Can patient navigation improve receipt of recommended breast cancer care? Evidence from the National Patient Navigation Research Program.
Poor and underserved women face barriers in receiving timely and appropriate breast cancer care. Patient navigators help individuals overcome these barriers, but little is known about whether patient navigation improves quality of care. The purpose of this study is to examine whether navigated women with breast cancer are more likely to receive recommended standard breast cancer care. Women with breast cancer who participated in the national Patient Navigation Research Program were examined to determine whether the care they received included the following: initiation of antiestrogen therapy in patients with hormone receptor-positive breast cancer; initiation of postlumpectomy radiation therapy; and initiation of chemotherapy in women younger than age 70 years with triple-negative tumors more than 1 cm. This is a secondary analysis of a multicenter quasi-experimental study funded by the National Cancer Institute to evaluate patient navigation. Multiple logistic regression was performed to compare differences in receipt of care between navigated and non-navigated participants. Among participants eligible for antiestrogen therapy, navigated participants (n = 380) had a statistically significant higher likelihood of receiving antiestrogen therapy compared with non-navigated controls (n = 381; odds ratio [OR], 1.73; P = .004) in a multivariable analysis. Among the participants eligible for radiation therapy after lumpectomy, navigated participants (n = 255) were no more likely to receive radiation (OR, 1.42; P = .22) than control participants (n = 297). We demonstrate that navigated participants were more likely than non-navigated participants to receive antiestrogen therapy. Future studies are required to determine the full impact patient navigation may have on ensuring that vulnerable populations receive quality care.


A novel approach for analyzing electrochemical properties of mixed conducting solid oxide fuel cell anode materials by impedance spectroscopy.
For application of acceptor-doped mixed conducting oxides as solid oxide fuel cell (SOFC) anodes, high electrochemical surface activity as well as acceptable electronic and ionic conductivity are crucial. In a reducing atmosphere, particularly the electronic conductivity of acceptor-doped oxides can become rather low and the resulting complex interplay of electrochemical reactions and charge transport processes makes a mechanistic interpretation of impedance measurements very complicated. In order to determine all relevant resistive and capacitive contributions of mixed conducting electrodes in a reducing atmosphere, a novel electrode design and impedance-based analysis technique is therefore introduced. Two interdigitating metallic current collectors are placed in a microelectrode, which allows in-plane measurements within the electrode as well as electrochemical measurements versus a counter electrode. Equivalent circuit models for quantifying the spectra of both measurement modes are developed and applied to simultaneously fit both spectra, using the same parameter set. In this manner, the electronic and ionic conductivity of the material as well as the area-specific resistance of the surface reaction and the chemical capacitance can be determined on a single microelectrode in a H2-H2O atmosphere. The applicability of this new tool was demonstrated in SrTi0.7Fe0.3O(3-δ) (STFO) thin film microelectrodes, deposited on single-crystalline yttria-stabilized zirconia (YSZ) substrates. All materials parameters that contribute to the polarization resistance of STFO electrodes in a reducing atmosphere could thus be quantified.


Effective continuing professional development for translating shared decision making in primary care: A study protocol.
Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the healthcare professional and the patient. SDM is the essential element of patient-centered care, a core concept of primary care. However, SDM is seldom translated into primary practice. Continuing professional development (CPD) is the principal means by which healthcare professionals continue to gain, improve, and broaden the knowledge and skills required for patient-centered care. Our international collaboration seeks to improve the knowledge base of CPD that targets translating SDM into the clinical practice of primary care in diverse healthcare systems. Funded by the Canadian Institutes of Health Research (CIHR), our project is to form an international, interdisciplinary research team composed of health services researchers, physicians, nurses, psychologists, dietitians, CPD decision makers and others who will study how CPD causes SDM to be practiced in primary care. We will perform an environmental scan to create an inventory of CPD programs and related activities for translating SDM into clinical practice. These programs will be critically assessed and compared according to their strengths and limitations. We will use the empirical data that results from the environmental scan and the critical appraisal to identify knowledge gaps and generate a research agenda during a two-day workshop to be held in Quebec City. We will ask CPD stakeholders to validate these knowledge gaps and the research agenda. This project will analyse existing CPD programs and related activities for translating SDM into the practice of primary care. Because this international collaboration will develop and identify various factors influencing SDM, the project could shed new light on how SDM is implemented in primary care.


Robot-assisted general surgery.
With the initiation of laparoscopic techniques in general surgery, we have seen a significant expansion of minimally invasive techniques in the last 16 years. More recently, robotic-assisted laparoscopy has moved into the general surgeon's armamentarium to address some of the shortcomings of laparoscopic surgery. AESOP (Computer Motion, Goleta, CA) addressed the issue of visualization as a robotic camera holder. With the introduction of the ZEUS robotic surgical system (Computer Motion), the ability to remotely operate laparoscopic instruments became a reality. US Food and Drug Administration approval in July 2000 of the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) further defined the ability of a robotic-assist device to address limitations in laparoscopy. This includes a significant improvement in instrument dexterity, dampening of natural hand tremors, three-dimensional visualization, ergonomics, and camera stability. As experience with robotic technology increased and its applications to advanced laparoscopic procedures have become more understood, more procedures have been performed with robotic assistance. Numerous studies have shown equivalent or improved patient outcomes when robotic-assist devices are used. Initially, robotic-assisted laparoscopic cholecystectomy was deemed safe, and now robotics has been shown to be safe in foregut procedures, including Nissen fundoplication, Heller myotomy, gastric banding procedures, and Roux-en-Y gastric bypass. These techniques have been extrapolated to solid-organ procedures (splenectomy, adrenalectomy, and pancreatic surgery) as well as robotic-assisted laparoscopic colectomy. In this chapter, we review the evolution of robotic technology and its applications in general surgical procedures.


Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa.
Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. Pseudomonas aeruginosa is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of P. aeruginosa biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of P. aeruginosa produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the pel genes. The pel repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence, pel/psl mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in Caenorhabditis elegans The antibiofilm molecules also reduced P. aeruginosa PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of P. aeruginosa biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic P. aeruginosa infections.


Hematologic passport for athletes competing in endurance sports: a feasibility study.
Strategies based on the use of upper thresholds of hemoglobin or hematocrit to detect blood doping in endurance sports have essentially failed to deter this malpractice. With the aim of establishing a more effective strategy, we analyzed the biological variations of hematologic parameters in professional athletes and investigated the possibility of defining subject-specific reference ranges that could distinguish between physiologic and abnormal variability. Hemoglobin concentration, hematocrit, reticulocyte count, serum ferritin and soluble transferrin receptor levels were sequentially evaluated in 923 professional football players. Using the analysis of variance we tested the effect of age, ethnicity, exercise modalities and training phases on hematologic parameters and then estimated components of variation. The significance of the difference between two measures was obtained from the distribution of the within-subject variance (the so-called reference change). Subject-specific reference ranges were centered around the individual mean value with dispersion based on the 95th percentile of the coefficient of variation distribution. A total of 2,506 hematologic determinations were made. Exercise modalities were found to have important effects on hematologic parameters. Hemoglobin and hematocrit values were higher at the beginning of the competition season, and then declined in well-trained athletes. Aerobic exercise was clearly associated with lower values, suggesting that marginally low hemoglobin and hematocrit values should physiologically be found in endurance sports. At least five determinations were required to define subject-specific reference ranges reliably. Considering athletes showing normal indices of red cell production (i.e., reticulocyte count and soluble transferrin receptor), the 95th percentile of the coefficient of variation distribution was lower than 5% for both hemoglobin and hematocrit. Increases exceeding 10% in these latter parameters should to be considered abnormal. Score systems capable of efficiently detecting non-physiologic increases in red cell production were developed. Using proper sequential determinations of hematologic variables subject-specific reference ranges can be defined for hemoglobin and hematocrit. Thus, the hematologic passport is feasible and might be employed to exclude athletes with non-physiologic increases in hemoglobin and hematocrit from competitions. The hematologic passport should be used within a global strategy to deter blood doping.


SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies.
Germline mutations in the SAMD9 and SAMD9L genes, located in tandem on chromosome 7, are associated with a clinical spectrum of disorders including the MIRAGE syndrome, ataxia-pancytopenia syndrome and myelodysplasia and leukemia syndrome with monosomy 7 syndrome. Germline gain-of-function mutations increase SAMD9 or SAMD9L's normal antiproliferative effect. This causes pancytopenia and generally restricted growth and/or specific organ hypoplasia in non-hematopoietic tissues. In blood cells, additional somatic aberrations that reverse the germline mutation's effect, and give rise to the clonal expansion of cells with reduced or no antiproliferative effect of SAMD9 or SAMD9L include complete or partial chromosome 7 loss or loss-of-function mutations in SAMD9 or SAMD9L. Furthermore, the complete or partial loss of chromosome 7q may cause myelodysplastic syndrome in these patients. SAMD9 mutations appear to associate with a more severe disease phenotype, including intrauterine growth restriction, developmental delay and hypoplasia of adrenal glands, testes, ovaries or thymus, and most reported patients died in infancy or early childhood due to infections, anemia and/or hemorrhages. SAMD9L mutations have been reported in a few families with balance problems and nystagmus due to cerebellar atrophy, and may lead to similar hematological disease as seen in SAMD9 mutation carriers, from early childhood to adult years. We review the clinical features of these syndromes, discuss the underlying biology, and interpret the genetic findings in some of the affected family members. We provide expert-based recommendations regarding diagnosis, follow-up, and treatment of mutation carriers.


