MRI findings of juvenile psoriatic arthritis.
The aim of this study was to describe the magnetic resonance imaging (MRI) features of juvenile psoriatic arthritis (JpsA) in children in order to facilitate early diagnosis and proper management. Two pediatric radiologists retrospectively reviewed in consensus a total of 37 abnormal MRI examinations from 31 pediatric patients (nine boys, 22 girls; age range 1-17 years; mean age 9.4 years) who had a definite diagnosis of JpsA and underwent MRI. Each MRI was evaluated for synovium abnormality (thickening and enhancement), joint effusion (small, moderate, and large), bone marrow abnormality (edema, enhancement, and location of abnormality), soft tissue abnormality (edema, enhancement, atrophy, and fatty infiltration), tendon abnormality (thickening, edema, tendon sheath fluid, and enhancement), and articular abnormality (joint space narrowing and erosion). The distribution of abnormal MRI findings among the six categories for the 37 MRI examinations was evaluated. The number of abnormal MRI findings for each MRI examination was assessed. Age at MRI examination and all six categories of abnormal MRI findings according to gender were evaluated. There were a total 96 abnormal MRI findings noted on 37 abnormal MRI examinations from 31 pediatric patients. The 37 abnormal MRI examinations included MRI of the hand (n = 8), knee (n = 8), ankle (n = 5), pelvis (n = 5), temporomandibular joint (n = 4), wrist (n = 3), foot (n = 2), elbow (n = 1), and shoulder (n = 1). Twenty-eight diffuse synovial thickening and/or enhancement were the most common MRI abnormality (29.2%). Joint effusion comprised 22 abnormal MRI findings (22.9%). There were 16 abnormal MRI bone marrow edema and/or enhancement findings (16.7%), and in seven (7.3%) the edema involved non-articular sites. Soft tissue abnormality manifested as edema and/or enhancement constituted 14 abnormal MRI findings (14.5%). There were ten MRI abnormalities (10.4%) involving tendons. Articular abnormality seen as joint space narrowing and/or bone erosion comprised six abnormal MRI findings (6.2%). Most MRI examinations had more than one abnormal finding (84%). Age at which MRI examinations were performed was not significantly different between boys and girls. All six categories of abnormal MRI findings were not significantly different between boys and girls. Children with JpsA typically present with more than one abnormal finding on their MRI studies. While synovial abnormality is the most common MR finding in children with JpsA, multi-focal bone marrow edema and enhancement at both articular and non-articular sites are also notable findings in children with JpsA. The rate of articular abnormality is much lower in children with JpsA in comparison to adults with psoriatic arthritis. Our findings suggest that MRI can play a useful role in the diagnosis and ongoing assessment of this uncommon, though important, pediatric rheumatologic disorder.


Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols.
Variability in the subfertile patient population excludes the possibility of a single approach to controlled ovarian stimulation (COS) covering all the requirements of a patient. Modern technology has led to the development of new drugs, treatment options and quantitative methods that can identify single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted based on genotype. Unfortunately, despite the predictive power of these measures, no single biomarker can stand alone as a guide to determine the best treatment option. In the future, hormonal, functional and genetic biomarkers will be used together to personalise COS.


Monitoring Disease Progression With a Quantitative Severity Scale for Retinopathy of Prematurity Using Deep Learning.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but clinical diagnosis is subjective and qualitative. To describe a quantitative ROP severity score derived using a deep learning algorithm designed to evaluate plus disease and to assess its utility for objectively monitoring ROP progression. This retrospective cohort study included images from 5255 clinical examinations of 871 premature infants who met the ROP screening criteria of the Imaging and Informatics in ROP (i-ROP) Consortium, which comprises 9 tertiary care centers in North America, from July 1, 2011, to December 31, 2016. Data analysis was performed from July 2017 to May 2018. A deep learning algorithm was used to assign a continuous ROP vascular severity score from 1 (most normal) to 9 (most severe) at each examination based on a single posterior photograph compared with a reference standard diagnosis (RSD) simplified into 4 categories: no ROP, mild ROP, type 2 ROP or pre-plus disease, or type 1 ROP. Disease course was assessed longitudinally across multiple examinations for all patients. Mean ROP vascular severity score progression over time compared with the RSD. A total of 5255 clinical examinations from 871 infants (mean [SD] gestational age, 27.0 [2.0] weeks; 493 [56.6%] male; mean [SD] birth weight, 949 [271] g) were analyzed. The median severity scores for each category were as follows: 1.1 (interquartile range [IQR], 1.0-1.5) (no ROP), 1.5 (IQR, 1.1-3.4) (mild ROP), 4.6 (IQR, 2.4-5.3) (type 2 and pre-plus), and 7.5 (IQR, 5.0-8.7) (treatment-requiring ROP) (P < .001). When the long-term differences in the median severity scores across time between the eyes progressing to treatment and those who did not eventually require treatment were compared, the median score was higher in the treatment group by 0.06 at 30 to 32 weeks, 0.75 at 32 to 34 weeks, 3.56 at 34 to 36 weeks, 3.71 at 36 to 38 weeks, and 3.24 at 38 to 40 weeks postmenstrual age (P < .001 for all comparisons). The findings suggest that the proposed ROP vascular severity score is associated with category of disease at a given point in time and clinical progression of ROP in premature infants. Automated image analysis may be used to quantify clinical disease progression and identify infants at high risk for eventually developing treatment-requiring ROP. This finding has implications for quality and delivery of ROP care and for future approaches to disease classification.


Indole alkaloids from the Marquesan plant Rauvolfia nukuhivensis and their effects on ion channels.
In addition to the already reported nukuhivensiums 1 and 2, 11 indole alkaloids were isolated from the bark of the plant Rauvolfia nukuhivensis, growing in the Marquesas archipelago. The known sandwicine (3), isosandwicine (4), spegatrine (8), lochneram (9), flavopereirine (13) have been found in this plant together with the norsandwicine (5), isonorsandwicine (6), Nb-methylisosandwicine (7), 10-methoxypanarine (10), nortueiaoine (11), tueiaoine (12). The structure elucidation was performed on the basis of a deep exploration of the NMR and HRESIMS data as well as comparison with literature data for similar compounds. Norsandwicine, 10-methoxypanarine, tueiaoine, and more importantly nukuhivensiums, were shown to significantly induce a reduction of IKr amplitude (HERG current). Molecular modelling through docking was performed in order to illustrate this result.


Nitrogen storage and remobilization by trees: ecophysiological relevance in a changing world.
The role of carbon (C) and nitrogen (N) storage by trees will be discussed in terms of uncoupling their growth from resource acquisition. There are profound differences between the physiology of C and N storage. C storage acts as a short-term, temporary buffer when photosynthesis cannot meet current sink demand and remobilization is sink driven. However, the majority of C allocated to non-structural carbohydrates such as starch is not reused so is in fact sequestered, not stored. In contrast, N storage is seasonally programmed, closely linked to tree phenology and operates at temporal scales of months to years, with remobilization being source driven. We examine the ecological significance of N storage and remobilization in terms of regulating plant N use efficiency, allowing trees to uncouple seasonal growth from N uptake by roots and allowing recovery from disturbances such as browsing damage. We also briefly consider the importance of N storage and remobilization in regulating how trees will likely respond to rising atmospheric carbon dioxide concentrations. Most studies of N storage and remobilization have been restricted to small trees growing in a controlled environment where (15)N can be used easily as a tracer for mineral N. We highlight the need to describe and quantify these processes for adult trees in situ where most root N uptake occurs via ectomycorrhizal partners, an approach that now appears feasible for deciduous trees through quantification of the flux of remobilized N in their xylem. This opens new possibilities for studying interactions between N and C allocation in trees and associated mycorrhizal partners, which are likely to be crucial in regulating the response of trees to many aspects of global environmental change.


Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.
Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.


Association of interferon-gamma responses to pre-erythrocytic stage vaccine candidate antigens of Plasmodium falciparum in young Kenyan children with improved hemoglobin levels: XV. Asembo Bay Cohort Project.
Previous studies in animal models have revealed an association between interferon-gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-gamma can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-gamma and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN-gamma positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN-gamma non-responders, suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN-gamma production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.


