Force irradiation effects during upper limb diagonal exercises on contralateral muscle activation.
The aim of this study was to explore the force irradiation effects of upper limb isometric diagonal exercises on shoulder muscle activities. Interactions among diagonal directions, contraction intensities (moderate and maximum) and sex were assessed. Thirty healthy subjects (11 males) performed isometric unilateral diagonal exercises based on proprioceptive neuromuscular facilitation technique in an isokinetic dynamometer with their dominant upper limbs. The second diagonal for flexion and for extension were assessed while the participants performed their maximum isometric torque (MIT) and at 25% of their MIT. During the exercise the muscle activity of the medial deltoid, pectoralis major and upper trapezius in the non-dominant (non-exercised) upper limbs of the participants was recorded by surface electromyography. The highest muscle activity occurred in the upper trapezius during the diagonal for flexion (27% of maximum isometric voluntary contractions). Upper trapezius and pectoralis major were more active during the diagonal for flexion than diagonal for extension (p < 0.001), while similar values between both diagonals were observed for the medial deltoid (p > 0.05). In conclusion, we observed that force irradiation during upper limb diagonal exercises is affected by diagonal direction, contraction intensity and sex when performed by healthy participants.


Bone mineral density in lifelong trained male football players compared with young and elderly untrained men.
The purpose of the present controlled cross-sectional study was to investigate proximal femur and whole-body bone mineral density (BMD), as well as bone turnover profile, in lifelong trained elderly male football players and young elite football players compared with untrained age-matched men. One hundred and forty healthy, non-smoking men participated in the study, including lifelong trained football players (FTE, n = 35) aged 65-80 years, elite football players (FTY, n = 35) aged 18-30 years, as well as untrained age-matched elderly (UE, n = 35) and young (UY, n = 35) men. All participants underwent a regional dual-energy X-ray Absorptiometry (DXA) scan of the proximal femur and a whole-body DXA scan to determine BMD. From a resting blood sample, the bone turnover markers (BTMs) osteocalcin, carboxy-terminal type-1 collagen crosslinks (CTX-1), procollagen type-1 amino-terminal propeptide (P1NP), and sclerostin were measured. FTE had 7.3%-12.9% higher (p < 0.05) BMD of the femoral neck, wards, shaft, and total proximal femur in both legs compared to UE, and 9.3%-9.7% higher (p < 0.05) BMD in femoral trochanter in both legs compared to UY. FTY had 24.3%-37.4% higher (p < 0.001) BMD in all femoral regions and total proximal femur in both legs compared to UY. The whole-body DXA scan confirmed these results, with FTE showing similar whole-body BMD and 7.9% higher (p < 0.05) leg BMD compared to UY, and with FTY having 9.6% higher (p < 0.001) whole-body BMD and 18.2% higher (p < 0.001) leg BMD compared to UY. The plasma concentration of osteocalcin, CTX-1, and P1NP were 29%, 53%, and 52% higher (p < 0.01), respectively, in FTY compared to UY. BMD of the proximal femur and whole-body BMD are markedly higher in lifelong trained male football players aged 65-80 years and young elite football players aged 18-30 years compared to age-matched untrained men. Elderly football players even show higher BMD in femoral trochanter and leg BMD than untrained young despite an age difference of 47 years.


Differential micro ribonucleic acid expression profiling in ovarian endometrioma with leuprolide acetate treatment.
Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues. We compared the miRNA expression profiles of the three groups by performing TaqMan Array MicroRNA Card and bioinformatic analysis. Two miRNAs, miR-939 and miR-154, were upregulated in endometriotic tissue and downregulated in leuprolide acetate-treated endometriotic tissue. Five miRNAs (miR-146a, miR-142-3p, miR-136*, miR-125b-1* and miR-15b*) were unchanged in endometriotic tissue but were upregulated under leuprolide acetate treatment. Ingenuity pathway analysis using predicted target genes for the seven identified miRNAs suggested the involvement of a range of pathways, including axonal guidance, bone morphogenetic protein, phosphatase and tensin homolog and nitric oxide signaling; molecular mechanisms of cancer; and the adipogenesis and signal transducer and activator of transcription 3 (STAT3) pathways. To our knowledge, this is the first report profiling the miRNAs of endometrioma under leuprolide acetate treatment. The expression of seven miRNAs was modulated, concomitant with the disease state. This result gives new insight into the effects of leuprolide acetate treatment. Further investigation using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry will allow us to validate the results of this study and to explore new therapeutic targets and biomarkers of endometriosis.


The relationship of Medicaid expansion to psychiatric comorbidity care within substance use disorder treatment programs.
Co-occurring mental health disorders are common among substance use disorder (SUD) patients. Medicaid expansion aimed to reduce barriers to SUD and mental health care and thereby improve treatment outcomes. We estimated change in the proportion of United States SUD treatment sites offering treatment for psychiatric comorbidities following Medicaid expansion as part of implementation of the Affordable Care Act (ACA) in 2014. Using panel data from the 2013-2014, n = 660, and 2016-2017, n = 638, waves of the National Drug Abuse Treatment System Survey (NDATSS), we estimated change in the proportion of sites offering antidepressant medication, other psychiatric medication, behavioral treatment, or any combination thereof for treatment of mental health comorbidities (i.e., beyond services focused on SUD). We modeled the impact of Medicaid expansion as an interaction between year and date of Medicaid expansion. We constructed a mixed-effects linear regression model for each outcome, with the interaction variable as the main exposure, site as a random effect, and site's average duration of treatment, proportion of clients with psychiatric comorbidities, average caseload per treatment prescribing-clinician on staff, type of facility and geographic region as covariates, to estimate a difference-in-differences (D-I-D) equation. The adjusted D-I-D analysis indicated that the proportion of SUD treatment sites offering antidepressants for psychiatric treatment increased 10% (95% CI 1%, 18%) in the Medicaid expansion sites compared to non-expansion sites. The D-I-D for other psychiatric medications was also 10% (95% 1%, 19%). No significant changes were observed in behavioral treatment or the combination measure. The strongest association between Medicaid expansion and offering medication for mental health comorbidities was the 34% increase observed for residential treatment settings (95% CI 10%, 59%). Availability of psychiatric medication treatment in SUD treatment settings increased following Medicaid expansion, particularly in residential SUD facilities. This policy change has facilitated integrated treatment for the substantial share of SUD treatment patients with mental health comorbidities, with the greatest benefit for patients receiving SUD treatment in residential programs.


The effect of ageing on in vivo human ciliary muscle morphology and contractility.
To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Seventy-nine subjects, aged 19-70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 μm/year nasally (R = 0.54, P < 0.001) and 3.0 μm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.


Genomic evolution of the Coronaviridae family.
The current outbreak of coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 poses unparalleled challenges to global public health. SARS-CoV-2 is a Betacoronavirus, one of four genera belonging to the Coronaviridae subfamily Orthocoronavirinae. Coronaviridae, in turn, are members of the order Nidovirales, a group of enveloped, positive-stranded RNA viruses. Here we present a systematic phylogenetic and evolutionary study based on protein domain architecture, encompassing the entire proteomes of all Orthocoronavirinae, as well as other Nidovirales. This analysis has revealed that the genomic evolution of Nidovirales is associated with extensive gains and losses of protein domains. In Orthocoronavirinae, the sections of the genomes that show the largest divergence in protein domains are found in the proteins encoded in the amino-terminal end of the polyprotein (PP1ab), the spike protein (S), and many of the accessory proteins. The diversity among the accessory proteins is particularly striking, as each subgenus possesses a set of accessory proteins that is almost entirely specific to that subgenus. The only notable exception to this is ORF3b, which is present and orthologous over all Alphacoronaviruses. In contrast, the membrane protein (M), envelope small membrane protein (E), nucleoprotein (N), as well as proteins encoded in the central and carboxy-terminal end of PP1ab (such as the 3C-like protease, RNA-dependent RNA polymerase, and Helicase) show stable domain architectures across all Orthocoronavirinae. This comprehensive analysis of the Coronaviridae domain architecture has important implication for efforts to develop broadly cross-protective coronavirus vaccines.


Antibiotic use in acute upper respiratory tract infections.
Upper respiratory tract infections account for millions of visits to family physicians each year in the United States. Although warranted in some cases, antibiotics are greatly overused. This article outlines the guidelines and indications for appropriate antibiotic use for common upper respiratory infections. Early antibiotic treatment may be indicated in patients with acute otitis media, group A beta-hemolytic streptococcal pharyngitis, epiglottitis, or bronchitis caused by pertussis. Persistent cases of rhinosinusitis may necessitate the use of antibiotics if symptoms persist beyond a period of observation. Antibiotics should not be considered in patients with the common cold or laryngitis. Judicious, evidence-based use of antibiotics will help contain costs and prevent adverse effects and drug resistance.