Does acute exposure to the electromagnetic field emitted by a mobile phone influence visual evoked potentials? A pilot study.
To search for a potential negative influence on the central nervous system (CNS) of the electromagnetic field emitted by a mobile phone, the authors performed a pilot experimental study of the influence of a single short acute exposure to the GSM mobile phone Motorola 8700, using visual evoked potentials (VEP) examination as an electrophysiological marker of CNS dysfunction. The study group consisted of 20 healthy volunteers. The duration of exposure was 5 minutes. The output power of the device was 1.5 W when the antenna was pulled up. Five parameters of VEP were evaluated by means of multifactorial ANOVA. Confounding effects of age, sex, and of the call in itself were taken into consideration. No statistically significant influence of the above-described exposure to the electromagnetic field emitted by the mobile phone on latencies or amplitudes of VEP was observed.


Unilateral Vocal Cord Paralysis of a Great Jewish Opera Singer.
George London was one of the most compelling vocal artists of the early twentieth century. At the age of 47, the great bass-baritone retired from singing. It has been suggested that the premature ending of his operatic career was due to unilateral vocal cord palsy (UVCP). When London retired, the common belief was that this UVCP was caused by viral hepatitis, although there is no evidence to support such an etiology. London's medical records eliminate the possible etiology of a neck neoplasm, and the long period of time between a heart attack he experienced and his diagnosis of UVCP makes a cardiovascular etiology an unlikely causative factor. London's relatively young age, the diagnosis of laryngitis prior to his UVCP, and the course of his disease indicate that the underlying cause of the termination of his singing career was post-viral neuropathy. This paper describes the clinical evidence related to London's vocal cord function and explores the possible causes for his UVCP, which apparently led to his early retirement.


A procedure for the safety evaluation of natural flavor complexes used as ingredients in food: essential oils.
A scientifically based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for commerce. Being products of common plant biochemical pathways, the chemically identified constituents are organized according to a limited number of well-established chemical groups called congeneric groups. The safety of the intake of the each congeneric group from consumption of the essential oil is evaluated in the context of data on absorption, metabolism, and toxicology of members of the congeneric group. The intake of the group of unidentified constituents is evaluated in the context of the consumption of the essential oil as a food, a highly conservative toxicologic threshold, and toxicity data on the essential oil or an essential oil of similar chemotaxonomy. The flexibility of the guide is reflected in the fact that high intake of major congeneric groups of low toxicologic concern will be evaluated along with low intake of minor congeneric groups of significant toxicological concern (i.e., higher structural class). The guide also provides a comprehensive evaluation of all congeneric groups and constituents that account for the majority of the composition of the essential oil. The overall objective of the guide is to organize and prioritize the chemical constituents of an essential oil in order that no reasonably possible significant risk associated with the intake of essential oil goes unevaluated. The guide is, however, not intended to be a rigid checklist. The Flavor and Extract Manufacturers Association (FEMA) Expert Panel will continue to evaluate each essential oil on a case by case basis applying their scientific judgment to insure that each natural flavor complex is exhaustively evaluated.


A developmental perspective on alcohol use and heavy drinking during adolescence and the transition to young adulthood.
This article offers a developmental perspective on college drinking by focusing on broad developmental themes during adolescence and the transition to young adulthood. A literature review was conducted. The transition to college involves major individual and contextual change in every domain of life; at the same time, heavy drinking and associated problems increase during this transition. A developmental contextual perspective encourages the examination of alcohol use and heavy drinking in relation to normative developmental tasks and transitions and in the context of students' changing lives, focusing on interindividual variation in the course and consequences of drinking and on a wide range of proximal and distal influences. Links between developmental transitions and alcohol use and other health risks are discussed in light of five conceptual models: Overload, Developmental Mismatch, Increased Heterogeneity, Transition Catalyst and Heightened Vulnerability to Chance Events. We review normative developmental transitions of adolescence and young adulthood, focusing on the domains of physical and cognitive development, identity, affiliation and achievement. As shown in a selective review of empirical studies, these transitions offer important vantage points for examining increasing (and decreasing) alcohol and other drug use during adolescence and young adulthood. We conclude with a consideration of research and intervention implications.


[ASSOCIATION BETWEEN MUSCULAR FITNESS AND PHYSICAL HEALTH STATUS AMONG CHILDREN AND ADOLESCENTS FROM BOGOTÁ, COLOMBIA].
epidemiological and experimental evidence suggest the role of muscular strength has been increasingly recognized in the prevention of chronic disease in early life, and features of the cardiometabolic disease have also been negatively associated with muscle strength in adulthood. The aim of this study was to examine whether the association between muscular fitness and physical health status among children and adolescents from Bogotá, Colombia. cross-sectional study in 921 schoolchildren aged 8-11 years from Bogotá, Colombia. A muscular fitness score (MFS) was measured using handgrip strength and standing long jump and vertical jump. Each of these variables was standardized as follows: standardized value = (value = mean)/SD. The muscle fitness score was calculated as the mean of the three standardized scores. MFS was recoded into quartiles Q1 (low fitness) to Q4 (high fitness). The body mass index (BMI), skinfold thickness, waist and hip circumference, body composition by bioimpedance (BIA), blood pressure and self-declaration sexual maturation were measured such as indicators associated with future cardiovascular events. the average age was 13.0 ± 2.6 years. Participants with Q4 (high fitness), show a better physical health status (BMI, blood pressure, body fat and waist circumference (BMI, blood pressure, body fat and waist circumference, p[linear X2] = 0.01). Individuals with Q1 and Q3 (low fitness) had 4.06 times (95%CI 2.60 to 6.34; p = 0.043) risk of excess body fat and 1.57 times (95%CI 1.02 -1.89; p = 0.020) risk of abdominal obesity. our results show that muscle fitness is associated with better physical health status. The testing of muscle strength at early ages should be included in health- monitoring systems.


Utility of real-time PCR for detection of Exserohilum rostratum in body and tissue fluids during the multistate outbreak of fungal meningitis and other infections.
Exserohilum rostratum was the major cause of the multistate outbreak of fungal meningitis linked to contaminated injections of methylprednisolone acetate produced by the New England Compounding Center. Previously, we developed a fungal DNA extraction procedure and broad-range and E. rostratum-specific PCR assays and confirmed the presence of fungal DNA in 28% of the case patients. Here, we report the development and validation of a TaqMan real-time PCR assay for the detection of E. rostratum in body fluids, which we used to confirm infections in 57 additional case patients, bringing the total number of case patients with PCR results positive for E. rostratum to 171 (37% of the 461 case patients with available specimens). Compared to fungal culture and the previous PCR assays, this real-time PCR assay was more sensitive. Of the 139 identical specimens from case patients tested by all three methods, 19 (14%) were positive by culture, 41 (29%) were positive by the conventional PCR assay, and 65 (47%) were positive by the real-time PCR assay. We also compared the utility of the real-time PCR assay with that of the previously described beta-d-glucan (BDG) detection assay for monitoring response to treatment in case patients with serially collected CSF. Only the incident CSF specimens from most of the case patients were positive by real-time PCR, while most of the subsequently collected specimens were negative, confirming our previous observations that the BDG assay was more appropriate than the real-time PCR assay for monitoring the response to treatment. Our results also demonstrate that the real-time PCR assay is extremely susceptible to contamination and its results should be used only in conjunction with clinical and epidemiological data.


The NK1 receptor antagonist N-acetyl-L-tryptophan reduces dyskinesia in a hemi-parkinsonian rodent model.
Dyskinesia or abnormal involuntary movements (AIMs) are a disabling effect of chronic L-DOPA administration and consequent pulsatile stimulation of dopamine receptors. This abnormal activation causes maladaptive changes including upregulation of FosB expression in dynorphin containing striatal cells. Substance P (SP) is co-localized within dynorphin positive cells and is increased within the substantia nigra by L-DOPA (L-3,4-dihydroxyphenylalanine) treatment. Accordingly, we determined if treatment with a SP NK1 receptor antagonist reduced the onset of L-DOPA induced dyskinesia (LID) in the hemi-parkinsonian rodent model. Adult male Sprague-Dawley rats underwent unilateral 6-OHDA (6-hydroxydopamine-hydrobromide) lesions of the medial forebrain bundle. At day 21, daily administration commenced of either L-DOPA (6 mg/kg plus 15 mg/kg of benseraside), L-DOPA with the NK1 antagonist N-acetyl-L-tryptophan (NAT) or equal volume of saline. Animals were tested with the rodent AIM scale assessing axial, contralateral forelimb and orolingual AIMs. Assessment of L-DOPA induced turning was undertaken, and motor function determined using the accelerating rotarod and adjusting step test. Dopaminergic neuronal counts and immunoreactivity for SP and FosB were undertaken. All animals treated with L-DOPA alone developed dyskinesia, whereas combined administration of NAT with L-DOPA significantly reduced onset of AIMs and prevented mild to moderate dyskinesia. In non-dyskinetic NAT treated animals, similar numbers of FosB+ striatal cells were recorded as in saline treated animals. Importantly NAT treatment did not interfere with the anti-parkinsonian effect of L-DOPA. Daily administration of a SP NK1 receptor antagonist may represent a novel treatment regime that reduces the onset of LID whilst conserving motor function.


