Cross-sectional observational study of the availability of evidence supporting novel implantable devices used in gastrointestinal surgery.
Evidence supporting the implementation of novel surgical devices is unstandardized, despite recommendations for assessing novel innovations. This study aimed to determine the proportion of novel implantable devices used in gastrointestinal surgery that are supported by evidence from RCTs. A list of novel implantable devices placed intra-abdominally during gastrointestinal surgery was produced. Systematic searches were performed for all devices via PubMed and clinical trial registries. The primary outcome measure was the availability of at least one published RCT for each device. Published RCTs were appraised using the Cochrane tool for assessing risk of bias. A total of 116 eligible devices were identified (implantable mesh 42, topical haemostatics 22, antiadhesion barriers 10, gastric bands 8, suture and staple-line reinforcement 7, artificial sphincters 5, other 22). One hundred and twenty-eight published RCTs were found for 33 of 116 devices (28·4 per cent). Most were assessed as having a high risk of bias, with only 12 of 116 devices (10·3 per cent) supported by a published RCT considered to be low risk. A further 95 ongoing and 23 unpublished RCTs were identified for 42 of 116 devices (36·2 per cent), but many (64 of 116, 55·2 per cent) had no evidence from published, ongoing or unpublished RCTs. The highest stage of innovation according to the IDEAL Framework was stage 1 for 11 devices, stage 2a for 23 devices, stage 2b for one device and stage 3 for 33 devices. The remaining 48 devices had no relevant clinical evidence. Only one in ten novel implantable devices available for use in gastrointestinal surgical practice is supported by high-quality RCT evidence.


Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction.
The aim of the present study was to evaluate the solanesol (SNL)-mediated coenzyme-Q10 restoration to ameliorate 3-nitropropionic (3-NP)-induced behavioral, biochemical, and histological changes which resemble Huntington's disease (HD)-like symptoms in men. Various behavioral and biochemical parameters were carried out to evaluate the activity of SNL on 3-NP-treated rats. To determine the therapeutic significance of SNL on HD, different behavioral tests such as memory task, locomotor activity, grip strength, and beam cross and some biochemical test along with histopathological findings were done. Chronic 3-NP, 10 mg/kg i.p., caused physical and mental abnormalities in animals, including memory impairment, weak grip strength, abnormal posture, and cognitive deficit. Biochemical analysis of brain homogenate in 3-NP-treated rats showed altered mitochondrial complexes, oxidative stress, and elevated lipid biomarkers. Neurohistological alterations of hippocampus, basal ganglia, and cerebral cortex of 3-NP-treated rats exhibit severe neuronal space, irregular damaged cells, and dense pyknotic nuclei-associated marked focal diffused gliosis. SNL administered for 15 days significantly improved motor performance and cognitive behavior task and restored the histopathological changes. Further, SNL treatment significantly improved mitochondrial complexes such as coenzyme-Q10 enzyme activity and attenuated inflammatory and oxidative damage of rat brain. In the present research work, SNL (5, 10, and 15 mg/kg p.o.) provided notable neuroprotective effect, which was confirmed by behavioral paradigms and biochemical test. It restored the behavioral and biochemical alteration caused by 3-NP and confirmed the strong neuroprotective mechanism of SNL in 3-NP-intoxicated memory and cognitive abnormalities.


Beating crystallization in glass-forming metals by millisecond heating and processing.
The development of metal alloys that form glasses at modest cooling rates has stimulated broad scientific and technological interest. However, intervening crystallization of the liquid in even the most robust bulk metallic glass-formers is orders of magnitude faster than in many common polymers and silicate glass-forming liquids. Crystallization limits experimental studies of the undercooled liquid and hampers efforts to plastically process metallic glasses. We have developed a method to rapidly and uniformly heat a metallic glass at rates of 10(6) kelvin per second to temperatures spanning the undercooled liquid region. Liquid properties are subsequently measured on millisecond time scales at previously inaccessible temperatures under near-adiabatic conditions. Rapid thermoplastic forming of the undercooled liquid into complex net shapes is implemented under rheological conditions typically used in molding of plastics. By operating in the millisecond regime, we are able to "beat" the intervening crystallization and successfully process even marginal glass-forming alloys with very limited stability against crystallization that are not processable by conventional heating.


Clinical Use of GalaFLEX in Facial and Breast Cosmetic Plastic Surgery.
Resolution of ptosis is a key step to the success of many plastic surgery procedures. Ptosis is a manifestation of tissue stretch. Tissue stretch can occur as a result of the natural aging process or health of the patient, or tissue may stretch under added weight or volume, such as when implants are placed. Surgical rejuvenation of ptotic tissues is very effective and results in marked changes in the patient profile yet the tissue that resulted in the need for the procedure first place has not improved and ptosis can recur. Recent developments in long-term resorbable porous materials have provided surgeons with the opportunity to experiment with tissue reinforcement in plastic surgery procedures. These new materials have a low profile, rapid tissue integration, and a long-term strength retention profile. Long-term resorbable scaffolds such as poly-4-hydroxybutyrate (P4HB) natural scaffold (GalaFLEX scaffold, Galatea Surgical, Inc., Lexington, MA) have shown promise for a host of plastic surgery indications. This article presents clinical experience with GalaFLEX for soft tissue reinforcement in three different clinical applications; including the reinforcement of the superficial muscular aponeurotic system (SMAS) in minimally invasive facelift, reinforcement of the skin envelope in mastopexy, and reinforcement of the breast capsule (pocket) in revisional breast surgery. Soft tissue reinforcement has been shown to provide increased mechanical strength as well as improved maintenance of postoperative results. 5 Therapeutic.


HIV prevention among African American youth: how well have evidence-based interventions addressed key theoretical constructs?
Certain constructs are demonstrated in the research literature to be related to HIV risk behaviors among African American adolescents. This study examines how well these constructs are addressed in evidence-based interventions (EBIs) developed for this population. A literature review on variables for sexual risk behaviors among African American adolescents was undertaken. Simultaneously, a review was conducted of the contents of HIV-prevention EBIs. To facilitate comparison, findings from both were organized into constructs from prominent behavior change theories. Analysis showed that environmental conditions and perceived norms were frequently associated with sexual risk behaviors in the literature, while EBIs devoted considerable time to knowledge, skills, and self-efficacy. Findings imply that (a) EBIs might be complemented with activities that focus on important constructs identified in the literature and (b) researchers should better assess the relationship between skill development and HIV risk behaviors. Implications for practice and research are discussed.


What everyone else is eating: a systematic review and meta-analysis of the effect of informational eating norms on eating behavior.
There is interest in the hypothesis that social norms are a determinant of healthy and unhealthy dietary practices. The objective of our work was to assess the weight of evidence that experimentally manipulated information about eating norms influences food intake and choice. This systematic review of experimental studies examined whether providing information about other peoples' eating habits influences food intake or choices. To inform the review, three electronic databases (PsycINFO, MEDLINE, and the Social Sciences Citation Index) were searched during July 2012. A narrative approach was used to synthesize studies that examined the influence of norms on food choice and meta-analyses were used to synthesize the effect that informational eating norms have on quantity of food consumed. Fifteen experimental studies were reviewed. There was evidence that both high intake norms (Z=3.84; P=0.0001; standardized mean difference 0.41, 95% confidence interval 0.20 to 0.63) and low intake norms (Z=2.78; P=0.005; standard mean difference -0.35, 95% confidence interval -0.59 to -0.10) exerted moderate influence on amounts of food eaten. There was consistent evidence that norms influenced food choices; norm information indicating that others make low-energy or high-energy food choices significantly increased the likelihood that participants made similar choices. Information about eating norms influences choice and quantity of food eaten, which could be used to promote healthy changes to dietary behavior.


