Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

Reproductive and hormonal factors and mortality among women with colorectal cancer in the NIH-AARP Diet and Health Study

BACKGROUND: Although use of menopausal hormone therapy (MHT) and some reproductive factors have been associated with colorectal cancer (CRC) risk, relations between these factors and survival after CRC diagnosis are unclear. METHODS: Among 2053 post-menopausal women diagnosed with incident CRC in the NIH-AARP Diet and Health Study, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards regression to test associations between oral contraceptive (OC) use, menarche age, age at first birth, parity, menopausal age, and MHT use with all-cause and CRC-specific mortality. RESULTS: There were 759 deaths (332 CRC-related deaths) over a median follow-up of 7.7 years. We observed no statistically significant associations between OC use, menarche age, age at first birth, parity, menopausal age, and mortality. Compared with never MHT use, former use was not associated with mortality, but we found an inverse association among baseline current users, for both all-cause (HR=0.79, 95% CI 0.66–0.94) and CRC mortality (0.76, 0.59–0.99). CONCLUSION: Future studies should further focus on the mechanisms by which exogenous oestrogen exposure might affect tumour progression and CRC survival

Development, characterization, and stability of O/W pepper nanoemulsions produced by high-pressure homogenization

Interest in the utilization of bioactive plant compounds in foods has increased due to their biochemical activities (antioxidant, antimicrobial, etc.), and as alternatives in the reduction of the use of high concentrations of chemical substances. However, some of these additives are hydrophobic, thus being harder to disperse into the food matrix, which is generally water-based. A good alternative is the use of low concentrations of these compounds as nanoemulsions. The objective of the present study was to develop oil-in-water nanoemulsions containing dedo-de-moça pepper extract for food applications. Research in the development of these nanoemulsions was carried out using a high-speed homogenizer, followed by a high-pressure homogenizer. The influence of the following parameters was assessed: type and concentration of surfactants, hidrophilic-lipophilic balance, lipid/aqueous phase ratio, surfactant/oil ratio, pepper extract composition in nanoemulsion, and processing conditions. Nanoemulsions were evaluated by environmental (centrifugal and thermal) and storage stabilities, characterized by average droplet size and -potential measurements, color, interfacial tension, atomic force, and cryo-scanning electron microscopy. Those with average droplet size between 132 ± 2.0 and 145 ± 1.0 nm were developed depending on working pressure and number of cycles; -potential was around 36.71 ± 0.62 mV and the best nanoemulsion was stable to centrifugation and most of the thermal stresses. Droplets were characterized with cryo-scanning electron microscopy as being spherical, homogeneous, and stable, and remained stable when stored at 4 °C and room temperature for over 120 days. The pepper nanoemulsion, developed in the present study, has potential applications in the food industry.The first author gratefully acknowledges the CNPq and CAPES (National Council for Scientific and Technological Development, Program Science without Boarder) for the BSWE^ PhD (Process 236877/2012-1) fellowship, and CAPES for the national PhD fellowship. The last author acknowledges the São Paulo Research Foundation (FAPESP) Brazil, for the grant (CEPID-FoRC, 2013/07914-8).info:eu-repo/semantics/publishedVersio

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change

Identification and characterization of microRNAs expressed in the African malaria vector Anopheles funestus life stages using high throughput sequencing

Background: Over the past several years, thousands of microRNAs (miRNAs) have been identified in the genomes of various insects through cloning and sequencing or even by computational prediction. However, the number of miRNAs identified in anopheline species is low and little is known about their role. The mosquito Anopheles funestus is one of the dominant malaria vectors in Africa, which infects and kills millions of people every year. Therefore, small RNA molecules isolated from the four life stages (eggs, larvae, pupae and unfed adult females) of An. funestus were sequenced using next generation sequencing technology. Results: High throughput sequencing of four replicates in combination with computational analysis identified 107 mature miRNA sequences expressed in the An. funestus mosquito. These include 20 novel miRNAs without sequence identity in any organism and eight miRNAs not previously reported in the Anopheles genus but are known in non-anopheles mosquitoes. Finally, the changes in the expression of miRNAs during the mosquito development were determined and the analysis showed that many miRNAs have stage-specific expression, and are co-transcribed and co-regulated during development. Conclusions: This study presents the first direct experimental evidence of miRNAs in An. funestus and the first profiling study of miRNA associated with the maturation in this mosquito. Overall, the results indicate that miRNAs play important roles during the growth and development. Silencing such molecules in a specific life stage could decrease the vector population and therefore interrupt malaria transmission.IS

Using rapid diagnostic tests as source of malaria parasite DNA for molecular analyses in the era of declining malaria prevalence

BACKGROUND: Malaria prevalence has recently declined markedly in many parts of Tanzania and other sub-Saharan African countries due to scaling-up of control interventions including more efficient treatment regimens (e.g. artemisinin-based combination therapy) and insecticide-treated bed nets. Although continued molecular surveillance of malaria parasites is important to early identify emerging anti-malarial drug resistance, it is becoming increasingly difficult to obtain parasite samples from ongoing studies, such as routine drug efficacy trials. To explore other sources of parasite DNA, this study was conducted to examine if sufficient DNA could be successfully extracted from malaria rapid diagnostic tests (RDTs), used and collected as part of routine case management services in health facilities, and thus forming the basis for molecular analyses, surveillance and quality control (QC) testing of RDTs. METHODS: One hyper-parasitaemic blood sample (131,260 asexual parasites/μl) was serially diluted in triplicates with whole blood and blotted on RDTs. DNA was extracted from the RDT dilution series, either immediately or after storage for one month at room temperature. The extracted DNA was amplified using a nested PCR method for Plasmodium species detection. Additionally, 165 archived RDTs obtained from ongoing malaria studies were analysed to determine the amplification success and test applicability of RDT for QC testing. RESULTS: DNA was successfully extracted and amplified from the three sets of RDT dilution series and the minimum detection limit of PCR was <1 asexual parasite/μl. DNA was also successfully amplified from (1) 70/71 (98.6%) archived positive RDTs (RDTs and microscopy positive) (2) 52/63 (82.5%) false negative RDTs (negative by RDTs but positive by microscopy) and (3) 4/24 (16.7%) false positive RDTs (positive by RDTs but negative by microscopy). Finally, 7(100%) negative RDTs (negative by RDTs and microscopy) were also negative by PCR. CONCLUSION: This study showed that DNA extracted from archived RDTs can be successfully amplified by PCR and used for detection of malaria parasites. Since Tanzania is planning to introduce RDTs in all health facilities (and possibly also at community level), availability of archived RDTs will provide an alternative source of DNA for genetic studies such as continued surveillance of parasite resistance to anti-malarial drugs. The DNA obtained from RDTs can also be used for QC testing by detecting malaria parasites using PCR in places without facilities for microscopy

Polymorphism in the Tyrosine Hydroxylase (TH) Gene Is Associated with Activity-Impulsivity in German Shepherd Dogs

We investigated the association between repeat polymorphism in intron 4 of the tyrosine hydroxylase (TH) gene and two personality traits, activity-impulsivity and inattention, in German Shepherd Dogs. The behaviour of 104 dogs was characterized by two instruments: (1) the previously validated Dog-Attention Deficit Hyperactivity Disorder Rating Scale (Dog-ADHD RS) filled in by the dog owners and (2) the newly developed Activity-impulsivity Behavioural Scale (AIBS) containing four subtests, scored by the experimenters. Internal consistency, inter-observer reliability, test-retest reliability and convergent validity were demonstrated for AIBS

Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system

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