Conversant or clueless? Chlamydia-related knowledge and practice of general practitioners in Western Australia.
A survey of Western Australia's general practitioners' (GPs') knowledge and practices relating to genital chlamydia infection was conducted in mid-2005, prior to a multi-media campaign which encouraged 15-24 year olds to seek chlamydia testing through their general practitioner (GP). The survey aimed to raise GPs' awareness of chlamydia in preparation for the campaign and to establish a baseline measure of their chlamydia-related knowledge and practices. All 2038 GPs registered on the Australian Medical Publishing Company's database as practising in Western Australia were sent a survey which covered clinical features of chlamydia, investigations, treatment and public health issues; 576 (29%) responded. Most GPs were aware of chlamydia being common in the 20-24 year old age group, but less than half were aware that it is common in 15-19 year olds. GPs missed many opportunities for chlamydia testing in patients likely to be at risk of STIs, largely because they thought the patient would be embarrassed. It is of concern that public health responsibilities in relation to chlamydia, ie notification and contact tracing, were not undertaken by all GPs. Australia is currently piloting chlamydia screening. For this to be successful, GPs will need to maintain current knowledge and clinical suspicion about chlamydia, and be comfortable in asking and receiving information about sexual behaviours. Only then will GPs have a significant impact on curbing Australia's ever-increasing rates of chlamydia.


The dynamic nexus: exploring the interplay of BMI before, during, and after pregnancy with Metabolic Syndrome (MetS) risk in Chinese lactating women.
The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016-2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P < 0.0001). There were significant positive correlations between BMI in each stage and ORs of MetS during lactation (P < 0.05). The best cut-off values for BMI in the four stages were 23.47, 30.49, 26.04 and 25.47 kg/m2. The non-linear spline test at BMI in 42 days postpartum, current and MetS in lactation was statistically significant (P non-linear = 0.0223, 0.0003). The mediation effect of all chains have to work through lactation BMI. The total indirect effect accounted for 80.95% of the total effect. The risk of MetS in lactating women is due to a high BMI base before pregnancy and postpartum. High BMI in all stages of pregnancy and postpartum were risk factors for MetS in lactation. BMI during lactation plays a key role in the risk of MetS.


Integrated analysis of incidence, progression, regression and disappearance probabilities.
Age-related maculopathy (ARM) is a leading cause of vision loss in people aged 65 or older. ARM is distinctive in that it is a disease which can transition through incidence, progression, regression and disappearance. The purpose of this study is to develop methodologies for studying the relationship of risk factors with different transition probabilities. Our framework for studying this relationship includes two different analytical approaches. In the first approach, one can define, model and estimate the relationship between each transition probability and risk factors separately. This approach is similar to constraining a population to a certain disease status at the baseline, and then analyzing the probability of the constrained population to develop a different status. While this approach is intuitive, one risks losing available information while at the same time running into the problem of insufficient sample size. The second approach specifies a transition model for analyzing such a disease. This model provides the conditional probability of a current disease status based upon a previous status, and can therefore jointly analyze all transition probabilities. Throughout the paper, an analysis to determine the birth cohort effect on ARM is used as an illustration. This study has found parallel separate and joint analyses to be more enlightening than any analysis in isolation. By implementing both approaches, one can obtain more reliable and more efficient results.


Change in quality of life among community-dwelling older adults: population-based longitudinal study.
This population-based study aimed to determine 5-year change in multidimensional QoL among community-dwelling older people, and to identify predictors of QoL change among demographic, socioeconomic, and health characteristics. Data of the 2011 and 2016 annual assessments of 1845 older men and women (age range 68-77 years) from the Lc65 + cohort study were used. QoL was assessed using a 28-item instrument yielding a QoL overall score and seven domain-specific QoL subscores. Additional ratings of QoL included a single item (excellent; very good; good; fair; poor), expected QoL in 1 year (better; worse; same as today), and retrospective assessment of QoL 5-year change (better; worse; same as 5 years ago). The predictors of 5-year change in the QoL score were assessed using linear regression, controlling for baseline QoL score. All prospective and retrospective indicators of QoL converged towards a slight deterioration over 5 years. QoL subscores significantly decreased in domains "Close entourage" (P = 0.004), "Social and cultural life" (P < 0.001), "Esteem and recognition" (P = 0.001), "Health and mobility" (P < 0.001), and "Autonomy" (P < 0.001), whereas "Material resources" (P = 0.345) and "Feeling of safety" (P = 0.380) remained stable. A stronger decrease in QoL was observed in the most vulnerable profiles at baseline in terms of demographic, socioeconomic, and health characteristics. Changes in depressive symptoms and in disability-either worsening or improving-predicted QoL change in the expected direction. Age-related decline in QoL may be limited through the prevention of disability and depressive symptoms, and more generally by devoting special attention to vulnerable profiles.


Why pens have rubbery grips.
The process by which human fingers gives rise to stable contacts with smooth, hard objects is surprisingly slow. Using high-resolution imaging, we found that, when pressed against glass, the actual contact made by finger pad ridges evolved over time following a first-order kinetics relationship. This evolution was the result of a two-stage coalescence process of microscopic junctions made between the keratin of the stratum corneum of the skin and the glass surface. This process was driven by the secretion of moisture from the sweat glands, since increased hydration in stratum corneum causes it to become softer. Saturation was typically reached within 20 s of loading the contact, regardless of the initial moisture state of the finger and of the normal force applied. Hence, the gross contact area, frequently used as a benchmark quantity in grip and perceptual studies, is a poor reflection of the actual contact mechanics that take place between human fingers and smooth, impermeable surfaces. In contrast, the formation of a steady-state contact area is almost instantaneous if the counter surface is soft relative to keratin in a dry state. It is for this reason that elastomers are commonly used to coat grip surfaces.


Compensatory signals associated with the activation of human GC 5' splice sites.
GC 5' splice sites (5'ss) are present in ∼1% of human introns, but factors promoting their efficient selection are poorly understood. Here, we describe a case of X-linked agammaglobulinemia resulting from a GC 5'ss activated by a mutation in BTK intron 3. This GC 5'ss was intrinsically weak, yet it was selected in >90% primary transcripts in the presence of a strong and intact natural GT counterpart. We show that efficient selection of this GC 5'ss required a high density of GAA/CAA-containing splicing enhancers in the exonized segment and was promoted by SR proteins 9G8, Tra2β and SC35. The GC 5'ss was efficiently inhibited by splice-switching oligonucleotides targeting either the GC 5'ss itself or the enhancer. Comprehensive analysis of natural GC-AG introns and previously reported pathogenic GC 5'ss showed that their efficient activation was facilitated by higher densities of splicing enhancers and lower densities of silencers than their GT 5'ss equivalents. Removal of the GC-AG introns was promoted to a minor extent by the splice-site strength of adjacent exons and inhibited by flanking Alu repeats, with the first downstream Alus located on average at a longer distance from the GC 5'ss than other transposable elements. These results provide new insights into the splicing code that governs selection of noncanonical splice sites.


Functional and emotional outcomes after transient ischemic attack: A 12-month prospective controlled cohort study.
Symptoms of transient ischemic attack are believed to fully resolve within 24 h of onset. Emerging evidence suggests that there may be prolonged functional and psychological impact, although studies have not been able to robustly identify whether these are the effect of transient ischemic attack or changes usually associated with ageing. We describe trajectories of disability and risk of anxiety and depression among patients seen at transient ischemic attack clinics over 12 months, compared to healthy controls. Thirty transient ischemic attack clinics across England participated. A total of 1320 participants were included: 373 diagnosed with transient ischemic attack, 186 with minor stroke, 310 with "possible transient ischemic attack," 213 with another condition mimicking a transient ischemic attack and 238 controls recruited from primary care providers. Participants completed questionnaires after diagnosis then after 3, 6 and 12 months. Outcomes were the Nottingham Extended Activities of Daily Living Scale and the Hospital Anxiety and Depression Scale. Mixed effects regression was used to estimate group differences and trajectories. At baseline, confirmed transient ischemic attack patients scored 1.31 HADS-Anxiety points (s.e. = 0.28; p < 0.001) , 0.51 HADS-Depression points (s.e. = 0.26; p = 0.056), and 2.6 NEADL points (s.e. = 1.1; p = 0.020) worse than controls. At 12 months, the deficits were 0.78 (s.e. = 0.30; p = 0.008), 0.97 (s.e. = 0.23; p < 0.001), and 0.96 (s.e. = 0.92; p = 0.294) respectively. Differences among patients diagnosed with minor stroke were like or worse than transient ischemic attack patients. Transient ischemic attack clinic patients may have functional and emotional impairments compared to the general population irrespective of final diagnosis. The presence of emotional symptoms or risk of developing anxiety or depression did not always fully recover and may increase.