Diffusion of insulin-like growth factor-I and ribonuclease through fibrin gels.
A fluorescence-based method for simultaneously determining the diffusion coefficients of two proteins is described, and the diffusion coefficient of insulin-like growth factor (IGF-I) and ribonuclease (RNase) in a 0.27% fibrin hydrogel is reported. The method is based on two-color imaging of the relaxation of the protein concentration field with time and comparing the results with a transport model. The gel is confined in a thin (200 microm) capillary and the protein is labeled with a fluorescent dye. The experimentally determined diffusion coefficient of RNase (D = 1.21 x 10(-6) cm(2)/s) agrees with literature values for dilute gels and bulk aqueous solutions, thus indicating the gel and the dye had a negligible effect on diffusion. The experimental diffusion coefficient of IGF-I (D = 1.59 x 10(-6) cm(2)/s), in the absence of binding to the fibrin matrix, is consistent with the dimensions of the molecule known from x-ray crystallography and a correlation between D and molecular weight based on 14 other proteins. The experimental method developed here holds promise for determining molecular transport properties of biomolecules under a variety of conditions, for example, when the molecule adsorbs to the gel or is convected through the gel by fluid transport.


A PEGylated Fab' fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action.
Antibodies, having a high specificity for their particular target, are increasingly being used as therapeutic agents with functions including agonist, antagonist, and targeted drug delivery. The use of many biologic therapies, including antibody fragments, is generally limited by their rapid clearance from plasma. A commonly used approach to extend exposure to biologic therapies is the attachment of polyethylene glycol.Tumor necrosis factor (TNF)-alpha is a multifunctional cytokine involved in the regulation of immune responses. Elevated levels of TNFalpha are found in a wide range of diseases, including the chronic inflammatory conditions rheumatoid arthritis, psoriasis, and Crohn disease (CD). Anti-TNFalpha antibodies have proved highly efficacious in the treatment of these conditions. In addition, they have proved invaluable for investigating the role of TNFalpha in disease etiology. Based on evidence showing that neutralizing antibodies to TNFalpha were effective in animal models of CD, anti-TNFalpha antibody treatments were assessed in clinical trials. Interestingly, the anti-TNFalpha antibody etanercept proved ineffective at achieving remission in active CD despite potently neutralizing soluble TNFalpha. This indicated that an additional mode of action is also involved in the efficacy of the anti-TNFalpha agents adalimumab, certolizumab pegol, and infliximab in CD; one suggestion was apoptosis. However, etanercept, like adalimumab and infliximab, can induce apoptosis. Furthermore, certolizumab pegol (which has demonstrated efficacy in CD) does not cause complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, apoptosis, or necrosis of neutrophils, all measured in vitro. These functional differences observed with certolizumab pegol stem from its unique structure that does not include the crystallizable fragment (Fc) portion present in the other anti-TNFalpha agents, and the way in which it signals through membrane TNF. It is well established that bacteria are a major part of the inflammatory process in CD. The property identified that reflected the efficacies of the anti-TNFalpha agents etanercept, adalimumab, certolizumab pegol, and infliximab in CD was the ability to inhibit the cytokine production by monocytes that is induced by bacterial lipopolysaccharide. It may therefore be the case that this mode of action is important for efficacy in CD.


Theoretical versus observed gas-particle partitioning of carbonyl emissions from motor vehicles.
A state-of-the-science thermodynamic model describing gas-particle absorption processes was used to predict the gas-particle partitioning of mixtures of approximately 60 carbonyl compounds emitted from low-emission gasoline-powered vehicles, three-way catalyst gasoline-powered vehicles, heavy-duty diesel vehicles under the idle-creep condition (HDDV idle), and heavy-duty diesel vehicles under the five-mode test (HDDV 5-mode). Exhaust was diluted by a factor of 120-580 with a residence time of approximately 43 sec. The predicted equilibrium absorption partitioning coefficients differed from the measured partitioning coefficients by several orders of magnitude. Time scales to reach equilibrium in the dilution sampling system were close to the actual residence time during the HDDV 5-mode test and much longer than the actual residence time during the other vehicle tests. It appears that insufficient residence time in the sampling system cannot uniformly explain the failure of the absorption mechanism to explain the measured partitioning. Other gas-particle partitioning mechanisms (e.g., heterogeneous reactions, capillary adsorption) beyond the simple absorption theory are needed to explain the discrepancy between calculated carbonyl partitioning coefficients and observed partitioning. Both of these alternative partitioning mechanisms imply great challenges for the measurement and modeling of semi-volatile primary organic aerosol (POA) species from motor vehicles. Furthermore, as emitted particle concentrations from newer vehicles approach atmospheric background levels, dilution sampling systems must fundamentally change their approach so that they use realistic particle concentrations in the dilution air to approximately represent real-world conditions. Samples collected with particle-free dilution air yielding total particulate matter concentrations below typical ambient concentrations will not provide a realistic picture of partitioning for semi-volatile compounds.


The cumulative and residual changes in eccentric knee flexor strength indices following soccer-specific treadmill running: Novel considerations of angle specific torque.
With potential implications for recovery and conditioning practices, the aim of this study was to assess the cumulative and residual response of angle specific eccentric knee flexor (eccKF) strength indices following soccer-specific activity. Thirteen semi-professional soccer players were therefore required to complete a 90-minute soccer-specific treadmill running. with eccKF isokinetic strength assessments completed pre-trial, immediately post-trial, and 48 hours post-trial. The strength assessments comprised the completion of 5 repetitions at angular velocities of 60 and 300 deg·s-1. Isokinetic data was analysed for measures of peak torque (PT), angle of peak torque (APT), functional range (FR), and angle specific torque (AST). Significant post-trial impairments were observed for measures of slow velocity PT60 (6.6%) and AST300 (12.5%). Further significant differences were observed 48 hours post-trial for PT300 (10.7%) and PT60 (12.8%) PT, APT60 (~15°), and AST300 (>13.6%). These data have implications for post exercise recovery monitoring and the prescription of recovery modalities and conditioning practices in the 2 days following match-play. The AST and APT responses highlight the importance of analysis of the entire strength-angle curve and at a range of angular velocities.


Epigenetic inheritance of disease and disease risk.
Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated.


What impact has England's Teenage Pregnancy Strategy had on young people's knowledge of and access to contraceptive services?
To describe young people's knowledge and use of contraceptive services over initial stages of England's Teenage Pregnancy Strategy, and to investigate factors associated with use of different services. A random location sample of young people aged 13-21 years (n = 8879) was interviewed in 12 waves over 2000-2004. Individual data were analysed to investigate factors associated with knowledge and use of contraceptive services and to observe trends over time. Area-level data were analyzed to explore differences in key variables. In all, 77% of young women and 65% of young men surveyed knew a service they could use to obtain information about sex. Amongst those who had had vaginal sexual intercourse, the most common source of contraceptive supplies was general practice for young women (54%) and commercial venues for young men (54%). Young women's use of school-based services to obtain supplies increased significantly from 15.4% in Year 1 to 24.4% in Year 4, p < .001. Young men's use of the commercial sector declined significantly over the same time period (60.3% to 50.6%, p = .002), while their use of general practice and family planning clinics increased (from 8.9% to 12.4%, p = .008, and 21.2% to 29.1%, p = .054, respectively). Use of family planning clinics and designated young people's clinics was associated with first vaginal intercourse before the 16th birthday and living in a deprived area. Young people's patterns of contraceptive service use have changed since implementation of the Strategy; although no increase in overall service use was observed. The contribution of school-based services needs further exploration.


