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Immunoassays are a powerful tool for sensitive and quantitative analysis of a wide range of biomolecular analytes in the clinic and in research laboratories. However, enzyme-linked immunosorbent assay (ELISA)-the gold-standard assay-requires significant user intervention, time, and clinical resources, making its deployment at the point-of-care (POC) impractical. Researchers have made great strides toward democratizing access to clinical quality immunoassays at the POC and at an affordable price. In this review, we first summarize the commercially available options that offer high performance, albeit at high cost. Next, we describe strategies for the development of frugal POC assays that repurpose consumer electronics and smartphones for the quantitative detection of analytes. Finally, we discuss innovative assay formats that enable highly sensitive analysis in the field with simple instrumentation.An optical microscope is probably the most intuitive, simple, and commonly used instrument to observe objects and discuss behaviors through images. Although the idea of imaging electrochemical processes operando by optical microscopy was initiated 40 years ago, it was not until significant progress was made in the last two decades in advanced optical microscopy or plasmonics that it could become a mainstream electroanalytical strategy. This review illustrates the potential of different optical microscopies to visualize and quantify local electrochemical processes with unprecedented temporal and spatial resolution (below the diffraction limit), up to the single object level with subnanoparticle or single-molecule sensitivity. Developed through optically and electrochemically active model systems, optical microscopy is now shifting to materials and configurations focused on real-world electrochemical applications.Raman spectroscopy is a viable tool within process analytical technologies due to recent technological advances. In this article, we evaluate the feasibility of Raman spectroscopy for in-line applications in the food industry by estimating the concentration of the fatty acids EPA + DHA in ground salmon samples (n = 63) and residual bone concentration in samples of mechanically recovered ground chicken (n = 66). The samples were measured under industry like conditions They moved on a conveyor belt through a dark cabinet where they were scanned with a wide area illumination standoff Raman probe. Such a setup should be able to handle relevant industrial conveyor belt speeds, and it was studied how different speeds (i.e., exposure times) influenced the signal-to-noise ratio (SNR) of the Raman spectra as well as the corresponding model performance. For all samples we applied speeds that resulted in 1 s, 2 s, 4 s, and 10 s exposure times. Samples were scanned in both heterogenous and homogenous state. The slowest speed (10 s exposure) yielded prediction errors (RMSECV) of 0.41%EPA + DHA and 0.59% ash for the salmon and chicken data sets, respectively. The more in-line relevant exposure time of 1 s resulted in increased RMSECV values, 0.84% EPA + DHA and 0.84% ash, respectively. The increase in prediction error correlated closely with the decrease in SNR. Further improvements of model performance were possible through different noise reduction strategies. Model performance for homogenous and heterogenous samples was similar, suggesting that the presented Raman scanning approach has the potential to work well also on intact heterogenous foods. The estimation errors obtained at these high speeds are likely acceptable for industrial use, but successful strategies to increase SNR will be key for widespread in-line use in the food industry.
Physical inactivity, sugar sweetened beverage consumption, alcohol use, smoking, poor sleep and excessive recreational screen time (the 'Big 6' lifestyle risk behaviours) often co-occur and are key risk factors for psychopathology. However, the best fitting latent structure of the Big 6 is unknown and links between multiple lifestyle risk behaviours and hierarchical dimensions of psychopathology have not been explored among adolescents. This study aimed to address these gaps in the literature.
Confirmatory factor analysis, latent class analysis and factor mixture models were conducted among 6640 students (
= 12.7 years) to identify the latent structure of the Big 6 lifestyle risk behaviours. Structural equation models were then used to examine associations with psychopathology.
A mixture model with three classes, capturing mean differences in a single latent factor indexing overall risk behaviours, emerged as the best fitting model. This included relatively low-risk (Class 1 30%), moderate-risk (Clastic intervention approaches may be valuable for reducing risk of psychopathology.
