Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans.
1. Myoadenylate deaminase (AMPD) deficiency is present in 1--2 % of the population. In theory, this deficiency may alter exercise energy metabolism by impairing the purine nucleotide cycle (PNC) and reducing tricarboxylic acid (TCA) cycle anaplerosis. The role of the PNC in TCA cycle anaplerosis is still a debated issue in physiology. Using patients with the AMPD1 mutation will allow a human 'knockout' approach to answering this question. 2. Muscle AMPD activity and genotype (whole blood AMPD1 analysis) was used to classify participants into three groups: n = 3 with absence of AMPD activity and -/- AMPD1 genotype (homozygous); n = 4 with less than 50 % normal AMPD activity and +/- genotype (heterozygous) and n = 12 with normal AMPD activity and +/+ genotype (control). Biopsies were taken from the vastus lateralis muscle before and after incremental cycle ergometry exercise to exhaustion. The muscle biopsies were analysed for AMPD activity, purine nucleotides/nucleosides and bases, creatine, phosphocreatine, amino acids, and the TCA cycle intermediates malate, citrate and fumarate. 3. Time to exhaustion on the cycle ergometer was not different between groups. Muscle adenosine monophosphate increased significantly with exercise for homozygous subjects as compared with the other groups (P < 0.05). Inosine monophosphate increased significantly after exercise for control (P < 0.05) but not for the homozygous subjects. There were no other between-group differences for any other measured variables. 4. In summary, complete and partial muscle AMPD deficiency did not affect TCA cycle anaplerosis, phosphocreatine hydrolysis, energy charge or exercise performance.


The medical student as behavioural psychotherapist.
A group of medical students were randomly selected from a larger group to carry out behaviour therapy under supervision. Ten patients with phobic disorders and two with obsessive-compulsive neurosis were treated, and the results, assessed by ratings of proved reliability, compared favourably with other studies in which psychiatrists or nurses acted as therapists. A questionnaire survey showed that students involved in therapy had a more favourable opinion about this kind of treatment than those receiving only theoretical instruction. The results suggested not only that medical students make good behavioural psychotherapists but also that the subject is a worthwhile training experience which warrants inclusion in the curriculum.


Differences between African-American adolescent females with and without human papillomavirus infection.
An important policy question is whether high-risk populations can be identified and prioritised for human papillomavirus (HPV) immunisation. Data collection included an audio computer-assisted survey interview and testing of Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, and HPV among 295 African-American adolescent females. The results indicated that 43.1% tested positive for HPV. Logistic regression analyses indicated that HPV prevalence was not associated with other sexually transmissible infections (prevalence ratio (PR)=0.85, 95% confidence interval (CI)=0.51-1.41), unprotected vaginal sex (PR=1.04, 95% CI=0.56-1.92), having sex with an older male partner (PR=1.12, 95% CI=0.64-1.96), and having a casual partner (PR=0.89, 95% CI=0.54-1.48). Additionally, t-tests indicated that HPV prevalence was not associated with frequency of vaginal sex (t=0.17, P=0.87), protected sex (t=-0.16, P=0.87), number of recent (t=0.40, P=0.69) or lifetime (t=1.45, P=0.15) sexual partners. However, those testing positive for HPV were younger (t=1.97, P=0.05) and reported current use of birth control pills (PR=2.38, 95% CI=1.00-5.63). It may not be possible to identify those with elevated risk of HPV acquisition. Thus, HPV vaccination, regardless of risk indicators, may be the most efficacious public health strategy.


Community supports after surviving extremely low-birth-weight, extremely preterm birth: special outpatient services in early childhood.
To determine special outpatient services (SOS) use, need, associated factors, and neurodevelopmental and functional outcomes among extremely preterm infants at 18 to 22 months' corrected age. Retrospective analysis. National Institute of Child Health and Human Development (NICHD) Neonatal Research Network. Infants younger than 28 weeks' gestational age who had been born weighing less than 1000 g at an NICHD Neonatal Research Network center from January 1, 1997, to December 31, 2000, and who were receiving follow-up at 18 to 22 months' corrected age. Questionnaires were administered at the 18- to 22-month follow-up visit regarding SOS use since hospital discharge and the current need for SOS (social work, visiting nurse, medical specialty, early intervention, speech and language services, occupational therapy and physical therapy, and neurodevelopmental and behavioral services). The use of and need for SOS were analyzed by gestational age. Logistic regression analysis identified factors independently associated with the use of more than 5 services and with the need for any services. Of 2315 infants, 54.7% used more than 3 SOS by 18 to 22 months, and 19.1% used 6 to 7 SOS. The need for any SOS was reported by approximately 37%. The following variables that were commonly associated with adverse neurodevelopmental outcomes were also associated with the use of more than 5 SOS: sepsis, birth weight, postnatal corticosteroid use, bronchopulmonary dysplasia, and cystic periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage. Male sex was associated with the need for any SOS. Although high SOS use was more likely among children with adverse neurodevelopmental outcomes, a reported need for SOS was common even among those with mild developmental impairment (39.7%) and mild cerebral palsy (42.2%). High SOS use is common, has identifiable neonatal risk factors, and is associated with neurodevelopmental impairment. Extremely preterm survivors have substantial need for community supports regardless of their impairment level. Efforts to improve comprehensive delivery of family-centered community-based services are urgently needed.


Preparation and characterization of fouling-resistant photocatalytic metal membrane embedded with self-organized TiO₂ nano tube.
A self-organized nano-structured, photocatalytic TiO₂ membrane with large surface area of anatase crystallites was successfully fabricated by anodization. The nano-structured anodized TiO₂ membrane was characterized using SEM, XRD and TEM techniques and the operational parameters to fabricate such as anodization time and applied anodic potential were also investigated. The anodized TiO₂ membrane showed high photocatalytic performance in terms of refractory organics decomposition, bacteria inactivation and membrane permeability, which suggests that problems of conventional photocatalytic treatment and membrane filtration in water and wastewater treatment may be reduced using this combined process.


Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure.
MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF. Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 μg kg(-1)min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ΔLV dP/dt(max)). These are Group I (n=7) with ΔLV dP/dt(max)>90%, and Group II (n=7) with ΔLV dP/dt(max)<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p<0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups. Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF.


A network of synaptic genes associated with schizophrenia and bipolar disorder.
Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ.


Graduate primary care training: a collaborative alternative for family practice, internal medicine, and pediatrics.
The Residency Program in Social Medicine at Montefiore Medical Center is a collaborative, integrated training program for primary care pediatricians, internists, and family physicians within one interdisciplinary organization. Since 1970 we have trained more than 200 physicians, prepared them for board certification in their specialty, emphasized the psychosocial aspects and social determinants of health and illness, and shared a faculty, curriculum, and commitment to provide medical care for inner-city, underserved populations. We discuss the program's history and curriculum, administrative and academic structure, shared "cross-track" faculty units (psychosocial; social medicine; and research, education, and evaluation), and graduates' practice outcomes. The interdisciplinary character of the Residency Program in Social Medicine helps physicians successfully serve the underserved and exemplifies that interdisciplinary medical education succeeds when interdisciplinary health care teams are organized for optimal patient care. Only the federal government has the perspective and power to foster more interdisciplinary collaboration and strengthen primary care education in a period of shrinking resources.


Low levels of foot-and-mouth disease virus 3C protease expression are required to achieve optimal capsid protein expression and processing in mammalian cells.
The foot-and-mouth disease virus (FMDV) capsid protein precursor (P1-2A) is processed by the virus-encoded 3C protease (3C(pro)) to produce VP0, VP3, VP1 and 2A. Within the virus-encoded polyprotein, the P1-2A and 3C(pro) can be expected to be produced at equivalent concentrations. However, using transient-expression assays, within mammalian cells, it is possible to modify the relative amounts of the substrate and protease. It has now been shown that optimal production of the processed capsid proteins from P1-2A is achieved with reduced levels of 3C(pro) expression, relative to the P1-2A, compared with that achieved with a single P1-2A-3C polyprotein. Expression of the FMDV 3C(pro) is poorly tolerated by mammalian cells and higher levels of the 3C(pro) greatly inhibit protein expression. In addition, it is demonstrated that both the intact P1-2A precursor and the processed capsid proteins can be efficiently detected by FMDV antigen detection assays. Furthermore, the P1-2A and the processed forms each bind to the integrin αvβ6, the major FMDV receptor. These results contribute to the development of systems which efficiently express the components of empty capsid particles and may represent the basis for safer production of diagnostic reagents and improved vaccines against foot-and-mouth disease.


