ER-positive infiltrating ductal carcinoma (adjusted P values < or = 0.05). We also observed high-level amplifications in ER-negative infiltrating ductal carcinoma in regions of 8q24 and 17q12 encompassing the c-myc and c-erbB-2 genes and apparent homozygous deletions in 3p21, 5q33, 8p23, 8p21, 9q34, 16q24, and 19q13. ER-positive infiltrating ductal carcinoma showed a higher frequency of gain in 16p13 and loss in 16q21 than ER-negative infiltrating ductal carcinoma. Correlation analysis highlighted regions of change commonly seen together in ER-negative infiltrating ductal carcinoma. ER-positive infiltrating lobular carcinoma differed from ER-positive infiltrating ductal carcinoma in the frequency of gain in 1q and loss in 11q and showed high-level amplifications in 1q32, 8p23, 11q13, and 11q14. These results indicate that array comparative genomic hybridization can identify significant differences in the genomic alterations between subtypes of breast cancer.


Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study.
Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were high-functioning subjects. The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development.


Testing the constant-volume hypothesis by magnetic resonance imaging of Mytilus galloprovincialis heart.
The constant-volume (CV) hypothesis was tested using the Mytilus galloprovincialis heart under two conditions. The volume of the ventricle, auricles and pericardium, and the flow in the heart and adjacent vessels were measured by magnetic resonance imaging. In synthetic seawater at 23°C (immersed condition), the end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) were 50%, 21% and 29% of the heart volume, respectively, and the auricle volume (VA) was maximized at end-systole. Assuming a constant volume of the heart, venous return to the auricles (IV) was constant, and out-flow from the pericardium to the kidney (IPK) was 2/3 of SV. During aerial exposure (emersed condition), EDV, ESV and SV decreased to 33%, 22% and 11%, respectively. VA was maximized at end-diastole and associated with the decrease of systolic IV to 1/2 of diastolic IV, while IPK remained at 80% of the immersed condition. Based on these results--in addition to two postulates of the CV hypothesis: (1) the total volume of the heart is always the same, and (2) ventricle contraction causes a decrease in pressure in the pericardium--we modified two postulates: (3) the low pericardial pressure maintains venous return from the anterior oblique vein to the auricle, and (4) the pressure difference between the auricle and the pericardium drives haemolymph filtration through the auricle walls. We also added a new postulate: (5) dilatation of the ventricle is associated with the haemolymph output to the kidney via the renopericardial canals.


Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.
Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance.


Insights into an intriguing gas sorption mechanism in a polar metal-organic framework with open-metal sites and narrow channels.
Simulations of H2 and CO2 sorption were performed in the metal-organic framework (MOF), [Cu(Me-4py-trz-ia)]. This MOF was recently shown experimentally to exhibit high uptake for H2 and CO2 sorption and this was reproduced and elucidated through the simulations performed herein. Consistent with experiment, the theoretical isosteric heat of adsorption, Q(st), values were nearly constant across all loadings for both sorbates. The simulations revealed that sorption directly onto the open-metal sites was not observed in this MOF, ostensibly a consequence of the low partial positive charges of the Cu(2+) ions as determined through electronic structure calculations. Sorption was primarily observed between adjacent carboxylate oxygen atoms (site 1) and between nearby methyl groups (site 2) of the organic linkers. In addition, saturation of the most energetically favorable sites (site 1) is possible only after filling a nearby site (site 2) first due to the MOF topology. This suggests that the lack of dependence on loading for the Q(st) is due to the concurrent filling of sites 1 and 2, leading to an observed average Q(st) value.


Preliminary observations on the training of Burmese elephants using xylazine.
A traditional elephant training method was chosen to be modified by the use of xylazine as a sedative and muscle relaxant. Three elephant calves with different degrees of tameness were trained using xylazine. The drug was helpful in the training process. Xylazine made restraint of the elephants much easier and safer. During training, repeated doses of xylazine were used to prevent beatings, the wounds worsening and to pacify the elephants. The tamest elephant calf was punished less and took less time to be trained than the others. It is important to play with elephant calves to win their acceptance of man. A tame calf still needs training to learn about fettering, walking, sitting, etc. Elephants need to be considered man's working companions, and deserve sympathy and humane treatment.


