Abstract Background Patients’ online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health ...records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users’ overall experiences with national PAEHR services. Methods The study analysed the MHC-part of the NORDeHEALTH 2022 Patient Survey, a large-scale multi-country survey. The survey consisted of 45 questions, including demographic variables and questions related to users’ experiences with ORA. We focused on the questions concerning positive experiences (benefits), negative experiences (errors, omissions, offence), and breaches of security and privacy. Participants were included in this analysis if they reported receiving mental healthcare within the past two years. Descriptive statistics were used to summarise data, and percentages were calculated on available data. Results 6,157 respondents were included. In line with previous research, almost half (45%) reported very positive experiences with ORA. A majority in each country also reported improved trust (at least 69%) and communication (at least 71%) with healthcare providers. One-third (29.5%) reported very negative experiences with ORA. In total, half of the respondents (47.9%) found errors and a third (35.5%) found omissions in their medical documentation. One-third (34.8%) of all respondents also reported being offended by the content. When errors or omissions were identified, about half (46.5%) reported that they took no action. There seems to be differences in how patients experience errors, omissions, and missing information between the countries. A small proportion reported instances where family or others demanded access to their records (3.1%), and about one in ten (10.7%) noted that unauthorised individuals had seen their health information. Conclusions Overall, MHC patients reported more positive experiences than negative, but a large portion of respondents reported problems with the content of the PAEHR. Further research on best practice in implementation of ORA in MHC is therefore needed, to ensure that all patients may reap the benefits while limiting potential negative consequences.
Using a family study design, we describe the motor and nonmotor phenotype in probands with LRRK2 G2019S mutations and family members and compare these individuals to patients with idiopathic ...Parkinson disease (iPD) and unrelated controls.
Probands with G2019S mutations and their first-degree relatives, subjects with iPD, and unrelated control subjects were identified from 4 movement disorders centers. All underwent neurologic examinations and tests of olfaction, color vision, anxiety, and depression inventories.
Tremor was more often a presenting feature among 25 individuals with LRRK2-associated PD than among 84 individuals with iPD. Subjects with LRRK2-PD had better olfactory identification compared with subjects with iPD, higher Beck Depression Inventory scores, and higher error scores on Farnsworth-Munsell 100-Hue test of color discrimination. Postural or action tremor was more common among 29 nonmanifesting mutation carriers compared with 53 noncarriers within the families. Nonparkinsonian family members had higher Unified Parkinson's Disease Rating Scale motor scores, more constipation, and worse color discrimination than controls, regardless of mutation status.
Although tremor is a more common presenting feature of LRRK2-PD than iPD and some nonmotor features differed in degree, the phenotype is largely overlapping. Postural or action tremor may represent an early sign. Longitudinal evaluation of a large sample of nonmanifesting carriers will be required to describe any premotor phenotype that may allow early diagnosis.
The enzymatic degradation of recalcitrant plant biomass is one of the key industrial challenges of the 21st century. Accordingly, there is a continuing drive to discover new routes to promote ...polysaccharide degradation. Perhaps the most promising approach involves the application of "cellulase-enhancing factors," such as those from the glycoside hydrolase (CAZy) GH61 family. Here we show that GH61 enzymes are a unique family of copper-dependent oxidases. We demonstrate that copper is needed for GH61 maximal activity and that the formation of cellodextrin and oxidized cellodextrin products by GH61 is enhanced in the presence of small molecule redox-active cofactors such as ascorbate and gallate. By using electron paramagnetic resonance spectroscopy and single-crystal X-ray diffraction, the active site of GH61 is revealed to contain a type II copper and, uniquely, a methylated histidine in the copper's coordination sphere, thus providing an innovative paradigm in bioinorganic enzymatic catalysis.
Summary
Background The JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling pathway is known to play an important role in many cellular processes including ...inflammation. The activation of STAT1 is dependent on tyrosine 701 and serine 727 phosphorylation, which leads to the formation of the STAT dimer and modulation of STAT1 activity, respectively.