Histone Deacetylase 3 Is Required for T Cell Maturation.
Recent thymic emigrants are newly generated T cells that need to undergo postthymic maturation to gain functional competency and enter the long-lived naive T cell pool. The mechanism of T cell maturation remains incompletely understood. Previously, we demonstrated that the transcriptional repressor NKAP is required for T cell maturation. Because NKAP associates with histone deacetylase 3 (HDAC3), we examined whether HDAC3 is also required for T cell maturation. Although thymic populations are similar in CD4-cre HDAC3 conditional knockout mice compared with wild-type mice, the peripheral numbers of CD4(+) and CD8(+) T cells are dramatically decreased. In the periphery, the majority of HDAC3-deficient naive T cells are recent thymic emigrants, indicating a block in T cell maturation. CD55 upregulation during T cell maturation is substantially decreased in HDAC3-deficient T cells. Consistent with a block in functional maturation, HDAC3-deficient peripheral T cells have a defect in TNF licensing after TCR/CD28 stimulation. CD4-cre HDAC3 conditional knockout mice do not have a defect in intrathymic migration, thymic egress, T cell survival, or homeostasis. In the periphery, similar to immature NKAP-deficient peripheral T cells, HDAC3-deficient peripheral T cells were bound by IgM and complement proteins, leading to the elimination of these cells. In addition, HDAC3-deficient T cells display decreases in the sialic acid modifications on the cell surface that recruit natural IgM to initiate the classical complement pathway. Therefore, HDAC3 is required for T cell maturation.


Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.
Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.


Swedish nursing students' experience of stress during clinical practice in relation to clinical setting characteristics and the organisation of the clinical education.
To describe nursing students' experience of stress during clinical practice and evaluate the risk of stress in relation to the clinical setting characteristics and the organisation of the clinical education. Stress during clinical practice is well documented, but there is a lack of knowledge concerning whether the clinical setting characteristics and the organisation of the education make a difference. A cross-sectional study with evaluative design. Data were collected by means of a numerical rating scale for the assessment of stress and questions about the clinical setting characteristics and the organisation of the education. One hundred and eighty-four students who had completed their final year on the nursing programme at three universities in Sweden were included. Nearly half of the students (43%) experienced high level of stress during clinical practice. Measured by decision in the tree analysis, the absolute risk of stress was 57% in students with placements in hospital departments, as compared to 13% in students with placements in other clinical settings. The risk of stress increased to 71% if the students with placement in a hospital took the national clinical final examination. Performance of practice in a hospital department overcrowded with patients was also associated with increased risk of stress. The organisation of supervision and number of students at the clinical placement had an effect on the experience of stress, but did not prove to be risk factors in the analysis. The risk of stress in nursing students during their clinical practice differs depending on clinical setting characteristics. The taking of the national clinical final examination could be a source of stress, but this requires further investigation. It is important that supervisors are aware that students in hospital departments overcrowded with patients are at risk of stress and may have increased need of support.


Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature.
A few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). To analyse the efficacy of rituximab in a large CIDP cohort. A retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders. Nine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1-6) and lasted for a median period of 1 year (range, 1-5). Rituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.


Breastfeeding and childhood cancer.
The relationship between childhood cancer and having been breastfed in infancy was investigated in the UK Childhood Cancer Study (UKCCS), a national, population-based case-control study. Analyses included 3500 children with cancer (cases) of whom 1637 were diagnosed with leukaemia, 114 with Hodgkin's disease, 228 with non-Hodgkin's lymphoma and 1521 with other cancer and 6964 controls. 62% cases and 64% controls were reported to have ever been breastfed. There was weak evidence, of borderline statistical significance, that having been breastfed was associated with a small reduction in the odds ratios for leukaemia (odds ratio = 0.89, 95% Cl 0.80-1.00, P = 0.06), and for all cancers combined (odds ratio = 0.92, 95% Cl 0.84-1.00, P = 0.05). Combining data from the UKCCS with results from other published studies showed a small reduction in the odds ratios for leukaemia, Hodgkin's disease, non-haematological cancers, and all childhood cancers combined, associated with ever having been breastfed. It is unclear whether the apparent small reduction in the odds ratio for these various types of childhood cancer is a generalized effect of breastfeeding or whether it reflects some systematic bias in the majority of studies that have investigated the question.


Heparin use in hemodialysis patients following gastrointestinal bleeding.
Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB. We identified patients aged ≥ 67 who, from 2004-2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB. Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: -214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69-1.48; for recurrent GIB: 0.78; 0.39-1.57). The vast majority of these high-risk patients received heparin on the very first day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD.


A protein methylation pathway in Chlamydomonas flagella is active during flagellar resorption.
During intraflagellar transport (IFT), the regulation of motor proteins, the loading and unloading of cargo and the turnover of flagellar proteins all occur at the flagellar tip. To begin an analysis of the protein composition of the flagellar tip, we used difference gel electrophoresis to compare long versus short (i.e., regenerating) flagella. The concentration of tip proteins should be higher relative to that of tubulin (which is constant per unit length of the flagellum) in short compared with long flagella. One protein we have identified is the cobalamin-independent form of methionine synthase (MetE). Antibodies to MetE label flagella in a punctate pattern reminiscent of IFT particle staining, and immunoblot analysis reveals that the amount of MetE in flagella is low in full-length flagella, increased in regenerating flagella, and highest in resorbing flagella. Four methylated proteins have been identified in resorbing flagella, using antibodies specific for asymmetrically dimethylated arginine residues. These proteins are found almost exclusively in the axonemal fraction, and the methylated forms of these proteins are essentially absent in full-length and regenerating flagella. Because most cells resorb cilia/flagella before cell division, these data indicate a link between flagellar protein methylation and progression through the cell cycle.


Novel insights of dietary polyphenols and obesity.
The prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here, we evaluated the impact of commonly consumed polyphenols, including green tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on obesity and obesity-related inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the adenosine-monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, peroxisome proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor-κB that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area and are inconsistent about the antiobesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols.


Chronic pain in multi-traumatized outpatients with a refugee background resettled in Norway: a cross-sectional study.
Traumatized refugees often report significant levels of chronic pain in addition to posttraumatic stress disorder symptoms, and more information is needed to understand pain in refugees exposed to traumatic events. This study aimed to assess the frequency of chronic pain among refugee psychiatric outpatients, and to compare outpatients with and without chronic pain on trauma exposure, psychiatric morbidity, and psychiatric symptom severity. We conducted a cross-sectional study of sixty-one psychiatric outpatients with a refugee background using structured clinical diagnostic interviews to assess for traumatic events [Life Events Checklist (LEC)], PTSD (Posttraumatic Stress Disorder) and complex PTSD [Structured Clinical Interview for DSM-IV PTSD Module (SCID-PTSD) and Structured Interview for Disorders of Extreme Stress (SIDES)], chronic pain (SIDES Scale VI) and psychiatric symptoms [M.I.N.I. International Neuropsychiatric Interview (M.I.N.I.)]. Self-report measures were used to assess symptoms of posttraumatic stress [Impact of Event Scale-revised (IES-R)], depression and anxiety [Hopkins Symptom Checklist (HSCL-25)] and several markers of acculturation in Norway. Of the 61 outpatients included, all but one reported at least one chronic pain location, with a mean of 4.6 locations per patient. Chronic pain at clinical levels was present in 66% of the whole sample of outpatients, and in 88% of the outpatients with current PTSD diagnosis. The most prevalent chronic pain locations were head (80%), chest (74%), arms/legs (66%) and back (62%). Women had significantly more chronic pain locations than men. Comorbid PTSD and chronic pain were found in 57% of the outpatients. Significant differences were found between outpatients with and without chronic pain on posttraumatic stress, psychological distress, and DESNOS severity. Chronic pains are common in multi-traumatized refugees in outpatient clinics in Norway, and are positively related to symptomatology and severity of psychiatric morbidity. The presence of chronic pain, as well as comorbid chronic pain and PTSD, in psychiatric outpatients with a refugee background call for an integrated assessment and treatment for both conditions.


