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1.
New Solut ; 34(1): 10-21, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38426812

RESUMEN

Science can provide accurate information to society to inform decision-making and behavior. One contemporary topic in which the science is very clear, yet behavioral change has lagged, is climate change mitigation. Climate change scientists use evidence-based research to advocate to the public to adopt emission-reducing behaviors in various sectors such as transportation and food. However, scientists themselves often do not change their own behaviors according to the scientific consensus. We present a case study of a group of natural sciences PhD students, who, when presented with evidence and an opportunity for a behavioral change with implications for climate change mitigation, demonstrated defensive reactions that would undoubtedly frustrate these same scientists if they were doing public outreach about their own work. Our goal is to raise awareness that we scientists do not always practice what we preach but could perhaps overcome this by understanding the defense mechanisms that impede meaningful change.

5.
Clin Infect Dis ; 75(1): e241-e248, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34519774

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. METHODS: We recruited coronavirus disease 2019 (COVID-19) cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to 2 visits 2 days apart. We quantified and sequenced viral RNA, cultured virus, and assayed serum samples for anti-spike and anti-receptor binding domain antibodies. RESULTS: We enrolled 49 seronegative cases (mean days post onset 3.8 ±â€…2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 36% of fine (≤5 µm), 26% of coarse (>5 µm) aerosols, and 52% of fomite samples overall and in all samples from 4 alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6- to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4- to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. CONCLUSIONS: SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Humanos , Máscaras , ARN Viral , Aerosoles y Gotitas Respiratorias
6.
Indoor Air ; 32(1): e12965, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34816493

RESUMEN

The evolution of SARS-CoV-2 virus has resulted in variants likely to be more readily transmitted through respiratory aerosols, underscoring the increased potential for indoor environmental controls to mitigate risk. Use of tight-fitting face masks to trap infectious aerosol in exhaled breath and reduce inhalation exposure to contaminated air is of critical importance for disease control. Administrative controls including the regulation of occupancy and interpersonal spacing are also important, while presenting social and economic challenges. Indoor engineering controls including ventilation, exhaust, air flow control, filtration, and disinfection by germicidal ultraviolet irradiation can reduce reliance on stringent occupancy restrictions. However, the effects of controls-individually and in combination-on reducing infectious aerosol transfer indoors remain to be clearly characterized to the extent needed to support widespread implementation by building operators. We review aerobiologic and epidemiologic evidence of indoor environmental controls against transmission and present a quantitative aerosol transfer scenario illustrating relative differences in exposure at close-interactive, room, and building scales. We identify an overarching need for investment to implement building controls and evaluate their effectiveness on infection in well-characterized and real-world settings, supported by specific, methodological advances. Improved understanding of engineering control effectiveness guides implementation at scale while considering occupant comfort, operational challenges, and energy costs.


Asunto(s)
Microbiología del Aire , Contaminación del Aire Interior , Control de Enfermedades Transmisibles , Enfermedades Transmisibles , Aerosoles , COVID-19/prevención & control , Humanos
7.
Health Secur ; 19(5): 532-540, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34609918

RESUMEN

Emergency preparedness systems plan for antibiotic distribution and vaccine administration to respond to public health threats. The arrival of a COVID-19 vaccine underscores the importance of organized logistics for rapid administration to populations. The US Centers for Disease Control and Prevention Cities Readiness Initiative encourages frontline responders from 72 US cities and metropolitan statistical areas to use planning software, such as RealOpt-POD-v8.0.2, to design dispensing operations and predict staffing needs. However, planning can be difficult for local jurisdictions given uncertainty about how long it may take to complete various processes during a dispensing operation, including assessment of countermeasure needs for each person (eg, based on age or pregnancy status) and the careful dispensing of countermeasures and accompanying education. The Union County Health Department in Ohio gathered data on the timing of typical processes for an anthrax medical countermeasures distribution site through a small-scale drill and used these data to parameterize a RealOpt model capable of serving the rural county's population of just over 50,000 people within 24 hours. Results help fill a gap in parameterizing RealOpt-based planning models by highlighting the use of a small-scale drill to inform time estimates, which can be applied to RealOpt as part of county-level planning in advance of larger-scale drills to evaluate dispensing capabilities and effectiveness. The findings provide a methodological basis of future resource typing for adaptable and scalable dispensing, particularly for rural areas. Both the approach and resulting antibiotics dispensing schematic presented here could be tailored to support planning for population-based countermeasure administration to combat emerging pandemics.


