Remission in Rheumatoid Arthritis

With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal

An update on Cention N: An aesthetic direct bulk-fill restorative material

The demand for aesthetic restorative materials has increased in recent years. Glass ionomer cements (GIC), their modifications, and various composite restorative materials have been developed as direct tooth-coloured restorative materials. However, none of these materials can be compared to the properties of amalgam restorative materials. Recently, a new direct tooth-coloured, bulk-fill, and aesthetic restorative material, Cention N, was developed. This material is easy to handle and has properties similar to those of type-IX GIC. This article provides an update on the composition and properties of Cention N restorative material

Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential

BACKGROUND: In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. RESULTS: We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed. CONCLUSION: These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma

FLOTATION TECHNOLOGY

Lawrence K. Wang, Nazih K. Shammas, William A. Selke, and Donald B. Aulenbach (2010). Flotation Technology, Humana Press, Springer Nature, USA. 680 pages. doi = 10.1007/978-1-60327-133-2; ISBN : 978-1-58829-494-4 ....... ABSTRACT: This flotation technology book has four special features: (a) Detailed coverage of the principles of air flotation technology and the fundamentals of water and wastewater flotation and lake restoration; (b) Special emphasis on industry standards, trends in the field, full-scale operation and laboratory simulation of air flotation processes; (c) Ample examples of actual operating water and wastewater treatment plants based on air flotation; and (d) Plenty reference of practical use to scientists, researchers, educators and designers of water and wastewater treatment systems. .... KEYWORDS: Oil Water Separation; Dissolved Air Flotation; Electrocoagulation Flotation; Electroflotation; Filtration; Gas Dissolution; Ozone-Oxygen Oxidation Flotation; Paper Mills; Meat Processing Waste Pretreatment; Seafood Processing Wastewater Pretreatment; Wastewater Flotation; Lake Restoration; Algae Separation; Water Quality and Water Pollution; Laboratory Simulation and Testing; Pittsfield Water Treatment Plant; RBC; UV; Recreational Wastewater Treatmen

Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes

Objective In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures

Characterisation of the treatment provided for children with unilateral hearing loss

Background: Children with permanent unilateral hearing loss (UHL) are an understudied population, with limited data to inform the guidelines on clinical management. There is a funding gap in healthcare provision for the children with UHL in the United Kingdom, where genetic screening, support services, and devices are not consistently provided or fully funded in all areas. They are a disparate population with regard to aetiology and their degree of hearing loss, and hence their device choice and use. Despite having one “good ear”, some children with UHL can have similar outcomes, socially, behaviourally, and academically, to children with bilateral hearing loss, highlighting the importance of understanding this population. In this longitudinal cohort study, we aimed to characterise the management of the children with UHL and the gaps in the support services that are provided for the children in Nottingham, United Kingdom. Methods: A cohort study was conducted collecting longitudinal data over 17 years (2002–2019) for 63 children with permanent congenital confirmed UHL in a large tertiary regional referral centre for hearing loss in Nottingham, United Kingdom. The cases of UHL include permanent congenital, conductive, mixed, or sensorineural hearing loss, and the degree of hearing loss ranges from mild to profound. The data were taken from their diagnostic auditory brainstem responses and their two most recent hearing assessments. Descriptors were recorded of the devices trialled and used and the diagnoses including aetiology of UHL, age of first fit, degree of hearing loss, when and which type of device was used, why a device was not used, the support services provided, concerns raised, and who raised them. Results: Most children (45/63; 71%) trialled a device, and the remaining 18 children had no device trial on record. Most children (20/45; 44%) trialled a bone-conduction device, followed by contralateral routing of signal aid (15/45; 33%) and conventional hearing aids (9/45; 20%). Most children (36/45; 80%) who had a device indicated that they wore their device “all day” or every day in school. Few children (8/45; 18%) reported that they wore their device rarely, and the reasons for this included bullying (3/8), feedback from the device (2/8), and discomfort from the device (2/8). Only one child reported that the device was not helping with their hearing. The age that the children were first fitted with their hearing device varied a median of 2.5 years for hearing aids and bone-conduction devices and 7 years for a contralateral routing of signal aid. The length of time that the children had the device also varied widely (median of 26 months, range 3–135 months); the children had their bone-conduction hearing aid for the longest period of time (median of 32.5 months). There was a significant trend where more recent device fittings were happening for children at a younger age. Fifty-one children were referred by the paediatric audiologist to a support service, 72.5% (37/51) were subsequently followed up by the referred service with no issue, whilst the remaining 27.5% (14/51) encountered an issue leading to an unsuccessful provision of support. Overall, most children (65%, 41/63) had no reported concerns, and 28.5% (18/63) of the children went on to have a documented concern at some point during their audiological care: five with hearing aid difficulties, five with speech issues, four with no improvement in hearing, three facing self-image or bullying issues, and one case of a child struggling to interact socially with friends. Three of these children had not trialled a device. We documented every concern reported from the parents, clinicians, teachers of the deaf, and from the children themselves. Where concerns were raised, more than half (58.6%, 10/18) were by schools and teachers, the remaining four concerns were raised by the family, and further four concerns were raised by the children themselves. Conclusion: To discover what management will most benefit which children with permanent UHL, we first must characterise their treatment, their concerns, and the support services available for them. Despite the children with UHL being a highly disparate population—in terms of their aetiology, their device use, the degree of hearing loss, and the age at which they trial a device—the majority report they use their device mostly in school. In lieu of available data and in consideration of the devices that are available to them, it could be useful to support families and clinicians in understanding the devices which are most used and where they are used. Considering the reasons for cessation of regular device use counselling and support services would be vital to support the children with UHL