Evidence for the contribution of S cones to the detection of flicker brightness and red-green.
We were interested in the question of how cones contribute to the detection of brightness, red-green, and blue-yellow. The linear combination of cone signals contributing to flicker detection was determined by fitting a plane to 64 points (colors) of equal heterochromatic flicker brightness. A small S-cone contribution to flicker brightness of similar amplitude in all five subjects was identified. The ratio of L- to M-cone contribution was found to vary considerably among subjects (1.7-4.1). Chromatic detection thresholds were determined for small patches in the isoluminant plane defined by flicker brightness. These stimuli were presented at an eccentricity of 40 arc min. By using color naming at the detection threshold, one can attribute different segments of the resulting detection ellipses to different chromatic mechanisms. Linear approximation of these segments provided an estimate for the contribution of the different cone types to the detection of red-green and blue-yellow. The results are consistent with the hypothesis that S cones contribute to the red-green mechanism with the same sign as that of the contribution from L cones. The blue-yellow mechanism very probably subtracts S-cone contrast from luminance contrast. The detection ellipse can be mapped into a circle in cone difference space. The base of this canonical transformation is a set of three cone fundamentals that differs from previously published estimates. Projecting the circle onto the three cone difference axes produces sinusoidal changes within the respective excitations. We propose that simultaneous sinusoidal changes of equal increment in the three cone difference excitations generate stimuli differing by equal saliency.


Electric field-guided neuron migration: a novel approach in neurogenesis.
Effective directional neuron migration is crucial in development of the central nervous system and for neurogenesis. Endogenous electrical signals are present in many developing systems and crucial cellular behaviors such as neuronal cell division, cell migration, and cell differentiation are all under the influence of such endogenous electrical cues. Preclinical in vivo studies have used electric fields (EFs) to attempt to enhance regrowth of damaged spinal cord axons with some success. Recent evidence shows that small EFs not only guide axonal growth, but also direct the earlier events of neuronal migration and neuronal cell division. This raises the possibility that applied or endogenous EFs, perhaps in combination, may direct transplanted neural stem cells, or regenerating neurons, to the desired site after brain injury or neuron degeneration. The high complexity of both structure and function of the nervous system, however, poses significant challenges to techniques for applying EFs to promote neurogenesis. The evolution of functional biomaterials and nanotechnology may provide promising solutions for the application of EFs in guiding neuron migration and neurogenesis within the central nervous system.


Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume.
Juvenile pilocytic astrocytomas represent the largest group of pediatric brain tumors. The ideal management for these tumors is early, total surgical resection. To detect and track treatment response, a screening tool is needed to identify patients for surgical evaluation and assess the quality of treatment. The identification of aberrant miRNA profiles in the sera of juvenile pilocytic astrocytoma patients could provide such a screening tool. The authors reviewed the serum profiles of 84 oncologically relevant miRNAs in pediatric juvenile pilocytic astrocytoma patients via qPCR screening. miR-21, miR-15b, miR-23a, and miR-146b were significantly elevated in the sera of JPA patients as compared to non-oncologic controls, oncologic controls, and post-JPA resection samples (p < 0.001, 0.022, 0.034, 0.044). miR-21 had the highest AUC on ROC analysis (AUC > 0.99, sensitivity 75%, specificity 100%). All four miRNAs also correlated well with tumor mural nodule size, though they only poorly correlated with total tumor size, including cystic components (Spearman's R2: miR-21 91.7 vs 6.9%, miR-15b 86.3 vs 23.1%, miR-23a 85.8 vs 23.0%, miR-146b 59.8 vs 11.9%). In this small pilot study, pediatric juvenile pilocytic astrocytoma patients had significant elevations in serum miR-21, miR-15b, miR-23a, and miR-146b levels that do not appear to be driven by hydrocephalus or local distortion of the intracranial contents. These alterations correlate with solid tumor component volume and reverse with complete tumor resection, suggesting that this serum miRNA profile may delineate biomarkers for screening and tracking juvenile pilocytic astrocytoma patients. Additional studies, with a larger cohort, are needed to verify these results.


Addressing the challenge of informed decision making in prostate cancer community outreach to African American men.
African American men are disproportionately affected by prostate cancer. This project adopted a community-based participatory approach to design and pilot test an educational outreach strategy that promotes informed decision making about screening among African American men in community settings in St. Louis, Missouri. Interviews with local subject matter experts informed the design of the strategy. The revised curriculum was pilot tested in 2009 with 63 men who completed pre- and posttest surveys that measured knowledge, norms, beliefs, decision self-efficacy, and screening intention. The intervention resulted in statistically significant improvement in prostate cancer knowledge, decreased perceived risks and barriers, and increased screening decision self-efficacy. The educational outreach strategy offered in community settings was effective in improving knowledge, beliefs, and decision self-efficacy related to prostate cancer screening. This project sought to devise a screening outreach strategy that struck a balance between the imperatives of informed decision-making goals and the pragmatics of community settings. The findings suggest the need for further research to assess the effectiveness of community-based outreach efforts in enhancing engagement of men in decision making related to screening, diagnostics, and treatment.


Virio- and bacterioplankton microscale distributions at the sediment-water interface.
The marine sediment-water interface is an important location for microbially controlled nutrient and gas exchange processes. While microbial distributions on the sediment side of the interface are well established in many locations, the distributions of microbes on the water side of the interface are less well known. Here, we measured that distribution for marine virio- and bacterioplankton with a new two-dimensional technique. Our results revealed higher heterogeneity in sediment-water interface biomass distributions than previously reported with a greater than 45- and 2500-fold change cm(-1) found within bacterial and viral subpopulations compared to previous maxima of 1.5- and 1.4-fold cm(-1) in bacteria and viruses in the same environments. The 45-fold and 2500-fold changes were due to patches of elevated and patches of reduced viral and bacterial abundance. The bacterial and viral hotspots were found over single and multiple sample points and the two groups often coincided whilst the coldspots only occurred over single sample points and the bacterial and viral abundances showed no correlation. The total mean abundances of viruses strongly correlated with bacteria (r = 0.90, p<0.0001, n = 12) for all three microplates (n = 1350). Spatial autocorrelation analysis via Moran's I and Geary's C revealed non-random distributions in bacterial subpopulations and random distributions in viral subpopulations. The variable distributions of viral and bacterial abundance over centimetre-scale distances suggest that competition and the likelihood of viral infection are higher in the small volumes important for individual cell encounters than bulk measurements indicate. We conclude that large scale measurements are not an accurate measurement of the conditions under which microbial dynamics exist. The high variability we report indicates that few microbes experience the 'average' concentrations that are frequently measured.


Transfer coefficient models for escherichia coli O157:H7 on contacts between beef tissue and high-density polyethylene surfaces.
Risk studies have identified cross-contamination during beef fabrication as a knowledge gap, particularly as to how and at what levels Escherichia coli O157:H7 transfers among meat and cutting board (or equipment) surfaces. The objectives of this study were to determine and model transfer coefficients (TCs) between E. coli O157:H7 on beef tissue and high-density polyethylene (HDPE) cutting board surfaces. Four different transfer scenarios were evaluated: (i) HDPE board to agar, (ii) beef tissue to agar, (iii) HDPE board to beef tissue to agar, and (iv) beef tissue to HDPE board to agar. Also, the following factors were studied for each transfer scenario: two HDPE surface roughness levels (rough and smooth), two beef tissues (fat and fascia), and two conditions of the initial beef tissue inoculation with E. coli O157:H7 (wet and dry surfaces), for a total of 24 treatments. The TCs were calculated as a function of the plated inoculum and of the cells recovered from the first contact. When the treatments were compared, all of the variables evaluated interacted significantly in determining the TC. An overall TC-per-treatment model did not adequately represent the reduction of the cells on the original surface after each contact and the interaction of the factors studied. However, an exponential model was developed that explained the experimental data for all treatments and represented the recontamination of the surfaces with E. coli O157:H7. The parameters for the exponential model for cross-contamination with E. coli O157:H7 between beef tissue and HDPE surfaces were determined, allowing for the use of the resulting model in quantitative microbial risk assessment.


SUM1, an apparent positive regulator of the cryptic mating-type loci in Saccharomyces cerevisiae.
The mating-type information residing at the HML and HMR loci in Saccharomyces cerevisiae is kept unexpressed by the action of at least four MAR (or SIR) loci. To determine possible interactions between the MAR/SIR gene products and to find new regulatory loci, we sought extragenic suppressors of the mar1-1 mutation. A strain with the genotype HMLa MAT alpha HMRa mar1-1 is unable to mate because of the simultaneous expression of a and alpha information. A mutant of this strain was isolated that exhibits an alpha phenotype and, therefore, presumably fails to express the HML and HMR loci. We designate the new locus SUM1 (suppressor of mar). The mutation is recessive, centromere unlinked and does not correspond to the MAT, HML, HMR, SIR1, MAR1, MAR2 (SIR3) or SIR4 loci. The sum1 mutation affects expression of both a and alpha information at the HM loci. Suppression by sum1-1 is neither allele specific nor locus specific as it suppresses a deletion mutation of the MAR1 locus and mutations in SIR3 and SIR4. The sum1-1 mutation has no discernible phenotype in a Mar+ strain. We propose that the MAR/SIR gene products negatively regulate the SUM1 locus, the gene product of which is necessary for expression of the HM loci.


