Abstract
The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health ...implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.
This Scientific Statement critically reviews the definition of obesity, providing a list of assessment methods, obesity-related diseases, and prevention measures.
SUMMARY
Arabidopsis thaliana ABSCISIC ACID INSENSITIVE3 (ABI3) is a transcription factor in the B3 domain family. ABI3, along with B3 domain transcription factors LEAFY COTYLEDON2 (LEC2) and FUSCA3 ...(FUS3), and LEC1, a subunit of the CCAAT box‐binding complex, form the so‐called LAFL network to control various aspects of seed development and maturation. ABI3 also contributes to the abscisic acid (ABA) response. We report on chromatin immunoprecipitation‐tiling array experiments to map binding sites for ABI3 globally. We also assessed transcriptomes in response to ABI3 by comparing developing abi3‐5 and wild‐type seeds and combined this information to ascertain direct and indirect responsive ABI3 target genes. ABI3 can induce and repress its transcription of target genes directly and some intriguing differences exist in cis motifs between these groups of genes. Directly regulated targets reflect the role of ABI3 in seed maturation, desiccation tolerance, entry into a quiescent state and longevity. Interestingly, ABI3 directly represses a gene encoding a microRNA (MIR160B) that targets AUXIN RESPONSE FACTOR (ARF)10 and ARF16 that are involved in establishment of dormancy. In addition, ABI3, like FUS3, regulates genes encoding MIR156 but while FUS3 only induces genes encoding this product, ABI3 induces these genes during the early stages of seed development, but represses these genes during late development. The interplay between ABI3, the other LAFL genes, and the VP1/ABI3‐LIKE (VAL) genes, which are involved in the transition to seedling development are examined and reveal complex interactions controlling development.
Significance Statement
Genome‐wide determination of ABSCISIC ACID INSENSITIVE3 (ABI3) targets reveals that not only does ABI3 show the expected direct induction of expression of target genes, but surprisingly also directly represses some targets, and instances exist where the influence of ABI3 changes depending on developmental stage. Intriguing differences in cis motifs exist between the directly induced and repressed genes, as well as between binding sites for ABI3 and the related B3 domain embryo transcription factor FUS3.
Nanoparticle-based labels are emerging as simpler and more sensitive alternatives to traditional fluorescent small molecules and radioactive reporters in biomarker assays. The determination of ...biomarker levels is a recommended clinical practice for the assessment of many diseases, and detection of multiple analytes in a single assay, known as multiplexing, can increase predictive accuracy. While multiplexed detection can also simplify assay procedures and reduce systematic variability, combining multiple assays into a single procedure can lead to complications such as substrate cross-reactivity, signal overlap, and loss of sensitivity. By combining the specificity of biomolecular interactions with the tunability of quantum dot optical properties, we have developed a detection system capable of simultaneous evaluation of the activity of two critical enzyme classes, proteases and kinases. We avoid cross-reactivity and signal overlap by synthesizing enzyme-specific peptide sequences with orthogonal terminal functionalization for attachment to quantum dots with distinct emission spectra. Enzyme activity is reported via binding of either gold nanoparticle–peptide conjugates or FRET acceptor dye-labeled antibodies, which mediate changes in quantum dot emission spectra. To the best of our knowledge, this is the first demonstration of the multiplexed sensing of the activity of two different classes of enzymes via a nanoparticle-based activity assay. Using the quantum dot-based assay described herein, we were able to detect the protease activity of urokinase-type plasminogen activator at concentrations ≥ 50 ng/mL and the kinase activity of human epidermal growth factor receptor 2 at concentrations ≥ 7.5 nM, levels that are clinically relevant for determination of breast cancer prognosis. The modular nature of this assay design allows for the detection of different classes of enzymes simultaneously and represents a generic platform for high-throughput enzyme screening in rapid disease diagnosis and drug discovery.
In this longitudinal multiinformant study negative emotionality and sensory processing sensitivity were compared as susceptibility markers among kindergartners. Participating children (N = 264, 52.9% ...boys) were Dutch kindergartners (Mage = 4.77, SD = 0.60), followed across three waves, spaced seven months apart. Results show that associations between parenting and child behavior did not depend on children's negative emotionality. Sensory processing sensitivity, however, interacted with both (changes in) negative and (changes in) positive parenting in predicting externalizing, but not prosocial, behavior. Depending on the interaction, vantage sensitivity and differential susceptibility models were supported. The findings suggest that sensory processing sensitivity may be a more proximal correlate of individual differences in susceptibility, compared with negative emotionality.