Is the Mitochondrial Function of Keloid Fibroblasts Affected by Cytoglobin?
A keloid is a benign skin tumour characterised by excessive proliferation of fibroblasts, a process that requires a sufficient amount of energy. The energy needs are associated with adequate oxygen (O2) flow and well-functioning mitochondria. It is known that cytoglobin (CYGB) has a function in O2 distribution. The aim of the present study was to explore whether the inhibition of CYGB expression caused impaired mitochondrial function of keloid fibroblasts. An in vitro study was conducted on a keloid fibroblast derived from our previous study. The study was carried out in the laboratory of the Biochemistry & Molecular Biology Department, Faculty of Medicine, Universitas Indonesia (FMUI), from July to December 2018. CYGB expression was inhibited by small interfering ribonucleic acid (siRNA) and CYGB. Analysis of mitochondrial function was observed through peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a mitochondrial biogenesis marker and the activity of the succinate dehydrogenase (SDH) enzyme in mitochondria. The CYGB gene and protein were downregulated after treatment with CYGB siRNA. Inhibition of CYGB expression with siRNA also tended to decrease the levels of PGC-1α messenger ribonucleic acid (mRNA) and protein, as well as SDH enzyme activity. Inhibition of CYGB expression with siRNA tended to decrease mitochondrial biogenesis and function. This may be useful for understanding the excessive proliferation of fibroblasts in keloids and for development of treatment for keloids.


Fitness alters the associations of BMI and waist circumference with total and abdominal fat.
We tested the following hypotheses in black and white men and women: 1) for a given BMI or waist circumference (WC), individuals with moderate cardiorespiratory fitness (CRF) have lower amounts of total fat mass and abdominal subcutaneous and visceral fat compared with individuals with low CRF; and 2) exercise training is associated with significant reductions in total adiposity and abdominal fat independent of changes in BMI or WC. The sample included 366 sedentary male (111 blacks and 255 whites) and 462 sedentary female (203 blacks and 259 whites) participants in the HERITAGE Family Study. The relationships between BMI and WC with total fat mass (determined by underwater weighing) and abdominal subcutaneous and visceral fat (determined by computed tomography) were compared in subjects with low (lower 50%) and moderate (upper 50%) CRF. The effects of a 20-week aerobic exercise training program on changes in these adiposity variables were examined in 86% of the subjects. Individuals with moderate CRF had lower levels of total fat mass and abdominal subcutaneous and visceral fat than individuals with low CRF for a given BMI or WC value. The 20-week aerobic exercise program was associated with significant reductions in total adiposity and abdominal fat, even after controlling for reductions in BMI and WC. With few exceptions, these observations were true for both men and women and blacks and whites. These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.


Probing the structure and function of locus coeruleus projections to CNS motor centers.
The brainstem nucleus locus coeruleus (LC) sends projections to the forebrain, brainstem, cerebellum and spinal cord and is a source of the neurotransmitter norepinephrine (NE) in these areas. For more than 50 years, LC was considered to be homogeneous in structure and function such that NE would be released uniformly and act simultaneously on the cells and circuits that receive LC projections. However, recent studies have provided evidence that LC is modular in design, with segregated output channels and the potential for differential release and action of NE in its projection fields. These new findings have prompted a radical shift in our thinking about LC operations and demand revision of theoretical constructs regarding impact of the LC-NE system on behavioral outcomes in health and disease. Within this context, a major gap in our knowledge is the relationship between the LC-NE system and CNS motor control centers. While we know much about the organization of the LC-NE system with respect to sensory and cognitive circuitries and the impact of LC output on sensory guided behaviors and executive function, much less is known about the role of the LC-NE pathway in motor network operations and movement control. As a starting point for closing this gap in understanding, we propose using an intersectional recombinase-based viral-genetic strategy TrAC (Tracing Axon Collaterals) as well as established ex vivo electrophysiological assays to characterize efferent connectivity and physiological attributes of mouse LC-motor network projection neurons. The novel hypothesis to be tested is that LC cells with projections to CNS motor centers are scattered throughout the rostral-caudal extent of the nucleus but collectively display a common set of electrophysiological properties. Additionally, we expect to find these LC projection neurons maintain an organized network of axon collaterals capable of supporting selective, synchronous release of NE in motor circuitries for the purpose of coordinately regulating operations across networks that are responsible for balance and movement dynamics. Investigation of this hypothesis will advance our knowledge of the role of the LC-NE system in motor control and provide a basis for treating movement disorders resulting from disease, injury, or normal aging.


The chicken NKX2.8 homeobox gene: A novel member of the NK-2 gene family.
We have isolated the chicken homeobox gene NKX2.8, which represents a novel member of the NK-2 gene family. Besides the homeodomain, the NKX2.8 protein contains two other conserved sequences, a TN and an NK2 domain. NKX2.8 is expressed in the ventral foregut, the developing heart, in the epithelial layers of the branchial arches and in the dorsal mesocardium. Thus, its expression overlaps partially, but also differs significantly from another chicken tinman orthologue, the NKX2.5 gene. It is suggestive that NKX2.8 and NKX2.5 play a cooperative role in early heart development.


Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells.
Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers-disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)-were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patients.


Effects of sodium hyaluronate and triamcinolone acetonide on glucosaminoglycan metabolism in equine articular chondrocytes treated with interleukin-1.
OBJECTIVE-To determine whether the effects of a high-molecular-weight sodium hyaluronate alone or in combination with triamcinolone acetonide can mitigate chondrocyte glyocosaminoglycan (GAG) catabolism caused by interleukin (IL)-1 administration. SAMPLE POPULATION-Chondrocytes collected from metacarpophalangeal joints of 10 horses euthanized for reasons unrelated to joint disease. PROCEDURES-Chondrocyte pellets were treated with medium (negative control), medium containing IL-1 only (positive control), or medium containing IL-1 with hyaluronic acid only (0.5 or 2.0 mg/mL), triamcinolone acetonide only (0.06 or 0.6 mg/mL), or hyaluronic acid (0.5 or 2.0 mg/mL) and triamcinolone acetonide (0.06 or 0.6 mg/mL) in combination. Chondrocyte pellets were assayed for newly synthesized GAG, total GAG content, total DNA content, and mRNA for collagen type II, aggrecan, and cyclooxygenase (COX)-2. RESULTS-High-concentration hyaluronic acid increased GAG synthesis, whereas high-concentration triamcinolone acetonide decreased loss of GAG into the medium. High concentrations of hyaluronic acid and triamcinolone acetonide increased total GAG content. There was no change in DNA content with either treatment. Triamcinolone acetonide reduced COX-2 mRNA as well as aggrecan and collagen type II expression. Treatment with hyaluronic acid had no effect on mRNA for COX-2, aggrecan, or collagen type II. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that high concentrations of hyaluronic acid or triamcinolone acetonide alone or in combination mitigated effects of IL-1 administration on GAG catabolism of equine chondrocytes.


Genome-wide identification of small heat-shock protein (HSP20) gene family in grape and expression profile during berry development.
Studies have shown that HSP20 (heat-shock protein 20) genes play important roles in regulating plant growth, development, and stress response. However, the grape HSP20 gene family has not been well studied. A total of 48 VvHSP20 genes were identified from the grape genome, which were divided into 11 subfamilies (CI, CII, CIII, CV, CVI, CVII, MI, MII, ER, CP and PX/Po) based on a phylogenetic analysis and subcellular localization. Further structural analysis showed that most of the VvHSP20 genes (93.8%) had no intron or only one intron, while genes that clustered together based on a phylogenetic tree had similar motifs and evolutionarily conserved structures. The HSP20s share a conservedα-crystalline domain (ACD) and the different components of the ACD domain suggest the functional diversity of VvHSP20s. In addition, the 48 VvHSP20 genes were distributed on 12 grape chromosomes and the majority of VvHSP20 genes were located at the proximal or distal ends of chromosomes. Chromosome mapping indicated that four groups of VvHSP20 genes were identified as tandem duplication genes. Phytohormone responsive, abiotic and biotic stress-responsive, and plant development-related cis-elements were identified from the cis-regulatory elements analysis of VvHSP20s. The expression profiles of VvHSP20s genes (VvHSP20-1, 11, 14, 17, 18, 19, 20, 24, 25, 28, 31, 39, 42, and 43) were largely similar between RNA-Seq and qRT-PCR analysis after hydrogen peroxide (H2O2) treatment. The results showed that most VvHSP20s were down-regulated by H2O2 treatment during fruit development. VvHSP20s genes were indeed found to be involved in the grape berry development and differences in their transcriptional levels may be the result of functional differentiation during evolution. Our results provide valuable information on the evolutionary relationship of genes in the VvHSP20 family, which is useful for future studies on the functional characteristics of VvHSP20 genes in grape.


Could Artificial Intelligence/Machine Learning and Inclusion of Diet-Gut Microbiome Interactions Improve Disease Risk Prediction? Case Study: Coronary Artery Disease.
Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems. Therefore, timely and precise identification of people at high risk of CAD is urgently required. Most current CAD risk prediction approaches are based on a small number of traditional risk factors (age, sex, diabetes, LDL and HDL cholesterol, smoking, systolic blood pressure) and are incompletely predictive across all patient groups, as CAD is a multi-factorial disease with complex etiology, considered to be driven by both genetic, as well as numerous environmental/lifestyle factors. Diet is one of the modifiable factors for improving lifestyle and disease prevention. However, the current rise in obesity, type 2 diabetes (T2D) and CVD/CAD indicates that the "one-size-fits-all" approach may not be efficient, due to significant variation in inter-individual responses. Recently, the gut microbiome has emerged as a potential and previously under-explored contributor to these variations. Hence, efficient integration of dietary and gut microbiome information alongside with genetic variations and clinical data holds a great promise to improve CAD risk prediction. Nevertheless, the highly complex nature of meals combined with the huge inter-individual variability of the gut microbiome poses several Big Data analytics challenges in modeling diet-gut microbiota interactions and integrating these within CAD risk prediction approaches for the development of personalized decision support systems (DSS). In this regard, the recent re-emergence of Artificial Intelligence (AI) / Machine Learning (ML) is opening intriguing perspectives, as these approaches are able to capture large and complex matrices of data, incorporating their interactions and identifying both linear and non-linear relationships. In this Mini-Review, we consider (1) the most used AI/ML approaches and their different use cases for CAD risk prediction (2) modeling of the content, choice and impact of dietary factors on CAD risk; (3) classification of individuals by their gut microbiome composition into CAD cases vs. controls and (4) modeling of the diet-gut microbiome interactions and their impact on CAD risk. Finally, we provide an outlook for putting it all together for improved CAD risk predictions.


Socioeconomic status and the health of youth: a multilevel, multidomain approach to conceptualizing pathways.
Previous research has clearly established associations between low socioeconomic status (SES) and poor youth physical health outcomes. This article provides an overview of the main pathways through which low SES environments come to influence youth health. We focus on 2 prevalent chronic health problems in youth today, asthma and obesity. We review and propose a model that encompasses (a) multiple levels of influence, including the neighborhood, family and person level; (b) both social and physical domains in the environment; and finally (c) dynamic relationships between these factors. A synthesis of existing research and our proposed model draw attention to the notion of adverse physical and social exposures in youth's neighborhood environments altering family characteristics and youth psychosocial and behavioral profiles, thereby increasing youth's risk for health problems. We also note the importance of acknowledging reciprocal influences across levels and domains (e.g., between family and child) that create self-perpetuating patterns of influence that further accentuate the impact of these factors on youth health. Finally, we document that factors across levels can interact (e.g., environmental pollution levels with child stress) to create unique, synergistic effects on youth health. Our model stresses the importance of evaluating influences on youth's physical health not in isolation but in the context of the broader social and physical environments in which youth live. Understanding the complex relationships between the factors that link low SES to youth's long-term health trajectories is necessary for the creation and implementation of successful interventions and policies to ultimately reduce health disparities.


[Synchronizing role of serotonin in regulating hypophyseal gonadotropic function in female rats].
The influence of local serotonin injection into the preoptic region (PR) or arcuate nucleus-medial eminence (ARN-ME) on the hypophyseal and blood luteinizing hormone (LH) level was studied in experiments on intact female rats. It was shown that a serotonin inhibiting effect is limited by a definite time interval of the proestrus phase, whereas within other phases of the estrous cycle this monoamine exerts the opposite action on LH secretion (the morning time of diestrus 1 and diestrus 2 stages), testifying to the modulating serotonin role in the control of the hypophyseal gonadotropic function. In experiments on ovariectomized female rats, some of which were given estradiol benzoate, it was shown that serotonin injection into PR was accompanied by a decrease in the blood LH level only in ovariectomized rats, treated with estradiol, and did not change LH secretion in sterilized female rats. Serotonin stimulation of ARN-ME region lowered the LH level only in ovariectomized rats and did not influence LH secretion in the animals given estradiol.