Objective To determine STAT1 expression and activation in psoriatic skin.
Methods Biopsies were collected from patients with psoriasis. mRNA expression was evaluated by quantitative polymerase chain reaction, whereas the protein and phosphorylation level of STAT1 were evaluated by Western blotting. STAT1 localization was determined by immunofluorescence analysis and STAT1‐induced transcriptional activity was analysed in cultured human keratinocytes using a reporter assay.
Results The expression of STAT1 was demonstrated to be significantly increased at both mRNA and protein level in lesional psoriatic skin. In addition, the phosphorylation level of STAT1(Tyr701) and STAT1(Ser727) was significantly increased in lesional compared with nonlesional psoriatic skin. Luciferase assays showed a significant induction of the STAT1‐induced transcriptional activity when cultured human keratinocytes were stimulated with either interferon (IFN)‐α or IFN‐γ. STAT1(Ser727) phosphorylation induced by IFN‐α, IFN‐γ or ultraviolet B was mediated by a protein kinase C (PKC)‐δ‐ and p38 mitogen‐activated protein kinase‐dependent mechanism in human keratinocytes, whereas IFN‐α‐induced STAT1(Tyr701) phosphorylation was mediated by a PKC‐δ‐dependent mechanism.
Conclusions This study demonstrates for the first time that the phosphorylation level of STAT1(Tyr701) and STAT1(Ser727) is increased in lesional psoriatic skin. In addition, specific signalling pathways leading to this phosphorylation have been identified. Together, our data indicate an important role of STAT1 in the pathogenesis of psoriasis.
What’s already known about this topic?
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The expression of STAT1 is increased in lesional psoriatic skin.
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STAT1 has an increased nuclear expression in psoriatic epidermis.
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STAT1 can be phosphorylated on two different phosphorylation sites: a tyrosine 701 site and a serine 727 site.
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STAT1 is involved in the regulation of interferon‐responsive genes.
What does this study add?
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The phosphorylation level of STAT1(Tyr701) and STAT1(Ser727) is increased in lesional psoriatic skin.
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The two kinases, p38 mitogen‐activated protein kinase and protein kinase C‐δ, are involved in the phosphorylation of STAT1 in cultured human keratinocytes.
The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes.
Automated measurements of the ratio of concentrations ...of methane and carbon dioxide, CH4:CO2, in breath from individual animals (the so-called “sniffer technique”) and estimated CO2 production can be used to estimate CH4 production, provided that CO2 production can be reliably calculated. This would allow CH4 production from individual cows to be estimated in large cohorts of cows, whereby ranking of cows according to their CH4 production might become possible and their values could be used for breeding of low CH4-emitting animals. Estimates of CO2 production are typically based on predictions of heat production, which can be calculated from body weight (BW), energy-corrected milk yield, and days of pregnancy. The objectives of the present study were to develop predictions of CO2 production directly from milk production, dietary, and animal variables, and furthermore to develop different models to be used for different scenarios, depending on available data. An international dataset with 2,244 records from individual lactating cows including CO2 production and associated traits, as dry matter intake (DMI), diet composition, BW, milk production and composition, days in milk, and days pregnant, was compiled to constitute the training dataset. Research location and experiment nested within research location were included as random intercepts. The method of CO2 production measurement (respiration chamber RC or GreenFeed GF) was confounded with research location, and therefore excluded from the model. In total, 3 models were developed based on the current training dataset: model 1 (“best model”), where all significant traits were included; model 2 (“on-farm model”), where DMI was excluded; and model 3 (“reduced on-farm model”), where both DMI and BW were excluded. Evaluation on test dat sets with either RC data (n = 103), GF data without additives (n = 478), or GF data only including observations where nitrate, 3-nitrooxypropanol (3-NOP), or a combination of nitrate and 3-NOP were fed to the cows (GF+: n = 295), showed good precision of the 3 models, illustrated by low slope bias both in absolute values (−0.22 to 0.097) and in percentage (0.049 to 4.89) of mean square error (MSE). However, the mean bias (MB) indicated systematic overprediction and underprediction of CO2 production when the models were evaluated on the GF and the RC test datasets, respectively. To address this bias, the 3 models were evaluated on a modified test dataset, where the CO2 production (g/d) was adjusted by subtracting (where measurements were obtained by RC) or adding absolute MB (where measurements were obtained by GF) from evaluation of the specific model on RC, GF, and GF+ test datasets. With this modification, the absolute values of MB and MB as percentage of MSE became negligible. In conclusion, the 3 models were precise in predicting CO2 production from lactating dairy cows.
