MOLECULAR CHARACTERIZATION OF PgiC IN A TETRAPLOID PLANT AND ITS DIPLOID RELATIVES.
Allotetraploid plant species combine the genomes of related diploid species, but little is known about whether homologous genes from the diploid genomes are expressed, how they interact, or whether they evolve differently when in a common tetraploid nucleus. Polyploidy may lead to gene silencing, but few molecular characterizations of silenced genes encoding enzymes in polyploids and related diploids have been reported. Here we describe the PgiC genes in the tetraploid Clarkia gracilis and related diploid species, which are native from California to southern Washington. PgiC encodes the cytosolic isozyme of phosphoglucose isomerase (PGIC; EC 18.104.22.168). The gene was duplicated in the basal stock of Clarkia and now both genes, PgiC1 and PgiC2, are active in about half of the diploid species, whereas only PgiC1 is active in the others. Clarkia gracilis was found to have three PgiC genes: two PgiC1s and a PgiC2. Reverse-transcriptase-polymerase chain reaction (RT-PCR) experiments, starting with mRNAs prepared from seedling leaves of C. gracilis, showed that the three genes are expressed. Analysis of their sequences showed they are evolving at similar rates to their homologues and that they have the same intron-exon structure. The presence of an expressed PgiC2 in C. gracilis was unexpected because all related diploid species, including one identified as a parent, have only active PgiC1s. The donor of the PgiC2 is now presumed extinct, but parsimony analysis identified its phylogenetic position. None of the PgiC genes that were active when C. gracilis arose were silenced. A possible example of gene conversion involving a 300-nuclectide region of one PgiC1 and PgiC2 was identified, but it probably occurred in the diploid parental species rather than in C. gracilis. PgiC2 is the first known example of an active locus in a tetraploid plant species that is no longer expressed in its diploid relatives.


Quantification of IDP-73152, a novel antibiotic, in plasma from mice, rats and humans using an ultra-high performance liquid chromatography/tandem mass spectrometry method for use in pharmacokinetic studies.
IDP-73152, a novel inhibitor of a bacterial peptide deformylase, was recently approved as a new, investigational drug in Korea for the clinical management of infections caused by Gram positive bacteria. The objective of this study was to develop/validate a simple and robust analytical method for the determination of IDP-73152 in plasma samples from rodents and humans, and to assess the feasibility of the assay for use in pharmacokinetic studies using animal models. Plasma samples were processed using a standard method for protein precipitation and an aliquot of the extract then injected onto an UHPLC-MS/MS system. The drug and IDP-117293, an internal standard, were analyzed in the positive ion-mode by electrospray ionization and quantified by monitoring the transition at m/z 555.2→245.2 for IDP-73152 and 563.3→253.1 for the internal standard, respectively. The lower and upper limit of the assay was determined to be 5 and 10000ng/ml, respectively, with an acceptable linearity (R>0.999) in the response-concentration relationship. Validation parameters, including accuracy, precision, dilution, recovery, matrix effect and stability were found to be within the acceptable ranges recommended by the assay validation guidelines of the United States FDA. The method was successfully applied to the quantification of IDP-73152 in plasma from mice/rats that had received a single oral administration of 80mg/kg IDP-73152, in the form of the mesylate salt. These findings suggest that the validated assay can be used in preclinical and clinical pharmacokinetic studies of IDP-73152.


Marker-free site-specific gene integration in rice based on the use of two recombination systems.
Transgene integration mediated by heterologous site-specific recombination (SSR) systems into the dedicated genomic sites has been demonstrated in a few different plant species. This approach of plant transformation generates a precise site-specific integration (SSI) structure consisting of a single copy of the transgene construct. As a result, stable transgene expression correlated with promoter strength and gene copy number is observed among independent transgenic lines and faithfully transmitted through subsequent generations. Site-specific integration approaches use selectable marker genes, removal of which is necessary for the implementation of this approach as a biotechnology application. As SSR systems are also excellent tools for excising marker genes from transgene locus, a molecular strategy involving gene integration followed by marker excision, each mediated by a distinct recombination system, was earlier proposed. Experimental validation of this approach is the focus of this work. Using FLPe-FRT system for site-specific gene integration and heat-inducible Cre-lox for marker gene excision, marker-free SSI lines were developed in the first generation itself. More importantly, progeny derived from these lines inherited the marker-free locus, indicating efficient germinal transmission. Finally, as the transgene expression from SSI locus was not altered upon marker excision, this method is suitable for streamlining the production of marker-free SSI lines.


[Submitral annular aneurysm, postpartum cardiomyopathy, and anti-Chlamydia pneumoniae antibodies in Niamey (Niger)].
Idiopathic annular submitral left ventricular aneurysm has been described mainly in young Africans living in tropical countries. Association with peripartum cardiomyopathy has been previously pointed out. The purpose of this report is to describe 3 patients with idiopathic annular submitral left ventricular aneurysm identified in a series 50 patients with peripartum cardiomyopathy in Niamey, Republic of Niger. Anti-Chlamydia pneumoniae antibody status was determined in all 50 patients using the micro-immunofluorescence technique that differentiates IgG, IgA and IgM antibodies. Findings showed that all 3 patients with annular submitral left ventricular aneurysm had significantly elevated plasma IgG and IgA anti-Chlamydia pneumoniae antibody levels at the time of diagnosis. In one patient analysis of 2 samples collected 3 months apart indicated chronic elevation with exceptionally high IgG antibody levels (1/2048e). These previously unreported data suggest a possible link between Chlamydia pneumoniae and development of peripartum cardiomyopathy and annular submitral left ventricular aneurysm. This possibility is supported by recent evidence that specific IgA anti-Chlamydia pneumoniae antibodies may be predictive of aortic abdominal aneurysms.


A computer-assisted psychiatric assessment unit.
The authors discuss the rationale and functional design for an innovative approach to psychiatric intake decision making, stressing the crucial role of an on-line computer support system. The description of the prototype computer-assisted psychiatric assessment process includes an outline of computer and staffing requirements. The authors discuss the initial impact of this psychiatric assessment unit on the hospital's mental health care delivery system.


Treatment techniques and outcomes in multidimensional family therapy for adolescent behavior problems.
The link between treatment techniques and long-term treatment outcome was examined in an empirically supported family-based treatment for adolescent drug abuse. Observational ratings of therapist interventions were used to predict outcomes at 6 and 12 months posttreatment for 63 families receiving multidimensional family therapy. Greater use of in-session family-focused techniques predicted reduction in internalizing symptoms and improvement in family cohesion. Greater use of family-focused techniques also predicted reduced externalizing symptoms and family conflict, but only when adolescent focus was also high. In addition, greater use of adolescent-focused techniques predicted improvement in family cohesion and family conflict. Results suggest that both individual and multiperson interventions can exert an influential role in family-based therapy for clinically referred adolescents.


Endoscopic endonasal dacryocystorhinostomy with ostial stent intubation following nasolacrimal duct stent incarceration.
To study the feasibility of endoscopic endonasal dacryocystorhinostomy (EE-DCR) with novel lacrimal ostial stent (LOS) intubation for patients with chronic dacryocystitis with incarceration of a previously implanted nasolacrimal duct stent (NDS). According to surgical procedure, 166 patients (167 eyes) were divided into two groups: EE-DCR with LOS intubation was performed on 126 patients (127 eyes) in the EE-DCR group; while external dacryocystorhinostomy (E-DCR) with silicone tube intubation was performed on 40 patients (40 eyes) in the E-DCR group. The LOS or silicone tube was retained for 3-6 months. All patients were followed up for 12-36 months. Success rate of tear drainage reconstruction (TDR) and complications were retrospectively compared. Excluding patients with early detachment of the LOS or the silicone tube, or with incomplete follow-up period, 117 patients (117 eyes) in the EE-DCR group and 36 patients (36 eyes) in the E-DCR group were included. The mean surgical time was 45.8 ± 11.5 min in the EE-DCR group and 68.1 ± 23.8 min in the E-DCR group (p < 0.001). Intraoperatively, the lacrimal sac was observed to become very small and its walls were thin, hyperemic and fragile, firmly attaching to the NDS by fibrous bands in all eyes. Upon final review, success rate of TDR was 83.8% (98/117) in the EE-DCR group, while 58.3% (21/36) in the E-DCR group (p < 0.01). Failure of TDR due to ostial closure by excessive fibrosis occurred in 14 out of 19 patients in the EE-DCR group, significantly less than the 11 out of 15 patients with failed TDR in the E-DCR group (χ(2 )= 6.959, p < 0.01). No significant difference existed in failures due to granuloma occluding the ostium or common canaliculus obstruction. EE-DCR with LOS intubation may be an effective procedure to manage the special subgroup of patients with chronic dacryocystitis with incarcerations of a previously implanted NDS.


Outcome of patients with biochemical recurrence of prostate cancer after PSMA PET/CT-directed radiotherapy or surgery without systemic therapy.
Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy. This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [18F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients' characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up. Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6-32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2-5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not. This study suggests that RT or surgery based on [18F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes. Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312.


In vivo toxicology of carbon dots by 1H NMR-based metabolomics.
Owing to the promising applications of C-dots in biomedical engineering, concerns about their safety have drawn increasing attention recently. In this study, mice were intraperitoneally injected at different C-dot concentrations (0, 6.0, 12.0 and 24.0 mg kg-1) once every 2 days for 30 days. A 1H NMR-based metabolic approach supplemented with biochemical analysis and histopathology was used for the first time to explore the toxicity of C-dots in vivo. Histopathological inspection revealed that C-dots did not induce any obvious impairment in tissues. Biochemical assays showed no significant alterations of most measured biochemical parameters in tissues and serum, except for a slight reduction of the albumin level in serum as well as AChE activity in the liver and kidneys. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis and SUS-plots disclosed that C-dots not only triggered the immune system but also disturbed the function of cell membranes as well as the normal liver clearance, indicating that the 1H NMR based metabolomics approach provided deep insights into the toxicity of C-dots in vivo and gained an advantage over traditional toxicological means, and should be helpful for the understanding of its toxic mechanism.