Should schools expect poor physical and mental health, social adjustment, and participation outcomes in students with disability?
The literature on whether students with disabilities have worse physical and mental health, social adjustment, and participation outcomes when compared to their peers without disabilities is largely inconclusive. While the majority of case control studies showed significantly worse outcomes for students with disabilities; the proportion of variance accounted for is rarely reported. The current study used a population cross-sectional approach to determine the classification ability of commonly used screening and outcome measures in determining the disability status. Furthermore, the study aimed to identify the variables, if any, that best predicted the presence of disability. Results of univariate discriminant function analyses suggest that across the board, the sensitivity of the outcome/screening tools to correctly identify students with a disability was 31.9% higher than the related Positive Predictive Value (PPV). The lower PPV and Positive Likelihood Ratio (LR+) scores suggest that the included measures had limited discriminant ability (17.6% to 40.3%) in accurately identifying students at-risk for further assessment. Results of multivariate analyses suggested that poor health and hyperactivity increased the odds of having a disability about two to three times, while poor close perceived friendship and academic competences predicted disability with roughly the same magnitude. Overall, the findings of the current study highlight the need for researchers and clinicians to familiarize themselves with the psychometric properties of measures, and be cautious in matching the function of the measures with their research and clinical needs.


Breast cancer research output, 1945-2008: a bibliometric and density-equalizing analysis.
Breast cancer is the most common form of cancer among women, with an estimated 194,280 new cases diagnosed in the United States in 2009 alone. The primary aim of this work was to provide an in-depth evaluation of research yield in breast cancer from 1945 to 2008, using large-scale data analysis, the employment of bibliometric indicators of production and quality, and density-equalizing mapping. Data were retrieved from the Web of Science (WOS) Science Citation Expanded database; this was searched using the Boolean operator, 'OR', with different terms related to breast cancer, including "breast cancer", "mammary ductal carcinoma" and "breast tumour". Data were then extracted from each file, transferred to Excel charts and visualised as diagrams. Mapping was performed as described by Groneberg-Kloft et al. in 2008. A total of 180,126 breast cancer-associated items were produced over the study period; these had been cited 4,136,224 times. The United States returned the greatest level of output (n = 77,101), followed by the UK (n = 18,357) and Germany (n = 12,529). International cooperation peaked in 2008, with 3,127 entries produced as a result; relationships between the United States and other countries formed the basis for the 10 most common forms of bilateral cooperation. Publications from nations with high levels of international cooperation were associated with greater average citation rates. A total of 4,096 journals published at least one item on breast cancer, although the top 50 most prolific titles together accounted for over 43% (77,517/180,126) of the total output. Breast cancer-associated research output continues to increase annually. In an era when bibliometric indicators are increasingly being employed in performance assessment, these findings should provide useful information for those tasked with improving that performance.


Faecal microbiota transplantation for Clostridioides difficile infection: Four years' experience of the Netherlands Donor Feces Bank.
The Netherlands Donor Feces Bank provides standardized ready-to-use donor faecal suspensions for faecal microbiota transplantation treatment of patients with recurrent Clostridioides difficile infection. The purpose of this study was evaluation of safety, feasibility and outcome of faecal microbiota transplantation facilitated by a national stool bank. The methods used included: observational cohort study of donors and recipients of faecal suspensions; assessment of donor screening and patient selection performed by an expert panel of medical microbiologists, gastroenterologists and infectious disease specialists; and patient outcome evaluated at different timepoints after faecal microbiota transplantation. Of 871 volunteers who registered as a potential faeces donor, 16 (2%) became active donors. Nine donors stopped or were excluded after a mean donation period of 5.7 months. In 2016-2019, 47 (27%) of 176 requests for faecal microbiota transplantations were deemed not indicated by the expert panel. In total, 129 patients with recurrent C. difficile infection were treated with 143 faecal suspensions in 40 different hospitals. The cure rate at two months after a single infusion was 89% (107/120). Of 84 patients, long-term follow-up (median 42 weeks) was available and sustained cure was achieved in 61 (73%). Early C. difficile infection relapses (within two months after faecal microbiota transplantation) and late recurrences (after more than two months) occurred more frequently in patients who received non-C. difficile antibiotics within three weeks after faecal microbiota transplantation and in moderately to severely immunocompromised patients. Of 21 patients with C. difficile infection after faecal microbiota transplantation, 14 were cured with anti-C. difficile antibiotics and seven with a second transplantation. No faecal microbiota transplantation-related serious adverse events were observed, but gastro-intestinal complaints (nausea, abdominal pain or diarrhoea) persisted in 32% of the treated patients at long-term follow-up. Faecal suspensions provided by a centralized stool bank, supported by a multidisciplinary expert team, resulted in effective, appropriate and safe application of faecal microbiota transplantation for recurrent C. difficile infection. Level II, prospective cohort study.


Does scale matter? The costs of HIV-prevention interventions for commercial sex workers in India.
To explore how the scale of a project affects both the total costs and average costs of HIV prevention in India. Economic cost data and measures of scale (coverage and service volume indicators for number of cases of sexually transmitted infections (STIs) referred, number of STIs treated, condoms distributed and contacts made with target groups) were collected from 17 interventions run by nongovernmental organizations aimed at commercial sex workers in southern India. Nonparametric methods and regression analyses were used to look at the relationship between total costs, unit costs and scale. Coverage varied from 250 to 2008 sex workers. Annual costs ranged from US$ 11 274 to US$ 52 793. The median cost per sex worker reached was US$ 19.21 (range = US$ 10.00-51.00). The scale variables explain more than 50% of the variation in unit costs for all of the unit cost measures except cost per contact. Total costs and unit costs have non-linear relationships to scale. Average costs vary with the scale of the project. Estimates of resource requirements based on a constant average cost could underestimate or overestimate total costs. The results highlight the importance of improving scale-specific cost information for planning.


Infection in massive bone allografts.
We studied a series of 945 patients who received cadaveric allografts implanted for nonpelvic bone or soft tissue tumor lesions since 1971. We specifically were interested in the role of infection in the graft process, and, more specifically its history, frequency, and affect on outcome. Primary infections (not related to reoperations for nonunions or fractures of the graft) occurred in 75 patients (7.9%), and an additional 46 patients had infections related to reoperations, increasing the total number of patients with infections to 121 (12.8%). The highest frequency of infection occurred in patients with soft tissue tumors, radiated sites, Musculoskeletal Tumor Society Stage IIB tumors, or surgeries consisting of an allograft arthrodesis. Most of the infected grafts failed; however, none of the patients died. One patient had hepatitis C develop, and one patient became HIV positive after receiving the virus from a blood transfusion. A comparison with other series of surgically treated patients, including those receiving metallic devices, suggests that the infection rate may be related to the surgery or the graft's immunologic resistance, rather than the graft. The problem of infection is a major issue for tumor surgeons. Suggestions regarding how to decrease the frequency of this complication are presented.


