Two structurally distinct kappa B sequence motifs cooperatively control LPS-induced KC gene transcription in mouse macrophages.
The mouse KC gene is an alpha-chemokine gene whose transcription is induced in mononuclear phagocytes by LPS. DNA sequences necessary for transcriptional control of KC by LPS were identified in the region flanking the transcription start site. Transient transfection analysis in macrophages using deletion mutants of a 1.5-kb sequence placed in front of the chloramphenicol acetyl transferase (CAT) gene identified an LPS-responsive region between residues -104 and +30. This region contained two kappa B sequence motifs. The first motif (position -70 to -59, kappa beta 1) is highly conserved in all three human GRO genes and in the mouse macrophage inflammatory protein-2 (MIP-2) gene. The second kappa B motif (position -89 to -78, kappa B2) was conserved only between the mouse and the rat KC genes. Consistent with previous reports, the highly conserved kappa B site (kappa B1) was essential for LPS inducibility. Surprisingly, the distal kappa B site (kappa B2) was also necessary for optimal response; mutation of either kappa B site markedly reduced sensitivity to LPS in RAW264.7 cells and to TNF-alpha in NIH 3T3 fibroblasts. Although both kappa B1 and kappa B2 sequences were able to bind members of the Rel homology family, including NF kappa B1 (P50), RelA (65), and c-Rel, the kappa B1 site bound these factors with higher affinity and functioned more effectively than the kappa B2 site in a heterologous promoter. These findings demonstrate that transcriptional control of the KC gene requires cooperation between two kappa B sites and is thus distinct from that of the three human GRO genes and the mouse MIP-2 gene.


Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis.
The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area. Weighted and Fleiss kappa were used to calculate intra- and interrater agreement on classification of ulcers, and intraclass correlation coefficient (ICC) was used to assess agreement on ulcer area. Because the traditional ICC calculations relied on a small number of ulcers, ICCs were recalculated using the results of linear mixed models to evaluate the variance components of observations on all the data. Intrarater kappa for classifying DU as not an ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and interrater kappa was moderate (0.53). The ICC for ulcer area using the linear mixed models was moderate both for intrarater (0.57) and interrater (0.48) measurements. A consensus for the classification of DUs in SSc was developed, and after a training session, rheumatologists with expertise in SSc are able to reliably classify DUs and to measure ulcer area.


Rapid correction of early metabolic acidaemia in comparison with placebo, no intervention or slow correction in LBW infants.
Metabolic or mixed (metabolic and respiratory) acidosis are commonly encountered problems in the low birth weight (LBW) infant after delivery, and they may contribute to mortality and morbidity. Causes for the lactic acidosis are multiple and include maternal, placental and fetal factors. It is unclear whether metabolic acidaemia in the first 24 hours of life in LBW infants should be corrected by rapid infusion of alkali. The main objective was to assess the short and long-term effects of the rapid correction of early (first 24 hours) metabolic acidaemia in LBW (<2500g birth weight) neonates. Searches were undertaken of MEDLINE from October 2001 back to 1966 and the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2001). The title and abstract of each retrieved study were examined to assess eligibility. If there was uncertainty, the full paper was examined. Types of studies All randomised controlled trials where short or long term effects of treatment with alkalising agents by rapid infusion were compared with placebo or no treatment, or where rapid infusion of alkalising agents was compared with slow infusion. Types of participants Newborn infants with birth weight <2500g and less than 24 hours of age with proven metabolic acidaemia (on arterial blood gas). Types of interventions Rapid correction of acidaemia with alkalising agents (sodium bicarbonate and/or THAM) given as a bolus over 5 minutes or less compared with either placebo, no intervention or slow infusion (>5 minutes). Types of outcome measures 1) maximal oxygen requirement in first 24 hours 2) duration of oxygen therapy 3) need for and duration of assisted ventilation 4) intraventricular haemorrhage and/or periventricular leucomalacia 5) survival to discharge 6) long term survival (to 24 months of age) 7) neurological and developmental outcome at 24 months of age Each reviewer assessed eligibility, trial quality and extracted data separately, then compared and resolved differences. Study authors were contacted for additional information if necessary. No studies were found meeting the criteria for inclusion in this review. There is no evidence available from randomised controlled trials to support or refute the rapid correction of metabolic acidaemia, in LBW infants in the first 24 hours of life, as compared with slow or no correction.


MHC antigens and cancer: implications for T-cell surveillance.
Evidence for a direct involvement of cell-mediated immune mechanisms in the control of human tumours remains sketchy. The past year, however, has seen advances in our understanding of the relationship between the immune system and tumour cells, and has given rise to new prospects for immunological treatment and the prevention of cancers.


Long-term hygienic barrier efficiency of a compact on-site wastewater treatment system.
The long-term use of a filter-based, on-site wastewater treatment system increases nutrient discharge to receiving waters and may reduce its hygienic barrier efficiency. The main purpose of this research was to assess the hygienic barrier efficiency and the associated health risks of an on-site system that had exceeded its 5-yr design capacity with respect to phosphorus (P) removal. The system was investigated for bacteria and virus removal and assessed with respect to potential health risks in relation to reuse of effluent for irrigation. The system consists of a septic tank, a pressure-dosed vertical flow biofilter, and an up-flow filter unit with lightweight clay aggregates. The total P concentration in the effluent had increased gradually from initially <0.1 mg P L(-1) during the first 2 yr of operation to 1.8 mg P L(-1) after 5.3 yr. Escherichia coli was used as an indicator organism for fecal bacteria removal, whereas bacteriophages phiX174 and Salmonella typhimurium phage 28B (S.t. 28B) were used to model enteric virus removal. An overall decrease in E. coli removal occurred from a complete (approximately 5.6 log10) reduction during the first 3 yr of operation to 2.6 log10 reduction. The removal amounts of the bacteriophages phiX174 and S.t. 28B were 3.9 and 3.7 log10, respectively. Based on removal of S.t. 28B, the risks of rotavirus infection and disease for the investigated scenarios were above the acceptable level of 10(-4) and 10(-3), respectively, as defined by the World Health Organization.


A gender comparison of central and peripheral neuromuscular function after exercise.
Central and peripheral muscle fatigue during exercise may exacerbate neuromuscular factors that increase risk for noncontact anterior cruciate ligament injury. To compare lower extremity motor-evoked potentials (MEPs), muscle strength, and electromyography (EMG) activation after an exercise protocol. Pretest, posttest group comparison. University laboratory. 34 healthy volunteers (17 female, age = 21.9 ± 2.3 years, weight = 77.8 ± 3.0 kg, height = 171.1 ± 6.6 cm, and 17 male, age = 23.4 ± 6.5 years, weight = 81.6 ± 3.3 kg, height = 179.6 ± 7.3 cm). A standardized 30-min exercise protocol that involved 5 repeated cycles of uphill walking, body-weight squatting, and step-ups. Quadriceps and hamstring MEP amplitude (mV) and transmission velocity normalized to subject height (m/s) were elicited via transcranial magnetic stimulation and measured via surface EMG. Quadriceps and hamstring peak EMG activation (% MVIC) and peak torque (Nm/kg) were measured during MVICs. Separate ANCOVAs were used to compare groups after exercise while controlling for baseline measurement. At baseline, males exhibited significantly greater knee-extension torques (males = 2.47 ± 0.68 Nm/kg, females = 1.95 ± 0.53 Nm/kg; P = .036) and significantly higher hamstring MEP amplitudes (males = 223.5 ± 134.0 mV, females = 89.3 ± 77.6 mV; P = .007). Males exhibited greater quadriceps MEP amplitude after exercise than females (males = 127.2 ± 112.7 mV, females = 32.3 ± 34.9 mV; P = .016). Males experienced greater peripheral neuromuscular changes manifested as more pronounced reductions in quadriceps torque after exercise. Females experienced greater central neuromuscular changes manifested as more pronounced reduction in quadriceps MEP amplitude. Reduced central neural drive of the quadriceps coupled with knee-extension torque preservation after exercise may increase risk of knee injury in females.


Multisensory hypersensitivity in women with fibromyalgia: implications for well being and intervention.
To document sensory sensitivities to nonnoxious sensory stimuli in daily life for participants with fibromyalgia (FM). Descriptive study of a convenience sample using a self-report survey of sensory processing. Participants were recruited from the general community. The procedure took place in a research room at the University of Wisconsin-Madison. Women with FM (n=27) were compared with women with rheumatoid arthritis (RA) (n=28) and healthy pain-free women (controls) (n=28) (N=83). Not applicable. A self-report measure of sensory sensitivity to stimuli encountered in daily life. Items ask participants if they are sensitive to sensations that do not seem to bother other people or avoid common activities or environments because of sensory stimuli. The FM group reported significantly increased sensory sensitivities to both somatic (tactile) and nonsomatic (eg, auditory and olfactory) sensory stimuli compared with the RA and control groups. The RA and control groups did not differ in reported hypersensitivities. Women with fibromyalgia reported increased sensitivities to stimuli in the environment and could experience more stress related to sensory conditions in daily life.


Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve.
The genetic loss of endothelial-derived nitric oxide synthase (eNOS) in mice impairs vascular endothelial growth factor (VEGF) and ischemia-initiated blood flow recovery resulting in critical limb ischemia. This result may occur through impaired arteriogenesis, angiogenesis, or mobilization of stem and progenitor cells. Here, we show that after ischemic challenge, eNOS knockout mice [eNOS (-/-)] have defects in arteriogenesis and functional blood flow reserve after muscle stimulation and pericyte recruitment, but no impairment in endothelial progenitor cell recruitment. More importantly, the defects in blood flow recovery, clinical manifestations of ischemia, ischemic reserve capacity, and pericyte recruitment into the growing neovasculature can be rescued by local intramuscular delivery of an adenovirus encoding a constitutively active allele of eNOS, eNOS S1179D, but not a control virus. Collectively, our data suggest that endogenous eNOS-derived NO exerts direct effects in preserving blood flow, thereby promoting arteriogenesis, angiogenesis, and mural cell recruitment to immature angiogenic sprouts.


Hidden disseminated extracutaneous AIDS-related Kaposi sarcoma.
A 68-year-old man with past medical history of multiple cerebral infarctions presented to our hospital with subacute paresis. His vital signs on presentation were normal, and his physical examination, other than his neurological findings, was unremarkable. Neurological examinations suggested cerebellar ataxia. Laboratory testing confirmed positive for human immunodeficiency virus (HIV) infection. His CD4-positive lymphocyte count was 45/μL, and HIV-RNA was 2.3 × 105 copies/mL. Brain computed tomography (CT) scan revealed multiple mass lesions and brain magnetic resonance imaging (MRI) with fluid-attenuated inversion-recovery (FLAIR) revealed periventricular hyperintensities, which suggested multiple malignant lymphoma and HIV encephalopathy. His state of consciousness had gradually worsened. Eventually, he died one month after admission. The autopsy unexpectedly showed disseminated Kaposi's sarcoma (KS). KS lesions were found in the stomach, small intestine, liver, spleen, mesentery and lungs. KS was not observed on his skin. Gross findings revealed multiple nodular lesions in each organ, and hematoxylin and eosin staining showed proliferation of spindle cells with vascular proliferation. Immunostaining was positive both for endothelial marker (CD31 and von Willebrand factor) and lymphatic endothelial marker (D2-40), which were consistent with KS.KS is the most common tumor in AIDS patients. It is caused by the human herpes-virus 8 infection. It manifests an indolent clinical course and mostly involves cutaneous lesions over the lower limbs, trunk and oral cavity. In this case, autopsy revealed disseminated KS pathologically, which was unrecognized before his death. This case highlights the possible existence of disseminated KS even without its cutaneous findings.


Mechanical stress in Arabidopsis leaves orients microtubules in a 'continuous' supracellular pattern.
Cortical microtubules form a dynamic network and continuously undergo shrinking (catastrophe), pausing and rebuilding (rescue). The advantage of such a dynamic system is that it may mediate appropriate responses in a short time span. Microtubules are known to play a pivotal role in determining the orientation of the cellulose microfibril deposition in the plant cell wall. The latter is a solid exoskeleton surrounding the protoplast. It forms the physical framework that interconnects most cells and has to bear the tensile stresses within the tissue. Here we describe the effect of externally applied pressure on microtubule organization in growing Arabidopsis leaves. Confocal microscopy examination of transgenic plants bearing GFP-tagged TUA6 proteins led to the observation that application of an additional mechanical pressure on growing Arabidopsis leaves triggers an excessive bundling of microtubules within the individual cell. Besides, the microtubules seem to align in neighboring cells, creating a 'continuous' supracellular pattern. This effect occurs within 3 hours after applied external force and is age-dependent, whereby only cells of leaves up to 19 days after sowing (DAS) are susceptible to the applied pressure. Upon externally applied pressure on developing Arabidopsis leaves, microtubules bundle and rearrange to form seemingly continuous supracellular patterns. As microtubules guide the cellulose synthase complexes, this observed reorganisation pattern probably affects the cellulose deposition, contributing to the reinforcement of the cell wall in a particular position to cope with the extra-applied pressure. The age-effect is reasonable, since younger cells, which are actively shaping their cell walls, are more vulnerable to altered mechanical stresses while in leaves older than 19 DAS, the walls are more robust and therefore can sustain the applied forces.


Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction.
Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium.


Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat.
Subcutaneous injection of formalin into the dorsal surface of the hindpaw evoked a two-phased flinching (phase 1:0-9 min; phase 2: 10-60 min) of the injected paw. Intrathecal administration of the nonsteroidal anti-inflammatory drugs (NSAID) produced minimal effects upon phase 1, but showed a significant, though submaximal, dose-dependent suppression of the phase 2 response. Ordering of i.t. potency was (ID50 in nmol): indomethacin (1.9) > or = flurbiprofen (2.1) > ketorolac (5.2) > or = zomepirac (5.9) > S(+)ibuprofen (16) > or = ibuprofen(racemic) (19) > acetylsalicylic acid (27) > acetaminophen (250) > R(-)ibuprofen (> 270) = 0. Intraperitoneal administration also produced a dose-dependent inhibition of phase 2, but only at doses which were 100 to 1000 times higher than those required to produce similar effects after i.t. injection. Intrathecal and i.p. dose-response curves showed similar distinct plateaus of maximum achievable inhibition (intrinsic activity) of the phase 2 behavior, ranging from 20 to 50% of the control response. Varying the time of drug injection reveals that injection 9 min after formalin yielded effects the same as those observed when the agent was given 2 min before formalin. Pretreatment at longer intervals indicated that the duration of the antinociceptive effect was between 3 to 6 hr after the i.t. injection. The i.t. injection of the highest doses of the several NSAID were without significant effect upon the 52.5 degrees C hot plate test. These studies indicate that NSAID have a powerful effect upon spinal nociceptive processing evoked by the s.c. injection of formalin.


Iatrogenic epilepsy due to antidepressant drugs.
AN ANALYSIS OF THE CASE HISTORIES OF NINE PATIENTS WHO DEVELOPED EPILEPTIC FITS SHORTLY AFTER STARTING TRICYCLIC ANTIDEPRESSANT DRUGS SHOWED THAT ALL OF THEM HAD ONE OR MORE OF THE FOLLOWING FACTORS: previous or family history of epilepsy, pre-existing brain damage, cerebral arteriosclerosis, alcoholism, withdrawal of barbiturates, and history of previous electric convulsive therapy. Before prescribing antidepressant drugs these factors should be sought for in the history, and if any are present prophylactic anticonvulsant medication is indicated. From a limited experience we do not think that chlordiazepoxide is adequate to counteract the convulsant effect of antidepressant drugs.


The parent-child relationship and adolescent alcohol use: a systematic review of longitudinal studies.
Alcohol use among adolescents has become a major public health problem in the past decade and has large short- and long-term consequences on their health. The aim of this systematic review was to provide an overview of longitudinal cohort studies that have analyzed the association between the parent-child relationship (PCR) and change in alcohol use during adolescence. A search of the literature from 1985 to July 2011 was conducted in Medline, PsycINFO, and EMBASE in order to identify longitudinal, general population studies regarding the influence of the PCR on alcohol use during adolescence. The studies were screened, and the quality of the relevant studies was assessed. A best-evidence synthesis was used to summarize the results. Twenty-eight relevant studies were identified. Five studies found that a negative PCR was associated with higher levels of alcohol use. Another seven papers only found this association for certain subgroups such as boys or girls, or a specific age group. The remaining sixteen studies did not find any association. We found weak evidence for a prospective association between the PCR and adolescent alcohol use. Further research to the association of the PCR with several types of alcohol use (e.g., initiation or abuse) and to the potential reversed causality of the PCR and alcohol use is required.


Effect of the Sonas Programme on Communication in People with Dementia: A Randomized Controlled Trial.
Strategies to improve communication in people with dementia are warranted. We examined the effect of the Sonas programme on communication ability in persons with moderate to severe dementia. A 24-week 3-armed (Sonas, reading, and control group) randomized controlled trial including 120 nursing home residents with dementia was conducted; 105 completed the follow-up assessments. The main outcome was change in communication abilities measured by the Holden Communication Scale (HCS). We found no overall significant effect of the Sonas programme with regard to communication ability as measured by the HCS. However, an effect between the Sonas group and the reading group and between the Sonas group and the control group from T0 to T1 and T2 was found, as well as a significant improvement in communication in the Sonas group. Among people with severe dementia, the Sonas group scored significantly better on the HCS compared to the reading group after 12 weeks, but not after 24 weeks. This study failed to document an overall effect of the Sonas programme on communication; however, the findings indicate that the Sonas programme has a significant effect on communication among those with severe dementia.