Computerised protocols for laboratory investigation and their effect on use of medical time and resources.
To devise a computerised management system protocol which not only proposes the laboratory investigations to be performed on each patient but also performs related clinical functions. The system was designed by senior members of staff. The protocols defined all laboratory investigations including haematology, biochemistry, immunology and cross-matching, and included static and dynamic rules. Patients can be changed to different or additional protocols, as required; likewise proposed tests can be deleted or added. The software is written in MUMPS and runs on a 386 PC running MSM MUMPS under MSDOS. The number of clinical chemistry tests requested per patient per day fell by 9.5% (p less than 0.01) for transplant recipients and by 28.8% (p less than 0.01) for non-transplant recipients. The average time spent by junior medical staff requesting laboratory investigations and enquiring about results fell from 10 minutes per patient per day to 4.1 minutes (p less than 0.001). The introduction of this system in no way abrogates clinicians' responsibility for the management of patients, because all proposed investigations must be confirmed or modified by the authorising doctor. The system allows for the audit of requesting patterns and subsequent improvement in protocols by recording any alterations made to the proposed investigations. Significant benefits in terms of better use of house officer time and medical resources were also achieved.


Treating to target in psoriatic arthritis: how to implement in clinical practice.
Treating to target is becoming the standard of care in many medical specialities, including rheumatology. The Tight Control of Psoriatic Arthritis (TICOPA) trial has recently provided evidence of the benefit of treating to target in psoriatic arthritis (PsA), and the revised European League Against Rheumatism (EULAR) recommendations on the management of PsA suggest this approach. However, the question of the optimal measure to use and the practicalities of incorporating this into routine clinical practice remain problematic.


High contrast ratio and compact-sized prism for DLP projection system.
In this paper, a novel light separator with contrast ratio enhancement but maintaining the optical efficiency of the DLP projection system is proposed. The main capability of the novel light separator is to direct the uncontrolled light away from the image system. The working theorem for the novel light separator is derived as well. Uncontrolled light is kept away from the image system by a total internal reflection surface, thereby effectively improving the image quality. Compared with the conventional contrast ratio enhancement method, the FO:FO contrast ratio can be improved from 839:1 to 48250:1, the ANSI contrast ratio can be improved from 180:1 to 306:1, while the image system efficiency remains at 76.2%.


The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetised rat.
Noxious intestinal distention elicits a reflex depressor response in the sodium pentobarbitone anaesthetised rat, which can be used as an index of visceral nociception. 5-HT(3) receptor antagonists inhibit this reflex. Repeated colorectal distention (CRD) induces Fos like immunoreactivity (Fos-LI) in the rat spinal cord. To examine the effect of the 5-HT(3) receptor antagonist alosetron on the depressor response to CRD, and on Fos expression in the lumbosacral spinal cord. Male rats were anaesthetised with sodium pentobarbitone, and mean arterial blood pressure monitored during repeated colorectal balloon inflation before and after treatment with alosetron or saline. Rats anaesthetised with urethane and treated with alosetron or saline underwent a repeated CRD paradigm, after which the lumbosacral spinal cord was removed and processed for visualisation of Fos-LI. CRD elicited reproducible, volume dependent falls in arterial blood pressure, and repeated distention-effect curves were constructed. Alosetron (1-100 microg/kg intravenously) inhibited the depressor response to CRD in a dose related manner, with an ID(50) value of 3.0 microg/kg. Following repeated CRD, numbers of Fos-LI neurones were significantly increased to 1246 (total in 12 sections at 120 microm intervals from L6 to S1) compared with 49 in sham distended animals. Pretreatment with alosetron (100 microg/kg) significantly reduced numbers of Fos-LI neurones to 479.8. The 5-HT(3) receptor antagonist alosetron inhibits the depressor response to CRD in a potent and dose dependent manner. It also inhibits CRD induced Fos-LI in the spinal cord. These results suggest that 5-HT(3) receptors are involved in visceral nociceptive transmission, perhaps located on primary afferent or spinal neurones.


Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development.
Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome-wide and targeted DNA copy number profiling and resequencing in early-onset and familial polyposis/CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC.


Evaluation of cotton leaf curl virus resistance in BC1, BC2, and BC3 progenies from an interspecific cross between Gossypium arboreum and Gossypium hirsutum.
Cotton leaf curl virus disease (CLCuD) is an important constraint to cotton production. The resistance of G. arboreum to this devastating disease is well documented. In the present investigation, we explored the possibility of transferring genes for resistance to CLCuD from G. arboreum (2n = 26) cv 15-Mollisoni into G. hirsutum (2n = 52) cv CRSM-38 through conventional breeding. We investigated the cytology of the BC1 to BC3 progenies of direct and reciprocal crosses of G. arboreum and G. hirsutum and evaluated their resistance to CLCuD. The F1 progenies were completely resistant to this disease, while a decrease in resistance was observed in all backcross generations. As backcrossing progressed, the disease incidence increased in BC1 (1.7-2.0%), BC2 (1.8-4.0%), and BC3 (4.2-7.0%). However, the disease incidence was much lower than that of the check variety CIM-496, with a CLCuD incidence of 96%. Additionally, the disease incidence percentage was lower in the direct cross 2(G. arboreum)×G. hirsutum than in that of G. hirsutum×G. arboreum. Phenotypic resemblance of BC1 ∼BC3 progenies to G. arboreum confirmed the success of cross between the two species. Cytological studies of CLCuD-resistant plants revealed that the frequency of univalents and multivalents was high in BC1, with sterile or partially fertile plants, but low in BC2 (in both combinations), with shy bearing plants. In BC3, most of the plants exhibited normal bearing ability due to the high frequency of chromosome associations (bivalents). The assessment of CLCuD through grafting showed that the BC1 to BC3 progenies were highly resistant to this disease. Thus, this study successfully demonstrates the possibility of introgressing CLCuD resistance genes from G. arboreum to G. hirsutum.


Early detection of COPD combined with individualized counselling for smoking cessation: a two-year prospective study.
Though the prevalence of COPD is related to the definition, even with this proviso COPD remains under-diagnosed. Screening can detect many new COPD cases, but its effects on smoking cessation remain unknown. To evaluate symptoms in "healthy" cigarette smokers, to screen new COPD cases using international and national guidelines, and to assess the success of a smoking cessation. Healthy asymptomatic smokers with a >20 pack-years smoking history were recruited. The first visit included a standardized personal interview, Fagerstom nicotine dependence test (FNDT) and individualized smoking counselling by Motivational Interviewing. At the follow-up visit two years later, the same analyses were repeated and smoking status assessed. To avoid bias in the counselling attributable to spirometry, the test was evaluated at the two-year follow-up assessment. Almost all, 93.2%, of 584 participants attended the second visit. Spirometry revealed COPD by GOLD criteria in 11.0% and by national guidelines in 15.3%, mid-expiratory flow (MEF50) had significantly declined in 19.5%, chronic cough or sputum production was detected in 62% of the subjects. After two years, 23.3% had succeeded in giving up smoking. There were four predictors of successful quitting, i.e. positive attitude to the intervention, pharmacotherapy, older age, and higher BMI, whereas other factors such as cough, obstruction, gender, pack-years, or nicotine dependence showed no association with ability to achieve successful cessation. Significant numbers of "healthy" smokers experience symptoms, according to detailed questionnaires, and have COPD. Motivation is the most significant factor in determining the chance of stopping smoking.


Optimizing footwear for older people at risk of falls.
Footwear influences balance and the subsequent risk of slips, trips, and falls by altering somatosensory feedback to the foot and ankle and modifying frictional conditions at the shoe/floor interface. Walking indoors barefoot or in socks and walking indoors or outdoors in high-heel shoes have been shown to increase the risk of falls in older people. Other footwear characteristics such as heel collar height, sole hardness, and tread and heel geometry also influence measures of balance and gait. Because many older people wear suboptimal shoes, maximizing safe shoe use may offer an effective fall prevention strategy. Based on findings of a systematic literature review, older people should wear shoes with low heels and firm slip-resistant soles both inside and outside the home. Future research should investigate the potential benefits of tread sole shoes for preventing slips and whether shoes with high collars or flared soles can enhance balance when challenging tasks are undertaken.


AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment.
We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.


How does the environment affect fighting? The interaction between extrinsic fighting ability and resource value during contests.
An individual's performance during a fight is influenced by a combination of their capacity and willingness to compete. While willingness to fight is known to be determined by both intrinsic and extrinsic drivers, an individual's capacity to fight is generally thought of as solely intrinsic, being driven by a host of physiological factors. However, evidence indicates that variation in fighting ability can also be generated through exposure to different environmental conditions. Environmental contributions to fighting ability may be particularly important for animals living in spatially and temporally heterogeneous habitats, in which fights can occur between rivals recently exposed to different environmental conditions. The rapidly changing environment experienced within intertidal zones, for example, means that seawater parameters, including dissolved oxygen content and temperature, can vary across small spatial and temporal scales. Here, we investigated the relative importance of these extrinsic contributions to fighting ability and resource value on contest dynamics in the beadlet sea anemone Actinia equina We manipulated the extrinsic fighting ability of both opponents (through dissolved oxygen concentration prior to fights) and resource value (through seawater flow rate during the fight). Our results indicate that the extrinsic fighting ability of both opponents can interact with resource value to drive escalation patterns and that extrinsic drivers can be more important in determining contest dynamics than the intrinsic traits commonly studied. Our study highlights the need to combine data on intrinsic state and extrinsic conditions in order to gain a more holistic view of the factors driving contest behaviour.


Modelling and predicting the simultaneous growth of Listeria monocytogenes and psychrotolerant lactic acid bacteria in processed seafood and mayonnaise-based seafood salads.
A new combined model for Listeria monocytogenes and psychrotolerant Lactobacillus spp. was constructed and evaluated for processed seafood and mayonnaise-based seafood salads. The new model was constructed by combining existing cardinal parameter models for L. monocytogenes and Lactobacillus spp. using the classical Jameson effect to model microbial interaction. Maximum population density (MPD) values of L. monocytogenes were accurately predicted in processed seafood with a known initial cell concentration of Lactobacillus spp. For these experiments, average MPD values of 4.5 and 4.3 log (cfu/g) were observed and predicted, respectively for L. monocytogenes. In seafood salads, growth of L. monocytogenes continued at a reduced growth rate after Lactobacillus sakei had reached their MPD. This growth pattern was successfully described by an expanded version of the classical Jameson effect model, but only for products with pH of 6.0 or higher. For seafood salads with pH below 6.0 the performance of the new model was unacceptable, primarily due to prediction of no-growth by L. monocytogenes when growth was actually observed. Within its range of applicability the new model can be valuable for risk assessment and risk management of processed seafood as well as for evaluating the compliance of products with the EU regulation for ready-to-eat foods.


Waste management in Small and Medium Enterprises (SMEs) - A barrier to developing circular cities.
The Commercial and Industrial (C&I) waste stream is complex due to the diversity of material generated and variation in businesses by activity and size. Businesses in England generate more waste than households but despite this the C&I waste stream has historically been overlooked in waste policy. Many Small and Medium Enterprises (SMEs) do not segregate dry recyclable materials and biowaste for separate collection leading to resources being wasted. Implementing smarter systems for managing waste from SMEs will be a key component of developing circular cities. In England the government has pledged to improve the management of waste from businesses - however it is uncertain what interventions, if any, it will make. This paper evaluates the mandatory requirement for businesses to separate out dry recyclable materials and biowaste in 42 global cities. The results highlight the patchwork of legislation towards C&I waste with 27 cities having no mandatory requirement for businesses to segregate material. Where the requirement was mandatory, the approach varied from being fully mandated to having exemptions based on the type and size of business, and levels of waste generated. From the legislation in these cities eight scenarios were modelled to assess what impact these interventions could have in England based on waste data collected from 62 SMEs. Mandatory separation of dry recyclable materials and biowaste for all SMEs based on the approach in San Francisco would have the biggest impact leading to 67.2% additional waste being separated - an average of 31.1 kg/week for the SMEs sampled.


Mercury from maternal "silver" tooth fillings in sheep and human breast milk. A source of neonatal exposure.
Neonatal uptake of mercury (Hg) from milk was examined in a pregnant sheep model, where radioactive mercury (Hg203)/silver tooth fillings (amalgam) were newly placed. A crossover experimental design was used in which lactating ewes nursed foster lambs. In a parallel study, the relationship between dental history and breast milk concentration of Hg was also examined in 33 lactating women. Results from the animal studies showed that, during pregnancy, a primary fetal site of amalgam Hg concentration is the liver, and, after delivery, the neonatal lamb kidney receives additional amalgam Hg from mother's milk. In lactating women with aged amalgam fillings, increased Hg excretion in breast milk and urine correlated with the number of fillings or Hg vapor concentration levels in mouth air. It was concluded that Hg originating from maternal amalgam tooth fillings transfers across the placenta to the fetus, across the mammary gland into milk ingested by the newborn, and ultimately into neonatal body tissues. Comparisons are made to the U. S. minimal risk level recently established for adult Hg exposure. These findings suggest that placement and removal of "silver" tooth fillings in pregnant and lactating humans will subject the fetus and neonate to unnecessary risk of Hg exposure.


Adeno-associated virus (AAV) vectors in the CNS.
Adeno-associated virus (AAV) vectors exhibit a number of properties that have made this vector system an excellent choice for both CNS gene therapy and basic neurobiological investigations. In vivo, the preponderance of AAV vector transduction occurs in neurons where it is possible to obtain long-term, stable gene expression with very little accompanying toxicity. Promoter selection, however, significantly influences the pattern and longevity of neuronal transduction distinct from the tropism inherent to AAV vectors. AAV vectors have successfully manipulated CNS function using a wide variety of approaches including expression of foreign genes, expression of endogenous genes, expression of antisense RNA and expression of RNAi. With the discovery and characterization of different AAV serotypes, the potential patterns of in vivo vector transduction have been expanded substantially, offering alternatives to the more studied AAV 2 serotype. Furthermore, the development of specific AAV chimeras offers the potential to further refine targeting strategies. These different AAV serotypes also provide a solution to the immune silencing that proves to be a realistic likelihood given broad exposure of the human population to the AAV 2 serotype. These advantageous CNS properties of AAV vectors have fostered a wide range of clinically relevant applications including Parkinson's disease, lysosomal storage diseases, Canavan's disease, epilepsy, Huntington's disease and ALS. Each individual application, however, presents a unique set of challenges that must be solved in order to attain clinically effective gene therapies.


Evaluation of Tp-Te Interval and Tp-Te/QT Ratio in Patients with Coronary Slow Flow Tp-Te/QT Ratio and Coronary Slow Flow.
Coronary slow flow (CSF) phenomenon is described by angiographically normal coronary arteries with delayed opacification of the distal vasculature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-Te) may correspond to the transmural dispersion of the repolarization and that increased Tp-Te interval and Tp-Te/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate the ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CSF. This study included 50 CSF patients (40 male, mean age 48.6±12.5 years) and 40 control individuals (23 male, mean age 47.8±12.5 years). Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared in groups. Baseline characteristics of the study groups were comparable. In electrocardiographic parameters analysis, QT and corrected QT were similar in CSF patients compared to the controls (357±35.2 vs 362±38.0 milliseconds and 419±25.8 vs 430±44.2 milliseconds, all p value >0.05). Tp-Te interval, Tp-Te/QT and Tp-Te/QTc ratio were significantly higher in CSF patients (85±13.7 vs 74±9.9 milliseconds and 0.24±0.03 vs 0.20±0.02 and 0.20±0.03 vs 0.17±0.02 all p value <0.001). Our study revealed that QTd, Tp-Te interval and Tp-Te/QT ratio are prolonged in patients with CSF.


The costs of future polio risk management policies.
Decisionmakers need information about the anticipated future costs of maintaining polio eradication as a function of the policy options under consideration. Given the large portfolio of options, we reviewed and synthesized the existing cost data relevant to current policies to provide context for future policies. We model the expected future costs of different strategies for continued vaccination, surveillance, and other costs that require significant potential resource commitments. We estimate the costs of different potential policy portfolios for low-, middle-, and high-income countries to demonstrate the variability in these costs. We estimate that a global transition from routine immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) would increase the costs of managing polio globally, although routine IPV use remains less costly than routine OPV use with supplemental immunization activities. The costs of surveillance and a stockpile, while small compared to routine vaccination costs, represent important expenditures to ensure adequate response to potential outbreaks. The uncertainty and sensitivity analyses highlight important uncertainty in the aggregated costs and demonstrates that the discount rate and uncertainty in price and administration cost of IPV drives the expected incremental cost of routine IPV vs. OPV immunization.


