RESUMO
NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.
RESUMO
The prediction of a supersonic solar wind1 was first confirmed by spacecraft near Earth2,3 and later by spacecraft at heliocentric distances as small as 62 solar radii4. These missions showed that plasma accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy5-7. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams8. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii9-11, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age12-14.
RESUMO
During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.
RESUMO
Antarctica has been isolated and progressively glaciated for over 30 million years, with only approximately 0.3 % of its area currently ice-free and capable of supporting terrestrial ecosystems. As a result, invertebrate populations have become isolated and fragmented, in some cases leading to speciation. Terrestrial invertebrate species currently found in Antarctica often show multi-million year, and even Gondwanan, heritage, with little evidence of recent colonisation. Mesobiotus is a globally distributed tardigrade genus. It has commonly been divided into two "groups", referred to as harmsworthi and furciger, with both groups currently considered cosmopolitan, with global reports including from both the Arctic and the Antarctic. However, some authors considered that Meb. furciger, as originally described, may represent an Antarctic-specific lineage. Using collections of tardigrades from across the Antarctic continent and publicly available sequences obtained from online databases, we use mitochondrial and nuclear ribosomal sequence data to clarify the relationships of Antarctic Mesobiotus species. Our analyses show that all Antarctic members belong to a single lineage, evolving separately from non-Antarctic representatives. Within this Antarctic lineage there are further deep divisions among geographic regions of the continent, consistent with the presence of a species complex. Based on our data confirming the deep divisions between this Antarctic lineage, which includes representatives of both groups, we recommend that the use of furciger and harmsworthi group terminology is now abandoned, as it leads to systematic and biogeographical confusion.
Assuntos
Ecossistema , Tardígrados , Animais , Regiões Antárticas , Regiões Árticas , Filogenia , Tardígrados/genéticaRESUMO
BACKGROUND: Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms. OBJECTIVES: Assess the efficacy of an 8-week duloxetine treatment compared to usual care in end-stage knee and hip OA patients with a level of centralized pain. DESIGN: Pragmatic, enriched, open-label RCT. METHODS: Patients were randomized to duloxetine or to care-as-usual. Primary outcome was pain in the index joint, measured with the pain domain of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS). The intention-to-treat principle was used, with mixed-model repeated measures to analyze the effect. RESULTS: One hundred eleven patients were randomized. Nearly 44% felt much to very much better after duloxetine usage compared to 0% in the care-as-usual group (p < 0.001). The duloxetine group scored 11.3 points (95%CI: 5.8, 16.8) better on the pain domain of the KOOS/HOOS (p < 0.001). Knee patients improved significantly more than hip patients (18.7 [95%CI: 11.3, 26.1] versus 6.0 [95%CI: - 2.6, 14.5] points better). CONCLUSIONS: Adding duloxetine treatment seems to be beneficial for end-stage knee OA patients with neuropathic-like symptoms (at risk of CS). End stage Hip OA patients seem to be nonresponsive to duloxetine. TRIAL REGISTRATION: Dutch Trial Registry with number NTR 4744 (15/08/2014) and in the EudraCT database with number 2013-004313-41 .
Assuntos
Dor Crônica , Osteoartrite do Quadril , Osteoartrite do Joelho , Cloridrato de Duloxetina/efeitos adversos , Humanos , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Governments need people to work to older ages, but the prevalence of chronic disease and comorbidity increases with age and impacts work ability. AIMS: To investigate the effects of objective health diagnoses on exit from paid work amongst older workers. METHODS: Health and Employment After Fifty (HEAF) is a population cohort of adults aged 50-64 years recruited from English GP practices which contribute to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about health and work at baseline and annually for 2 years: their responses were linked with their objective health diagnoses from the CPRD and data analysed using Cox regression. RESULTS: Of 4888 HEAF participants ever in paid work, 580 (25%) men and 642 (25%) women exited employment, 277 of them mainly or partly for a health reason (health-related job loss (HRJL)). Amongst HEAF participants who remained in work (n = 3666) or who exited work but not for health reasons (n = 945), there was a similar prevalence of background health conditions. In men and women, HRJL was associated with inflammatory arthritis, sleep disorders, common mental health conditions and musculoskeletal pain. There were however gender differences: widespread pain and lower limb osteoarthritis were associated with HRJL in women but hypertension and cardiovascular disease in men. CONCLUSIONS: Improved diagnosis and management of common conditions might be expected to increase working lives. Workplace well-being interventions targeting obesity and increasing mobility might contribute to extended working lives. Employers of predominantly female, as compared with male workforces may need different strategies to retain older workers.
Assuntos
Emprego , Local de Trabalho , Adulto , Feminino , Masculino , Humanos , Inquéritos e Questionários , Estudos de Coortes , PrevalênciaRESUMO
BACKGROUND: UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing). AIMS: To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database. METHODS: Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman's correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures. RESULTS: Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0-7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman's coefficient = 0.50). For time spent standing (1-5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman's coefficient = 0.56). CONCLUSIONS: While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.
Assuntos
Bancos de Espécimes Biológicos , Exposição Ocupacional , Humanos , Exposição Ocupacional/efeitos adversos , Ocupações , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
The effects of multigenerational Cu exposure on the freshwater gastropod Isidorella newcombi were investigated. Snails were exposed to a range of treatment-specific Cu concentrations in the parental to F2 generations, and a common Cu concentration in the F3 generation. In the parental to F2 generations, some general responses to 3 days Cu exposures included reduced survival and feeding in snails exposed to higher Cu concentrations. This suggested that the snails exposed to the high Cu concentration were experiencing Cu-induced stress that may apply selection pressure. In the F3 generation, when all treatments were exposed to a common Cu concentration, increased survival was correlated with the pre-exposure Cu concentration history. Snails that had been pre-exposed to Cu also displayed reduced stress at a sub-lethal level, indicated by lower lysosomal destabilisation (LD). Mortality and LD responses in the F3 generation were not related to Cu tissue concentrations, indicating increased tolerance and reduced stress were not related to changes in Cu bioaccumulation. Total antioxidant capacity increased in the higher Cu concentration pre-exposure treatments which could be associated with lower Cu-induced stress, however, this is not supported by the oxidative damage marker lipid peroxidation, which also increased. While Cu tissue concentrations and oxidative stress markers were assessed to determine underlying reasons for increased tolerance in snails from a population with a multi-generational exposure history to Cu, the results were not conclusive. Despite this, it was demonstrated through increased survival and reduced LD that Cu tolerance can develop over a short evolutionary time scale.
Assuntos
Cobre , Poluentes Químicos da Água , Animais , Biomarcadores , Cobre/análise , Cobre/toxicidade , Água Doce , Estresse Oxidativo , Caramujos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: The adoption of sanitary measures due to the SARS-CoV-2 pandemic hampered teaching and learning methods in medicine. AIM: To communicate the results of a wound suture training workshop, based on the Basic Procedural Skills Training methodology and adapted to the pandemic context. MATERIAL AND METHODS: One hundred fourteen students were randomized in small groups due to sanitary measures and trained with a modification of the Basic Procedural Skills Training methodology. An informed consent was obtained from every student. The suturing skills were evaluated before and after the intervention with "The Objective Structured Assessment Of Technical Skills" (OSATS) instrument. The perception of the workshop and the implementation of the COVID-19 prevention measures were also evaluated. RESULTS: The students showed a statistically significant improvement after the intervention. In the OSATS verification list, the average score increased from 4.5 to 8.6 (p < 0.01). In the OSATS global scale, the average score increased from 13.0 to 25.3 (p < 0.01). The perception of the workshop and the prevention measures were well evaluated. CONCLUSIONS: Despite all the limitations of the pandemic context, we achieved a significant improvement after the intervention and a very good perception by the students.
Assuntos
COVID-19 , Estudantes de Medicina , Humanos , Competência Clínica , Avaliação Educacional/métodos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
The high temperatures and strong magnetic fields of the solar corona form streams of solar wind that expand through the Solar System into interstellar space. At 09:33 UT on 28 April 2021 Parker Solar Probe entered the magnetized atmosphere of the Sun 13 million km above the photosphere, crossing below the Alfvén critical surface for five hours into plasma in casual contact with the Sun with an Alfvén Mach number of 0.79 and magnetic pressure dominating both ion and electron pressure. The spectrum of turbulence below the Alfvén critical surface is reported. Magnetic mapping suggests the region was a steady flow emerging on rapidly expanding coronal magnetic field lines lying above a pseudostreamer. The sub-Alfvénic nature of the flow may be due to suppressed magnetic reconnection at the base of the pseudostreamer, as evidenced by unusually low densities in this region and the magnetic mapping.
RESUMO
BACKGROUND: Night/shift work may be increasing but there are few data about the prevalence amongst older workers. With governments encouraging people to work to older ages, it is important to know how feasible night/shift work is for them and whether there are any adverse health consequences. AIMS: Amongst current older workers (aged 50-64 years), to explore the prevalence of night/shift working and evaluate its health impacts and sustainability over 4 years of follow-up. METHODS: Data from the Health and Employment After Fifty cohort were used to describe the demographic, job and health characteristics of men and women undertaking night/shift work. Longitudinal data were used to examine the number and nature of exits annually thereafter. RESULTS: Amongst the 5409 working at baseline, 32% reported night/shift work in sectors which differed by sex. Night/shift workers were more likely to be: current smokers; doing physically demanding work; struggling to cope at work; dissatisfied with their hours; depressed; sleeping poorly; rating their health poorly. Women whose job involves night work were more likely to exit the workforce over 4 years. CONCLUSIONS: Almost one in three contemporary UK older workers report night/shift work. We found some evidence of adverse impacts on health, sleep and well-being and higher rates of job exit amongst women. More research is needed but night/shift work may be challenging to sustain for older workers and could have health consequences.
Assuntos
Jornada de Trabalho em Turnos , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Jornada de Trabalho em Turnos/efeitos adversos , Sono , Reino Unido/epidemiologia , Tolerância ao Trabalho ProgramadoRESUMO
Purpose This study compared the preoperative levels and postoperative recovery courses of physical and mental impairments, activity limitations and participation restrictions of working-age patients who return to work (RTW) by 3, 6 or 12 months after total knee arthroplasty (TKA). Methods A prospective survey study including TKA patients (aged < 65) (n = 146) who returned to work (RdTW) in the first postoperative year. Three groups were compared: those who returned by 3 (n = 35), 6 (n = 40) or 12 (n = 29) months. Surveys were completed preoperatively and at 6 weeks and 3, 6 and 12 months postoperatively. Outcomes represented domains of the International Classification of Functioning, i.e. physical impairments (pain, stiffness, vitality), mental impairments (mental health and depressive symptoms), activity limitations (physical functioning) and participation restrictions (social and work functioning). Results Preoperative knee-specific pain and physical functioning levels were better among patients who RdTW by 3 months, compared to those who returned by 12 months. Patients who RdTW by 3 months experienced significantly better recovery from physical impairments than those who returned by 6 months (on general pain) or 12 months (on general and knee-specific pain and on stiffness). Patients returning by 3 months experienced significantly better recovery from activity limitations (on knee-specific physical functioning). Conclusions To optimize return to work outcome after TKA surgery, the focus should lie on physical impairments (general and knee-specific pain, stiffness) and activity limitations (knee-specific physical functioning) during recovery.
Assuntos
Artroplastia do Joelho , Idoso , Humanos , Lactente , Período Pós-Operatório , Estudos Prospectivos , Retorno ao Trabalho , Inquéritos e QuestionáriosRESUMO
Purpose Objective measurements of sedentary and physical activity (PA) behavior are scarce among working-age patients who undergo total knee arthroplasty (TKA). Aim was to assess sedentary and PA behaviors using accelerometers and to identify compensation effects between occupational and leisure time of sedentary and PA behavior. Methods One year post-TKA, 51 patients wore an ActiGraph(GT3x) accelerometer for 7 days. Sedentary time, prolonged sedentary bouts (≥ 30 min) and PA (light-intensity and moderate-to-vigorous PA) were examined. Compliance with the guideline of > 150 min moderate-to-vigorous PA per week was calculated. Compensation effects were analyzed using multilevel models, splitting effects into routine and within-day compensation, stratifying by physical and non-physical jobs. The routine compensation effects are the ones of interest, representing habitual compensation during a week. Results Participants spent 60% of time in sedentary bouts and 17% in prolonged sedentary bouts, with 37% of PA spent in light-intensity and 3% in moderate-to-vigorous activity. About 70% of patients met the PA guideline. Routine compensation effects were found for workers in physical jobs, who compensated for their occupational light-intensity PA with less light-intensity PA during leisure time. Workers in non-physical jobs did not compensate for their occupational prolonged sedentary bouts, as these continued during leisure time. Conclusion This study showed that working TKA patients are highly sedentary 1 year after surgery, but most met the PA guideline. Especially those with non-physical jobs do not compensate for their occupational prolonged sedentary bouts. This stresses the need to stimulate PA among TKA patients not complying with the guidelines and those with non-physical jobs.
Assuntos
Artroplastia do Joelho , Acelerometria , Idoso , Exercício Físico , Feminino , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Comportamento SedentárioRESUMO
The solar wind is slowed, deflected, and heated as it encounters Venus's induced magnetosphere. The importance of kinetic plasma processes to these interactions has not been examined in detail, due to a lack of constraining observations. In this study, kinetic-scale electric field structures are identified in the Venusian magnetosheath, including plasma double layers. The double layers may be driven by currents or mixing of inhomogeneous plasmas near the edge of the magnetosheath. Estimated double-layer spatial scales are consistent with those reported at Earth. Estimated potential drops are similar to electron temperature gradients across the bow shock. Many double layers are found in few high cadence data captures, suggesting that their amplitudes are high relative to other magnetosheath plasma waves. These are the first direct observations of plasma double layers beyond near-Earth space, supporting the idea that kinetic plasma processes are active in many space plasma environments.
RESUMO
INTRODUCTION: In the Emergency Department, regional anesthesia is increasingly used in elderly patients with hip fractures. An example is a Fascia Iliaca Compartment Block (FICB). Traditionally, this block is administered below the inguinal ligament. There is no Emergency Department data regarding effectivity of an alternative, more cranial approach above the inguinal ligament. The objective was to determine analgesic effects of an ultrasound-guided supra-inguinal FICB in hip fracture patients in the Emergency Department. METHODS: This case series included all Emergency Department hip fracture patients who were treated with a supra-inguinal FICB during a period of 10â¯months. All data were recorded prospectively. Primary study outcome was decrease in Numerical Rating Scale (NRS) pain scores 60â¯min after the FICB. Secondary outcomes included the proportion of patients achieving 1.5 NRS points decrease at 60â¯min; NRS differences at 30 and 120â¯min compared to baseline; need for additional analgesia and occurrence of adverse events. RESULTS: A total of 22 patients were included in the study. At 60â¯min median NRS pain scores decreased from 6.0 to 3.0 (pâ¯<â¯0.001). Of all patients, a total of 59% achieved a decrease in 1.5 NRS points after 60â¯min. Median pain scores at 30 and 120â¯min were 4.0 (Interquartile Range (IQR) 2.0-5.0) and 2.5 (IQR 0.8-3.0). Seven patients (31.8%) required additional opioid analgesia after the FICB. No adverse events were recorded. CONCLUSION: An ultrasound-guided supra-inguinal FICB decreases NRS pain scores in hip fracture patients both clinically relevant and statistically significantly after 60â¯min. CLINICAL TRIAL REGISTRATION: The study was registered in the ISRCTN database (ISRCTN74920258).
Assuntos
Fraturas do Quadril/tratamento farmacológico , Bloqueio Nervoso/métodos , Idoso , Idoso de 80 Anos ou mais , Analgesia/instrumentação , Analgesia/métodos , Distribuição de Qui-Quadrado , Serviço Hospitalar de Emergência/organização & administração , Feminino , Fraturas do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/instrumentação , Manejo da Dor/métodos , Manejo da Dor/tendências , Medição da Dor/métodos , Estudos Prospectivos , Ultrassonografia de Intervenção/métodosRESUMO
The native freshwater gastropod Isidorella newcombi attacks the roots of developing rice plants in southern Australia and is controlled using copper sulphate. The apparent tolerance of this species to moderate levels of copper (Cu) exposure led us to investigate its potential usefulness as a biomonitor species. To assess its response to chronic Cu exposure, adult I. newcombi were exposed to 0-120 µg L-1 of Cu for 28 days. Lethal and sublethal responses were investigated. The relationships between subcellular biomarkers and life history traits also were explored. At exposure concentrations of 60 µg L-1 Cu and above, 100% mortality was observed during the 28-day exposure period. In these treatments, there was an exposure concentration dependent decrease in the time that the snails survived. In the surviving snails, there was an exposure concentration-dependent increase in tissue Cu concentration. In the snails exposed to Cu concentrations above 15 µg L-1, no eggs were produced during the final week of copper exposure, indicating that populations would not persist at Cu concentrations above 15 µg L-1. The general stress biomarker lysosomal membrane destabilisation (LD) indicated organisms exposed to 10 µg L-1 Cu and above were experiencing Cu induced stress. This suggests that LD could act as an early warning system for responses at higher levels of biological organisation in I. newcombi exposed to copper.
Assuntos
Cobre/toxicidade , Caramujos/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores , Cobre/análise , Sulfato de Cobre , Água Doce , Reprodução , Testes de Toxicidade Crônica , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Boot camps are used to acquire skills in simple surgical procedures, such as sutures, in a short period of time. AIM: To assess the retention of the procedural skills of medical students who participated in a simulation-based suture workshop. MATERIAL AND METHODS: One hundred five medical students were trained using the EPROBA methodology (Entrenamiento PROcedimental BAsico), with prior informed consent. The instrument "Objective Structured Assessment Of Technical Skills" (OSATS) was applied prior to and after the workshop, and during retention module, which was carried out between three and four months after the suture workshop. Participants were classified according to the level of previous knowledge in sutures. RESULTS: The students showed significant improvement in their scores after the workshop (improvement from 12.9 to 28.5 points, p < 0.001). No significant differences were found between scores after the workshop and those obtained in the retention module (28.5 to 28.1 points, respectively, p = 0.235). No difference in scores were observed when retention was evaluated according to previous knowledge levels. CONCLUSIONS: Simulation programs are useful for the acquisition of procedural skills which are retained over time.
Assuntos
Medicina , Treinamento por Simulação , Estudantes de Medicina , Competência Clínica , Avaliação Educacional , HumanosRESUMO
Vascular endothelial growth factor (VEGF)-A is differentially spliced to give two functionally different isoform families; pro-angiogenic, pro-permeability VEGF-Axxx and anti-angiogenic, anti-permeability VEGF-Axxxb. VEGF-A splicing is dysregulated in several pathologies, including cancer, diabetes, and peripheral arterial disease. The bichromatic VEGF-A splicing-sensitive fluorescent reporter harboured in a transgenic mouse is a novel approach to investigate the splicing patterns of VEGF-A in vivo. We generated a transgenic mouse harbouring a splicing-sensitive fluorescent reporter designed to mimic VEGF-A terminal exon splicing (VEGF8ab) by insertion into the ROSA26 genomic locus. dsRED expression denotes proximal splice site selection (VEGF-Axxx) and eGFP expression denotes distal splice site selection (VEGF-Axxxb). We investigated the tissue-specific expression patterns in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, and determined whether the splicing pattern could be manipulated in the same manner as endogenous VEGF-A by treatment with the SRPK1 inhibitor SPHINX 31. We confirmed expression of both dsRED and eGFP in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, with the highest expression of both fluorescent proteins observed in the exocrine pancreas. The ratio of dsRED and eGFP matched that of endogenous VEGF-Axxx and VEGF-Axxxb. Treatment of the VEGF8ab mice with SPHINX 31 increased the mRNA and protein eGFP/dsRED ratio in the exocrine pancreas, mimicking endogenous VEGF-A splicing. The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess splicing regulation in the individual cell-types and tissues, which provides a useful screening process for potentially therapeutic splicing regulatory compounds in vivo.