Asunto(s)
COVID-19 , Planificación en Desastres , Contramedidas Médicas , Vacunas contra la COVID-19 , Femenino , Humanos , Embarazo , SARS-CoV-2 , Programas Informáticos
8.
J Infect Dis ; 224(10): 1730-1734, 2021 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34534320

RESUMEN

Mobile phones are among the most highly touched personal objects. As part of a broader study on the contribution of fomites to influenza transmission, between 2017 and 2019, we swabbed mobile phones from 138 patients with influenza in 2 locations. Influenza viral RNA detection rates were 23% (23 of 99 phones) and 36% (14 of 39) in Hong Kong and Maryland, respectively. In Hong Kong, infectious influenza virus was recovered from 3 of 23 mobile phones which had influenza viral RNA detected. Mobile phone influenza contamination was positively associated with upper respiratory tract viral load and negatively associated with age. Cleaning personal objects of patients with influenza should be recommended, and individuals should avoid sharing objects with these patients.


Asunto(s)
Teléfono Celular , Enfermedades Transmisibles , Gripe Humana , Orthomyxoviridae , Hong Kong/epidemiología , Humanos , Gripe Humana/epidemiología , ARN Viral , Estados Unidos
9.
Environ Res ; 197: 111075, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33798519

RESUMEN

OBJECTIVE: We investigated the effects of chronic exposures to particulate and traffic-related air pollution on allostatic load (AL) score, a marker of cumulative biological risk, among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants were drawn from five clinical sites of the SEARCH for Diabetes in Youth (SEARCH) study (n = 2338). Baseline questionnaires, anthropometric measures, and a fasting blood test were taken at a clinic visit between 2001 and 2005. AL was operationalized using 10 biomarkers reflecting cardiovascular, metabolic, and inflammatory risk. Annual residential exposures to PM2.5 and proximity to heavily-trafficked major roadways were estimated for each participant. Poisson regression models adjusted for sociodemographic and lifestyle factors were conducted for each exposure. RESULTS: No significant associations were observed between exposures to PM2.5 or proximity to traffic and AL score, however analyses were suggestive of effect modification by race for residential distance to heavily-trafficked major roadways (p = 0.02). In stratified analyses, residing <100, 100-<200 and 200-<400 m compared to 400 m or more from heavily-trafficked major roadways was associated with 11%, 26% and 14% increases in AL score, respectively (95% CIs: -4, 29; 9, 45; -1, 30) for non-white participants compared to 6%, -2%, and -2% changes (95% CIs: -2, 15; -10, 7; -8, 6) for white participants. CONCLUSIONS: Among this population of youth with type 1 diabetes, we did not observe consistent relationships between chronic exposures to particulate and traffic-related air pollution and changes in AL score, however associations for traffic-related pollution exposures may differ by race/ethnicity and warrant further examination.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Alostasis , Diabetes Mellitus Tipo 1 , Contaminación por Tráfico Vehicular , Adolescente , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/epidemiología , Exposición a Riesgos Ambientales/análisis , Humanos , Material Particulado/análisis , Material Particulado/toxicidad , Emisiones de Vehículos/análisis , Emisiones de Vehículos/toxicidad
10.
PLoS Pathog ; 16(7): e1008704, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32658939

RESUMEN

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols.


Asunto(s)
Gripe Humana/transmisión , Aerosoles , Femenino , Humanos , Subtipo H3N2 del Virus de la Influenza A , Masculino
11.
J Phys Condens Matter ; 32(30): 305802, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32213680

RESUMEN

Research in spintronics has attracted much attention in the last few years due to the technological progress in generating and manipulating spin currents in miniaturized devices. Notwithstanding dissipative effects are inherent to experiments, in many theoretical works the damping of spin waves is included later by phenomenological arguments or even disregarded. Among the many techniques that have been used to treat magnetic models, bosonic representations is one of them. In this work, we chose the Holstein-Primakoff bosonic formalism to treat a ferromagnetic model with a priori inclusion of the damping term. Damping is included through a non-Hermitian term in the Hamiltonian and we showed that the well-known coherent state formalism can be generalized to properly represent the dissipative magnon model. The obtained results are then used to describe the precession magnetization in spintronic experiments, as the spin pumping process.