Clinical Outcomes and Development of Symptomatic Osteoarthritis 2 to 24 Years After Surgical Treatment of Tarsometatarsal Joint Complex Injuries.
Injuries to the tarsometatarsal (TMT) joint complex, or Lisfranc injuries, have been reported to result in osteoarthritis (OA) following surgical treatment. Good outcomes with respect to short and medium-term results have been reported. However, long-term results, specifically regarding clinical outcomes and the development of symptomatic OA, are limited. The objectives of this study were to assess clinical outcomes, the occurrence of symptomatic OA, and risk factors for OA at 2 to 24 years after a Lisfranc injury treated surgically with open reduction and internal fixation (ORIF) or with primary arthrodesis. This was a retrospective study involving 61 patients treated surgically at our institution between 1988 and 2009 for an injury to the TMT joint complex. Patients underwent either ORIF with transarticular screws or primary arthrodesis when joint comminution at the TMT level was such that ORIF was not possible. Functional outcomes were assessed according to the American Orthopaedic Foot & Ankle Society (AOFAS) score, the Foot Function Index (FFI), and a visual analog scale (VAS) for pain. Global health was evaluated with the Short Form (SF)-12 Health Survey physical component summary (PCS). Sixty-one of the 128 patients were available for clinical evaluation, including the use of questionnaires, and radiographic assessment at a mean of 10.9 years postoperatively (range, 2.4 to 23.9 years). Mean scores were as follows: AOFAS score, 79.0; FFI, 16.9, and VAS for pain, 2.5. Radiographic evidence of OA was noted in 44 (72.1%) of the patients, and symptomatic OA, in 54.1%, the latter having worse outcomes. Risk factors for OA were nonanatomic reduction, fracture classification of Myerson type C, and a history of smoking. Two to 24 years following surgical treatment to restore and maintain joint anatomy for Lisfranc injuries, we found satisfactory clinical outcome scores and a large number of patients who had returned to their previous level of functioning and employment, with little need for secondary procedures. However, there was a substantial occurrence of posttraumatic OA, as evident on radiographs, albeit the occurrence of symptomatic OA was lower. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Disclosure strategies in adults with epilepsy when telling, "I have epilepsy": The How2tell study.
To generate evidence-based knowledge about the strategies that adult people with epilepsy (PWEs) use in the process of telling others about their epilepsy. In-depth, one-to-one interviews explored PWEs' first-hand experiences of self-disclosure (or not), and grounded theory methods of inductive-deductive analysis were used to identify strategies used in disclosing. Interviews were audio-recorded, transcribed, coded, and independently recoded by two researchers using a coding framework specifically developed in this study. To account for maximum variation, PWEs (aged 18+ years) with different life experiences and situations relating to (1) gender, (2) age, (3) employment status, (4) personal relationships, (5) family relationship, (6) support group involvement, and (7) seizure frequency were included. Given the many variables and psychosocial issues associated with epilepsy, demographic details and validated measures including Quality of Life in Epilepsy-10-P, Coping Inventory of Stressful Situations-Adult, and Patient Health Questionnaire-9 were used to describe the characteristics of participants and to contextualize the results. Forty-nine adults with epilepsy participated. Data analysis revealed six interrelated categories (with subcategories) of the strategies that PWEs reported using in the process of disclosure: (1) concerns about disclosing; (2) weighing up who and when to tell; (3) opportunities for telling; (4) moment of disclosure-how to construct the message; (5) tailoring the message to audience needs-altering the message when telling family members, partner, friends, children, or employer and workplace colleagues; and (6) managing reactions by making it ordinary. People with epilepsy use a range of different strategies during the process of disclosing their epilepsy. These strategies were used to inform the development of the How2tell multimedia self-management resource for PWEs on self-disclosure in everyday social and life situations. How2tell is designed to benefit PWEs by empowering them with practical information about the process of telling another person, "I have epilepsy."


Test of CP invariance in vector-boson fusion production of the Higgs boson using the Optimal Observable method in the ditau decay channel with the ATLAS detector.
A test of CP invariance in Higgs boson production via vector-boson fusion using the method of the Optimal Observable is presented. The analysis exploits the decay mode of the Higgs boson into a pair of [Formula: see text] leptons and is based on 20.3 [Formula: see text] of proton-proton collision data at [Formula: see text] = 8 [Formula: see text] collected by the ATLAS experiment at the LHC. Contributions from CP-violating interactions between the Higgs boson and electroweak gauge bosons are described in an effective field theory framework, in which the strength of CP violation is governed by a single parameter [Formula: see text]. The mean values and distributions of CP-odd observables agree with the expectation in the Standard Model and show no sign of CP violation. The CP-mixing parameter [Formula: see text] is constrained to the interval [Formula: see text] at 68% confidence level, consistent with the Standard Model expectation of [Formula: see text].


Sustained effects of incredible years as a preventive intervention in preschool children with conduct problems.
The present study evaluated preventive effects of the Incredible Years program for parents of preschool children who were at risk for a chronic pattern of conduct problems, in the Netherlands. In a matched control design, 72 parents of children with conduct problems received the Incredible Years program. These families (intervention group) were compared with 72 families who received care as usual (control group). Two years after termination of the intervention, it appeared that observed and selfrated parenting skills were significantly improved in the intervention group. Likewise, in this group, observed child conduct problems showed sustained intervention effects. The decrease in observed critical parenting mediated the decrease in observed child conduct problems over time. In addition, it appeared that parental influence increased over time.


Oocyte meiotic spindle morphology is a predictive marker of blastocyst ploidy-a prospective cohort study.
To evaluate oocyte meiotic spindle (OMS) morphology at intracytoplasmic sperm injection (ICSI) as a predictor of blastocyst ploidy and whether OMS morphology could aid standard morphology-based blastocyst selection. Prospective cohort study. In vitro fertilization clinic. Patients undergoing ICSI cycles with an intention to perform preimplantation genetic testing for aneuploidy (PGT-A) from October 2014 to December 2017. The OMS was visualized with the use of polarized light microscopy at the time of ICSI and the morphology classified as normal, dysmorphic, translucent, not visible, or in telophase. Blastocyst biopsy for PGT-A was performed on embryos with suitable development. The association of OMS morphology with the resulting blastocyst ploidy was evaluated on an "intention-to-treat" (ITT) and an "as-treated analysis" (ATA) basis. The morphology of 2,056 OMSs were classified. A strong association of OMS morphology with fertilization, cleavage to at least 6 cells on day 3, and good/top-quality blastocyst formation was present. Normal OMS was positively associated with blastocyst euploidy compared with all other OMS types combined, per either ITT or ATA. Even after controlling for female age, blastocyst quality, and developmental stage, the presence of a normal OMS was strongly associated with the probability of blastocyst euploidy. OMS morphology is a predictive marker of blastocyst ploidy and can potentially aid standard morphology-based blastocyst selection.


Blue urticaria: a previously unreported adverse event associated with isosulfan blue.
The sentinel node hypothesis is predicated on the fact that a metastasis, if it exists, will have traveled on a direct path from the primary tumor through the efferent lymphatic channels to the first draining lymph node in the regional lymphatic basin, the sentinel node. Lymphatic mapping with isosulfan blue and sentinel lymphadenectomy is being increasingly used in the management of patients with melanoma, breast cancer, and other solid tumors. This trend is exposing an increasing number of patients to isosulfan blue. Although this compound is generally safe, severe reactions have been reported. We describe 2 patients who developed "blue hives" after isosulfan blue injection.


Resveratrol ameliorates motor neuron degeneration and improves survival in SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
Resveratrol has recently been used as a supplemental treatment for several neurological and nonneurological diseases. It is not known whether resveratrol has neuroprotective effect on amyotrophic lateral sclerosis (ALS). To assess the effect of resveratrol on the disease, we tested this agent on an ALS model of SOD1(G93A) transgenic mouse. Rotarod measurement was performed to measure the motor function of the ALS mice. Nissl staining and SMI-32 immunofluorescent staining were used to determine motor neurons survival in the spinal cord of the ALS mice. Hematoxylin-eosin (H&E), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) staining were applied to pathologically analyze the skeletal muscles of the ALS mice. We found that resveratrol treatment significantly delayed the disease onset and prolonged the lifespan of the ALS mice. Furthermore, resveratrol treatment attenuated motor neuron loss, relieved muscle atrophy, and improved mitochondrial function of muscle fibers in the ALS mice. In addition, we demonstrated that resveratrol exerted these neuroprotective effects mainly through increasing the expression of Sirt1, consequently suppressing oxidative stress and downregulating p53 and its related apoptotic pathway. Collectively, our findings suggest that resveratrol might provide a promising therapeutic intervention for ALS.


Age-related differences in judgments of inappropriate behavior are related to humor style preferences.
Identifying social gaffes is important for maintaining relationships. Older adults are less able than young to discriminate between socially appropriate and inappropriate behavior in video clips. One open question is how these social appropriateness ratings relate to potential age differences in the perception of what is actually funny or not. In the present study, young, middle-aged, and older adults were equally able to discriminate between appropriate and inappropriate social behavior in a diverse set of clips relevant across age groups. However, young and middle-aged adults rated the gaffe clips as funnier than control clips and young adults smiled more during the inappropriate clips than the control clips. Older adults did not show this pattern, suggesting that they did not find the inappropriate clips funny. Additionally, young adults endorsed a more aggressive humor style than middle-aged and older adults and aggressive humor style endorsement mediated age differences in social appropriateness ratings. Results are discussed in terms of possible mechanisms such as cohort differences in humor and developmental prioritization of certain humor styles, as well as the importance of investigating age differences in both abilities and preferences.


Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006.
The purpose of this study was to examine the prevalence of individual risk factors for metabolic syndrome as well as the prevalence of metabolic syndrome in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. The analytic sample consisted of 3,423 adults, 20 years of age and over, from NHANES 2003-2006. The National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) guidelines were used to identify adults who met their criteria for metabolic syndrome. Prevalence estimates were calculated for each risk factor for metabolic syndrome in addition to the prevalence of metabolic syndrome. Prevalence estimates and odds ratios were analyzed by sex and by age group, race and ethnicity, and body mass index (BMI) stratified by sex. Approximately 34% of adults met the criteria for metabolic syndrome. Males and females 40-59 years of age were about three times as likely as those 20-39 years of age to meet the criteria for metabolic syndrome. Males 60 years of age and over were more than four times as likely and females 60 years of age and over were more than six times as likely as the youngest age group to meet the criteria. Non-Hispanic black males were about one-half as likely as non-Hispanic white males to meet the criteria for metabolic syndrome, while non-Hispanic black and Mexican-American females were about 1.5 times as likely as non-Hispanic white females to meet the criteria. Overweight males were about six times as likely and obese males were about 32 times as likely as normal weight males to meet the criteria. Overweight females were more than five times as likely and obese females were more than 17 times as likely as normal weight females to meet the criteria. These results demonstrate that metabolic syndrome is prevalent and that it increases with age and with BMI. The prevalence varied by race and ethnicity but the pattern was different for males and females.


Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer.
2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of oleanolic acid, and its C28 methyl ester derivative (CDDO-Me), have shown potent antitumorigenic activity against a wide range of cancer cell lines, including prostate cancer cells in vitro, and inhibited the development of liver and lung cancer in vivo. In the present study, we examined the efficacy of CDDO-Me in preventing the development and progression of prostate cancer in the transgenic adenocarinoma of the mouse prostate (TRAMP) model. CDDO-Me inhibited the growth of murine TRAMPC-1 prostate cancer cells by inducing apoptosis through the inhibition of antiapoptotic p-Akt, p-mTOR and NF-κB. Early intervention with CDDO-Me (7.5 mg/kg) initiated at five weeks of age for 20 wk inhibited the progression of the preneoplastic lesions (low-grade PIN and high-grade-PIN) to adenocarcinoma in the dorsolateral prostate (DLP) and ventral prostate (VP) lobes of TRAMP mice. Even delayed administration of CDDO-Me started at 12 wk of age for 12 wk inhibited the development of adenocarcimona of the prostate. Both early and late treatment with CDDO-Me inhibited the metastasis of tumor to the distant organs. Treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and NF-κB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells sensitized them to CDDO-Me. These findings indicated that Akt is a target for apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for inhibition of prostate cancer in vivo.


Secretive females or swaggering males? An assessment of the quality of sexual partnership reporting in rural Tanzania.
In population-based surveys on sexual behaviour, men consistently report higher numbers of sexual partners than women, which may be associated with male exaggeration or female under-reporting or with issues related to sampling, such as exclusion of female sex workers. This paper presents an analysis of data collected in the context of a longitudinal study in rural Tanzania, where a sexual partnership module was applied to all participating men and women in the study population. Since the study design included all men and women of reproductive ages and did not involve sampling, these data provide a unique opportunity to compare the consistency of aggregate measures of sexual behaviour between men and women living in the same villages. The analysis shows that non-marital partnerships were common amongst single people of both sexes--around 70% of unmarried men and women report at least one sexual partner in the last year. However, 40% of married men also report having non-marital partners, but only 3% of married women did so. Single women reported about half as many multiple partnerships in the last year as men. Under-reporting of non-marital partnerships was much more common among single women than among married women and men. Furthermore, women were more likely to report longer duration partnerships and partnership with urban men or more educated men than with others. If a woman reports multiple partners, biological data indicate that she is at high risk of contracting HIV. For men, however, there is only a weak association between number of partnerships and the risk of HIV, and it cannot be excluded that men, especially single men, exaggerate the number of sexual partners.


Quantifying early diabetic retinopathy.
A precise and accurate method of numerically quantifying diabetic retinopathy, on standardised retinal colour photographs, has been developed which allows small changes and trends to be monitored. Colour slides are projected onto a screen and features noted on an acetate sheet which provides a permanent record. Sector analysis showed microaneurysms and haemorrhages to occur most often at the temporal-to-macula area, exudates at the macula and cotton wool spots on the nasal side of the retina. Seventy percent of microaneurysms appeared in the previous year, irrespective of the severity of the retinopathy. In proportion to their usual relative prevalences, after normalisation of distribution, the various features can be combined to provide a single value, the Retinopathy Index. This provides an overall assessment of retinopathy which is suitable for comparing the progress of mild retinopathy in prospective studies.


Methodology for characterizing proficiency in interpreting sputum smear microscopy results in the diagnosis of tuberculosis.
To propose a methodology for characterizing proficiency in sputum smear microscopy for acid-fast bacilli (AFB) in the diagnosis of tuberculosis and to determine the number of microscopies necessary to establish this proficiency, as well as the quality of the transcription of results, the causes of the discrepancies in the readings (rater or microscope used), and the criterion for classification of microscopy results that poses the most difficulty in characterizing proficiency. Four hundred sputum smear microscopies for the diagnosis of tuberculosis were analyzed through double-blind readings by six professionals who usually read/supervise microscopies performed in public health care facilities. The sample was stratified to obtain, at least, a reliability of 90% in the double-blind readings, an alpha error of 5%, and a precision of 3%. The results were analyzed using observed reliability and the kappa index. Thirteen errors (0.27%) were found in the transcription of results. Reliability increased when the three distinct categories of positive results (AFB+, AFB++, and AFB+++) were grouped or when inconclusive results were excluded from the analysis. The quantification of the bacterial load was the classification criterion that posed the most difficulty in establishing proficiency. Using higher quality microscopes increased reliability. Reliability values stabilized only from the reading of 75 microscopies onward. Double-blind sputum smear microscopy readings using a panel containing 75 slides (36 negative, 4 inconclusive, and 35 positive) proved to be appropriate for characterizing proficiency in sputum smear microscopy for the diagnosis of tuberculosis when such proficiency is intended to reproduce laboratory routine.


Effects of School-Based Physical Activity Interventions on Cognition and Academic Achievement: A Systematic Review.
Schools are an ideal setting to implement physical activity programs targeted at youths' learning and intellectual abilities, as exercise has been associated with improvement in cognitive skills and academic proficiency. A systematic review of the literature was performed to examine the effects of school-based physical activity interventions on academic achievement and cognitive outcomes. A search for relevant papers was carried out on PubMed/Medline, Scopus and Google Scholar. Only quasi-experimental and experimental studies were included, if focused on school-based physical activity interventions targeting 3 to 18 year-old healthy pupils, and designed to establish a relationship between exercise performed in a school setting and cognitive/academic performance. Thirty-one papers were retrieved by the search, reporting the findings of twenty-eight school-based physical activity interventions. Most of the included studies were published in the past five years. A large majority of the studies showed positive results in terms of academic achievement and, above all, cognitive skills. In the recent years, the number of studies on school-based physical interventions aimed to establish a relationship between physical activity performed in school setting and cognitive/academic outcomes significantly increased, as well as high quality assessments and designs. This review highlights the effectiveness of school-based physical activity interventions on academic achievement and, above all, on youths' cognitive performance. Some interesting findings come from studies assessing brain functional changes, from interventions targeting culturally diverse or low-income samples, and from interventions where physical activity is in the form of active videogames.