Organ distribution of erythropoietin messenger RNA in normal and uremic rats.
We used RNAase protection assays to measure low levels of erythropoietin messenger RNA (EPO mRNA) in the organs of unstimulated rats, and to compare basal and stimulated levels of EPO mRNA in the kidneys and extrarenal organs of rats rendered uremic by subtotal nephrectomy, with pair-fed controls. Using this sensitive assay, EPO mRNA was measured in the kidneys of unstimulated control animals and was detectable, at lower levels, in the liver and lung. After exposure to hypoxia, there was a 150-fold increase in renal EPO mRNA. Hepatic EPO mRNA was also greatly increased and accounted for 39 +/- 10% of the total. The small quantity of EPO mRNA in lung did not increase, but EPO mRNA became detectable in spleen. Animals subjected to subtotal nephrectomy became uremic and anemic (hematocrit 0.32 +/- 0.04 vs. 0.43 +/- 0.04 in controls, P = 0.002), but serum EPO concentrations were not significantly increased (32 +/- 9 vs. 24 +/- 6 mU/ml, P = 0.14). However, after hypoxic exposure, uremic animals increased serum EPO concentrations greatly, although the response was less than in controls (349 +/- 82 vs. 1009 +/- 238 mU/ml, P = 0.002). After hypoxia, extrarenal EPO mRNA levels in uremic animals were similar to controls. In particular, the large hepatic potential for EPO mRNA synthesis was unchanged but accounted for a greater proportion (84 +/- 5%) of the total EPO mRNA. The renal EPO mRNA content was reduced, as expected, after subtotal nephrectomy, but increased 50-fold after hypoxia. In this model of chronic renal failure, despite anemia, a large potential for EPO synthesis exists in liver and remnant kidney.


The behaviour of tomato golden mosaic virus DNA in cultured cells isolated from systemically infected tobacco leaves.
When callus tissue was cultured from leaf pieces taken from a Nicotiana tabacum cv. Xanthi nc. plant systemically infected with tomato golden mosaic virus (TGMV), TGMV-specific DNA persisted for up to 6 months in culture. Analysis of TGMV-specific intracellular DNA forms indicated a decrease in double-stranded relative to single-stranded forms and an increase in sub-genomic relative to genomic single-stranded DNA species in the callus tissue compared to those in the original leaf explant. The implications of the results with regard to TGMV replication are discussed.


Catalytic antibody activity elicited by active immunisation. Evidence for natural variation involving preferential stabilization of the transition state.
1. The hydrolytic activity of IgG purified from (a) 13 samples of ovine antiserum collected from three animals during a two-year immunisation programme using a phosphate immunogen (comprising the amide conjugate bonded through the carboxy group of 4-nitrophenyl 4-carboxymethylphenyl hydrogen phosphate and amino groups of keyhole-limpet haemocyanin) and (b) a sample of ovine antiserum collected from another animal during an 18-week immunisation programme using an analogous sulphone immunogen (comprising the amide conjugate bonded through the amino group of 4-nitrobenzyl, 4-(4-aminobutoxy)benzyl sulphone and carboxyl groups of keyhole-limpet haemocyanin) were evaluated kinetically by using 4-nitrophenyl 4-(3-aza-2-oxoheptyl)phenyl carbonate and 4-nitrophenyl 4-(2-hydroxyethoxy)phenyl carbonate as substrates. 2. Catalytic activity was found in all 13 samples of anti-phosphate IgG but was absent in the sample of anti-sulphone IgG as well as in all samples of IgG isolated from the serum of non-immunised animals. These findings, taken together with the lack of catalytic activity of the anti-phosphate IgG towards the 2-nitrophenyl 4-(3-aza-2-oxoheptyl)phenyl carbonate, compel the view that the catalytic activity of the anti-phosphate IgG preparation is entirely antibody-mediated and is not due to contaminant hydrolytic enzymes. The fact that catalytic activity was found in all 13 samples of the anti-phosphate IgG provides the first evidence that it is possible, as a routine, to elicit a catalytic antibody response in a host animal via active immunisation. 3. The nature of the, albeit small, variation in the catalytic characteristics of the anti-phosphate IgG (increase in both kcat, the catalytic rate constant calculated as V/2[IgG] and kcat/Km, the apparent second-order rate constant for the overall catalysed conversion of substrate to products, with increase in Km suggests simultaneous improvement in transition state binding and deterioration in substrate binding as predicted from immunogen design and the postulated general mechanistic basis of antibody catalysis. 4. This interpretation is supported by the difference in the values of the dissociation constant Ki for the competitive inhibition by the transition-state analogue 4-methylphenyl 4-nitrophenyl hydrogen phosphate of reactions catalysed by two representative anti-phosphate IgG samples: for the catalysis with Km = 4.5 microM, Ki = 9 nM and for that with Km = 1.3 microM, Ki = 80 nM.(ABSTRACT TRUNCATED AT 400 WORDS)


Time-varying magnetic fields: effect on DNA synthesis.
Human fibroblasts have exhibited enhanced DNA synthesis when exposed to sinusoidally varying magnetic fields for a wide range of frequencies (15 hertz to 4 kilohertz) and amplitudes (2.3 X 10(-6) to 5.6 X 10(-4) tesla). This effect, which is at maximum during the middle of the S phase of the cell cycle, appears to be independent of the time derivative of the magnetic field, suggesting an underlying mechanism other than Faraday's law. The threshold is estimated to be between 0.5 X 10(-5) and 2.5 X 10(-5) tesla per second. These results bring into question the allegedly specific magnetic wave shapes now used in therapeutic devices for bone nonunion. The range of magnetic field amplitudes tested encompass the geomagnetic field, suggesting the possibility of mutagenic interactions directly arising from short-term changes in the earth's field.


Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding.
Cellular inhibitor of apoptosis (cIAP) proteins, cIAP1 and cIAP2, are important regulators of tumor necrosis factor (TNF) superfamily (SF) signaling and are amplified in a number of tumor types. They are targeted by IAP antagonist compounds that are undergoing clinical trials. IAP antagonist compounds trigger cIAP autoubiquitylation and degradation. The TNFSF member TWEAK induces lysosomal degradation of TRAF2 and cIAPs, leading to elevated NIK levels and activation of non-canonical NF-kappaB. To investigate the role of the ubiquitin ligase RING domain of cIAP1 in these pathways, we used cIAP-deleted cells reconstituted with cIAP1 point mutants designed to interfere with the ability of the RING to dimerize or to interact with E2 enzymes. We show that RING dimerization and E2 binding are required for IAP antagonists to induce cIAP1 degradation and protect cells from TNF-induced cell death. The RING functions of cIAP1 are required for full TNF-induced activation of NF-kappaB, however, delayed activation of NF-kappaB still occurs in cIAP1 and -2 double knock-out cells. The RING functions of cIAP1 are also required to prevent constitutive activation of non-canonical NF-kappaB by targeting NIK for proteasomal degradation. However, in cIAP double knock-out cells TWEAK was still able to increase NIK levels demonstrating that NIK can be regulated by cIAP-independent pathways. Finally we show that, unlike IAP antagonists, TWEAK was able to induce degradation of cIAP1 RING mutants. These results emphasize the critical importance of the RING of cIAP1 in many signaling scenarios, but also demonstrate that in some pathways RING functions are not required.


Why do Hispanics have so little employer-sponsored health insurance?
This paper investigates low rates of employer health insurance coverage among Hispanics using national data from the Community Tracking Study Household Survey. Interview language served as a proxy for the degree of assimilation. Findings indicate that English-speaking Hispanics are more similar to whites in their labor market experiences and coverage than they are to Spanish-speaking Hispanics. Spanish-speakers' very low human capital (including their inability to speak English) results in much less access to job-based insurance. Though less important, Spanish-speaking Hispanics' demand for employer-sponsored insurance appears lower than that of English-speaking Hispanics or whites. Results suggest that language and job training may be the most effective way to bolster Hispanics' insurance coverage.