Long-term outcomes of Metacognitive Narrative Psychotherapy for people diagnosed with schizophrenia.
This study investigated long-term outcomes of Metacognitive Narrative Psychotherapy. Previous studies have shown the approach to be effective in enhancing recovery and metacognition in people with a diagnosis of schizophrenia. A 2-year longitudinal follow-up case study design. Eight people with a diagnosis of schizophrenia received an average of 52 sessions over 13-26 months. Follow-up interviews were conducted and self-report measures administered at approximately 2 years (22-30 months) post-completion of therapy. The majority of participants demonstrated reliable improvement from pre-treatment to 2-year follow-up on one or more of the outcome measures with some variation in patterns of improvement. This study provides the first evidence that therapeutic gains in recovery and metacognition during Metacognitive Narrative Psychotherapy for people with a diagnosis of schizophrenia can be maintained at 2-year follow-up. Larger, controlled trials are warranted to ascertain the most important factors contributing to the facilitation and maintenance of gains over time. Research demonstrates the value of longer-term psychotherapy for patients with more severe and longer-term difficulties resulting from psychotic spectrum disorders. Metacognitive Narrative Psychotherapy has been demonstrated to facilitate improvement in a proportion of patients who present with a diagnosis of schizophrenia. Components of Metacognitive Narrative Psychotherapy can be incorporated into a range of therapeutic approaches for the benefit of patients.


First trans-eunicellane terpene synthase in bacteria.
Terpenoids are the largest family of natural products, but prokaryotes are vastly underrepresented in this chemical space. However, genomics supports vast untapped biosynthetic potential for terpenoids in bacteria. We discovered the first trans-eunicellane terpene synthase (TS), AlbS from Streptomyces albireticuli NRRL B-1670, in nature. Mutagenesis, deuterium labeling studies, and quantum chemical calculations provided extensive support for its cyclization mechanism. In addition, parallel stereospecific labeling studies with Bnd4, a cis-eunicellane TS, revealed a key mechanistic distinction between these two enzymes. AlbS highlights bacteria as a valuable source of novel terpenoids, expands our understanding of the eunicellane family of natural products and the enzymes that biosynthesize them, and provides a model system to address fundamental questions about the chemistry of 6,10-bicyclic ring systems.


Synthesis of models of the BC ring systems of MPC1001 and MPC1001F.
Piperazinedione 13, representing the BC rings of the anti-prostate cancer fungal metabolite MPC1001, was prepared by a route in which a sulfur-stabilized carbanion derived from 22 cyclizes onto the terminal ester of the pendant chain attached to N(1). Another model, 14, was synthesized by cyclization of an α-ketoamide nitrogen onto an ester; 14 represents the BC rings of MPC1001F.


Glyphosate impairs aversive learning in bumblebees.
Agrochemicals represent prominent anthropogenic stressors contributing to the ongoing global insect decline. While their impact is generally assessed in terms of mortality rates, non-lethal effects on fitness are equally important to insect conservation. Glyphosate, a commonly used herbicide, is toxic to many animal species, and thought to impact a range of physiological functions. In this study, we investigate the impact of long-term exposure to glyphosate on locomotion, phototaxis and learning abilities in bumblebees, using a fully automated high-throughput assay. We find that glyphosate exposure had a very slight and transient impact on locomotion, while leaving the phototactic drive unaffected. Glyphosate exposure also reduced attraction towards UV light when blue was given as an alternative and, most strikingly, impaired learning of aversive stimuli. Thus, glyphosate had specific actions on sensory and cognitive processes. These non-lethal perceptual and cognitive impairments likely represent a significant obstacle to foraging and predator avoidance for wild bumblebees exposed to glyphosate. Similar effects in other species could contribute to a widespread reduction in foraging efficiency across ecosystems, driven by the large-scale application of this herbicide. The high-throughput paradigm presented in this study can be adapted to investigate sublethal effects of other agrochemicals on bumblebees or other important pollinator species, opening up a critical new avenue for the study of anthropogenic stressors.


Chitosan-Collagen Electrospun Nanofibers Loaded with Curcumin as Wound-Healing Patches.
Composite chitosan-collagen nanofibrous mats embedded with curcumin were prepared via a single-step electrospinning procedure and explored as wound-healing patches with superior biological activity. A mild crosslinking protocol consisting of a short exposure to ammonia vapor and UV radiation was developed to ensure proper stability in physiological-like conditions without affecting the intrinsic biocompatibility of chitosan and collagen. The fabricated composite patches displayed a highly porous, homogeneous nanostructure consisting of fibers with an average diameter of 200 nm, thermal stability up to 200 °C, mechanical features able to ensure protection and support to the new tissues, and water-related properties in the ideal range to allow exudate removal and gas exchange. The release kinetic studies carried out in a simulated physiological environment demonstrated that curcumin release was sustained for 72 h when the mats are crosslinked hence providing prolonged bioactivity reflected by the displayed antioxidant properties. Remarkably, combining chitosan and collagen not only ensures prolonged stability and optimal physical-chemical properties but also allows for better-promoting cell adhesion and proliferation and enhanced anti-bacteriostatic capabilities with the addition of curcumin, owing to its beneficial anti-inflammatory effect, ameliorating the attachment and survival/proliferation rates of keratinocytes and fibroblasts to the fabricated patches.


Salivary gland aplasia: an ectodermal disorder?
A case of a patient presenting with the symptoms of lifelong xerostomia is discussed. Clinical investigation demonstrated aplasia of all the major salivary glands, lacrimal gland hypoplasia and enamel hypoplasia. The management and aetiology of the case is discussed.


Kyphosis and pulmonary function in cystic fibrosis.
Spine deformity and chronic pulmonary disease are commonly seen in patients with cystic fibrosis (CF). In order to assess the prevalence of kyphosis, a retrospective evaluation of all initial standing chest radiographs of our CF patients matched with our "reference" population was undertaken. We also studied the possible correlation between the degree of kyphosis and the pulmonary function tests ( PFTs ), consisting of thoracic gas volume and maximal expiratory flows. In our population, the study confirmed an increased prevalence of kyphosis in CF patients (p less than .01), which occurred mostly in girls after 12 years of age (p less than .018). The kyphosis appeared to be, in most instances, of mild degree and was not related to any of the PFTs . No measurable increase of kyphosis was observed over a 3-year period in the group. Longer prospective study and the relationship of kyphosis to endocrine function in CF at puberty should be undertaken.


Wafer-Scale Epitaxial Growth of an Atomically Thin Single-Crystal Insulator as a Substrate of Two-Dimensional Material Field-Effect Transistors.
As the electron mobility of two-dimensional (2D) materials is dependent on an insulating substrate, the nonuniform surface charge and morphology of silicon dioxide (SiO2) layers degrade the electron mobility of 2D materials. Here, we demonstrate that an atomically thin single-crystal insulating layer of silicon oxynitride (SiON) can be grown epitaxially on a SiC wafer at a wafer scale and find that the electron mobility of graphene field-effect transistors on the SiON layer is 1.5 times higher than that of graphene field-effect transistors on typical SiO2 films. Microscale and nanoscale void defects caused by heterostructure growth were eliminated for the wafer-scale growth of the single-crystal SiON layer. The single-crystal SiON layer can be grown on a SiC wafer with a single thermal process. This simple fabrication process, compatible with commercial semiconductor fabrication processes, makes the layer an excellent replacement for the SiO2/Si wafer.


Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression-An Animal Model Study.
Basal levels of monoamines and DHEA in four main limbic brain regions were measured in prepubertal Wistar Kyoto (WKY) rats (a putative animal model of childhood depression). Basal levels of "Brain-Derived Neurotrophic Factor (BDNF)" were also determined in two regions in the hippocampus, compared with Wistar strain controls. In the second phase, we examined the responsiveness of prepubertal WKY rats to different types of chronic antidepressant treatments: Fluoxetine, Desipramine, and dehydroepiandrosterone sulfate (DHEAS). WKY prepubertal rats exhibited different monoamine levels in the limbic system, reduced DHEA levels in the VTA and lower levels of BDNF in the hippocampus CA3 region compared to controls. In prepubertal WKY rats, only treatment with DHEAS produced a statistically significant decrease in immobility, compared to saline-administered controls in the forced swim test. Wistar controls were not affected by any antidepressant. The results imply that DHEA(S) and BDNF may be involved in the pathophysiology and pharmacotherapy of childhood depression.


Outcomes at 18-24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013-2017: A Nationwide Cohort Study.
This study aimed to investigate the outcomes of infants at 18-24 months born in the Korean Neonatal Network with a birth weight <500 g. The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013-2017 and followed up at a corrected age of 18-24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician's referral to developmental specialists. At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18-24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.


INTRAFAMILIAL AND MIDPARENTAL-CHILD CORRELATIONS AND HERITABILITY ESTIMATES OF ANTHROPOMETRIC MEASUREMENTS IN PRADER-WILLI SYNDROME FAMILIES.
To determine the effects of familial background on anthropometric dimensions in Prader-Willi syndrome (PWS), we measured weight; height; sitting height; longitude and breadth of the head, hands, and feet; head, arm, and calf circumferences; and triceps and subscapular skinfolds in 28 individuals with the syndrome and their natural parents. Midparental-child correlations were significant for height and foot length, with heritability estimates of 0.52 and 0.68, respectively. Significant mother-child correlations were found for weight, height, foot length, and minimal frontal diameter for the total group; in addition, hand length and breadth, and calf and arm circumferences were significant for the patients age 12.5 years or under. These data provide evidence for maternal effects on several physical characteristics in PWS, particularly in younger patients.