The aim of the study was to investigate the effects of substituting silage of chopped grass with pulp silage of grass fractionated once or twice in a biorefinery using a screw press on fiber ...kinetics, protein value, and production of CH4 in dairy cows. Six lactating multiparous Holstein cows in mid-lactation (176 ± 93 d in milk), cannulated in the rumen, duodenum, and ileum, were used in an incomplete 6 × 4 Latin square design with a 2 × 3 factorial arrangement of treatments. Perennial ryegrass was harvested in third regrowth from the same field at early and late developmental stage (35 and 44 d of regrowth, respectively) and subjected to 1 of 3 types of processing within each developmental stage. Grass was either harvested for normal silage making (mowed, wilted, chopped, and ensiled), or harvested fresh and fractionated using a screw press. Half of the pulp from the first fractionation was ensiled, whereas the other half of the pulp was rehydrated, fractionated a second time, and pulp hereof was ensiled. The grass and pulp silages were used with concentrates (65:35 forage to concentrate ratio) to make total mixed rations (TMR) based on either silage of chopped grass (GS), pulp silage of grass fractionated once (1×P), or pulp silage of grass fractionated twice (2×P), harvested either at early (E) or late (L) developmental stage resulting in 6 different TMR treatments (EGS, E1×P, E2×P, LGS, L1×P, L2×P). The TMR were fed for ad libitum intake and samples of intestinal digesta and feces were collected for determination of digestibility. The effect of processing on ash-free neutral detergent fiber (aNDFom) concentration in silages depended on developmental stage, but showed that within each developmental stage, pulp silage of grass fractionated twice had higher aNDFom concentration than pulp silage of grass fractionated once and silage of chopped grass. The 2×P resulted in lower (14.9 ± 0.55 vs. 17.5 ± 0.54 kg/d) dry matter intake (DMI) compared with GS. The effects of processing and developmental stage interacted such that apparent total-tract aNDFom digestibility was higher (784 ± 13 vs. 715 ± 13 g/kg) for L2×P compared with LGS, whereas no difference was found between E2×P and EGS. Moreover, the protein value was higher (106 ± 5 vs. 92 ± 5 g AA digested in the small intestine/kg of DMI) for 2×P compared with GS. Unexpectedly, processing had no effect on fractional rate of digestion of digestible aNDFom or CH4 yield (L/kg of DMI), whereas feeding forages harvested at early compared with late developmental stage resulted in lower CH4 yield. Feeding pulp silage of grass fractionated once generally yielded results intermediate to cows fed silage of chopped grass and pulp silage of grass fractionated twice. This study showed that pulp silage of fractionated grass could serve as feed for dairy cows because the fiber digestibility and protein value improved, but further research investigating effects of physical processing of forage on fiber kinetics is required.
