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BACKGROUND AND PURPOSE Instruments developed specifically to measure nurse caring behaviors need to be assessed in different cultural contexts. The purpose was to translate the Caring Behaviors Inventory (CBI) into Turkish and evaluate its psychometric properties. NSC-185 purchase METHODS This was a methodological study with 356 nurses and 363 patients. Linguistic, content validity, and construct validity tested for the validity of scale. Internal consistency and test-retest were calculated for reliability of scale. RESULTS Exploratory factor analysis identified 30 items that could be categorized under three factors. Cronbach's α for the CBI was .97 for nurses and .99 for patients. CONCLUSIONS The Turkish version of the CBI is a valid and reliable instrument for measuring caring behaviors. © Copyright 2020 Springer Publishing Company, LLC.BACKGROUND AND PURPOSE Despite the importance of health literacy (HL) in health outcomes, most HL assessment tools are developed and used in first world, English speaking countries, and their applicability in low and middle-income countries (LMICs) is unclear. The purpose of this review is to examine valid and reliable tools used to assess HL among people in LMICs. METHODS A literature search of three databases was conducted with 20 final articles. RESULTS Current HL assessment tools used in LMICs rely on participant's literacy and focus on measuring people's functional HL rather than reflecting the evolving definitions of HL. CONCLUSIONS More research needs to be conducted to better understand how people with limited literacy acquire and apply HL, and HL assessment tools need to assess various aspects of HL beyond one's functional HL. © Copyright 2020 Springer Publishing Company, LLC.OBJECTIVE The aim of this study was to evaluate the discriminant capability of the Patient Acceptable Symptom State (PASS) according to disease activity, remission/low disease activity indices and quality of life indices in patients with psoriatic arthritis (PsA). METHODS Consecutive patients with PsA were enrolled in this cross-sectional study. At each visit, the patients underwent a complete physical examination and their clinical/laboratory data were collected. Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and remission/low disease activity using the DAPSA minimal disease activity (MDA) and very low disease activity (VLDA) criteria. link2 The Psoriatic Arthritis Impact of Disease (PsAID) and the Health Assessment Questionnaire-Disability Index scores were also collected. Finally, PASS was assessed by asking all patients to answer yes or no to a single question. RESULTS Patients who answered yes to PASS showed a significantly better overall mean DAPSA score than those who were not in PASS. Furthermore, patients in PASS showed a significantly lower level of systemic inflammation, lower Leeds Enthesitis Index score, a significantly lower impact of disease (PsAID), lower pain and better function than patients who answered no to PASS. A moderate to good agreement was found between PASS, MDA, DAPSA low disease activity and PsAID score ≤4. Good sensitivity and specificity were found with PASS with respect to DAPSA low disease activity, and although PASS is sensitive in the identification of patients with MDA, DAPSA remission and VLDA it lacks of specificity. DISCUSSION This study showed that PASS might be used as an alternative to determine disease activity in patients with PsA in real clinical practice, mainly in patients with low disease activity according to DAPSA criteria. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.It is important to identify, assess and address current barriers to implementation of post approval changes that are intended to ensure continued (un-interrupted) operations, drive innovation and continual improvement in a maximally efficient, agile, flexible Pharmaceutical manufacturing sector. Leveraging ICH Q10 provides regulatory relief when it comes to addressing changes related to excipients, specifically excipient supplier's name and address changes which will ensure and sustainable reliable global supply and availability of high quality product to patients through the entire commercial lifecycle of a product without extensive regulatory oversight. Copyright © 2020, Parenteral Drug Association.Cleaning validation acceptance criteria in multiproduct facilities are established using maximum allowable carryover calculations. Carryover calculations incorporate the shared equipment surface area between two products to ensure that an acceptable limit for residue from the previously manufactured product to the subsequent product is determined. Shared surface area can be limited to areas where carryover presents the highest risk to product quality or patient safety. In these cases, specifically for biologic drug substance manufacturing, the shared surface area is limited to equipment after the purification process based on the assumption that the purification process would remove potential product fragment residues from the previous product. Until now, this assumption has been based on empirical knowledge without experimental data quantifying the clearance or removal of potential residues. We present a three-part study that determined the effects of cleaning conditions on selected monoclonal antibodies (mAm shared surface areas by the purification process in multiproduct biologic drug substance manufacturing facilities. Copyright © 2020, Parenteral Drug Association.Product specifications are ideally based on knowledge of patient needs or requirements of subsequent manufacturing steps. However in most applications, knowledge of patient needs is neither precise nor comprehensive enough to fully define specifications. The prevailing practice is to base specifications on process experience, setting limits to assure consistency of future results with initial results representative of clinical material. Developers