Predicting having a best friend in young children: individual characteristics and friendship features.
In this study, the authors investigated the characteristics that predict best friend status in young children. One hundred and twenty-four preschool, kindergarten, and first-grade children identified their "best friend" and up to four "other friends" in their class. Teachers completed a questionnaire about each friendship to determine positive and negative features of the relationships. First, the authors used individual characteristics to predict if a child had a best friend. The variables age, gender, and peer acceptance predicted that a child would have a best friend. Second, positive friendship features positively predicted best friendships in analyses of all friendship pairs. Best friendships are meaningful relationships to children even at this young age and offer children more positive experiences than do other friendships.


Patient participation in general practice based undergraduate teaching: a focus group study of patient perspectives.
Patients make a crucial contribution to undergraduate medical education. Although a national resource is available for patients participating in research, none is as yet available for education. This study aimed to explore what information patients would like about participation in general practice based undergraduate medical education, and how they would like to obtain this information. Two focus groups were conducted in London-based practices involved in both undergraduate and postgraduate teaching. Patients both with and without teaching experience were recruited using leaflets, posters, and patient participation groups. An open-ended topic guide explored three areas: perceived barriers that participants anticipated or had experienced; patient roles in medical education; and what help would support participation. Focus groups were audiorecorded, transcribed, and analysed thematically. Patients suggested ways of professionalising the teaching process. These were: making information available to patients about confidentiality, iterative consent, and normalising teaching in the practice. Patients highlighted the importance of relationships, making information available about their GPs' involvement in teaching, and initiating student-patient interactions. Participants emphasised educational principles to maximise exchange of information, including active participation of students, patient identification of student learner needs, and exchange of feedback. This study will inform development of patient information resources to support their participation in teaching and access to information both before and during general practice based teaching encounters.


What do relatives of people with schizophrenia find helpful about family intervention?
While research indicates that family intervention is of benefit to schizophrenia patients and their relatives, it remains unclear why it is beneficial. Methodologies developed in psychotherapy process research may be of use in answering this question. The present study examines the applicability of one such methodology to a clinically based family intervention program. Relatives' (n = 20) reports of what they found helpful and unhelpful about the program were examined and the perceived therapeutic impacts of the program are reported. The implications of these results for future research are discussed.


The surgery and early postoperative radicular pain in cases with multifocal lumbar disc herniation.
Persistence of postoperative radicular pain after surgery for multifocal disc herniation (MFDH) is a clinical problem. This study aims to evaluate the effects of a combined treatment approach compared with unilateral stabilization on early postoperative radicular pain in patients with MFDH.Age, sex, level of operation, clinical findings, and radicular pain visual analogue scale (VAS) scores before surgery in the early postoperative period and at 3 months after surgery were retrospectively reviewed for 20 cases of multifocal lumbar disc herniation. The combined approach (translaminar and far lateral) was used for 13 cases. Seven cases underwent transforaminal lumbar interbody fusion (TLIF) and unilateral transpedicular stabilization following total facetectomy.The mean age of the sample was 49.4 ± 10.1 years and the female-to-male ratio was 8:12. The mean VAS scores for radicular pain in cases treated with the combined approach were 8.2, 4.07, and 2.3 in the preoperative and early postoperative periods and 3 months after surgery, respectively. The mean score for radicular pain improved by 50.4% in the early postoperative period and by 72% in the late postoperative period. The mean VAS scores for radicular pain in cases who underwent TLIF and unilateral stabilization after facetectomy were 8.4, 2.1, and 1.4 in the preoperative and early postoperative periods and 3 months after surgery, respectively. The mean VAS score for radicular pain improved by 75% in the early postoperative period and by 83.3% in the late postoperative period.The combined approach is an effective alternative in cases with MFDH. TLIF and unilateral segmental stabilization provide substantial decompression and eliminate mechanical compression by conserving the height of the intervertebral foramen in the event that sufficient decompression is unable to obtain. We suggest that elimination of chemical mediators, particularly those causing pain in the dorsal ganglion, contributes to the absence of early radicular pain.


Identification of the sites in myelin basic protein that are phosphorylated by meiosis-activated protein kinase p44mpk.
Myelin basic protein serves as a convenient substrate for detection of a 44 kDa protein-serine/threonine kinase (p44mpk) that is activated near the time of germinal vesicle breakdown in maturing echinoderm and amphibian oocytes. In vitro phosphorylation by purified p44mpk from sea star oocytes was primarily on threonine residues on a single tryptic peptide of bovine brain myelin basic protein. Amino acid composition analysis of the isolated posphopeptide revealed that it was rich in proline residues. Automated solid-phase sequencing by Edman degradation identified the major site as Thr-97 in the sequence NIVTPRTPPPSQGK, which corresponds to residues 91-104 in bovine brain myelin basic protein. Thr-94 was also phosphorylated by p44mpk to a very minor extent.


Purification and properties of the soluble cytochromes c-550 and c-556 from the bacterium Aquaspirillum itersonii.
Two c-type cytochromes were isolated from cells of the gram-negative bacterium Aquaspirillum itersonii grown under low aeration in the presence of nitrate. The major component, cytochrome c-550, was equated with the (single) c-type cytochrome previously reported to be present in this organism [Clark-Walker, G. D. & Lascelles, J. (1970) Arch. Biochem. Biophys. 136, 153-159], although a significantly higher molecular mass was apparent in the present work. The complete amino acid sequence of this cytochrome is reported in the accompanying paper. A second soluble c-type cytochrome, designated c-556, was also isolated. The molecular mass, isoelectric point, spectrum, midpoint oxidation reduction potential and amino acid composition of this monoheam cytochrome are reported. The possible relationship of this cytochrome to other cytochromes c-556 is discussed.


Motivational Interviewing and Return to Work for People with Musculoskeletal Disorders: A Systematic Mapping Review.
Purpose There is limited knowledge about motivational interviewing (MI) for people on sick leave with musculoskeletal disorders. Hence, our objective was to investigate what research on MI as a method to facilitate return to work for individuals who are on sick leave due to musculoskeletal disorders exists, and what are the results of the research? Methods We systematically searched MEDLINE, PsycINFO, EMBASE, Cochrane Library, CINAHL, Web of Science, Sociological Abstracts, Epistemonikos, SveMed + and DARE & HTA (covering 1983 to August 2019). We also searched the MINT bulletin and relevant web pages. Eligibility criteria: empirical studies investigating MI and return to work for people with musculoskeletal disorders. Two authors independently screened the records, critically appraised the studies and charted the data using a data extraction form. Results The searches identified 1264 records of which two studies were included. One randomized controlled trial (RCT) found no effect of MI on return to work for disability pensioner with back pain (n = 89, high risk of bias), while a cluster RCT found that MI increased return to work for claimants with chronic musculoskeletal disorders (n = 728, low risk of bias). Conclusions This mapping review identified a huge gap in research on MI to increase return to work for individuals with musculoskeletal disorders. Registration Current Research Information System in Norway, project id: 635823 ( https://app.cristin.no/projects/show.jsf?id=635823 ).


The adaptation and resistance of Clostridium aminophilum F to the butyrivibriocin-like substance of Butyrivibrio fibrisolvens JL5 and monensin.
When the amino acid-fermenting bacterium Clostridium aminophilum F was inoculated into media containing 1 microM monensin or a bacteriocin-like inhibitory substance (BLIS) from Butyrivibrio fibrisolvens JL5, the cultures lagged and growth was not observed for more than 12 h. The monensin- and BLIS-treated cultures eventually grew rapidly and did not lag a second time. Because cross-resistance could not be demonstrated, it appeared that the adaptation was specific. Non-adapted cells that were incubated with monensin lost their ability to produce ammonia from amino acids, and ATP, intracellular potassium, and electrical potential (DeltaPsi) were lower than untreated cells. Monensin-adapted cells regained their ability to produce ammonia, and intracellular potassium and DeltaPsi increased, but ATP was still 40% lower than untreated cells. When non-adapted cells were treated with the BLIS, ammonia production did not decline. Non-adapted cells were agglutinated by lysozyme, but in each case, adapted cells were not agglutinated. Adapted cells had more cellular polysaccharide and bound less of either inhibitor. Based on these results, it appears that the adapted cells had altered cell wall characteristics that prevented the binding of either monensin or the B. fibrisolvens JL5 BLIS.


Diarrheal Diseases and Climate Change in Cambodia.
The DRIP-SWICCH (Developing Research and Innovative Policies Specific to the Water-related Impacts of Climate Change on Health) project aimed to increase the resilience of Cambodian communities to the health risks posed by climate change-related impacts on water. This article follows a review of climate change and water-related diseases in Cambodia and presents the results of a time series analysis of monthly weather and diarrheal disease data for 11 provinces. In addition, correlations of diarrheal disease incidence with selected demographic, socioeconomic, and water and sanitation indicators are described, with results suggesting education and literacy may be most protective against disease. The potential impact of climate change on the burden of diarrheal disease in Cambodia is considered, along with the implications of these findings for health systems adaptation.


Stabilized phosphogypsum: class C fly ash: Portland type II cement composites for potential marine application.
Phosphogypsum (PG, CaSO4 x H20), a byproduct of phosphoric acid manufacturing, contains low levels of Ra226. PG can be stabilized with portland type II cement and class C fly ash for use in marine environments, thus eliminating the airborne vector of transmission for radon gas. An augmented simplex centroid design with pseudocomponents was used to select 10 PG:class C fly ash:portland type II cement compositions. The 43 cm3 blocks were fabricated and subjected to a 1.5-yr field submergence test and a 28-d saltwater dynamic leaching study. All field composites survived with no signs of degradation. Dynamic leaching resulted in effective calcium diffusion coefficients ranging from 0.21 to 7.5 x 10(-14)m2 s(-1). Effective diffusion depths, calculated for t=1 and 30 yr, ranged from 0.4 to 2.2 mm and from 2.0 to 11.9 mm, respectively. Scanning electron microscopy and wavelength dispersive microprobe and X-ray diffraction analyses of the leached composites identified a 40-60-microm calcite layer that was absent in the control composites. This suggests that a reaction between the composites and the saltwater results in the precipitation of calcite onto the block surface, encapsulating the composites and protecting them from saltwater attack and dissolution.