Electrogastrography, Near-infrared Spectroscopy, and Acoustics to Measure Gastrointestinal Development in Preterm Babies.
The aim of the study was to obtain objective measures indicative of gastrointestinal maturity using 3 noninvasive technologies. Electrogastrography (EGG), abdominal near-infrared spectroscopy (NIRS), and bowel sound/acoustics (AC) monitoring were used simultaneously to obtain physiologic measures of the gastrointestinal system of 18 preterm and 5 term neonates who were tolerating enteral feedings. Measures of EGG slow wave voltage (EGG dominant power) and AC signal amplitude (AC dominant power) were obtained after spectral density analysis. Mean abdominal regional saturations (A-rSO2) were obtained directly from NIRS. The relationship of these 3 measures with postmenstrual age (PMA) was assessed. The results of the 3 methods differed depending on whether the measurements were pre- or postprandial. Postprandial EGG dominant power increases with PMA (r = 0.67, P = 0.003), both pre- and postprandial abdominal NIRS mean regional saturation increase with PMA (r = 0.73, P < 0.001 and r = 0.55, P = 0.009), and postprandial AC dominant power (at 300-500 Hz) increases with PMA (r = -0.48, P = 0.025). EGG, abdominal NIRS, and AC, whenever used simultaneously, can provide objective and synergistic measures that correlate with PMA. These findings may be helpful in the assessment of feeding readiness because they reveal quantitative measures suggestive of the developmental process of the gut.


Stigma, discrimination, and HIV/AIDS knowledge among physicians in Barbados.
To determine the extent of clinical knowledge of HIV/AIDS that physicians in Barbados have and their attitudes towards persons living with HIV/AIDS. In 2000 the Barbados Association of Medical Practitioners conducted a survey in order to assess its members' views on HIV/AIDS issues. Over a two-month period 203 physicians (76% of all those practicing in the country) were interviewed. The survey included physicians working in private practice and the public sector. They were surveyed individually concerning their attitudes towards counseling as well as their clinical knowledge, perception of safe practices, fear of occupational exposure, views on ethical issues, experience treating HIV/AIDS patients, and background with HIV/AIDS continuing education. In comparison to physicians who had graduated in later years, physicians who had graduated in 1984 or earlier had seen fewer HIV/AIDS clients, had lower levels of knowledge about the disease, were more likely to test for HIV/AIDS without informed consent, and were less likely to have ever attended a continuing education training course on HIV/AIDS. Overall, knowledge of the clinical indications of HIV/AIDS was low, and 76% of the physicians did not think they had adequate counseling skills. Over 80% of the physicians were comfortable looking after HIV/AIDS patients. While 95% of the physicians would not release HIV test results without a patient's consent, 33% would test, without consent, a seriously ill patient, and 15% would test without consent a patient upon whom they had to perform an invasive procedure if they perceived the patient to be from a high-risk population such as gay men or commercial sex workers. Only 53% of the physicians had attended an HIV/AIDS in-service training program between 1995 and 1999. Physician training in Barbados should focus on all aspects of HIV/AIDS care, including clinical and emotional factors. Attendance at such training should be mandatory for public sector physicians, and medical school curricula need to be examined to ensure their HIV/AIDS content is current and comprehensive.


CerebroVis: Designing an Abstract yet Spatially Contextualized Cerebral Artery Network Visualization.
Blood circulation in the human brain is supplied through a network of cerebral arteries. If a clinician suspects a patient has a stroke or other cerebrovascular condition, they order imaging tests. Neuroradiologists visually search the resulting scans for abnormalities. Their visual search tasks correspond to the abstract network analysis tasks of browsing and path following. To assist neuroradiologists in identifying cerebral artery abnormalities, we designed CerebroVis, a novel abstract-yet spatially contextualized-cerebral artery network visualization. In this design study, we contribute a novel framing and definition of the cerebral artery system in terms of network theory and characterize neuroradiologist domain goals as abstract visualization and network analysis tasks. Through an iterative, user-centered design process we developed an abstract network layout technique which incorporates cerebral artery spatial context. The abstract visualization enables increased domain task performance over 3D geometry representations, while including spatial context helps preserve the user's mental map of the underlying geometry. We provide open source implementations of our network layout technique and prototype cerebral artery visualization tool. We demonstrate the robustness of our technique by successfully laying out 61 open source brain scans. We evaluate the effectiveness of our layout through a mixed methods study with three neuroradiologists. In a formative controlled experiment our study participants used CerebroVis and a conventional 3D visualization to examine real cerebral artery imaging data to identify a simulated intracranial artery stenosis. Participants were more accurate at identifying stenoses using CerebroVis (absolute risk difference 13%). A free copy of this paper, the evaluation stimuli and data, and source code are available at osf.io/e5sxt.


Cytologic evaluation of lymphadenopathy associated with mycosis fungoides and Sezary syndrome: role of immunophenotypic and molecular ancillary studies.
The most common presenting site of extracutaneous disease in mycosis fungoides and Sezary syndrome is the peripheral lymph node. Although fine-needle aspiration biopsy has been shown to be a valuable diagnostic technique in evaluating lymphadenopathy, its utility in patients with cutaneous T-cell lymphoma has not been extensively studied. With fine-needle aspiration biopsy, material can be collected for ancillary diagnostic studies and for morphologic evaluation. The authors report a series of 11 fine-needle aspiration biopsy specimens from 10 mycosis fungoides and Sezary syndrome patients. Flow cytometric immunophenotyping and T-cell receptor gamma chain polymerase chain reaction were performed on fine-needle aspiration biopsy material and correlated with cytologic findings. Seven of 10 patients had lymph node involvement by cutaneous T-cell lymphoma, with 3 cases exhibiting large-cell transformation and 4 cases exhibiting a small-cell pattern. Flow cytometric immunophenotyping identified an abnormal T-cell population in 6 cases. A clonal T-cell rearrangement by T-cell receptor gamma chain polymerase chain reaction (TCR-gamma PCR) was identified in 1 case in which insufficient events were present for evaluation by flow cytometry and in 1 case in which flow cytometry was not diagnostic of T-cell lymphoma. Two cases showed involvement by classic Hodgkin lymphoma diagnosed by immunohistochemistry on cell block material. Fine-needle aspiration biopsy in conjunction with immunophenotyping and T-cell receptor gamma chain polymerase chain reaction is significantly useful in evaluation of lymphadenopathy in patients with mycosis fungoides and Sezary syndrome, especially for triaging lymph nodes that would otherwise not be sampled or for evaluating multiple lymph nodes.


Modelling the feasibility of bovine tuberculosis eradication in Argentina.
The ability of countries to control and eradicate bovine tuberculosis (TB) has been jeopardised by various epidemiological and ecological features of the disease. The authors have used epidemiological modelling to develop an analytical framework to assess the likely success of a national TB eradication programme in Argentina. Study results suggest that the current control programme is financially feasible in the long term. However, considering that the costs of the TB eradication programme in Argentina are entirely borne by the producer, the initial investment required and the long-term horizon needed to gain revenue may prevent producers from endorsing the programme. Regionalised programmes that allow differential control strategies to be implemented in specific regions may increase the likelihood of success. This methodological approach could be extended to design and evaluate control and eradication programmes for TB and other infectious diseases in other regions of the world.


Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain.
To investigate the possible implications of polymorphism in the CRH promoter in rheumatoid arthritis (RA) susceptibility, we examined a series of patients with RA from a defined area of Northwest Spain. A total of 177 patients with RA and 147 ethnically matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for CRH polymorphisms in the 5' regulatory region of the gene at position 1273 (alleles A1 and A2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Patients were stratified for age at onset of disease and rheumatoid factor status. When the whole group of patients was examined, no significant differences in CRH allele or genotype frequency were found compared with controls. However, the CRH allele A2 was significantly increased in patients with late onset seronegative RA compared with the seronegative group with younger age of disease onset (p = 0.03). In addition, 4 (36.4%) of the 11 patients with late onset seronegative RA carried the CRH-A2 allele versus only 2 (6.6%) of 31 patients with seronegative RA beginning before age 61 (OR 8.3, 95% CI 1.4-47.0; p = 0.015). In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA.


Macronutrients mediate the functional relationship between Drosophila and Wolbachia.
Wolbachia are maternally inherited bacterial endosymbionts that naturally infect a diverse array of arthropods. They are primarily known for their manipulation of host reproductive biology, and recently, infections with Wolbachia have been proposed as a new strategy for controlling insect vectors and subsequent human-transmissible diseases. Yet, Wolbachia abundance has been shown to vary greatly between individuals and the magnitude of the effects of infection on host life-history traits and protection against infection is correlated to within-host Wolbachia abundance. It is therefore essential to better understand the factors that modulate Wolbachia abundance and effects on host fitness. Nutrition is known to be one of the most important mediators of host-symbiont interactions. Here, we used nutritional geometry to quantify the role of macronutrients on insect-Wolbachia relationships in Drosophila melanogaster. Our results show fundamental interactions between diet composition, host diet selection, Wolbachia abundance and effects on host lifespan and fecundity. The results and methods described here open a new avenue in the study of insect-Wolbachia relationships and are of general interest to numerous research disciplines, ranging from nutrition and life-history theory to public health.