Recommendations for Trauma and Emergency General Surgery Practice During COVID-19 Pandemic.
COVID-19 is a new disease, based on currently available limited information, older adults and people of any age who have severe underlying medical conditions may be at higher risk for severe illness from COVID-19. People of all age groups are also at risk. Healthcare providers have always been the professionals most exposed to the risk of contracting to any kind of infection due to the nature of their profession. Elective interventions have been postponed to give care of patients with COVID-19. However, some interventions cannot be delayed, such as trauma surgery, acute abdomen, and emergency endoscopies. To maintain the sustainability of the healthcare system, the protection of healthcare providers should be the top priority. On the other hand, patients, who need emergency healthcare, should also be provided with appropriate treatment. Healthcare professionals should choose a treatment method appropriately in the circumstances to protect themselves and their patients as much as possible. This paper aims to summarize how a surgeon may act appropriately when an intervention is inevitable during the COVID-19 pandemic.


Pneumococcal disease surveillance in Europe.
Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD) - mainly meningitis and septicaemia - and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100 000 in the general population, with a total of 23 470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.


Goal striving, coping, and well-being: a prospective investigation of the self-concordance model in sport.
Developing upon cross-sectional research (Smith, Ntoumanis, & Duda, 2007) supporting the self-concordance model (Sheldon & Elliot, 1999) as a framework for contextual goal striving, the current study investigated the assumptions of the model in relation to season-long goal striving in sport. The study additionally examined the role of coping strategies in the persistence of goal-directed effort. Structural equation modeling analysis with a sample of 97 British athletes indicated that start-of-season autonomous goal motives were linked to midseason effort, which subsequently predicted end-of-season goal attainment. Attainment was positively related to changes in psychological need satisfaction, which, in turn, predicted changes in emotional well-being. In a second model, autonomous and controlled motives positively predicted task- and disengagement-oriented coping strategies, respectively. In turn, these strategies were differentially associated with effort. The findings provide support for contextual adaptations of the self-concordance model and demonstrate the role of coping strategies in the goal striving process.


The Healthy Primary School of the Future: study protocol of a quasi-experimental study.
Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined. In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019. A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific foundation, these integrated programmes have the potential to form a template for primary schools worldwide. The effects of this approach may extend further than the outcomes associated with well-being and academic achievement, potentially impacting legal and cultural aspects in our society. The study protocol was registered in the database ClinicalTrials.gov on 14-06-2016 with the reference number NCT02800616 .


α-Synuclein forms non-selective cation channels and stimulates ATP-sensitive potassium channels in hippocampal neurons.
In Parkinson's disease, the protein α-synuclein (αS) is produced within neurons and also appears in the extracellular fluid. In this study in hippocampal neurons, αS formed non-selective cation channels with multiple levels of conductance and rectification depending on their insertion site. αS channels induced local spontaneous increases in intracellular Na(+) and Ca(2+), depolarized neurons, augmented bursting activity and stimulated the opening of ATP-sensitive K(+) channels. Non-selective channels were also observed in neurons transfected with either wild-type or mutant A53T αS, and after extracellular application of these proteins. The properties of αS channels in neuronal membranes suggest that extracellular αS is more toxic than αS produced within neurons. In Parkinson's disease and several other neurodegenerative diseases, the protein α-synuclein (αS) is produced within neurons and accumulates in the extracellular fluid. Several mechanisms of αS action are proposed, one of which is the formation of cation-permeable pores that may mediate toxicity. αS induces non-selective cation channels in lipid bilayers, but whether this occurs in living neurons and which properties the channels possess have not yet been examined. In this study the properties of αS channels in dissociated hippocampal neurons are documented. In cell-attached recordings the incorporation of αS into membranes was driven by applied negative potentials. These channels exhibited multiple levels of conductance (30, 70 and 120 pS at -100 mV) and inward rectification. The persistent activity of αS channels induced local changes in intracellular Na(+) and Ca(2+), depolarized neurons and augmented bursting activity. αS channels formed by adding αS to the intracellular membrane in inside-out patches exhibited outward rectification. αS channels were equally permeable to Na(+), K(+) and Ca(2+). These channels were also observed in neurons transfected with wild-type or mutant A53T αS, and after extracellular application of wild-type or mutant A53T αS proteins. Opening of αS channels stimulated opening of ATP-sensitive K(+) (KATP ) channels and did not interfere with the activity of delayed rectifier K(+) channels. The properties of αS channels in neuronal membranes suggest stronger toxicity of extracellularly applied αS than intracellular αS. Enhancement of neuronal excitability and distortions in ion homeostasis may underlie the toxic effects of αS that can be dampened by KATP channels.


Order-restricted dose-related trend tests.
Methods of isotonic regression are proposed to increase the power of common trend tests in situations where a monotonicity constraint is imposed upon the dose-response function. Isotonic versions of Cochran-Armitage type trend tests for binary response data are developed, and the bootstrap method is used in finding the empirical distributions of the test statistics and their critical values. The isotonic likelihood ratio test with a survival adjustment is also proposed. This survival adjustment can be applied to the likelihood ratio test for either the order-restricted or unrestricted parameter cases. To achieve the isotonic modifications, an amalgamation algorithm is applied when the observed dose-response is non-monotonic. A Monte Carlo simulation study comparing these trend tests shows the advantages of the isotonic modifications and survival adjustment. By applying the proposed methods to data from a toxicology and carcinogenesis study conducted as part of the National Toxicology Program, the effect of CI Pigment Red 23 is investigated.


Regulation of cortical actin cytoskeleton assembly during polarized cell growth in budding yeast.
We have established an in vitro assay for assembly of the cortical actin cytoskeleton of budding yeast cells. After permeabilization of yeast by a novel procedure designed to maintain the spatial organization of cellular constituents, exogenously added fluorescently labeled actin monomers assemble into distinct structures in a pattern that is similar to the cortical actin distribution in vivo. Actin assembly in the bud of small-budded cells requires a nucleation activity provided by protein factors that appear to be distinct from the barbed ends of endogenous actin filaments. This nucleation activity is lost in cells that lack either Sla1 or Sla2, proteins previously implicated in cortical actin cytoskeleton function, suggesting a possible role for these proteins in the nucleation reaction. The rate and the extent of actin assembly in the bud are increased in permeabilized delta cap2 cells, providing evidence that capping protein regulates the ability of the barbed ends of actin filaments to grow in yeast cells. Actin incorporation in the bud can be stimulated by treating the permeabilized cells with GTP-gamma S, and, significantly, the stimulatory effect is eliminated by a mutation in CDC42, a gene that encodes a Rho-like GTP-binding protein required for bud formation. Furthermore, the lack of actin nucleation activity in the cdc42 mutant can be complemented in vitro by a constitutively active Cdc42 protein. These results suggest that Cdc42 is closely involved in regulating actin assembly during polarized cell growth.


Using Growth and Transpiration Phenotyping Under Controlled Conditions to Select Water Efficient Banana Genotypes.
Water deficit is one of the world's major constraints in agriculture and will aggravate in the future. Banana (Musa spp.) is an important crop that needs vast amounts of water for optimal production. The International Transit Center of Bioversity International holds the world's biggest collection of banana biodiversity (>1,500 accessions). The long-term aim of this research is to evaluate the potential within this collection for climate smart agricultural usage. Therefore, we developed a phenotyping setup under controlled environmental conditions and we selected 32 representatives of the Musa biodiversity (29 cultivars and 3 wild relatives) for evaluation. The best performing genotypes accumulated six to seven times more biomass than the least performing. Eight genotypes (five ABB, one AAB, and two AAA) invest under osmotic stress significantly more in root growth than in leaf growth. We predict therefore that these genotypes have potential for high productivity under rain fed conditions with a short dry season. To gain more insight in the transpiration physiology, we gravimetrically monitored individual plant transpiration over the diurnal period. All analyzed genotypes showed a marked reduction in transpiration rate in the afternoon. Moreover, the timing of this onset, as well as its impact on total transpiration, was genotype dependent. This phenomenon was more pronounced in 13 genotypes (eight ABB, two AAB, two AA, one BB). Banana is a crop originating from the humid tropics and has developed a strong root pressure to maintain an efficient water and nutrient transport even under saturated relative humidity conditions. Therefore, we hypothesize that the diurnal transpiration decline contributes to a higher water use efficiency without compromising the nutrient transport. Of the eight genotypes that had the best growth under osmotic stress, all analyzed ABB cultivars have a lower maximal transpiration rate, keep this maximal transpiration for a shorter time and therefore consume less water per day. We conclude that lab models are very useful to study the biodiversity and to identify different traits that contribute to a better drought tolerance/avoidance. We encourage researchers investigating other crops to start exploring their collections.


