Mild hyponatremia has traditionally been considered benign, but it may be associated with gait and attention deficits and an increased risk of falls that may result in fracture. A retrospective study ...was conducted to quantify the association of hyponatremia with fracture occurrence and to examine whether this relationship is independent of osteoporosis.
This study analyzed 1408 consecutive female patients who underwent bone mineral density measurement (Lunar IDXA) between September 1, 2006 and April 11, 2007 and who had available laboratory data. Self reported fracture occurrence was confirmed by radiology report or attendance at a fracture clinic. The significance and independence of the association of hyponatremia with fracture was quantified using logistic regression.
The mean (SD) serum sodium (Na(+)) was 140.6 (3.0) mmol/L; 59 (4.2%) had Na(+) < 135 mmol/L. Forty-five percent of subjects were osteoporotic and 18% had a prior fracture. Hyponatremia was present in 8.7% of those with versus 3.2% of those without a confirmed fracture (P < 0.001). On multivariate logistic regression analysis controlling for age, T-score, chronic kidney disease stage, osteoporotic risk factors (amenorrhea, family history, regular steroid use, smoking history, alcohol use, history of liver disease, and low-calcium diet), and osteoporosis treatments (calcium and vitamin D supplements, antiresorptives, and hormonal replacement therapy), Na(+) < 135 versus Na(+) >or= 135 mmol/L remained significantly and independently associated with fracture occurrence (P < 0.01).
Mild hyponatremia may be a readily identifiable and potentially modifiable risk factor for fracture.
Abstract Background The clinical outcomes following rituximab (RTX) treatment in patients with SLE is highly variable. We aimed to identify predictive and prognostic factors associated with RTX ...therapy outcomes in patients with SLE. Methods Studies in adults and paediatric patients with SLE were included. We included randomized clinical trials (RCTs) for predictors of differential treatment effect and cohort studies for potential prognostic factors in patients treated with RTX (global clinical, cutaneous and renal either response or relapse and side effects). Methodological quality was assessed using Cochrane Collaboration Risk of Bias tool and the Quality In Prognosis Studies Tool (QUIPS) for RCTs and cohort studies, respectively. The quality of subgroup analyses testing predictors of differential treatment response was also evaluated. A best evidence synthesis was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results Sixteen articles were included (3 from 2 RCTs and 13 from 6 cohort studies). The overall quality of evidence (QoE) was low to very low (GRADE framework). QoE for predictive factors based on RCTs analysing sociodemographic variables, was rated very low due lack interaction tests, limited power of subgroup analyses, study limitations and imprecisions. Disease-related factors including clinical phenotype and severity, baseline anti-ENA antibodies and anti-Ro antibodies, interleukin (IL) 2/21 single nucleotide polymorphism (SNP), as well as post-RTX complete B cell depletion and earlier B cell repopulation showed some evidence for prognostic value, but were rated low to very low QoE because of early phase of investigation (exploratory analysis), insufficient adjustment for confounding in most studies, high risk of bias, inconsistency and imprecisions. Conclusions To date studies addressing prognostic factors are hypothesis generating and cannot be used to make any specific recommendations for routine clinical practice. A number of potential predictors/prognostic factors were identified which require to be validated as being specific for response to RTX therapy and to enable more personalised use of this agent.
Cogan’s syndrome, typified by the combination of interstitial keratitis and immune-mediated sensorineural hearing loss, is a rare condition, and commonly associated with a diagnostic delay. Using a ...standard search protocol, we review the literature to date, focusing on a number of key areas pertaining to diagnosis, presentation and treatment. Using a case illustration of atypical disease which led to fulminant aortic regurgitation, we highlight the need for continued and collaborative research in order to identify negative prognostic factors and thus tailor therapeutic regimens. Atypical Cogan’s syndrome is more commonly associated with systemic manifestations than typical disease, and may be refractory to immunosuppressive treatment. We discuss the application of laboratory (e.g antibodies targeting inner ear antigens) and radiological (PET-CT) aids to disease confirmation and detection of sub-clinical vascular inflammation. As illustrated by the included case description, some patients remain refractory to intense immunosuppression and delineation of adverse prognostic factors which may direct treatment, perhaps including the use of PET-CT, will contribute in the future to improving patient outcomes
Barriers to accessibility are defined as 'factors in a person's environment that, through their absence or presence, limit functioning and create disability' 1. There are four elements that are ...incorporated into this term which includes: physical environment, lack of assistive technology, attitudes of others and the lack of or restrictive services, systems and policies 1. These barriers to accessibility are present for 13% of the Irish population. Many initiatives have been developed and implemented for people with physical disabilities; however, people with intellectual disabilities (ID) remain invisible. This invisible population accounts for 9.7% of our population or 75% of the population of people with disabilities 2. Thus, it is imperative that we commence to implement Universal Design (UD) approaches that increase accessibility and empower the invisible to become visible. One such invisible group that holds substantial potential to bring immense value to companies is that of people with Autism Spectrum Disorders (ASD) 3. ASD currently impacts 1 in 68 people worldwide with this figure growing annually at a rate of 10-17% 4. 80% of people with ASD are either unemployed or underemployed; this can be attributed to barriers to accessibility 5. Two of the most common barriers to accessibility experienced by those with ASD are environmental and attitudes of others 6,7. These barriers have the potential to be overcome through the use of Virtual Reality (VR) technology to provide training and education to managers. VR technology is being used to empower managers to reduce these barriers, increase accessibility and develop inclusive environments and cultures. VR technology can be used to empower managers to recognise and reduce the barriers facing those with ASD. VR is a catalyst for managers to be able to identify the environmental barriers facing people with ASD within a work environment. This solution also provides them with the skills necessary to commence making adaptations to the environment to reduce or eliminate these barriers. The use of this technology and paradigm shift brings many benefits for the individual and the company. A mixed method approach has been used for the purposes of data collection. The tools that were utilised were interviews with HR managers and people with ASD; and surveys were circulated to HR managers, senior managers, Chief Executive Officers and people with ASD. The results of these were positive and clearly verified that there is a need to empower managers to increase accessibility within their organisations.
Sensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for use at the point-of-need are critical for the emerging field of personalised medicine for which companion diagnostics ...are essential, as well as for application in low resource settings. Here we report on the development of a point-of-care nucleic acid lateral flow test for the direct detection of isothermally amplified DNA. The recombinase polymerase amplification method is modified slightly to use tailed primers, resulting in an amplicon with a duplex flanked by two single stranded DNA tails. This tailed amplicon facilitates detection via hybridisation to a surface immobilised oligonucleotide capture probe and a gold nanoparticle labelled reporter probe. A detection limit of 1 × 10
M (190 amol), equivalent to 8.67 × 10
copies of DNA was achieved, with the entire assay, both amplification and detection, being completed in less than 15 minutes at a constant temperature of 37 °C. The use of the tailed primers obviates the need for hapten labelling and consequent use of capture and reporter antibodies, whilst also avoiding the need for any post-amplification processing for the generation of single stranded DNA, thus presenting an assay that can facilely find application at the point of need.
In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the ...specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5' or 3' end or at both ends. The TT-tail at the 5' end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed.
Family interventions have been found to be effective in pediatric bipolar disorder (BD). This study examined the moderating effects of parental expressed emotion (EE) on the 2-year symptomatic ...outcomes of adolescent BD patients assigned to family-focused therapy for adolescents (FFT-A) or a brief psychoeducational treatment (enhanced care EC).
A referred sample of 58 adolescents (mean age 14.5 +/- 1.6 years, range 13-17 years) with BD I, II, or not otherwise specified was randomly allocated after a mood episode to FFT-A or EC, both with protocol pharmacotherapy. Levels of EE (criticism, hostility, or emotional overinvolvement) in parents were assessed through structured interviews. Adolescents and parents in FFT-A underwent 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training, whereas adolescents and parents in EC underwent 3 psychoeducation sessions. Independent "blind" evaluators assessed adolescents' depressive and manic symptoms every 3 to 6 months for 2 years.
Parents rated high in EE described their families as lower in cohesion and adaptability than parents rated low in EE. Adolescents in high-EE families showed greater reductions in depressive and manic symptoms in FFT-A than in EC. Differential effects of FFT-A were not found among adolescents in low-EE families. The results could not be attributed to differences in medication regimens.
Parental EE moderates the impact of family intervention on the symptomatic trajectory of adolescent BD. Assessing EE before family interventions may help determine which patients are most likely to benefit from treatment.
Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis in mice. Here, we report that this is explained by an ∼60% ...reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein structure, lipid binding, and transport. The ApoE promoter contains a functional Zfp125-binding element that is also present in 17 other lipid-related genes repressed by Zfp125. While liver-specific knockdown of Zfp125 causes an “Alb-D2KO-like” metabolic phenotype, liver-specific normalization of Zfp125 expression in Alb-D2KO mice rescues the phenotype, restoring normal susceptibility to diet-induced obesity, liver steatosis, and hypercholesterolemia.
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•Zfp125 is a liver transcriptional repressor of lipid-related genes•Hepatic Zfp125 expression is induced by fasting and Foxo1•Zfp125 reduces lipoprotein assembly and VLDL secretion•Zfp125 expression promotes lipid accumulation and liver steatosis in mice
Mice with liver-specific disruption of the type 2 deiodinase gene are resistant to both diet-induced obesity and hepatosteatosis. Fernandes et al. show that this is due to a reduction in liver expression of zinc-finger protein-125, a Foxo1-inducible transcriptional repressor that causes lipid accumulation by reducing hepatic secretion of VLDL.
Advances in aptamers-based lateral flow assays Jauset-Rubio, Miriam; El-Shahawi, Mohammad S.; Bashammakh, Abdulaziz S. ...
TrAC, Trends in analytical chemistry (Regular ed.),
December 2017, 2017-12-00, Letnik:
97
Journal Article
Recenzirano
The use of lateral flow assays exploiting antibodies is well established in different fields due to their advantages, which include low cost, ease of production and rapid response, with the only ...required end-user intervention being sample addition. In recent years, aptamer-based lateral flow assays are garnering increasing interest offering a highly cost-effective and more flexible alternative to antibodies. In this review, an overview of the aptamer-based lateral flow assays developed to date is provided, highlighting the advantages of using aptamers and their ability to be incorporated into formats not possible with antibodies.
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