Test-retest reliability of the Purdue Pegboard for persons with multiple sclerosis.
The Purdue Pegboard test often is used in clinical settings to evaluate changes in clients' fine motor dexterity. The purpose of this study was to determine the test-retest reliability and practice effects of the Purdue Pegboard for persons with multiple sclerosis. In addition, this study compared the reliability of one-trial administration to three-trial administration of the four subtests. Thirty-two volunteers from a midwestern community-based maintenance rehabilitation center for persons with multiple sclerosis participated in this study. The participants were administered the four subtests of the Purdue Pegboard, three trials in a row. A second administration was completed 1 week later. Data from 25 participants were analyzed using paired t tests, Pearson product-moment correlations, and intraclass correlation coefficients. The test-retest reliability coefficients ranged from .85 to .90 for one-trial administration and from .92 to .96 for the sum of three trials. No significant practice effects existed except for the sum of three trials of both hands. This study suggests that the one-trial administration of the Purdue Pegboard is a sufficiently reliable assessment to use with persons with multiple sclerosis. Findings further suggest that for a person with multiple sclerosis, any changes in Purdue Pegboard scores using one-trial administration may reflect actual change in that person's dexterity, as no practice effect was demonstrated in this study.


shift from acetoclastic to H2-dependent methanogenesis in a west Siberian peat bog at low pH values and isolation of an acidophilic Methanobacterium strain.
Methane production and archaeal community composition were studied in samples from an acidic peat bog incubated at different temperatures and pH values. H(2)-dependent methanogenesis increased strongly at the lowest pH, 3.8, and Methanobacteriaceae became important except for Methanomicrobiaceae and Methanosarcinaceae. An acidophilic and psychrotolerant Methanobacterium sp. was isolated using H(2)-plus-CO(2)-supplemented medium at pH 4.5.


Associations between Dietary Patterns and Blood Pressure in a Clinical Sample of Overweight Adults.
Dietary pattern analysis provides important evidence revealing diet-disease relationships. It may be especially useful in areas less well researched, such as diet and hypertension in clinical populations. The aim of this study was to identify the association between dietary patterns and blood pressure (BP) in a sample of overweight adults volunteering for a clinical trial for weight loss. This cross-sectional analysis used baseline data from the HealthTrack study, a 12-month randomized controlled trial. Dietary intake was evaluated with 4-day food records. Participants were 328 adults recruited from the Illawarra region of New South Wales, Australia, between May 2014 and April 2015. Resting BP and 24-hour urine sodium and potassium were measured. Dietary patterns were derived by principal component analysis from 21 food groups. Multiple regression analysis was performed to assess the association between the extracted dietary patterns and BP. The participants' mean age was 43.6±8.0 years, mean body mass index was 32.4±4.2, and mean systolic BP/diastolic BP was 124.9±14.5/73.3±9.9 mm Hg. Six major dietary patterns were identified: "nuts, seeds, fruit, and fish," "milk and meat," "breads, cereals, and snacks," "cereal-based products, fats, and oils," "alcohol, eggs, and legumes," and "savoury sauces, condiments, and meat." The "nuts, seeds, fruit, and fish" dietary pattern was significantly and inversely associated with systolic BP (F [7,320]=15.248; P<0.0005; adjusted R2=0.234 and diastolic BP (F [7,320]=17.351; P<0.0005; adjusted R2=0.259) and sodium-to-potassium ratio (F [7,320]=6.210; P<0.0005; adjusted R2=0.100). A dietary pattern rich in nuts, seeds, fruit, and fish was inversely associated with blood pressure in this clinical sample. The findings suggest that current dietary guidelines are relevant to an overweight clinical population and support the value of dietary pattern analysis when exploring the diet-disease relationship.


The effect of long-term opioid use on back-specific disability and health-related quality of life in patients with chronic low back pain.
Opioids are commonly utilized for the treatment of chronic pain. However, research regarding the long-term (≥12 months) outcomes of opioid therapy remains sparse. This study aims to evaluate the effects of long-term opioid therapy on measures of back-specific disability and health-related quality of life in patients with chronic low back pain. In this retrospective cohort study, patients with chronic low back pain who reported consistent opioid use or abstinence for at least 12 months while enrolled in the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation Pain Research Registry were classified as long-term opioid users or nonusers, respectively. For comparison, intermediate-term and short-term opioid users and nonusers were also identified. Multiple linear regression analysis was performed to compare back-specific disability (Roland-Morris Disability Questionnaire [RMDQ]) and health-related quality of life (29-item Patient-Reported Outcomes Measurement Information System [PROMIS]) between opioid users and nonusers while controlling for pain intensity, depression, age, body mass index (BMI), and eight common comorbid conditions (herniated disc, sciatica, osteoporosis, osteoarthritis, heart disease, hypertension, diabetes, and asthma). Statistically significant findings were assessed for clinical relevance. There were 96 long-term opioid users and 204 long-term opioid nonusers. After controlling for potential confounders, long-term opioid use was a predictor of worse back-specific disability (adjusted mean difference=2.85, p<0.001), physical function (adjusted mean difference=-2.90, p=0.001), fatigue (adjusted mean difference=4.32, p=0.001), participation in social roles (adjusted mean difference=-4.10, p<0.001), and pain interference (adjusted mean difference=3.88, p<0.001) outcomes. Intermediate-term opioid use was a predictor of worse back-specific disability (adjusted mean difference=2.41, p<0.001), physical function (adjusted mean difference=-2.26, p=0.003), fatigue (adjusted mean difference=3.70, p=0.002), and sleep disturbance outcomes (adjusted mean difference=3.03, p=0.004), whereas short-term opioid use was a predictor of worse back-specific disability (adjusted mean difference=2.42, p<0.001) and physical function outcomes (adjusted mean difference=-1.90, p<0.001). The findings of this study are largely consistent with existing literature regarding the outcomes of long-term opioid therapy. Taken in conjunction with the well-established risks of opioid medications, these findings draw into question the utility of long-term opioid therapy for chronic low back pain.


An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.
Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. A total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).


Clostridium difficile infections in patients with severe burns.
With improved survival in burn patients, Clostridium difficile infection (CDI) remains a significant potential complication. The incidence of, risk factors for, and outcomes of CDI in severely burned patients are poorly studied and remain unclear. This study involves retrospective case control and cohort studies using electronic medical records from February 1, 2002 to January 31, 2009 at the US Department of Defense's only burn unit. Demographic, risk factor, and outcome data were collected for all C. difficile toxin positive patients in the burn, medical, and surgical intensive care units and the hospital's step down unit along with an additional analysis of a 2:1 matched control of C. difficile toxin negative to positive burn patients. In the burn intensive care unit (BICU) population there was an incidence of 7.9 cases per 10,000 patient days; less than the non-burn unit rate of 15.2 cases (p-value < 0.01). The BICU patients were young males with a median 42% total body surface area burns. There were higher frequencies of operations and prior aminoglycoside use, with longer unit stays and times until death or discharge. There was no difference in treatments, morbidity, or mortality. The comparison of patients with positive and negative C. difficile toxin among those in the BICU revealed few significant differences in risk factors or outcomes. Differences in risk factors between burn and non-burn patients were likely markers of the populations rather than independent risk factors for CDI in the burn population with overall lower rates likely reflective of younger, healthier patients in the BICU and more aggressive infection control practices.


Disruption of TWIST1 translation by 5' UTR variants in Saethre-Chotzen syndrome.
Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region. To determine whether non-coding variants also contribute to SCS, we screened 14 genetically undiagnosed SCS patients using targeted capture sequencing, and identified novel single nucleotide variants (SNVs) in the 5' untranslated region (UTR) of TWIST1 in two unrelated SCS cases. We show experimentally that these variants, which create translation start sites in the TWIST1 leader sequence, reduce translation from the main open reading frame (mORF). This is the first demonstration that non-coding SNVs of TWIST1 can cause SCS, and highlights the importance of screening the 5' UTR in clinically diagnosed SCS patients without a coding mutation. Similar 5' UTR variants, particularly of haploinsufficient genes, may represent an under-ascertained cause of monogenic disease.


HIV-1 prophylactic vaccines: state of the art.
The quest for an effective HIV-1 vaccine began early in the course of the HIV pandemic. Over time, the paradigm has evolved from B cell- towards T cell-based vaccines. Results from initial Phase II/III trials have been disappointing; however, while modest, the unexpected results of the Phase II/III RV144 trial in Thailand have re-energised the field. Indeed a clear correlation was demonstrated in this trial between protection and immunological biomarkers, namely non-neutralising antibodies against the V1V2 region. Recent data obtained from cohorts of recently HIV-1-infected individuals have enabled exploration of the role of neutralising antibodies and their potential use in HIV-1 prevention. Results from non-human primate models using a cytomegalovirus vector have also shown the potential for a prophylactic HIV vaccine to induce effective T cell responses. Finally, the development of new vaccine vectors and trial strategies has also allowed progress in the field. Therefore, HIV-1 vaccine research remains a dynamic field that has also been stimulated by the recent positive results of pre-exposure prophylaxis strategies with antiretrovirals.


Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM): rationale and methods of a longitudinal observational study.
Mortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV prevalence. Children continue to be at high risk of morbidity, mortality and relapse after discharge from hospital although long-term outcomes are not well documented. Better understanding the pathogenesis of SAM and the factors associated with poor outcomes may inform new therapeutic interventions. The Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) study is a longitudinal observational cohort that aims to evaluate the short-term and long-term clinical outcomes of HIV-positive and HIV-negative children with complicated SAM, and to identify the risk factors at admission and discharge from hospital that independently predict poor outcomes. Children aged 0-59 months hospitalised for SAM are being enrolled at three tertiary hospitals in Harare, Zimbabwe and Lusaka, Zambia. Longitudinal mortality, morbidity and nutritional data are being collected at admission, discharge and for 48 weeks post discharge. Nested laboratory substudies are exploring the role of enteropathy, gut microbiota, metabolomics and cellular immune function in the pathogenesis of SAM using stool, urine and blood collected from participants and from well-nourished controls. The study is approved by the local and international institutional review boards in the participating countries (the Joint Research Ethics Committee of the University of Zimbabwe, Medical Research Council of Zimbabwe and University of Zambia Biomedical Research Ethics Committee) and the study sponsor (Queen Mary University of London). Caregivers provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.


Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial.
Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM. 43 client-owned cats with subclinical HCM. Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA. No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups. Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.


Effects of Lamotrigine on brain nitrite and cGMP levels during focal cerebral ischemia in rats.
Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2, 4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. Experiments in primary neuronal cultures implicate nitric oxide (NO) as a mediator of glutamatergic neurotoxicity acting via N-Methyl-D-Aspartate (NMDA) receptors. The effect of glutamate release inhibitor, Lamotrigine upon NO and cGMP production has been examined in focal cerebral ischemia in rats. Focal cerebral ischemia was produced by the permanent occlusion of right middle cerebral artery (MCA) in urethane anesthetized rats. A number of indicators of brain NO production (nitrite, cGMP) were determined in ipsilateral and contralateral cerebral cortex and cerebellum after 0, 10, 60 min of focal cerebral ischemia. The same parameters were measured in rats treated with Lamotrigine (20 mg/kg, i.p.) 30 min before or just after the occlusion of the right MCA.


Molecular and Biological Characterization of Distinct Strains of Jatropha mosaic virus from the Dominican Republic Reveal a Potential to Infect Crop Plants.
In the Dominican Republic (DO), jatropha plants with yellow mosaic symptoms are commonly observed in and around fields of various crop plants. Complete nucleotide sequences of DNA-A and DNA-B components of four bipartite begomovirus isolates associated with symptomatic jatropha plants collected from three geographical locations in the DO were determined. Sequence comparisons revealed highest identities (91 to 92%) with the DNA-A component of an isolate of Jatropha mosaic virus (JMV) from Jamaica, indicating that the bipartite begomovirus isolates from the DO are strains of JMV. When introduced into jatropha seedlings by particle bombardment, the cloned components of the JMV strains from the DO induced stunting and yellow mosaic, indistinguishable from symptoms observed in the field, thereby fulfilling Koch's postulates for the disease. The JMV strains also induced disease symptoms in Nicotiana benthamiana, tobacco, and several cultivars of common bean from the Andean gene pool, including one locally grown in the DO. Asymmetry in the infectivity and symptomatology of pseudorecombinants provided further support for the strain designation of the JMV isolates from the DO. Thus, JMV in the DO is a complex of genetically distinct strains that have undergone local evolution and have the potential to cause disease in crop plants.


Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.
The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. Bill & Melinda Gates Foundation.


White light oblique incidence reflectometer formeasuring absorption and reduced scatteringspectra of tissue-like turbid media.
We designed a quick and inexpensive system for spectral measurements of optical properties including absorption coefficient and reduced scattering coefficient. The system was based on oblique incidence reflectometry.[1] A broad band light source was coupled into an optic fiber to deliver light obliquely to turbid media. Nine detection optic fibers were used to collect the diffuse reflectance as a function of source-detector distance. The relative diffuse reflectance profile was used to deduce the absorption and reduced scattering spectra. The system was able to acquire data in a wavelength range of 256 nm within a fraction of a second.


Recombinant proteins for neurodegenerative diseases: the delivery issue.
Tackling neurodegenerative diseases represents a formidable challenge for our ageing society. Recently, major achievements have been made in understanding the molecular mechanisms responsible for such diseases, and, simultaneously, numerous proteins such as neurotrophic factors, anti-apoptotic or anti-oxidant have been identified as potential therapeutic agents. Although many neurotrophic factors have been tested on individuals suffering from various neurodegenerative disorders, to date none has shown efficacy. Inadequate protein delivery is believed to be part of the problem. Recent improvements in pump technology, as well as in cell and gene therapy, are providing innovative ways to allow localized, regulatable delivery of proteins in brain parenchyma, opening new avenues for clinical trials in the not so distant future.


Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres.
A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS.


Detection of gamma rays from a starburst galaxy.
Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of approximately 10(15) electron volts. We report the detection of gamma rays--tracers of such cosmic rays--from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H.E.S.S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.


Relationship between body composition, leg strength, anaerobic power, and on-ice skating performance in division I men's hockey athletes.
The purpose of this study was to examine relationships between laboratory tests and on-ice skating performance in division I men's hockey athletes. Twenty-one men (age 20.7 +/- 1.6 years) were assessed for body composition, isokinetic force production in the quadriceps and hamstring muscles, and anaerobic muscle power via the Wingate 30-second cycle ergometer test. Air displacement plethysmography was used to determine % body fat (%FAT), fat-free mass (FFM), and fat mass. Peak torque and total work during 10 maximal effort repetitions at 120 degrees .s were measured during concentric muscle actions using an isokinetic dynamometer. Muscle power was measured using a Monark cycle ergometer with resistance set at 7.5% of body mass. On-ice skating performance was measured during 6 timed 89-m sprints with subjects wearing full hockey equipment. First length skate (FLS) was 54 m, and total length skate (TLS) was 89 m with fastest and average skating times used in the analysis. Correlation coefficients were used to determine relationships between laboratory testing and on-ice performance. Subjects had a body mass of 88.8 +/- 7.8 kg and %FAT of 11.9 +/- 4.6. First length skate-Average and TLS-Average skating times were moderately correlated to %FAT ([r = 0.53; p = 0.013] and [r = 0.57; p = 0.007]) such that a greater %FAT was related to slower skating speeds. First length skate-Fastest was correlated to Wingate percent fatigue index (r = -0.48; p = 0.027) and FLS-Average was correlated to Wingate peak power per kilogram body mass (r = -0.43; p = 0.05). Laboratory testing of select variables can predict skating performance in ice hockey athletes. This information can be used to develop targeted and effective strength and conditioning programs that will improve on-ice skating speed.