The sexual selection continuum.
The evolution of mate choice for genetic benefits has become the tale of two hypotheses: Fisher's 'run-away' and 'good genes', or viability indicators. These hypotheses are often pitted against each other as alternatives, with evidence that attractive males sire more viable offspring interpreted as support for good genes and with a negative or null relationship between mating success of sons and other components of fitness interpreted as favouring the Fisher process. Here, we build a general model of female choice for indirect benefits that captures the essence of both the 'Fisherian' and 'good-genes' models. All versions of our model point to a single process that favours female preference for males siring offspring of high reproductive value. Enhanced mating success and survival are therefore equally valid genetic benefits of mate choice, but their relative importance varies depending on female choice costs. The relationship between male attractiveness and survival may be positive or negative, depending on life-history trade-offs and mating skew. This relationship can change sign in response to increased costliness of choice or environmental change. Any form of female preference is subject to self-reinforcing evolution, and any relationship (or lack thereof) between male display and offspring survival is inevitably an indicator of offspring reproductive values. Costly female choice can be maintained with or without higher offspring survival.


Unsaturated aldehydes as alkene equivalents in the Diels-Alder reaction.
A one-pot procedure is described for using alpha,beta-unsaturated aldehydes as olefin equivalents in the Diels-Alder reaction. The method combines the normal electron demand cycloaddition with aldehyde dienophiles and the rhodium-catalyzed decarbonylation of aldehydes to afford cyclohexenes with no electron-withdrawing substituents. In this way, the aldehyde group serves as a traceless control element to direct the cycloaddition reaction. The Diels-Alder reactions are performed in a diglyme solution in the presence of a catalytic amount of boron trifluoride etherate. Subsequent quenching of the Lewis acid, addition of 0.3% of [Rh(dppp)2Cl] and heating to reflux achieves the ensuing decarbonylation to afford the product cyclohexenes. Under these conditions, acrolein, crotonaldehyde and cinnamaldehyde have been reacted with a variety of 1,3-dienes to afford cyclohexenes in overall yields between 53 and 88%. In these transformations, the three aldehydes serve as equivalents of ethylene, propylene and styrene, respectively.


Adequacy of Nutrients Intake among Jordanian Pregnant Women in Comparison to Dietary Reference Intakes.
Maternal nutrition is considered an important pillar in the pregnancy outcomes for both mother and infant. A mother's malnutrition and inadequate nutrient intake is associated with many undesirable pregnancy outcomes. Hence, assessing the nutritional status of the mother in the early stages of the pregnancy and preventing any inadequacy can preclude many health problems for both mother and infant. Therefore, this study aimed to assess the adequacy of nutrient intakes among Jordanian pregnant women as compared to their corresponding dietary reference intakes (DRIs). This cross-sectional study was conducted at a major University Hospital in Jordan. Three hundred pregnant women were invited to participate in the study and 286 agreed to participate. Fifty pregnant women were enrolled at week 9, then 96 pregnant women were at week 20 and 137 pregnant women were at week 30 of pregnancy. The participants completed the interview-based demographic questionnaire, pregnancy physical activity questionnaire, and quantitative food frequency questionnaire (FFQ). The mean energy intake was 2768.9 ± 767.8 kcal/day and it was significantly higher in the 3rd trimester (p < 0.05). Women in the 3rd trimester consumed significantly more protein, carbohydrates, and sugar than women in the 1st and 2nd trimesters (p < 0.05). The pregnant women in the 3rd trimester consumed more sodium than women in the 1st and 2nd trimesters (p < 0.05). The vitamin K intake was significantly (p = 0.045) lower in the 2nd trimester than the 1st and 3rd trimesters. The calcium intake was significantly higher in the 3rd trimester than the 1st and 2nd trimesters (p = 0.021). The total micronutrient (vitamins B1, B2, B3, B6, B12, and D, calcium, and iron) intakes derived from dietary supplements and food sources throughout the 3 trimesters was significantly higher in the 3rd trimester than the 1st and 2nd trimesters (p < 0.05). The vitamin D, calcium, and iron intakes had the most significant increases between the 1st and 3rd trimesters (p < 0.001), while folic acid intake was significantly higher in the 1st trimester than the 2nd and 3rd trimester (p < 0.001). Most women exceeded the tolerable upper intake level (UL) for sodium in all trimesters, while 82% of women exceeded the UL of folic acid in the 1st trimester and from the supplement, not the diet. While the intake of some nutrients from food alone remains below the DRIs in the diets of pregnant women, the intake of other nutrients is above the UL. Raising the awareness of pregnant women about their diet and how a supplement intake can reduce the risk of inadequate intake for many micronutrients and improve their pregnancy outcomes is of great importance.


Analyzing personalized policies for online biometric verification.
Motivated by India's nationwide biometric program for social inclusion, we analyze verification (i.e., one-to-one matching) in the case where we possess similarity scores for 10 fingerprints and two irises between a resident's biometric images at enrollment and his biometric images during his first verification. At subsequent verifications, we allow individualized strategies based on these 12 scores: we acquire a subset of the 12 images, get new scores for this subset that quantify the similarity to the corresponding enrollment images, and use the likelihood ratio (i.e., the likelihood of observing these scores if the resident is genuine divided by the corresponding likelihood if the resident is an imposter) to decide whether a resident is genuine or an imposter. We also consider two-stage policies, where additional images are acquired in a second stage if the first-stage results are inconclusive. Using performance data from India's program, we develop a new probabilistic model for the joint distribution of the 12 similarity scores and find near-optimal individualized strategies that minimize the false reject rate (FRR) subject to constraints on the false accept rate (FAR) and mean verification delay for each resident. Our individualized policies achieve the same FRR as a policy that acquires (and optimally fuses) 12 biometrics for each resident, which represents a five (four, respectively) log reduction in FRR relative to fingerprint (iris, respectively) policies previously proposed for India's biometric program. The mean delay is [Formula: see text] sec for our proposed policy, compared to 30 sec for a policy that acquires one fingerprint and 107 sec for a policy that acquires all 12 biometrics. This policy acquires iris scans from 32-41% of residents (depending on the FAR) and acquires an average of 1.3 fingerprints per resident.


Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos.
Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6 mg/L PFDoA for 120 h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6 mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6 mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system.


The Spermatozoal Ultrastructure of the Chinese Mitten Crab (Eriocheir sinensis).
The Chinese mitten crab (Eriocheir sinensis) is an economically important aquatic species in China. The artificial breeding crabs are also increasing in number day by day. However, knowledge about spermatozoal organization of the crab is still very limited. In the present study, the spermatozoal ultrastructure of the E. sinensis is illustrated for improving artificial breeding technique. The spermatozoa are observed by light microscopy and transmission electron microscopy. Spermatozoa are located in the lumen of seminiferous tubules. The spermatocytes and spermatids are observed in the wall of seminiferous tubules. The spermatophores are both present in the lumen of vas deferens and seminal vesicles. A mature spermatozoon consists of a central electron dense acrosome and a peripheral electron lucent nucleus within structures-organelles complex. The acrosome is divided into three zones, including inner acrosome zone, outer acrosome zone and zonal texture. The centre of acrosome is the perforatorium within parallel arranged perforatorial tubules along vertical axis. The highest electron dense operculum surrounds the head side of perforatorium. The ultrastructure of spermatozoa of E. sinensis is illustrated. In particular, the outermost part of the acrosome appears as concentric circles and is described as zonal texture.


Single-Cell Sequencing of the Healthy and Diseased Heart Reveals Cytoskeleton-Associated Protein 4 as a New Modulator of Fibroblasts Activation.
Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells. Here, we present a method to obtain high-quality RNA from digested cardiac tissue from adult mice for automated single-cell sequencing of both the healthy and diseased heart. After optimization, we were able to perform single-cell sequencing on adult cardiac tissue under both homeostatic conditions and after ischemic injury. Clustering analysis based on differential gene expression unveiled known and novel markers of all main cardiac cell types. Based on differential gene expression, we could identify multiple subpopulations within a certain cell type. Furthermore, applying single-cell sequencing on both the healthy and injured heart indicated the presence of disease-specific cell subpopulations. As such, we identified cytoskeleton-associated protein 4 as a novel marker for activated fibroblasts that positively correlates with known myofibroblast markers in both mouse and human cardiac tissue. Cytoskeleton-associated protein 4 inhibition in activated fibroblasts treated with transforming growth factor β triggered a greater increase in the expression of genes related to activated fibroblasts compared with control, suggesting a role of cytoskeleton-associated protein 4 in modulating fibroblast activation in the injured heart. Single-cell sequencing on both the healthy and diseased adult heart allows us to study transcriptomic differences between cardiac cells, as well as cell type-specific changes in gene expression during cardiac disease. This new approach provides a wealth of novel insights into molecular changes that underlie the cellular processes relevant for cardiac biology and pathophysiology. Applying this technology could lead to the discovery of new therapeutic targets relevant for heart disease.