[Evidences of safety and tolerability of the zoledronic acid 5 mg yearly in the post-menopausal osteoporosis: the HORIZON project].
Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Despite evidence supporting the anti-fracture efficacy of aminobisphosphonates approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within the first year. Poor compliance is associated with negative outcomes, including increased fracture risk. Tolerability and safety are among the causes of poor compliance. Intravenous bisphosphonates avoids the gastrointestial intolerance and the complex dosing instruction of the oral route ensuring full compliance which may provide improved efficacy. However, there are some concerns regarding potent intravenous bisphosphonates as zoledronic acid with respect to tolerability, mainly the acute phase response and to safety, mainly a theoretical risk of over suppression of bone turnover, renal toxicity and osteonecrosis of the jaw. In the HORIZON study, 152 patients on active treatment (82) or placebo (70) underwent to a bone biopsy after double tetracycline labeling. Bone biopsies (iliac crest) were obtained at the final visit at month 36, 1 year after the last infusion. The biopsies were analyzed by histomorphometry on bone sections and by micro-CT (microCT) analysis. One hundred forthy-three biopsies (76 zoledronic acid, 67 placebo) had at least one microCT parameter measured and 111 were available for quantitative histomorphometry (59 zoledronic acid, 52 placebo). Micro-CT analysis of bone structure revealed higher trabecular bone volume (BV/TV), decreased trabecular separation (Tb.Sp), and a strong trend towards improvement in connectivity density in biopsies obtained from patients treated with zoledronic acid, indicating preservation of trabecular bone structure with respect to placebo. Histomorphometric analysis obtained from patients treated with zoledronic acid exhibited reduction of bone turnover, as suggested by decreased activation frequency (Ac.F) by 63%, mineralizing surface (MS/BS), bone formation rate (BFR/BV). In addition, mineral appositional rate (MAR), reflecting the bone-forming capacity of osteoblastic teams at the bone multicellular unit (BMU) level, was significantly higher in patients on active treatment. No sign of excessive suppression of bone turnover or mineralization impairment was detected, confirming the safety of the treatment with intravenous zoledronic acid once a year. These interesting findings are discussed in the article, particularly in terms of new histomorphometric results and clinical findings supporting the tolerability and safety of zoledronic acid.


Streptococcus pneumoniae and Haemophilus influenzae type b carriage in Chinese children aged 12-18 months in Shanghai, China: a cross-sectional study.
The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009. Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests. Among 614 children, 16.6% had pneumococcal carriage and 8.0% Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9%); serotype coverage was 68.6% for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3% for PCV-13. Household residency and father's education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0%). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2% of isolates were resistant to ampicillin. The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.


Simulated hip arthroscopy skills: learning curves with the lateral and supine patient positions: a randomized trial.
Hip arthroscopy can be performed with the patient in the lateral or supine position, but it remains technically demanding. We aimed to objectively quantify and compare learning curves between two groups of orthopaedic trainees randomized to learn simulated hip arthroscopy with the patient in either a lateral or a supine position. We also compared learning curves between senior and junior trainees. A hip arthroscopy simulator with anterolateral and anterior portals, a 70° arthroscope, and fixed distraction was used. Rotation of the simulator by 90° enabled arthroscopy with the patient in a supine or lateral position. Twenty orthopaedic trainees with minimal hip arthroscopy experience were randomized into lateral and supine position groups, and were asked to perform a diagnostic hip arthroscopy of the central compartment on twelve occasions. Each episode involved a change in the portal and repetition of the diagnostic round. A validated motion analysis system objectively measured surgical performance by recording time taken, total path-length of the hands, and number of hand movements. Both groups demonstrated learning with objective improvement in all parameters (p < 0.001). Initially, the lateral group was significantly slower and more variable in their performance during the second diagnostic round, after portal exchange (p = 0.006). However, they achieved parity with the supine group in all parameters by nine episodes. During the first three episodes, the junior trainees performed significantly worse for the first diagnostic round (p = 0.005) but not for the second diagnostic round (p = 0.200), and they rapidly achieved parity with the senior trainees, performing at a similar level by the end of the study period. Trainees with minimal experience with hip arthroscopy progressively learn and objectively improve their performance when using a hip simulator. Orientation after portal exchange is difficult for all trainees but particularly for those learning with a simulated patient lateral position. Trainees are likely to benefit from simulator training to learn orientation and basic competence prior to performing hip arthroscopy on patients.


Merizocotyle euzeti sp. n. (Monogenea: Monocotylidae) from the nasal tissue of three deep sea skates (Rajidae) in the southwestern Atlantic Ocean.
A new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) is described from the nasal tissues of three deep sea rajid skates: the southern thorny skate, Amblyraja doellojuradoi (Pozzi), broadnose skate, Bathyraja brachyurops (Fowler), and yellownose skate, Zearaja chilensis (Guichenot), collected off Buenos Aires Province, Argentina, southwest Atlantic Ocean. Two additional species of sympatric rajid, the white-dotted skate, Bathyraja albomaculata (Norman), and the Patagonian skate, Bathyraja macloviana (Norman), were also examined but no merizocotylines were found. The taxonomy of the Merizocotylinae is not widely accepted and, as a result, the status of Thaumatocotyle and Mycteronastes, and their proposed synonymy with Merizocotyle are currently under discussion. The new species differs from its congeners by having a unique haptoral structure, 6 peripheral loculi that are asymmetrically arranged (one much smaller, indistinctly located in the left or right side of the haptor). The presence of the new species in three sympatric species of Rajidae belonging to distinct genera and subfamilies, as well as its absence in sympatric congenerics indicates the lack of phylogenetic host specificity. Host ecology and geographical distribution appear to be more important than host phylogeny in determining the distribution of this parasite across potential hosts in the region. This constitutes the first record of Merizocotyle in the southwestern Atlantic Ocean.


Limb regeneration in axolotl: is it superhealing?
The ability of axolotls to regenerate their limbs is almost legendary. In fact, urodeles such as the axolotl are the only vertebrates that can regenerate multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list goes on) throughout their lives. It is therefore surprising to realize, although we have known of their regenerative potential for over 200 years, how little we understand the mechanisms behind this achievement of adult tissue morphogenesis. Many observations can be drawn between regeneration and other disciplines such as development and wound healing. In this review, we present new developments in functional analysis that will help to address the role of specific genes during the process of regeneration. We also present an analysis of the resemblance between wound healing and regeneration, and discuss whether axolotls are superhealers. A better understanding of these animals' regenerative capacity could lead to major benefits by providing regenerative medicine with directions on how to develop therapeutic approaches leading to regeneration in humans.


Metabolic transformation and urinary excretion of selenium (Se) in rats fed a Se-enriched defatted rapeseed (Brassica napus, L.) diet.
Se-Enriched defatted rapeseed (Se-DRS), a by-product of rapeseed oil production, is high in Se. This study aimed to detect possible changes in Se-metabolism after Se-DRS consumption and to assess its suitability as a Se supplement in monogaster feed. In this experiment, rats were fed three types of diets differing in Se-form: soybean meal, Se-salt and Se-DRS. Potential differences in Se-metabolism were evaluated based on the total Se concentrations along with non-protein Se speciation patterns in the urine and blood serum of the rats. The total Se concentrations were determined using inductively coupled plasma-mass spectrometry (ICP-MS). Se compounds in the samples were identified through high-performance liquid chromatography/ICP-MS. The total Se excretion rate was dose-dependent, and excess of dietary Se was eliminated in the form of Se-sugar 1, regardless of the administered Se-form. The excretion dynamics of dietary selenomethionine (soybean meal) and methylselenocysteine (Se-DRS) were different to that of the mineral Se (Se-salt). The proportions of Se species in the urine were significantly influenced by the Se source. A specific metabolic pathway, resulting in urinary excretion of Se-sugar 2, was observed in animals fed Se-DRS. Neither the total Se concentrations nor the serum Se speciation patterns differed between the animals fed the conventional diet and those fed the Se-DRS-enriched diet. Based on these results, Se-DRS can be considered a suitable Se supplement for monogaster nutrition in Se-deficient regions.


Thrombin generation - a potentially useful biomarker of thrombotic risk in Philadelphia-negative myeloproliferative neoplasms.
The diagnosis of essential thrombocythemia and polycythemia vera is often made during a thrombotic event which can be serious. Philadelphia-negative chronic myeloproliferative neoplasia patients have an increased thrombotic risk. This is assessed using various scoring systems but these are far from ideal and individual risk. The currend trend to personalised medicine requires finding the most useful thrombotic risk biomarker in these patients. Routine tests for coagulation do not take account of both pro- and anti-coagulant factors which is why these tests are not useful in patients with Philadelphia-negative myeloproliferative neoplasms. Thrombin generation reflects more accurately the balance between pro- and anti-coagulant factors. Some parameters of thrombin generation such as the endogenous thrombin potential are higher in Philadelphia-negative myeloproliferative neoplasm patients, especially in JAK2 V617F carriers than in healthy controls. They are even higher in those with reactive thrombocytosis. The JAK2 V617F allele burden correlates more with a higher thrombin generation potential in patients who are not treated with hydroxycarbamidum. Instead, JAK2 V617F-positive patients with Philadelphia-negative myeloproliferative neoplasms were the most sensitive to hydroxycarbamidum, as was reflected in lower values of platelet thrombin generation potential. The use of thrombin generation examination in these patients would enable detection of imminent thrombosis and personalised prophylactic management.