Bicycle balance assist system reduces roll and steering motion for young and older bicyclists during real-life safety challenges.
Bicycles are more difficult to control at low speeds due to the vehicle's unstable low-speed dynamics. This issue might be exacerbated by factors such as aging, disturbances, and multi-tasking. To address this issue, we developed a prototype 'balance assist system' with Royal Dutch Gazelle and Bosch eBike Systems at Delft University of Technology, which includes an electric motor capable of providing additional steering torque. We implemented a speed-adaptive feedback controller to generate the additional steering torque to that of the rider. We conducted a study with 18 older and 14 younger cyclists to first examine the effect of aging, disturbances, and multi-tasking on cycling at lower forward speeds, and evaluate the effectiveness of the system in improving the stability of the rider-bicycle system while facing these challenges. The study consisted of two scenarios: a single-task scenario where participants rode the bicycle on a marked narrow straight-line track, and a multi-task scenario where participants performed a shoulder check task and followed visual cues while tracking the straight-line. We introduced handlebar disturbances using the steer motor in half of the trials in both scenarios. All trials were repeated with and without the balance assist system. We calculated the bicycle mean magnitude of roll and steering rate-as indicators of bicycle balance control and required steering actions, respectively-and the rider's mean magnitude of lean rate with respect to the ground to investigate the effect of the balance assist system on rider's lateral motion. Our results showed that aging, disturbances, and multi-tasking increased the roll rate, and the balance assist system was able to significantly reduce it. The effect size of the balance assist system in reducing the roll rate across all conditions was found to be larger in older cyclists, indicating a more substantial impact compared to younger cyclists. Disturbances and multi-tasking increased the steering rate, which was successfully reduced by the balance assist system. Aging did not significantly affect the steering rate. The rider's lean rate was not significantly affected by age, disturbances, or the balance assist, indicating that the upper body plays a minor role when riders have good steering control authority. Overall, our findings suggest that lateral motion and required steering action can be affected by age, multi-tasking, and handlebar disturbances which can endanger cyclists' safety, and the balance assist system has the potential to improve cycling safety and reduce the incidence of single-actor crashes. Further investigation on riders' contribution to control actions is required.


Estradiol in severe asthma with premenstrual worsening.
To describe the beneficial effects of estradiol in a severely asthmatic woman with premenstrual worsening of asthma. A 50-year-old white woman, with a 14-year history of severe steroid-dependent asthma and monthly premenstrual worsening of asthma, was randomized to receive estradiol 2 mg or placebo for 6 days during the late luteal phase (days 23-28) of 2 successive menstrual cycles. Despite greater prednisone and inhaled beta-agonist use during the late luteal phase of the placebo cycle, the patient exhibited improved asthma symptoms, pulmonary function, and peak expiratory flows, as well as lower values for biomarkers of airway inflammation during the same time period of the estradiol cycle. This subject's response to estradiol was in contrast to results of a randomized, controlled trial involving patients with predominantly mild asthma under excellent control. The discrepant observations for this case versus the majority of subjects in the randomized, controlled study suggest that premenstrual asthma (PMA) and a beneficial response to estradiol may be more likely in women with severe asthma. The administration of estradiol during the late luteal phase of the menstrual cycle to a woman with severe asthma with PMA was associated with improved asthma symptoms, pulmonary function, and peak expiratory flows, and lower serum eosinophil protein X and urinary leukotriene E(4) biomarker concentrations. Thus, estradiol's potential role in women with severe asthma and PMA may warrant further exploration in this subgroup.


Three-dimensional localization of point acoustic sources using a planar microphone array combined with beamforming.
This paper presents a beamforming-based acoustic imaging (BBAI) method employing a two-dimensional (2D) microphone array that not only can locate an acoustic source in the XY plane parallel to the array, but can also identify the distance between the source and array in the Z direction, denoted as the source depth, and thus provides three-dimensional (3D) localization ability. In this method, the acoustic field is reconstructed on virtual XY planes at different distances along the Z direction. The source depth is then determined according to the virtual plane providing the maximum response of the acoustic field. The location of the source in the X and Y directions of the identified virtual plane can then be easily determined based on the standard beamforming principles of a planar array. The proposed BBAI method is evaluated based on simulations involving single- and multiple-point sources, and corresponding experimental evaluations are similarly conducted in an anechoic chamber. Both simulation and experimental results demonstrate that the proposed method is capable of locating acoustic sources in 3D space.


Obesity, sedentarism and TMD-pain in adolescents.
Obesity is a chronic and prevalent disorder, affecting individuals of all age. Previous evidence suggests that it is associated with some types of chronic pain, especially musculoskeletal pain. In addition, sedentarism is also associated with an increase of the inflammatory factors and chronic pain. So, we conducted a cross-sectional study to evaluate the association between obesity, sedentarism and the presence of TMD-pain in adolescents. Temporomandibular Disorders were classified according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Obesity was assessed by the body mass index (BMI), bioimpedance (BIA), skinfold (triceps and subscapular) and circumferences (arm and abdominal). The level of physical activity was rated according to the instrument adopted by the Brazilian National School Health Survey. Descriptive statistics, univariate logistic regression and odds ratios (OR) with 95% confidence intervals (CI) were used to study the associations of interest. The sample consisted of 690 individuals with a mean age of 12.7 (±0.76) years of whom 389 (56.4%) were girls. Of the total, 112 (16.2%) had TMD-pain, 110 (15.9%) were obese according to BMI, 74 (10.8%) according to BIA, and 127 (18.4%) following the skinfolds and circumferences assessments. There was no significant association between TMD-pain and obesity according to BMI (P = 0.95), BIA (P = 0.16), skinfold and circumference (P = 0.22), and neither with sedentarism (P = 0.94). Obesity and sedentarism were not associated with the presence of TMD-pain in adolescents.


[Effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome].
To investigate the effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome (PCOS). Seventy-six PCOS infertile women undergoing intrauterine insemination (IUI) or with anovulation were divided into two groups and received oral letrozole at the daily dose of 2.5 (n=36) or 5.0 mg (n=40) from the 3rd to the 7th day of the menstrual cycle. Three days after discontinuation of the medication (the 10th day of the menstrual cycle ), ultrasound scanning was performed to monitor the follicle development. When the diameter of the biggest follicle reached 14 mm, the presence of luteinizing hormone (LH) was monitored; when LH positivity was detected, blood samples were drawn to test follicle-stimulating hormone (FSH), LH, estradiol (E2) and testosterone (T) levels. Human chorionic gonadotropin (hCG, 10 000 U) was then injected to induce ovulation. The ovulation rate, stimulation follicle days, diameter of the biggest follicle on the day of LH positivity and the thickness of endometrium were all similar between the two groups (P>0.05). But in women receiving 5.0 mg letrozole, both the number of mature follicles and pregnancy rate were significantly higher than those in women having the half dose (P<0.05). The levels of FSH, LH, E2, and T on the third day of menstruation and on the day of HCG injection were similar between the two groups (P<0.05). Letrozole at the dose of 5.0 mg/day produces higher pregnancy rate and more mature follicles in fertile women with PCOS.


[Faecal calprotectin : a useful tool for the primary care physician ?]
Faecal calprotectin (FC) is a marker of intestinal inflammation. FC dosing has a sensitivity between 80‑100% for differentiating functional and organic intestinal disease. It is therefore a very useful diagnostic tool in general practice, where the prevalence of functional disease is particularly high. Nevertheless, FC is not specific for inflammatory bowel diseases and cannot distinguish between various inflammatory conditions. FC cut-off values are not clearly defined. Nevertheless, levels < 150 µg/g are considered ruling out organic disease and levels > 150 µg/g warrant an endoscopy. In the intermediate range 50‑150 µg/g, the result is indeterminate and the decision to perform further tests should be made on an individual basis.


Serum survivin predicts responses to treatment in active rheumatoid arthritis: a post hoc analysis from the SWEFOT trial.
The identification of biomarkers that predict optimal and individual choices of treatment for patients with rheumatoid arthritis gains increasing attention. The purpose of this study was to investigate if the proto-oncogene survivin might aid in treatment decisions in early rheumatoid arthritis. Serum survivin levels were measured in 302 patients who completed the Swedish pharmacotherapy (SWEFOT) trial at baseline, 3, 12, and 24 months. Survivin levels > 0.45 ng/mL were considered positive. Based on the survivin status, core set outcomes measuring disease activity, functional disability, as well as global health and pain were evaluated after methotrexate (MTX) monotherapy at 3 months, and at 12 and 24 months of follow-up. Treatment of non-responders was randomly intensified with either a combination of disease-modifying antirheumatic drugs (triple therapy: MTX, sulfasalazine, and hydroxychloroquine) or by adding antibodies against tumor necrosis factor (anti-TNF). Antirheumatic treatment resulted in an overall decrease of serum survivin levels. Survivin-positive patients at baseline who initially responded to MTX had a higher risk of disease re-activation (OR 3.21 (95% CI 1.12-9.24), P = 0.032) and failed to improve in their functional disability (P = 0.018) if having continued on MTX monotherapy compared to survivin-negative patients. Ever-smokers who were survivin-positive were less likely to respond to MTX than those who were survivin-negative (OR 1.91 (1.01-3.62), P = 0.045). In survivin-positive patients, triple therapy led to better improvements in disease activity than did MTX + anti-TNF. At 24 months, survivin-positive patients randomized to anti-TNF had a higher risk of active disease than those randomized to triple therapy (OR 3.15 (1.09-9.10), P = 0.037). We demonstrate for the first time that survivin is a valuable serologic marker that can distinguish drug-specific clinical responses in early rheumatoid arthritis through the pragmatic clinical setting of the care-based SWEFOT trial. Although treatment response cannot solely be attributable to survivin status, per protocol sensitivity analyses confirmed the superior effect of triple therapy on survivin-positive patients. Survivin-positive patients have poor outcomes if treated with MTX monotherapy. A decrease of survivin levels during treatment is associated with better clinical responses. For survivin-positive patients who fail MTX, triple therapy is associated with better outcomes than anti-TNF therapy. WHO database at the Karolinska University Hospital: CT20080004 ; ClinicalTrials.gov: NCT00764725, registered 1 October 2008.