Comprehensive N-glycome profiling of cultured human epithelial breast cells identifies unique secretome N-glycosylation signatures enabling tumorigenic subtype classification.
The secreted cellular sub-proteome (secretome) is a rich source of biologically active glycoproteins. N-Glycan profiling of secretomes of cultured cancer cells provides an opportunity to investigate the link between protein N-glycosylation and tumorigenesis. Utilizing carbon-LC-ESI-CID-MS/MS of protein released native N-glycans, we accurately profiled the secretome N-glycosylation of six human epithelial breast cells including normal mammary epithelial cells (HMEC) and breast cancer cells belonging to luminal A subtype (MCF7), HER2-overexpressing subtype (SKBR3), and basal B subtype (MDA-MB157, MDA-MB231, HS578T). On the basis of intact molecular mass, LC retention time, and MS/MS fragmentation, a total of 74 N-glycans were confidently identified and quantified. The secretomes comprised significant levels of highly sialylated and fucosylated complex type N-glycans, which were elevated in all cancer cells relative to HMEC (57.7-87.2% vs 24.9%, p < 0.0001 and 57.1-78.0% vs 38.4%, p < 0.0001-0.001, respectively). Similarly, other glycan features were found to be altered in breast cancer secretomes including paucimannose and complex type N-glycans containing bisecting β1,4-GlcNAc and LacdiNAc determinants. Subtype-specific glycosylation were observed, including the preferential expression of α2,3-sialylation in the basal B breast cancer cells. Pathway analysis indicated that the regulated N-glycans were biosynthetically related. Tight clustering of the breast cancer subtypes based on N-glycome signatures supported the involvement of N-glycosylation in cancer. In conclusion, we are the first to report on the secretome N-glycosylation of a panel of breast epithelial cell lines representing different subtypes. Complementing proteome and lipid profiling, N-glycome mapping yields important pieces of structural information to help understand the biomolecular deregulation in breast cancer development and progression, knowledge that may facilitate the discovery of candidate cancer markers and potential drug targets.


Is metallothionein in Mimachlamys varia a suitable biomarker of trace elements in the waters of the French Atlantic coast?
The development of human activities along the Atlantic coast is responsible for the chronic pollution of the environment with organic and inorganic contaminants. In recent years, environmental regulations such as the MSFD (2008/56/EC) and the OSPAR commission have been developed to preserve coastal environments, giving rise to studies in aquatic biomonitoring. One of them is to use biomarkers to observe the pollutants impact on coastal species such as the bivalve Mimachlamys varia. A defence biomarker was considered in this research to study metal accumulation, with metallothioneins (Mts) involved in the uptake, storage and excretion of metals. To achieve this, bivalves were collected in March 2016 in seven sites along the French Atlantic coasts (open area) and in harbours (semi-open area) with contrasting levels of pollution. Biomarker assays were performed to compare the responses in several tissues (digestive glands, gonads, gills) to inorganic pollutants. The results showed that the accumulation of trace element was different depending on the site and the organ. Mts concentrations were greater in digestive gland compared with gills. Usually, Mts levels were decreased in site showing elevated levels of trace element which explained by downregulation of Mts. Furthermore, results of correlation between Mts and inorganic contaminants and the influence of abiotic factors on Mts suggested that Mts in M. varia is not a relevant biomarker in environments exposed to cocktails of contaminants.


Attaching-effacing bacteria in animals.
Enteric bacteria with a demonstrable or potential ability to form attaching-effacing lesions, so-called attaching-effacing (AE) bacteria, have been found in the intestinal tracts of a wide variety of warm-blooded animal species, including man. In some host species, for example cattle, pigs, rabbits and human beings, attaching-effacing Escherichia coli (AEEC) have an established role as enteropathogens. In other host species, AE bacteria are of less certain significance. With continuing advances in the detection and typing of AE strains, the importance of these bacteria for many hosts is likely to become clearer. The pathogenic effects of AE bacteria result from adhesion to the intestinal mucosa by a variety of mechanisms, culminating in the formation of the characteristic intimate adhesion of the AE lesion. The ability to induce AE lesions is mediated by the co-ordinated expression of some 40 bacterial genes organized within a so-called pathogenicity island, known as the "Locus for Enterocyte Effacement". It is also believed that the production of bacterial toxins, principally Vero toxins, is a significant virulence factor for some AEEC strains. Recent areas of research into AE bacteria include: the use of Citrobacter rodentium to model human AEEC disease; quorum-sensing mechanisms used by AEEC to modulate virulence gene expression; and the potential role of adhesion in the persistent colonization of the intestine by AE bacteria. This review of AE bacteria covers their molecular biology, their occurrence in various animal species, and the diagnosis, pathology and clinical aspects of animal diseases with which they are associated. Reference is made to human pathogens where appropriate. The focus is mainly on natural colonization and disease, but complementary experimental data are also included.


Role modeling humanistic behavior: learning bedside manner from the experts.
Humanistic care is regarded as important by patients and professional accrediting agencies, but little is known about how attitudes and behaviors in this domain are taught in clinical settings. To answer this question, the authors studied how excellent clinical teachers impart the behaviors and attitudes consistent with humanistic care to their learners. Using an observational, qualitative methodology, the authors studied 12 clinical faculty identified by the medical residents enrolled from 2003 to 2004 as excellent teachers of humanistic care on the inpatient medical services at four medical universities in the United States (University of Minnesota Medical School, Emory University, University of Rochester School of Medicine, and Baylor College of Medicine). Observations were conducted by the authors using standardized field notes. After each encounter, the authors debriefed patients, learners (residents and medical students), and the teaching physicians in semistructured interviews. Clinical teachers taught primarily by role modeling. Although they were highly aware of their significance as role models, they did not typically address the human dimensions of care overtly. Despite the common themes of role modeling identified, each clinical teacher exhibited unique teaching strategies. These clinical teachers identified self-reflection as the primary method by which they developed and refined their teaching strategies. Role modeling is the primary method by which excellent clinical teachers try to teach medical residents humanistic aspects of medical care. Although clinical teachers develop unique teaching styles and strategies, common themes are shared and could be used for the future development of clinical faculty.


Molecular beacon lighting up on graphene oxide.
A molecular beacon (MB) is comprised of a fluorophore and a quencher linked by a DNA hairpin. MBs have been widely used for homogeneous DNA detection. In addition to molecular quenchers, many nanomaterials such as graphene oxide (GO) also possess excellent quenching efficiency. Most reported fluorescent sensors relied on DNA probes physisorbed by GO, which may suffer from nonspecific probe displacement and false positive signal. In this work, we report the preparation and characterization of a MB using graphene oxide (GO) as quencher, where an amino and FAM (6-carboxyfluorescein) dual labeled DNA was covalently attached to GO via an amide linkage. A major challenge was to remove noncovalently attached probes due to strong DNA adsorption by GO. While DNA desorption was favored at low salt, high pH, high temperature, and by using organic solvents, the cDNA was required to achieve complete desorption of noncovalently linked DNA probes. The DNA adsorption energy was measured using isothermal titration calorimetry, revealing the heterogeneous nature of GO. The covalent probe has a detection limit of 2.2 nM using a sample volume of 0.05 mL. With a 2 mL sample, the detection limit can reach 150 pM. The covalent probe is highly resistant to nonspecific probe displacement and will find applications in serum and cellular samples where high probe stability is demanded.


Metabolism of very low density lipoproteins after cessation of cholesterol feeding in rabbits. A factor potentially contributing to the slow regression of atheromatous plaques.
Aortic atheromatous plaques regress slowly in cholesterol-fed rabbits that have been returned to normal laboratory diet. To delineate metabolic factors potentially responsible for persistence of atherosclerosis under these conditions, the physical, chemical, and metabolic characteristics were determined for lipoproteins of d less than 1.006 g/ml; such lipoproteins are thought to be the major determinant of progression of atherosclerotic lesions in cholesterol-fed rabbits. At the time of return to a normal laboratory diet regimen after 3 mo of feeding with cholesterol-enriched laboratory diet, plasma cholesterol concentrations were 2,275 +/- 252 mg/dl, mostly attributable to cholesteryl ester-rich very low density lipoproteins (VLDL). On the hypercholesterolemic diet, fractional catabolic rates of plasma clearance of 125I-labeled VLDL were reduced (0.011 +/- 0.002 vs. 0.151 +/- 0.015 h-1), but the total VLDL catabolic rate was increased considerably (17.1 +/- 2.2 vs. less than 1.2 +/- 0.4 mg of protein/kg X d), because of the expansion of the endogenous pool of cholesteryl ester-rich VLDL. The total catabolic rate of VLDL was maintained above estimated control values (5.8 +/- 0.7 mg protein/kg X d) even 10 wk after return of the rabbits to a normal chow regimen, an effect attributable to continued high rates of cholesteryl ester-rich VLDL synthesis in liver. Accumulation of cholesteryl ester-rich VLDL into aortic tissue persisted at a high rate. Thus the persistence of aortic atheromatous lesions after cessation of cholesterol feeding was attributable in part to continued high rates of hepatic production of cholesteryl ester-rich VLDL and its persistent delivery into the aortic wall.