Heterogeneity of Leishmania donovani parasites complicates diagnosis of visceral leishmaniasis: comparison of different serological tests in three endemic regions.
Diagnostic tests for visceral leishmaniasis that are based on antigens of a single Leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. The aim of this study was to investigate and compare the performance of five serological tests, based on different Leishmania antigens, in three endemic countries for visceral leishmaniasis. A total number of 231 sera of symptomatic and asymptomatic cases and controls from three endemic regions of visceral leishmaniasis in East Sudan, North India and South France were evaluated by following serological tests: rKLO8- and rK39 ELISA, DAT (ITMA-DAT) and two rapid tests of rK39 (IT LEISH) and rKE16 (Signal-KA). Overall, rKLO8- and rK39 ELISA were most sensitive in immunocompetent patients from all endemic regions (96-100%) and the sensitivity was reduced to 81.8% in HIV co-infected patients from France. Sera of patients from India demonstrated significantly higher antibody responses to rKLO8 and rK39 compared with sera from Sudan (p<0.0001) and France (p<0.0037). Further, some Indian and Sudanese patients reacted better with rKLO8 than rK39. Sensitivity of DAT (ITMA-DAT) was high in Sudan (94%) and India (92.3%) but low in France being 88.5% and 54.5% for VL and VL/HIV patients, respectively. In contrast, rapid tests displayed high sensitivity only in patients from India (96.2%) but not Sudan (64-88%) and France (73.1-88.5% and 63.6-81.8% in VL and VL/HIV patients, respectively). While the sensitivity varied, all tests showed high specificity in Sudan (96.7-100%) and India (96.6%).Heterogeneity of Leishmania parasites which is common in many endemic regions complicates the diagnosis of visceral leishmaniasis. Therefore, tests based on homologous Leishmania antigens are required for particular endemic regions to detect cases which are difficult to be diagnosed with currently available tests.


Pharmacological properties of 5-Hydroxytryptamine(4) receptor antagonists on constitutively active wild-type and mutated receptors.
We studied the pharmacological properties of twenty-four 5-hydroxytryptamine (5-HT)(4) receptor ligands known to act as antagonists on 5-HT(4) receptors positively coupled to adenylyl cyclase endogenously expressed in mouse colliculi neurons. In COS-7 cells expressing human or mouse 5-HT(4(a)) receptors (100-8000 fmol/mg of protein), we found neutral antagonists, partial agonists, and inverse agonists. The majority of neutral antagonists belong to the benzodioxanyl ketone class, whereas partial agonists belong to different chemical classes. We found only two inverse agonists, GR 125487 and SB 207266, which are both indoles. Analysis of pharmacological characteristics of the constitutively active wild-type and constitutively active mutated receptors revealed that 1) the ratio between the efficiencies of the full agonist 5-HT and the partial agonist RS 23597 was invariable when the receptor density increased, but was dependent on receptor structure; 2) similarly, the efficacy of the inverse agonist SB 207266 was not dependent on receptor density but was dependent on receptor structure; 3) when the receptor concentration increased, the EC(50) values of the full agonist 5-HT were not modified and the increase in basal constitutive activity, as well as its stimulation by 5-HT, followed a parallel evolution; and 4) the stimulation of basal constitutive activity by 5-HT was not modified by the overexpression of Galphas. All these results indicate that in COS-7 cells, the coupling of the 5-HT(4) receptor to adenylyl cyclase was linear with no indication of spare receptors even at high receptor density (8 pmol/mg). These results are also in accordance with a precoupling between the activated receptor (f(R*)) and adenylyl cyclase. Such observations allowed us to use the two-state model to calculate the constant J, i.e., the equilibrium allosteric constant denoting the ratio of the receptor in the inactive versus active state (J = [R]/[R*]). We found that J was a receptor structural characteristic, independent of receptor density.


Methylation of serum DNA is an independent prognostic marker in colorectal cancer.
Aberrant CpG island hypermethylation is a feature of a subgroup of colorectal cancers, which can be detected in the serum of affected patients. This study was designed to identify methylation targets with prognostic significance in the serum of patients with colorectal cancer. In a gene evaluation set consisting of sera from 24 patients with local colorectal cancers, 14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF, and hMLH1 were identified as potential serum DNA methylation markers. These genes were further analyzed in a test set of sera of 104 patients with colorectal cancer. Methylation of HLTF, HPP1/TPEF, and hMLH1 was found to be significantly correlated with tumor size, and methylation of HLTF and HPP1/TPEF was significantly associated with metastatic disease and tumor stage. Moreover, methylation of HPP1/TPEF was also associated with serum carcinoembryonic antigen. The prognostic relevance of methylation of these genes was tested in pretherapeutic sera of 77 patients with known follow-up. Patients with methylation of HPP1/TPEF or HLTF were found to have unfavorable prognosis (P = 0.001 and 0.008). In contrast, serum methylation of hMLH1 was not associated with a higher risk of death. Multivariate analysis showed methylated HPP1 and/or HLTF serum DNA to be independently associated with poor outcome and a relative risk of death of 3.4 (95% confidence interval, 1.4-8.1; P = 0.007). These data show that the methylation status of specific genes in the serum of patients with colorectal cancer has the potential to become a pretherapeutic predictor of outcome.


Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis.
Inducible cyclooxygenase (Cox-2), also known as prostaglandin H synthase 2 (PGH-2) is a key enzyme in the formation of prostaglandins and thromboxanes. Cox-2 is the product of an immediate-early gene that is expressed in response to growth factors, tumor promoters, or cytokines. Overexpression of Cox-2 is associated with both human colon cancers and suppression of apoptosis in cultured epithelia] cells, an activity that is reversed by the nonsteroidal anti-inflammatory drug, sulindac sulfide. To address the relationship between Cox-2, apoptosis, and tumor development in vivo, we studied C57BL/6J-Min/+(Min) mice, a strain containing a fully penetrant dominant mutation in the Apc gene, leading to the development of gastrointestinal adenomas by 110 days of age. Min mice were fed AIN-76A chow diet and given sulindac (0.5 +/- 0.1 mg/day) in drinking water. Control Min mice and homozygous C57BL/6J-+/+ normal littermates lacking the Apc mutation (+/+) were fed AIN-76A diet and given tap water to drink. At 110 days of age, all mice were sacrificed, and their intestinal tracts were examined. Control Min mice had 11.9 +/- 7.8 tumors per mouse compared to 0.1 +/- 0.1 tumors for sulindac-treated Min mice. As expected, +/+ littermates had no macroscopic tumors. Examination of histologically normal-appearing small bowel from Min animals revealed increased amounts of Cox-2 and prostaglandin E(2) compared to +/+ littermates. Using two different in situ techniques, terminal transferase-mediated dUTP nick end labeling and a direct immunoperoxidase method, Min animals also demonstrated a 27-47% decrease in enterocyte apoptosis compared to +/+ animals. Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis. These data suggest that overexpression of Cox-2 is associated with tumorigenesis in the gastrointestinal epithelium, and that both are inhibited by sulindac administration.


A review of ecosystem service benefits from wild bees across social contexts.
In order to understand the role of wild bees in both social and ecological systems, we conducted a quantitative and qualitative review of publications dealing with wild bees and the benefits they provide in social contexts. We classified publications according to several attributes such as services and benefits derived from wild bees, types of bee-human interactions, recipients of direct benefits, social contexts where wild bees are found, and sources of changes to the bee-human system. We found that most of the services and benefits from wild bees are related to food, medicine, and pollination. We also found that wild bees directly provide benefits to communities to a greater extent than individuals. In the social contexts where they are found, wild bees occupy a central role. Several drivers of change affect bee-human systems, ranging from environmental to political drivers. These are the areas where we recommend making interventions for conserving the bee-human system.


Spontaneous Deracemizations.
Spontaneous deracemizations is a challenging, multidisciplinary subject in current chirality research. In the absence of any chiral inductors, an achiral substance or a racemic composition is driven into an enantioenriched or even homochiral state through a selective energy input, e.g., chemical potential, photoirradiation, mechanical grinding, ultrasound waves, thermal gradients, etc. The most prominent examples of such transformations are the Soai reaction and the Viedma deracemization. In this review, we track the most recent developments in this topic and recall that many other deracemizations have been reported for solutions from mesophases to conglomerate crystallizations. A compiled set of simply available achiral organic, inorganic, organometallic, and MOF compounds, yielding conglomerate crystals, should give the impetus to realize new experiments on spontaneous deracemizations. Taking into account thermodynamic constraints, modeling efforts have shown that structural features alone are not sufficient to describe spontaneous deracemizations. As a guideline of this review, particular attention is paid to the physicochemical origin and symmetry requirements of such processes.