Optimization of Micro-Drilling of Laminated Aluminum Composite Panel (Al-PE) Using Taguchi Orthogonal Array Design.
Aluminum Matrix Composite (AMC) represents an innovative class of materials that is extensively utilized in industries such as automotive, defense, aerospace, structural engineering, sports, and electronics. This study investigates the thrust force, exit burr formation, changes in the micro-tool, and drilled hole diameters during the micro-drilling of an aluminum-polyethylene composite panel (Al-PE). The panel consists of 3501 series aluminum skin materials bonded to a polyethylene (PE) core. Micro-drilling test parameters were designed using Taguchi's L16 (42 23) orthogonal array. Tests were conducted with five control parameters: cutting speed with four levels (10 m/min, 20 m/min, 30 m/min, 40 m/min), feed rate with four levels (0.5 µm/rev, 1 µm/rev, 2 µm/rev, 4 µm/rev), the tool diameter with two levels (0.7 mm, 1 mm), and tool point angle with two levels (100°, 140°) using both AlTiN-coated and uncoated drills. The maximum thrust force (Fz), maximum burr height, and changes in both the drill tool and hole diameters were measured for analysis of variance (ANOVA). The results showed that, in terms of impact on Fz, tool point angle had the highest positive influence (64.54%) on the micro-drill at the entrance of composite (upper aluminum plate). The cutting speed had the highest positive influence (45.32%) on the tool in the core layer (PE core layer). The tool point angle also had the highest positive influence (68.95%) on the micro-drill at the lower layer of the composite (the lower aluminum plate). There was noticeable chip adhesion on the major cutting edge and nose area under micro-drilling conditions with higher thrust forces and burr height. The AlTiN coating had a positive effect on tool wear and hole diameter deviations, but it adversely affected the burr height.


Measurements of radial profile of isotope density ratio using bulk charge exchange spectroscopy.
A bulk charge exchange spectroscopy (BCXS) system using a grism (grating prism) spectrometer has been applied to measure the profile of the deuterium (D) fraction in deuterium and hydrogen (H) mixture plasma in the Large Helical Device. The observed spectrum can be fitted with four Gaussian functions successfully by reduction of free parameters for the least-squares fit. The plasma flow velocity and ion temperature profile measured by charge exchange spectroscopy using carbon impurity are used for estimation of the wavelength shift of hot components to reduce the free parameter. The ion temperature is used to estimate the apparent wavelength shift due to the energy dependent emission cross section only and is not used to set the Doppler width for H and D in the fitting. The sensitivity of the evaluated D fraction on the velocity is increased for a higher D fraction. The error of the D fraction is calculated from the error in the fitted parameter and sensitivity on the velocity of the hot component. The difference in the profile and time trace of the D fraction with D pellet and H pellet injection was observed clearly by BCXS using a grism spectrometer.


Transitioning from genotypes to epigenotypes: why the time has come for medulloblastoma epigenomics.
Recent advances in genomic technologies have allowed for tremendous progress in our understanding of the biology underlying medulloblastoma, a malignant childhood brain tumor. Consensus molecular subgroups have been put forth by the pediatric neuro-oncology community and next-generation genomic studies have led to an improved description of driver genes and pathways somatically altered in these subgroups. In contrast to the impressive pace at which advances have been made at the level of the medulloblastoma genome, comparable studies of the epigenome have lagged behind. Complementary data yielded from genomic sequencing and copy number profiling have verified frequent targeting of chromatin modifiers in medulloblastoma, highly suggestive of prominent epigenetic deregulation in the disease. Past studies of DNA methylation-dependent gene silencing and microRNA expression analyses further support the concept of medulloblastoma as an epigenetic disease. In this Review, we aim to summarize the key findings of past reports pertaining to medulloblastoma epigenetics as well as recent and ongoing genomic efforts linking somatic alterations of the genome with inferred deregulation of the epigenome. In addition, we predict what is on the horizon for medulloblastoma epigenetics and how aberrant changes in the medulloblastoma epigenome might serve as an attractive target for future therapies.


Branched-Chain Fatty Acid Content Modulates Structure, Fluidity, and Phase in Model Microbial Cell Membranes.
Recent progress in understanding the importance and origins of lipid rafts in microbial cell membranes has focused attention on membranes containing branched-chain fatty acids. The working hypothesis is that branched fatty acids increase the fluidity of the bilayer, analogous to unsaturated fatty acids in membranes of higher organisms. Here, we perform a series of 7 μs long atomistic simulations on biomimetic, branched-chain lipid containing bilayer patches, systematically varying the amount of the straight-chain fatty acid component, n16:0, from 7.0 to 47.3 mol %. The simulations reveal thickening and ordering of the bilayer as well as higher bilayer viscosity and bending modulus with increasing n16:0 content, thus providing quantitative support that branched fatty acids increase the bilayer fluidity. A sharp transition in these properties is observed at ∼20% n16:0 content, resembling a phase change. The simulations provide the first access to ordered and disordered phases in a bacterial cell membrane mimic containing branched-chain lipids. Granted several assumptions, a comparison of these phases provides estimates of physical properties such as hydrophobic mismatch (∼1.2 Å), difference in bending moduli (∼15.7 kBT), and the line tension (∼0.6 pN) for a putative lipid raft in the cell membrane of an organism such as Bacillus subtilis or Staphylococcus aureus.


Young children's knowledge about printed names.
Four experiments examined young children's knowledge about the visual characteristics of writing, specifically personal names. Children younger than 4 years of age, even those who could read no simple words, showed some knowledge about the horizontal orientation of English names, the Latin letters that make them up, and their left-to-right directionality. Preschoolers also had some familiarity with the shapes of the letters in their own first name, especially the leftmost letter. Knowledge of the conventional capitalization pattern for English names emerged later, after a period during which children preferred names in all uppercase letters. When tested with personal names, the kind of word they know best, young children are surprisingly knowledgeable about the visual characteristics of writing.


Initiation of protein synthesis in bacteria at a translational start codon of mamalian cDNA: effects of the preceding nucleotide sequence.
Plasmids containing a mouse cDNA sequence encoding the enzyme dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 126.96.36.199) have been used to study the efficiency of initiation of protein synthesis at an ATG (AUG) translational start codon indigenous to the eukaryotic CDNA. differences in DHFR production assayed phenotypically, enzymatically, and immunologically were correlated with the primary structure of the DNA segment that precedes the translational start codon. Our results indicate that initiation of a structurally discrete and biologically functional eukaryotic protein can occur in bacteria on a fused mRNA molecule, and that the efficiency of expression is strongly affected by: (i) the extent of homology of the translational control region with the 3'-OH end of 16S ribosomal RNA, and (ii) the distance between the protein start codon and the ribosome-binding sequence on the mRNA.


Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas?
Uterine carcinosarcomas (malignant mixed Mullerian tumours) are highly aggressive and have traditionally been regarded as a subtype of uterine sarcoma. However, in recent years convincing evidence has suggested that most, but not all, are monoclonal in origin rather than true collision tumours. Data confirm that the carcinomatous element is the "driving force" and that the sarcomatous component is derived from the carcinoma or from a stem cell that undergoes divergent differentiation. Thus, uterine carcinosarcomas are best regarded as metaplastic carcinomas, although the designation carcinosarcoma is likely to remain. Adjuvant treatment for uterine carcinosarcoma should probably be similar to that directed against aggressive high grade endometrial carcinomas rather than being sarcoma based. Importantly, a small proportion of uterine carcinosarcomas are true collision tumours and should be recognised as such because, in some instances, the prognosis may be better than for a similar stage carcinosarcoma.


Regulation of thymic NKT cell development by the B7-CD28 costimulatory pathway.
Invariant NKT (iNKT) cells are a population of TCRalphabeta-expressing cells that are unique in several respects. In contrast to conventional T cells, iNKT cells are selected in the thymus for recognition of CD1, rather than conventional MHC class I or II, and are selected by CD1-expressing double-positive thymocytes, rather than by the thymic stromal cells responsible for positive selection of conventional T cells. We have probed further the requirements for thymic iNKT cell development and find that these cells are highly sensitive to B7-CD28 costimulatory interactions, as evidenced by the substantially decreased numbers of thymic iNKT cells in CD28 and in B7 knockout mice. In contrast to the requirement for CD1, B7-CD28 signaling does not affect early iNKT cell lineage commitment, but exerts its influence on the subsequent intrathymic expansion and differentiation of iNKT cells. CD28 wild-type/CD28-deficient mixed bone marrow chimeras provided evidence of both cell-autonomous and non-cell-autonomous roles for CD28 during iNKT cell development. Paradoxically, transgenic mice in which thymic expression of B7 is elevated have essentially no measurable thymic iNKT cells. Taken together, these results demonstrate that the unique pathway involved in iNKT cell development is marked by a critical role of B7-CD28 interactions and that disruption or augmentation of this costimulatory interaction has substantial effects on iNKT cell development in the thymus.