[Phlebotomines (Diptera: Psychodidae) focusing visceral leishmaniasis in the State of Mato Grosso do Sul, Brazil].
In the Americas, Lutzomyia longipalpis has been incriminated as the vector of visceral leishmaniasis in almost all the areas in which this disease has been reported. The notification of human cases of visceral leishmaniasis and the presence of dogs with an appearance suggestive of the disease in the country of Corumbá, Mato Grosso do Sul State, Brazil, led us to undertake an entomological investigation in this area, for the purpose of identifying the phlebotomine vector. The county of Corumbá is located in the Pantanal region and its urban area is situated at 18 degrees 59' 44" South and 57 degrees 39' 16" West. The research project was carried out in peri and intradomiciliary environments, in three urban districts, one of which was central and the other two on the outskirts, and in a cave situated outside the urban perimeter. Most of the captures were made weekly with light automatic traps, in the period from February 1984 to December 1986. Meteorological data for this period were obtained from the city's meteorological station and those for the period from 1925 to 1982 from the literature. The urban phlebotomine fauna consisted of eight species and was similar to that of the cave, except that in the latter the species were more abundant. Lutzomyia cruzi was predominant in the peri and intradomiciliary environments. Its prevalence in the central district was of 90.3% and lower in the outskirts. Lu. forattinii presented considerable prevalence (39.0%) in one of the outlying districts too. In the cave, Lu. corumbaensis was the predominant species, followed by Lu. sordellii, Lu. forattinii, Lu. peresi and Lu. cruzi. The impact of the climatic condition and the action of insecticides in the urban area on the frequency of the species, as well as the use of the cave as a breeding ground by the phlebotomines, in view of the changes in the sex rate, are commented. Data on anthropophily and captures of Lu. forattinii using dog bait have been added. The predominance of Lu. cruzi in the urban area; the great prevalence of Lu. forattinii in most of the outlying areas studied and the anthropophily of this latter species, as well as the strong affinity of these species with Lu. longipalpis, the main vector of visceral leishmaniais in other areas of the Americas, suggest the participation of both in the transmission of the disease in Corumbá.


In Vivo Characterization of an AHR-Dependent Long Noncoding RNA Required for Proper Sox9b Expression.
Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most-reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long noncoding RNA (slincR) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2 dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurologic and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway.


MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress.
Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3-5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.


Epidemiology of health effects of radiofrequency exposure.
We have undertaken a comprehensive review of epidemiologic studies about the effects of radiofrequency fields (RFs) on human health in order to summarize the current state of knowledge, explain the methodologic issues that are involved, and aid in the planning of future studies. There have been a large number of occupational studies over several decades, particularly on cancer, cardiovascular disease, adverse reproductive outcome, and cataract, in relation to RF exposure. More recently, there have been studies of residential exposure, mainly from radio and television transmitters, and especially focusing on leukemia. There have also been studies of mobile telephone users, particularly on brain tumors and less often on other cancers and on symptoms. Results of these studies to date give no consistent or convincing evidence of a causal relation between RF exposure and any adverse health effect. On the other hand, the studies have too many deficiencies to rule out an association. A key concern across all studies is the quality of assessment of RF exposure. Despite the ubiquity of new technologies using RFs, little is known about population exposure from RF sources and even less about the relative importance of different sources. Other cautions are that mobile phone studies to date have been able to address only relatively short lag periods, that almost no data are available on the consequences of childhood exposure, and that published data largely concentrate on a small number of outcomes, especially brain tumor and leukemia.


Transplant-associated skin cancer: role of reducing immunosuppression.
This article explores the role of reducing immunosuppression as a therapeutic strategy for the problem of transplant-associated skin cancer. The specific issue of immunosuppression reduction is based on a brief historic review of the epidemiology of skin cancer in transplant patients, followed by a description of the role of immunosuppression as a cause of skin cancer. Finally, the literature pertaining to the hypothesis that reducing immunosuppression in solid organ transplant recipients favorably impacts both the incidence of cutaneous malignancy and outcomes relating to individual aggressive malignancies is presented.


Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.
Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml-1 fluconazole and 64 μg ml-1 or 128 μg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.


Research subject advocacy: program implementation and evaluation at clinical and translational science award centers.
In 2000, the National Center for Research Resources mandated that general research centers create a research subject advocate (RSA) position. In 2008, the Clinical and Translational Science Award (CTSA) consortium endorsed a new advocacy model based on four RSA Best Practice Functions. The authors surveyed CTSA centers to learn about their implementation of programs to fulfill the RSA functions. In 2010, the RSA taskforce developed a two-part online survey to examine leadership, organizational structure, governance, scope, collaboration and integration, and funding and evaluation of RSA activities implemented at CTSA centers. Respondents from 45 RSA programs at 43 CTSA centers completed the survey. Senior university or CTSA officials led all programs. Ninety-six percent (43/45) of programs were funded by a CTSA core. Eighty percent (36/45) designated an individual "RSA." Ninety-eight percent (44/45) provided diverse services either in collaboration with or complementary to other departments, including development of data and safety monitoring plans (16/45; 36%), informed consent observation (10/45; 22%), training responsive to audit findings (12/45; 27%), and direct advocacy services to participants (11/45; 24%). Eighty-six percent (24/28) reported qualitative evaluation methods for these activities. RSA programs conduct both collaborative and unique research protection activities. This survey, an initial step in developing a more robust mechanism for evaluating RSA programs, collected valuable feedback. The authors recommend defining and developing outcome-based evaluation measures that take the heterogeneity of the individual RSA programs into account while advancing their value and effectiveness in protecting human research subject participants.


Evaluation of compressive strength and stiffness of grouted soils by using elastic waves.
Cement grouted soils, which consist of particulate soil media and cementation agents, have been widely used for the improvement of the strength and stiffness of weak ground and for the prevention of the leakage of ground water. The strength, elastic modulus, and Poisson's ratio of grouted soils have been determined by classical destructive methods. However, the performance of grouted soils depends on several parameters such as the distribution of particle size of the particulate soil media, grouting pressure, curing time, curing method, and ground water flow. In this study, elastic wave velocities are used to estimate the strength and elastic modulus, which are generally obtained by classical strength tests. Nondestructive tests by using elastic waves at small strain are conducted before and during classical strength tests at large strain. The test results are compared to identify correlations between the elastic wave velocity measured at small strain and strength and stiffness measured at large strain. The test results show that the strength and stiffness have exponential relationship with elastic wave velocities. This study demonstrates that nondestructive methods by using elastic waves may significantly improve the strength and stiffness evaluation processes of grouted soils.


A general classification of New World Leishmania using numerical zymotaxonomy.
More than 250 strains of Leishmania isolated from different localities and hosts in the New World were analyzed by enzyme electrophoresis, and their electromorphic profiles were compared with 19 reference strains representing most of the described species of this parasite. The 18 enzymic loci analyzed were very polymorphic, and the strains were classified into 44 zymodemes, each grouping strains with the same enzyme profiles. Each zymodeme was considered as an elementary taxon and the phenetic and phylogenetic relationships were determined by agglomerative hierarchical, ordination, and cladistic techniques. The different classification methods produced very similar results. The 44 zymodemes could be clustered into two groups, corresponding to the subgenera Leishmania and Viannia, by the numerical methods. The subgenus Viannia was shown to be monophyletic and could be further divided into species complexes representing L. braziliensis, L. naiffi, and L. guyanensis/L. panamensis/L. shawi, as well as some isolated taxa including L. lainsoni. The subgenus Leishmania, on the other hand, was polyphyletic, with New World isolates related to L. major clustered separately from the L. mexicana species complex. Most of the other zymodemes in this group represented independent taxa. The results confirm Viannia as a valid taxon but suggest that the status of the subgenus Leishmania should be further investigated. Leishmania braziliensis and L. naiffi were shown to be the most polymorphic species, while L. guyanensis, in spite of being the most common species found in this study, was remarkably homogeneous. The only variants were found south of the Amazon river. North of this river, the species was monomorphic.


Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet.
Both foscarnet (PFA) and zidovudine (AZT) select for drug-resistant variants of human immunodeficiency virus type 1 (HIV-1), but the interactions between the mutations causing such resistance are unknown. The introduction of the previously identified PFA resistance mutation W to G at codon 88 (W88G), E89K, L92I, or Q161L into an HIV-1 strain having the four known AZT resistance mutations completely reversed high-level AZT resistance. Two additional PFA resistance mutations, W88S and S156A, partially suppressed AZT resistance. Phenotypic reversion of AZT resistance by W88S, W88G, E89K, L921, and S156A was associated with a concomitant suppression of PFA resistance. The degree to which PFA resistance mutations reversed AZT resistance was directly correlated with each mutation's ability to confer high-level PFA resistance (> or = 5.0-fold) and AZT hypersusceptibility in a wild-type genetic background. Highly PFA-resistant HIV- 1 strains were hypersusceptible to AZT; conversely, AZT-resistant strains with M41L and T215Y; M41L, L210W, and T215Y; or M41L, D67N, K70R, and T215Y mutations were 2.2- to 2.5-fold hypersusceptible to PFA. Prolonged in vitro selection of wild-type or AZT-resistant HIV-1 strains with the combination AZT and PFA failed to generate coresistant virus, indicating that dual resistance was relatively difficult to achieve. Strains selected by passage in PFA plus AZT were phenotypically PFA resistant and AZT susceptible despite multiple reverse transcriptase mutations known to confer AZT resistance. These data show that PFA resistance mutations can phenotypically reverse AZT resistance and that AZT and PFA resistance might be mutually exclusive. The reciprocal interactions between AZT and PFA resistance-conferring mutations have implications for structure-function studies of the HIV-1 reverse transcriptase.