Mood-as-input hypothesis and perseverative psychopathologies.
Mood-as-input hypothesis is a theory of task perseveration that has been applied to the understanding of perseveration across psychopathologies such as pathological worrying, compulsive checking, depressive rumination, and chronic pain. We review 10 years of published evidence from laboratory-based analogue studies and describe their relevance for perseveration in clinical populations. In particular, mood-as-input hypothesis predicts that perseveration at a task will be influenced by interactions between the individual's stop rules for the task and their concurrent mood, and that the valency of an individual's concurrent mood is used as information about whether the stop rule-defined goals for the task have been met. The majority of the published research is consistent with this hypothesis, and we provide evidence that clinical populations possess characteristics that would facilitate perseveration through mood-as-input processes. We argue that mood-as-input research on clinical populations is long overdue because (1) it has potential as a transdiagnostic mechanism helping to explain the development of perseveration and its comorbidity across a range of different psychopathologies, (2) it is potentially applicable to any psychopathology where perseveration is a defining feature of the symptoms, and (3) it has treatment implications for dealing with clinical perseveration.


GmDREB2A;2, a canonical DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN2-type transcription factor in soybean, is posttranslationally regulated and mediates dehydration-responsive element-dependent gene expression.
Soybean (Glycine max) is an important crop around the world. Abiotic stress conditions, such as drought and heat, adversely affect its survival, growth, and production. The DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN2 (DREB2) group includes transcription factors that contribute to drought and heat stress tolerance by activating transcription through the cis-element dehydration-responsive element (DRE) in response to these stress stimuli. Two modes of regulation, transcriptional and posttranslational, are important for the activation of gene expression by DREB2A in Arabidopsis (Arabidopsis thaliana). However, the regulatory system of DREB2 in soybean is not clear. We identified a new soybean DREB2 gene, GmDREB2A;2, that was highly induced not only by dehydration and heat but also by low temperature. GmDREB2A;2 exhibited a high transactivation activity via DRE and has a serine/threonine-rich region, which corresponds to a negative regulatory domain of DREB2A that is involved in its posttranslational regulation, including destabilization. Despite the partial similarity between these sequences, the activity and stability of the GmDREB2A;2 protein were enhanced by removal of the serine/threonine-rich region in both Arabidopsis and soybean protoplasts, suggestive of a conserved regulatory mechanism that involves the recognition of serine/threonine-rich sequences with a specific pattern. The heterologous expression of GmDREB2A;2 in Arabidopsis induced DRE-regulated stress-inducible genes and improved stress tolerance. However, there were variations in the growth phenotypes of the transgenic Arabidopsis, the induced genes, and their induction ratios between GmDREB2A;2 and DREB2A. Therefore, the basic function and regulatory machinery of DREB2 have been maintained between Arabidopsis and soybean, although differentiation has also occurred.


Continuous Transversus Abdominis Plane Nerve Blocks: Does Varying Local Anesthetic Delivery Method-Automatic Repeated Bolus Versus Continuous Basal Infusion-Influence the Extent of Sensation to Cold?: A Randomized, Triple-Masked, Crossover Study in Volunteers.
It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion. Bilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6. Although there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval -2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval -1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6. No evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.


Interleukin levels in cerebrospinal fluid from children with neurocysticercosis.
No information about the levels of pro-inflammatory interleukins has been described in children with neurocysticercosis (NCC). The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-5, IL-6, and IL-12 in the cerebrospinal fluid from children with NCC were determined by enzyme-linked immunosorbent assay (ELISA). Twelve children with NCC, six with active and six with inactive disease, and six children without NCC were studied. TNF-alpha was undetectable in CSF from controls and five children with inactive NCC, whereas the levels were significantly higher (median 22.1 pg/ml; P = 0.008) in all children with active NCC. Levels of IL-6 were low in active and inactive NCC patients but two subjects with active subarachnoid disease had high levels. IL-5 and IL-12 were not detected. This study shows that high levels of TNF-alpha are present in CSF from children with active NCC. IL-6 levels are higher when infection occurs in the subarachnoid space.


Hemodynamic changes by drug interaction of adrenaline with chlorpromazine.
Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 μg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol-pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the β-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.


Short- and Long-Term Outcome of Microscopic Lumbar Spine Surgery in Patients with Predominant Back or Predominant Leg Pain.
This study assessed whether predominant back pain (pBP) represents a negative outcome predictor in patients undergoing microscopic spine surgery without fusion for a lumbar disc herniation (LDH) or spinal stenosis (LSS). Retrospective analysis of prospectively collected data on consecutive patients with LDH or LSS at 2 centers. Patients with visual analog scale (VAS) back pain ≥VAS leg pain were assigned to the pBP group, and compared with patients with predominant VAS leg pain (pLP). Outcome measures included the Roland-Morris Disability Index (RMDI), Oswestry Disability Index (ODI), health-related quality of life measures, Short-Form (SF)-12 Physical Component Summary (PCS), and EuroQol (EQ-5D) index at 3 days, 6 weeks (W6), 6 months, and 1 year postoperatively. A total of 325 patients (154 [47.4%] with pBP and 171 [52.6%] with pLP) were included. Patients with pBP were about 6 years older and more often had LSS. There was no significant difference between the group means of the RMDI, ODI, SF-12 PCS, or EQ-5D at any postoperative time point. The most improvement was observed until the W6 follow-up with little or no improvement thereafter up to 1 year postoperatively. Patients with pBP were as likely as patients with pLP to be W6 responders on the RMDI (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.38-2.16; P = 0.831), ODI (OR, 1.00; 95% CI 0.52-1.92; P = 0.996), SF-12 PCS (OR, 1.09; 95% CI 0.58-2.04; P = 0.791), and EQ-5D (OR, 0.62; 95% CI 0.32-1.21; P = 0.164). Disease-specific subgroup analyses confirmed the results. The present data suggest that patients with pBP have comparable functional and health-related quality of life outcomes after surgery for LDH or LSS with those of patients with pLP.


Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits.
Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.


Psychosocial aspects before and up to 2 years after heart or lung transplantation: Experience of patients and their next of kin.
Psychosocial factors are important for patients undergoing heart (HTx) or lung (LTx) transplantation and for their next of kin (NoK). To describe health-related quality of life (HRQoL; patients only), anxiety, depression, stress, coping ability, and burden (NoK only) for patients and their NoK before and up to 2 years after HTx or LTx. Adult patients (28 hearts and 26 lungs) and their appointed NoK were surveyed with questionnaires about specific psychosocial topics when they were accepted for the transplantation waiting list and 6 months, 1 year, and 2 years after transplantation. Patients' coping ability and self-perceived health were low at baseline and improved over time after transplantation. However, lung patients took longer time to recover in terms of HRQoL, depression, and stress than heart patients. Similarly, NoK of lung patients experienced a higher burden and more stress 1 year after transplantation than NoK of heart patients. Healthcare professionals should be aware of the psychosocial challenges patients and their NoK face in daily living and provide support both before and after heart or lung transplantation.


eHealth in the future of medications management: personalisation, monitoring and adherence.
Globally, healthcare systems face major challenges with medicines management and medication adherence. Medication adherence determines medication effectiveness and can be the single most effective intervention for improving health outcomes. In anticipation of growth in eHealth interventions worldwide, we explore the role of eHealth in the patients' medicines management journey in primary care, focusing on personalisation and intelligent monitoring for greater adherence. eHealth offers opportunities to transform every step of the patient's medicines management journey. From booking appointments, consultation with a healthcare professional, decision-making, medication dispensing, carer support, information acquisition and monitoring, to learning about medicines and their management in daily life. It has the potential to support personalisation and monitoring and thus lead to better adherence. For some of these dimensions, such as supporting decision-making and providing reminders and prompts, evidence is stronger, but for many others more rigorous research is urgently needed. Given the potential benefits and barriers to eHealth in medicines management, a fine balance needs to be established between evidence-based integration of technologies and constructive experimentation that could lead to a game-changing breakthrough. A concerted, transdisciplinary approach adapted to different contexts, including low- and middle-income contries is required to realise the benefits of eHealth at scale.