[Migraine and stroke].
Both migraine and stroke are common illness. However, each disorder usually occurs in different generation, migraine in younger, while stroke in elder, and seems to have little in common. Migraine has been supposed to be benign, not life-threatening illness occurring throughout the life-time. Whereas, stroke is an acute illness with certain degree of disabilities consequently, even fatal in case. In spite of such differences, some of recent studies suggested migraine as a risk factor of stroke or subclinical brain damage. There seems to be several types of stroke associated with migraine. One is "migrainous infarction", which is defined as one or more migrainous aura symptoms associated with an ischemic brain lesion in appropriate territory demonstrated neuroimaging, in the International Classification of Headache Disorders (ICHD-II). The other is stroke occurring in those who had been suffering from migraine in their younger time. The former is seldom to observe, and the latter is in dispute. Recent elaborate epidemiological studies disclosed the risk of stroke is increase in people with migraine, particularly marked in those with migraine with aura, further increased in those taking oral contraceptives. However, several issues such as strict diagnostic criteria for stroke and migraine, history of medication for migraine treatment, etc. for those studies should be settled. The well organized prospective studies for the issue "migraine as a risk factor of stroke" should be considered necessary.


Highly efficient multi-channel drop filter in a two-dimensional hetero photonic crystal.
An in-plane, multi-channel drop filter with high efficiency, in a two-dimensional photonic crystal (PC) slab, is experimentally demonstrated. Based on the concept of heterostructure photonic crystals proposed previously, the device consists of multiple simply connected, PC-based filter units, in which each unit has a structure proportional to an optimized basic unit and operates at a different wavelength. Four-channel drop operation was successfully obtained, with high efficiencies of almost 100%, and equal quality factors, across all channels.


Sexual health care in persons with intellectual disabilities.
In the past, preventive health concerning sexuality of people with intellectual disabilities was addressed through surgical sterilization as part of nationwide eugenic programs in many countries. For more than 30 years now, it has come progressively to light in the scientific literature that, besides major ethical and legal problems, these programs also failed to assess many of the individual's needs in sexual health. The fact that an increasing number of people with intellectual disabilities live in the community rather than in institutions has heightened public awareness that these individuals have sexual expectancies, desires, and needs that must be supported through both education and health services. The emergence of AIDS, including descriptions of cases among people with intellectual disabilities, has further demonstrated that surgical sterilization cannot be considered a global option to achieve preventive sexual health. The aim of this paper is to review scientific studies that have assessed the expectancies and support needs of persons with intellectual disabilities in terms of sexual health. These needs vary widely from one individual to another, according to life milieu, level of disability, and potential comorbidity. From this review, it appears that hygiene management, global gynecological care, and prevention of unplanned pregnancy, sexually transmitted diseases, and abuse have been frequently identified as areas in which the presence of intellectual disability dictates specific support needs. Different approaches that have been evaluated to address these issues will also be discussed.


Epidemiology and burden of chronic constipation.
Chronic constipation is an important component of clinical gastroenterology practice worldwide. Based on the definition, either self-reported or using Rome criteria, chronic constipation can affect from 2% to 27% of the population. Constipation is physically and mentally troublesome for many patients, and can significantly interfere with their daily living and well-being. Although only a proportion of patients with constipation seek medical care, most of them use prescribed or over-the-counter medication to improve their condition. The health care costs of constipation are significant as evidenced by the hundreds of million dollars spent yearly on laxatives alone. Because constipation is more common in older patients and life expectancy is increasing, an increase in the prevalence of constipation is expected in the years to come, with the associated impact on quality of life and socioeconomic burden.


Compartment syndrome associated with distal radial fracture and ipsilateral elbow injury.
Forearm compartment syndrome is an uncommon sequela of distal radial fractures. This investigation tested the hypothesis that the risk of forearm compartment syndrome associated with an unstable, operatively treated fracture of the distal end of the radius is higher with a concomitant injury of the ipsilateral elbow. All patients who sustained an unstable fracture of the distal end of the radius and/or injury to the elbow (a fracture of the proximal end of the radius and/or ulna, simple elbow dislocation, elbow fracture-dislocation, or distal humeral fracture) and were operatively treated at two level-I trauma centers over a five-year period were identified from a comprehensive database. The prevalence of compartment syndrome in a cohort with an isolated distal radial fracture and a cohort with a simultaneous distal radial fracture and elbow injury were compared. Nine (15%) of fifty-nine patients who sustained a simultaneous ipsilateral distal radial fracture and elbow injury had forearm compartment syndrome develop compared with three (0.3%) of 869 patients with an isolated unstable distal radial fracture (p < 0.001, relative risk = 50). The average time from presentation to the development of compartment syndrome and subsequent fasciotomy was twenty-seven hours. Three of the nine patients with injuries to both the elbow and the wrist had a compartment syndrome develop after initial operative treatment of the injuries, requiring a return to the operating room for fasciotomy. Forearm compartment syndrome is a frequent complication of simultaneous unstable injuries to the elbow and the distal end of the radius. Heightened vigilance for compartment syndrome is paramount in patients with this combination of injuries.


Downy Mildew Caused by Peronospora radii on Marguerite Daisy (Argyranthemum frutescens) in California.
In California, marguerite daisy (Argyranthemum frutescens [= Chyrsanthemum frutescens]) is an important, commercially grown, perennial flowering plant that is used as a potted plant, cutflower, and landscape plant. For two seasons (2003 and 2004), a downy mildew disease has been affecting marguerite daisy at wholesale container and field cutflower nurseries and retail nurseries in coastal California (Monterey, Santa Cruz, and San Mateo counties). The disease occurred early in the season (January) and continued to infect new foliage throughout the year whenever cool, foggy weather occurred. The disease primarily affected newly expanded young leaves on shoot tips. Such leaves were chlorotic, twisted and bent, and stunted. In some cases, leaflet tips turned black and necrotic. The abaxial sides of affected leaves were heavily colonized by the extensive purplish brown growth of downy mildew. Older, fully expanded foliage was unaffected. Flowers could be infected with the fungus growing on the undersides of petals and resulting in slightly twisted, bent shapes. Symptomatic plants and cutflower stems were unmarketable. Hyaline conidiophores emerged from stomata, branched dichotomously (rarely trichotomously), and had branches ending in slender, curved branchlets that did not have swollen tips. Conidia were slightly brown, ovoid, mostly nonpapillate, and measured 28.5 to 40.0 × 19.0 to 28.0 μm. Oospores were not observed in plant tissue. On the basis of symptoms and morphology of the organism, the pathogen was identified as Peronospora radii (1,2). To prove pathogenicity, plants were spray inoculated with conidial suspensions, incubated for 24 h in a dew chamber (18 to 20°C), and then maintained in a greenhouse (22 to 24°C).After 18 to 20 days, symptoms and signs of downy mildew developed only on the newest foliage of inoculated plants, and the pathogen morphology matched that of the originally observed pathogen. Untreated control plants did not develop downy mildew. To our knowledge, this is the first report of downy mildew caused by P. radii on marguerite daisy in California and the United States. The pathogen has not been reported on other hosts in California. P. radii is found on marguerite daisy in England, Germany, Israel, Mexico, and the former Yugoslavia (1,2). References: (1) I. S. Ben-Ze'ev et al. Phytoparasitica 15:51, 1987. (2) O. Constantinescu. Sydowia Ann. Mycol. 41:79, 1989.


The large plasmids of Shiga-toxin-producing Escherichia coli (STEC) are highly variable genetic elements.
Shiga-toxin-producing Escherichia coli (STEC) of different serotypes are known to harbour large plasmids. The aim of this study was to investigate, using the example of the plasmid-encoded serine protease EspP, whether these plasmids are a uniform genetic element present in STEC. Examination of 201 diarrhoeagenic E. coli strains using a newly developed espP-specific PCR showed that espP is specific for STEC and present in 57% of STEC belonging to 16 different serotypes. The espP genes of the 16 STEC serotypes varied to a certain extent, as shown by nucleotide sequence and restriction enzyme analyses, but the DNA regions adjacent to the espP gene were completely different. When two further STEC-plasmid markers, the catalase-peroxidase gene katP and the enterohaemorrhagic E. coli-haemolysin gene EHEC-hlyA were included, many combinations of the three markers were found, depending in part on the serotype. In addition, strains possessing none of the three markers still harboured large plasmids. In the most prevalent STEC serogroup, O157, it was observed that the plasmid of sorbitol-fermenting STEC O157:H- lacks the espP and katP genes although both genes are present in the plasmid of the non-sorbitol-fermenting STEC O157:H7. The EHEC-hlyA gene, however, is present in both. In conclusion, this study shows that the large plasmids of STEC are not uniform genetic elements but heterogeneous in both their gene composition and arrangement.