A rapid, quantitative enzyme-linked immunosorbent assay (ELISA) for the immunodiagnosis of Chagas' disease.
A rapid, quantitative enzyme-linked immunosorbent assay (ELISA) for the immunodiagnosis of Chagas' disease is described. The ELISA was standardized with the Falcon assay screening test (F.A.S.T.) system using a purified Trypanosoma cruzi epimastigote fraction (PEF) obtained by ion exchange chromatography. The ELISA technique and an indirect immunofluorescence (IIF) test were used to search for T.cruzi--specific IgG antibodies in 73 patients with chronic Chagas' disease, 58 patients with heterologous infections and 20 healthy controls. The ELISA exhibited 98.6% sensitivity and 98.7% specificity, whereas the sensitivity and specificity of the IIF test were 94.5% and 96.2%, respectively. The excellent performance with regard to sensitivity and specificity, as well as the short assay time make the F.A.S.T. system--based ELISA with PEF a potentially useful tool in screening for antibodies against T. cruzi.


PICNIC Architecture.
The PICNIC architecture aims at supporting inter-enterprise integration and the facilitation of collaboration between healthcare organisations. The concept of a Regional Health Economy (RHE) is introduced to illustrate the varying nature of inter-enterprise collaboration between healthcare organisations collaborating in providing health services to citizens and patients in a regional setting. The PICNIC architecture comprises a number of PICNIC IT Services, the interfaces between them and presents a way to assemble these into a functioning Regional Health Care Network meeting the needs and concerns of its stakeholders. The PICNIC architecture is presented through a number of views relevant to different stakeholder groups. The stakeholders of the first view are national and regional health authorities and policy makers. The view describes how the architecture enables the implementation of national and regional health policies, strategies and organisational structures. The stakeholders of the second view, the service viewpoint, are the care providers, health professionals, patients and citizens. The view describes how the architecture supports and enables regional care delivery and process management including continuity of care (shared care) and citizen-centred health services. The stakeholders of the third view, the engineering view, are those that design, build and implement the RHCN. The view comprises four sub views: software engineering, IT services engineering, security and data. The proposed architecture is founded into the main stream of how distributed computing environments are evolving. The architecture is realised using the web services approach. A number of well established technology platforms and generic standards exist that can be used to implement the software components. The software components that are specified in PICNIC are implemented in Open Source.


Cardiovascular responses to avoidance conditioning in the dog: effects of beta adrenergic blockade.
Five laboratory dogs were trained to press a response panel to postpone shocks during 1-hr free-operant avoidance conditioning sessions. In addition, each dog was confined in the experimental environment for 1 hr immediately prior to each avoidance session. During these 2-hr sessions, blood pressure and heart rate were monitored continuously from indwelling catheters. After repeated exposure to the schedule, the onset of the avoidance contingency elicited acute increases in systolic and diastolic pressure and heart rate, which were maintained throughout the session. During the preavoidance interval, systolic and diastolic pressure increased gradually while heart rate decreased. Blockade of beta adrenergic receptor activity in these behaviorally-trained dogs by infusions of propranolol was associated with a significant attenuation of the tachycardia normally maintained during avoidance. Beta blockade did not prevent the rise in blood pressure or fall in heart rate during preavoidance. The results are consistent with the view that the cardiovascular pattern sustained during avoidance is mediated by activation of the sympathetic nervous system, but that the progressive change in cardiovascular activity during preavoidance intervals is mediated by other than sympathetic influences.


Target-Dependent Gating of Nanopores Integrated with H-Cell: Toward A General Platform for Photoelectrochemical Bioanalysis.
Herein we present a proof-of-concept study of target-dependent gating of nanopores for general photoelectrochemical (PEC) bioanalysis in an H-cell. The model system was constructed upon a left chamber containing ascorbic acid (AA), the antibody modified porous anodic alumina (AAO) membrane separator, and a right chamber placed with the three-electrode system. The sandwich immunocomplexation and the associated enzymatic generation of biocatalytic precipitation (BCP) in the AAO nanopores would regulate the diffusion of AA from the left cell to the right cell, leading to a varied photocurrent response of the ZnInS nanoflakes photoelectrode. Exemplified by fatty-acid-banding protein (FABP) as the target, the as-developed protocol achieved good performance in terms of sensitivity, selectivity, reproducibility, as well as efficient reutilization of the working electrode. On the basis of an H-cell, this work features a new protocol of target-dependent gating-based PEC bioanalysis, which can serve as a general PEC analytical platform for various other targets of interest.


[Microbial corrosion of dental alloy].
There is a very complicated electrolytical environment in oral cavity with plenty of microorganisms existing there. Various forms of corrosion would develop when metallic prosthesis functions in mouth. One important corrosive form is microbial corrosion. The metabolic products, including organic acid and inorganic acid, will affect the pH of the surface or interface of metallic prosthesis and make a change in composition of the medium, thus influencing the electron-chemical reaction and promoting the development of corrosion. The problem of develpoment of microbial corrosion on dental alloy in the oral environment lies in the primary condition that the bacteria adhere to the surface of alloy and form a relatively independent environment that promotes corrosion.


Controversies Concerning the Canadian Not Criminally Responsible Reform Act.
In Canada, individuals found not criminally responsible on account of mental disorder are subject to the disposition recommendations of the Provincial or Territorial Review Board of the jurisdiction where the offense was committed. Bill C-14, known as "The Not Criminally Responsible Reform Act" made changes to the postverdict disposition process of these individuals. This legislation was consistent with a broader "tough-on-crime" agenda of the previous federal government. The legislative changes codify that Review Boards take public safety as the "paramount consideration" in making their recommendations. The legislation also creates a new "high-risk" category for certain offenders and imposes limitations on their liberty. Further, Bill C-14 seeks to enhance victim involvement in the disposition process. The passage of this legislation has generated significant controversy in the medical and legal fields. Critics have stated that there is an absence of empirical evidence on which to base the amendments, that the legislation was an overreaction to high-profile cases, and that Bill C-14 is in questionable compliance with the Canadian Charter of Rights and Freedoms. In this review, we explore the potential catalysts involved in the creation of Bill C-14, the controversy surrounding the legislation, and the potential future impact on practicing forensic psychiatrists and on the forensic mental health system in Canada.


Black corals (Anthozoa: Antipatharia) from the deep (916 m-2542 m) Coral Sea, north-eastern Australia.
Black corals (Anthozoa: Antipatharia) occur in all the world's oceans in a wide range of habitats from shallow-water coral reefs to the deep-sea. However, the taxonomy of black corals is poorly known compared to many other anthozoan groups. This knowledge gap is particularly acute for the deep-sea, where collecting specimens is logistically difficult and costly. Here, we identify 21 black coral specimens collected from the western Coral Sea adjacent to north-east Australia. The specimens represent five nominal species from five genera and two families. All species represent new records for the region, including the first record for the family Cladopathidae Brook, 1889. We describe the morphology of these specimens, note geographic and bathymetric range expansions, and provide evidence to support the hypothesis that Bathypathes seculata Opresko, 2005 is the juvenile stage of Bathypathes patula Brook, 1889, thus warranting synonymization. Our findings demonstrate that deep-sea antipatharians in this region are much more diverse than previously reported. Furthermore, this study highlights the importance of museum collections in terms of increasing our understanding of taxonomy and patterns of biodiversity, particularly for poorly-studied habitats such as the deep-sea.


Bread consumption patterns in a Swedish national dietary survey focusing particularly on whole-grain and rye bread.
Bread types with high contents of whole grains and rye are associated with beneficial health effects. Consumer characteristics of different bread consumption patterns are however not well known. To compare bread consumption patterns among Swedish adults in relation to selected socio-demographic, geographic, and lifestyle-related factors. For selected consumer groups, the further aim is to investigate the intake of whole grains and the context of bread consumption, that is, where and when it is consumed. Secondary analysis was performed on bread consumption data from a national dietary survey (n=1,435). Respondents were segmented into consumer groups according to the type and amount of bread consumed. Multiple logistic regressions were performed to study how selected socio-demographic, geographic, and lifestyle-related factors were associated with the consumer groups. Selected consumption groups were compared in terms of whole-grain intake and consumption context. Consumption in different age groups was analysed more in detail. One-third of the respondents consumed mainly white bread. Socio-demographic, geographic, and healthy-lifestyle-related factors were associated with the bread type consumed. White bread consumption was associated with younger age groups, less education, children in the family, eating less fruit and vegetables, and more candy and snacks; the opposite was seen for mainly whole-grain bread consumers. Older age groups more often reported eating dry crisp bread, whole-grain bread, and whole-grain rye bread with sourdough whereas younger respondents reported eating bread outside the home, something that also mainly white bread eaters did. Low consumers of bread also consumed less whole grain in total. Traditional bread consumption structures were observed, as was a transition among young consumers who more often consumed fast food bread and bread outside the home, as well as less rye and whole-grain bread. Target groups for communication strategies and product development of more sensorily attractive rye or whole-grain-rich bread should be younger age groups (18-30 years), families with children, and groups with lower educational levels.


Considering the factors of gender and body weight in the promotion of healthy behavior among adolescents.
Obesity among adolescents is increasing in both developed and developing countries. However, previous studies have paid little attention to the roles that gender and body weight variables play in health-related behavior. This article examines the effects of these two variables on health-related behavior in Taiwanese adolescents. A cross-sectional descriptive design was used with three body weight categories (underweight, average and overweight) and two gender categories (female and male). Data were analyzed using descriptive statistics, Student's t test, and one-way ANOVA with Scheffe's post hoc test. The results showed that average weight adolescents scored significantly higher than their overweight peers in the three dimensions of social support, health responsibility, and exercise behavior. Average weight adolescents also scored higher than the underweight group in the dimension of health responsibility. Girls scored significantly better than boys in five out of the total six health-related behavior - scoring lower only in the exercise dimension. These findings should sound an alarm for all public health professionals to take heed to what is happening to our youth. School and family health promotion counseling should be encouraged for overweight adolescents to improve their exercise and lifestyle habits. Based on the findings, school health promotion programs should focus on gender differences. Girls, in particular, need encouragement to improve their exercise habits.


