Mechanical ventilation (MV) is essential in the management of patients that underwent cardiac surgery and cardiopulmonary bypass. It has been demonstrated that MV dependence is directly related to ...morbidity incidence and ICU length of stay, with a strong impact on economic cost. Therefore identification of measures that can reduce MV interval, may reduce the incidence of respiratory complications and length of hospitalization. The aim of this study was to identify weaning indexes and adopt a weaning algorithm in order to optimize ventilatory support after cardiac surgery.
Forty-nine patients with low and medium Higgins risk score, who underwent, between February and November 1999, elective surgery at our Institution, were enrolled in this study. All patients were randomized into 2 groups: Group I (weaning group - 24 patients), extubated with the aid of a weaning protocol, and Group II (control group - 25 patients), extubated with conservative weaning, dependent on the physician's subjective clinical judgment. All patients were successfully weaned from mechanical support.
Intubation time was significantly lower in Group I than Group II and "Fast Track Recovery" group (p=0.05). ICU length of stay was also significantly lower in Group I (p=0.03). Analysis of weaning indexes did not show cut-off points predictive of successful weaning, except for PaO2/FiO2 ratio, which was higher in Group I (p=0.02).
These results confirm that the use of a weaning algorithm enables the MV interval and hospital length of stay to be shortened, suggesting that it should be used in the management following cardiac surgery.
ObjectiveHealth and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated ...by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men.DesignA longitudinal survey of 2736 community-dwelling men aged 40–79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±s.d.) 4.4±0.3 years later.ResultsPaired testosterone results were available for 2395 men. Mean (±s.d.) annualised hormone changes were as follows: testosterone −0.1±0.95 nmol/l; free testosterone (FT) −3.83±16.8 pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5 nmol/l and LH 0.08±0.57 U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic–pituitary–testicular (HPT) axis function.ConclusionsBody weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.
Axionlike particles (ALPs) are predicted in many extensions of the standard model, and their masses can naturally be well below the electroweak scale. In the presence of couplings to electroweak ...bosons, these particles could be emitted in flavor-changing B meson decays. We report herein a search for an ALP, a, in the reaction B^{±}→K^{±}a, a→γγ using data collected by the BABAR experiment at SLAC. No significant signal is observed, and 90% confidence level upper limits on the ALP coupling to electroweak bosons are derived as a function of ALP mass, improving current constraints by several orders of magnitude in the range 0.175 GeV<m_{a}<4.78 GeV.
Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 ...studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II
muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
A series of C4-substituted tertiary nitrogen-bearing 2'-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the ...2'-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound
was identified as the most potent AChE inhibitor (IC
: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound
interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound
based on its blood-brain barrier penetrating. Overall, the results suggest that this 2'-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Information
The dual‐specificity phosphatase 3 (DUSP3) regulates cell cycle progression, proliferation, senescence, and DNA repair pathways under genotoxic stress. This phosphatase ...interacts with HNRNPC protein suggesting an involvement in the regulation of HNRNPC‐ribonucleoprotein complex stability. In this work, we investigate the impact of DUSP3 depletion on functions of HNRNPC aiming to suggest new roles for this enzyme.
Results
The DUSP3 knockdown results in the tyrosine hyperphosphorylation state of HNRNPC increasing its RNA binding ability. HNRNPC is present in the cytoplasm where it interacts with IRES trans‐acting factors (ITAF) complex, which recruits the 40S ribosome on mRNA during protein synthesis, thus facilitating the translation of mRNAs containing IRES sequence in response to specific stimuli. In accordance with that, we found that DUSP3 is present in the 40S, monosomes and polysomes interacting with HNRNPC, just like other previously identified DUSP3 substrates/interacting partners such as PABP and NCL proteins. By downregulating DUSP3, Tyr‐phosphorylated HNRNPC preferentially binds to IRES‐containing mRNAs within ITAF complexes preferentially in synchronized or stressed cells, as evidenced by the higher levels of proteins such as c‐MYC and XIAP, but not their mRNAs such as measured by qPCR. Under DUSP3 absence, this increased phosphorylated‐HNRNPC/RNA interaction reduces HNRNPC‐p53 binding in presence of RNAs releasing p53 for specialized cellular responses. Similarly, to HNRNPC, PABP physically interacts with DUSP3 in an RNA‐dependent manner.
Conclusions and Significance
Overall, DUSP3 can modulate cellular responses to genotoxic stimuli at the translational level by maintaining the stability of HNRNPC‐ITAF complexes and regulating the intensity and specificity of RNA interactions with RRM‐domain proteins.