Selection, integration, and conflict monitoring; assessing the nature and generality of prefrontal cognitive control mechanisms.
Prefrontal cortex (PFC) supports flexible behavior by mediating cognitive control, though the elemental forms of control supported by PFC remain a central debate. Dorsolateral PFC (DLPFC) is thought to guide response selection under conditions of response conflict or, alternatively, may refresh recently active representations within working memory. Lateral frontopolar cortex (FPC) may also adjudicate response conflict, though others propose that FPC supports higher order control processes such as subgoaling and integration. Anterior cingulate cortex (ACC) is hypothesized to upregulate response selection by detecting response conflict; it remains unclear whether ACC functions generalize beyond monitoring response conflict. The present fMRI experiment directly tested these competing theories regarding the functional roles of DLPFC, FPC, and ACC. Results reveal dissociable control processes in PFC, with mid-DLPFC selectively mediating resolution of response conflict and FPC further mediating subgoaling/integration. ACC demonstrated a broad sensitivity to control demands, suggesting a generalized role in modulating cognitive control.


Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy.
The HIV-human metabolic relationship is a complex interaction convoluted even more by antiretroviral therapy (cART) and comorbidities. The ability of cART to undo the HIV induced metabolic dysregulation is unclear and under-investigated. Using targeted metabolomics and multiplex immune biomarker analysis, we characterized plasma samples obtained from 18 untreated HIV-1-infected adult patients and compared these to a non-HIV infected (n = 23) control population. The biogenic amine perturbations during an untreated HIV infection implicated altered tryptophan- nitrogen- and muscle metabolism. Furthermore, the lipid profiles of untreated patients were also significantly altered compared to controls. In untreated HIV infection, the sphingomyelins and phospholipids correlated negatively to markers of infection IP-10 and sIL-2R whereas a strong association was found between triglycerides and MCP-1. In a second cohort, we characterized plasma samples obtained from 28 HIV-1-infected adult patients before and 12 months after the start of cART, to investigate the immune-metabolic changes associated with cART. The identified altered immune-metabolic pathways of an untreated HIV infection showed minimal change after 12 months of cART. In conclusion, 12 months of cART impacts only mildly on the metabolic dysregulation underlying an untreated HIV infection and provide insights into the comorbidities present in virally suppressed HIV patients.


Hepatitis C Prevalence and Validation of a Clinical Prediction Score for Targeted Screening among People Living with HIV in Ghana.
WHO recommends hepatitis C (HCV) screening for all people living with HIV (PLHIV). Yet, HCV coinfection was shown to be rare in some Sub-Saharan HIV cohorts, and targeted testing was suggested more efficient for such settings. We studied HCV prevalence among Ghanaian PLHIV, and assessed the external validity of a score to guide targeted testing. This score was initially derived from a Cambodian HIV cohort, and uses as predictors: age, household member/partner with liver disease, diabetes, generalized pruritus, AST, platelets, and AST-to-platelet ratio index. We enrolled 4,023 PLHIV, most from Greater Accra and Central regions, 28.4% were male, median age was 47 years, and high-risk behavior was reported to be rare. HCV seroprevalence was 0.57%, and HCV-RNA was detectable in 0.5%. Sequencing revealed genotype 1(b) and 2(q/r) infections. The discriminatory performance of the score was suboptimal in the Ghanaian setting. The area under the curve was 0.69 (95% CI 0.59-0.79). HCV coinfection prevalence was very low in this Ghanaian PLHIV cohort with reported low-risk of onward transmission. To avoid the cost of screening all PLHIV in similar cohorts in resource-constrained settings, further research to develop better tools/scores to guide targeted HCV testing is needed.


Prothrombotic states in young people with idiopathic stroke. A prospective study.
Although 4% of cerebral infarcts in the young can be attributed to hematologic disturbances that predispose to thrombosis, the frequency of cerebral infarcts caused by prothrombotic states is not known. Recently, the association between cerebral infarction and deficiencies of elements of the natural anticoagulant system has been recognized. Thirty-six consecutive patients under 40 years of age with cerebral infarction of undetermined cause were prospectively studied. Quantitation of natural anticoagulants was done at least 3 months after the cerebral infarction. The following activity tests were performed, all by the chromogenic method: antithrombin III, protein C, plasminogen, tissue plasminogen activator, and inhibitor of tissue plasminogen activator. Protein S was quantified by the Laurell rocket method. All patients underwent a complete cardiological examination, including two-dimensional echocardiography, as well as four-vessel cerebral angiography. Some patients were also studied by transesophageal echocardiography. Of 36 patients, 17 were male, with a mean age of 28 years. Mean age for women was 25 years. Nine patients (25%; 5 women, 4 men) had a deficiency of one natural anticoagulant and constituted group I. In these patients, isolated protein S deficiency was detected in five cases (13.8%); in one case, we observed the association between protein S deficiency and antiphospholipid antibodies; and deficiency of protein C was seen in one case (2.7%), of antithrombin III in one case (2.7%), and of plasminogen in one case (2.7%). Instances of cerebral infarction without natural anticoagulant deficiency (group II) included 12 women and 15 men. There were no differences in clinical and radiological findings between the two groups. Considering the importance of prothrombotic state, especially caused by deficiency of protein S, in the development of cerebral infarcts, we suggest that it should be looked for in every young patient affected by this pathological entity and in whom no etiologic factors can be determined.


Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications.
Two high bandgap benzodithiophene-benzotriazole-based polymers were synthesized via palladium-catalysed Stille coupling reaction. In order to compare the effect of the side chains on the opto-electronic and photovoltaic properties of the resulting polymers, the benzodithiophene monomers were substituted with either octylthienyl (PTzBDT-1) or dihexylthienyl (PTzBDT-2) as side groups, while the benzotriazole unit was maintained unaltered. The optical characterization, both in solution and thin-film, indicated that PTzBDT-1 has a red-shifted optical absorption compared to PTzBDT-2, likely due to a more planar conformation of the polymer backbone promoted by the lower content of alkyl side chains. The different aggregation in the solid state also affects the energetic properties of the polymers, resulting in a lower highest occupied molecular orbital (HOMO) for PTzBDT-1 with respect to PTzBDT-2. However, an unexpected behaviour is observed when the two polymers are used as a donor material, in combination with PC61BM as acceptor, in bulk heterojunction solar cells. Even though PTzBDT-1 showed favourable optical and electrochemical properties, the devices based on this polymer present a power conversion efficiency of 3.3%, considerably lower than the efficiency of 4.7% obtained for the analogous solar cells based on PTzBDT-2. The lower performance is presumably attributed to the limited solubility of the PTzBDT-1 in organic solvents resulting in enhanced aggregation and poor intermixing with the acceptor material in the active layer.


Serotonergic responsivity in obsessive-compulsive disorder. Effects of chronic clomipramine treatment.
Clomipramine is a potent serotonin reuptake blocker that decreases the symptoms of obsessive-compulsive disorder (OCD). To investigate whether clomipramine treatment in OCD affects brain serotonergic responsiveness, metachlorophenylpiperazine (mCPP), a selective serotonin agonist, and placebo were given under double-blind conditions to nine patients with OCD before and after treatment with clomipramine. Unlike our previous observations of a marked transient increase in obsessional symptoms and anxiety following 0.5 mg/kg of mCPP, readministration of mCPP after four months of treatment with clomipramine did not significantly increase obsessional symptoms and anxiety. Similarly, the hyperthermic effect of mCPP observed before treatment was eliminated after treatment with clomipramine. These findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment. A similar alteration in the response to endogenous serotonin may mediate clomipramine's antiobsessional effects.


Sequential pattern formation in a model for skin morphogenesis.
During morphogenesis regular patterns often develop behind a frontier of pattern formation which travels across the prospective tissue. Here the authors consider the propagating patterns exhibited in a two-dimensional domain by a tissue interaction mechanochemical model for skin pattern formation. It is shown that the model can exhibit travelling waves of complex spatial pattern formation. Two alternative mechanisms that can produce such sequential patterning are presented. In particular, it is demonstrated that the specification of a simple quasi-one-dimensional pattern is all that is required to determine a complex two-dimensional pattern. Finally, the model solutions are related to actual pattern propagation during chick feather primordia initiation.


Analytical solution for soil water redistribution during evaporation process.
Simulating the dynamics of soil water content and modeling soil water evaporation are critical for many environmental and agricultural strategies. The present study aims to develop an analytical solution to simulate soil water redistribution during the evaporation process. This analytical solution was derived utilizing an exponential function to describe the relation of hydraulic conductivity and water content on pressure head. The solution was obtained based on the initial condition of saturation and an exponential function to model the change of surface water content. Also, the evaporation experiments were conducted under a climate control apparatus to validate the theoretical development. Comparisons between the proposed analytical solution and experimental result are presented from the aspects of soil water redistribution, evaporative rate and cumulative evaporation. Their good agreement indicates that this analytical solution provides a reliable way to investigate the interaction of evaporation and soil water profile.