Suppression by wortmannin of platelet responses to stimuli due to inhibition of pleckstrin phosphorylation.
Studies were made of inhibition by wortmannin, a fungal metabolite, of human platelet responses to various stimuli. Wortmannin at concentrations as low as 1-100 nM inhibited several receptor-agonist-induced 5-hydroxytryptamine release from platelets, without affecting agonist-induced increases in the intracellular concentration of Ca2+. Phorbol 12-myristate 13-acetate (PMA), an active tumour promoter, caused 5-hydroxytryptamine release when combined with a low concentration of ionomycin, and platelet aggregation by itself; these effects of the phorbol ester were also inhibited by wortmannin as well as by staurosporine, a potent, although non-specific, protein kinase C (PKC) inhibitor, in a similar molar concentration range. The platelet responses to the receptor agonists or PMA were accompanied by increased incorporation of [32P]Pi into pleckstrin, a protein selectively expressed in platelets and other blood cells arising from haematopoietic stem cells, as a result of PKC activation in the intact cells. The pleckstrin phosphorylation was inhibited by wortmannin in ways mostly similar to those in which it inhibited the 5-hydroxytryptamine-release responses. Nevertheless, wortmannin failed to inhibit PKC activity measurable in a cell-free assay system which is highly susceptible to staurosporine. Nor did it inhibit the translocation of cytosolic PKC to membranes induced by addition of PMA to platelet cells. Thus wortmannin, which is not a direct inhibitor of PKC, could interfere with the kinase-dependent phosphorylation of pleckstrin, which may play an important role in the cellular responses to receptor stimulation.


A fluorescent probe for estimation of adenosine diphosphate and monitoring of glucose metabolism.
An ADP selective fluorescent probe working in aqueous medium was identified and the change in fluorescence as a function of ADP concentration was standardized. Using this probe, all the steps of glycolysis coupled with ATP/ADP inter-conversion and oxidative breakdown of pyruvate in the mitochondria were monitored and the consumption/production of ATP/ADP at each step was quantified. The quantity of ADP present in the mitochondria, taken from different body parts of a pig, was also determined. It is hypothesized that an appropriate modification of the technique may provide a diagnostic tool for monitoring biochemical pathways as well as for quick estimation of ADP in the mitochondria and other cell organelles.


Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events. Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.).


Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.
Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both in vitro and in vivo, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu(-/-) mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.


Induction of phagocytosis and intracellular signaling by an inhibitory channel catfish leukocyte immune-type receptor: evidence for immunoregulatory receptor functional plasticity in teleosts.
Immunoregulatory receptors are categorized as stimulatory or inhibitory based on their engagement of unique intracellular signaling networks. These proteins also display functional plasticity, which adds versatility to the control of innate immunity. Here we demonstrate that an inhibitory catfish leukocyte immune-type receptor (IpLITR) also displays stimulatory capabilities in a representative myeloid cell model. Previously, the receptor IpLITR 1.1b was shown to inhibit natural killer cell-mediated cytotoxicity. Here we expressed IpLITR 1.1b in rat basophilic leukemia-2H3 cells and monitored intracellular signaling and functional responses. Although IpLITR 1.1b did not stimulate cytokine secretion, activation of this receptor unexpectedly induced phagocytosis as well as extracellular signal-related kinase 1/2- and protein kinase B (Akt)-dependent signal transduction. This novel IpLITR 1.1b-mediated response was independent of an association with the FcRγ chain and was likely due to phosphotyrosine-dependent adaptors associating with prototypical signaling motifs within the distal region of its cytoplasmic tail. Furthermore, compared to a stimulatory IpLITR, IpLITR 1.1b displayed temporal differences in the induction of intracellular signaling, and IpLITR 1.1b-mediated phagocytosis had reduced sensitivity to EDTA and cytochalasin D. Overall, this is the first demonstration of functional plasticity for teleost LITRs, a process likely important for the fine-tuning of conserved innate defenses.


Bioactive Flavonoids and Catechols as Hif1 and Nrf2 Protein Stabilizers - Implications for Parkinson's Disease.
Flavonoids are known to trigger the intrinsic genetic adaptive programs to hypoxic or oxidative stress via estrogen receptor engagement or upstream kinase activation. To reveal specific structural requirements for direct stabilization of the transcription factors responsible for triggering the antihypoxic and antioxidant programs, we studied flavones, isoflavones and catechols including dihydroxybenzoate, didox, levodopa, and nordihydroguaiaretic acid (NDGA), using novel luciferase-based reporters specific for the first step in HIF1 or Nrf2 protein stabilization. Distinct structural requirements for either transcription factor stabilization have been found: as expected, these requirements for activation of HIF ODD-luc reporter correlate with in silico binding to HIF prolyl hydroxylase. By contrast, stabilization of Nrf2 requires the presence of 3,4-dihydroxy- (catechol) groups. Thus, only some but not all flavonoids are direct activators of the hypoxic and antioxidant genetic programs. NDGA from the Creosote bush resembles the best flavonoids in their ability to directly stabilize HIF1 and Nrf2 and is superior with respect to LOX inhibition thus favoring this compound over others. Given much higher bioavailability and stability of NDGA than any flavonoid, NDGA has been tested in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-animal model of Parkinson's Disease and demonstrated neuroprotective effects.


Treatment of isolated injuries of the lunotriquetral ligament. A comparison of arthrodesis, ligament reconstruction and ligament repair.
We studied 57 patients with isolated lunotriquetral injuries treated by arthrodesis, direct ligament repair, or ligament reconstruction. The outcomes were compared by using written questionnaires, the Disabilities of the Arm, Shoulder and Hand (DASH) score, range of movement, strength, morbidity and rates of reoperation. Isolated lunotriquetral injury was confirmed by arthroscopy or arthrotomy. The mean age of the patients was 30.7 years (15.4 to 53.7) and the injuries were subacute or chronic in 98.2%. Eight patients underwent lunotriquetral reconstruction using a distally-based strip of the tendon of extensor carpi ulnaris, 27 had lunotriquetral repair and 22 had lunotriquetral arthrodesis. The mean follow-up was 9.5 years (2 to 22). The probability of remaining free from complications at five years was 68.6% for reconstruction, 13.5% for repair, and less than 1% for arthrodesis. Of the lunotriquetral arthrodeses, 40.9% developed nonunion and 22.7% developed ulnocarpal impaction. The probability of not requiring further surgery at five years was 68.6% for reconstruction, 23.3% for repair and 21.8% for arthrodesis. The DASH scores for each group were not significantly different. Objective improvements in strength and movement, subjective indicators of pain relief and satisfaction were significantly higher in the lunotriquetral repair and reconstruction groups than in those undergoing arthrodesis.


Implementation of patient-focused care: before-after effects.
The purpose of this paper is to evaluate an organizationally oriented, patient-focused care (PFC) model's effects on care quality and work climate. The study has a before-after (PFC implementation) design. The sample included 1,474 patients and 458 healthcare providers in six participating wards before and after PFC implementation, plus five additional randomly chosen wards, which only featured in the post-assessment. No pre-post differences were found regarding care perceptions or provider work climate evaluations. Statistically significant improvements were noted among provider care evaluations. Using aggregate-level ward data, multiple regression analyses showed that high adherence to PFC principles and a positive work climate contributed significantly to variance among care quality ratings. Among healthcare providers, questions related to specific PFC aspects during evenings, nights and weekends had to be dropped owing to a low response rate. An important requirement for both practice and research is to tailor PFC to various health and social care contexts. The study is large-scale before-after PFC model review, where patient and provider data were collected using well-established measurements.


Gut microbiome composition and diversity are related to human personality traits.
The gut microbiome has a measurable impact on the brain, influencing stress, anxiety, depressive symptoms and social behaviour. This microbiome-gut-brain axis may be mediated by various mechanisms including neural, immune and endocrine signalling. To date, the majority of research has been conducted in animal models, while the limited number of human studies has focused on psychiatric conditions. Here the composition and diversity of the gut microbiome is investigated with respect to human personality. Using regression models to control for possible confounding factors, the abundances of specific bacterial genera are shown to be significantly predicted by personality traits. Diversity analyses of the gut microbiome reveal that people with larger social networks tend to have a more diverse microbiome, suggesting that social interactions may shape the microbial community of the human gut. In contrast, anxiety and stress are linked to reduced diversity and an altered microbiome composition. Together, these results add a new dimension to our understanding of personality and reveal that the microbiome-gut-brain axis may also be relevant to behavioural variation in the general population as well as to cases of psychiatric disorders.


Principles of Good Clinical Trial Design.
Clinical trials are a fundamental component of medical research and serve as the main route to obtain evidence of the safety and efficacy of treatment before its approval. A trial's ability to provide the intended evidence hinges on appropriate design, background knowledge, trial rationale to sample size, and interim monitoring rules. In this article, we present some general design principles for investigators and their research teams to consider when planning to conduct a trial.


The ABC's of disaster response.
The readiness of our healthcare facilities to respond to terrorist acts or naturally occurring epidemics and disasters has been at the center of public attention since September 11, 2001. The many other tragic events that have occurred throughout the world since then further reinforce the need for all healthcare facilities and medical personnel to increase their level of preparedness if they wish to optimize outcomes. Maximizing survival rates and minimizing disability during any MCI hinges on rapid, seamless, and coordinated response between first responders and first receivers. The Incident Command System and the HEICS are organizational tools that form the foundation for such a rapid and coordinated response. The ICS provides a simple and adaptable management structure that is capable of being expanded or contracted to meet the needs of a specific situation. The HEICS adapts the ICS into the hospital setting and, in addition to the benefits stated above; its use of the ICS nomenclature and terminology facilitates the communication and the sharing of resources between all agencies and health care institutions involved. A basic knowledge and understanding of the ICS principles and structure is essential for all individuals participating in a disaster response. Previous efforts at disaster preparedness have focused predominantly on the pre-hospital and rescue phase of the disaster response, but a complete and coordinated community response requires creation of integrated disaster plans. True readiness can only be achieved by testing and modifying these plans through integrated simulation drills and table top exercises. Hospital-wide drills are essential to educate all staff members as to their institutional plan and serve as the only substitute at present to first hand experience. At present, there is no evidence-based literature to define what constitutes the best medical response by medical personnel within a disaster setting. This information will likely evolve over the next several decades as we now recognize Disaster Medicine as a separate scientific and medical entity. In the interim, we can develop and modify our response plans based on the "lessons learned" from past experience. Prior events have demonstrated that general surgeons and surgical subspecialists are critical components to a successful hospital response for the vast majority of all mass casualty incidents. Thus, surgeons must take responsibility for increasing their knowledge and understanding of basic disaster management principles and must play an active role in developing their institutional disaster plans.