Analysis of Consumption of Energy Drinks by a Group of Adolescent Athletes.
Energy drinks (EDs) have become widely popular among young adults and, even more so, among adolescents. Increasingly, they are consumed by athletes, particularly those who have just begun their sporting career. Uncontrolled and high consumption of EDs, in addition to other sources of caffeine, may pose a threat to the health of young people. Hence, our objective was to analyze the consumption of EDs among teenagers engaged in sports, including quantity consumed, identification of factors influencing consumption, and risks associated with EDs and EDs mixed with alcohol (AmEDs). The study involved a specially designed questionnaire, which was completed by 707 students, 14.3 years of age on average, attending secondary sports schools. EDs were consumed by 69% of the young athletes, 17% of whom drank EDs quite often: every day or 1-3 times a week. Most respondents felt no effects after drinking EDs, but some reported symptoms, including insomnia, anxiety, tachycardia, nervousness and irritability. The major determinant of the choice of EDs was taste (47%), followed by price (21%). One in ten respondents admitted to consumption of AmEDs. Among the consequences reported were: abdominal pains, nausea, vomiting, amnesia, headache, and hangover. EDs consumption among adolescent athletes was relatively high. Considering the habit of AmEDs and literature data, it is worth emphasizing that it may lead to health problems in the near future, alcohol- or drug-dependence, as well as other types of risk behaviour.


Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with 211At-EGF.
The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ['Iressa' (trademark of the AstraZeneca group of companies), ZD1839] increases the cellular uptake of radiolabelled epidermal growth factor (EGF). We investigated gefitinib treatment combined with astatine-211 EGF targeting in vitro using two cell lines expressing high levels of EGFR: A431 (sensitive to gefitinib) and U343MGaCl2:1 (resistant to gefitinib). In both cell lines, the uptake of 211At-EGF was markedly increased by concomitant treatment with gefitinib. Survival was investigated using both a clonogenic survival assay and a cell growth assay. Combined gefitinib and 211At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with 211At-EGF alone. In A431 cells, 211At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. These results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours and decrease the effect of such therapy in gefitinib-sensitive tumours.


Combination of Goldman risk and initial cardiac troponin I for emergency department chest pain patient risk stratification.
Accurate identification of low-risk emergency department (ED) chest pain patients who may be safe for discharge has not been well defined. Goldman criteria have reliably risk-stratified patients but have not identified any subset safe for ED release. Cardiac troponin I (cTnI) values have also been shown to risk-stratify patients but have not identified a subset safe for ED release. To test the hypothesis that ED chest pain patients with a Goldman risk of < or =4% and a single negative cTnI (< or =0.3 ng/mL) at the time of ED presentation would be safe for discharge [<1% risk for death, acute myocardial infarction (AMI), revascularization]. A prospective cohort study was performed in which consecutive ED chest pain patients were enrolled from July 1999 to November 2000. Data collected included patient demographics, medical and cardiac history, electrocardiogram, and creatine kinase-MB and cTnI. Goldman risk stratification score was calculated while patients were still in the ED. Hospital course was followed daily. Telephone follow-up occurred at 30 days. The main outcome was death, AMI, or revascularization (percutaneous transluminal coronary angioplasty/stents/coronary artery bypass grafting) within 30 days. Of 2,322 patients evaluated, 998 had both a Goldman risk < or =4% and a cTnI < or =0.3 ng/mL. During the initial hospitalization, 37 patients met the composite endpoint (3.7%): 6 deaths (0.7%), 17 AMIs (1.7%), 18 revascularizations (1.8%). Between the time of hospital discharge and 30-day follow-up, 15 patients met the composite endpoint: 4 deaths (0.4%), 6 AMIs (0.6%), and 5 revascularizations (0.5%). Overall, 49 patients met the composite endpoint (4.9%; 95% CI = 3.6% to 6.2%): 10 deaths (1.0%; 95% CI = 0.4% to 1.6%); 23 AMIs (2.3%; 95% CI = 1.4% to 3.2%), and 23 revascularizations (2.3%; 95% CI = 1.4% to 3.2%) within 30 days of presentation. The combination of two risk stratification modalities for ED chest pain patients (Goldman risk < or =4% and cTnI < or =0.3 ng/mL) did not identify a subgroup of chest pain patients at <1% risk for death, AMI, or revascularization within 30 days.


Prospective evaluation of ambient operating room temperature on the core temperature of injured patients undergoing emergent surgery.
Although uncomfortable for the operating team, trauma operating room (OR) temperatures have traditionally been kept warm in an attempt to mitigate intraoperative heat loss. The purpose of this study was to examine how ambient OR temperatures impact core temperature in patients undergoing emergent surgery for trauma. Injured adult patients requiring emergent surgery at a Level 1 trauma center were prospectively enrolled between July 2008 and January 2010. Standardized warming measures were used for all patients. Ambient OR temperature was recorded in 5-minute intervals with the Fourier Microlog EC600 temperature data logger. Intraoperative core patient temperatures were compared with ambient OR temperature. Patients experiencing intraoperative core temperature decreases were compared with those who did not, to examine the impact of ambient temperature changes on the risk of perioperative hypothermia. During the 18-month study period, 118 patients requiring emergent surgery (73% laparotomy, 5% thoracotomy, 7% combined, 15% other) were enrolled. Incidence of hypothermia (<35°C) at admission to the OR was 29.7%. Crude mortality increased as the final patient core temperature achieved in the OR decreased (4.2% for temperatures >35°C and as high as 50% for temperatures ≤32°C). Overall, core temperature decreased in 46 patients (39.0%) but remained stable or increased by the end of the procedure in 72 (61%). There were no significant differences in the admission temperature, clinical demographics, or volume of fluids and blood products between the two groups. In a forward logistic regression analysis, a lower ambient OR temperature was not associated with a drop in the patient's core temperature. In this prospective study, the ambient OR temperature did not affect the core temperature of injured patients undergoing emergent surgery. Prognostic study, level III; therapeutic study, level IV.


Cephalosporin-NO-donor prodrug PYRRO-C3D shows β-lactam-mediated activity against Streptococcus pneumoniae biofilms.
Bacterial biofilms show high tolerance towards antibiotics and are a significant problem in clinical settings where they are a primary cause of chronic infections. Novel therapeutic strategies are needed to improve anti-biofilm efficacy and support reduction in antibiotic use. Treatment with exogenous nitric oxide (NO) has been shown to modulate bacterial signaling and metabolic processes that render biofilms more susceptible to antibiotics. We previously reported on cephalosporin-3'-diazeniumdiolates (C3Ds) as NO-donor prodrugs designed to selectively deliver NO to bacterial infection sites following reaction with β-lactamases. With structures based on cephalosporins, C3Ds could, in principal, also be triggered to release NO following β-lactam cleavage mediated by transpeptidases/penicillin-binding proteins (PBPs), the antibacterial target of cephalosporin antibiotics. Transpeptidase-reactive C3Ds could potentially show both NO-mediated anti-biofilm properties and intrinsic (β-lactam-mediated) antibacterial effects. This dual-activity concept was explored using Streptococcus pneumoniae, a species that lacks β-lactamases but relies on transpeptidases for cell-wall synthesis. Treatment with PYRRO-C3D (a representative C3D containing the diazeniumdiolate NO donor PYRRO-NO) was found to significantly reduce viability of planktonic and biofilm pneumococci, demonstrating that C3Ds can elicit direct, cephalosporin-like antibacterial activity in the absence of β-lactamases. While NO release from PYRRO-C3D in the presence of pneumococci was confirmed, the anti-pneumococcal action of the compound was shown to arise exclusively from the β-lactam component and not through NO-mediated effects. The compound showed similar potency to amoxicillin against S. pneumoniae biofilms and greater efficacy than azithromycin, highlighting the potential of C3Ds as new agents for treating pneumococcal infections.


Healthy range for serum ALT and the clinical significance of "unhealthy" normal ALT levels in the Korean population.
It remains unclear whether the currently-used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. The present study was conducted to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels. We reviewed the medical records, including questionnaires and the results of laboratory and radiological tests conducted at the Health Promotion Center at Korea University Anam Hospital between March 2005 and February 2007. The records, written in questionnaire form, included baseline data, such as physical status, social behaviors, medication history, and past and present disease histories. The mean age of the 7403 enrolled patients was 48 years, and 49.9% of these patients were male. A healthy cohort was selected after excluding patients who showed any abnormalities of the factors that were significantly associated with the serum ALT level upon multivariate regression analysis. The upper limit of the healthy range of the serum ALT level (i.e. 95th percentile) in the healthy population was 31 IU/L for males and 23 IU/L for females. The prevalence of metabolic syndrome and insulin resistance (IR) were significantly higher in patients with an 'unhealthy' normal ALT level than in those with a healthy ALT level. In our study, the upper limit of the healthy range of the serum ALT level was 31 IU/L for males and 23 IU/L for females. An unhealthy normal ALT level was associated with a higher prevalence of metabolic syndrome and IR.


Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments in the Valencia region, Spain. The baseline characteristics of the ESOSVAL cohort.
This study provides information on the prevalence of the most important risk factors for osteoporosis and osteoporotic fracture in a large sample of women and men from the Valencia region and also provides the FRAX 10-year major and hip fracture risks for this population, as well as data about the use of diagnostic tests and antiosteoporotic treatments. The purpose of this study was to describe demographic characteristics, osteoporosis risk factors, the 10-year risk of osteoporotic fracture, and the use of densitometry and antiosteoporotic treatments in the Valencia region, Spain. A cross-sectional study using the ESOSVAL cohort baseline data was conducted. We analyze the data from 5,310 women and 5,725 men aged 50 and over who attended to 272 collaborating primary care centers in 2009-2010. We collected the demographic, anthropometric, clinical, and pharmacy data from the electronic medical record. The mean age of participants was 64.3 years old for women and 65.6 years old for men. The most frequent fracture risk factors were sedentary life (22.2 %) and previous fracture (15.8 %) in women and low calcium intake (21.4 %) and current smoker (20.9 %) in men. According to FRAX(®), the 10-year risk of presenting a major fracture was 5.5 % for the women and 2.8 % for the men. The 10-year risk for hip fracture was 1.9 and 1.1 % for the women and the men, respectively; 23.8 % of the women and 5.2 % of the men had a densitometry test, 27.7 % of the women and 3.5 % of the men were taking calcium and/or vitamin D supplements, and 28.2 % of the women (22.0 % in the 50-64 age group) and 2.3 % of the men were taking antiosteoporotic drugs. The prevalence of certain fracture risk factors not included in the FRAX tool (sedentary life, falls, low calcium intake) is high. In young women, their low risks estimated by FRAX contrast with the high figures for densitometry testing and treatment.


The effects of SRS-A and histamine antagonists on antigen-induced contraction of guinea pig trachea.
Spirally cut tracheae from actively sensitized guinea pigs were challenged with antigen in the presence and absence of indomethacin. In the absence of indomethacin, the SRS-A antagonist FPL55712, added 30 min before challenge had no effect on antigen-induced contraction (ATC) when added in concentrations less than or equal to 1.7 X 10(-6) M. However with the highest concentration employed (5.2 X 10(-6) M) the duration of ATC was reduced by 45%. Furthermore the enhancement by indomethacin of the peak height of ATC was reduced even by lower (5.2 X 10(-7) M) concentrations of FPL55712. The inhibition of FPL55712 was time-dependent, suggesting that its action was not confined to competitive receptor antagonism. Hence, although our previous data indicate that a lipoxygenase product is involved in ATC, the current findings suggest that lipoxygenase products in addition to SRS-A contribute to the response. THe H1-antagonists mepyramine, chlorpheniramine and diphenhydramine inhibited ATC only in the first minute, and the peak height was reduced only by diphenhydramine. The H2-antagonist cimetidine had no effect on ATC. These data suggest that the contribution of histamine to ATC is small, confined to the first minute following antigen challenge and mediated via H1-receptors. Reduction of the peak height by diphenhydramine may be unrelated to its H1-antagonist properties.


The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade.
The effects of modafinil on glutamatergic and GABAergic transmission in the rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA and PH. Local perfusion with the GABAA agonist muscimol (10 microM), reduced, while the GABAA antagonist bicuculline (1 microM and 10 microM) increased glutamate levels. The modafinil (100 mg/kg)-induced increase of glutamate levels was antagonized by local perfusion with bicuculline (1 microM). When glutamate levels were increased by the local perfusion with the glutamate uptake inhibitor L-trans-PDC (0.5 mM), modafinil produced an additional enhancement of glutamate levels. Modafinil (1-33 microM) failed to affect [3H]glutamate uptake in hypothalamic synaptosomes and slices. These findings show that modafinil increases glutamate and decreases GABA levels in MPA and PH. The evidence that bicuculline counteracts the modafinil-induced increase of glutamate levels strengthens the evidence for an inhibitory GABA/glutamate interaction in the above regions controlling the sleep-wakefulness cycle.


Ultrasound and white blood cell counts in suspected acute appendicitis.
The use of radiological studies as diagnostic tools in patients with suspected acute appendicitis has increased recently. In this setting, abdominal ultrasonography is viewed as a possible means of avoiding unnecessary surgery. This retrospective study of patients who underwent laparotomy for suspected acute appendicitis was undertaken to determine the sensitivity and specificity of ultrasound in diagnosing acute appendicitis and the frequency of leucocytosis in patients in whom the diagnosis was confirmed by histology. The ultrasound and surgery registers were reviewed to identify 254 referrals for abdominal ultrasound between January 2001 and December 2002 because of a clinical suspicion of acute appendicitis. Of these cases, 223 did not proceed to surgery. The study sample comprised 31 patients who had appendectomies after abdominal ultrasonography. The ultrasound reports, pathological diagnoses and white blood cell counts of these patients were obtained and formed the basis for the analysis. A histological diagnosis was available for 30 cases, in 17 of whom appendicitis was confirmed In these patients, positive ultrasound and leucocytosis were present in five (29%) and nine (53%) respectively. Ultrasound showed 92% specificity and 29% sensitivity for the pre-operative diagnosis of appendicitis. The positive predictive value of ultrasonography (83%) was higher than that of leucocytosis (69%). The sensitivity and specificity of ultrasound and leucocytosis in this study indicate limited utility as preoperative diagnostic tools.


Clustered-minority-pixel error diffusion.
We present a clustered-minority-pixel error-diffusion halftoning algorithm for which the quantizer threshold is modified on the basis of the past output and a dot activation map. Dot area, dot shape, and dot distribution are more controllable than with other clustered-dot halftone algorithms such as Levien's algorithm. This method also effectively reduces structured mazelike artifacts in midtones that occur in Levien's algorithm. The dot distribution is further improved by using different error-diffusion weights for different input gray levels.


First Report of Dolabra nepheliae Associated with Corky Bark Disease of Rambutan and Pulasan in Honduras.
In the last decade, rambutan (Nephelium lappaceum L., Sapindaceae) and pulasan (N. mutabile Blume) have been cultivated in Honduras to produce exotic fruits for export to North America (2). Recently, a disease was observed that produces dark brown to black fissured cankers from 1 to 3 cm long and 1 to 4 cm wide. The infected bark tissue becomes swollen with the middle region 3 to 8 mm thick. Symptoms appear when the trees are approximately 3 years old. As the trees mature, the cankers increase in size and weaken the branches, often resulting in breakage with the weight of the fruit causing substantial plant damage and fruit loss. In August 2010, fissured branch samples of rambutan and pulasan were collected from 6- to 8-year-old trees from the Humid Tropical Demonstrative Agroforestry Center in Honduras, Atlantida, La Masica (15°33'47.4″N, 87°05'2.5″W, elevation 106 m). A fungus associated with the cankers was identified as Dolabra nepheliae. It produces black, stipitate, elongate ascomata, 312 to 482 × 250 to 281 μm with broadly cylindric, bitunicate asci, 120 to 138 × 11.2 to 15.0 μm, and filiform, hyaline ascospores, 128 to 135 × 2.8 to 3.2 μm. Fungi from rambutan and pulasan were isolated on cornmeal agar plus 0.5% dextrose and antibiotics. On potato dextrose agar, the ascospores produced slow-growing colonies, 5 mm per week. In culture, isolates from both hosts produced pycnidia with elongated, slightly to strongly curved or S-shaped, hyaline conidia, 22.8 to 46.4 × 2.8 to 3.7 μm. This fungus was first reported on rambutan and pulasan from Malaysia (1,4), and later reported on rambutan and litchi in Hawaii and Puerto Rico (3). To our knowledge, this is the first report of D. nepheliae on pulasan and rambutan from Honduras. Specimens have been deposited at the U.S. National Fungus Collections (BPI 882442 on N. lappaceum and BPI 882443 on N. mutabile). Cultures were deposited at the Centraalbureau voor Schimmelcultures (CBS) as CBS 131490 on N. lappaceum and CBS 131491 on N. mutabile. Sequences of the internal transcribed spacer (ITS) region including ITS1, 5.8S, and ITS2 intergenic spacers were deposited in GenBank (Accession No. JQ004281 on N. lappaceum and Accession No. JQ004280 on N. mutabile). A BLAST search and pairwise comparison using the GenBank web server were used to compare ITS sequence data and recovered the following results: (i) CBS 131490 on N. lappaceum is 99% (538 of 544) identical to D. nepheliae CBS 123297 on Litchi chinensis from Puerto Rico; and (ii) CBS 131491 on N. mutabile is 99% (527 of 533) identical to the same strain of D. nepheliae. On the basis of the ITS sequence data, the isolates from Honduras were confirmed as the same species, D. nepheliae from Puerto Rico. Efforts to develop resistant germplasm and management strategies to control this disease have been initiated. References: (1) C. Booth and W. P. Ting. Trans. Brit. Mycol. Soc. 47:235, 1964. (2) T. Ramírez et al. Manual Para el Cultivo de Rambutan en Honduras. Fundación Hondureña de Investigación Agrícola. La Lima, Cortes, Honduras, 2003. (3) A. Y. Rossman et al. Plant Dis. 91:1685, 2007. (4) H. Zalasky et al. Can. J. Bot. 49:559, 1971.