Unusual combination of presenting features in multiple myeloma.
Initial oral signs of multiple myeloma may involve pain, paraesthesia, swelling, tooth mobility and radiolucency. A 62-year-old female patient presented with the chief complaint of numbness in the right lower jaw. Intraoral examination revealed no abnormalities and her history was non-contributory. A panoramic radiograph revealed an irregular, small radiopacity in the premolar region and small, multiple and diffuse osteolytic alterations in the mandible. Computed tomography revealed maxillary and mandibular cortical destruction. An incisional biopsy was performed. The histopathological diagnosis was plasma cell myeloma and further investigations lead to the diagnosis of multiple myeloma. Dysfunction of a nerve coursing through diseased bone is an ominous sign and may be an indication that a malignant process is present.


Hip resurfacing arthroplasty.
Hip resurfacing arthroplasty is a type of hip replacement that involves capping the femoral head and preserving bone of the proximal femur. Metal-on-metal surface replacements have been manufactured since the early 1990s. Recent studies indicate excellent clinical results with low failure rates at 1- to 5-year follow-up. Although these early results are encouraging, resurfacing devices must be used with caution because less is known about their long-term safety and efficacy. The best candidates for resurfacing are patients younger than age 60 years with good bone stock. The surgical approach is similar to that for standard total hip replacements, but with slightly more dissection because the femoral head must be preserved and displaced to visualize the acetabulum. To reduce complications, resurfacing arthroplasty should be performed by surgeons who have received training specifically in this technique.


Imaging comparison of pelvic ring disruption and injury reduction with use of the junctional emergency treatment tool for preinjury and postinjury pelvic dimensions: a cadaveric study with computed tomography.
Complex dismounted blast injuries from (improvised) explosive devices have caused amputations of the lower extremities associated with open injuries to the pelvic ring, resulting in life-threatening hemorrhage from disruption of blood vessels near the pelvic ring. Provisional stabilization of the skeletal pelvis by circumferential pelvic compression provides stability for intrapelvic clots and reduces the volume of the pelvis, thereby limiting the amount of hemorrhage. The Junctional Emergency Treatment Tool (JETTtm; North American Rescue Products, http://www.narescue.com) is a junctional hemorrhage control device developed to treat pelvic and lower extremity injuries sustained in high-energy trauma on the battlefield and in the civilian environment. Our purpose was to evaluate the compressive function of the JETT in the reduction of pelvic ring injuries in a cadaveric model. Radiographic comparison of pre (intact) and post pelvic ring disruption and injury was compared with radiographic measurements post reduction with the JETT device in two cadavers. The device's ability to reduce pelvic disruption and injury in a human cadaver model was assessed through measurements of the anteroposterior (AP) and transverse diameters obtained at the inlet and outlet of the pelvis. Computed tomography (CT) scans demonstrated that JETT application effectively induced circumferential soft tissue compression that was evoked near anatomic reduction of the sacroiliac joint and symphysis pubis. The JETT is capable of effectively reducing an AP compression type III injury (APC III) pelvic ring disruption and injury by approximating the inlet and outlet dimensions toward predisruption measurements. Such a degree of reduction suggests that the JETT device may be suitable in the acute setting for provisional pelvic stabilization.


Olfactory sensitivity for six predator odorants in CD-1 mice, human subjects, and spider monkeys.
Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species' olfactory sensitivity. Analysis of odor structure-activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity.


TGF-β2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine.
Premature neonates are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis. We investigated whether NEC occurs in the preterm intestine due to incomplete noninflammatory differentiation of intestinal macrophages, which increases the risk of a severe mucosal inflammatory response to bacterial products. We compared inflammatory properties of human/murine fetal, neonatal, and adult intestinal macrophages. To investigate gut-specific macrophage differentiation, we next treated monocyte-derived macrophages with conditioned media from explanted human fetal and adult intestinal tissues. Transforming growth factor-β (TGF-β) expression and bioactivity were measured in fetal/adult intestine and in NEC. Finally, we used wild-type and transgenic mice to investigate the effects of deficient TGF-β signaling on NEC-like inflammatory mucosal injury. Intestinal macrophages in the human preterm intestine (fetus/premature neonate), but not in full-term neonates and adults, expressed inflammatory cytokines. Macrophage cytokine production was suppressed in the developing intestine by TGF-β, particularly the TGF-β(2) isoform. NEC was associated with decreased tissue expression of TGF-β(2) and decreased TGF-β bioactivity. In mice, disruption of TGF-β signaling worsened NEC-like inflammatory mucosal injury, whereas enteral supplementation with recombinant TGF-β(2) was protective. Intestinal macrophages progressively acquire a noninflammatory profile during gestational development. TGF-β, particularly the TGF-β(2) isoform, suppresses macrophage inflammatory responses in the developing intestine and protects against inflammatory mucosal injury. Enterally administered TGF-β(2) protected mice from experimental NEC-like injury.


A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity.
Alzheimer's disease (AD) researchers commonly use MRI as a quantitative measure of disease severity. Historically, hippocampal volume has been favored. Recently, "AD signature" measurements of gray matter (GM) volumes or cortical thicknesses have gained attention. Here, we systematically evaluate multiple thickness- and volume-based candidate-methods side-by-side, built using the popular FreeSurfer, SPM, and ANTs packages, according to the following criteria: (a) ability to separate clinically normal individuals from those with AD; (b) (extent of) correlation with head size, a nuisance covariatel (c) reliability on repeated scans; and (d) correlation with Braak neurofibrillary tangle stage in a group with autopsy. We show that volume- and thickness-based measures generally perform similarly for separating clinically normal from AD populations, and in correlation with Braak neurofibrillary tangle stage at autopsy. Volume-based measures are generally more reliable than thickness measures. As expected, volume measures are highly correlated with head size, while thickness measures are generally not. Because approaches to statistically correcting volumes for head size vary and may be inadequate to deal with this underlying confound, and because our goal is to determine a measure which can be used to examine age and sex effects in a cohort across a large age range, we thus recommend thickness-based measures. Ultimately, based on these criteria and additional practical considerations of run-time and failure rates, we recommend an AD signature measure formed from a composite of thickness measurements in the entorhinal, fusiform, parahippocampal, mid-temporal, inferior-temporal, and angular gyrus ROIs using ANTs with input segmentations from SPM12.


Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.
To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis. A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical. A population based cohort in Sweden established in 1987. 61,433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort. Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires. During follow-up, 14,738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32). Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.


Atom-transfer radical addition reactions catalyzed by RuCp* complexes: a mechanistic study.
Kinetic and spectroscopic analyses were performed to gain information about the mechanism of atom-transfer radical reactions catalyzed by the complexes [RuCl2Cp*(PPh3)] and [RuClCp*(PPh3)2] (Cp*=pentamethylcyclopentadienyl), in the presence and in the absence of the reducing agent magnesium. The reactions of styrene with ethyl trichloroacetate, ethyl dichloroacetate, or dichloroacetonitrile were used as test reactions. The results show that for substrates with high intrinsic reactivity, such as ethyl trichloroacetate, the oxidation state of the catalyst in the resting state is +3, and that the reaction is zero-order with respect to the halogenated compound. Furthermore, the kinetic data suggest that the metal catalyst is not directly involved in the rate-limiting step of the reaction.


Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals.
Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine.


Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes.
. Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies.