Water vapour absorption in the penicillate millipede Polyxenus lagurus (Diplopoda: Penicillata: Polyxenida): microcalorimetric analysis of uptake kinetics.
The aberrant millipedes of the order Polyxenida are minute animals that inhabit xeric microclimates of bark and rock faces. The lichens and algae that provide their main food substrates tolerate extensive dehydration, effectively eliminating a liquid water source during periods of drought. In this study, we used microcalorimetry to test whether Polyxenus lagurus (L.) exploits active water vapour absorption (WVA) for water replenishment. Individual animals were pre-desiccated to 10-20% mass-loss and heat fluxes then monitored using a TAM 2277 microcalorimeter. The calorimetric cell was exposed to an air stream increasing progressively in humidity from 84% to 96%. WVA was distinguishable as large exothermic fluxes seen in > or = 86% RH. Owing to very small and opposing heat fluxes from metabolism and passive water loss, the measured flux provided a good measure of water uptake. WVA showed an uptake threshold of 85% RH and linear sorption kinetics until >94% RH, when uptake became asymptotic. Uptake was rapid, and would allow recovery from 20% dehydration (by mass) in little over 5 h. The uptake flux scales proportional, variant mass (0.61), suggesting an area-limited mechanism. Polyxenus possesses a cryptonephric system, analogous to that of tenebrionid beetle larvae. Measurements of water absorption and desorption from faecal pellets voided in different humidities gave an estimated rectal humidity of 85.5%. The close congruence between this value and the WVA threshold provides evidence for a cryptonephric uptake mechanism derived independently from that of tenebrionids. Polyxenus represents the first documented example of WVA in the myriapod classes.


Can we predict the outcome for people with patellofemoral pain? A systematic review on prognostic factors and treatment effect modifiers.
Patellofemoral pain (PFP) is a multifactorial and often persistent knee condition. One strategy to enhance patient outcomes is using clinically assessable patient characteristics to predict the outcome and match a specific treatment to an individual. A systematic review was conducted to determine which baseline patient characteristics were (1) associated with patient outcome (prognosis); or (2) modified patient outcome from a specific treatment (treatment effect modifiers). 6 electronic databases were searched (July 2016) for studies evaluating the association between those with PFP, their characteristics and outcome. All studies were appraised using the Epidemiological Appraisal Instrument. Studies that aimed to identify treatment effect modifiers underwent a checklist for methodological quality. The 24 included studies evaluated 180 participant characteristics. 12 studies investigated prognosis, and 12 studies investigated potential treatment effect modifiers. Important methodological limitations were identified. Some prognostic studies used a retrospective design. Studies aiming to identify treatment effect modifiers often analysed too many variables for the limiting sample size and typically failed to use a control or comparator treatment group. 16 factors were reported to be associated with a poor outcome, with longer duration of symptoms the most reported (>4 months). Preliminary evidence suggests increased midfoot mobility may predict those who have a successful outcome to foot orthoses. Current evidence can identify those with increased risk of a poor outcome, but methodological limitations make it difficult to predict the outcome after one specific treatment compared with another. Adequately designed randomised trials are needed to identify treatment effect modifiers.


Knowledge and practices of seeking informed consent for medical examinations and procedures by health workers in the Democratic Republic of Congo.
Informed consent (IC) is linked to the ethical principle of respecting patient autonomy, respect for human rights and ethical practice, while in many countries it is a standard procedure. Anecdotally, it should be noted that in the Democratic Republic of Congo (DRC) in many instances ICs are not obtained systematically. To date, no research appears to have been conducted on this matter. This study aimed to assess the knowledge and practice of obtaining IC from patients among health care providers (HCP) in the DRC. This was a cross-sectional study, with a convenient sampling of 422 participants. Data from the questions were collected on an imported Microsoft Excel spreadsheet for review at INSTAT.TM The authors set IC's accurate knowledge and practice at 80% or higher. The Fisher Exact test was used to compare categorical association results, and a p-value < 0.05 was considered statistically significant. Results showed that giving information in detail to patients on their medical condition was associated with formal training on medical ethics and IC (p: 0.0028; OR: 1.894; CI: 1.246 to 2.881), which was also associated with answering the patient's questions in detail (p: 0.0035; OR: 1.852; CI: 1.236 to 2.774). About 127(30.09 %) of participants scored 80% or higher. Extracurricular training was associated with withholding information from patients, up to 27 times more than other factors (p< 0.0001; OR: 27.042; CI: 13.628 to 53.657). when it comes to get IC, HCP with many years of practice scored better than others, in one of the question the odd ratio was closer to 7 (p< 0.0001; OR: 6.713; CI: 4.352 to 10.356). Only 47(11.14%) of the participants scored 80% or more of the questions about practice of IC. For a variety of reasons, knowledge and practice of IC among HCPs was very low. A common programme for the country as part of formal training might lead to an improvement. In addition, patients' education on IC should be displayed in waiting areas at all medical centres.


Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3.
Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 as well as Huntington's disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ) tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora) and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.


Surgical management of acute aortic dissection complicated by stroke.
Although patients with acute type A aortic dissection are best managed by emergency surgical intervention, preoperative stroke is known to be an independent predictor of late mortality and is considered by some to be a contraindication to operation because of the risk of precipitating hemorrhagic cerebral infarction and poor long-term outcome. In a series of 272 consecutive, unselected patients with aortic dissection undergoing surgical treatment during a 25-year span (1963-1987), 128 (47 +/- 3% [+/- 70% confidence level (CL)]) had an acute type A dissection. A total of seven patients with acute type A dissection (2.6 +/- 1% of all patients, 5.5 +/- 2% of the acute type A cohort) developed a new stroke preoperatively. Thirteen (4.8 +/- 1%) patients had a diminished or absent carotid pulse, only four (31 +/- 13%) of whom sustained a stroke. One patient died in the immediate postoperative period due to severe brain injury, yielding an operative mortality rate of 14 +/- 14%. Two patients had persistent neurological deficits and died within 4 months of operation; the actuarial survival estimate at 1 year was 57 +/- 19% (mean +/- SEM). One patient recovered function of one upper extremity (preoperative left hemiparesis compounded by paraplegia) but died 6 years later. The remaining three long-term survivors (43 +/- 19%) had major resolution of their neurological deficits and are clinically well 2-8 years postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)


An investigation of breast cancer risk factors in Cyprus: a case control study.
Breast cancer is the most common form of malignancy affecting women worldwide. It is also the leading cancer in females in Cyprus, with approximately 400 new cases diagnosed annually. It is well recognized that genetic variation as well as environmental factors modulate breast cancer risk. The main aim of this study was to assess the strength of associations between recognized risk factors and breast cancer among Cypriot women. This is the first epidemiological investigation on risk factors of breast cancer among the Cypriot female population. We carried out a case-control study, involving 1,109 breast cancer patients and a group of 1,177 controls who were recruited while participating in the National screening programme for breast cancer. Information on demographic characteristics and potential risk factors were collected from both groups during a standardized interview. Logistic regression analysis was used to assess the strength of the association between each risk factor and breast cancer risk, before and after adjusting for the possible confounding effect of other factors. In multivariable models, family history of breast cancer (OR 1.64, 95% CI 1.23, 2.19) was the strongest predictor of breast cancer risk in the Cypriot population. Late menarche (OR 0.64, 95% CI 0.45, 0.92 among women reaching menarche after the age of 15 vs. before the age of 12) and breastfeeding (OR 0.74, 95% CI 0.59, 0.92) exhibited a strong protective effect. In the case of breastfeeding, the observed effect appeared stronger than the effect of pregnancy alone. Surprisingly, we also observed an inverse association between hormone replacement therapy (HRT) although this may be a product of the retrospective nature of this study. Overall the findings of our study corroborate with the results of previous investigations on descriptive epidemiology of risk factors for breast cancer. This investigation provides important background information for designing detailed studies that aim to improve our understanding of the epidemiology of breast cancer in the Cypriot population, including the study of gene-environment interactions. Furthermore, our study provides the first scientific evidence for formulating targeted campaigns for prevention and early diagnosis of breast cancer in Cyprus.


Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses.
H3N2 influenza viruses have now circulated in the human population for 43 years since the pandemic of 1968, accumulating sequence changes in the hemagglutinin (HA) and neuraminidase (NA) that are believed to be predominantly due to selection for escape from antibodies. Examination of mutations that persist and accumulate led to identification of antigenically significant mutations that are contained in five antigenic sites (A-E) mapped on to the H3 HA. In early H3N2 isolates, antigenic site A appeared to be dominant while in the 1990s site B seemed more important. To obtain experimental evidence for dominance of antigenic sites on modern H3 HAs, we have measured antibodies in plasma of human subjects who received the 2006-07 trivalent subunit influenza vaccine (H3 component A/Wisconsin/67/05) or the 2008-09 formulation (H3 component A/Uruguay/716/07). Plasmas were tested against expressed HA of Wisconsin-like influenza A/Oklahoma/309/06 and site-directed mutants in antigenic site A (NNES121-124ITEG, N126T, N133D, TSSS135-138GSNA, K140I, RSNNS142-146PGSG), and antigenic site B (HL156-157KS, KFK158-160GST, NDQI189-192QEQT, A196V). "Native ELISA" analysis and escape mutant selection with two human monoclonal antibodies demonstrated that antibody E05 binds to antigenic site A and 1_C02 binds to site B. We find that most individuals, after vaccination in seasons 2006-07 and/or 2008-09, showed dominance of antigenic site B recognition over antigenic site A. A minority showed dominance of site A in 2006 but these were reduced in 2008 when the vaccine virus had a site A mutation. A better understanding of immunodominance may allow prediction of future antigenic drift and assist in vaccine strain selection.


Frequency ratio of Al+ and Hg+ single-ion optical clocks; metrology at the 17th decimal place.
Time has always had a special status in physics because of its fundamental role in specifying the regularities of nature and because of the extraordinary precision with which it can be measured. This precision enables tests of fundamental physics and cosmology, as well as practical applications such as satellite navigation. Recently, a regime of operation for atomic clocks based on optical transitions has become possible, promising even higher performance. We report the frequency ratio of two optical atomic clocks with a fractional uncertainty of 5.2 x 10(-17). The ratio of aluminum and mercury single-ion optical clock frequencies nuAl+/nuHg+ is 1.052871833148990438(55), where the uncertainty comprises a statistical measurement uncertainty of 4.3 x 10(-17), and systematic uncertainties of 1.9 x 10(-17) and 2.3 x 10(-17) in the mercury and aluminum frequency standards, respectively. Repeated measurements during the past year yield a preliminary constraint on the temporal variation of the fine-structure constant alpha of alpha/alpha = (-1.6+/-2.3) x 10(-17)/year.


Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging.
An unrealized potential to understand the genetic basis of aging in humans, is to consider the immense survival advantage of the rare individuals who live 100 years or more. The Longevity Gene Study was initiated in 1998 at the Albert Einstein College of Medicine to investigate longevity genes in a selected population: the "oldest old" Ashkenazi Jews, 95 years of age and older, and their children. The study proved the principle that some of these subjects are endowed with longevity-promoting genotypes. Here we reason that some of the favorable genotypes act as mechanisms that buffer the deleterious effect of age-related disease genes. As a result, the frequency of deleterious genotypes may increase among individuals with extreme lifespan because their protective genotype allows disease-related genes to accumulate. Thus, studies of genotypic frequencies among different age groups can elucidate the genetic determinants and pathways responsible for longevity. Borrowing from evolutionary theory, we present arguments regarding the differential survival via buffering mechanisms and their target age-related disease genes in searching for aging and longevity genes. Using more than 1,200 subjects between the sixth and eleventh decades of life (at least 140 subjects in each group), we corroborate our hypotheses experimentally. We study 66 common allelic site polymorphism in 36 candidate genes on the basis of their phenotype. Among them we have identified a candidate-buffering mechanism and its candidate age-related disease gene target. Previously, the beneficial effect of an advantageous cholesteryl ester transfer protein (CETP-VV) genotype on lipoprotein particle size in association with decreased metabolic and cardiovascular diseases, as well as with better cognitive function, have been demonstrated. We report an additional advantageous effect of the CETP-VV (favorable) genotype in neutralizing the deleterious effects of the lipoprotein(a) (LPA) gene. Finally, using literature-based interaction discovery methods, we use the set of longevity genes, buffering genes, and their age-related target disease genes to construct the underlying subnetwork of interacting genes that is expected to be responsible for longevity. Genome wide, high-throughput hypothesis-free analyses are currently being utilized to elucidate unknown genetic pathways in many model organisms, linking observed phenotypes to their underlying genetic mechanisms. The longevity phenotype and its genetic mechanisms, such as our buffering hypothesis, are similar; thus, the experimental corroboration of our hypothesis provides a proof of concept for the utility of high-throughput methods for elucidating such mechanisms. It also provides a framework for developing strategies to prevent some age-related diseases by intervention at the appropriate level.


Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis.
The oxidative modification of low density lipoprotein (LDL) has been implicated as an early step in the formation of atheromatous lesions. In vitro studies suggest it to be accelerated, or even initiated, by transition metals such as iron or copper in combination with a reducing agent. Even if such metals have been demonstrated in atheroma gruels, their origin and precise localisation within human atheroma are presently unknown. In the initial part of this study we applied Pearl's method, energy dispersive X-ray microanalysis, and a modified Timm sulphide silver method (SSM) to demonstrate the occurrence of iron in early atherosclerotic lesions from a number of consecutive autopsy cases with evident, general atheromatosis. With the very sensitive SSM, but not with the other techniques, we found foam cells to contain heavy metals with a mainly lysosomal localization. On the basis of the hypothesis that such a lysosomal accumulation of iron might be due to erythrophagocytosis by migrating tissue-bound macrophages that later develop into foam cells, we designed an in vitro model system where human monocyte-derived macrophages were exposed to artificially aged, UV-exposed erythrocytes. The macrophages were then exposed to LDL in serum-and iron-free RPMI medium, occasionally in the presence of the potent iron-chelator desferrioxamine. The capacity of macrophages to oxidise LDL was much enhanced following erythrophagocytosis, and the process was shown to involve secretion of iron. Consequently, LDL oxidation was greatly inhibited by desferrioxamine. We conclude that iron may be exocytosed by macrophages that previously had their lysosomal apparatus enriched with iron, e.g. due to erythrophagocytosis. Oxidation of LDL may result in ensuing foam cell-formation secondary to scavenger-receptor mediated endocytosis by macrophages.


Revisiting long-term adherence to highly active antiretroviral therapy in Senegal using latent class analysis.
Adherence is one of the main predictors of antiretroviral treatment success. A governmental initiative was launched in 1998 for HIV-infected patients in Senegal to provide access to highly active antiretroviral therapy. Between August 1998 and April 2002, 404 adult patients were enrolled. Adherence measurements, defined as pills taken/pills prescribed, were assessed between November 1999 and April 2009 using a pill count along with a questionnaire for 330 patients. Predictors of adherence were explored through a random-intercept Tobit model and a latent class analysis (LCA) was performed to identify adherence trajectories. We also performed a survival analysis taking into account gender and latent adherence classes. Median treatment duration was 91 months (interquartile range, 84-101). On average, adherence declined by 7% every year, was 30% lower for patients taking indinavir, and 12% higher for those receiving cotrimoxazole prophylaxis. Based on the predicted probability of having an adherence ≥ 95%, LCA revealed 3 adherence behaviors and a better adherence for women. A quarter of patients had a high adherence trajectory over time and half had an intermediate one. Male gender and low adherence behavior over time were independently associated with a higher mortality rate. This study shows that an overall good adherence can be obtained in the long term in Senegal. LCA suggests a better adherence for women and points out a large subsample of patients with intermediate level of adherence behavior who are at risk for developing resistance to antiretroviral drugs. This study warrants further research into gender issues.


Determination of fluoroquinolone antibiotics in environmental water samples based on magnetic molecularly imprinted polymer extraction followed by liquid chromatography-tandem mass spectrometry.
A simple method based on magnetic separation for selective extraction of fluoroquinolones (FQs) from environmental water samples has been developed using magnetic molecularly imprinted polymer (MMIP) as sorbent. The MMIP has been prepared using ciprofloxacin as template molecule, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linking agent and Fe(3)O(4) magnetite as magnetic component. The polymer has been characterized by scanning electron microscopy, Fourier-transform infrared spectrometry and vibrating sample magnetometry. Various parameters affecting the extraction efficiency were evaluated in order to achieve optimal concentration and reduce non-specific interactions. The analytes desorbed from the polymers were determined by liquid chromatography-tandem mass spectrometry. The matrix effect was evaluated by using different washing solvents for removing interfering compounds from the MMIPs after sample loading. Under the optimal conditions, the linearity of the method obtained is in the range of 20-2000 ng L(-1). The detection limits of FQs are in the range of 3.2-6.2 ng L(-1). The relative standard deviations of intra- and inter-day tests ranging from 2.5 to 7.2% and from 3.6 to 9.1% are obtained. In all three spiked levels (20, 100 and 200 ng L(-1)), the recoveries of FQs are in the range of 76.3-94.2%. The proposed method was successfully applied to determine FQs including ciprofloxacin, enrofloxacin, lomefloxacin, levofloxacin, fleroxacin and sparfloxacin in different water samples, such as lake water, river water, primary and final sewage effluent. Ciprofloxacin and fleroxacin were found in primary and final sewage effluent samples with the contents in the range of 26-87 ng L(-1).