Neural network dysfunction in bipolar depression: clues from the efficacy of lamotrigine.
One strategy to understand bipolar disorder is to study the mechanism of action of mood-stabilizing drugs, such as valproic acid and lithium. This approach has implicated a number of intracellular signalling elements, such as GSK3beta (glycogen synthase kinase 3beta), ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) or protein kinase C. However, lamotrigine does not seem to modulate any of these targets, which is intriguing given that its profile in the clinic differs from that of valproic acid or lithium, with greater efficacy to prevent episodes of depression than mania. The primary target of lamotrigine is the voltage-gated sodium channel, but it is unclear why inhibition of these channels might confer antidepressant efficacy. In healthy volunteers, we found that lamotrigine had a facilitatory effect on the BOLD (blood-oxygen-level-dependent) response to TMS (transcranial magnetic stimulation) of the prefrontal cortex. This effect was in contrast with an inhibitory effect of lamotrigine when TMS was applied over the motor cortex. In a follow-up study, a similar prefrontal specific facilitatory effect was observed in a larger cohort of healthy subjects, whereas valproic acid inhibited motor and prefrontal cortical TMS-induced BOLD response. In vitro, we found that lamotrigine (3-10 microM) enhanced the power of gamma frequency network oscillations induced by kainic acid in the rat hippocampus, an effect that was not observed with valproic acid (100 microM). These data suggest that lamotrigine has a positive effect on corticolimbic network function that may differentiate it from other mood stabilizers. The results are also consistent with the notion of corticolimbic network dysfunction in bipolar disorder.


Sustained delivery of GDNF: towards a treatment for Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of nigral dopaminergic neurons. Although symptomatic therapies to substitute for the missing neurotransmitter dopamine are efficient at the early stages of the disease, the goal is to find alternative therapies which could protect dopaminergic neurons from the degenerative process. We have used two distinct gene therapy approaches to deliver the neuroprotective molecule glial cell line-derived neurotrophic factor (GDNF) in animal models of the disease: (i) an encapsulated genetically engineered cell line releasing GDNF (ex vivo gene therapy); and (ii) a lentiviral vector encoding the GDNF gene (in vivo gene therapy). Both approaches allowed protection of nigral dopaminergic neurons against lesion-induced cell death in rodent as well as monkey models of PD. Behavioral symptoms were also ameliorated in these animals. In addition, co-transplantation of embryonic dopaminergic neuronal grafts and a GDNF-releasing capsule allowed improvement of graft survival and differentiation, thereby accelerating behavioral recovery. These results should lead to clinical application in the near future.


Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening.
Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.


Physiological Recording in the MRI Environment (PRiME): MRI-Compatible Hemodynamic Recording System.
Hemodynamic recording during interventional cardiovascular procedures is essential for procedural guidance, monitoring patient status, and collection of diagnostic information. Recent advances have made interventions guided by magnetic resonance imaging (MRI) possible and attractive in certain clinical scenarios. However, in the MRI environment, electromagnetic interference (EMI) can cause severe distortions and artifacts in acquired hemodynamic waveforms. The primary aim of this paper was to develop and validate a system to minimize EMI on electrocardiogram (ECG) and invasive blood pressure (IBP) signals. A system was developed which incorporated commercial MRI compatible ECG leads and pressure transducers, custom electronics, user interface, and adaptive signal processing. Measurements were made on pediatric patients (N = 6) during MRI-guided catheterization. Real-time interactive scanning, which is known to produce significant EMI due to fast gradient switching and varying imaging plane orientations, was selected for testing. The effectiveness of the adaptive algorithms was determined by measuring the reduction of noise peaks, amplitude of noise peaks, and false QRS triggers. During real-time gradient-intensive imaging sequences, peak noise amplitude was reduced by 80% and false QRS triggers were reduced to a median of 0. There was no detectable interference on the IBP channels. A hemodynamic recording system front-end was successfully developed and deployed, which enabled high-fidelity recording of ECG and IBP during MRI scanning. The schematics and assembly instructions are publicly available to facilitate implementation at other institutions. Researchers and clinicians are provided a critical tool in investigating and implementing MRI guided interventional cardiovascular procedures.


The alpha-5 segment of Bacillus thuringiensis delta-endotoxin: in vitro activity, ion channel formation and molecular modelling.
A peptide with a sequence corresponding to the highly conserved alpha-5 segment of the Cry delta-endotoxin family (amino acids 193-215 of Bacillus thuringiensis CryIIIA [Gazit and Shai (1993) Biochemistry 32, 3429-3436]), was investigated with respect to its interaction with insect membranes, cytotoxicity in vitro towards Spodoptera frugiperda (Sf-9) cells, and its propensity to form ion channels in planar lipid membranes (PLMs). Selectively labelled analogues of alpha-5 at either the N-terminal amino acid or the epsilon-amine of its lysine, were used to monitor the interaction of the peptides with insect membranes. The fluorescent emission spectra of the 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)-labelled alpha-5 peptides displayed a blue shift upon binding to insect (Spodoptera littoralis) mid-gut membranes, reflecting the relocation of the fluorescent probes to an environment of increased apolarity, i.e. within the lipidic constituent of the membrane. Moreover, midgut membrane-bound NBD-labelled alpha-5 peptides were protected from enzymic proteolysis. Functional characterization of alpha-5 has revealed that it is cytotoxic to Sf-9 insect cells, and that it forms ion channels in PLMs with conductances ranging from 30 to 1000 pS. A proline-substituted analogue of alpha-5 is less cytolytic and slightly more exposed to enzymic digestion. Molecular modelling utilizing simulated annealing via molecular dynamics suggests that a transbilayer pore may be formed by alpha-5 monomers that assemble to form a left-handed coiled coil of approximately parallel helices. These findings further support a role for alpha-5 in the toxic mechanism of delta-endotoxins, and assign alpha-5 as one of the transmembrane helices which form the toxic pore. The suggested role is consistent with the recent finding that cleavage of CryIVB delta-endotoxin in a loop between alpha-5 and alpha-6 is highly important for its larvicidal activity [Angsuthanasombat, Crickmore and Ellar (1993) FEMS Microbiol. Lett. 111, 255-262].


Determinants of mammography in women with intellectual disabilities.
Women with intellectual disabilities have the same rate of breast cancer as other women but are less likely to undergo screening mammography. Characteristics associated with mammography for women with intellectual disabilities in the United States are unknown. This study was based on a secondary data analysis of the Massachusetts Department of Developmental Services database, comparing women who had a mammogram within 2 years with women who had not on variables related to the ecological model. Bivariate analyses, logistic regression, and assessment of interactions were performed. The study sample's (n = 2907) mean age was 54.7 years; 58% lived in 24-hour residential settings, 52% received nursing health coordination, and more than 25% had clinical examination needs (eg, sedation). Residential setting, health coordination, and recent influenza vaccination were all associated with mammography. Having a guardian, higher level of activities of daily living needs, and examination needs (requiring sedation or limited wait time for examinations) were associated with lower rates. Interactions between health coordination and examination needs confirmed the potential of the nurse to ameliorate barriers to mammography. Several system-level variables were significantly associated with mammography and, in some cases, seemed to ameliorate intrapersonal/behavioral barriers to mammography. Community agencies caring for intellectually disabled women have potential to impact mammography rates by using health coordination.


Caffeine as an analgesic adjuvant for acute pain in adults.
This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events. We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review. The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.