The objective of this study was to investigate the effects of heat treatment (toasting) and particle size alterations (grinding; rolling) on nutrient utilization, ruminal fermentation, and supply of ...metabolizable protein (MP), and to study the interaction between processing conditions of fava beans and forage type. Six Danish Holstein dairy cows fitted with ruminal, duodenal, and ileal cannulas were used in a 6 × 4 incomplete Latin square design with 4 periods of 21-d duration. Cows were fed ad libitum with 6 experimental diets: diets high in either grass-clover silage or corn silage were combined with ground untoasted, ground toasted, or rolled untoasted fava beans. Samples of ruminal fluid, digesta from duodenum and ileum, and feces were collected, and nutrient digestibility was estimated using Cr2O3 and TiO2 as flow markers. Diets high in corn silage resulted in higher ruminal pH and higher proportion of propionate in ruminal volatile fatty acids compared with diets high in grass-clover silage. Diets high in corn silage resulted in higher apparent total-tract digestibility of crude protein and starch but lower apparent ruminal and total-tract digestibility of neutral detergent fiber compared with diets high in grass-clover silage. Rolling of fava beans decreased the in situ small intestinal disappearance of rumen-undegradable protein corrected for particle losses. Compared with grinding, rolling of fava beans reduced apparent ruminal digestibility of starch, true ruminal digestibility of organic matter, crude protein, and AA, and small intestinal digestibility of AA and starch. Grinding of fava beans increased apparent ruminal digestibility of neutral detergent fiber and reduced the proportion of propionate in ruminal volatile fatty acids compared with rolling of fava beans. In addition, rolling of fava beans had no effect on MP supply. Toasting of fava beans had no effect on in vivo nutrient digestibility except for an interaction with forage source on apparent ruminal dry matter and organic matter digestibility. Toasting of fava beans did not affect small intestinal digestion of individual and total AA, and therefore failed to increase MP supply. In conclusion, neither replacing grass-clover silage with corn silage, nor toasting nor rolling of fava beans had an effect on supply of MP.
Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to ...right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of PAH with an approximate female to male ratio of 4:1, depending on the underlying disease pathology. Overall, the therapeutic strategy for PAH remains suboptimal with poor survival rates observed in both genders. Endogenous sex hormones, in particular 17β oestradiol and its metabolites, have been implicated in the development of the disease; however, the influence of sex hormones on the underlying pathobiology remains controversial. Further understanding of the influence of sex hormones on the normal and diseased pulmonary circulation will be critical to our understanding the pathology of PAH and future therapeutic strategies. In this review, we will discuss the influence of sex hormones on the development of PAH and address recent controversies.
Linked Articles
This article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐3
The PLATO 2.0 mission Rauer, H.; Catala, C.; Benz, W. ...
Experimental astronomy,
11/2014, Letnik:
38, Številka:
1-2
Journal Article, Web Resource
Recenzirano
Odprti dostop
PLATO 2.0 has recently been selected for ESA’s M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses ...fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg
2
) and a large photometric magnitude range (4–16 mag). It focusses on bright (4–11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4–10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2–3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA’s Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
The concept of zoonotic hepatitis E in industrialized countries has emerged with the discovery of swine strains of hepatitis E virus (HEV) genotype 3, closely related to human HEV. Different routes ...of zoonotic HEV transmission have been recognized, including contact with infected pigs. Workers occupationally exposed to swine (WOES) have been considered a risk group for HEV infection, but contradictory results have been reported. In the present study, we searched for anti-HEV IgG in WOES (butchers, slaughterhouse workers, veterinarians and pig farmers;
n
= 114) and in the general population (
n
= 804) in order to investigate the potential occupational risk of zoonotic HEV infection in this work group. A significantly higher (
p
= 0.008) anti-HEV IgG seroprevalence was found in WOES (30.7 %) when compared with the general population (19.9 %). Multivariate analysis showed that having professions with exposure to pigs for more than 16.5 years was a risk factor for being positive for anti-HEV IgG (aOR of 5.4, 95 % CI 1.9–15.6,
p
= 0.002). To our knowledge, this is the first study on the prevalence of anti-HEV IgG in WOES in Portugal, also showing increased probability for infection in this group.
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