12.
Purinergic Signal ; 16(1): 85-96, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32043211

RESUMEN

The improvement of cryopreserved oocyte survival is imperative for the preservation of female fertility. In this study, we investigate whether P2Y2 receptors (P2Y2R) can be directly implicated in calcium (Ca2+) homeostasis misbalances observed during the cryopreservation process of cumulus oocyte complexes (COC). Firstly, RNA was extracted from bovine immature and mature oocytes and cumulus cells and real-time PCR performed to identify P2Y2R transcripts (experiment 1). Changes in intracellular calcium concentration [Ca2+]i of mature COC and oocytes (experiment 2) were measured upon exposure to cryoprotectants (CPA), UTP (P2Y2R stimulator, 100 µM), and/or suramin (P2Y2R inhibitor, 100 and 300 µM). The functional role of P2Y2R was investigated by analyzing the effect on oocyte viability of its modulation prior and during oocyte exposure to CPA (experiment 3). Mature COC were randomly divided into groups, and exposed to CPA and different P2Y2 modulators. Oocytes' viability, cortical granules location, and competence for development were assessed. Results showed that P2Y2R mRNAs are expressed in both oocytes and cumulus cells. Stimulation with UTP and CPA led to [Ca2+]i increase, and this effect was totally or partially blocked by suramin (P2Y2R inhibitor). Oocyte exposure to CPA and UTP reduced embryo rates compared with control and suramin100µM (P ≤ 0.04). The observed enhanced premature zona hardening in oocytes exposed to CPA (P = 0.04) and UTP (P = 0.005) stimulus was inhibited by suramin 100 µM. In conclusion, inhibition of P2Y2R during cryoprotectant exposure reduces premature intracellular Ca2+ release and significantly improves the developmental competence of exposed bovine oocytes.


Asunto(s)
Calcio/metabolismo , Crioprotectores/toxicidad , Células del Cúmulo/efectos de los fármacos , Oocitos/crecimiento & desarrollo , Receptores Purinérgicos P2Y2/metabolismo , Animales , Bovinos , Supervivencia Celular/efectos de los fármacos , Criopreservación/métodos , Células del Cúmulo/metabolismo , Femenino , Oocitos/efectos de los fármacos , Oocitos/metabolismo
13.
Med Vet Entomol ; 33(2): 322-325, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30652325

RESUMEN

Lutzomyia longipalpis (Diptera: Psychodidae) is the primary vector of Leishmania infantum (Kinetoplastida: Trypanosomatidae) in the Americas. Studies have been carried out to identify new alternatives for monitoring and controlling this sandfly species, particularly with the use of chemical baits. The attractiveness of odours emitted by foxes and alcohols found in some plants has already been demonstrated in laboratory tests with Lu. longipalpis. However, no studies have evaluated the responses of these insects to volatile organic compounds (VOCs) emitted by dogs. The present study was carried out to investigate the effects on Lu. longipalpis of individual and blends of VOCs identified in hair from dogs infected with L. infantum. Effects in male and female Lu. longipalpis were assessed using wind tunnel methodology. Individual compounds including octanal, nonanal, decanal and heptadecane showed capacity for activating and/or attracting male Lu. longipalpis. Only decanal and nonanal showed effects on females. The combination of octanal, decanal and heptadecane increased activation and attraction behaviour in male sandflies, as did the blend of octanal and decanal. These findings indicate that VOCs emitted by dogs may be an interesting source of new attractants of sandflies.


Asunto(s)
Quimiotaxis , Leishmania infantum/fisiología , Psychodidae/fisiología , Compuestos Orgánicos Volátiles/metabolismo , Animales , Biomarcadores/metabolismo , Enfermedades de los Perros/parasitología , Perros , Femenino , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/veterinaria , Masculino
14.
Theriogenology ; 115: 124-132, 2018 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-29754043