K-ras mutations in sinonasal cancers in relation to wood dust exposure.
Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, ras mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations. We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-ras codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data. Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0-55.0]. K-ras was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G-->A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT --> GAT transition as the most common and often related to wood dust exposure. Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-ras mutations, were almost exclusively G --> A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-ras mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G-->A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-ras mutations in development of sinonasal cancer.


Psychological well-being of Australian hospital clinical staff during the COVID-19 pandemic.
Objective This study assessed the psychological well-being of Australian hospital clinical staff during the COVID-19 pandemic. Methods An anonymous online cross-sectional survey was conducted in a large metropolitan tertiary health service located in Melbourne, Australia. The survey was completed by nurses, midwives, doctors and allied health (AH) staff between 15 May and 10 June 2020. The Depression, Anxiety and Stress Scale - 21 items (DASS-21) assessed the psychological well-being of respondents in the previous week. Results In all, 668 people responded to the survey (nurses/midwives, n=391; doctors, n=138; AH staff, n=139). Of these, 108 (16.2%) had direct contact with people with a COVID-19 diagnosis. Approximately one-quarter of respondents reported symptoms of psychological distress. Between 11% (AH staff) and 29% (nurses/midwives) had anxiety scores in the mild to extremely severe ranges. Nurses and midwives had significantly higher anxiety scores than doctors (P<0.001) and AH staff (P<0.001). Direct contact with people with a COVID-19 diagnosis (P<0.001) and being a nurse or midwife (P<0.001) were associated with higher anxiety scores. Higher ratings of the health service's pandemic response and staff support strategies were protective against depression (P<0.001), anxiety (P<0.05) and stress (P<0.001). Conclusions The COVID-19 pandemic had a significant effect on the psychological well-being of hospital clinical staff, particularly nurses and midwives. Staff would benefit from (additional) targeted supportive interventions during the current and future outbreaks of infectious diseases. What is known about the topic? The outbreak of COVID-19 is having, and will have, a considerable effect on health services. No Australian data about the effect of COVID-19 on the psychological well-being of hospital clinical staff are available. What does this paper add? Australia healthcare providers have experienced considerable emotional distress during the COVID-19 pandemic, particularly nurses and midwives and clinical staff who have had direct contact with people with a COVID-19 diagnosis. In this study, nurses and midwives had significantly higher levels of anxiety, depression and stress during the pandemic than general Australian adult population norms, and significantly more severe anxiety symptoms than medical and AH staff. Despite a lower number of COVID-19 cases and a lower death rate than in other countries, the proportion of Australian hospital clinical staff experiencing distress is similar to that found in other countries. What are the implications for practitioners? Targeted well-being interventions are required to support hospital clinical staff during the current and future outbreaks of infectious diseases and other 'crises' or adverse events.


Propolis modulates fibronectin expression in the matrix of thermal injury.
The aim of the study was to assess the propolis effect on fibronectin metabolism in the course of burn wounds healing process. A model of burn wound healing of pig skin was applied. The amount of the released glycoprotein was assessed by a surface plasmon resonance. The profile of extracted fibronectin components was also assessed by an electrophoresis in polyacrylamide gel, with a subsequent immunodetection by Western Blotting. Propolis burn treatment decreased the release of fibronectin components from healing wounds in relation to damages treated with silver sulfadiazine. The main reason of decreased extraction of fibronectin components from wounds treated with propolis was a substantial decrease of degradation product release of the mentioned glycoprotein, which was observed particularly from the 3rd to 5th day of the repair. Wounds treatment with propolis demonstrated, especially in relation to damages treated with silver sulfadiazine, the decreased release of synthesized fibronectin molecules. The obtained results suggest that propolis modifies fibronectin metabolism in the course of wound healing process. The influence of propolis is reflected in prevention of fibronectin biosynthesis as well as its degradation in the wound area. The above-mentioned metabolic changes may decrease the risk of complications in the repair wounds process.


Evaluating the adequacy of disease control in patients with rheumatoid arthritis: a RAND appropriateness panel.
There is a lack of agreement on assessing disease activity in patients with RA and determining when the RA treatment should be changed or continued. A panel of rheumatologists was convened to develop guidelines to assess adequacy of disease control, focusing on the use of disease-modifying anti-rheumatic drugs. The Research and Development/University of California in Los Angeles (RAND/UCLA) Appropriateness Method was used to evaluate disease control adequacy. After a literature review, 108 scenarios were developed to simulate situations most likely to be encountered in clinical practice and rated on a 9-point scale by a 10-member expert panel. Final appropriateness rankings for the scenarios were as follows: 37% 'appropriate', 48% 'inappropriate', and 16% 'neutral'. The panelists felt that patients with disease control in the 'appropriate' range have adequate control with their current therapy, whereas those in the 'inappropriate' range should be considered for a change in therapy. Those in 'neutral' areas should have their therapy reviewed carefully. The panelists recommended that the clinically active joint count should be considered the most important decision factor. In patients with no clinically active joints, regardless of other factors no change in therapy was felt to be warranted. Patients with five or more active joints should be considered inadequately treated, and in patients with one to four active joints other variables must be considered in the decision to change therapy. These preliminary guidelines will assist the clinician in determining when a patient's clinical situation warrants therapy escalation and when continuing the current regimen would be appropriate.


A new method for valuing health: directly eliciting personal utility functions.
Standard methods for eliciting the preference data upon which 'value sets' are based generally have in common an aim to 'uncover' people's preferences by asking them to evaluate a subset of health states, then using their responses to infer their preferences over all dimensions and levels. An alternative approach is to ask people directly about the relative importance to them of the dimensions, levels and interactions between them. This paper describes a new stated preference approach for directly eliciting personal utility functions (PUFs), and reports a pilot study to test its feasibility for valuing the EQ-5D. A questionnaire was developed, designed to directly elicit PUFs from general public respondents via computer-assisted personal interviews, with a focus on helping respondents to reflect and deliberate on their preferences. The questionnaire was piloted in England. Seventy-six interviews were conducted in December 2015. Overall, pain/discomfort and mobility were found to be the most important of the EQ-5D dimensions. The ratings for intermediate improvements in each dimension show heterogeneity, both within and between respondents. Almost a quarter of respondents indicated that no EQ-5D health states are worse than dead. The PUF approach appears to be feasible, and has the potential to yield meaningful, well-informed preference data from respondents that can be aggregated to yield a value set for the EQ-5D. A deliberative approach to health state valuation also has the potential to complement and develop existing valuation methods. Further refinement of some elements of the approach is required.


Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.


Plasma levels of the beta chemokine regulated upon activation, normal T cell expressed, and secreted (RANTES) correlate with severe brain injury.
The expression of the beta chemokine RANTES (regulated upon activation, normal T cell expressed, and secreted) has previously been shown to be elevated after traumatic brain injury (TBI) in animal models, but it was unknown whether the plasma level of RANTES was predictive of TBI in critically injured trauma patients. A prospective study was conducted on 108 critically ill trauma patients. Patients were stratified by radiologic diagnosis of TBI. Severe TBI was classified as the presence of diffuse axonal injury, midline shift, or herniation based on admission head computed tomography findings. Serum levels were evaluated at admission and hospital day 7. RANTES was measured using Luminex multiplex assays. Fifty-four patients with and without TBI were compared. Severe TBI was diagnosed in 23 of the 54 TBI patients (43%) and mild/moderate TBI was found in 31 (57%) patients. The mean age of the study population was 43 +/- 20 years with a mean Injury Severity Score of 29 +/- 14. There was no significant difference between groups in age, sex, and Injury Severity Score. At admission, RANTES was significantly higher in patients with severe brain injury than in non-TBI patients (mean 1,339 pg/mL vs. 708 pg/mL, p = 0.046), and there was a trend toward significance when comparing patients with severe versus mild/moderate brain injury (mean 1,339 pg/mL vs. 752 pg/mL, p = 0.069). There was no statistically significant difference on day 7. RANTES was a significant early marker of severe TBI in critically injured trauma patients, consistent with animal models. Future research on the role of RANTES in the pathogenesis of human TBI is warranted.


Pleiotropy and GAL pathway degeneration in yeast.
Traits that do not contribute to fitness are expected to be lost during the course of evolution, either as a result of selection or drift. The Leloir pathway of galactose metabolism (GAL) is an extensively studied metabolic pathway that degenerated on at least three independent occasions during the evolutionary diversification of yeasts, suggesting that the pathway is costly to maintain in environments that lack galactose. Here I test this hypothesis by competing GAL pathway deletion mutants of Saccharomyces cerevisiae against an isogenic strain with an intact GAL pathway under conditions where expression of the pathway is normally induced, repressed, or uninduced. These experiments do not support the hypothesis that pleiotropy drives GAL pathway degeneration, because mutations that knock out individual GAL genes do not tend to increase fitness in the absence of galactose. At a molecular level, this result can be explained by the fact that yeast uses inexpensive regulatory proteins to tightly regulate the expression of structural genes that are costly to express. I argue that these results have general relevance for our understanding of the fitness consequences of gene disruption in yeast.