Dendritic organization of the human spinal cord: the motoneurons.
The dendritic organization of motoneurons was analyzed with the Golgi stain and a morphometric method in the immature and adult human spinal cord. Each motoneuronal column was found to be characterized by a specific orientation of dendritic trees and by a distinct pattern of dendritic bundling. Ventromedial motoneurons have a pyramidal dendritic tree with numerous, short longitudinal branches and elongated dorsal branches. The latter form thick bundles oriented toward the ventral gray commissure. Longitudinal dendrites form a narrow-meshed dendritic plexus, containing abundant microbundles. Motoneurons of the ventromedial column have fewer primary dendrites and a lower ramification index than other motoneurons. Central motoneurons are predominantly oriented longitudinally. The meshes of the rostrocaudal dendritic plexus are looser and the microbundles are finer. Most transverse dendrites run laterally and participate in dendritic bundles which penetrate into the ventrolateral funiculus. The rostrocaudal dendritic domain of ventrolateral motoneurons is the largest dendritic domain of all spinal neurons. The longitudinal dendritic network contains fine microbundles and appears wide-meshed. Transverse dendrites form lateral or medial dendritic bundles depending upon the position of their perikaryon. Dorsolateral motoneurons differ from other motoneurons by their multipolar organization with a slight preponderance of dorsoventral dendritic spread. Rudimentary lateral dendrite bundles are restricted to marginal neurons. The longitudinal plexuses of motoneuronal dendrites and the verticotransverse dendrite bundles of the ventromedial column are well developed in the 26-28-week-old fetus. In contrast, the horizontotransverse dendrite bundles of central and ventrolateral motoneurons can only be recognized from 36 weeks on. The possible specific functions of the various types of dendrites bundles are examined and a laminar dendroarchitectonic schema of the human cord is proposed.


Profile and follow-up of patients with tuberculosis in a priority city in Brazil.
OBJECTIVE To analyze the cases of tuberculosis and the impact of direct follow-up on the assessment of treatment outcomes. METHODS This open prospective cohort study evaluated 504 cases of tuberculosis reported in the Sistema de Informação de Agravos de Notificação (SINAN - Notifiable Diseases Information System) in Juiz de Fora, MG, Southeastern Brazil, between 2008 and 2009. The incidence of treatment outcomes was compared between a group of patients diagnosed with tuberculosis and directly followed up by monthly consultations during return visits (287) and a patient group for which the information was indirectly collected (217) through the city's surveillance system. The Chi-square test was used to compare the percentages, with a significance level of 0.05. The relative risk (RR) was used to evaluate the differences in the incidence rate of each type of treatment outcome between the two groups. RESULTS Of the outcomes directly and indirectly evaluated, 18.5% and 3.2% corresponded to treatment default and 3.8% and 0.5% corresponded to treatment failure, respectively. The incidence of treatment default and failure was higher in the group with direct follow-up (p < 0.05) (RR = 5.72, 95%CI 2.65;12.34, and RR = 8.31, 95%CI 1.08;63.92, respectively). CONCLUSIONS A higher incidence of treatment default and failure was observed in the directly followed up group, and most of these cases were neglected by the disease reporting system. Therefore, effective measures are needed to improve the control of tuberculosis and data quality.


The growing cancer burden particularly among less developed countries requires local data to plan and evaluate cancer control measures. This article describes the development of a population-based cancer registry network (PBCRN) in Mexico that took place between 2017 and 2020 and present related data. The PBCRN, led by the National Cancer Institute (Incan), included nine registries representing 11.3% of the Mexican population. Definitions, coding, and operative processes were based on international standards. All cities were visited to set up local structure; personnel were hired by Incan and trained in basic cancer registration in Merida. A specific software was developed. Regular virtual meetings took place for data verification and quality control. Data collection included institutions of the public and private health system. Personnel included 34 registrars, nine local leaders, and 12 staff members at the Incan. A total of 13 517 cases were recorded between 2017-2020, 64% percent of them were among females. Breast cancer was the more frequent malignancy (23.3%), followed by digestive organs with (18.4%) and female genital cancers (13.5%). Childhood (0-14 years) and adolescents cancer represented 4.4% of the total new cancer cases. The network was suspended in 2020. The present effort lacked sustainability and data were only partial. However, the experience provides valuable insights to be considered for the renewed cancer registration efforts that are currently ongoing in Mexico.


Formation of an adenine-thymine photoadduct in the deoxydinucleoside monophosphate d(TpA) and in DNA.
A photoadduct is formed between the adenine (A) and thymine (T) bases of the deoxydinucleoside monophosphate d(TpA) when it is irradiated at 254 nanometers in aqueous solution. Treatment of the photoadduct with acid converts it specifically into a fluorescent hydrolysis product, C7H7N3O, incorporating the position-8 carbon of adenine and the methyl group of thymine. Isolation of the fluorescent hydrolysis product from acid hydrolyzates of oligo- and polydeoxyribonucleotides has shown that the photoadduct is formed by ultraviolet irradiation of d(pTpA), d(TpApT), d(TpApTpA), poly(dA-dT), and both single- and double-stranded DNA.


Use of iron(VI) and iron(V) in water and wastewater treatment.
Fe(VI) (Fe(VI)O4(2-)) and Fe(V) (Fe(V)O4(3-)) have high oxidizing power, selectivity, and upon decomposition produce a non-toxic by-product, Fe(III), which makes them potential oxidants in water and wastewater treatment. Rates of oxidation increase with a decrease in pH and are related to protonation of Fe(VI)O4(2-) and Fe(V)O4(3-). Oxidation of sulfur- and nitrogen-containing pollutants by Fe(VI) can be accomplished in seconds to minutes with formation of non-hazardous products. Fe(VI) can easily oxidize the amino acid components of microcystins and is a suitable disinfectant for detoxifying toxins in water. The oxidation of pollutants and amino acids with Fe(V) is 3-5 orders of magnitude faster than with Fe(VI). The use of ionizing radiation and photocatalytic techniques in the presence of Fe(VI) results in Fe(V) formation and may have synergistic effects on the oxidation of pollutants and removal of toxins in water and wastewater. This paper summarizes the results of multi-functional properties of Fe(VI) and Fe(V) to treat water and wastewater.


Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives.
A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds 6, 7, 8 and 9 were the most active, with IC50 values comparable to or lower than that of chemotherapeutic agent amsacrine. 8 and 9 were especially effective in the A549 cell line (IC50 ≈ 6 μM), which is of special interest since amsacrine is not sufficiently active in lung cancer patients. Cell cycle analysis revealed that 7 and 9 caused G2/M block, amsacrine caused arrest in the S phase, while 6 and 8 induced apoptotic cell death independently of the cell cycle regulation. In comparison to amsacrine, 6, 7, 8, and 9 showed similar inhibitory potential towards topoisomerase II, whereas only 7 showed DNA intercalation properties. In contrast to amsacrine, 6, 7, 8 and 9 showed a lack of toxicity towards unstimulated normal human leucocytes.


Layered hydrazinium titanate: advanced reductive adsorbent and chemical toolkit for design of titanium dioxide nanomaterials.
LHT-9, a layered hydrazinium titanate with an interlayer spacing of ~9 Å, is a new nanohybrid compound combining the redox functionality of hydrazine, the ion-exchange properties of layered titanate, the large surface area of quasi-two-dimensional crystallites, surface Brønsted acidity, and the occurrence of surface titanyl bonds. LHT-9, ideally formulated as (N(2)H(5))(1/2)Ti(1.87)O(4), relates to a family of lepidocrocite-type titanates. It possesses a high uptake capacity of ~50 elements of the periodic table. Irreversibility of reductive adsorption allows LHT-9 to be used for cumulative extraction of reducible moieties (noble metals, chromate, mercury, etc.) from industrial solutions and wastewaters. Unlike sodium titanates that do not tolerate an acidic environment, LHT-9 is capable of uptake of transition metals and lanthanides at pH > 3. Adsorption products loaded with the desired elements retain their layered structures and can be used as precursors for tailored titanium dioxide nanomaterials. In this respect, the uptake of metal ions by LHT-9 can be considered as a method complementary to electrostatic self-assembly deposition (ESD) and layer-by-layer self-assembly (LBL) techniques. LHT-9 is readily synthesized in one step by a mild fluoride route involving hydrazine-induced hydrolysis of hexafluorotitanic acid under near-ambient conditions.


Leukocytes and the risk of ischemic diseases.
Predictive indexes for atherosclerotic risk are imperfect, suggesting that there are predictive factors not commonly considered. Such a factor may be the white blood cell (WBC) count. Epidemiologic studies have shown correlations between the WBC count and the risk of myocardial infarction and stroke. The risk of acute myocardial infarction is approximately four times as great in persons with WBC counts high in the normal range (greater than 9000/microL [9 X 10(9)/L]) as in persons with WBC counts low in the normal range (less than 6000/microL [6 X 10(9)/L]); only 50% to 65% of the excess risk of the high-count individuals is explainable by tobacco smoking (which covaries with WBC count). A high WBC count also predicts greater risk of reinfarction and of in-hospital death. Less rigorously studied, the constitutional neutropenia of Yemenite Jews appears to afford protection against atherosclerotic disease. Among WBC types, the strongest epidemiologic association has been with the neutrophil count. Such a predictive value of WBC count is plausible and satisfying, because WBCs make a major contribution to the rheologic properties of blood; alter adhesive properties under stress--including the stress of ischemia, enhancing their rheologic importance; and participate in endothelial injury, both acutely and chronically, by adhering to endothelium and damaging it with toxic oxygen compounds and proteolytic enzymes. Techniques newly developed or under development may allow us to refine the predictive value of the WBC count by combining it with measures of cell activation and/or activatability.