Five years of ChemRxiv: where we are and where we go from here.
ChemRxiv was launched on August 15, 2017 to provide researchers in chemistry and related fields a home for the immediate sharing of their latest research. In the past five years, ChemRxiv has grown into the premier preprint server for the chemical sciences, with a global audience and a wide array of scholarly content that helps advance science more rapidly. On the service's fifth anniversary, we would like to reflect on the past five years and take a look at what is next for ChemRxiv.


Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson's Disease.
Parkinson's disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.


Synthetic double-stranded RNA induces interleukin-32 in bronchial epithelial cells.
Interleukin (IL)-32 is a novel cytokine and is involved in the pathogenesis of various inflammatory diseases, including asthma and COPD. However, the regulatory mechanisms of IL-32 expression and its precise pathogenic role remain to be defined. Given that viral infections are known to potentially cause and exacerbate airway inflammation, in this study, we investigated the expression of IL-32 induced by synthetic double-stranded (ds) RNA, and its signaling mechanisms involved. Bronchial epithelial cells were stimulated with synthetic dsRNA poly I:C. The levels of IL-32 expression were analyzed using real-time PCR and ELISA. The involvement of transforming growth factor β-activated kinase 1 (TAK1) and a subunit of nuclear factor-κB (NF-κB), p65 was determined by western blot analyses. TAK1 inhibitor, 5Z-7-Oxozeaenol and NF-κB inhibitor, BAY 11-7082 were added to the culture to identify key signaling events leading to the expression of IL-32. Finally, the effect of short interfering RNAs (siRNAs) targeting TAK1 and p65 was investigated. dsRNA significantly induced IL-32 gene and protein expression, concomitant with activation of TAK1 and p65. Pretreatment of 5Z-7-Oxozeaenol diminished dsRNA-induced phosphorylation of NF-κB. Both 5Z-7-Oxozeaenol and BAY 11-7082 significantly abrogated dsRNA-induced IL-32 production. Moreover, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-32. The expression of IL-32 is induced by dsRNA via the TAK1-NF-κB signaling pathway in bronchial epithelial cells. IL-32 is involved in the pathogenesis of airway inflammation, and may be a novel therapeutic target for airway inflammatory diseases.


A strategy for intestinal obstruction of peritoneal carcinomatosis.
Obstruction of the small intestine caused by peritoneal carcinomatosis is properly palliated by resection, bypass, and stoma formation. If none of these procedures is applicable, palliation may be achieved by the permanent placement of a long intraluminal decompressive (Baker) tube. Twelve patients have been treated in this manner, nine of them living long enough to exhibit the capacity to eat and drink without repetitive vomiting. The Baker tube was passed across the abdominal wall, inserted into the proximal jejunum, and then passed as far as practical down to the surgically nontreatable obstruction. Venting of the small intestine distally allows continuing decompression, which thereby permits mucosal functions proximally. This technique allows the surgeon to do something beneficial for these unfortunate patients when the established maneuvers of bypass, resection, or stoma formation are pointless.


Comparative study of the word capacity and episodic memory of patients with degenerative dementia.
Although the absence of memory impairment was considered among the diagnostic criteria to differentiate Alzheimer's disease (AD) from Behavioural Variant of Frontotemporal Dementia (bvFTD), current and growing evidence indicates that a significant percentage of cases of bvFTD present with episodic memory deficits. In order to compare the performance profile of the naming capacity and episodic memory in patients with AD and bvFTD the present study was designed. Cross-sectional and analytical study with control group (32 people). The study included 42 people with probable AD and 22 with probable bvFTD, all over 60 years old. Uniform Data Set instruments validated in Spanish were used: Multilingual Naming Test (MINT), Craft-21 history and Benson's complex figure, among others. A higher average age was observed among the patients with AD. The naming capacity was much lower in patients with bvFTD compared to patients with AD, measured according to the MINT and the nouns/verbs naming coefficient. All patients with bvFTD, 73.81% of those with AD and only 31.25% of the control group failed to recognise Benson's complex figure. All differences were statistically significant (p < 0.001). This study confirms the amnesic profile of patients with AD and reveals the decrease in naming capacity in patients with bvFTD, an area of language that is typically affected early on with executive functions, according to recent findings. Patients with AD perform worse in verbal and visual episodic memory tasks, while patients with bvFTD perform worse in naming tasks. These findings open the possibility of exploring the mechanisms of prefrontal participation in episodic memory, typically attributed to the hippocampus.


AtRAB-H1b and AtRAB-H1c GTPases, homologues of the yeast Ypt6, target reporter proteins to the Golgi when expressed in Nicotiana tabacum and Arabidopsis thaliana.
Ypt/Rab GTPases act as key regulators of intracellular traffic through the conformational differences exhibited by their GTP or GDP-bound forms. In this paper, two Arabidopsis Ypt6 homologues, AtRAB-H1(b) and AtRAB-H1(c) were characterized and compared. Using a live cell imaging approach, it is shown that yellow fluorescent protein-fusions (YFP) of AtRAB-H1(b) and AtRAB-H1(c) locate to the Golgi and to the cytosol in both Nicotiana tabacum and in Arabidopsis thaliana. In addition, YFP-AtRAB-H1(b) targets an as yet unknown compartment not labelled by YFP-AtRAB-H1(c) or Golgi markers. It is also shown that the subcellular location of YFP-AtRAB-H1(b) and YFP-AtRAB-H1(c) is affected by the state of GTP-binding and that expression of a GTP-deficient mutant results in increased apoplastic fluorescence of a secretory form of YFP.


1D and 2D arrays of coupled photonic crystal cavities with a site-controlled quantum wire light source.
We investigated experimentally 1D and 2D arrays of coupled L3 photonic crystal cavities. The optical modes of the coupled cavity arrays are fed by a site-controlled quantum wire light source. By performing photoluminescence measurements and relying on near-field calculation of the cavitiy modes, we evidence optical coupling between the cavities as well as supermode delocalization. In particular, for small cavity separations, fabrication induced disorder effects are shown to be negligible compared to optical coupling between cavities.


Targeting of plasminogen activator inhibitor-1 activity promotes elimination of chronic myeloid leukemia stem cells.
Therapeutic strategies that target leukemic stem cells (LSCs) provide potential advantages in the treatment of chronic myeloid leukemia (CML). Here, we show that selective blockade of plasminogen activator inhibitor-1 (PAI-1) enhances the susceptibility of CML-LSCs to tyrosine kinase inhibitor (TKI), which facilitates the eradication of CML-LSCs and leads to sustained remission of the disease. We demonstrated for the first time that TGF-β-PAI-1 axis was selectively augmented in CML-LSCs in the bone marrow (BM), whereby protecting CML-LSCs from TKI treatment. Furthermore, the combined administration of TKI plus a PAI-1 inhibitor, in a mouse model of CML, significantly enhanced the eradication of CML cells in the BM and prolonged the survival of CML mice. The combined therapy of imatinib and a PAI-1 inhibitor prevented the recurrence of CML-like disease in serially transplanted recipients, indicating the elimination of CML-LSCs. Interestingly, PAI-1 inhibitor treatment augmented membrane-type matrix metalloprotease-1 (MT1-MMP)-dependent motility of CML-LSCs, and the anti-CML effect of PAI-1 inhibitor was extinguished by the neutralizing antibody for MT1-MMP, underlining the mechanistic importance of MT1-MMP. Our findings provide evidence of, and a rationale for, a novel therapeutic tactic, based on the blockade of PAI-1 activity, for CML patients.