Aims/hypothesis
The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes.
Methods
A sample of 302 diabetic patients aged ...≥70 years was assessed for dementia or cognitive impairment without dementia in 2001–2002 and a subsample of non-demented patients (
n
= 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH.
Results
There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06–8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43–12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline.
Conclusions/interpretation
Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.
In patients with ischemic stroke and a proximal cerebral arterial occlusion and salvageable tissue on imaging, alteplase followed by thrombectomy with a stent retriever was more effective than ...alteplase alone in improving reperfusion, neurologic recovery, and functional outcome.
The results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial,
1
which showed reduced disability among patients with ischemic stroke who were treated with endovascular thrombectomy in addition to standard care, represent an advance in stroke care. The MR CLEAN study followed several trials that had neutral findings with respect to the use of endovascular thrombectomy.
2
–
4
In the largest of these trials, the Interventional Management of Stroke 3 (IMS-3) study, investigators compared the administration of 0.9 mg of alteplase per kilogram of body weight to a bridging strategy of . . .
Marine seismic surveys produce high intensity, low-frequency impulsive sounds at regular intervals, with most sound produced between 10 and 300Hz. Offshore seismic surveys have long been considered ...to be disruptive to fisheries, but there are few ecological studies that target commercially important species, particularly invertebrates. This review aims to summarise scientific studies investigating the impacts of low-frequency sound on marine fish and invertebrates, as well as to critically evaluate how such studies may apply to field populations exposed to seismic operations. We focus on marine seismic surveys due to their associated unique sound properties (i.e. acute, low-frequency, mobile source locations), as well as fish and invertebrates due to the commercial value of many species in these groups. The main challenges of seismic impact research are the translation of laboratory results to field populations over a range of sound exposure scenarios and the lack of sound exposure standardisation which hinders the identification of response thresholds. An integrated multidisciplinary approach to manipulative and in situ studies is the most effective way to establish impact thresholds in the context of realistic exposure levels, but if that is not practical the limitations of each approach must be carefully considered.
•Generalisations about impacts are often inappropriate due to the vast gap in our knowledge about sound thresholds and recovery from impact.•A disparity exists between results obtained in the field and results obtained from the laboratory.•A multidisciplinary approach to lab & field studies is ideal, but if not practical, the limitations of each approach must be carefully considered.
Predicting soil carbon loss with warming van Gestel, Natasja; Shi, Zheng; van Groenigen, Kees Jan ...
Nature (London),
02/2018, Letnik:
554, Številka:
7693
Journal Article
Two randomized, phase 3, open-label noninferiority trials compared vadadustat with darbepoetin alfa in patients with non–dialysis-dependent chronic kidney disease. Vadadustat, as compared with ...darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not for cardiovascular safety.
•The first study to profile FA from diverse yeasts grown in three culture conditions.•Discovery of thirteen new oleaginous yeast species.•FA proportion varied with the growth conditions regardless of ...taxonomic affiliation.•Dominant fatty acid were oleic acid, palmitic acid, linoleic acid and stearic acid.•Nitrogen starvation boosted accumulation of linoleic acid in many species.
Oleaginous yeasts have been studied for oleochemical production for over 80years. Only a few species have been studied intensely. To expand the diversity of oleaginous yeasts available for lipid research, we surveyed a broad diversity of yeasts with indicators of oleaginicity including known oleaginous clades, and buoyancy. Sixty-nine strains representing 17 genera and 50 species were screened for lipid production. Yeasts belonged to Ascomycota families, Basidiomycota orders, and the yeast-like algal genus Prototheca. Total intracellular lipids and fatty acid composition were determined under different incubation times and nitrogen availability. Thirteen new oleaginous yeast species were discovered, representing multiple ascomycete and basidiomycete clades. Nitrogen starvation generally increased intracellular lipid content. The fatty acid profiles varied with the growth conditions regardless of taxonomic affiliation. The dominant fatty acids were oleic acid, palmitic acid, linoleic acid, and stearic acid. Yeasts and culture conditions that produced fatty acids appropriate for biodiesel were identified.
PDF