Sulphate as a xylem-borne chemical signal precedes the expression of ABA biosynthetic genes in maize roots.
Recent reports suggest that early sensing of soil water stress by plant roots and the concomitant reduction in stomatal conductance may not be mediated by root-sourced abscisic acid (ABA), but that other xylem-borne chemicals may be the primary stress signal(s). To gain more insight into the role of root-sourced ABA, the timing and location of the expression of genes for key enzymes involved in ABA biosynthesis in Zea mays roots was measured and a comprehensive analysis of root xylem sap constituents from the early to the later stages of water stress was conducted. Xylem sap and roots were sampled from plants at an early stage of water stress when only a reduction in leaf conductance was measured, as well as at later stages when leaf xylem pressure potential decreased. It was found that the majority of ABA biosynthetic genes examined were only significantly expressed in the elongation region of roots at a later stage of water stress. Apart from ABA, sulphate was the only xylem-borne chemical that consistently showed significantly higher concentrations from the early to the later stages of stress. Moreover, there was an interactive effect of ABA and sulphate in decreasing maize transpiration rate and Vicia faba stomatal aperture, as compared to ABA alone. The expression of a sulphate transporter gene was also analysed and it was found that it had increased in the elongation region of roots from the early to the later stages of water stress. Our results support the suggestion that in the early stage of water stress, increased levels of ABA in xylem sap may not be due to root biosynthesis, ABA glucose ester catabolism or pH-mediated redistribution, but may be due to shoot biosynthesis and translocation to the roots. The analysis of xylem sap mineral content and bioassays indicate that the anti-transpirant effect of the ABA reaching the stomata at the early stages of water stress may be enhanced by the increased concentrations of sulphate in the xylem which is also transported from the roots to the leaves.


Instances of erroneous DNA barcoding of metazoan invertebrates: Are universal cox1 gene primers too "universal"?
The cytochrome c oxidase subunit I (cox1) gene is the main mitochondrial molecular marker playing a pivotal role in phylogenetic research and is a crucial barcode sequence. Folmer's "universal" primers designed to amplify this gene in metazoan invertebrates allowed quick and easy barcode and phylogenetic analysis. On the other hand, the increase in the number of studies on barcoding leads to more frequent publishing of incorrect sequences, due to amplification of non-target taxa, and insufficient analysis of the obtained sequences. Consequently, some sequences deposited in genetic databases are incorrectly described as obtained from invertebrates, while being in fact bacterial sequences. In our study, in which we used Folmer's primers to amplify COI sequences of the crustacean fairy shrimp Branchipus schaefferi (Fischer 1834), we also obtained COI sequences of microbial contaminants from Aeromonas sp. However, when we searched the GenBank database for sequences closely matching these contaminations we found entries described as representatives of Gastrotricha and Mollusca. When these entries were compared with other sequences bearing the same names in the database, the genetic distance between the incorrect and correct sequences amplified from the same species was c.a. 65%. Although the responsibility for the correct molecular identification of species rests on researchers, the errors found in already published sequences data have not been re-evaluated so far. On the basis of the standard sampling technique we have estimated with 95% probability that the chances of finding incorrectly described metazoan sequences in the GenBank depend on the systematic group, and variety from less than 1% (Mollusca and Arthropoda) up to 6.9% (Gastrotricha). Consequently, the increasing popularity of DNA barcoding and metabarcoding analysis may lead to overestimation of species diversity. Finally, the study also discusses the sources of the problems with amplification of non-target sequences.


Solitary rib lesions in bone scans of patients with breast carcinoma.
The aetiology of solitary rib lesions detected on bone scans was evaluated retrospectively. Seventy-five patients with breast carcinoma, and each with a solitary hot spot on a bone scan, were included in the study. The aetiology of the solitary rib lesions was determined by using all available clinical, laboratory and radiological data, and was clarified in 65 of the 75 patients, and not clarified in the remaining 10. In 17 of those 65 (26.1%), the aetiology of increased uptake was malignant; while in 48 of the 65 (73.8%) it was benign in origin. Linear lesions were mainly metastatic in origin (seven of nine, 77.7%) whereas focal lesions were mostly benign in origin (46 of 56, 82.19%). In the group of 16 hot spots located at the anterior rib end, 14 (87.5%) were benign, and two (12.5%) were malignant in origin. The relation between mastectomy side and the distribution of anterior and anterior rib end localization of hot spots was also investigated. Twenty-three of 32 rib lesions (71.8%) were on the same side as the surgery. In conclusion, solitary rib lesions on bone scans in patients with breast carcinoma are frequently benign in origin, especially if they are focal and located at the anterior rib end.


Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure.
Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value regarding the response to CRT. This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed with the use of gas chromatography-mass spectrometry and nuclear magnetic resonance. The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolomic profile. The succinate-glutamate ratio, an index of Krebs cycle activity, improved from 0.58 ± 0.13 to 2.84 ± 0.60 (P < .05). The glucose-palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96 ± 0.05 to 1.54 ± 0.09 (P < .01). Compared with nonresponders to CRT, responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P < .05). CRT improves the plasma metabolomic profile of HF patients, indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolomic profile as a potential biomarker for predicting CRT outcome.


Managing Prolactinomas during Pregnancy.
Prolactinomas are the most prevalent functional benign pituitary tumors due to a pituitary micro- or macroadenoma. The majority of patients presents with infertility and gonadal dysfunction. A dopamine agonist (DA) (bromocriptine or cabergoline) is the treatment of choice that can normalize prolactin levels, reduce tumor size, and restore ovulation and fertility. Cabergoline generally preferred over bromocriptine because of its higher efficacy and tolerability. Managing prolactinomas during pregnancy may be challenging. During pregnancy, the pituitary gland undergoes global hyperplasia due to a progressive increase in serum estrogens level that may lead to increase of the tumor volume with potential mass effect and visual loss. The risk of tumor enlargement may occur in 3% of those with microadenomas, 32% in those with macroadenomas that were not previously operated on, and 4.8% of those with macroadenomas with prior ablative treatment. Though both drugs appear to be safe during pregnancy, the data on fetal exposure to DAs during pregnancy have been reported with bromocriptine far exceeds that of cabergoline with no association of increased risk of pregnancy loss and premature delivery. It is advisable to stop the use of DAs immediately once pregnancy is confirmed, except in the case of women with invasive macroprolactinomas or pressure symptoms. This review outlines the therapeutic approach to prolactinoma during pregnancy, with emphasis on the safety of available DA therapy.


Alleles at the PRH1 locus coding for the human salivary-acidic proline-rich proteins Pa, Db, and PIF.
We cloned and sequenced the entire exon and intron structures of Db and Pa genetic determinants at the PRH1 locus. Their derived amino acid sequences and that previously determined for the PIF protein completely explain the electrophoretic phenotypes of the acidic proline-rich proteins (PRPs) Pa, Db, and PIF. Thus, the Cys substitution near Arg 106 in the Pa protein sterically interferes with proteolytic cutting at Arg 106 and accounts for the single-banded phenotype. In contrast, the Db and PIF proteins are proteolytically cut at Arg 106 and show a double-banded phenotype. The Db protein has an extra 21-amino acid repeat that accounts for its larger size compared with the equal sized Pa monomer and PIF proteins. Several amino acid substitutions account for the charge and mobility differences of the Pa, Db, and PIF proteins in isoelectric-focusing gels. These DNA/protein correlations, as well as the extremely similar genomic-DNA sequences that differ by less than 1%, establish that Pa, Db, and PIF are alleles at the PRH1 locus. On the basis of the DNA sequences, we conclude that Db and Pa alleles diverged more recently from a common precursor than did the PIF allele from its precursor.


Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons.
The effect of 5-HT on activity of noradrenergic locus coeruleus (LC) neurons was studied using microiontophoretic and micropressure drug application in anesthetized rats. 5-HT had no consistent effect on LC spontaneous discharge, eliciting a modest decrease overall. However, 5-HT reliably attenuated responses of LC neurons to excitatory amino acids (EAAs), one of the major classes of transmitters in afferents to these neurons. This effect was specific for EAA responses because it occurred for glutamate and kainate but not for ACh. In contrast, iontophoretic norepinephrine (NE) selectively attenuated spontaneous activity but not responses evoked by either glutamate or ACh. The responsiveness of LC neurons to EAAs as quantified by a response-contrast measure (evoked excitation/basal activity) was markedly reduced by 5-HT, but was increased by NE. For ACh, such responsiveness of LC cells was not changed by 5-HT, but was increased by NE. The effects of 5-HT were prevented and reversed by iontophoretically applied antagonists of 5-HT receptors, methysergide and methiothepin. Thus, 5-HT appears to selectively interact with EAA responses of LC neurons, acting as a filter to attenuate LC activity linked to its major EAA inputs while allowing other channels afferent to the LC (e.g., those utilizing ACh) to be expressed.


Cholinergic nerve function in monkey ciliary arteries innervated by nitroxidergic nerve.
We sought to determine the control of ciliary arterial tone by neurogenic acetylcholine (ACh) acting directly on smooth muscle and in conjunction with vasodilator nerves. Isolated posterior ciliary arteries from monkeys responded to ACh (10(-8)-10(-5) M) with dose-related contractions, which were endothelium independent. The response was not affected by cyclooxygenase inhibitors but was abolished by atropine. Relaxations induced at 10(-4) M ACh in the atropine-treated arterial strips were abolished by hexamethonium and NG-nitro-L-arginine (L-NNA), and L-arginine (L-Arg) reversed the response suppressed by L-NNA. Similar results were also obtained on the nicotine (10(-4) M)-induced relaxation. Contractions due to transmural electrical stimulation in the endothelium-denuded strips treated with L-NNA were potentiated by physostigmine and depressed by atropine; the remaining contraction in the presence of atropine was abolished by prazosin. Relaxations associated with electrical stimulation, sensitive to tetrodotoxin, were abolished or reversed to contractions by L-NNA and restored by L-Arg. Stimulation-induced relaxation was attenuated by exogenous ACh and physostigmine and was potentiated by atropine. ACh did not affect the relaxation caused by nitric oxide (NO). Nerve fibers and bundles containing NADPH diaphorase and acetylcholinesterase were histologically demonstrated in the adventitia of ciliary arteries. We conclude that 1) endogenous and exogenous ACh contracts monkey ciliary arteries by acting on muscarinic receptors in smooth muscle cell membranes, 2) vasodilatation elicited by nerve stimulation with electrical pulses or nicotine is mediated by NO synthesized from L-Arg, 3) neurogenic ACh seems to interfere with the nitroxidergic nerve function by acting on prejunctional muscarinic receptors, and 4) high concentrations of ACh stimulate nicotinic receptors in vasodilator nerve terminals and promote the synthesis and/or release of NO.