Grasha-Richmann college students' learning styles of classroom participation: role of gender and major.
This study aimed to investigate the male and female students' learning styles of classroom participation and these styles' differences between Humanities and Science majors. 1039 individuals were selected through the proportional stratified random sampling method among undergraduate and graduate students in Humanities (n=421) and Science (n=618) faculties of Tehran University. In the Humanities group, there were 285 females and 136 males, and in the Science group, there were 208 females and 410 males. The participants answered the Grasha-Riechmann student learning styles scale. The findings indicated that the females obtained significantly higher means in collaborative, participative, and dependent styles than males, but in avoidant, and independent styles, the means for males were higher than those for females. Also, the science group's means in collaborative, participative, dependent, and competitive styles were significantly higher than those for the humanities group. According to the findings, it seems that due to psychological characteristics, female students tend to collaborate with other students of the same sex and participate in their activities. In this way, they also are more dependent on their teacher and classroom, because otherwise they will face some problems such as anxiety. In addition, it seems that science students in comparison to humanities students are more participative and collaborative because they need more collaboration in their projects and course work.


Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment.
Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain, change in bowel habit, and bloating. It has traditionally been viewed as a disorder of visceral hypersensitivity heavily influenced by stress, and therefore therapeutic strategies to date have largely reflected this. However, more recently, there is good evidence for a role of the gastrointestinal (GI) microbiota in its pathogenesis. Changes in fecal microbiota, the use of probiotics, the phenomenon of postinfectious IBS, and the recognition of an upregulated host immune system response suggest that an interaction between the host and GI microbiota may be important in the pathogenesis of IBS. This article explores the role of the GI microbiota in IBS and how their modification might lead to therapeutic benefit.


Patent ductus arteriosus repair in general practice.
A 3-month-old female German Shepherd puppy was presented for routine vaccination. Clinical evaluation revealed a grade 5/6 continuous murmur with the point of maximal intensity over the left 4th intercostal space. Echocardiography revealed a patent ductus arteriosus (PDA). The PDA was closed by a team of general practitioners using the Jackson-Henderson technique, via a standard 4th intercostal thoracotomy. A multi-modal approach to analgesia and premedication was employed. A successful outcome was achieved with no murmur or evidence of cardiac disease present 6 months after surgical occlusion. The literature is reviewed with an emphasis placed on choosing techniques that are appropriate to the level of expertise of the surgical and anaesthetic teams, as well as the surgical facilities available.


Effectiveness of an HIV prevention program for women visiting their incarcerated partners: the HOME Project.
Having an incarcerated partner presents a unique HIV risk for women, particularly low-income women of color. We developed a population-specific risk reduction intervention for women visiting men in prison that was peer educator-based and included individual and community-level intervention components. Women who were assessed prior to the intervention period had a positive association between the number of unprotected penetrative intercourse (UPI) episodes prior to their partners' incarceration and the number of UPI episodes following partners' release from prison. However, this association was negated among women assessed during the intervention. Intervention participants also were more likely to be tested for HIV, to have partners who got tested, and to talk with their partners about significantly more HIV-related topics. Conducting intervention and evaluation activities with women visiting incarcerated men is feasible and is a useful model for reaching more at-risk women.


Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease.
Purpose To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on April 6, 2017.


Effects of follicle size and electrolytes and glucose in maturation medium on nuclear maturation and developmental competence of bovine oocytes.
The concentrations of electrolytes (Na, K, Cl, Mg and Ca) and glucose in small follicle (SF) follicular fluid (SFF) and large follicle (LF) follicular fluid (LFF) from slaughterhouse-derived ovaries were studied. Oocytes were matured in medium based on synthetic oviductal fluid. The effects of various concentrations of electrolytes (Na, K, Ca and Mg) and glucose in the maturation medium on the progression of nuclear maturation and subsequent development were also studied. K in SFF was significantly greater than that in LFF. The Mg concentration in follicular fluid (FF) is 2.0-2.3 mM, which is greater than the concentration present in medium generally used for culture. The glucose concentration in FF is about 3.5-3.9 mM and rapidly decreases during the preservation of ovaries. LF oocytes resumed nuclear maturation and progressed to the M2 stage significantly faster than those collected from SF oocytes. In addition, more LF oocytes developed to blastocysts than did SF oocytes. Changing the Na/K ratio in the maturation medium from 16 to 24 did not affect either the progression of nuclear maturation or the rate of development. A low concentration of Mg (0.5 mM) combined with a low Ca concentration (0.5 mM) inhibited the rate of development, but did not affect the progression of nuclear maturation. On the other hand, increasing the Mg concentration to 2.0 mM from 0.5 mM hastened the progression of nuclear maturation and improved the rate of blastulation, irrespective of the Ca concentration. The progression of nuclear maturation was faster and the rate of development was greater with 5.56 mM glucose than with 1.5 mM glucose. The difference in time needed to progress to M2 among the experiment was about 2-3 h. Therefore, prolonging the maturation periods from 21 to 24 h did not change the rate of development. Our results show that the concentrations of Mg and glucose in the maturation medium and the follicle size enveloping the oocyte affect the progression of nuclear maturation and subsequent development. The time requirement for oocytes to reach M2 is strongly related to the developmental competence of the oocytes.


Sparse Representation of Deformable 3D Organs with Spherical Harmonics and Structured Dictionary.
This paper proposed a novel algorithm to sparsely represent a deformable surface (SRDS) with low dimensionality based on spherical harmonic decomposition (SHD) and orthogonal subspace pursuit (OSP). The key idea in SRDS method is to identify the subspaces from a training data set in the transformed spherical harmonic domain and then cluster each deformation into the best-fit subspace for fast and accurate representation. This algorithm is also generalized into applications of organs with both interior and exterior surfaces. To test the feasibility, we first use the computer models to demonstrate that the proposed approach matches the accuracy of complex mathematical modeling techniques and then both ex vivo and in vivo experiments are conducted using 3D magnetic resonance imaging (MRI) scans for verification in practical settings. All results demonstrated that the proposed algorithm features sparse representation of deformable surfaces with low dimensionality and high accuracy. Specifically, the precision evaluated as maximum error distance between the reconstructed surface and the MRI ground truth is better than 3 mm in real MRI experiments.


Blueberry-Based Meals for Obese Patients with Metabolic Syndrome: A Multidisciplinary Metabolomic Pilot Study.
A pilot study was carried out on five obese/overweight patients suffering from metabolic syndrome, with the aim to evaluate postprandial effects of high fat/high glycemic load meals enriched by blueberries. Postprandial urine samples were analyzed by 1H-NMR spectroscopy after 2 and 4 h from ingestion to identify potential markers of blueberry intake. Significant decrease of methylamines, acetoacetate, acetone and succinate, known indicators of type 2 diabetes mellitus, were observed after the intake of meals enriched with blueberries. On the other hand, an accumulation of p-hydroxyphenyl-acetic acid and 3-(3'-hydroxyphenyl)-3-hydropropionic acid originating from gut microbial dehydrogenation of proanthocyanidins and procyanidins was detected. Real-time PCR-analysis of mRNAs obtained from mononuclear blood cells showed significant changes in cytokine gene expression levels after meals integrated with blueberries. In particular, the mRNAs expression of interleukin-6 (IL-6) and Transforming Growth Factor-β (TGF-β), pro and anti-inflammation cytokines, respectively, significantly decreased and increased after blueberry supplementation, indicating a positive impact of blueberry ingestion in the reduction of risk of inflammation. The combined analysis of the urine metabolome and clinical markers represents a promising approach in monitoring the metabolic impact of blueberries in persons with metabolic syndrome.


Input-specific control of reward and aversion in the ventral tegmental area.
Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.


Spinal Subdural Abscess Following Laminectomy for Symptomatic Stenosis: A Report of 2 Cases and Review of the Literature.
BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.