677 research outputs found

    Improving Stroke Management through Specialized Stroke Units in Nigeria: A situational Review

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    Background: Stroke therapy is aimed at re-opening blocked arteries and increasing the survival of cells that are injured in addition to the early rehabilitation of the stroke patient. The establishment of stroke units has been found to improve the survival of patients and significantly reduce disability by rendering holistic care. Early intervention to rapidly restore and maintain blood supply to the ischemic area in the brain, minimize brain damage and hence impairment as well as disability and secondary complications which will reduce the risk of death is more likely achievable in specialized care settings. The objective of this review is to discuss the role and feasibility of implementing stroke care in specialized stroke units(SSUs).Methods: Key literature detailing the care of stroke patients at the different tier of health institutions in Nigeria and abroad were reviewed using Medline and Google search utilizing the following keywords' Strokeunit; Management; Shared Burden and Nigeria. The difficulties associated with the provision of care for stroke patients in specialized stroke units were identified while the implications and suggestions for the development of such units in Nigeria are addressed.Results: The care of stroke patients remains mainly uncoordinated and usually managed in the general medical wards with suboptimal management. Issues that may affect establishment of specialized Stroke Unit include lack of Neurologists, Geriatricians with special interest in stroke management, allied health professionals and Nurses trained in providing supportive care. The challenges of the start –up cost, and public education in seeking help early enough are also highlighted.Conclusion: The evidence for the need for change from the usual care of stroke patient's in general medical wards to specialized stroke units is undisputable. Establishment of such units in Nigeria is desirable, urgent and feasible. The establishment of these SSUs can be started by having specific designated beds in a section of the medical wards with the care assigned to specially trained medical and allied health providers.Key Words: Sharing; burden; stroke unit; Nigeria

    Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease.

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    The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene

    Good Care in Ongoing Dialogue. Improving the Quality of Care Through Moral Deliberation and Responsive Evaluation

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    Recently, moral deliberation within care institutions is gaining more attention in medical ethics. Ongoing dialogues about ethical issues are considered as a vehicle for quality improvement of health care practices. The rise of ethical conversation methods can be understood against the broader development within medical ethics in which interaction and dialogue are seen as alternatives for both theoretical or individual reflection on ethical questions. In other disciplines, intersubjectivity is also seen as a way to handle practical problems, and methodologies have emerged to deal with dynamic processes of practice improvement. An example is responsive evaluation. In this article we investigate the relationship between moral deliberation and responsive evaluation, describe their common basis in dialogical ethics and pragmatic hermeneutics, and explore the relevance of both for improving the quality of care. The synergy between the approaches is illustrated by a case example in which both play a distinct and complementary role. It concerns the implementation of quality criteria for coercion in Dutch psychiatry

    Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

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    Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury

    A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging

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    Despite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho‐nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6‐nitroverataldehyde, three drug–fluorophore conjugates were synthesized: Taxol‐TNB‐fluorescein, Taxol‐TNB‐coumarin, and doxorubicin‐TNB‐coumarin, and long‐wavelength UVA light‐triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell‐based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real‐time monitoring of drug activation at the delivery site.Binary photocage: An ortho‐nitrobenzaldehyde‐derived dual arm photocage was developed for real‐time monitoring of the simultaneous release of two payloads linked to a single cage unit. Light‐controlled uncaging of the drug–fluorophore conjugate resulted in increased cellular fluorescence, which was found to correlate with cytotoxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135367/1/cbic201600494.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135367/2/cbic201600494-sup-0001-misc_information.pd
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