Vaccination for hepatitis C virus: closing in on an evasive target.
Hepatitis C virus (HCV) infects more than 170 million people globally and is a leading cause of liver cirrhosis, transplantation and hepatocellular carcinoma. Current gold-standard therapy often fails, has significant side effects in many cases and is expensive. No vaccine is currently available. The fact that a significant proportion of infected people spontaneously control HCV infection in the setting of an appropriate immune response suggests that a vaccine for HCV is a realistic goal. A comparative analysis of infected people with distinct clinical outcomes has enabled the characterization of many important innate and adaptive immune processes associated with viral control. It is clear that a successful HCV vaccine will need to exploit and enhance these natural immune defense mechanisms. New HCV vaccine approaches, including peptide, recombinant protein, DNA and vector-based vaccines, have recently reached Phase I/II human clinical trials. Some of these technologies have generated robust antiviral immunity in healthy volunteers and infected patients. The challenge now is to move forward into larger at-risk or infected populations to truly test efficacy.


A quiet ego quiets death anxiety: humility as an existential anxiety buffer.
Five studies tested the hypothesis that a quiet ego, as exemplified by humility, would buffer death anxiety. Humility is characterized by a willingness to accept the self and life without comforting illusions, and by low levels of self-focus. As a consequence, it was expected to render mortality thoughts less threatening and less likely to evoke potentially destructive behavior patterns. In line with this reasoning, Study 1 found that people high in humility do not engage in self-serving moral disengagement following mortality reminders, whereas people low in humility do. Study 2 showed that only people low in humility respond to death reminders with increased fear of death, and established that this effect was driven uniquely by humility and not by some other related personality trait. In Study 3, a low sense of psychological entitlement decreased cultural worldview defense in response to death thoughts, whereas a high sense of entitlement tended to increase it. Study 4 demonstrated that priming humility reduces self-reported death anxiety relative to both a baseline and a pride priming condition. Finally, in Study 5, experimentally induced feelings of humility prevented mortality reminders from leading to depleted self-control. As a whole, these findings obtained from relatively diverse Internet samples illustrate that the dark side of death anxiety is brought about by a noisy ego only and not by a quiet ego, revealing self-transcendence as a sturdier, healthier anxiety buffer than self-enhancement.


Loss of adenomatous polyposis coli gene function disrupts thymic development.
Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated beta-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) beta, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and alphabeta TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of beta-catenin signaling and is essential for T cell differentiation.


Age estimation of a sample of Pakistani population using Coronal Pulp Cavity Index in molars and premolars on Orthopantomogram.
The aim of the present study was to assess the validity of tooth-coronal index (TCI) in the age estimation. This retrospective charts review was conducted at the Aga Khan University Hospital, Karachi from January 2016 to March 2016, and comprised 315 teeth of 80 individuals. The teeth were analysed on Orthopantomogram. TCI was calculated for unrestored mandibular premolars and molars. Pearson\\\'s correlation was applied to assess correlation between chronological age and TCI. Besides, 30(37.5%) subjects were male and 50(62.5%) female, and 140(44.4%) teeth were of male subjects and 175(55.6%) were of females. The mean correlation coefficient between chronological age and TCI was -0.27. The highest negative correlation was observed for tooth No.47 in males (r=-0.72) whereas among females the highest negative correlation was noted for tooth No.36 (r=-0.61).There was very weak correlation between age and TCI of a tooth. Therefore, TCI index could not be predictably used for age estimation in the studied population.


Cultural adaptation of an existing children's weight management programme: the CHANGE intervention and feasibility RCT.
Excess weight in children is a continuing health issue. Community-based children's weight management programmes have had some effect in promoting weight loss. Families from minority ethnic communities are less likely to complete these programmes but, to date, no programmes have been culturally adapted to address this. We aimed to (1) culturally adapt an existing weight management programme for children aged 4-11 years and their families to make it more suited to Pakistani and Bangladeshi communities but inclusive of all families and (2) evaluate the adapted programme to assess its feasibility and acceptability, as well as the feasibility of methods, for a future full-scale trial. In phase I, a cultural adaptation of a programme that was informed by formative research and guided by two theoretical frameworks was undertaken and in phase II this adapted programme was delivered in a cluster-randomised feasibility study (for which the clusters were the standard and adapted children's weight management programmes). Birmingham: a large, ethnically diverse UK city. In phase I, Pakistani and Bangladeshi parents of children with excess weight, and, in phase II, children aged 4-11 years who have excess weight and their families. A culturally adapted children's weight management programme, comprising six sessions, which was delivered to children and parents, targeting diet and physical activity and incorporating behaviour change techniques, was developed in phase I and delivered in the intervention arm to 16 groups in phase II. The eight groups in the comparator arm received the standard (unadapted) children's weight management programme. The primary outcome was the proportion of Pakistani and Bangladeshi families completing (attending ≥ 60% of) the adapted programme. Secondary outcomes included the proportion of all families completing the adapted programme, the feasibility of delivery of the programme, the programme's acceptability to participants, the feasibility of trial processes and the feasibility of collection of outcome and cost data. The proportion of Pakistani and Bangladeshi families and all families completing the adapted programme was 78.8% [95% confidence interval (CI) 64.8% to 88.2%] and 76.3% (95% CI 67.0% to 83.6%), respectively. The programme was feasible to deliver with some refinements and was well received. Ninety-two families participated in outcome data collection. Data collection was mostly feasible, but participant burden was high. Data collection on the cost of programme delivery was feasible, but costs to families were more challenging to capture. There was high attrition over the 6-month follow-up period (35%) and differential attrition in the two study arms (29% and 52% in the intervention and comparator arms, respectively). The study was not designed to address the issue of low participant uptake of children's weight management programmes. The design of a future trial may include individual randomisation and a 'minimal intervention' arm, the acceptability of which has not been evaluated in this study. The theoretically informed, culturally adapted children's weight management programme was highly acceptable to children and families of all ethnicities. Consideration should be given to a future trial to evaluate clinical effectiveness and cost-effectiveness of the adapted programme, but the design of a future trial would need to address the logistics of data collection, participant burden and study attrition. Current Controlled Trials ISRCTN81798055. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 33. See the NIHR Journals Library website for further project information. Kate Jolly is part-funded by the Collaboration for Leadership in Applied Health Research and Care West Midlands.


Revised nomenclature of Clostridium difficile toxins and associated genes.
Several different nomenclatures have been applied to the Clostridium difficile toxins and their associated genes. This paper summarizes the new nomenclature that has been agreed to by the research groups currently active in the field. The revised nomenclature includes C. difficile toxins and other related large clostridial toxins produced by Clostridium sordellii and Clostridium novyi, and corresponding toxin genes, as well as toxin production types of C. difficile strains.


Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control.
Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013-2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks.


Mechanism of the Primary Charge Transfer Reaction in the Cytochrome bc1 Complex.
The bc1 complex is a critical enzyme for the ATP production in photosynthesis and cellular respiration. Its biochemical function relies on the so-called Q-cycle, which is well established and operates via quinol substrates that bind inside the protein complex. Despite decades of research, the quinol-protein interaction, which initiates the Q-cycle, has not yet been completely described. Furthermore, the initial charge transfer reactions of the Q-cycle lack a physical description. The present investigation utilizes classical molecular dynamics simulations in tandem with quantum density functional theory calculations, to provide a complete and consistent quantitative description of the primary events that occur within the bc1 complex upon quinol binding. In particular, the electron and proton transfer reactions that trigger the Q-cycle in the bc1 complex from Rhodobacter capsulatus are studied. The coupled nature of these charge transfer reactions was revealed by obtaining the transition energy path connecting configurations of the Qo-site prior and after the transfers. The analysis of orbitals and partial charge distribution of the different states of the Qo-site has further supported the conclusion. Finally, key structural elements of the bc1 complex that trigger the charge transfer reactions were established, manifesting the importance of the environment in the process, which is furthermore evidenced by free energy calculations.