DUSP3 knockdown increases tyrosine phosphorylation levels of HNRNPC. Phosphorylated HNRNPC has increased capacity for RNA recognition and binding but reduced p53 binding. DUSP3 is present in the 40S subunit of ribosome, monosomes and polysomes interacting with HNRNPC. In DUSP3‐depleted cells the phosphorylated HNRNPC preferentially binds IRES containing mRNAs such as c‐myc and xiap increasing their protein levels, but not their mRNAs.
The effect of cimetidine administration on the disposition of acetaminophen was evaluated in seven men and six women. One gram of acetaminophen was administered to each volunteer after an overnight ...fast on two occasions in a balanced crossover design with and without cimetidine, 300 mg every 6 hours beginning 50 hours before acetaminophen administration and continuing for 22 hours after. N‐Acetylcysteine was administered on both occasions when acetaminophen was ingested to protect against glutathione depletion. Blood samples were collected serially for 12 hours after acetaminophen administration, and total urine volume was collected for 24 hours. Fractional clearances of acetaminophen through renal and metabolic routes (sulfation, glucuronidation, 3‐hydroxylation, and glutathione conjugate formation) were not altered by cimetidine administration. Studies in microsomes prepared from two human organ donors indicated that cimetidine inhibited acetaminophen reactive metabolite formation noncompetitively, with Ki values of 0.35 mmol/L and 0.32 mmol/L for the respective livers, which is 5 to 10 times the putative cimetidine concentration required for therapeutic effect.
Clinical Pharmacology and Therapeutics (1989) 46, 591–597; doi:10.1038/clpt.1989.190
▶ Fisheries can impact species, habitats and ecological communities. ▶ We describe a risk-based framework to assess these impacts. ▶ Novel features include a hierarchical structure and a ...precautionary approach. ▶ This framework has applicability in a wide range of fisheries.
Management of fisheries around the world is challenged by fishing impacts on habitats, bycatch species, threatened and endangered species, and even associated ecological communities. One response to these other factors has been a call for ecosystem-based fisheries management (EBFM), which demands consideration of the above non-target interactions. A challenge with implementation of EBFM is the scale and range of issues to be considered, all of which cannot be addressed at the same level of detail as for target species, due to data or time constraints. We developed an approach to progress the EBFM mandate in Australia, using a new ecological risk assessment framework applied to fisheries, termed Ecological Risk Assessment for the Effects of Fishing (ERAEF). Novel features of this framework include its hierarchical structure and its precautionary approach to uncertainty. The amount of information required increases through the hierarchy, and allows application in data-limited situations. The ERAEF framework has been applied to over 30 fisheries in Australia and elsewhere. The efficiencies in application of the hierarchical approach are illustrated by the south-east otter trawl fishery, where following Level 1 assessment of all components, an initial set of 600 species and 158 habitats was reduced to a group of concern of 159 species and 46 habitats using the Level 2 analysis, with the number of species of concern further reduced to 25 following Level 3 analysis. As a result of the assessments in Australia, management actions have been enacted for a range of the high risk species. Overall, the ERAEF approach offers a realistic method to assess ecological risk in an EBFM context, and has applicability in a wide range of fisheries. The interactive and inclusive nature of the approach also has the advantage of bringing stakeholders, scientists and managers together to develop management solutions.
Abstract Objective To investigate the impacts of vitamin D status, supplementation and vitamin D receptor (VDR) gene polymorphisms on tuberculosis (TB). Methods We conducted a systematic review of ...published studies pertaining to case–control and randomized-control trials from 2002 to 2014 using the PubMed database. Results and conclusion Individuals with TB have lower vitamin D status than healthy individuals. Some VDR gene polymorphisms are associated with increased susceptibility to TB while others may not. Supplementation with vitamin D leads to improved clinical outcomes. However, further studies with a larger patient population and different ethnicities are needed to confirm these effects.
We present measurements of branching fractions and CP-violating asymmetries for two-body neutral B meson decays to charged pions and kaons based on a sample of about 88x10(6) Upsilon(4S)-->BB decays. ...From a time-independent fit we measure the charge-averaged branching fractions B(B0-->pi+pi-)=(4.7+/-0.6+/-0.2)x10(-6), B(B0-->K+pi-)=(17.9+/-0.9+/-0.7)x10(-6), and the direct CP-violating charge asymmetry A(Kpi)=-0.102+/-0.050+/-0.016 -0.188,-0.016, where the ranges in square brackets indicate the 90% confidence intervals. From a time-dependent fit we measure the B0-->pi+pi- CP-violating parameters S(pipi)=0.02+/-0.34+/-0.05 -0.54,+0.58 and C(pipi)=-0.30+/-0.25+/-0.04 -0.72,+0.12.
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