Clinical experience of intraorbital optic nerve sheath meningioma--report of eight cases.
Eight cases of primary optic nerve sheath meningioma were treated between 1980 and 1988. Five were females aged 37-61 years. The other three were two boys, one with neurofibromatosis, and an old male aged 71 years. They were first seen by the ophthalmologist with complaints of unilateral progressive visual loss or proptosis. Although blindness of the affected eye mainly occurred between 1 month and 3 years after the initial symptoms, the diagnosis tended to be made late in the adult cases. Intracranial extension was demonstrated in four of the six adult cases when contralateral visual loss or disturbance of consciousness presented. Larger intraorbital meningiomas were easily diagnosed by a combination of computed tomographic (CT) scanning, magnetic resonance (MR) imaging, and carotid angiography. MR imaging provided clear delineation of the optic nerve and its course through the tumor, and perioptic meningioma could be diagnosed. However, it was difficult to make a diagnosis without biopsy at the early stage, for example, when just the enlargement of the optic nerve was demonstrated by CT or MR imaging. Tumor removal was performed when blindness developed after definitive diagnosis by biopsy, intracranial extension was demonstrated, and advanced proptosis presented. The transcranial supraorbital approach or transcranial transorbital approach with resection of the supraorbital rim was used for these large intraorbital meningiomas. From our clinical experience, early diagnosis and early treatment should be emphasized.


A Systematic Review Protocol of the Barriers to Both Physical Activity and Obesity Counselling in the Secondary Care Setting as Reported by Healthcare Providers.
Physical activity and obesity counselling have both been gaining increasing interest in preventive health and treatment. However, most healthcare professionals do not provide advice on these topics nearly as often as they should. There are many reasons for this. Common barriers for the provision of brief advice on physical activity and obesity in both primary and secondary care are lack of time, motivation and knowledge. Systematic reviews have been published on the barriers of physical activity and obesity counselling in the primary care setting, but there is no published work on the barriers present in secondary care. This systematic review aims to assess all published data that discuss the barriers of physical activity and obesity counselling as noted by healthcare providers in secondary care. Four databases will be searched using the same search strategy, and the findings will be compiled using the COM-B model to explore the frequency of a reported barrier. This systematic review will be beneficial not only to practicing healthcare providers, but also the educational and managerial staff of secondary care facilities, as it may highlight the need for further training to fill gaps in the provision of preventive healthcare.


Domestic violence: ethical issues in the health care system.
Domestic violence is a highly prevalent event in the United States. Health providers frequently treat abused patients; however, many do not routinely assess for family violence or suspect it when the injuries seem fairly obvious. Because abused women feel stigmatized by the violence, they are hesitant to volunteer the abuse. In 1990, the Joint Commission on the Accreditation of Healthcare Organizations added requirements for emergency and ambulatory care services to develop and use protocols for the identification of violence among patients. This article addresses the ethical and legal dilemmas facing nurses that influence their assessment and intervention in family violence.


Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.
Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.


Biological fate of ingested lipid-based nanoparticles: current understanding and future directions.
In recent decades, lipid-based nanoparticles (LN) have received considerable attention as nanoscale delivery systems to improve oral bioavailability of poorly absorbed bioactive compounds for health promotion and disease prevention. However, scientific studies on the biological fate of orally administered LN are very limited and the molecular mechanisms by which they are absorbed through the intestinal lumen into the circulation remain unclear. This paper aims to provide an overview of the biological fate of orally administered LN by reviewing recent studies on both cell and animal models. In general, the biological fate of ingested LN in the gastrointestinal tract is primarily determined by their initial physicochemical characteristics (such as the particle size, surface properties, composition and structure), and their absorption mainly occurs within the small intestine. In particular, depending upon the composition, LN can be either digestible or indigestible, with two distinct biological fates for each type of LN. The detailed absorption mechanisms and uptake pathways at molecular, cellular and whole body levels for each type of LN are discussed in detail. Limitations of current research and our vision for future directions to study the biological fate of ingested LN are also provided in this critical review.


Dietary treatment of fatty liver: High dietary protein content has an antisteatotic and antiobesogenic effect in mice.
Few studies have assessed the effect of changing ratios of dietary macronutrients on fat accumulation in adipose tissue and organs such as the liver in a 3×n(n≥3) factorial design. We investigated the effects of 7 diets from a single manufacturer containing 11-58en% protein (casein), 0-81en% carbohydrates (CHO; sucrose, maltrodextrin-10 and corn starch), and 8-42en% fat (triheptanoin, olive oil or cocoa butter) in C57BL/6J mice, a good model for diet-induced obesity and fatty liver. The diets were fed for 3weeks to wild-type and hyperlipidemic male and female mice. Caloric intake was mainly determined by dietary fat. Body weight, liver lipid and cholesterol content, NFκB activation, and fat-pad size decreased only in mice fed a high-protein diet. A high dietary protein:CHO ratio reduced plasma FGF21 concentration, and increased liver PCK1 protein content and plasma triglyceride concentration. The dietary protein:CHO ratio determined hepatic expression of Pck1 and Ppargc1a in males, and Fgf21 in females, whereas the dietary CHO:fat ratio determined that of Fasn, Acaca1, and Scd1 in females. Hepatic glycogen content was determined by all three dietary components. Both hepatic PCK1 and plasma FGF21 correlated strongly and inversely with hepatic TG content, suggesting a key role for PCK1 and increased gluconeogenesis in resolving steatosis with a high-protein diet, with FGF21 expression reflecting declining cell stress. We propose that a diet containing ~35en% protein, 5-10en% fat, and 55-60en% carbohydrate will prevent fatty liver in mice without inducing side effects.


[Susceptibility to chemotherapeutic agents of Schistosoma mansoni isolates from patients treated with oxamniquine and praziquantel and not cured].
Ten inhabitants of Itaquara, Bahia, Brazil treated with oxamniquine and subsequently praziquantel were not cured. Schistosoma mansoni isolates derived from these patients were studied. Snails were infected with miracidia derived from the feces of these patients and the cercariae produced used to infect albino mice. The animals were then treated with a single oral dose of oxamniquine (25, 50 and 100mg/kg) or praziquantel (100, 200 and 400 mg/kg). The response to chemotherapy was significantly different in some of the isolates although it was not possible to characterize any of them as resistant. In addition, DNA analysis of the isolates by means of "Random Amplified Polymorphic DNA" indicated a low degree of variability as compared with a laboratory strain, LE. Thus, it was not possible to characterize these organisms at a genetic level as a distinct strain.


[Spontaneous activity of myenteric plexus neurons in the intact rabbit small intestine].
In rabbits intact myenteric plexus segments of the intestine, two types of neurons in regard to their electric discharges, were found: 1) units with single spontaneous spikes at the mean firing rate 2.3/sec and with interspike intervals from 140 to 900 msec; 2) units firing bursts of 3--12 spikes with interspike intervals of about 30 msec.


Aristotle: stratified causal discovery for omics data.
There has been a simultaneous increase in demand and accessibility across genomics, transcriptomics, proteomics and metabolomics data, known as omics data. This has encouraged widespread application of omics data in life sciences, from personalized medicine to the discovery of underlying pathophysiology of diseases. Causal analysis of omics data may provide important insight into the underlying biological mechanisms. Existing causal analysis methods yield promising results when identifying potential general causes of an observed outcome based on omics data. However, they may fail to discover the causes specific to a particular stratum of individuals and missing from others. To fill this gap, we introduce the problem of stratified causal discovery and propose a method, Aristotle, for solving it. Aristotle addresses the two challenges intrinsic to omics data: high dimensionality and hidden stratification. It employs existing biological knowledge and a state-of-the-art patient stratification method to tackle the above challenges and applies a quasi-experimental design method to each stratum to find stratum-specific potential causes. Evaluation based on synthetic data shows better performance for Aristotle in discovering true causes under different conditions compared to existing causal discovery methods. Experiments on a real dataset on Anthracycline Cardiotoxicity indicate that Aristotle's predictions are consistent with the existing literature. Moreover, Aristotle makes additional predictions that suggest further investigations.


Novel morphogenesis in Ax-3, a mutant strain of the cellular slime mould Dictyostelium discoideum.
The cellular slime mould Dictyostelium discoideum constructs a succession of characteristic structures (grexes) in the multicellular phase of its life cycle. Compared with the wild-type strain, NC-4, grexes of a mutant strain, Ax-3, exhibited a profound prolongation of the early mound stage of development and a premature and exaggerated tendency to construct short, broad and bulbous forms. The aberrant Ax-3 phenotype was partially corrected by increasing the temperature of development, decreasing the plating density, perfusing with fresh air, or by introducing 0.1 nm-formycin B or 3-deazaadenosine into the agar. Mixtures of NC-4 and Ax-3 formed hybrid grexes which often became transformed into toruses by spiral centrifugal movement of the cells. Under other conditions, hybrid mounds developed into binary grex structures, cylindrical columns on top of hemispherical mounds, each component of which completed the morphogenetic sequence independently. The narrow upper structure appeared to be composed primarily of NC-4 cells. These novel patterns of morphogenesis support our hypothesis that the shape of the organism is controlled by the specification of the circumference of loops of cells within the grex.


Nutrition of Children With Cancer in Brazil: A Systematic Review.
The objective of this systematic review was to describe nutrition-related publications on children and adolescents diagnosed with cancer in Brazil. The methodology followed that of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medline, LILACS (the Latin American & Caribbean Health Sciences Literature), and Embase were searched in April 2019, and data extraction and rating of methodologic study quality (according to the National Institutes of Health quality score assessment) were performed independently by reviewers. Twenty-seven studies met the inclusion criteria, reporting on 3,509 patients from 1994 to 2018. Most of the studies (74%) were of poor quality in methodology and reporting. Different cancer diagnoses were included in 52% of studies, whereas acute leukemia was the exclusive focus in 41%. The majority of the articles (70%) were from institutions in the Southeast Region of Brazil, mainly the state of São Paulo (74%); no publications were from the North Region of the country. Twelve studies addressed nutritional status and body composition, reporting an abundance of malnourished patients in the Brazilian population of children and adolescents with cancer. Six studies on micronutrients pointed to possible deficiencies in this population, with a yet unclear but promising role for supplementation during treatment. Evidence indicates that there is great interest in the impact of nutrition on childhood cancer treatment and clinical outcomes in Brazil. However, there is a need to focus on high-quality research, particularly with multicentric/national studies. This will help establish research priorities and better planned clinical interventions, adapted to each region of the country.


Ryanodine receptor point mutant E4032A reveals an allosteric interaction with ryanodine.
The ryanodine receptor (RyR) family of proteins constitutes a unique type of calcium channel that mediates Ca(2+) release from endoplasmic reticulum/sarcoplasmic reticulum stores. Ryanodine has been widely used to identify contributions made by the RyR to signaling in both muscle and nonmuscle cells. Ryanodine, through binding to high- and low-affinity sites, has been suggested to block the channel pore based on its ability to induce partial conductance states and irreversible inhibition. We examined the effect of ryanodine on an RyR type 1 (RyR1) point mutant (E4032A) that exhibits a severely compromised phenotype. When expressed in 1B5 (RyR null/dyspedic) myotubes, E4032A is relatively unresponsive to stimulation by cell membrane depolarization or RyR agonists, although the full-length protein is correctly targeted to junctions and interacts with dihydropyridine receptors (DHPRs) inducing their arrangement into tetrads. However, treatment of E4032A-expressing cells with 200-500 microM ryanodine, concentrations that rapidly activate and then inhibit wild-type (wt) RyR1, restores the responsiveness of E4032A-expressing myotubes to depolarization and RyR agonists. Moreover, the restored E4032A channels remain resistant to subsequent exposure to ryanodine. In single-channel studies, E4032A exhibits infrequent (channel-open probability, P(o) < 0.005) and brief (<250 micros) gating events and insensitivity to Ca(2+). Addition of ryanodine restores Ca(2+)-dependent channel activity exhibiting full, 3/4, 1/2, and 1/4 substates. This evidence suggests that, whereas ryanodine does not occlude the RyR pore, it does bind to sites that allosterically induce substantial conformational changes in the RyR. In the case of E4032A, these changes overcome unfavorable energy barriers introduced by the E4032A mutation to restore channel function.


Macromolecules on nano-outlets responding to electric field and pH for dual-mode drug delivery.
Macromolecules responsive to both electric field and pH are modified on the outlets of mesoporous silica nanospheres to form a novel dual-mode drug delivery system. Dual drug delivery modes are indicated by the release patterns obtained by simulating the body's gastric and intestinal fluid ex vivo. In a pH 1.4 release medium (simulated gastric fluid, SGF) without an alternating electric field, only 8.5% of the total payload is found to leach in 8 h, whereas 50.3% and 60.2% of the total payload are released in the same time period by elevating the pH of the release medium or applying an alternating electric field. The two stimuli signals can work independently or corporately to regulate the release kinetics to form a dual-mode drug delivery mechanism, which makes it more flexible for use in certain complicated situations.


Re-engineering methadone-Cost-effectiveness analysis of a patient-centered approach to methadone treatment.
Methadone maintenance treatment has proven effectiveness in the treatment of opioid use disorder, but significant barriers remain to treatment retention. In a randomized clinical trial, 300 newly-admitted methadone patients were randomly assigned to patient-centered methadone (PCM) v. treatment-as-usual (TAU). In PCM, participants were treated under revised program rules which permitted voluntary attendance at counseling and other changes focused on reducing involuntary discharge, and different staff roles which shifted disciplinary responsibility from the participant's counselor to the supervisor. The study found no significant differences in treatment retention, measures of opioid use, or other patient outcomes. This paper employs an activity-based costing approach to estimate the cost and cost-effectiveness of the two study conditions. We found that service use and costs were similar between PCM and TAU. Specifically, the average cost for PCM patients was $2396 compared to $2292 for standard methadone, while the average length of stay was 2 weeks longer for PCM patients. Incremental cost-effectiveness ratios (ICER) for self-reported heroin use, opioid positive urine screens, and meeting DSM-IV criteria for opioid dependence were mixed, with TAU achieving non-significantly better outcomes at lower treatment episode costs (i.e., economically dominating) for opioid positive urine screens. PCM patients reported slightly more days abstinent from heroin and fewer meet the opioid dependence criteria. While these differences are small and not statistically significant, we can still examine the cost-effectiveness implications. For days, abstinent from heroin, the ICER was $242 for one additional day of abstinence, however, there was notable uncertainty around this estimate. For opioid dependence criteria, the ICER was $1160 for a one-percentage point increase in the probability that a participant no longer met criteria for opioid dependence at follow-up. This economic study finds that patient choice concepts can be introduced into methadone treatment without significant impacts on costs or patient outcomes.


The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes.
Cardiac troponins are currently the markers of choice for diagnosis of acute myocardial infarction and risk assessment in acute coronary syndrome (ACS). With the introduction of the new high-sensitivity cardiac troponin T (hs-cTnT) assay, it has become possible to measure cTnT even in healthy subjects. However, how the hs-cTnT assay compares with the old cTnT assay for risk assessment in ACS is still unknown. Cardiac troponin T levels were measured with the new hs-cTnT assay and the old third-generation cTnT assay in serum samples collected 48 hours after randomization in 1,452 randomly selected ACS patients enrolled in the GUSTO-IV trial. During 30 days of follow-up, deaths and myocardial infarctions were recorded. At 12 months, only all-cause mortality was collected. The 16% of the patients that had levels higher than the 99th percentile cutoff for hs-cTnT but less than for cTnT had a similar 1-year mortality as the 60% that were positive for both assays (9.2% vs 10.7%, P = .52) and a higher 1-year mortality compared with the 24% that were negative for both assays (9.2% vs 2.6%, P = .001). For death or acute myocardial infarction at 30 days, the group that was positive only for hs-cTnT had an intermediate risk compared with the groups negative or positive for both assays (2.4%, 5.2%, and 8.7%; P < .001). The new hs-cTnT assay, compared with the old cTnT assay, identified more patients with myocardial damage and who were at an increased risk for new cardiac events.


Genetic diversity analysis of volunteer wheat based on SSR markers.
Volunteer wheat is a kind of wheat with weed characteristics, distributed widely in the main wheat-producing areas of China. It seriously damages the yield and quality of cultivated wheat. To study the genetic diversity and population structure within and between volunteer wheat and cultivated wheat (Triticum aestivum L.), 195 volunteer wheat seeds and 29 cultivated wheat seeds were analysed based on 16 pairs of highly-polymorphic microsatellite simple sequence repeats (SSR) primers and a microchip capillary electrophoresis (MCE) detection system. A total of 110 polymorphic alleles were detected by MCE with each pair of primers identifying 2-15 alleles with an average of 6.875 alleles. The polymorphic information content (PIC) ranged from 0.1089 to 0.7843, with an average of 0.5613. Genetic diversity arguments from 224 samples showed that the volunteer wheat was more varied than cultivated wheat. Based on the SSR information, the 224 samples were classified into seven groups, which corresponded to the volunteer wheats and cultivated wheats through principal coordinates analysis (PCA). We propose that the volunteer wheat and cultivated wheat have rather distant phylogenetic relationships. Hence, it is important for wheat breeding to study the genetic relationship between volunteer wheat and cultivated wheat.


Patent foramen ovale and migraine: a cross-sectional study from the Northern Manhattan Study (NOMAS).
A causal relationship between patent foramen ovale (PFO) and migraine has been hypothesized, and improvement of migraine frequency and severity after percutaneous PFO closure has been reported. Population-based data on the relationship between PFO and migraine are sparse, however. The objective of this study was to examine the association between PFO and migraine among stroke-free individuals in an urban, population-based, multiethnic cohort. As a part of the ongoing Northern Manhattan Study (NOMAS), 1101 stroke-free subjects were assessed for self-reported history of migraine. The presence of PFO was assessed by transthoracic echocardiography. The mean age of the group was 69+/-10 years; 58% were women. Forty-eight percent were Caribbean Hispanic, 24% were white, 26% were black, and 2% were another race/ethnicity. The prevalence of self-reported migraine was 16% (13% migraine with aura). The prevalence of PFO was 15%. Migraine was significantly more frequent among younger subjects, women, and Hispanics. The prevalence of PFO was not significantly different between subjects who had migraine (26/178, or 14.6%) and those who did not (138/923, or 15.0%; P=0.9). In an adjusted multivariate logistic regression model, the presence of PFO was not associated with increased prevalence of migraine (odds ratio 1.01, 95% confidence interval 0.63 to 1.61). Increasing age was associated with lower prevalence of migraine in both subjects with a PFO (odds ratio 0.94, 95% confidence interval 0.90 to 0.99 per year) and those without PFO (odds ratio 0.97, 95% confidence interval 0.95 to 0.99 per year). The observed lack of association between PFO and migraine (with or without aura) was not modified by diabetes mellitus, hypertension, cigarette smoking, or dyslipidemia. In this multiethnic, elderly, population-based cohort, PFO detected with transthoracic echocardiography and agitated saline was not associated with self-reported migraine. The causal relationship between PFO and migraine remains uncertain, and the role of PFO closure among unselected patients with migraine remains questionable.