Novelty processing and memory formation in Parkinson's disease.
Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic cells, resulting in dopamine depletion. This depletion is counteracted through dopamine replacement therapy (DRT). Dopamine has been suggested to affect novelty processing and memory, which suggests that these processes are also implicated in PD and that DRT could affect them. To investigate word learning and novelty processing in patients with PD as indexed by the P2 and P3 event-related potential components, and the role of DRT in these processes. 21 patients with PD and 21 matched healthy controls were included. Patients with PD were tested on and off DRT in two sessions in a counterbalanced design, and healthy controls were tested twice without intervention. Electroencephalogram (EEG) was measured while participants performed a word learning Von Restorff task. Healthy controls showed the typical Von Restorff effect, with better memory for words that were presented in novel fonts, than for words presented in standard font. Surprisingly, this effect was reversed in the patients with PD. In line with the behavioral findings, the P3 was larger for novel than for standard font words in healthy controls, but not in patients with PD. For both groups the P2 and P3 event-related components were larger for recalled versus forgotten words. DRT did not affect these processes. Learning of novel information is compromised in patients with PD. Likewise, the P2 and P3 components that predict successful memory encoding are reduced in PD patients. This was true both on and off DRT, suggesting that these findings reflect abnormalities in learning and memory in PD that are not resolved by dopaminergic medication.


Reevaluation of transient ischemic attacks as a risk factor for early mortality.
The prevailing belief that transient ischemic attack is a risk factor for cardiovascular morbidity and mortality is based primarily on comparisons of survival of patients after transient ischemic attacks to that of an age-, race-, and sex-adjusted general population. Concomitant conditions that carry a high risk of premature mortality or morbidity, such as ischemic heart disease, hypertension, and diabetes, are very prevalent among patients with transient ischemic attacks. Hence, the poor prognosis of such patients may be attributable to these factors rather than their transient ischemic attack per se, which may only serve to bring patients into the medical system. We compared the survival of 336 patients after transient ischemic attack to that of a control group with a similar risk factor profile consisting of 6,710 patients evaluated for cardiac catheterization. Survival estimates, both unadjusted and adjusted for risk factors, did not differ between the two groups. Three-year survival estimates, after adjustment to the mean value of covariates, were 94% for the patients with transient ischemic attacks and 91% for the controls. These results suggest that the transient ischemic attack may not be an independent risk factor for mortality, although it may identify patients already at increased risk from coexisting conditions.


Effect of some medicinal plant extracts on the oxidative stress status in Alzheimer's disease induced in rats.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Increased oxidative stress has been shown to be a prominent and early feature in AD. Medicinal plants with antioxidant activities have been used traditionally in the treatment of several human diseases. The present study aims to investigate the effect of Salvia triloba and Piper nigrum plant extracts on the oxidative stress status in Alzheimer's disease induced in rats. 70 male rats were enrolled in this study and were classified into 7 groups (ten each). Group 1: control group, group 2: AD-induced rats by aluminum chloride, and served as positive control; group 3: AD group treated with Rivastigmine in a dose of 0.3 mg/kg b. wt. daily for three months; group 4 & 5: AD group treated with total extract of Salvia triloba in a dose of 750 or 375 mg/kg b. wt. respectively, daily for three months; group 6 & 7: AD group treated with total extract Piper nigrum in a dose of 187.5 or 93.75 mg/kg b. wt. respectively, daily for three months. After three months of treatment animals' sera and brain samples were collected. Malondialdehyde (MDA), nitric oxide (NO) and total antioxidant capacity (TAC) were determined in serum while superoxide dismutase (SOD) in erythrocyte. Brain samples were divided sagitally into two portions, the first portion was separated for determination of acetylcholine (Ach) and acetycholinesterase (AchE). The second portion was used for histopathological investigation. The results indicated that extracts of Salvia triloba and Piper nigrum as well as Rivastigmine showed significant increase in brain Ach, serum TAC and SOD and significant decreases in brain AchE, MDA and NO in AD-induced rats. Moreover, histological investigation of brain sections showing nearly normal histological structure of hippocampus. Treatment with Salvia triloba in a dose of 750 mg/kg b. wt. was more powerful in protection from Alzheimer's disease than Piper nigrum, as indicated by both biochemical and histopathological findings. This study revealed that the treatment of AD-induced rats with Salvia triloba and Piper nigrum, total plant extracts significantly reduced the oxidative stress status and ameliorates the neurodegeneration characteristic of Alzheimer's diseases in rats. Noteworthy, Salvia triloba extract showed more interest in improvement Alzheimer's disease in rats.


[Evolution of children one year post liver transplant].
Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93% and 86% respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.


Periodic trends and hidden dynamics of magnetic properties in three series of triazacyclononane lanthanide complexes.
In three structurally related series of nine-coordinate lanthanide(iii) complexes (Ln = Tb, Dy, Ho, Er, Tm and Yb) based on triazacyclononane, solution NMR studies and DFT/CASSCF calculations have provided key information on the magnetic susceptibility anisotropy. Both experimental and computational approaches have revealed a poor correlation to Bleaney's theory of magnetic anisotropy. CASSCF calculations suggested that the magnetic susceptibility is very sensitive to small geometric variations within the first coordination sphere, whereas DFT analyses indicate that it is the thermal accessibility of low energy vibrational modes that may lead to distortion. Parallel NMRD and EPR studies on the three Gd(iii) complexes revealed good correspondence in estimating the electronic relaxation time. The Gd(iii) tris-pyridinecarboxylate complex possesses a very long electronic relaxation time making it a promising starting point for responsive gadolinium EPR probe design.


French maritime pine bark extract Pycnogenol reduces thromboxane generation in blood from diabetic male rats.
The protective effect of Pycnogenol against cardiovascular diseases was clearly demonstrated. Nevertheless, little is known about its antithrombotic effect, especially in diabetes associated with enhanced thromboxane synthesis leading to severe vascular complications. Therefore, the main purpose of our study was to evaluate the effect of long-term Pycnogenol intake on synthesis of prothrombotic thromboxane A(2) (TXA(2)) in animal model of insulin-dependent diabetes. The levels of main plasma TXA(2) metabolite, thromboxane B(2) (TXB(2)), were assessed by enzyme-linked immunosorbent assay. Diabetes was induced in Wistar male rats by single injection of streptozotocin, resulting after 8 weeks in significant body weight reduction, increased plasma glucose concentrations, and decreased plasma C-peptide levels, compared to non-diabetic animals. There was no significant reduction of plasma glucose concentrations after Pycnogenol ingestion. It was found, however, that daily administration of either Pycnogenol (5mg/kg b.wt.) or acetylsalicylic acid (ASA, 10mg/kg b.wt.) significantly reduced plasma TXB(2) concentrations, and this inhibitory effect was higher in the latter case. Nonetheless, simultaneous administration of Pycnogenol and ASA did not improve effectiveness of ASA-mediated decrease in TXB(2) generation. The results of the present study suggest that Pycnogenol might have a beneficial antithrombotic effect when administered alone or as a supplementation of standard antiplatelet therapy in diabetic patients.


Using the Fast Track randomized prevention trial to test the early-starter model of the development of serious conduct problems.
The Fast Track prevention trial was used to test hypotheses from the Early-Starter Model of the development of chronic conduct problems. We randomly assigned 891 high-risk first-grade boys and girls (51% African American) to receive the long-term Fast Track prevention or not. After 4 years, outcomes were assessed through teacher ratings, parent ratings, peer nominations, and child self-report. Positive effects of assignment to intervention were evident in teacher and parent ratings of conduct problems, peer social preference scores, and association with deviant peers. Assessments of proximal goals of intervention (e.g., hostile attributional bias, problem-solving skill, harsh parental discipline, aggressive and prosocial behavior at home and school) collected after grade 3 were found to partially mediate these effects. The findings are interpreted as consistent with developmental theory.


Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities.
The genetic mechanisms that regulate the complex morphogenesis of generating cartilage elements in correct positions with precise shapes during organogenesis, fundamental issues in developmental biology, are still not well understood. By focusing on the developing mouse limb, we confirm the importance of transcription factors encoded by the Sall gene family in proper limb morphogenesis, and further show that they have overlapping activities in regulating regional morphogenesis in the autopod. Sall1/Sall3 double null mutants exhibit a loss of digit1 as well as a loss or fusion of digit2 and digit3, metacarpals and carpals in the autopod. We show that Sall activity affects different pathways, including the Shh signaling pathway, as well as the Hox network. Shh signaling in the mesenchyme is partially impaired in the Sall mutant limbs. Additionally, our data suggest an antagonism between Sall1-Sall3 and Hoxa13-Hoxd13. We demonstrate that expression of Epha3 and Epha4 is downregulated in the Sall1/Sall3 double null mutants, and, conversely, is upregulated in Hoxa13 and Hoxd13 mutants. Moreover, the expression of Sall1 and Sall3 is upregulated in Hoxa13 and Hoxd13 mutants. Furthermore, by using DNA-binding assays, we show that Sall and Hox compete for a target sequence in the Epha4 upstream region. In conjunction with the Shh pathway, the antagonistic interaction between Hoxa13-Hoxd13 and Sall1-Sall3 in the developing limb may contribute to the fine-tuning of local Hox activity that leads to proper morphogenesis of each cartilage element of the vertebrate autopod.