Cryopreserved femoral vein grafts for difficult hemodialysis access.
Improved survival of patients with renal failure has led to the need for complex angioaccess procedures. The use of cryopreserved femoral vein for angioaccess when prosthetic arteriovenous grafts (AVG) could not be placed, owing to infection or the loss of conventional angioaccess sites from multiple AVG failures, was prospectively evaluated. Forty-eight cryopreserved femoral vein AVGs were placed in 44 patients. Thirty-eight (82%) of the cryopreserved femoral vein AVGs were placed for infection, whereas the other 10 (18%) were placed for multiple graft failures with compromised venous outflow. Even with implantation of the cryoveins into infected patients, there were no cryopreserved femoral vein AVG infections. The 1-year primary graft patency rate was 49% and the secondary graft patency rate was 75%. During the same time interval, 68 prosthetic brachial artery-to-axillary vein AVGs were placed. The 1-year primary and secondary patency rates for the prosthetic AVGs were 65 and 78%, respectively. In this study the overall patency rate of the cryopreserved femoral vein AVGs was similar to that for the PTFE AVGs (p = 0.519). In conclusion, the cryopreserved femoral vein proved useful in difficult angioaccess cases. The lack of infection after cryovein implantation around an infected area shows promise for salvaging an angioaccess site that would otherwise have been abandoned.


Comparison of multi-enzyme and thermophilic bacteria on the hydrolysis of mariculture organic waste (MOW).
Mariculture organic waste (MOW) is rich in organic matter, which is a potential energy resource for anaerobic digestion. In order to enhance the anaerobic fermentation, the MOW was hydrolyzed by multi-enzyme and thermophilic bacteria. It was advantageous for soluble chemical oxygen demand (SCOD) release at MOW concentrations of 6 and 10 g/L with multi-enzyme and thermophilic bacteria pretreatments. For multi-enzyme, the hydrolysis was not obvious at substrate concentrations of 1 and 3 g/L, and the protein and carbohydrate increased with hydrolysis time at substrate concentrations of 6 and 10 g/L. For thermophilic bacteria, the carbohydrate was first released at 2-4 h and then consumed, and the protein increased with hydrolysis time. The optimal enzyme hydrolysis for MOW was determined by measuring the changes of SCOD, protein, carbohydrate, ammonia and total phosphorus, and comparing with acid and alkaline pretreatments.


Probabilistic TFCE: A generalized combination of cluster size and voxel intensity to increase statistical power.
The threshold-free cluster enhancement (TFCE) approach integrates cluster information into voxel-wise statistical inference to enhance detectability of neuroimaging signal. Despite the significantly increased sensitivity, the application of TFCE is limited by several factors: (i) generalisation to data structures, like brain network connectivity data is not trivial, (ii) TFCE values are in an arbitrary unit, therefore, P-values can only be obtained by a computationally demanding permutation-test. Here, we introduce a probabilistic approach for TFCE (pTFCE), that gives a simple general framework for topology-based belief boosting. The core of pTFCE is a conditional probability, calculated based on Bayes' rule, from the probability of voxel intensity and the threshold-wise likelihood function of the measured cluster size. In this paper, we provide an estimation of these distributions based on Gaussian Random Field theory. The conditional probabilities are then aggregated across cluster-forming thresholds by a novel incremental aggregation method. pTFCE is validated on simulated and real fMRI data. The results suggest that pTFCE is more robust to various ground truth shapes and provides a stricter control over cluster "leaking" than TFCE and, in many realistic cases, further improves its sensitivity. Correction for multiple comparisons can be trivially performed on the enhanced P-values, without the need for permutation testing, thus pTFCE is well-suitable for the improvement of statistical inference in any neuroimaging workflow. Implementation of pTFCE is available at https://spisakt.github.io/pTFCE.


Preconceptional sex selection: past, present, and future.
Predetermination of sex in human and in farm animals is reviewed. Preconceptional sex selection has generated great interest and controversy over the years. Medical and commercial benefits outweigh the ethical issues. Technology has not yet provided a routine method for separating the X- and Y-chromosome-bearing sperm. Flow cytometry is the only technique that produces a clinically significant enrichment of X- or Y-bearing spermatozoa However, concern has been raised about the methodological implications of the flow technique because of the use of DNA stains and UV light. Some other techniques, such as gradient columns, appear to produce a slight enrichment of one type of sperm over the other, but this level of enrichment appears unlikely to affect the sex ratio at birth. It thus remains speculative whether 100% pure preparation of X or Y sperm can be obtained unless a major improvement in methodology is achieved. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are currently the methods of choice for evaluating the validity of the sex selection procedure. In view of the extraordinary pace of the technological and scientific progress, it can be expected that the clinical and commercial application of the technology of preconceptional sex selection by X and Y sperm separation will be a reality in near future.


Diphtheritic polyneuropathy in the wake of resurgence of diphtheria.
To study the clinical profile and outcome in children with diphtheritic polyneuropathy (DP). 13 children with polyneuropathy were included in this study. Their demographic profile, age, sex and immunization status were recorded. Detailed clinical and neurological examination was done. Investigations like CSF analysis, NCV studies, MRI brain were done. The results were tabulated and analyzed. All the children presented with bulbar palsy and had h/o membranous tonsillitis. Isolated palatal palsy was seen in 7 children (53%). 6 (46.1%) children developed quadriparesis. 1 child expired and recovery is complete in rest of the 12 children. Children with isolated bulbar palsy recovered within 2 to 4 weeks while children with quadriparesis recovered within 5-6 wks. Any child diagnosed with diphtheria should be followed for 3-6 months in anticipation of neurological complications. DP carries good prognosis hence timely diagnosis and differentiation from other neuropathies is a prerequisite for rational management.


Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells.
Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer. First, we found that arctigenin inhibited the viability of the MCF-7 cells, and colony formation assay confirmed that this effect was cytotoxic rather than cytostatic. The cytotoxic effects were not mediated by cell cycle arrest, apoptosis, or necroptosis, despite DNA damage, as indicated by poly(ADP-ribose) polymerase (PARP) cleavage and phosphorylated H2A.X. An increase in lipidated LC3, a marker of autophagosome formation, was observed, indicating that autophagy was induced by arctigenin, which was found to be triggered by the inhibition of the mechanistic target of rapamycin (mTOR) pathway. We then examined the effects of arctigenin on ERα expression and determined whether it affects the sensitivity of the cells to tamoxifen, as tamoxifen is commonly used against hormone-responsive cancers and is known to act via the ERα. We found that treatment with arctigenin effectively downregulated ERα expression, which was found to be a consequence of the inhibition of the mTOR pathway. However, treatment with arctigenin in combination with tamoxifen did not affect the sensitivity of the cells to tamoxifen, but instead, exerted a synergistic effect. On the whole, our data indicate that the phytoestrogen, arctigenin, mainly targeted the mTOR pathway in ERα-positive MCF-7 human breast cancer cells, leading to autophagy-induced cell death and the downregulation of ERα expression. Furthermore, the synergistic effects between arctigenin and tamoxifen suggest that the consumption of arctigenin is not only safe for patients with hormone-sensitive cancers, but may also be an effective co-treatment.


Trypanozoon: infectivity to humans is linked to reduced transmissibility in tsetse. II. Genetic mechanisms.
Trypanozoon infections are less likely to mature in female tsetse than in males. Analysis of maturation data from 37 Trypanozoon isolates in Glossina m. morsitans showed that while the proportion of mature infections (salivary gland infections as a proportion of established midgut infections) varied from isolate to isolate, the proportion of mature infections in female flies was consistently smaller than the proportion in male flies. The log of the probability of maturation in females is, on average, twice the log of the probability in males (estimate of the ratio of the logged proportions is 2.09, 95% confidence interval (CI) 1.8 to 2.5). Human serum-resistant isolates were less likely to mature than human serum-sensitive isolates (ratio of logged proportions maturing was 1.5, 95% CI 1.3 to 1.8, in both male and female tsetse). Data for four other trypanosome stocks show that the probability of maturation decreases as the maturation time (the delay between the infected bloodmeal and maturation) increases. The decrease is approximately exponential with twice the half-life in male flies compared to that in female flies (estimate of the ratio of the exponential parameters is 1.97, 95% CI 0.7 to 3.3). A model is proposed to explain these observations which assumes that product(s) from an X-linked gene(s) kills or otherwise prevents migrating parasites from establishing a mature infection. Longer maturation times are associated with a heavy penalty in terms of transmissibility as measured by the vectorial capacity.