Non-small cell lung cancer presenting with choroidal metastasis as first sign and showing good response to chemotherapy alone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Metastatic tumors are the most common intra-ocular malignancies and choroid is by far the most common site for intra-ocular malignancies. Multiple foci are usually involved, and bilateral involvement is frequently seen. The primary sites for choroidal metastasis in decreasing order and by gender are: breast, lung, unknown primary, gastrointestinal and pancreas, skin melanoma and other rare sources in females, and lung, unknown primary, gastrointestinal and pancreas, prostate, kidney, skin melanoma and other rare sources in males. Available treatment options are external beam radiotherapy and plaque radiotherapy, while new methods like surgical resection, transpupillary thermotherapy and intravitreal chemotherapy offer promises for the future. The use of chemotherapy alone for choroidal metastases is not widely reported.</p> <p>Case presentation</p> <p>We report the case of a 50-year-old Indian man who had a unilateral solitary lesion in his right eye. He was found to have an adenocarcinoma of the lung with choroidal metastasis as the first presenting sign. There were no findings of metastasis involving his contralateral eye. He was administered chemotherapy based on gemcitabine and carboplatin. He had significant progressive subjective and objective improvement since his first chemotherapy. His current best corrected visual acuity is 20/60 after three cycles of chemotherapy.</p> <p>Conclusions</p> <p>Chemotherapy alone can be used as an effective mode of treatment in patients who have primary tumors that respond to chemotherapy.</p

A Systematic Literature Review of Students as Partners in Higher Education

“Students as Partners” (SaP) in higher education re-envisions students and staff as active collaborators in teaching and learning. Understanding what research on partnership communicates across the literature is timely and relevant as more staff and students come to embrace SaP. Through a systematic literature review of empirical research, we explored the question: How are SaP practices in higher education presented in the academic literature? Trends across results provide insights into four themes: the importance of reciprocity in partnership; the need to make space in the literature for sharing the (equal) realities of partnership; a focus on partnership activities that are small scale, at the undergraduate level, extracurricular, and focused on teaching and learning enhancement; and the need to move toward inclusive, partnered learning communities in higher education. We highlight nine implications for future research and practice.</jats:p

Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression