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The ability of proteins to sense and transmit mechanical forces underlies many biological processes, but characterizing these forces in biological systems remains a challenge. Existing genetically encoded force sensors typically rely on fluorescence or bioluminescence resonance energy transfer (FRET or BRET) to visualize tension. However, these force sensing modules are relatively large, and interpreting measurements requires specialized image analysis and careful control experiments. Here, we report a compact molecular tension sensor that generates a bioluminescent signal in response to tension. This sensor (termed PILATeS) makes use of the split NanoLuc luciferase and consists of the H. sapiens titin I10 domain with the insertion of a 10-15 amino acid tag derived from the C-terminal ß-strand of NanoLuc. Mechanical load across PILATeS mediates exposure of this tag to recruit the complementary split NanoLuc fragment, resulting in force-dependent bioluminescence. We demonstrate the ability of PILATeS to report biologically meaningful forces by visualizing forces at the interface between integrins and extracellular matrix substrates. We further use PILATeS as a genetically encoded sensor of tension experienced by the mechanosensing protein vinculin. We anticipate that PILATeS will provide an accessible means of visualizing molecular-scale forces in biological systems.
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Técnicas Biosensibles , Luciferasas , Mediciones Luminiscentes , Humanos , Luciferasas/química , Luciferasas/metabolismo , Luciferasas/genética , Técnicas Biosensibles/métodos , Mediciones Luminiscentes/métodos , Conectina/química , Conectina/metabolismo , Vinculina/metabolismo , Vinculina/químicaRESUMEN
INTRODUCTION: The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE. METHODS AND ANALYSIS: REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial. ETHICS AND DISSEMINATION: All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide. TRIAL REGISTRATION NUMBER: NCT03374800.
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Neumonía Asociada al Ventilador , Inhibidores de la Bomba de Protones , Adolescente , Adulto , Humanos , Hemorragia Gastrointestinal/terapia , Unidades de Cuidados Intensivos , Pantoprazol , Inhibidores de la Bomba de Protones/uso terapéutico , Respiración Artificial , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The water sector could play a major role towards a Net Zero greenhouse gas (GHG) future if Scope 3 emissions were embraced and operationalised. Significant opportunities and challenges exist in tackling Scope 3 emissions including those associated with customer hot water use. Present GHG emission reduction practices predominantly focus on Scope 1 "within utility" and Scope 2 "purchased energy" emissions. In the urban water cycle, Scope 3 "indirect" emissions dominate, and water use is only one example of Scope 3 emissions. Over 90% of all water cycle GHG emissions can be attributed to water use in residential, industrial and commercial premises, collectively some 7% of global GHG emissions. One possibility is for water utilities to actively support efficient hot water use such as new ultra-low flow shower heads. Scope 3 opportunities also offer a range of cost-effective emissions-reduction opportunities, particularly when the wider perspective of "community value" is considered and not just a "business financial perspective". Hot water efficiency is additionally essential to Net Zero carbon futures, even with decarbonised grids, because most major Net Zero roadmaps require energy efficiency gains. Scientific and management advance needed includes: accounting methodologies, clear roles, collaboration, new business models, and clear definitions. The water sector has the opportunity to play a significant role in achieving Net Zero cities. The decision how much is yet to be made.
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CD39 (ENTPD1) is a key enzyme responsible for degradation of extracellular ATP and is upregulated in the tumor microenvironment (TME). Extracellular ATP accumulates in the TME from tissue damage and immunogenic cell death, potentially initiating proinflammatory responses that are reduced by the enzymatic activity of CD39. Degradation of ATP by CD39 and other ectonucleotidases (e.g., CD73) results in extracellular adenosine accumulation, constituting an important mechanism for tumor immune escape, angiogenesis induction, and metastasis. Thus, inhibiting CD39 enzymatic activity can inhibit tumor growth by converting a suppressive TME to a proinflammatory environment. SRF617 is an investigational, anti-CD39, fully human IgG4 Ab that binds to human CD39 with nanomolar affinity and potently inhibits its ATPase activity. In vitro functional assays using primary human immune cells demonstrate that inhibiting CD39 enhances T-cell proliferation, dendritic cell maturation/activation, and release of IL-1ß and IL-18 from macrophages. In vivo, SRF617 has significant single-agent antitumor activity in human cell line-derived xenograft models that express CD39. Pharmacodynamic studies demonstrate that target engagement of CD39 by SRF617 in the TME inhibits ATPase activity, inducing proinflammatory mechanistic changes in tumor-infiltrating leukocytes. Syngeneic tumor studies using human CD39 knock-in mice show that SRF617 can modulate CD39 levels on immune cells in vivo and can penetrate the TME of an orthotopic tumor, leading to increased CD8+ T-cell infiltration. Targeting CD39 is an attractive approach for treating cancer, and, as such, the properties of SRF617 make it an excellent drug development candidate.
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Inmunoglobulina G , Activación de Linfocitos , Humanos , Animales , Ratones , Anticuerpos Monoclonales , Adenosina Trifosfatasas , Adenosina TrifosfatoRESUMEN
BACKGROUND: Previous research has shown that, in comparison with non-pregnant women of reproductive age, pregnant women with COVID-19 are more likely to be admitted to critical care, receive invasive ventilation, and die. At present there are limited data in relation to outcomes and healthcare utilisation following hospital discharge of pregnant and recently pregnant women admitted to critical care. METHODS: A national cohort study of pregnant and recently pregnant women who were admitted to critical care in Scotland with confirmed or suspected COVID-19. We examined hospital outcomes as well as hospital re-admission rates. RESULTS: Between March 2020 and March 2022, 75 pregnant or recently pregnant women with laboratory-confirmed COVID-19 were admitted to 24 Intensive Care Units across Scotland. Almost two thirds (n=49, 65%) were from the most deprived socio-economic areas. Complete 90-day acute hospital re-admission data were available for 74 (99%) patients. Nine (12%) women required an emergency non-obstetric hospital re-admission within 90â¯days. Less than 5% of the cohort had received any form of vaccination. CONCLUSIONS: This national cohort study has demonstrated that pregnant or recently pregnant women admitted to critical care with COVID-19 were more likely to reside in areas of socio-economic deprivation, and fewer than 5% of the cohort had received any form of vaccination. More targeted public health campaigning across the socio-economic gradient is urgently required.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Embarazo , Femenino , Humanos , Masculino , Estudios de Cohortes , Unidades de Cuidados Intensivos , Cuidados Críticos , Escocia/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/terapiaRESUMEN
BACKGROUND: Over 5 billion people worldwide have no access to surgery worldwide, typically in low-resource settings, despite it being a primary life-saving treatment. Gas Insufflation-Less Laparoscopic Surgery (GILLS) can address this inequity, by improving current GILLS instrumentation to modern surgical standards. OBJECTIVE: to develop and translate a new Retractor for Abdominal Insufflation-less Surgery (RAIS) into clinical use and thus provide a context-appropriate system to advance GILLS surgery. METHODS: A collaborative multidisciplinary team from the UK and India was formed, embedding local clinical stakeholders and an industry partner in defining user and contextual needs. System development was based on a phased roadmap for 'surgical device design in low resource settings' and embedded participatory and frugal design principles in an iterative process supported by traditional medical device design methodologies. Each phase of development was evaluated by the stakeholder team through interactive workshops using cadaveric surgical simulations. A Commercialisation phase undertook Design to Manufacture and regulatory approval activities. Clinical validation was then conducted with rural surgeons performing GILLS procedures using the RAIS system. Semi-structured questionnaires and interviews were used to evaluate device performance. RESULTS: A set of user needs and contextual requirements were defined and formalised. System development occurred across five iterations. Stakeholder participation was instrumental in converging on a design which met user requirements. A commercial RAIS system was then produced by an industry partner under Indian regulatory approval. This was successfully used in clinical validation to conduct 12 surgical procedures at two locations in rural India. Surgical feedback showed that the RAIS system provided a valuable and usable surgical instrument which was appropriate for use in low-resource contexts. CONCLUSIONS: Using a context-specific development approach with close engagement of stakeholders was crucial to develop the RAIS system for low-resource regions. The outcome is translation from global health need into a fully realized commercial instrument which can be used by surgeons in low-resource regions across India.
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Insuflación , Cirujanos , Retroalimentación , Humanos , Participación de los Interesados , Encuestas y CuestionariosRESUMEN
Sediment, nutrients, organic carbon and pollutants are funnelled down submarine canyons from continental shelves by sediment-laden flows called turbidity currents, which dominate particulate transfer to the deep sea. Post-glacial sea-level rise disconnected more than three quarters of the >9000 submarine canyons worldwide from their former river or long-shore drift sediment inputs. Existing models therefore assume that land-detached submarine canyons are dormant in the present-day; however, monitoring has focused on land-attached canyons and this paradigm remains untested. Here we present the most detailed field measurements yet of turbidity currents within a land-detached submarine canyon, documenting a remarkably similar frequency (6 yr-1) and speed (up to 5-8 ms-1) to those in large land-attached submarine canyons. Major triggers such as storms or earthquakes are not required; instead, seasonal variations in cross-shelf sediment transport explain temporal-clustering of flows, and why the storm season is surprisingly absent of turbidity currents. As >1000 other canyons have a similar configuration, we propose that contemporary deep-sea particulate transport via such land-detached canyons may have been dramatically under-estimated.
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Sedimentos Geológicos , Ríos , Estaciones del AñoRESUMEN
Anaesthetists have a higher incidence of substance use disorder when compared with other doctors. This might be due to the ease of access to intravenous opioids, propofol, midazolam, inhalational agents and other anaesthetic drugs. Alcohol use disorder continues to be the most common problem. Unfortunately, the first sign that something is amiss might be the anaesthetist's death from an accidental or deliberate overdose. While there are few accurate data, suicide is presumed to be the cause of death in approximately 6-10% of all anaesthetists. If we are to prevent this, substance use disorder must be recognised early, we should ensure the anaesthetist is supported by their department and hospital management and that the anaesthetist engages fully with treatment. Over 75% of anaesthetists return to full practice if they co-operate fully with the required treatment and supervision.
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Anestesiología , Anestésicos , Trastornos Relacionados con Sustancias , Anestesiólogos , Anestesistas , Humanos , Trastornos Relacionados con Sustancias/prevención & controlRESUMEN
Context: The Centre for Health Record Linkage (CHeReL) was established in 2006 as a dedicated health and human services data linkage facility for two Australian jurisdictions, New South Wales and the geographically-nested Australian Capital Territory. The two jurisdictions have their own Governments and separate Health and Human Service systems. Purpose and Operations: The primary purpose of the CHeReL is to make linked administrative and routinely collected health data available to researchers and government within relevant regulatory and governance frameworks. The CHeReL's data governance and technical operations draw on international best practice and have been refined by learnings from other data linkage centres. Outcomes: Over twelve years of operation, more than 2,320 unique investigators from 140 institutions have used the CHeReL, producing 615 publications in peer-reviewed literature. A robust pipeline of new development is expected to further amplify the use of linked data for cutting edge medical research and support a vision of data-informed policy and data-driven government services.
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BACKGROUND: UK adult gender identity clinics (GICs) are implementing a new streamlined service model. However, there is minimal evidence from these services underpinning this. It is also unknown how many service users subsequently 'detransition'. AIMS: To describe service users' access to care and patterns of service use, specifically, interventions accessed, reasons for discharge and re-referrals; to identify factors associated with access; and to quantify 'detransitioning'. METHOD: A retrospective case-note review was performed as a service evaluation for 175 service users consecutively discharged by a tertiary National Health Service adult GIC between 1 September 2017 and 31 August 2018. Descriptive statistics were used for rates of accessing interventions sought, reasons for discharge, re-referral and frequency of detransitioning. Using multivariate analysis, we sought associations between several variables and 'accessing care' or 'other outcome'. RESULTS: The treatment pathway was completed by 56.1%. All interventions initially sought were accessed by 58%; 94% accessed hormones but only 47.7% accessed gender reassignment surgery; 21.7% disengaged; and 19.4% were re-referred. Multivariate analysis identified coexisting neurodevelopmental disorders (odds ratio [OR] = 5.7, 95% CI = 1.7-19), previous adverse childhood experiences (ACEs) per reported ACE (OR = 1.5, 95% CI = 1.1-1.9), substance misuse during treatment (OR = 4.3, 95% CI = 1.1-17.6) and mental health concerns during treatment (OR = 2.2, 95% CI 1.1-4.4) as independently associated with accessing care. Twelve people (6.9%) met our case definition of detransitioning. CONCLUSIONS: Service users may have unmet needs. Neurodevelopmental disorders or ACEs suggest complexity requiring consideration during the assessment process. Managing mental ill health and substance misuse during treatment needs optimising. Detransitioning might be more frequent than previously reported.
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Birth seasonality is a phenomenon whereby populations can be characterized by a single month or season in which births peak. While non-human animal research suggests that seasonal birth-pulses are related to variation in climate and local energy availability, social scientists debate the mechanisms responsible for it in humans. Here we investigate the role of precipitation, temperature, and energy availability on seasonal conception and birth pulses using a historical dataset from the Baja California peninsula - a hot, arid desert that experiences seasonal climatic fluctuations associated with the North American Monsoon. Analyses suggest that 1) local energy availability had a negative relationship with conception pulses; and 2) birth pulses had a positive relationship with local energy availability and a negative relationship with temperature. Taken together, our analyses suggest that women timed conceptions when local energy availability was lowest (challenging expectations of conception rates as simply reflecting ecological influences on female fecundity), so that children were born during the seasonal "green-up" associated with the North American Monsoon. Given our results, we speculate that birth seasonality represents a form of traditional ecological knowledge to improve neonate health and wellbeing.
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Ecosistema , Animales , Femenino , Humanos , México , Estaciones del Año , TemperaturaRESUMEN
We report the first detection of hepatitis E virus in rabbits in Australia. While conducting metatranscriptomic sequencing of liver samples collected from domestic rabbits that had died, we detected hepatitis E virus in three samples. Two viral genome sequences were obtained, which shared 96% nucleotide identity and clustered with hepatitis E strains isolated from rabbits and humans in Europe. This raises a potential public health risk in Australia, as the abundance of wild rabbits and the increasing popularity of domestic rabbits as pets represent a substantial human/rabbit interface to allow for potential zoonotic infections to occur.
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Virus de la Hepatitis E , Animales , Australia/epidemiología , Europa (Continente) , Genotipo , Virus de la Hepatitis E/genética , Filogenia , ARN Viral , Conejos , ZoonosisRESUMEN
Liver fibrosis is the common consequence of chronic liver diseases (CLD). Recently liver stiffness measurements (LSM) ≥ 9.1 kPa, as determined by transient elastography (TE), were demonstrated to predict significant fibrosis (stages ≥ F2) in a population-based setting. The PNPLA3 (adiponutrin) p.I148M polymorphism enhances the risk of liver injury. The aim of our study was to investigate the association between the procholestatic ABCB4 polymorphism c.711A>T and LSM ≥ 9.1 kPa in humans as well as the interaction between ABCB4 and PNPLA3 in a mouse model of chronic cholestasis. Prospectively, we recruited 712 patients with CLD (278 women, age 50 ± 13 years) with available TE results; liver biopsy results were available in 165 individuals. The ABCB4 c.711 genotype was determined by PCR-based assays. PNPLA3 expression and liver injury were studied in Abcb4-/- mice and wild-type controls. Overall, median LSM in our cohort was 6.7 kPa, and 226 individuals had LSM ≥ 9.1 kPa. Carriers of the ABCB4 variant c.711A presented more frequently with LSM ≥ 9.1 kPa (OR = 1.33, P = 0.020) and FIB-4 score ≥ 2.67 (OR = 1.38, P = 0.040). The presence of the risk allele was associated (P = 0.002) with FIB-4. In a multivariate model, the ABCB4 variant (OR = 1.43, P = 0.047) as well as BMI (P = 0.043, OR = 1.04) and age (OR = 1.02, P < 0.010) were independent risk factors for fibrosis stage ≥ F2. Abcb4 deficiency in mice led to enhanced liver injury, coupled with a decrease (P = 0.020) of hepatic PNPLA3 expression. To conclude, the procholestatic variant ABCB4 c.711A>T might represent a new genetic risk factor for clinically significant liver fibrosis. Lower expression of PNPLA3 in fibrotic Abcb4-/- livers points to the interaction between phospholipid metabolism and PNPLA3 in progressive liver injury.
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Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Cirrosis Hepática Experimental/genética , Cirrosis Hepática/genética , Hígado/metabolismo , Fosfolípidos/metabolismo , Polimorfismo de Nucleótido Simple , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/metabolismo , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratones Noqueados , Persona de Mediana Edad , Fenotipo , Fosfolipasas A2 Calcio-Independiente/genética , Fosfolipasas A2 Calcio-Independiente/metabolismo , Medición de Riesgo , Factores de Riesgo , Adulto Joven , Miembro 4 de la Subfamilia B de Casete de Unión a ATPRESUMEN
Models predicting disease transmission are vital tools for long-term planning of malaria reduction efforts, particularly for mitigating impacts of climate change. We compared temperature-dependent malaria transmission models when mosquito life-history traits were estimated from a truncated portion of the lifespan (a common practice) versus traits measured across the full lifespan. We conducted an experiment on adult female Anopheles stephensi, the Asian urban malaria mosquito, to generate daily per capita values for mortality, egg production and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature-trait relationships estimated from truncated data versus observed lifetime values. Incorporating these temperature-trait relationships into an expression governing the thermal suitability of transmission, relative R0(T), resulted in minor differences in the breadth of suitable temperatures for Plasmodium falciparum transmission between the two models constructed from only An. stephensi trait data. However, we found a substantial increase in thermal niche breadth compared with a previously published model consisting of trait data from multiple Anopheles mosquito species. Overall, this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based suitability predictions of transmission.
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Anopheles/parasitología , Malaria Falciparum/transmisión , Plasmodium falciparum , Factores de Edad , Animales , Femenino , Malaria/transmisión , Mosquitos Vectores , TemperaturaRESUMEN
Mercury (Hg) biomagnification in aquatic food webs is a global concern; yet, the ways species traits and interactions mediate these fluxes remain poorly understood. Few pathways dominated Hg flux in the Colorado River despite large spatial differences in food web complexity, and fluxes were mediated by one functional trait, predation resistance. New Zealand mudsnails are predator resistant and a trophic dead end for Hg in food webs we studied. Fishes preferred blackflies, which accounted for 56 to 80% of Hg flux to fishes, even where blackflies were rare. Food web properties, i.e., match/mismatch between insect production and fish consumption, governed amounts of Hg retained in the river versus exported to land. An experimental flood redistributed Hg fluxes in the simplified tailwater food web, but not in complex downstream food webs. Recognizing that species traits, species interactions, and disturbance mediate contaminant exposure can improve risk management of linked aquatic-terrestrial ecosystems.
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Mercurio , Animales , Colorado , Ecosistema , Monitoreo del Ambiente , Peces/metabolismo , Cadena Alimentaria , RíosRESUMEN
BACKGROUND & AIM: Intermittent fasting (IF) is a dietary intervention that has been investigated as an alternative weight-loss diet due to conventional approaches having poor long-term adherence. However, the macronutrient and micronutrient intake and composition of IF diets have been overlooked. The primary aim of this study was to describe the macronutrient and micronutrient intake of individuals following the 5:2 intermittent fasting diet (IF 5:2). METHODS: Thirty eight overweight and obese participants were included from two previous studies of IF 5:2. The participants selected included 27 males and 11 females, with and without Type 2 Diabetes. The dietary intervention, IF 5:2, consisted of two days per week fasting, either consecutive or non-consecutive, and five days per week of habitual intake. Prospectively completed 4-day estimated food records were used to assess macronutrient and micronutrient intake at baseline and week six. The 4-day records were weighted to give a mean daily intake during IF 5:2. RESULTS: During IF 5:2 the median (25th, 75th quartile) daily macronutrient composition was 22 (19, 24)% from protein, 33 (29, 37)% from fat and 39 (36, 43)% from carbohydrates. The intake (g/d) of carbohydrates and fibre decreased significantly from baseline to week six (p < 0.001) as well as on fasting days compared to non-fasting days (p < 0.001). The intake of calcium, zinc, magnesium and potassium were lower than recommended guidelines. Sodium intake exceeded the suggested daily target. On fasting days, the percent of total energy from protein significantly increased from 21% to 25% (p = 0.02). Despite intake being unrestricted on non-fasting days the energy intake decreased by week six when compared with baseline. CONCLUSION: The composition of IF 5:2 was a high protein, moderate fat, low carbohydrate diet with a low fibre intake. Some micronutrients have lower than recommended intake. However, overall IF 5:2 is a safe acceptable weight-loss diet strategy.
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Restricción Calórica/métodos , Dieta Reductora/métodos , Ayuno , Micronutrientes/análisis , Nutrientes/análisis , Obesidad/dietoterapia , Adulto , Anciano , Encuestas sobre Dietas , Carbohidratos de la Dieta/análisis , Grasas de la Dieta/análisis , Proteínas en la Dieta/análisis , Ingestión de Alimentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ingesta Diaria RecomendadaRESUMEN
Capsular polysaccharide (CPS), isolated from Acinetobacter baumannii LUH5549 carrying the KL32 capsule biosynthesis gene cluster, was studied by sugar analysis, Smith degradation, and one- and two-dimensional 1H and 13C NMR spectroscopy. The K32 CPS was found to be composed of branched pentasaccharide repeats (K units) containing two residues of ß-D-GalpNAc and one residue of ß-D-GlcpA (ß-D-glucuronic acid) in the main chain and one residue each of ß-D-Glcp and α-D-GlcpNAc in the disaccharide side chain. Consistent with the established CPS structure, the KL32 gene cluster includes genes for a UDP-glucose 6-dehydrogenase (Ugd3) responsible for D-GlcA synthesis and four glycosyltransferases that were assigned to specific linkages. Genes encoding an acetyltransferase and an unknown protein product were not involved in CPS biosynthesis. Whilst the KL32 gene cluster has previously been found in the global clone 2 (GC2) lineage, LUH5549 belongs to the sequence type ST354, thus demonstrating horizontal gene transfer between these lineages.
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Acinetobacter baumannii/genética , Familia de Multigenes/genética , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/metabolismo , Cápsulas Bacterianas/química , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/metabolismo , Conformación de Carbohidratos , Biología Computacional , Polisacáridos Bacterianos/aislamiento & purificaciónRESUMEN
Sediment quality monitoring is widely used to quantify extent of river pollution, but requires knowledge of pre-disturbance conditions in the potentially altered landscape. This has long been identified as a critical aspect to develop for addressing concerns of river pollution in the Alberta Oil Sands Region. Here, we use analyses of sediment cores from eight floodplain lakes spanning a 67 river-km transect across the Athabasca Delta to define pre-1920 (pre-industrial) baseline concentrations for vanadium and five primary pollutants. We then evaluate if sediment metals concentrations have become enriched above baseline since onset of oil sands development and other industrial activities. Results demonstrate no enrichment of metals concentrations (except zinc at one lake) and absence of consistent temporal increases above pre-industrial baselines. Thus, natural processes continue to dominate metal deposition in floodplain lakes of the Athabasca Delta -- an important finding to inform stewardship decisions. The pre-1920 metals concentrations baselines offer a useful tool for ongoing sediment monitoring in aquatic ecosystems of the Athabasca Delta.