Assuntos
Processamento Alternativo , Animais Geneticamente Modificados , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas Luminescentes/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Éxons , Olho/metabolismo , Loci Gênicos , Proteínas de Fluorescência Verde/metabolismo , Íntrons , Rim/metabolismo , Proteínas Luminescentes/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Pâncreas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The main objective of this study was to evaluate evolutions in herd-level antimicrobial consumption (AMC) and in udder health and milk quality parameters between herds that received mastitis management input on a regular basis (actively advised by the first author; referred to as intervention herds) and herds that did not (referred to as control herds). Strikingly, herds in the intervention group had a significantly higher prevalence of new intramammary infections compared with those in the control group. No significant differences were observed in the percentage of chronically infected cows, the bulk milk somatic cell count, and the bacterial and coliform count between the intervention and control herds, nor did the herd-level AMC differ between them. Furthermore, the level of mastitis management applied in each herd was assessed and scored [mastitis management score (MMS); higher is better], as was the level of implementation of different recommended mastitis management practices over time, expressed as the mastitis management implementation score (MMIS; higher is better). A large variation was observed in MMS and MMIS in the intervention herds (median = 16 and range = 12 to 22; median = 13 and range = -5 to 31, respectively) and the control herds (median = 16 and range = 9 to 22; median = 9 and range = -13 to 22, respectively). Also, intervention herds in which the herd veterinarian attended each herd visit executed by the first author had a higher MMS and MMIS (median = 20 and 24, respectively) compared with herds in which the veterinarian sometimes (median = 16 and 17, respectively) or never (median = 16.5 and 7.5, respectively) attended the herd visits. Further, the association between MMS or MMIS on one hand and udder health, milk quality, and the herd-level AMC over time on the other was studied using the data of both groups of herds. Better mastitis management was associated with a reduction in the consumption of antimicrobials that are critically important for human health over time and with lower bacterial counts and bulk milk somatic cell count. Better mastitis management can be helpful in obtaining better milk quality and more responsible use of critically important antimicrobials on dairy farms.
Assuntos
Antibacterianos/uso terapêutico , Glândulas Mamárias Animais/fisiopatologia , Mastite Bovina/tratamento farmacológico , Leite/química , Animais , Carga Bacteriana/veterinária , Bélgica/epidemiologia , Bovinos , Contagem de Células/veterinária , Feminino , Incidência , Glândulas Mamárias Animais/efeitos dos fármacos , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Leite/microbiologia , PrevalênciaRESUMO
Different mycobacterial species are encountered in bovine medicine. The fastidiously growing mycobacteria (Mycobacterium bovis as the cause of bovine tuberculosis, and Mycobacterium avium ssp. paratuberculosis, MAP, as the cause of paratuberculosis) are well known and targeted in eradication/control or monitoring programs in different countries, whereas the rapidly growing species is only rarely identified from bovine disease. The latter have occasionally been reported as the cause of bovine clinical mastitis, but recent reports are scarce. In this study, Mycolicibacterium smegmatis (basonym Mycobacterium smegmatis) was identified as cause of granulomatous, relapsing clinical mastitis in 2 cows from one Belgian dairy herd. Milk, blood, and fecal samples were collected, as well as tissue samples after the cows were culled. Serological analysis conducted on milk and serum samples resulted in positive reactions for MAP, but negative for Mycobacterium bovis. Production of IFN-γ showed sensitization with mycobacteria or similar organisms, other than M. bovis, in one cow. Detection of MAP by bacteriological culture and IS900-based quantitative PCR on milk and feces remained negative. In conclusion, this paper describes M. smegmatis as a cause of bovine clinical mastitis in Belgium and suggests cross-reactivity of the intramammary M. smegmatis infection with routinely used serological tests for MAP.