Effects of titanium dioxide nanoparticles isolated from confectionery products on the metabolic stress pathway in human lung fibroblast cells.
Titanium dioxide (TiO2) is a common additive in many foods, pigments, personal care products, and other consumer products used in daily life. Despite the widespread use of nanoscale TiO2 and composites of nanoscale TiO2 in the food industry, there is a serious lack of awareness of the toxicity of TiO2 nanoparticles (NPs) among consumers and manufacturers. There is an urgent need for toxicological studies of TiO2 NPs. TiO2 food additives separated from marketed foods were characterized by transmission electron microscopy. In addition, the effects of TiO2 NPs on metabolic stress in WI-38 cells were analyzed. Cell viability, total ROS, mitochondrial transmembrane potential (ΔψM), cell cycle, and metabolism-related gene expression were analyzed. The results indicate that TiO2 NPs have a significant concentration-dependent toxic effect in lung cells. The ΔψM, the intracellular ROS level, and the stages of the WI-38 cell cycle were altered by increasing TiO2 concentrations after exposure for 24 and 48 h relative to the control. Cytochrome P450 1A, GSTM3, and glutathione S-transferase A4 upregulation in response to the TiO2 NPs was observed. These findings suggest that the toxicity of TiO2 from confectionery products in WI-38 cells may be mediated through an increase in oxidative stress. The results of this study clearly demonstrate the nanotoxicological effects of TiO2 on WI-38 cells and will be useful for nanotoxicological indexing.


Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis.
Low-back pain is a common and costly problem. We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care. In this pragmatic, multicentre, randomised controlled trial with parallel cost-effectiveness analysis undertaken in England, 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practices and received an active management advisory consultation. Participants were randomly assigned by computer-generated block randomisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention (n=468) or no further intervention (control; n=233). Primary outcomes were the change from baseline in Roland Morris disability questionnaire and modified Von Korff scores at 12 months. Assessment of outcomes was blinded and followed the intention-to-treat principle, including all randomised participants who provided follow-up data. This study is registered, number ISRCTN54717854. 399 (85%) participants in the cognitive behavioural intervention group and 199 (85%) participants in the control group were included in the primary analysis at 12 months. The most frequent reason for participant withdrawal was unwillingness to complete questionnaires. At 12 months, mean change from baseline in the Roland Morris questionnaire score was 1.1 points (95% CI 0.39-1.72) in the control group and 2.4 points (1.89-2.84) in the cognitive behavioural intervention group (difference between groups 1.3 points, 0.56-2.06; p=0.0008). The modified Von Korff disability score changed by 5.4% (1.99-8.90) and 13.8% (11.39-16.28), respectively (difference between groups 8.4%, 4.47-12.32; p<0.0001). The modified Von Korff pain score changed by 6.4% (3.14-9.66) and 13.4% (10.77-15.96), respectively (difference between groups 7.0%, 3.12-10.81; p<0.0001). The additional quality-adjusted life-year (QALY) gained from cognitive behavioural intervention was 0.099; the incremental cost per QALY was 1786 pound sterling, and the probability of cost-effectiveness was greater than 90% at a threshold of 3000 pound sterling per QALY. There were no serious adverse events attributable to either treatment. Over 1 year, the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider. National Institute for Health Research Health Technology Assessment Programme.


The reproducibility of the 50-g, 1-hour glucose screen for diabetes in pregnancy.
To explore the day-to-day reproducibility of the 50-g, 1-hour glucose screening test performed on 2 consecutive days in the same women. Eight women at 12-23.6 weeks' gestation (early subjects) and 80 women at 24-28 weeks (late subjects) without known diabetes mellitus were studied. The glucose screening test was performed in the morning on 2 consecutive days in the same women, under an identical or opposite sequence of fasting and fed conditions. The women were thus divided into four subgroups: fast-fast, fed-fed, fast-fed, and fed-fast. Duplicate serum glucose concentrations were measured by the glucose oxidase method. Paired Student t test was used to analyze day-1 versus day-2 glucose levels in each woman of each subgroup. The serum glucose concentrations were higher on day 1 than on day 2 in the subgroups fast-fast and fast-fed (P < .05) in both early and late patients, whereas the opposite was seen in the subgroups fed-fast (P < .05). No significant differences were observed in the subgroups of fed-fed. At three different glucose thresholds (130, 135, and 140 mg/dL), there was more than 90% daily reproducibility for normal results in both groups, and nearly 50 and 83% daily reproducibility for abnormal results in the early and late patients, respectively. Up to 28 weeks of pregnancy, the screening test had a high reproducibility for normal results. For abnormal results, daily reproducibility was better after than before 24 weeks' gestation, regardless of prior testing conditions. Depending on the pre-testing conditions, the use of a different serum glucose threshold seems warranted.


Effects of a group-based weight management programme on anxiety and depression: A randomised controlled trial (RCT).
The aim was to investigate the impact of a group-based weight management programme on symptoms of depression and anxiety compared with self-help in a randomised controlled trial (RCT). People with overweight (Body Mass Index [BMI]≥28kg/m2) were randomly allocated self-help (n = 211) or a group-based weight management programme for 12 weeks (n = 528) or 52 weeks (n = 528) between 18/10/2012 and 10/02/2014. Symptoms were assessed using the Hospital Anxiety and Depression Scale, at baseline, 3, 12 and 24 months. Linear regression modelling examined changes in Hospital Anxiety and Depression Scale between trial arms. At 3 months, there was a -0.6 point difference (95% confidence interval [CI], -1.1, -0.1) in depression score and -0.1 difference (95% CI, -0.7, 0.4) in anxiety score between group-based weight management programme and self-help. At subsequent time points there was no consistent evidence of a difference in depression or anxiety scores between trial arms. There was no evidence that depression or anxiety worsened at any time point. There was no evidence of harm to depression or anxiety symptoms as a result of attending a group-based weight loss programme. There was a transient reduction in symptoms of depression, but not anxiety, compared to self-help. This effect equates to less than 1 point out of 21 on the Hospital Anxiety and Depression Scale and is not clinically significant.


Risk, power and the possibility of pleasure: young women and safer sex.
This paper draws on the work of the Women Risk and AIDS Project (WRAP) which was undertaken by the authors working collectively. It reports on data from a sociological study of the sexual beliefs and practices of two samples each of 75 young women between 16 and 21 in the cities of London and Manchester in the UK. The period of data collection was 1988-1990. The paper sets out the methods used by the WRAP team and locates this research process within wider debates about feminist theory and methodology. There then follows a discussion of the main research findings--relating to the respondents sexual practice--which are then illustrated in some detail in relation to the themes of 'risk and trust' and 'power and empowerment'. Based on these findings conclusions are drawn about the need for a gendered dimension in the development of policy and practice for HIV and AIDS prevention.


Experimental habitat fragmentation disrupts nematode infections in Australian skinks.
Habitat conversion and fragmentation threaten biodiversity and disrupt species interactions. While parasites are recognized as ecologically important, the impacts of fragmentation on parasitism are poorly understood relative to other species interactions. This lack of understanding is in part due to confounding landscape factors that accompany fragmentation. Fragmentation experiments provide the opportunity to fill this knowledge gap by mechanistically testing how fragmentation affects parasitism while controlling landscape factors. In a large-scale, long-term experiment, we asked how fragmentation affects a host-parasite interaction between a skink and a parasitic nematode, which is trophically transmitted via a terrestrial amphipod intermediate host. We expected that previously observed amphipod declines resulting from fragmentation would result in decreased transmission of nematodes to skinks. In agreement, we found that nematodes were absent among skinks in the cleared matrix and that infections in fragments were about one quarter of those in continuous forest. Amphipods found in gut contents of skinks and collected from pitfall traps mirrored this pattern. A structural equation model supported the expectation that fragmentation disrupted this interaction by altering the abundance of amphipods and suggested that other variables are likely also important in mediating this effect. These findings advance understanding of how landscape change affects parasitism.


Methodology of the biological risk classification of animal pathogens in Belgium.
Since many micro-organisms are a biological hazard, they have been categorised into risk groups by many countries and organisations and classification lists have been developed. Current classification systems rely on criteria defined by the World Health Organization, which cover the severity of the disease the micro-organism might cause, its ability to spread and the availability of prophylaxis or efficient treatment. Animal pathogens are classified according to the definitions of the World Organisation for Animal Health, which also consider economic aspects of disease. In Europe, classification is often directly linked to containment measures. The Belgian classification system, however, only considers the inherent characteristics of the micro-organism, not its use, making the risk classification independent of containment measures. A common classification list for human and animal pathogens has been developed in Belgium using as comprehensive an approach as possible. The evolution of scientific knowledge will demand regular updating of classification lists. This paper describes the Belgian risk classification system and the methodology that was used for its peer-reviewed revision (with a focus on animal pathogens).