RESUMEN

An essential role of prion protein testis specific (PRNT) and prion protein 2 dublet (PRND) genes in the male reproductive function has been highlighted, although a deeper knowledge for the mechanisms involved is still lacking. Our goal was to determine the importance of the PRNT haplotypic variants and mRNA expression levels in ovine spermatozoa freezability and ability for fertilization and embryo developmental processes. Their association with the PRND gene polymorphisms was also analyzed. DNA from rams belonging to three Portuguese sheep breeds (n = 28) was screened by single-strand conformation polymorphism (SSCP) analysis to identify the PRNT and PRND polymorphisms. Semen collected from these rams was cryopreserved and fertility traits evaluated. The SSCP analyses revealed polymorphisms in the codons 6, 38, 43 and 48 of the PRNT coding region - respectively c.17C > T (p.Ser6Phe, which disrupts a consensus arginine-X-X serine/threonine motif); c.112G > C (p.Gly38 > Arg); and synonymous c.129T > C and c.144A > G. The polymorphisms in codons 6, 38 and 48 occur simultaneously while the one in codon 43 occurs independently. Six haplotypes were identified in the PRNT coding region, resulting in three different amino acid polymorphic variants (6S-38G-43C-48V, S6F-G38R-43C-48V and 6F-38R-43C-48V). The PRNT gene mRNA transcript level in spermatozoa was related to the identified haplotypic variants, either considering the codons 6-38-48 (P ≤ 0.0001) or the codon 43 alone (P ≤ 0.0001) or altogether (P ≤ 0.0001). An interaction between PRNT haplotypes and PRND genotypes on PRNT transcript level was also identified (P = 0.0003). Rams carrying the 17C-112G-144A PRNT haplotype had sperm with the highest post-thawed individual motility (P ≤ 0.03). Combined PRNT and PRND polymorphic variation influenced the post-thawed individual motility (P = 0.01). The male PRNT haplotypic, either considering the codons 6-38-48 and 43 altogether or the codon 43 alone, interfered (P ≤ 0.04) in embryo production rates. In conclusion, our data confirm that the PRNT gene is highly polymorphic in sheep and that the PRNT and PRND genotypes are associated. The identified polymorphisms of PRNT coding region seems to interfere on the ram spermatozoa mRNA transcript level and on male fertility, specifically in sperm freezability and ability for embryo development.


Asunto(s)
Polimorfismo Conformacional Retorcido-Simple/genética , Proteínas Priónicas/genética , ARN Mensajero/análisis , Oveja Doméstica/genética , Espermatozoides/química , Espermatozoides/fisiología , Animales , Codón/genética , Criopreservación/veterinaria , Fertilidad/genética , Fertilización In Vitro/veterinaria , Genotipo , Haplotipos , Masculino , Priones/genética , Preservación de Semen/veterinaria , Motilidad Espermática , Testículo/química
15.
Proc Natl Acad Sci U S A ; 115(5): 1081-1086, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29348203

RESUMEN

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1-3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.


Asunto(s)
Microbiología del Aire , Espiración , Gripe Humana/transmisión , Gripe Humana/virología , Infecciones del Sistema Respiratorio/virología , Aerosoles , Índice de Masa Corporal , Tos , Femenino , Humanos , Masculino , Modelos Teóricos , Prevalencia , ARN Viral/genética , Sistema Respiratorio , Estaciones del Año , Estudiantes , Temperatura , Universidades , Vacunación , Adulto Joven
16.
Reprod Fertil Dev ; 29(5): 985-997, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28442049

RESUMEN

The aim of the present study was to examine the role of Doppel protein in the capacitation process and fertilising ability of both fresh and frozen-thawed (FT) spermatozoa from rams carrying different prion protein 2 (dublet) (PRND) gene polymorphisms. The detection efficacy of new anti-Doppel monoclonal antibodies and PRND mRNA quantification were also explored in ovine spermatozoa. Three different genotypes (AA, GA, GG) were identified for codon 26 of ovine PRND-c.78G>A. Using flow cytometry, a higher fluorescence was detected in fresh compared with FT sperm samples incubated with anti-Doppel primary and fluorescein isothiocyanate-conjugated secondary antibodies (P<0.05). Capacitation was affected by semen treatment (fresh and FT) and male PRND genotype (P<0.05). After IVF, the use of fresh semen resulted in a higher cleavage rate than the use of FT spermatozoa (P=0.004). IVF using spermatozoa from individuals classified as carriers of the AA or GA PRND genotypes resulted in higher cleavage rates than seen using spermatozoa from GG carriers (P≤0.0006). Finally, using semen from rams with the AA PRND genotype resulted in the highest Day 6 and Day 8 embryo rates (P≤0.04). In conclusion, the results of the present study confirm that the identification of different PRND genotypes is important for studying the sperm capacitation process and for improving sperm cryoresistance and embryo production. Furthermore, the detection of Doppel in ejaculated ovine spermatozoa, along with its low expression after cryopreservation, strongly suggests an important physiological function of this protein in male fertility.


Asunto(s)
Fertilidad/genética , Proteínas Ligadas a GPI/genética , Priones/genética , Capacitación Espermática/genética , Espermatozoides/metabolismo , Animales , Criopreservación , Proteínas Ligadas a GPI/metabolismo , Genotipo , Masculino , Priones/metabolismo , Preservación de Semen/métodos , Ovinos , Motilidad Espermática/fisiología
17.
Anim Genet ; 47(1): 128-32, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26538093

RESUMEN

The objective of this study was to search for polymorphisms in the ovine prion-related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single-strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT-112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP).