Proposal of a high-field superconducting wiggler for a slow positron source at SPring-8.
A low-energy positron beam is a unique probe of materials. In high-energy electron and positron storage rings it is possible to generate intense synchrotron radiation with a photon energy of 1-3 MeV by installing a high-field (8-10 T) superconducting wiggler. High-energy photons are converted to low-energy positrons by using a suitable target-moderator system. For an 8 GeV electron storage ring at a beam current of 100 mA, final yields are estimated to be about 10(8)-10(10) slow-e(+) s(-1) or larger depending on the moderation efficiency, with the size of the positron source 10(1)-10(2) cm(2). In the present work a wiggler magnetic system of 10 T is proposed. The main parameters of the superconducting wiggler are presented.


Proliferation inhibition of murine pluripotent haemopoietic stem cells by interferon or poly I:C.
The effect of mouse serum interferon (IF) in vitro and an inducer in vivo on the proliferation of a pluripotent stem cell population with high turnover rate was studied. Proliferation rate was characterized by the number of CFUs in the S phase of the cell cycle. Increased proliferation of bone marrow stem cell populations was produced either by irradiating the donor mice with 3.36 Gy (336 rad) 60Co-gamma rays 7 days before the experiment or by incubating normal bone marrow cells with 10(-11) M concentration of isoproterenol. IF considerably reduced the number of CFUs in S phase in both cases without reducing the CFUs content of the samples. Injection of IF inducer (4 mg/kg poly I:C) into regenerating mice also inhibited the proliferation of CFUs without decreasing the femoral CFUs level. Regeneration kinetics of CFUs from irradiated poly I:C-treated mice ran parallel with that of irradiated untreated animals but showed a characteristic delay corresponding to approximately one CFUs doubling. A transient, non-cytotoxic proliferation inhibitory effect of IF or IF inducer is, therefore, proposed.


Avian macrophages: contribution to cellular microenvironment and changes in effector functions following activation.
The capacity of macrophages to generate metabolites and monokines having effector and regulatory functions can result in a major impact on their cellular microenvironment. Macrophage products synthesized in response to bacterial lipopolysaccharide stimulation include reactive oxygen and nitrogen intermediates as well as tumor necrosis factor (TNF). These secreted products of macrophages exhibit bioactivity either locally or systemically. Although the mechanism of action of avian monokines such as TNF-like factor may be similar to their mammalian counterparts, chicken TNF seems to lyse cells of chicken origin and not of mammalian origin. Furthermore, the generation and activity of products such as TNF is directly influenced by environmental stressors such as heat and toxins.


Soluble and stable heptazethrenebis(dicarboximide) with a singlet open-shell ground state.
A soluble and stable heptazethrene derivative was synthesized and characterized for the first time. This molecule exhibits a singlet biradical character in the ground state, which is the first case among zethrene homologue series. Exceptional stability of this heptazethrenebis(dicarboximide) raises the likelihood of its practical applications in materials science.


Multilinear Multitask Learning by Rank-Product Regularization.
Multilinear multitask learning (MLMTL) considers an MTL problem in which tasks are arranged by multiple indices. By exploiting the higher order correlations among the tasks, MLMTL is expected to improve the performance of traditional MTL, which only considers the first-order correlation across all tasks, e.g., low-rank structure of the coefficient matrix. The key to MLMTL is designing a rational regularization term to represent the latent correlation structure underlying the coefficient tensor instead of matrix. In this paper, we propose a new MLMTL model by employing the rank-product regularization term in the objective, which on one hand can automatically rectify the weights along all its tensor modes and on the other hand have an explicit physical meaning. By using this regularization, the intrinsic high-order correlations among tasks can be more precisely described, and thus, the overall performance of all tasks can be improved. To solve the resulted optimization model, we design an efficient algorithm by applying the alternating direction method of multipliers (ADMM). We also analyze the convergence and show that the proposed algorithm, with certain restriction, is asymptotically regular. Experiments on both synthetic and real data sets substantiate the superiority of the proposed method beyond the existing MLMTL methods in terms of accuracy and efficiency.


Challenges of modern day transition care in inflammatory bowel disease: From inflammatory bowel disease to biosimilars.
In this article we discuss the challenges of delivering a high quality Transition care. A good understanding of the adolescent needs with good communication between Transition care physicians and the patient is essential for good continuity of care. Despite availability of several guidelines, one model doesn't fit all and any transition service development should be determined by the local need and available healthcare facilities.


Transgender-inclusive measures of sex/gender for population surveys: Mixed-methods evaluation and recommendations.
Given that an estimated 0.6% of the U.S. population is transgender (trans) and that large health disparities for this population have been documented, government and research organizations are increasingly expanding measures of sex/gender to be trans inclusive. Options suggested for trans community surveys, such as expansive check-all-that-apply gender identity lists and write-in options that offer maximum flexibility, are generally not appropriate for broad population surveys. These require limited questions and a small number of categories for analysis. Limited evaluation has been undertaken of trans-inclusive population survey measures for sex/gender, including those currently in use. Using an internet survey and follow-up of 311 participants, and cognitive interviews from a maximum-diversity sub-sample (n = 79), we conducted a mixed-methods evaluation of two existing measures: a two-step question developed in the United States and a multidimensional measure developed in Canada. We found very low levels of item missingness, and no indicators of confusion on the part of cisgender (non-trans) participants for both measures. However, a majority of interview participants indicated problems with each question item set. Agreement between the two measures in assessment of gender identity was very high (K = 0.9081), but gender identity was a poor proxy for other dimensions of sex or gender among trans participants. Issues to inform measure development or adaptation that emerged from analysis included dimensions of sex/gender measured, whether non-binary identities were trans, Indigenous and cultural identities, proxy reporting, temporality concerns, and the inability of a single item to provide a valid measure of sex/gender. Based on this evaluation, we recommend that population surveys meant for multi-purpose analysis consider a new Multidimensional Sex/Gender Measure for testing that includes three simple items (one asked only of a small sub-group) to assess gender identity and lived gender, with optional additions. We provide considerations for adaptation of this measure to different contexts.


Spontaneous fast gamma activity in the septal hippocampal region correlates with spatial learning in humans.
Hippocampal neuronal populations exhibit multiple kinds of activity patterns, from the dominant theta rhythm during active exploration to high-frequency ripple-like activity during periods of relative inactivity. In animals, evidence is rapidly accruing that these high-frequency ripple activity patterns subserve retention of spatial learning performance. In a translational effort to address the possible function of offline hippocampal processes in humans, we measured spontaneous gamma activity during an awake rest period within a virtual spatial learning context. Whole-head magnetoencephalographic (MEG) recordings were taken while healthy participants (N=24) quietly rested (eyes open) between encoding and retrieval phases of a hippocampal-dependent virtual Morris water maze task. Results are that fast gamma activity (80-140 Hz) in the septal or posterior region of the hippocampus (bilaterally) was positively correlated across participants with subsequent within-session spatial learning rate. Fast gamma did not predict initial retrieval performance following rest, failing to provide evidence of a direct link between spontaneous high-frequency activity patterns during awake rest and consolidation of previous spatial memories. The findings nevertheless are consistent with a prospective role for offline human hippocampal processes in spatial learning and indicate that higher spontaneous gamma activity in the septal hippocampal region is related to faster updating of spatial knowledge in familiar virtual surroundings.


Normal human fibroblasts enable melanoma cells to induce angiogenesis in type I collagen.
We previously reported that fibroblasts induce human microvascular endothelial cells (HMVECs) to differentiate from monolayer to capillarylike morphology. We now test the hypothesis that fibroblasts modulate angiogenesis in melanoma cells. We tested 12 human melanoma lines (2 radial growth phase (RGP), 3 vertical growth phase (VGP), and 7 metastatic (MM)) for ability to induce HMVECs to invade/migrate into collagen and form capillarylike networks. HMVEC monolayers were overlaid with 3-dimensional collagen gels embedded with melanoma cells alone (M), fibroblasts alone (F), or a 1:1 mixture of the 2 cells (M+F). After 5 days, gels were removed, fixed, and HMVEC networks were quantified by von Willebrand's factor (vWF) immunofluorescence. The influence of soluble factors on HMVEC invasion/migration into collagen was assessed with the use of acellular 3-D collagen gels overlaid on HMVEC monolayers, cultured with conditioned media (CM) derived from monolayers of M, F, or M+F. Angiogenic growth factors involved in the observed invasion/migration were identified with the use of a RayBio Cytokine Antibody Array (RayBiotech, Norcross, Ga). Cell line-specific variability in melanoma-supported angiogenesis was observed only when in combination with fibroblasts (analysis of variance [ANOVA], P < .01). Melanoma plus fibroblasts uniformly resulted in a significantly higher angiogenic response than melanoma alone (P < .05). One vertical growth phase and one metastatic melanoma line, while weakly angiogenic alone, induced significantly higher angiogenesis than either fibroblast or melanoma alone (P < .05) when combined with fibroblasts. CM from M or M+F induced significantly less HMVEC invasion/migration into collagen than CM from fibroblasts alone. Interleukin 8, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-2 were identified as significantly elevated in the media derived from M+F cultures, compared with either cell type alone. To our knowledge, this is the first report demonstrating that melanoma-supported angiogenesis in collagen is more significantly influenced by normal skin-derived fibroblasts than by the intrinsic biology of the melanoma cell type. Interleukin 8, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-2 are implicated as potential paracrine factors regulating this observed effect.