Indirect genetic effects for growth rate in domestic pigs alter aggressive and manipulative biting behaviour.
Indirect genetic effects (IGEs) are heritable effects of an individual on phenotypic values of others, and may result from social interactions. We determined the behavioural consequences of selection for IGEs for growth (IGEg) in pigs in a G × E treatment design. Pigs (n = 480) were selected for high versus low IGEg with a contrast of 14 g average daily gain and were housed in either barren or straw-enriched pens (n = 80). High IGEg pigs showed from 8 to 23 weeks age 40% less aggressive biting (P = 0.006), 27% less ear biting (P = 0.03), and 40% less biting on enrichment material (P = 0.005). High IGEg pigs had a lower tail damage score (high 2.0; low 2.2; P = 0.004), and consumed 30 % less jute sacks (P = 0.002). Selection on high IGEg reduced biting behaviours additive to the, generally much larger, effects of straw-bedding (P < 0.01), with no G × E interactions. These results show opportunities to reduce harmful biting behaviours in pigs.


Breast cancer patients with lobular cancer more commonly have a father than a mother diagnosed with cancer.
The association between lobular breast cancer and family history is not clear. The aim of the study was to possibly identifying new hereditary patterns predisposing for cancer in the different histopathologic subtypes of breast cancer, with focus on patients with lobular breast cancer and cancer in their first degree relatives. In 1676 consecutive breast cancer patients detailed family history of cancer was related to histopathologic subtype of breast cancer. Patients with lobular breast cancer were found to be significantly positively associated with having a father diagnosed with cancer, OR 2.17 (95% confidence interval (CI) 1.37-3.46). The finding persisted after excluding breast cancer in the family. Ductal breast cancer was associated with having a mother diagnosed with cancer. There was a significant association between lobular breast cancer and having a father with prostate cancer, OR 2.4 (CI 1.1-5.3). The occurrence of having a father with prostate cancer for lobular breast cancer patients was higher in the younger patient group, OR 2.9 (CI 1.1-7.8), and was still high but lost statistical significance in the older patient group, OR 1.9 (CI 0.5-7.4). The association between lobular breast cancer and a father remained significant after excluding fathers with prostate cancer, OR 1.94 (CI 1.20-3.14). Other commonly occurring tumor types in the father included sarcoma and leukemia. We propose that lobular breast cancer is associated with having a father diagnosed with cancer, most commonly prostate carcinoma. Since the association remained after excluding family history of breast cancer, the association seems independent of classical breast cancer heredity. The association with a father diagnosed with cancer also remained after removing prostate cancer, indicating an independence from prostate cancer as well. The reason for this association is genetically unclear, but could involve sex-specific imprinting.


Virtue Quadratic Male Sling for stress incontinence-surgical guide for placement and delayed revision.
The algorithm for surgical management of post prostatectomy incontinence classically includes male slings and artificial urinary sphincter (AUS) placement. The Virtue Quadratic Male Sling was designed to provide both urethral elevation and prepubic compression making it a viable option for a wider spectrum of incontinent men whose symptoms range from mild to severe. With a focus on two key steps of the surgery, (I) sling fixation (II) use of intraoperative retrograde leak point pressure (RLPP), this guide is intended to outline a safe and efficacious treatment for post-prostatectomy incontinence. Intriguingly, the sling can be revised in the event of refractory or worsening leakage, and does not preclude the placement of an AUS should it be needed. This paper describes a step by step approach to performing the procedure as well as expert tips to improve outcomes and avoid/manage complications that have been learned over the years.


Deciphering the incognito role of water in a light driven proton coupled electron transfer process.
Light induced multisite electron proton transfer in two different phenol (simple and phenol carrying an intramolecularly hydrogen bonded base) pendants on acridinedione dye (ADD) and an NADH analogue was studied by following fluorescence quenching dynamics in an ultrafast timescale. In a simple phenol derivative (ADDOH), photo-excited acridinedione acquires an electron from phenol intramolecularly, coupled with the transfer of a proton to solvent water. But in a phenol carrying hydrogen bonded base (ADDDP), both electron and proton transfer occur completely intramolecularly. The sequence of this electron and proton transfer process was validated by discerning the pH dependency of the reaction kinetics. Since photo-excited ADDs are stronger oxidants, the sequential electron first proton transfer mechanism (ETPT) was observed in ADDOH and hence there is no change in the PCET reaction kinetics kETPT ∼ 6.57 × 109 s-1 in the entire pH range (pH 2-12). But the phenol carrying hydrogen bonded base (ADDDP) unleashes concerted electron proton transfer where the PCET reaction rate decreases upon decreasing the pH below its pKa. Noticeably, the concerted EPT process in ADDDP mimics the donor side of photosystem II and it occurs by two distinct pathways: (i) through direct intramolecular hydrogen bonding between the phenol and amine, kDEPT ∼ 12.5 × 1010 s-1 and (ii) through the bidirectional hydrogen bond extended by the water molecule trapped in between the proton donor and acceptor, which mediates the proton transfer and serves as a proton wire, kWMEPT ∼ 2.85 × 1010 s-1. These results unravel the incognito role played by water in mediating the proton transfer process when the structural elements do not favor direct hydrogen bonding between the proton donor and acceptor in a concerted PCET reaction.


Coherent structural dynamics of a prototypical charge-density-wave-to-metal transition.
Using femtosecond time-resolved x-ray diffraction, we directly monitor the coherent lattice dynamics through an ultrafast charge-density-wave-to-metal transition in the prototypical Peierls system K(0.3)MoO(3) over a wide range of relevant excitation fluences. While in the low fluence regime we directly follow the structural dynamics associated with the collective amplitude mode; for fluences above the melting threshold of the electronic density modulation we observe a transient recovery of the periodic lattice distortion. We can describe these structural dynamics as a motion along the coordinate of the Peierls distortion triggered by the prompt collapse of electronic order after photoexcitation. The results indicate that the dynamics of a structural symmetry-breaking transition are determined by a high-symmetry excited state potential energy surface distinct from that of the initial low-temperature state.


Follow-up by repeated signal-averaged surface QRS in patients with the syndrome of arrhythmogenic right ventricular dysplasia.
Repeated signal-averaged surface electrocardiograms were recorded with a mean interval of 32.5 months (range 14 to 55 months) in 12 patients with the syndrome of arrhythmogenic right ventricular dysplasia (ARVD). The mean differences in the amplitude and duration of the filtered QRS complex (FQRS), the root mean square voltage of the last 40 ms of the FQRS and the duration of the terminal potentials of less than 25 microV were not statistically significant between the recordings. A wide spectrum of changes in the voltage and duration of the terminal potentials was observed, irrespective of the clinical susceptibility to ventricular tachycardia. Three patients developed changes suggesting a progression, with a decreased voltage and prolonged duration of the terminal potentials, and four patients showed the opposite pattern. In five patients the signals were stationary. It is concluded that the properties of late potentials may change with time in patients with ARVD. Follow-up by repeated signal-averaged QRS does not appear to be useful in predicting the susceptibility to ventricular tachycardia in ARVD. Its application in predicting and following progressive right ventricular morphological changes remains to be determined.


Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae.
The capacity of Neisseria gonorrhoeae to resist structurally diverse hydrophobic agents (HAs) because of the mtr (multiple transferable resistance) efflux system was found to be regulated at the level of transcription by two distinct mechanisms. This was surmised because a deletion that removed > 90% of the coding sequence of the mtrR (multiple transferrable resistance regulator) gene or a single-base-pair deletion within a 13-bp inverted repeat sequence located in its promoter resulted in altered expression of the mtrC gene; mtrC encodes a 44-kDa membrane lipoprotein essential for the efflux of HAs. However, the single-base-pair deletion had the more significant impact on gene expression since it resulted in the loss of expression of mtrR and a threefold increase in the expression of mtrC. Hence, the mtr efflux system in gonococci is subject to both MtrR-dependent and MtrR-independent regulation, and the levels of mtrC mRNA correlate well with HA resistance levels in gonococci.