Asunto(s)
Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Priones/genética , Oveja Doméstica/genética , Animales , Cruzamiento , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Masculino , Portugal , Análisis de Secuencia de ADN
18.
Clin Pharmacol Ther ; 96(3): 314-23, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24862215

RESUMEN

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection.


Asunto(s)
Fármacos Anti-VIH/farmacocinética , Seronegatividad para VIH , Modelos Biológicos , Nitrilos/farmacocinética , Pirimidinas/farmacocinética , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/sangre , Química Farmacéutica , Relación Dosis-Respuesta a Droga , Femenino , VIH-1/efectos de los fármacos , VIH-1/crecimiento & desarrollo , Humanos , Inyecciones Intramusculares , Londres , Masculino , Persona de Mediana Edad , Nitrilos/administración & dosificación , Nitrilos/sangre , Estudios Prospectivos , Pirimidinas/administración & dosificación , Pirimidinas/sangre , Recto/metabolismo , Rilpivirina , Vagina/metabolismo , Adulto Joven
19.
Reprod Domest Anim ; 47(2): 196-202, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21806689

RESUMEN

The function of prion-like protein Doppel was suggested to be related to male fertility. In this study, the importance of ovine Doppel polypeptide on spermatozoa capacitation and fertilization was evaluated. After refolding, recombinant Doppel (rDpl) was supplemented with different concentrations (40, 80 or 190 ng/ml) to ovine spermatozoa during the capacitation process. In experiment 1, post-thawed ovine spermatozoa were incubated with different concentrations of rDpl during 1 h for swim-up, and changes in sperm motility, concentration, vigour, viability and capacitation were monitored (10 replicates). In experiment 2, the fertilization ability of post-swim-up spermatozoa incubated as above was tested through heterologous fertilization of bovine in vitro matured oocytes (n = 423, three replicates). Regardless of dosage, rDpl improved (p ≤ 0.03) spermatozoa viability. Sperm individual motility and vigour were the highest (p ≤ 0.04) for the group receiving 190 ng/ml rDpl. Sperm supplemented with the highest doses of rDpl achieved higher (p = 0.02) fertilization rates (56.0 ± 3.0%) than control (39.1 ± 2.2%) and 40 ng/ml rDpl (39.8 ± 2.7%). Preliminary data suggest that Doppel protein may enhance in vitro spermatozoa fertilizing ability.


Asunto(s)
Proteínas Ligadas a GPI/metabolismo , Priones/metabolismo , Oveja Doméstica/fisiología , Espermatozoides/fisiología , Animales , Clonación Molecular , Fertilización In Vitro/veterinaria , Proteínas Ligadas a GPI/genética , Regulación de la Expresión Génica/fisiología , Masculino , Priones/genética , Capacitación Espermática/fisiología , Motilidad Espermática/fisiología
20.
Anim Genet ; 41(3): 311-4, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19968641

RESUMEN

The establishment of an association between prion protein gene (PRNP) polymorphisms and scrapie susceptibility in sheep has enabled the development of breeding programmes to increase scrapie resistance in the European Union. Intense selection for PRNP genotype may lead to correlated selection for genes linked to PRNP. We intended to investigate if any association exists between genetic variation in prion-like protein Doppel gene (PRND) and scrapie susceptibility, determined through PRNP genotyping. Sampling included 460 sheep from eight Portuguese breeds and the PRND gene coding region was analysed by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP), whereas PRNP genotyping was carried out by primer extension. A synonymous substitution (c.78G>A) was detected in codon 26 of the PRND gene, in all breeds except Churra Mondegueira. Linkage disequilibrium was found between the PRND and PRNP loci (P = 0.000). Specifically, PRND was monomorphic in the 45 animals with the more resistant ARR/ARR PRNP genotype (P = 0.003), whereas a higher frequency of PRND heterozygotes (GA) was associated with ARQ/AHQ (P = 0.029). These results constitute preliminary evidence of an association between a polymorphism in the PRND gene and scrapie susceptibility, and indicate that the possibility of undesirable consequences from widespread selection for PRNP genotype on genetic diversity and reproduction traits needs to be further investigated.


Asunto(s)
Predisposición Genética a la Enfermedad , Priones/genética , Scrapie/genética , Animales , Femenino , Masculino , Ovinos
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