of new medicines are often required to set initial product specifications and other limits when only small amounts of process experience have been accumulated. Product developers and health authority reviewers share the mandate to protect patients from harm and assure the effectiveness of medical products, which motivates a tendency to set limits very tight. But although tighter limits give the impression of tighter control, limits alone accomplish no reduction in the variation that exists in established processes and test methods. Limits that are too tight do not represent the natural variability of the process and test methods. Unnaturally tight limits will result in a high number of excursions beyond the limits, potentially causing discards, supply disruptions, and higher cost of goods sold. In this article, we demonstrate how to deliberately control the probability of having intervals that are too tight during the early manufacturing process. Copyright © 2020, Parenteral Drug Association.Endotoxins, heat-stable lipopolysaccharides from Gram-negative bacteria, are potential contaminants that can be introduced during manufacturing of pharmaceutical products, including vaccines. Parental pharmaceutical products undergo endotoxin testing because endotoxins are pyrogenic in humans and can induce severe physiological reactions. Currently, animal-derived Limulus amoebocyte lysate (LAL) assays are widely used. Assays using recombinant Factor C (rFC), a non-animal-derived reagent, have been proposed as alternatives. Some components in the matrices of pharmaceutical products can interfere with these assays. We compared two LAL- and two rFC-based assays for endotoxin detection in four complex human vaccine matrices. We showed that the results for the rFC-based assays were at least equivalent to those for the LAL-based assays, although rFC-based assays were found to be adequate but slightly less suitable for one of the products which contained proteases and the methods used to inactivate the proteases reduced the assay performance. Likewise, LAL was adequate but less suitable for another product which contained glucans. The rFC assays offer a number of benefits, including compliance with the principles of the 3Rs, i.e., replacement, reduction and refinement of animal testing by safeguarding animal welfare and promoting more ethical and sustainable use of animals for testing. After they are fully validated, as per the compendial requirements, they could be considered as suitable replacement assays for the detection of endotoxin in the manufacturing processes of pharmaceutical products. In summary, we demonstrated that both LAL and rFC assays are adequate for testing and releasing four vaccine products. Copyright © 2020, Parenteral Drug Association.Chemical indicators are commonly used in hospitals to monitor steam sterilization conditions, indicating that medical devices are safe to be used. The results are stored for future evidence in the event of an infection incident root cause analysis. This type of indicator is also becoming an option for cycle monitoring in pharmaceutical steam sterilizers, improving cycle control. They are constructed and tested according to published standards, but contradictory results between chemical indicators and cycle printouts have a critical impact on process control. We found that type 6 chemical indicators used in steam sterilizer cycles did not perform according to their intended use, showing an ″approved″ result in a ″failed″ cycle (a false positive). This study demonstrated that type 6 chemical indicator specifications are not adequate for monitoring steam sterilizers. A change in standards is therefore needed. Copyright © 2020, Parenteral Drug Association.BACKGROUND UBA5 is the activating enzyme of UFM1 in the ufmylation post-translational modification system. Different neurological phenotypes have been associated with UBA5 pathogenic variants including epilepsy, intellectual disability, movement disorders and ataxia. METHODS AND RESULTS We describe a large multigenerational consanguineous family presenting with a severe congenital neuropathy causing early death in infancy. Whole exome sequencing and linkage analysis identified a novel homozygous UBA5 NM_024818.3 c.31C>T (p.Arg11Trp) mutation. link3 Protein expression assays in mouse tissue showed similar levels of UBA5 in peripheral nerves to the central nervous system. CRISPR-Cas9 edited HEK (human embrionic kidney) cells homozygous for the UBA5 p.Arg11Trp mutation showed reduced levels of UBA5 protein compared with the wild-type. The mutant p.Arg11Trp UBA5 protein shows reduced ability to activate UFM1. CONCLUSION This report expands the phenotypical spectrum of UBA5 mutations to include fatal peripheral neuropathy. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Although considerable effort has been put into decoding of the osteosarcoma genome, very little is known about germline mutations that underlie this primary malignant tumour of bone. METHODS AND RESULTS We followed here a coincidental finding in a multiple endocrine neoplasia family in which a 32-year-old patient carrying a germline pathogenic RET mutation developed an osteosarcoma 2 years after the resection of a medullary thyroid carcinoma. Sequencing analysis of additional 336 patients with osteosarcoma led to the identification of germline activating mutations in the RET proto-oncogene in three cases and somatic amplifications of the gene locus in five matched tumours (4%, n=5/124 tumours). Functional analysis of the pathogenic variants together with an integrative analysis of osteosarcoma genomes confirmed that the mutant RET proteins couple functional kinase activity to dysfunctional ligand binding. RET mutations further co-operated with alterations in TP53 and RB1, suggesting that osteosarcoma pathogenesis bears reminiscence to the stepwise model of medullary thyroid carcinoma.
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