Human pharmacogenetics of methyl conjugation.
Methyl conjugation is an important pathway in drug metabolism. Activities of three human drug-metabolizing methyltransferase enzymes, catechol-O-methyltransferase (COMT) (EC 184.108.40.206), thiopurine methyltransferase ( TPMT ) (EC 220.127.116.11), and thiol methyltransferase (TMT) (EC 184.108.40.206), are controlled by inheritance. COMT activity in the red blood cell (RBC) is regulated by a single genetic locus with two alleles, COMTL for low activity and COMTH for high activity. Gene frequencies of these two alleles were approximately equal in a white population sample of Northern European origin. The genetically controlled level of COMT activity in the RBC reflects the level of enzyme activity in other tissues and is significantly correlated with individual variations in the methyl conjugation of catechol drugs such as L-dopa and methyldopa. TPMT catalyzes the S-methylation of thiopurines and thiopyrimidines . RBC TPMT activity is also controlled by a single genetic locus with two alleles, TPMTL for low and TPMTH for high activity. The gene frequencies of these two alleles were 0.06 and 0.94, respectively, in a white population sample. RBC TPMT activity reflects the level of enzyme activity in other cells and tissues such as the lymphocyte and kidney. TMT catalyzes the S-methylation of aliphatic sulfhydryl compounds such as the drugs captopril and D-penicillamine. The heritability of the level of RBC membrane TMT activity has been estimated on the basis of family studies to be approximately 0.98. Regulation of these three methyl-conjugating enzymes by inheritance raises the possibility that genetically determined methylator status may be one factor responsible for variations in drug metabolism in humans.


Sticky signaling--adhesion class G protein-coupled receptors take the stage.
Adhesion-type heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (Adhesion-GPCRs) comprise a class of widely distributed seven-transmembrane spanning (7TM) receptors with unusual layout and properties. The key to understanding the function of Adhesion-GPCRs appears to be their hybrid architecture: They have an extracellular domain containing an extended array of protein folds fit for interactions, and structural elements of GPCRs with a 7TM and an intracellular domain. If and how these distinct protein portions interact is currently under intense investigation. Intriguingly, all Adhesion-GPCRs have a juxtamembrane GPCR autoproteolysis-inducing domain that, in many homologs, facilitates the autocatalytic processing into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which subsequently remain attached at the cell surface. The NTF provides the ability for combinatorial engagement with cellular or matrix-associated molecules facilitating cell adhesion, orientation, and positioning during development, immune responses, and tumor growth. The CTF, like in canonical GPCRs, initiates interactions with different types of signaling molecules, including heterotrimeric G proteins, small guanosine triphosphatases, and transmembrane protein partners, yet the agonistic potential of most known Adhesion-GPCR ligands is uncertain. Studies with truncated receptors suggest that the NTF and CTF of Adhesion-GPCRs may function as autonomous adhesive and signaling units, respectively, but other studies in nonvertebrates demonstrating NTF-CTF interplay challenge this view. We discuss the available data concerning the main structural elements of Adhesion-GPCRs in the context of receptor function and signaling.


Preparation and ex vivo evaluation of TEC as an absorption enhancer for poorly absorbable compounds in colon specific drug delivery.
In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 2(2) factorial design to optimize the preparation conditions. In ex vivo experiments, everted rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increase the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.


The endovascular management of penetrating carotid artery injuries: long-term follow-up.
To review a single-centre experience with stent-graft treatment of penetrating carotid artery injuries and long-term follow-up. All stable patients with carotid artery injuries presenting between August 1998 and February 2009 were considered for endovascular treatment. Patients were selected based on clinical and radiological criteria and data were prospectively collected. Follow-up was conducted clinically, angiographically and by telephonic contact. Endpoints were stroke, death and any other stent-graft-related complications. A total of 128 patients were treated, of whom only 19 were selected for endovascular management. The recorded technical success rate was 100%, with one early stroke and one non-stent-graft-related procedural death. A further four patients were lost to follow-up. The remaining 14 patients had a mean follow-up of nearly 4 years. No stent-graft-related late deaths, strokes or other complications were reported, although one instance of late stent-graft occlusion was documented. Endovascular management of penetrating carotid artery injuries is safe and the long-term outcomes justify a more liberal application of this technique in selected patients.


Modeling ancient Egyptian mummification on fresh human tissue: macroscopic and histological aspects.
Many studies have been concerned with the ancient Egyptian mummification method; nevertheless, little effort has been made to explore it experimentally. The goal of this study is to apply evidence-based diagnostic criteria and state-of-the art methodology in order to improve knowledge on soft tissues preservation and postmortem alterations. Two human lower limbs (LL) from a female donor were (1) "naturally" mummified by dry heat and (2) artificially in natron. At specific time intervals a macroscopic and radiological examination of the LL was performed and skin and muscle samples were taken for histological and biomolecular analysis. Temperature, humidity, pH, and weight of the LL were systematically measured. The mummification by dry heat was stopped after 7 days due to unexpected lack of mummification progress. The mummification in natron was completed successfully after 208 days. The humidity, the external temperature, and the pH were proven with Pearson correlation and principal component analysis as important factors for the mummification process. The steady removal of water from the tissues through the natron has prevented the putrefaction. This is also evident in the absence of bacteria or fungi through the microbiological analysis. The histological analysis revealed very good preservation of the skin and the muscle tissues. In the muscular sample certain degree of structural disintegration can be seen, particularly affecting the epimysium whilst in the skin samples the epidermis, especially the stratum corneum, is mostly affected. The samples show better preservation compared with ancient Egyptian sections and other mummified tissues from historic or forensic context.


In the search of novel urine biomarkers for the early diagnosis of prostate cancer. Intracellular or secreted proteins as the target group? Where and how to search for possible biomarkers useful in the everyday clinical practice.
To search which category of proteins can be detected in urine in order to examine subsequently its ability to improve our accuracy for the diagnosis of Prostate Cancer (PCa) as biomarkers in clinical useful fluids like urine and serum. Material and method(s): Urine samples of 127 patients were obtained after a vigorous transrectal prostatic massage to both lobes. The patients were considered to have a high risk for PCa according to their PSA (> 4 ng/ml), their digital rectal examination (DRE) (positive for suspicious prostatic lesions) or to their abnormal PSA kinetics (PSA velocity (PSAV > 0.75 ng/mL). All patients subsequently were subjected to an extended 10-core per prostatic lobe TRUS-b (total 20 prostatic samples). The proteins that were chosen to be detected in the urine samples with Western-blot, as possible biomarkers, were Glutathione peroxidase 3 precursor (GPx3), Cofilin-1 (CFL1), Heat shock protein-90β (HSP 90β), Zinc alpha 2-glycoprotein (ZAG) and secreted protein acidic and rich in cysteine (SPARC).These proteins have been detected previously in the prostatic tissue by proteomics proving their discriminative ability between patients with prostate cancer and benign prostatic hyperplasia. From the five proteins, only the secreted Zinc alpha 2-glycoprotein was detected in urine showing a promising ability in the improvement of our diagnostic accuracy for the early diagnosis of prostate cancer. From various categories of proteins that have already been detected in the tissue of prostate by proteomics, only secreted protein Zinc alpha 2-glycoprotein showed a clear signal in the urine, proving its discriminative potential for the early diagnosis of PCa.


Coronary Artery Occlusion during Transcatheter Aortic Valve Implantation: Early Recognition Have Better Outcome.
Transcatheter aortic valve implantation (TAVI) is one of the rapidly evolving treatment strategies for severe aortic stenosis. Included in this category are inoperable, high, intermediate, and low surgical risk patients. It has varying types of complications that may require urgent surgical or transcatheter interventions to prevent procedural mortality and morbidity. Coronary artery occlusion is a rare and dreaded complication of TAVI. Here, we report a 73-year-old man who was diagnosed with severe aortic stenosis and underwent transfemoral TAVI. Unfortunately, during preimplantation balloon valvuloplasty, the patient developed severe hypotension along with ischemic changes on the electrocardiographic monitor. Promptly, coronary angiography was performed which revealed complete occlusion of the left anterior descending artery secondary to embolic debris. He was successfully rescued by manual aspiration thrombectomy (MAT). MAT results in restoration of coronary flow and reversal of shock condition before completing TAVI procedure.


Out-of-hours primary care use at the end of life: a descriptive study.
Out-of-hours (OOH) primary care services are integral to the care of patients at end of life. Little is known about the OOH service usage of patients with palliative care needs. To describe patterns of usage of patients presenting to an OOH service and coded as 'palliative'. A descriptive study of data from the Oxfordshire OOH service. A database of all patient contacts with the Oxfordshire OOH service from a 4-year period (June 2010-August 2014) was used to extract demographic and service usage data for all contacts to which clinicians had applied a 'palliative' code. Observed differences in demographic features between palliative and non-palliative contacts were tested using logistic regression. Out of a total of 496 931 contacts, there were 6045 contacts coded palliative; those 'palliative' contacts provided care to 3760 patients. Patients contacting the OOH service with palliative care needs did so predominantly during weekend daytime periods, and over a third had more than one contact. Patients were predictably older than the average population, but contacts coded as 'palliative' were relatively less deprived than contacts to the OOH service for all causes, even after adjusting for age and sex. The current 'one-size-fits-most' model of OOH primary care may not allow for the specific needs of patients at the end of life. Wider analysis of palliative patient flow through urgent care services is needed to identify whether healthcare access at the end of life is inequitable, as well as the capacity requirements of a community-based service that can provide high-quality end-of-life care.