[Indications for using trental in the initial manifestations of inadequate blood supply to the brain].
The action of trental was studied in 125 patients with initial manifestations of cerebral circulation insufficiency (CCI) secondary to vasomotor dystonia or atherosclerosis. Trental was used in the form of tablets (100 mg 3 times daily) for 60 days. To assess the therapeutic effect of trental, the authors analyzed the time-course of subjective manifestations, parameters of echopulsography of cerebral vessels and biomicroscopy of the conjunctiva, and the data of the total blood count and the rheological properties of the blood. In patients with initial manifestations of CCI trental decreased the cerebral vascular resistance and improved the venous outflow, reduced platelet adhesive and aggregation properties and diminished blood viscosity. It also elevated the spontaneous fibrinolytic activity of the blood. The advisability of selective administration of the drug for treating initial manifestations of CCI was confirmed.


[Impact of the city recreation and sports environment on health of its residents].
Recreation and sports environment is an essential part of the urban space, which is the most important factor in improving and maintaining health of the citizens, contributing to better mental health, cognitive functions, lower overall mortality, higher life expectancy, lower morbidity and mortality from cardiovascular diseases, prevalence of obesity and type 2 diabetes, better pregnancy and birth outcomes. Recreation and sports environment of the urban space includes the city's greenery, recreational areas, areas for physical activities and sports, and waterfront areas. This study uses a correlation analysis to analyze the impact of the city recreation and sports environment on health of the working and post-working population. The study was conducted in 2019 on the example of large and huge urban cities of the Moscow region populated with more than 125,000 people. Based on the correlation analysis results, the authors have demonstrated the impact of the overall set of all sports facilities, sports structures, flat sports structures, swimming pools, sports halls, and public green spaces in cities on health of the post-working population. The study has also shown the impact of swimming pools, the overall set of all types of sports facilities, sports structures, flat sports structures, sports halls, and public green spaces in cities on health of the working-age population. The authors come to the conclusion that development and ongoing support and maintenance of the city recreation and sports environment serve as an important objective of the city administrations, resulting in the improved physical activity of the citizens and lower morbidity among the urban population.


Identification of two fungicide degrading Pseudomonas species by gas chromatography of cellular fatty acids.
Microorganisms can be identified in many ways. Conventional methods rely on the expression of certain properties that are usually mediated directly by enzyme activity. Extension of this approach to include numerical identification or automated systems to analyze results often strengthens conclusions. Identification of bacterial species using morphological characters and biochemical tests is often difficult and time consuming. Immunodiagnostic and nucleotide hybridization techniques have improved sensitivity, specify, precision, and ease of testing. Chemotaxonomy is also precise and can result in the definition of highly discriminatory properties. Cellular Fatty Acids (CFA) analyses fall into this category. One of the most convenient methods for the identification of fatty acids in bacterial cells is by gas-liquid chromatography of their methyl esters prepared from phospholipids, total lipids, or other lipid fractions. Two bacterial strains from Bahar Yossof. Al-Fayiurn governorates, Egypt tentatively identified as a species of pseudomonas by virtue of its physiological and biochemical characteristics. Confirmation of this identification was carried out using fatty acids profile analysis.


DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons.
Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m6A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m6A-specific DNA methyltransferase 1 (N6amt1) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6. Rescuing the decrease in N6amt1 reversed the loss of m6A at the promoter for inwardly rectifying potassium channel subfamily J member 16 (Kcnj16), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m6A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m6A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m6A modification may be a potential new target for analgesic and treatment strategies.


Development and Progression of Non-Alcoholic Fatty Liver Disease: The Role of Advanced Glycation End Products.
Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the adult population and is now a major cause of liver disease-related premature illness and deaths in the world. Treatment is largely based on lifestyle modification, which is difficult to achieve in most patients. Progression of simple fatty liver or steatosis to its severe form non-alcoholic steatohepatitis (NASH) and liver fibrosis has been explained by a 'two-hit hypothesis'. Whilst simple steatosis is considered the first hit, its transformation to NASH may be driven by a second hit. Of several factors that constitute the second hit, advanced glycation end products (AGEs), which are formed when reducing-sugars react with proteins or lipids, have been implicated as major candidates that drive steatosis to NASH via the receptor for AGEs (RAGE). Both endogenous and processed food-derived (exogenous) AGEs can activate RAGE, mainly present on Kupffer cells and hepatic stellate cells, thus propagating NAFLD progression. This review focuses on the pathophysiology of NAFLD with special emphasis on the role of food-derived AGEs in NAFLD progression to NASH and liver fibrosis. Moreover, the effect of dietary manipulation to reduce AGE content in food or the therapies targeting AGE/RAGE pathway on disease progression is also discussed.


Ontogenetic changes in embryonic and brain gene expression in progeny produced from migratory and resident Oncorhynchus mykiss.
Little information has been gathered regarding the ontogenetic changes that contribute to differentiation between resident and migrant individuals, particularly before the onset of gross morphological and physiological changes in migratory individuals. The aim of this study was to evaluate gene expression during early development in Oncorhynchus mykiss populations with different life histories, in a tissue known to integrate environmental cues to regulate complex developmental processes and behaviours. We sampled offspring produced from migrant and resident parents, collecting whole embryos prior to the beginning of first feeding, and brain tissue at three additional time points over the first year of development. RNA sequencing for 32 individuals generated a reference transcriptome of 30 177 genes that passed count thresholds. Differential gene expression between migrant and resident offspring was observed for 1982 genes. The greatest number of differentially expressed genes occurred at 8 months of age, in the spring a full year before the obvious physiological transformation from stream-dwelling parr to sea water-adaptable smolts begins for migrant individuals. Sex and age exhibited considerable effects on differential gene expression between migrants and resident offspring. Differential gene expression was observed in genes previously associated with migration, but also in genes previously unassociated with early life history divergence. Pathway analysis revealed coordinated differential expression in genes related to phototransduction, which could modulate photoperiod responsiveness and variation in circadian rhythms. The role for early differentiation in light sensitivity and biological rhythms is particularly intriguing in understanding early brain processes involved in differentiation of migratory and resident life history types.


Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth.
Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that intratumoral AAV-mediated maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for maspin protein and apoptosis in LNCaP tumors showed that the percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-maspin-treated tumors compared with the control tumors. These therapeutic responses were highly correlated to persistent maspin expression in tumors, confirmed by Western blot analysis until at least day 56 after treatment. Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV-mediated prolonged maspin expression efficiently suppresses human prostate tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.


Children With Single-Sided Deafness Use Their Cochlear Implant.
To assess acceptance of a cochlear implant (CI) by children with single-sided deafness (SSD) as measured by duration of CI use across daily listening environments. Datalogs for 7 children aged 1.1 to 14.5 years (mean ± SD: 5.9 ± 5.9 years old), who had SSD and were implanted in their deaf ear, were anonymized and extracted from their CI processors. Data for all available follow-up clinical appointments were included, ranging from two to six visits. Measures calculated from each datalog included frequency and duration of time the coil disconnected from the internal device, average daily CI use, and both duration (hr/day) and percentage of CI use (% daily use) in different intensity ranges and environment types. Linear mixed effects regression analyses were used to evaluate the relationships between CI experience, daily CI use, frequency of coil-offs, and duration of coil-off time. Nonlinear regression analyses were used to evaluate CI use with age in different acoustic environments. Children with SSD used their CI on average 7.4 hr/day. Older children used their CI for longer periods of the day than younger children. Longitudinal data indicated consistent CI use from the date of CI activation. Frequency of coil-offs reduced with CI experience, but did not significantly contribute to hours of coil-off time. Children used their CI longest in environments that were moderately loud (50 to 70 dB A) and classified as containing speech-in-noise. Preschoolers tended to spend less time in quiet but more time in music than infants/toddlers and adolescents. Children with SSD consistently use their CI upon activation in a variety of environments commonly experienced by children. CI use in children with SSD resembles reported bilateral hearing aid use in children but is longer than reported hearing aid use in children with less severe unilateral hearing loss, suggesting that (1) the normal-hearing ear did not detract from consistent CI use; and (2) a greater asymmetry between ears presents a significant impairment that may facilitate device use to access bilateral sound.


Etiology and Pathophysiology of Tinnitus - A Systematic Review.
Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal sensory state remain poorly understood. To determine the evidence for different etiologies and pathophysiology of tinnitus identified by clinical diagnostic tests in the adult population. Systematic literature review. Review of data base using PRISMA guidelines: Google Scholar, Medline, Springer Link, Pubmed. In addition, manual reference search of identified papers. Randomized controlled trials, case control study, prospective cohort studies, and retrospective reviews of consecutive patients in which clear data were reported with respect to etiology and pathophysiology of tinnitus. Sixty seven articles met the inclusion criteria. The papers searched recent studies from 2004 to 2018 for different etiologies such as noise exposure, age, ototoxic drugs, hearing loss among patients with tinnitus. Multiple pathophysiology were identified, including inner ear pathology, auditory nerve synchronisation, central nervous system anomalies and limbic and autonomous nervous system problems. The group of papers evaluated tinnitus patients with specific diagnostic tests such as pure tone audiometry, Immitance audiometry, otoacoustic emission, Auditory brainstem response and diagnostic imaging of fMRI, MRI and PET study. The results indicate a high level of heterogeneity between the studies for all the assessed areas. These results support the need for greater stratification of the tinnitus population and the importance of a standardized Puretone audiometry with extended high frequency, OAE, ABR and diagnostic imaging (fMRI, MRI & PET) method to make comparisons between studies possible. Diagnostic imaging is an important useful method for identification of intracranial pathology that can present with tinnitus as a primary symptom. Establishment of a direct causal link between tinnitus and these etiologies and pathophysiology remains elusive.


Public experiences of mass casualty decontamination.
In this article, we analyze feedback from simulated casualties who took part in field exercises involving mass decontamination, to gain an understanding of how responder communication can affect people's experiences of and compliance with decontamination. We analyzed questionnaire data gathered from 402 volunteers using the framework approach, to provide an insight into the public's experiences of decontamination and how these experiences are shaped by the actions of emergency responders. Factors that affected casualties' experiences of the decontamination process included the need for greater practical information and better communication from responders, and the need for privacy. Results support previous findings from small-scale incidents that involved decontamination in showing that participants wanted better communication from responders during the process of decontamination, including more practical information, and that the failure of responders to communicate effectively with members of the public led to anxiety about the decontamination process. The similarity between the findings from the exercises described in this article and previous research into real incidents involving decontamination suggests that field exercises provide a useful way to examine the effect of responder communication strategies on the public's experiences of decontamination. Future exercises should examine in more detail the effect of various communication strategies on the public's experiences of decontamination. This will facilitate the development of evidence-based communication strategies intended to reduce anxiety about decontamination and increase compliance among members of the public during real-life incidents that involve mass decontamination.


Incompatibility on brassica stigmas is overcome by treating pollen with cycloheximide.
Pollen of Brassica exhibited strong self-incompatibility. It did not germinate on, adhere to, or extend into the stigmatic tissues of the female parent plant. In contrast, pollen that had been treated with cycloheximide germinated on and penetrated into self-stigmas to the same degree as untreated pollen placed on crossstigmas (compatible). Germ tubes from cycloheximide-treated pollen did not continue growth through stylar tissues and therefore were unable to effect fertilization.


Kidney injury molecule (KIM)-1 is associated with insulin resistance: results from two community-based studies of elderly individuals.
Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1. Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years). Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria. Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.


Modelling of shoulder and torso perception of effort in manual transfer tasks.
The aim of the present study was to develop statistical models of perceived effort at the shoulder and torso levels associated with manual load transfer tasks. The motions were directed from a home location toward one of twenty-two target shelves distributed in the right hemisphere. A total of 2149 ratings were obtained from 31 subjects for effort perception at the selected joints, using a ten-point modified Borg scale. Regression models, developed for the perception associated with each body part, included target locations (azimuth, height and distance), posture constraints (standing or sitting), task types (one or two handed transfer conditions), and demographic and anthropometric measures (stature, body weight, gender, and age) as parameters. The models provide a prediction of effort perception with adjusted r-square coefficients of 0.41 and 0.50 for the shoulder and torso, respectively. The results indicate that space and posture interact in a complex way to affect the rating of perceived effort, and are in agreement with the hypothesis that the 'sense of effort' is primarily associated with the efference copy of the descending motor command. Since a level of effort is not associated with a unique pattern of motor command, it is proposed that effort perception is likely to result from a summation of the components of the motor command. The models can be applied to optimize the spatial organization of the work environment in an attempt to reduce the risk of musculoskeletal injury.


Trochanteric entry femoral nails yield better femoral version and lower revision rates-A large cohort multivariate regression analysis.
Intramedullary nailing (IMN) has become the standard of care for the treatment of most femoral shaft fractures. Different IMN options include trochanteric and piriformis entry as well as retrograde nails, which may result in varying degrees of femoral rotation. The objective of this study was to analyze postoperative femoral version between three types of nails and to delineate any significant differences in femoral version (DFV) and revision rates. Over a 10-year period, 417 patients underwent IMN of a diaphyseal femur fracture (AO/OTA 32A-C). Of these patients, 316 met inclusion criteria and obtained postoperative computed tomography (CT) scanograms to calculate femoral version and were thus included in the study. In this study, our main outcome measure was the difference in femoral version (DFV) between the uninjured limb and the injured limb. The effect of the following variables on DFV and revision rates were determined via univariate, multivariate, and ordinal regression analyses: gender, age, BMI, ethnicity, mechanism of injury, operative side, open fracture, and table type/position. Statistical significance was set at p<0.05. A total of 316 patients were included. Piriformis entry nails made up the majority (n=141), followed by retrograde (n=108), then trochanteric entry nails (n=67). Univariate regression analysis revealed that a lower BMI was significantly associated with a lower DFV (p=0.006). Controlling for possible covariables, multivariate analysis yielded a significantly lower DFV for trochanteric entry nails than piriformis or retrograde nails (7.9±6.10 vs. 9.5±7.4 vs. 9.4±7.8°, p<0.05). Using revision as an endpoint, trochanteric entry nails also had a significantly lower revision rate, even when controlling for all other variables (p<0.05). Comparative, objective comparisons between DFV between different nails based on entry point revealed that trochanteric nails had a significantly lower DFV and a lower revision rate, even after regression analysis. However, this is not to state that the other nail types exhibited abnormal DFV. Translation to the clinical impact of a few degrees of DFV is also unknown. Future studies to more in-depth study the intricacies of femoral version may lead to improved technology in addition to potentially improved clinical outcomes.


Genomics of Klebsiella pneumoniae ST16 producing NDM-1, CTX-M-15, and OXA-232.
Genomic characterization of the internationally spread sequence type (ST) 16 carbapenem-resistant Klebsiella pneumoniae. The complete genomes of three carbapenem producing ST16 K. pneumoniae from Italian patients were analysed by single-nucleotide polymorphism-based phylogeny, core genome multilocus sequence typing, resistance, plasmid, and virulence content and compared with ten genomes of ST16 strains isolated in other countries. Plasmids carrying blaNDM-1 or blaOXA-232 carbapenemase genes were assembled and sequences were analysed. The internationally spread ST16 K. pneumoniae clone showed variability in terms of distribution of NDM-1 and OXA-232 type carbapenemases. In some ST16 strains, up to six plasmids can be simultaneously present in the same cell, including ColE-like plasmids carrying blaOXA-232 and IncF plasmids carrying blaNDM-1. The differences observed in plasmid, resistance, and virulence content and core genome suggested that there is not a unique, highly conserved ST16 clone, but instead different variants of this lineage circulate worldwide. The ST16 K. pneumoniae clone has spread worldwide and may become a high-risk clone.


Altered hepatic mRNA expression of apoptotic genes during dimethylnitrosamine exposure.
The role of TNFalpha in regulating apoptotic signaling was investigated during subacute, low-dose (5.0 mg/kg) dimethylnitrosamine (DMN)-induced hepatotoxicity. In TNFalpha receptor (TNFR) intact (wild-type, WT) mice following 4 and 7 DMN exposures, hepatic transcripts for TNFalpha and TNFR-1 were elevated as compared to vehicle controls. DMN hepatotoxicity in WT and TNFR-1/TNFR-2 double knockout (DKO) mice were then compared over a 7-d exposure period. Liver RNA was isolated to measure hepatic expression of TNFalpha/Fas-related genes and the Bcl-2 family of genes that impact apoptosis. Hepatic mRNA levels for Fas, the apoptosis-promoting gene Bax, and the anti-apoptotic gene, Bcl-X(L), were up regulated following 4 and 7 DMN exposures in both WT and TNFR DKO mice as compared to vehicle controls. Notably, hepatic transcript levels for Bax were higher in TNFR DKO mice treated with DMN compared to identically treated WT mice. However, we detected approximately equal DMN-induced apoptotic degradation of liver DNA following 1, 4, and 7 exposures in WT and TNFR DKO mice. Taken together, these data show DMN-induced hepatic TNFalpha expression and suggest that TNFR-1 signaling may be up regulated following 4 and 7 daily DMN exposures. However, TNFalpha is not required for apoptotic signaling at the mRNA transcript level within the liver and instead may actually decrease Bax production.


Intra-specific variation and allometry of the skull of Late Cretaceous side-necked turtle Bauruemys elegans (Pleurodira, Podocnemididae) and how to deal with morphometric data in fossil vertebrates.
Previous quantitative studies on Bauruemys elegans (Suárez, 1969) shell variation, as well as the taphonomic interpretation of its type locality, have suggested that all specimens collected in this locality may have belonged to the same population. We rely on this hypothesis in a morphometric study of the skull. Also, we tentatively assessed the eating preference habits differentiation that might be explained as due to ontogenetic changes. We carried out an ANOVA testing 29 linear measurements from 21 skulls of B. elegans taken by using a caliper and through images, using the ImageJ software. First, a Principal Components Analysis (PCA) was performed with 27 measurements (excluding total length and width characters; =raw data) in order to visualize the scatter plots based on the form variance only. Then, a second PCA was carried out using ratios of length and width of each original measurement to assess shape variation among individuals. Finally, original measurements were log-transformed to describe allometries over ontogeny. No statistical differences were found between caliper and ImageJ measurements. The first three PCs of the PCA with raw data comprised 70.2% of the variance. PC1 was related to size variation and all others related to shape variation. Two specimens plotted outside the 95% ellipse in PC1∼PC2 axes. The first three PCs of the PCA with ratios comprised 64% of the variance. When considering PC1∼PC2, all specimens plotted inside the 95% ellipse. In allometric analysis, five measurements were positively allometric, 19 were negatively allometric and three represented enantiometric allometry. Many bones of the posterior and the lateral emarginations lengthen due to increasing size, while jugal and the quadratojugal decrease in width. ImageJ is useful in replacing caliper since there was no statistical differences. Yet iterative imputation is more appropriate to deal with missing data in PCA. Some specimens show small differences in form and shape. Form differences were interpreted as occuring due to ontogeny, whereas shape differences are related to feeding changes during growth. Moreover, all outlier specimens are crushed and/or distorted, thus the form/shape differences may be partially due to taphonomy. The allometric lengthening of the parietal, quadrate, squamosal, maxilla, associated with the narrowing of jugal and quadratojugal may be related to changes in feeding habit between different stages of development. This change in shape might represent a progressive skull stretching and enlargement of posterior and lateral emargination during ontogeny, and consequently, the increment of the feeding-apparatus musculature. Smaller individuals may have fed on softer diet, whereas larger ones probably have had a harder diet, as seen in some living species of Podocnemis. We conclude that the skull variation might be related to differences in feeding habits over ontogeny in B. elegans.


[Factors affecting prognosis in childhood Guillain Barré syndrome].
Guillain Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis in children. The factors that come to bear on its prognosis have not been properly determined in Latin America. Our aim was to establish the clinical and electrophysiological indicators of GBS in a group of paediatric patients attended in a tertiary care hospital. Patients and methods. We conducted a prospective study involving 67 patients who were hospitalised in the Instituto de Ortopedia Infantil Roosevelt between 1999 and 2002 after having been diagnosed as suffering from GBS. The clinical and electrophysiological characteristics were evaluated during the first month of illness and a clinical follow up was carried out until the patients reached stage III on Hughes' functional disability scale. Initially, it was observed that the protracted plateau time, the quadriplegia on day 10 of the disease and the electrical non excitability demonstrated by means of neuroconduction studies were variables linked to a protracted recovery time. Patients with a protracted recovery time required respiratory assistance more often, but this association was not statistically significant. In the Kaplan Meier survival analysis and the Cox analysis employed to determine the effects of covariance, the presence of quadriplegia associated to electrical non excitability were identified as significant variables in nine patients who required a longer time to reach Hughes stage III (mean: 172.7 days, 95% confidence intervals: 143.51 202.05). Patients with excitable motor nerves (EMN) and without quadriplegia reached functional stage III more quickly (mean: 39.51 days, 95% confidence intervals: 25.79 53.24). Children with GBS who display EMN and quadriplegia on day 10 of the illness are the group with the poorest prognosis and have a very long motor recovery time.


[Comparative study of the use of sennoside A and B vs polyethylene glycol and electrolytes in anterograde preparation of the colon].
Compare effectiveness of antegrade bowel preparation by liquid diet, polyethylenglycol (PEG) and electrolytes solution plus sennosides A and B, vs. liquid diet plus sennosides A and B only. Preparation for colonoscopy with a balanced solution (PEG and electrolytes) has some physiological advantages. Nonetheless, drawbacks of such preparation include nasty flavor, large volumes and low availability in our country. A randomized, comparative, prospective, transversal and blind trial that included 200 patients scheduled for colonoscopy were randomly assigned (one hundred each group) to receive: group 1: liquid diet, sennosides A and B and a two litter of solution with PEG and electrolytes; and group 2: liquid diet plus sennosides A and B. Compliance, tolerance and effectiveness of both preparations were evaluated blindly. The results were assessed by Student's T test. The effectiveness of group 2 preparation proved superior (p < 0.05) to group 1. Tolerance and side effects were similar for both groups with no related complications.


EMD: an ensemble algorithm for discovering regulatory motifs in DNA sequences.
Understanding gene regulatory networks has become one of the central research problems in bioinformatics. More than thirty algorithms have been proposed to identify DNA regulatory sites during the past thirty years. However, the prediction accuracy of these algorithms is still quite low. Ensemble algorithms have emerged as an effective strategy in bioinformatics for improving the prediction accuracy by exploiting the synergetic prediction capability of multiple algorithms. We proposed a novel clustering-based ensemble algorithm named EMD for de novo motif discovery by combining multiple predictions from multiple runs of one or more base component algorithms. The ensemble approach is applied to the motif discovery problem for the first time. The algorithm is tested on a benchmark dataset generated from E. coli RegulonDB. The EMD algorithm has achieved 22.4% improvement in terms of the nucleotide level prediction accuracy over the best stand-alone component algorithm. The advantage of the EMD algorithm is more significant for shorter input sequences, but most importantly, it always outperforms or at least stays at the same performance level of the stand-alone component algorithms even for longer sequences. We proposed an ensemble approach for the motif discovery problem by taking advantage of the availability of a large number of motif discovery programs. We have shown that the ensemble approach is an effective strategy for improving both sensitivity and specificity, thus the accuracy of the prediction. The advantage of the EMD algorithm is its flexibility in the sense that a new powerful algorithm can be easily added to the system.


Effects of melittin on molecular dynamics and Ca-ATPase activity in sarcoplasmic reticulum membranes: electron paramagnetic resonance.
We have performed electron paramagnetic resonance (EPR) experiments on nitroxide spin labels incorporated into rabbit skeletal sarcoplasmic reticulum (SR), in order to investigate the physical and functional interactions between melittin, a small basic membrane-binding peptide, and the Ca-ATPase of SR. Melittin binding to SR substantially inhibits Ca(2+)-dependent ATPase activity at 25 degrees C, with half-maximal inhibition at 9 mol of melittin bound per mole of Ca-ATPase. Saturation transfer EPR (ST-EPR) of maleimide spin-labeled Ca-ATPase showed that melittin decreases the submillisecond rotational mobility of the enzyme, with a 4-fold increase in the effective rotational correlation time (tau r) at a melittin/Ca-ATPase mole ratio of 10:1. This decreased rotational motion is consistent with melittin-induced aggregation of the Ca-ATPase. Conventional EPR was used to measure the submicrosecond rotational dynamics of spin-labeled stearic acid probes incorporated into SR. Melittin binding to SR at a melittin/Ca-ATPase mole ratio of 10:1 decreases lipid hydrocarbon chain mobility (fluidity) 25% near the surface of the membrane, but only 5% near the center of the bilayer. This gradient effect of melittin on SR fluidity suggests that melittin interacts primarily with the membrane surface. For all of these melittin effects (on enzymatic activity, protein mobility, and fluidity), increasing the ionic strength lessened the effect of melittin but did not alleviate it entirely. This is consistent with a melittin-SR interaction characterized by both hydrophobic and electrostatic forces. Since the effect of melittin on lipid fluidity alone is too small to account for the large inhibition of Ca-ATPase rotational mobility and enzymatic activity, we propose that melittin inhibits the ATPase primarily through its capacity to aggregate the enzyme, consistent with previous observations of decreased Ca-ATPase activity under conditions that decrease protein rotational mobility.


Pulmonary resection for metastasis from esophageal carcinoma.
Pulmonary metastasectomy has become the standard therapy for various metastatic malignancies to the lungs; however, few data have been available regarding lung metastasectomy for esophageal carcinoma. To confirm a role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. Between 2001 and 2007, five patients with pulmonary metastases from esophageal carcinoma underwent complete pulmonary resection. All patients had undergone curative resection of their primary esophageal carcinomas and also had obtained locoregional control of their primaries. Disease-free interval varied from 13 to 56 months, with a median of 21 months. In three patients, lung metastases were found to be unilateral and solitary. The other two patients presented several metastases in the unilateral or bilateral lungs. All patients underwent wedge resection or segmentectomy. Currently, four patients are alive without evidence of disease and one patient has died of disease. All patients undertook or were going to undertake chemotherapy after the pulmonary metastasectomy. Three patients with solitary metastasis are all alive without disease 13, 48, and 90 months after the first pulmonary metastasectomy, respectively. Pulmonary metastasectomy for esophageal carcinoma with postoperative chemotherapy was seemingly justified. Solitary pulmonary metastasis might be a good candidate for favorable prognostic factor.


Activity following reverse total shoulder arthroplasty: What should surgeons be advising?
Reverse total shoulder arthroplasty (RTSA) is now the most frequently performed form of shoulder arthroplasty. There is currently no consensus on recommended levels of activity and sport following RTSA. The aim of this review is to outline the current evidence and provide a guide for surgeons on what to advise their patients regarding activity level following RTSA. A systematic review of the literature was performed using the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was performed using the electronic databases PubMed and Medline. Included studies were of level 1 to 4 evidence in the English language evaluating complications and return to sport after RTSA. Eleven studies were selected and included a total of 621 patients (67% female) with a mean age of 73 years (range 22-92). All of the included patients participated in sports prior to RTSA. The rate of return to sport ranged from 60 to 86% and varied with the level of sport activity. Mean time to return to sport after surgery varied greatly between studies. Return to sport is tolerated following RTSA; however, studies are short to medium term only and although the reported complication rate is low, the studies did not include radiographic evaluation. Longer term studies with subgroup analysis evaluating common recreational activities after RTSA are required, particularly in the younger population, in order to establish clear post-operative guidelines.