Probing the high density behavior of the nuclear symmetry energy with high energy heavy-ion collisions.
High energy heavy-ion collisions are proposed as a novel means to constrain stringently the high density (HD) behavior of nuclear symmetry energy. Within an isospin-dependent hadronic transport model, it is shown for the first time that the isospin asymmetry of the HD nuclear matter formed in high energy heavy-ion collisions is uniquely determined by the HD behavior of the nuclear symmetry energy. Experimental signatures in two sensitive probes, i.e., pi(-) to pi(+) ratio and neutron-proton differential collective flow, are also investigated.


Lipopolysaccharide administration in vivo induces differential expression of cAMP-specific phosphodiesterase 4B mRNA splice variants in the mouse brain.
Many inflammatory processes involve cAMP. Pharmacological manipulation of cAMP levels using specific phosphodiesterase (PDE) inhibitors provokes an antiinflammatory response. The aim of this study was to investigate changes in the pattern and levels of expression of mRNAs coding for the cAMP-specific PDE4 family and subfamilies in mouse brain during the immediate acute immune response provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that showed altered expression. Whereas PDE4B2 presented increased expression at both 3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in endothelial and macrophage/neutrophil cell populations in the leptomeninges, and the downregulation of PDE4B3 was observed mainly in oligodendrocytes throughout the brain. Our results clearly illustrate the distinctive anatomical distribution and cellular localization of the PDE4Bs during neuroinflammation and emphasize the importance of PDE4B splice-variant-specific inhibitors as therapeutic tools.


Promoting academic and social-emotional school readiness: the head start REDI program.
Forty-four Head Start classrooms were randomly assigned to enriched intervention (Head Start REDI-Research-based, Developmentally Informed) or "usual practice" conditions. The intervention involved brief lessons, "hands-on" extension activities, and specific teaching strategies linked empirically with the promotion of: (a) social-emotional competencies and (b) language development and emergent literacy skills. Take-home materials were provided to parents to enhance skill development at home. Multimethod assessments of three hundred and fifty-six 4-year-old children tracked their progress over the course of the 1-year program. Results revealed significant differences favoring children in the enriched intervention classrooms on measures of vocabulary, emergent literacy, emotional understanding, social problem solving, social behavior, and learning engagement. Implications are discussed for developmental models of school readiness and for early educational programs and policies.


[Correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension].
To explore the correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension (PAH). The clinical data were retrospectively analyzed for 106 patients with PAH from Affiliated Shanghai Pulmonary Hospital, Tongji University from October 2010 to October 2013. The examinations included routine pulmonary function test, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test, right heart catheterization and cardiopulmonary exercise testing. And within the same period, matched 20 healthy subjects without smoking and cardiopulmonary diseases were selected as control group. Peak oxygen uptake (P-VO2), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) were significantly lower in patients with PAH than control group ((841 ± 257) vs (1 682 ± 284) ml/min, (661 ± 171) vs (1 041 ± 243) ml/min, 1.1 ± 0.4 vs 2.3 ± 0.4, 25.8 ± 5.2 vs 35.5 ± 4.0, respectively) (all P < 0.001). And the predicted parametric values (%pred) were also lower in PAH group than control group (all P < 0.001). While the lowest ventilation (VE)/CO2 output (VCO2) (L-VE/VCO2) and VE/VCO2 slope were significantly higher in PAH group than control group (50.5 ± 15.9 vs 30.5 ± 3.0 and 57.2 ± 23.2 vs 25.6 ± 2.8, both P < 0.001). Pearson correlation analysis showed, except for VE/VCO2 slope%pred, AT%pred, L-VE/VCO2%pred, OUES%pred and OUEP%pred were correlated with P-VO2 (all P < 0.001). According to multiple linear regression analysis, only AT%pred and OUES%pred were the independent predictors of P-VO2 (β = 0.394, 0.384, both P < 0.001) and OUES%pred might be better than AT%pred (the adjusted β = 0.674). When AT%pred < 58.0% or OUES%pred < 65.0%, exercise capacity in PAH declined obviously with the sensitivity was 92.3% and 96.2% and the specificity 81.2% and 75.5% respectively. Exercise capacity in patients with PAH is significantly lower than healthy subjects. OUES%pred and AT%pred may be used as an independent predictor of exercise capacity. And OUES%pred may be more powerful.


Contrast sensitivity and the detection of moving patterns and features.
Theories based on optimal sampling by the retina have been widely applied to visual ecology at the level of the optics of the eye, supported by visual behaviour. This leads to speculation about the additional processing that must lie in between-in the brain itself. But fewer studies have adopted a quantitative approach to evaluating the detectability of specific features in these neural pathways. We briefly review this approach with a focus on contrast sensitivity of two parallel pathways for motion processing in insects, one used for analysis of wide-field optic flow, the other for detection of small features. We further use a combination of optical modelling of image blur and physiological recording from both photoreceptors and higher-order small target motion detector neurons sensitive to small targets to show that such neurons operate right at the limits imposed by the optics of the eye and the noise level of single photoreceptors. Despite this, and the limitation of only being able to use information from adjacent receptors to detect target motion, they achieve a contrast sensitivity that rivals that of wide-field motion sensitive pathways in either insects or vertebrates-among the highest in absolute terms seen in any animal.


The Predictive Role of Tooth Extractions, Oral Infections, and hs-C-Reactive Protein for Mortality in Individuals with and without Diabetes: A Prospective Cohort Study of a 12 1/2-Year Follow-Up.
The predictive role of high-sensitivity C-reactive protein (hs-CRP), number of tooth extractions, and oral infections for mortality in people with and without diabetes is unclear. This prospective cohort study is a 12 1/2-year follow-up of the Oslo II study, a health survey in 2000. In all, 12,764 men were invited. Health information was retrieved from 6434 elderly men through questionnaire information, serum measurements, and anthropometric and blood pressure measurements. Diabetes was reported by 425 men. Distinct differences were observed in baseline characteristics in individuals with and without diabetes. In the diabetes group, age and hs-CRP were statistically significant whereas in the nondiabetes group, age, hs-CRP, number of tooth extractions, tooth extractions for infections and oral infections combined, nonfasting glucose, systolic blood pressure, total cholesterol, regular alcohol drinking, daily smoking, and level of education were independent risk factors. The number of tooth extractions <5 was inversely related whereas more extractions increased the risk. Multivariate analyses showed that hs-CRP was a significant predictor in persons with diabetes and tooth extractions and oral infections combined; the number of teeth extracted and hs-CRP were for persons without diabetes. Infection and inflammation were associated with mortality in individuals both with and without diabetes.


[Rapid intravenous injection of streptokinase in a high initial dose for therapy of a fulminant pulmonary embolism (author's transl)].
As a result of the case described the administration of streptokinase in a high initial dosage of about 750,000-1,000,000 U within a few minutes appears to be effective in serious lethal pulmonary embolism. In spite of hypoxic cardiac arrest a 35-year-old female patient was reanimated successfully 20 minutes after the occurrence of pulmonary embolism on the 10th day after caesarian section. The development indicated that the high dosage of streptokinase led to lysis of the embolus and thus to perfusion of the lungs. In spite of complications haemothorax 4,000 ml, uterine haemorrhage the fibrinolytic and later the anticoagulante therapy was continued until lysis of the embolus was assumed as judged by the condition of the patient. To prevent a renewed cardiac arrest a temporary pacemaker was applied. The patient survived without evidence of a cerebral lesion. This paper wants to advocate the administration of streptokinase in "exorbitant" dosage in hopeless cases of serious pulmonary embolism of which a high percentage die. It is essential that the injection be made within a few minutes and must not be extended over the normally recommended period of time.


Effects of different medial arch support heights on rearfoot kinematics.
Foot orthoses are usually assumed to be effective by optimizing mechanically dynamic rearfoot configuration. However, the effect from a foot orthosis on kinematics that has been demonstrated scientifically has only been marginal. The aim of this study was to examine the effect of different heights in medial arch-supported foot orthoses on rear foot motion during gait. Nineteen asymptomatic runners (36±11years, 180±5cm, 79±10kg; 41±22km/week) participated in the study. Trials were recorded at 3.1 mph (5 km/h) on a treadmill. Athletes walked barefoot and with 4 different not customized medial arch-supported foot orthoses of various arch heights (N:0 mm, M:30 mm, H:35 mm, E:40mm). Six infrared cameras and the `Oxford Foot Model´ were used to capture motion. The average stride in each condition was calculated from 50 gait cycles per condition. Eversion excursion and internal tibia rotation were analyzed. Descriptive statistics included calculating the mean ± SD and 95% CIs. Group differences by condition were analyzed by one factor (foot orthoses) repeated measures ANOVA (α = 0.05). Eversion excursion revealed the lowest values for N and highest for H (B:4.6°±2.2°; 95% CI [3.1;6.2]/N:4.0°±1.7°; [2.9;5.2]/M:5.2°±2.6°; [3.6;6.8]/H:6.2°±3.3°; [4.0;8.5]/E:5.1°±3.5°; [2.8;7.5]) (p>0.05). Range of internal tibia rotation was lowest with orthosis H and highest with E (B:13.3°±3.2°; 95% CI [11.0;15.6]/N:14.5°±7.2°; [9.2;19.6]/M:13.8°±5.0°; [10.8;16.8]/H:12.3°±4.3°; [9.0;15.6]/E:14.9°±5.0°; [11.5;18.3]) (p>0.05). Differences between conditions were small and the intrasubject variation high. Our results indicate that different arch support heights have no systematic effect on eversion excursion or the range of internal tibia rotation and therefore might not exert a crucial influence on rear foot alignment during gait.