Conservative interventions for treating distal radial fractures in adults.
Fracture of the distal radius is a common clinical problem particularly in elderly white women with osteoporosis. To determine the most appropriate conservative treatment for fractures of the distal radius in adults. We searched the Cochrane Musculoskeletal Injuries Group specialised register (November 2002), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to January week 1 2003), EMBASE (1988 to 2003 Week 3), CINAHL (1982 to December week 4 2002), the National Research Register (up to Issue 4, 2002), PEDro, conference proceedings and reference lists of articles. No language restrictions were applied. Randomised or quasi-randomised clinical trials involving skeletally mature patients with a fracture of the distal radius, which compared commonly applied conservative interventions for fracture fixation. These included the application of an external support (plaster cast or brace) and fracture manipulation. All trials, judged as fitting the selection criteria by both reviewers, were independently assessed by both reviewers for methodological quality. Data were extracted for anatomical, functional and clinical, including complications, outcomes. The trials were grouped into categories relating to manipulation of displaced fractures; use and extent, including forearm position, of immobilisation; use of braces; different casting materials and techniques; and duration of immobilisation. Although quantitative data from some trials are presented, the lack of good quality trials and trial heterogeneity inhibited pooling of results. Three trials were newly included in this update. In all, there are 36 trials, involving a total of 4114 mainly female and older patients, meeting the inclusion criteria for this review. Comprehensive details of the individual trials are provided in tabular form, and their results, grouped as indicated above, have been presented in text and analyses tables. The poor quality and heterogeneity in terms of patient characteristics, interventions compared and outcome measurement, of the included trials meant that no meta-analyses were undertaken. There remains insufficient evidence from randomised trials to determine which methods of conservative treatment are the most appropriate for the more common types of distal radial fractures in adults. Therefore, at present, practitioners applying conservative management should use an accepted technique with which they are familiar, and which is cost-effective from the perspective of their provider unit. Patient preferences and circumstances, and the risk of complications should also be considered. Prioritising research questions to clarify the most appropriate conservative treatment for this common fracture is warranted. Researchers should differentiate between extra-articular and intra-articular, and non-displaced and displaced fractures, ascertain patient preferences, and agree a core outcome data set.


Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy.
Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated by the HIV-1-specific inhibitors bis-heteroarylpiperazine (BHAP), 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-on e (TIBO) R82913, nevirapine, and the N3-methylthymine derivative of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO-m3T), as single agents or in combination, at escalating concentrations. When used individually, the compounds led to the emergence of drug-resistant virus strains within two to five subcultivations. The resulting strains were designated HIV-1/BHAP, HIV-1/TIBO, HIV-1/Nev, and HIV-1/TSAO-m3T, respectively. The mutant viruses showed the following amino acid substitutions in their reverse transcriptase (RT): Leu-100-->Ile for HIV-1/BHAP; Lys-103-->Asn for HIV-1/TIBO; Val-106-->Ala for HIV-1/Nev; and Glu-138-->Lys for HIV-1/TSAO-m3T. Both the Tyr-181-->Cys and Val-106-->Ala mutations were found in another mutant emerging following treatment with nevirapine at escalating concentrations. The BHAP-resistant virus remained fully sensitive to the inhibitory effects of nevirapine and TSAO-m3T, whereas the TSAO-m3T-resistant virus remained fully sensitive to the inhibitory effects of nevirapine and BHAP. When different pairs of nonnucleoside RT inhibitors (i.e., BHAP plus TSAO-m3T, nevirapine plus TSAO-m3T, TIBO plus TSAO-m3T, nevirapine plus TIBO, and BHAP plus nevirapine) were used, resistant virus emerged as fast as with single-drug therapy. In all cases the Tyr-181-->Cys mutation appeared; the virus showed markedly reduced sensitivity to all HIV-1-specific inhibitors but retained sensitivity to 2',3'-dideoxynucleoside analogs such as zidovudine, ddC, and ddI. Our findings argue against simultaneous combination of two different nonnucleoside RT inhibitors that are unable to inhibit HIV-1 mutant strains containing the Tyr-181-->Cys mutation when administered as single drugs.


Cardio-Ankle Vascular Index Reflects Impaired Exercise Capacity and Predicts Adverse Prognosis in Patients With Heart Failure.
Aims: We aimed to assess the associations of CAVI with exercise capacity in heart failure (HF) patients. In addition, we further examined their prognosis. Methods: We collected the clinical data of 223 patients who had been hospitalized for decompensated HF and had undergone both CAVI and cardiopulmonary exercise testing. Results: For the prediction of an impaired peak oxygen uptake (VO2) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. In the multivariate logistic regression analysis for predicting impaired peak VO2, high CAVI was found to be an independent factor (odds ratio 2.343, P = 0.045). We divided these patients based on CAVI: the low-CAVI group (CAVI < 8.9, n = 145) and the high-CAVI group (CAVI ≥ 8.9, n = 78). Patient characteristics and post-discharge cardiac events were compared between the two groups. The high-CAVI group was older (69.0 vs. 58.0 years old, P < 0.001) and had lower body mass index (23.0 vs. 24.1 kg/m2, P = 0.013). During the post-discharge follow-up period of median 1,623 days, 58 cardiac events occurred. The Kaplan-Meier analysis demonstrated that the cardiac event rate was higher in the high-CAVI group than in the low-CAVI group (log-rank P = 0.004). The multivariate Cox proportional hazard analysis revealed that high CAVI was an independent predictor of cardiac events (hazard ratio 1.845, P = 0.035). Conclusion: High CAVI is independently associated with impaired exercise capacity and a high cardiac event rate in HF patients.


Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform.
Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.


Affective Visualization Design: Leveraging the Emotional Impact of Data.
In recent years, more and more researchers have reflected on the undervaluation of emotion in data visualization and highlighted the importance of considering human emotion in visualization design. Meanwhile, an increasing number of studies have been conducted to explore emotion-related factors. However, so far, this research area is still in its early stages and faces a set of challenges, such as the unclear definition of key concepts, the insufficient justification of why emotion is important in visualization design, and the lack of characterization of the design space of affective visualization design. To address these challenges, first, we conducted a literature review and identified three research lines that examined both emotion and data visualization. We clarified the differences between these research lines and kept 109 papers that studied or discussed how data visualization communicates and influences emotion. Then, we coded the 109 papers in terms of how they justified the legitimacy of considering emotion in visualization design (i.e., why emotion is important) and identified five argumentative perspectives. Based on these papers, we also identified 61 projects that practiced affective visualization design. We coded these design projects in three dimensions, including design fields (where), design tasks (what), and design methods (how), to explore the design space of affective visualization design.


Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age.
To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer's disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia Study METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis. Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status. Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.


3D-QSAR studies on triclosan derivatives as Plasmodium falciparum enoyl acyl carrier reductase inhibitors.
3D-QSAR studies were carried out on a training set of 53 structurally highly diverse analogues of triclosan to investigate the correlation of the structural properties of triclosan derivatives with the inhibition of the activity of enoyl acyl carrier protein reductase in Plasmodium falciparum (PfENR) by employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The crystal structure bound conformation of triclosan, was used as a template for aligning molecules. The probable binding mode conformations of other inhibitors were explored according to molecular docking and molecular mechanics poisson-boltzmann surface area (MM/PBSA) solvation free energy estimation methods using grid based linear Poisson-Boltzmann calculations. Predictive 3D-QSAR models, established using routine database alignment rule based on crystallographic-bound conformation of template molecule, produced statistically significant results with cross-validated r2 cv values of 0.64 and 0.54 and non-cross-validated r2 ncv values of 0.96 and 0.97 for CoMFA and CoMSIA models, respectively. The statistically significant models were validated by a test set of nine compounds with predictive r(2) values of 0.534 and 0.765 for CoMFA and CoMSIA respectively. Our QSAR model is able to successfully explain the geometric and electrostatic complementarities between ligands and receptor and provides useful guidelines to design novel triclosan derivatives as Plasmodium falciparum enoyl acyl carrier reductase inhibitors.


Conditional symbolic modified signed-digit arithmetic using optical content-addressable memory logic elements.
A new conditional symbolic substitution rule for modified signed-digit arithmetic computation is introduced. Using this substitution rule, the numbers to be added or subtracted are first replaced by a pair of new equivalent strings, which in a second step are then subject to another substitution to generate both the addition or subtraction result and its complement. For an optical implementation, a holographic contentaddressable memory is used. Correspondingly, the input encoding, the logic reduction, and the optical processing techniques are described.


Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia.
Muscle atrophy-also known as muscle wasting-is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting. In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopenia and cachexia have begun to be elucidated. Growing evidence suggests that inflammatory cytokines may play an important role in the pathology of both syndromes. As one of the key cytokines involved in both sarcopenic and cachectic muscle wasting, tumor necrosis factor α (TNFα) and its downstream effectors provide an enticing target for pharmacological intervention. However, to date, no drugs targeting the TNFα signaling pathway have been successful as a remedial option for the treatment of muscle wasting. Thus, there is a need to identify new effectors in this important pathway that might prove to be more efficacious targets. Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFα-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia. In addition, investigations into the mechanism of iNOS-mediated muscle loss have begun to reveal potential therapeutic strategies. In this review, we will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia.


The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.
Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.


Two-stage injection locking of high-power semiconductor arrays.
A new multistage diode-array injection-locking technique is demonstrated. This approach permits higher power extraction or higher overall gain to be achieved than possible with single-stage designs. Using two antireflectioncoated 40-stripe multiple-quantum-well diode arrays, we characterize the amplifier small-signal and saturated gain performance. More than 500 mWof power is achieved with single frequency and narrow linewidth in a nearly diffraction-limited far-field lobe. With small-signal inputs, an overall gain of 25 dB with 290-mW locked output is obtained.


[Joint EFLM-COLABIOCLI recommendation for venous blood sampling].
This document provides a joint recommendation for venous blood sampling of the European federation of clinical chemistry and laboratory medicine (EFLM) Working Group for preanalytical phase (WG-PRE) and Latin American working group for preanalytical phase (WG-PRE-LATAM) of the Latin America confederation of clinical biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.


Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise.
The present study was intended to investigate the different components of fatty acid utilization during a 60-min period of moderate-intensity cycling exercise (50% of VO2max) in eight male type 2 diabetic subjects (aged 52.6 +/- 3.1 years, body fat 35.8 +/- 1.3%) and eight male obese control subjects (aged 45.1 +/- 1.4 years, body fat 34.2 +/- 1.3%) matched for age, body composition, and maximal aerobic capacity. To quantitate the different components of fatty acid metabolism, an isotope infusion of [U-13C]-palmitate was used in combination with indirect calorimetry. In separate experiments, the 13C label recovery in expired air was determined during infusion of [1,2-13C]-acetate (acetate recovery factor). There were no differences in energy expenditure or carbohydrate and total fat oxidation between the groups. The rate of appearance (Ra) of free fatty acid (FFA) (P < 0.05) and the exercise-induced increase in Ra of FFA were significantly lower (P < 0.05) in type 2 diabetic subjects compared with control subjects (baseline vs. exercise [40-60 min]; type 2 diabetes 11.9 +/- 0.9 vs. 19.6 +/- 2.2 micromol x kg(-1) fat-free mass [FFM] x min(-1) and control 15.8 +/- 1.8 vs. 28.6 +/- 2.1 micromol x kg(-1) FFM x min(-1)). The oxidation of plasma-derived fatty acids was significantly lower in type 2 diabetic subjects during both conditions (P < 0.05, baseline vs. exercise [40-60 min]; type 2 diabetes 4.2 +/- 0.5 vs. 14.1 +/- 1.9 micromol x kg(-1) FFM x min(-1) and control 6.2 +/- 0.6 vs. 20.4 +/- 1.9 micromol x kg(-1) FFM x min(-1)), whereas the oxidation of triglyceride-derived fatty acids was higher (P < 0.05). It is hypothesized that these impairments in fatty acid utilization may play a role in the etiology of skeletal muscle and hepatic insulin resistance.


Measuring how genetic and epigenetic variants can filter emotion perception.
Emotion perception has been extensively studied in cognitive neurosciences and stands as a promising intermediate phenotype of social cognitive processes and psychopathologies. Exciting imaging genetic studies have recently identified genetic and epigenetic variants affecting brain responses during emotion perception tasks, but characterizing how these variants interact and relate to higher-order cognitive processes remains a challenge. Here, we integrate works in parallel fields and propose a new psychophysical conceptualization to address this issue. This approach proposes to consider genetic variants as 'filters' of perceptual information that can interact to shape different perceptual profiles. Importantly, these perceptual profiles can be precisely described and compared between multivariate genetic groups using a new psychophysical method. Crucially, this approach represents a potentially powerful novel tool to address gene-by-gene and gene-by-environment interactions, and provides a new cognitive perspective to link social perceptive and social cognitive processes in the context of psychiatric disorders.


Interventions for Adolescent Substance Abuse: An Overview of Systematic Reviews.
Many unhealthy behaviors often begin during adolescence and represent major public health challenges. Substance abuse has a major impact on individuals, families, and communities, as its effects are cumulative, contributing to costly social, physical, and mental health problems. We conducted an overview of systematic reviews to evaluate the effectiveness of interventions to prevent substance abuse among adolescents. We report findings from a total of 46 systematic reviews focusing on interventions for smoking/tobacco use, alcohol use, drug use, and combined substance abuse. Our overview findings suggest that among smoking/tobacco interventions, school-based prevention programs and family-based intensive interventions typically addressing family functioning are effective in reducing smoking. Mass media campaigns are also effective given that these were of reasonable intensity over extensive periods of time. Among interventions for alcohol use, school-based alcohol prevention interventions have been associated with reduced frequency of drinking, while family-based interventions have a small but persistent effect on alcohol misuse among adolescents. For drug abuse, school-based interventions based on a combination of social competence and social influence approaches have shown protective effects against drugs and cannabis use. Among the interventions targeting combined substance abuse, school-based primary prevention programs are effective. Evidence from Internet-based interventions, policy initiatives, and incentives appears to be mixed and needs further research. Future research should focus on evaluating the effectiveness of specific interventions components with standardized intervention and outcome measures. Various delivery platforms, including digital platforms and policy initiative, have the potential to improve substance abuse outcomes among adolescents; however, these require further research.


CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.
High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25% of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help. To verify this assumption, we analyzed this cell population and show its specialized function in supporting humoral immune responses. Compared with their CXCR5(-) T(CM) counterparts, CXCR5(+) T(CM) expressed high levels of the chemokine CXCL13 and efficiently induced plasma cell differentiation and Ig secretion. We found that the distinct B cell helper qualities of CXCR5(+) T(CM) were mainly due to high ICOS expression and pronounced responsiveness to ICOS ligand costimulation together with large IL-10 secretion. Furthermore, B cell helper attributes of CXCR5(+) T(CM) were almost exclusively acquired on cognate interaction with B cells, but not with dendritic cells. This implies that a preferential recruitment of circulating CXCR5(+) T(CM) to CXCL13-rich B cell follicles is required for the promotion of a quick and efficient protective secondary humoral immune response. Taken together, we propose that CXCR5(+) T(CM) represent a distinct memory cell subset specialized in supporting Ab-mediated immune responses.


10 aJ-level sensing of nanosecond pulse below 10 THz by frequency upconversion detection via DAST crystal: more than a 4 K bolometer.
By using frequency upconversion detection of terahertz (THz) waves via 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) crystal with an optimized frequency conversion process, ultrahigh sensitivity has been achieved. Direct comparisons with a 4 K bolometer were implemented. By using a simple positive intrinsic negative (PIN) diode without either electrical amplification or optical amplification, frequency upconversion detection can compete with the commercial 4 K bolometer, while by replacing the PIN diode with an avalanche photo diode (APD), it performs more than three orders better than the 4 K bolometer. Based on power calibration, the minimum detectable THz pulse energy is in the order of 10 aJ (9-25 aJ) at 4.3 THz, with a pulse duration of 6 ns. Thus, the minimum number of THz photons that can be detected is down to the order of 10(3) at room temperature. The current THz detection system gives a noise equivalent power (NEP) in the order of 100 fW/Hz(1/2) (50-128 fW/Hz(1/2)). Moreover, by switching current optical detectors, the dynamic range is over six orders.