Classes representing differences in probabilities of the Big 6 lifestyle risk behaviours relate to varying levels of hierarchical dimensions of psychopathology, suggesting multiple health behaviour change and transdiagnostic intervention approaches may be valuable for reducing risk of psychopathology.Hydrogels are ideal materials for mimicking and engineering soft tissue. Hyaluronic acid is a linear polysaccharide native to the human extracellular matrix. In this study, we first develop and characterize two hydrogel compositions built from oxidized HA and gelatin with and without alginate-di-aldehyde (ADA) crosslinked by ionic and enzymatic agents with potential applications in soft tissue engineering and tissue mimicking structures. The stability under incubation conditions was improved by adjusting crosslinking times. Through large-strain mechanical measurements, the hydrogels' properties were compared to human brain tissue and the samples containing ADA revealed similar mechanical properties to the native tissue specimens in cyclic compression-tension. In vitro characterization demonstrated a high viability of encapsulated mouse embryonic fibroblasts and a spreading of the cells in case of ADA-free samples. Impact statement Brain mimicking materials are required in several medical and industrial fields for the development of safety gear, testing of medical imaging techniques, surgical training, tissue engineering, and modeling of the mechanical behavior of tissues. The materials must resemble the microstructure, chemistry, and mechanical properties of the native tissue extracellular matrix while being adjustable in degradation to suit the various applications. In this article, different methods are used to evaluate a novel hydrogel material and its suitability as brain mimicking matrix.Defined as congenital conditions in which development of chromosomal, gonadal, or anatomic sex is atypical, differences or disorders of sex development (DSDs) comprise many discrete diagnoses ranging from those associated with few phenotypic differences between affected and unaffected individuals to those where questions arise regarding gender of rearing, gonadal tumor risk, genital surgery, and fertility. Controversies exist in numerous areas including how DSDs are conceptualized, how to refer to the set of conditions and those affected by them, and aspects of clinical management that extend from social media to legislative bodies, courts of law, medicine, clinical practice, and scholarly research in psychology and sociology. In addition to these aspects, this review covers biological and social influences on psychosocial development and adjustment, the psychosocial and psychosexual adaptation of people born with DSDs, and roles for clinical psychologists in the clinical management of DSDs.The central goal of clinical psychology is to reduce the suffering caused by mental health conditions. Anxiety, mood, psychosis, substance use, personality, and other mental disorders impose an immense burden on global public health and the economy. Tackling this burden will require the development and dissemination of intervention strategies that are more effective, sustainable, and equitable. Clinical psychology is uniquely poised to serve as a transdisciplinary hub for this work. But rising to this challengerequires an honest reckoning with the strengths and weaknesses of current training practices. Building on new data, we identify the most important challenges to training the next generation of clinical scientists. We provide specific recommendations for the full spectrum of stakeholders-from funders, accreditors, and universities to program directors, faculty, and students-with an emphasis on sustainable solutions that promote scientific rigor and discovery and enhance the mental health of clinical scientists and the public alike.Evidence suggests that adjunctive psychosocial intervention for the treatment of pediatric bipolar spectrum disorders (BPSDs) is effective, feasible, and highly accepted as both an acute and maintenance treatment for youth with BPSD diagnoses as well as a preventive treatment for high-risk youth who are either asymptomatic or exhibit subsyndromal mood symptoms. Here, we provide a comprehensive review of all known evidence-based interventions, including detailed descriptions of treatment targets and core components, results of clinical trials, and updated research on mediators and moderators of treatment efficacy. Treatments are presented systematically according to level of empirical support (i.e., well established, probably efficacious, possibly efficacious, experimental, or questionable); upcoming and ongoing trials are included when possible. In line with a staging approach, preventive interventions are presented separately. Recommendations for best practices based on age, stage, and additional evidence-based child and family factors shown to affect treatment outcomes are provided.KRAS is a GTPase involved in the proliferation signaling of several growth factors. The KRAS gene is GC-rich, containing regions with known and putative G-quadruplex (G4) forming regions. Within the middle of the G-rich proximal promoter, stabilization of the physiologically active G4mid structure downregulates transcription of KRAS; the function and formation of other G4s within the gene are unknown. Herein we identify three putative G4-forming sequences (G4FS) within the KRAS gene, explore their G4 formation, and develop oligonucleotides targeting these three regions and the G4mid forming sequence. We tested Polypurine Reverse Hoogsteen hairpins (PPRHs) for their effects on KRAS regulation via enhancing G4 formation or displacing G-rich DNA strands, downregulating KRAS transcription and mediating an anti-proliferative effect. Five PPRH were designed, two against the KRAS promoter G4mid and three others against putative G4FS in the distal promoter, intron 1 and exon 5. PPRH binding was confirmed by gel electrophoresis. The effect on KRAS transcription was examined by luciferase, FRET Melt2, qRT-PCR. check details Cytotoxicity was evaluated in pancreatic and ovarian cancer cells. PPRHs decreased activity of a luciferase construct driven by the KRAS promoter. PPRH selectively suppressed proliferation in KRAS dependent cancer cells. PPRH demonstrated synergistic activity with a KRAS promoter selective G4-stabilizing compound, NSC 317605, in KRAS-dependent pancreatic cells. PPRHs selectively stabilize G4 formation within the KRAS mid promoter region and represent an innovative approach to both G4-stabilization and to KRAS modulation with potential for development into novel therapeutics.
Website: https://www.selleckchem.com/products/bgj398-nvp-bgj398.html
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