Lung deposition patterns of MWCNT vary with degree of carboxylation.
Functionalization of multi-walled carbon nanotubes (MWCNT) is known to affect the biological response (e.g. toxicity, inflammation) in vitro and in vivo. However, the reasons for these changes in vivo are not well described. This study examined the degree of MWCNT functionalization with regard to in vivo mouse lung distribution, particle retention, and resulting pathology. A commercially available MWCNT (source MWCNT) was functionalized (f-MWCNT) by systematically varying the degree of carboxylation on the particle's surface. Following a pilot study using seven variants, two f-MWCNT variants were chosen and for lung pathology and particle distribution using oropharyngeal aspiration administration of MWCNT in Balb/c mice. Particle distribution in the lung was examined at 7 and 28 days post-instillation by bright-field microscopy, CytoViva hyperspectral dark-field imaging, and Stimulated Raman Scattering (SRS) microscopy. Examination of the lung tissue by bright-field microscopy showed some acute inflammation for all MWCNT that was highest with source MWCNT. Hyperspectral imaging and SRS were employed to assess the changes in particle deposition and retention. Highly functionalized MWCNT had a higher lung burden and were more disperse. They also appeared to be associated more with epithelial cells compared to the source and less functionalized MWCNT that were mostly interacting with alveolar macrophages (AM). These results showing a slightly reduced pathology despite the extended deposition have implications for the engineering of safer MWCNT and may establish a practical use as a targeted delivery system.


Immigrants contributed an estimated $115.2 billion more to the Medicare Trust Fund than they took out in 2002-09.
Many immigrants in the United States are working-age taxpayers; few are elderly beneficiaries of Medicare. This demographic profile suggests that immigrants may be disproportionately subsidizing the Medicare Trust Fund, which supports payments to hospitals and institutions under Medicare Part A. For immigrants and others, we tabulated Trust Fund contributions and withdrawals (that is, Trust Fund expenditures on their behalf) using multiple years of data from the Current Population Survey and the Medical Expenditure Panel Survey. In 2009 immigrants made 14.7 percent of Trust Fund contributions but accounted for only 7.9 percent of its expenditures-a net surplus of $13.8 billion. In contrast, US-born people generated a $30.9 billion deficit. Immigrants generated surpluses of $11.1-$17.2 billion per year between 2002 and 2009, resulting in a cumulative surplus of $115.2 billion. Most of the surplus from immigrants was contributed by noncitizens and was a result of the high proportion of working-age taxpayers in this group. Policies that restrict immigration may deplete Medicare's financial resources.


Measurements of 3D relative locations of particles by Fourier Interferometry Imaging (FII).
In a large number of physical systems formed of discrete particles, a key parameter is the relative distance between the objects, as for example in studies of spray evaporation or droplets micro-explosion. This paper is devoted to the presentation of an approach where the relative 3D location of particles in the control volume is accurately extracted from the interference patterns recorded at two different angles. No reference beam is used and only ten (2 + 8) 2D-FFT have to be computed.


The protective role of pregnancy in breast cancer.
Epidemiological, clinical, and experimental data indicate that the risk of developing breast cancer is strongly dependent on the ovary and on endocrine conditions modulated by ovarian function, such as early menarche, late menopause, and parity. Women who gave birth to a child when they were younger than 24 years of age exhibit a decrease in their lifetime risk of developing breast cancer, and additional pregnancies increase the protection. The breast tissue of normally cycling women contains three identifiable types of lobules, the undifferentiated Lobules type 1 (Lob 1) and the more developed Lobules type 2 and Lobules type 3. The breast attains its maximum development during pregnancy and lactation (Lobules type 4). After menopause the breast regresses in both nulliparous and parous women containing only Lob 1. Despite the similarity in the lobular composition of the breast at menopause, the fact that nulliparous women are at higher risk of developing breast cancer than parous women indicates that Lob 1 in these two groups of women might be biologically different, or might exhibit different susceptibility to carcinogenesis. Based on these observations it was postulated that Lob 1 found in the breast of nulliparous women and of parous women with breast cancer never went through the process of differentiation, retaining a high concentration of epithelial cells that are targets for carcinogens and are therefore susceptible to undergo neoplastic transformation. These epithelial cells are called Stem cells 1, whereas Lob 1 structures found in the breast of early parous postmenopausal women free of mammary pathology, on the contrary, are composed of an epithelial cell population that is refractory to transformation, called Stem cells 2. It was further postulated that the degree of differentiation acquired through early pregnancy has changed the 'genomic signature' that differentiates Lob 1 of the early parous women from that of the nulliparous women by shifting the Stem cells 1 to Stem cells 2 that are refractory to carcinogenesis, making this the postulated mechanism of protection conferred by early full-term pregnancy. The identification of a putative breast stem cell (Stem cells 1) has, in the past decade, reached a significant impulse, and several markers also reported for other tissues have been found in the mammary epithelial cells of both rodents and humans. Although further work needs to be carried out in order to better understand the role of the Stem cells 2 and their interaction with the genes that confer them a specific signature, collectively the data presently available provide evidence that pregnancy, through the process of cell differentiation, shifts Stem cells 1 to Stem cells 2 - cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.


The repression of cell wall- and plastid-related genes and the induction of defense-related genes in rice plants infected with Rice dwarf virus.
An analysis, using microarrays, of gene expression in rice plants infected with Rice dwarf virus revealed significant decreases in levels of expression of genes that are involved in the formation of cell walls, reflecting the stunted growth of diseased plants. The expression of plastid-related genes also was suppressed, as anticipated from the white chlorotic appearance of infected leaves. By contrast, the expression of defense- and stress-related genes was enhanced after viral infection. These results suggest that virus-infected rice plants attempt to survive viral infection and replication by raising the levels of expression of defense- and stress-related genes while suppressing the expression of genes required for the elongation of cells and photosynthesis.


Cromakalim (BRL 34915) restores in vitro the membrane potential of depolarized human skeletal muscle fibres.
The purpose of the present study was to analyze the effects of cromakalim (BRL 34915), a potent drug from a new class of drugs characterized as "K+ channel openers", on the electrical activity of human skeletal muscle. Therefore, intracellular recordings were used to measure the effects of cromakalim on the membrane potential and input conductance of fibres from human skeletal muscle biopsies. Cromakalim in a concentration above 1 mumol/l induced an increase in membrane K+ conductance. This effect resulted in a membrane hyperpolarization. The magnitude of this polarization depended on the difference between resting and K+ equilibrium potential. The effect had a rapid onset and was quickly reversible after washing. Fibres from two patients with hyperkalaemic periodic paralysis showed an excessive membrane depolarization during and also after exposure to an slightly elevated extracellular K+ concentration. In the latter situation, cromakalim repolarized the fibres to the normal resting potential. Tolbutamide (1 mmol/l) and Ba2+ (3 mmol/l) strongly antagonized the effect of cromakalim. The data show that cromakalim hyperpolarizes depolarized human skeletal muscle fibres maintained in vitro. The underlying mechanism is probably an activation of otherwise "silent", ATP-regulated K+ channels. Such an effect may be of therapeutic benefit in a situation in which a membrane depolarization causes muscle paralysis.


Susceptibility and carrier status of impala, sable, and tsessebe for Cowdria ruminantium infection (heartwater).
Three species of wild African ruminants, impala (Aepyceros melampus), sable (Hippotragus equinus), and tsessebe (Damaliscus lunatus), were experimentally inoculated with in vitro culture-derived Cowdria ruminantium organisms, the tick-borne causative agent of heartwater in domestic ruminants, to determine their susceptibility to infection. No clinical disease was observed in any of the ruminants. However, C. ruminantium was detected in the sable by the transmission of heartwater to susceptible sheep, through the tick vector Amblyomma hebraeum, at 10 and 37 days postinfection (PI). Attempts to detect infection in the impala and tsessebe by tick transmission at 54 days PI failed. The impala and tsessebe were reinoculated with C. ruminantium organisms at 146 days after the first inoculation; however, a tick transmission attempt at 66 days after the reinoculation also failed. Seroconversion, as detected by immunoblotting, was demonstrated in the sable and the tsessebe but not in the impala. The results demonstrate that sable can be carriers of C. ruminantium. The susceptibility of tsessebe and impala, however, remains undetermined.


Effect of overexpression of LPAAT and GPD1 on lipid synthesis and composition in green microalga Chlamydomonas reinhardtii.
Biodiesel is an alternative energy source which has attracted increasing attention lately. Although algae-based biodiesel production has many benefits, it is still far from industrial application. Research suggests that improving lipid quality and production through genetic engineering of metabolic pathways will be the most promising way. To enhance lipid content, both lysophosphatidic acyltransferase gene (c-lpaat) and glycerol-3-phosphate dehydrogenase gene (c-gpd1), optimized according to the codon bias of Chlamydomonas reinhardtii, were inserted into the genomic DNA of model microalga C. reinhardtii by the glass bead method. Transgenic algae were screened by zeomycin resistance and RT-PCR. The transcription levels of inserted genes and the fatty acid content were significantly increased after intermittent heat shock. Most of all, the transcription levels of c-lpaat and c-gpd1 were increased 5.3 and 8.6 times after triple heat shocks, resulting in an increase of 44.5 and 67.5% lipid content, respectively. Furthermore, the content of long-chain saturated fatty acids and monounsaturated fatty acids, especially C18 and C18:1t, notably increased, while unsaturated fatty acids dramatically decreased. The results of this study offer a new strategy combining genetic manipulation and intermittent heat shock to enhance lipid production, especially the production of long-chain saturated fatty acids, using C. reinhardtii.