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PURPOSE: Total disc replacements, comprising all-metal articulations, are compromised by wear and particle production. Metallic wear debris and ions trigger a range of biological responses including inflammation, genotoxicity, cytotoxicity, hypersensitivity and pseudotumour formation, therefore we hypothesise that, due to proximity to the spinal cord, glial cells may be adversely affected. METHODS: Clinically relevant cobalt chrome (CoCr) and stainless steel (SS) wear particles were generated using a six-station pin-on-plate wear simulator. The effects of metallic particles (0.5-50 µm3 debris per cell) and metal ions on glial cell viability, cellular activity (glial fibrillary acidic protein (GFAP) expression) and DNA integrity were investigated in 2D and 3D culture using live/dead, immunocytochemistry and a comet assay, respectively. RESULTS: CoCr wear particles and ions caused significant reductions in glial cell viability in both 2D and 3D culture systems. Stainless steel particles did not affect glial cell viability or astrocyte activation. In contrast, ions released from SS caused significant reductions in glial cell viability, an effect that was especially noticeable when astrocytes were cultured in isolation without microglia. DNA damage was observed in both cell types and with both biomaterials tested. CoCr wear particles had a dose-dependent effect on astrocyte activation, measured through expression of GFAP. CONCLUSIONS: The results from this study suggest that microglia influence the effects that metal particles have on astrocytes, that SS ions and particles play a role in the adverse effects observed and that SS is a less toxic biomaterial than CoCr alloy for use in spinal devices. These slides can be retrieved under Electronic Supplementary Material.
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Prótesis Articulares de Metal sobre Metal , Reeemplazo Total de Disco , Materiales Biocompatibles , Aleaciones de Cromo/efectos adversos , Cobalto , Humanos , Falla de PrótesisRESUMEN
PURPOSE: To determine the prevalence of keratoconus among high school students in Wellington, New Zealand. METHOD: The Wellington Keratoconus Study was a population-based prospective cross-sectional study of 2 cohorts in Wellington: cohort 1 (year 9 students, mean age 13.9 years) and cohort 2 (year 11 students, mean age 15.5 years). RESULTS: A total of 1916 students with a mean age of 14.6 years participated from 20 schools in the region. Keratoconus was found in 1:191 (0.52%) participants overall and in 1:45 (2.25%) Maori participants. Pentacam mean Kmax of 48.7 diopters (D) (cohort 1, 45.5 D; cohort 2, 49.9 D), thinnest pachymetry of 494.05 µm (cohort 1, 479.0 µm; cohort 2, 499.5 µm), posterior elevation at the thinnest point of 23.4 (cohort 1, 15.2; cohort 2, 26.6), Belin/Ambrosio enhanced ectasia display overall D value of 4.30 (cohort 1, 3.2; cohort 2, 4.7) were noted in participants with keratoconus. In those with keratoconus, 8 of 10 had visual impairment of 0.2 Logarithm of the Minimum Angle of Resolution (LogMAR) or worse in the better eye; 7 of 10 did not use visual aids; 7 of 10 had atopy; and 6 of 10 were from a low school decile. In those without keratoconus, 43.8% had atopy. CONCLUSIONS: Keratoconus may affect up to 1 in 191 New Zealand adolescents and 1 in 45 Maori adolescents. Keratoconus appeared to be associated with Maori ethnicity, atopy, lower school decile, visual impairment, and the underutilization of visual aids. Nationwide screening programs may have a role in reducing the burden of disease associated with keratoconus.