NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy

Alzheimer’s disease (AD) is a devastating neurodegenerative disease causing irreversible cognitive decline in the elderly. There is no disease-modifying therapy for this condition and the mechanisms underpinning neuronal dysfunction and neurodegeneration are unclear. Compromised cytoskeletal integrity within neurons is reported in AD. This is believed to result from loss-of-function of the microtubule-associated protein tau, which becomes hyper-phosphorylated and deposits into neurofibrillary tangles in AD. We have developed a Drosophila model of tauopathy in which abnormal human tau mediates neuronal dysfunction characterised by microtubule destabilisation, axonal transport disruption, synaptic defects and behavioural impairments. Here we show that a microtubule-stabilising drug, NAPVSIPQ (NAP), prevents as well as reverses these phenotypes even after they have become established. Moreover, it does not alter abnormal tau levels indicating that it by-passes toxic tau altogether. Thus, microtubule stabilisation is a disease-modifying therapeutic strategy protecting against tau-mediated neuronal dysfunction, which holds great promise for tauopathies like AD

Is fenofibrate the missing piece in COVID-19 management?

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Using large group methods to develop effective quality cultures

It has become evident that higher education institutions in the Sultanate of Oman are currently experiencing change, in particular when it involves implementing quality management systems. The underlying principles of quality management are participatory decision making. Our methods for conducting improvements in quality management, strategic planning and other topics model this principle. Large group methods or interventions involve gathering an entire organization to talk about, influence or invent needed changes (Bunker &amp; Alban, 2002). Change is a result of purposeful social construction by organizational members. It involves a goal (approach/plan), implementation (deployment/act/so), evaluation (results/check) and modification (improvement). This paper explores the different large group methods being used in the field today and it proposes that large group methods allow a forum to overcome some of the hurdles and challenges that are being faced in Oman such as; How do you encourage sharing information in a fiercely competitive environment? And how do you establish an informal network of peers? We were witness to some of these challenges being over come when we used large group methods during various strategic planning workshops with members of staff from the different colleges in Oman. Results from the evaluations of the workshops highlighted that participants enjoyed the opportunity to network and share ideas with their peers as well as being involved in group discussions and brainstorming ideas. The paper will also propose that large group methods can be used effectively in Omani culture strengthening goals towards Omanisation.<br /

EVALUATING THE EFFECT OF MEDICAL REPRESENTATIVE ON PHYSICIAN PRESCRIBING PATTERN IN IRAQ

Objective: Evaluation of the interaction between medical representatives (MRs) and physicians and the effect of such interaction on physician prescribing behavior, according to the site of view for Iraqi pharmacists.Methods: A survey for 36 pharmacists in their private pharmacies in different areas of Baghdad governorate was done through the use of a specific set of questions in a questionnaire format.Results: Most participated pharmacists agreed that physicians at most times change their prescribing pattern by attendance of the MRs, additionally there is a significant decline in the number of prescriptions for the promoted drug by the absence of medical representative for long period of time, furthermore participated pharmacists agreed that there is an irrational prescribing patterns by most physicians in Iraq.Conclusion: The interaction between MRs and physicians in Iraq, usually result in non rational prescribing patterns, which may in turn negatively affecting the health of the patients and on the other hand increases the cost of medications.Keywords: Promotion, medical representative, prescribing pattern

An evaluation of Drosophila as a model system for studying tauopathies such as Alzheimer's disease

Work spanning almost two decades using the fruit fly, Drosophila melanogaster, to study tau-mediated neurodegeneration has provided valuable and novel insights into the causes and mechanisms of tau-mediated toxicity and dysfunction in tauopathies such as Alzheimer's disease (AD). The fly has proven to be an excellent model for human diseases because of its cost efficiency, and the availability of powerful genetic tools for use in a comparatively less-complicated, but evolutionarily conserved, in vivo system. In this review, we provide a critical evaluation of the insights provided by fly models, highlighting both the advantages and limitations of the system. The fly has contributed to a greater understanding of the causes of tau abnormalities, the role of these abnormalities in mediating toxicity and/or dysfunction, and the nature of causative species mediating tau-toxicity. However, it is not possible to perfectly model all aspects of human degenerative diseases. What sets the fly apart from other animal models is its genetic tractability, which makes it highly amenable to overcoming experimental limitations. The explosion of genetic technology since the first fly disease models were established has translated into fly lines that allow for greater temporal control in restricting tau expression to single neuron types, and lines that can label and monitor the function of subcellular structures and components; thus, fly models offer an unprecedented view of the neurodegenerative process. Emerging genetic technology means that the fly provides an ever-evolving experimental platform for studying disease.</p

The Influence of Entrepreneurial Supply Chain on Marketing: An Exploratory Case Study of General Company for Batteries Manufacturing

The current research examines the relationship of the Entrepreneurial supply chain dimensions (proactive approach, innovation, risk management and customer focus) with the supply chain strategies (undifferentiated marketing strategy, concentrated marketing strategy and differentiated marketing strategy). The focus of this investigation is to explore the role of adoption of entrepreneurial supply chains in the identification and selection of the appropriate strategy for the target market in the context of general company foe batteries manufacturing. The essence of entrepreneurial supply chains is its ability to facilitate alignment of all participants in the chain, eliminating moral hazard and opportunism risks. The importance of the research is derived from the significance of the matter. A company’s success or failure depends on the appropriate target market strategy. The questionnaire techniques was used as a data collection tool designed on the basis theoretical conceptualization of the model.  The research found a significant role of Entrepreneurial supply chain and its underlying dimensions on the selection of target market strategies. Furthermore, the relationship of the Entrepreneurial supply chain differentiated market strategy has found stronger among all. Hence company's management should adopt differentiated marketing strategy as the most appropriate in achieving its objective

Microtubule stabilising peptides rescue tau phenotypes in-vivo

The microtubule cytoskeleton is a highly dynamic, filamentous network underpinning cellular structure and function. In Alzheimer’s disease, the microtubule cytoskeleton is compromised, leading to neuronal dysfunction and eventually cell death. There are currently no disease-modifying therapies to slow down or halt disease progression. However, microtubule stabilisation is a promising therapeutic strategy that is being explored. We previously investigated the disease-modifying potential of a microtubule-stabilising peptide NAP (NAPVSIPQ) in a well-established Drosophila model of tauopathy characterised by microtubule breakdown and axonal transport deficits. NAP prevented as well as reversed these phenotypes even after they had become established. In this study, we investigate the neuroprotective capabilities of an analogous peptide SAL (SALLRSIPA). We found that SAL mimicked NAP’s protective effects, by preventing axonal transport disruption and improving behavioural deficits, suggesting both NAP and SAL may act via a common mechanism. Both peptides contain a putative ‘SIP’ (Ser-Ile-Pro) domain that is important for interactions with microtubule end-binding proteins. Our data suggests this domain may be central to the microtubule stabilising function of both peptides and the mechanism by which they rescue phenotypes in this model of tauopathy. Our observations support microtubule stabilisation as a promising disease-modifying therapeutic strategy for tauopathies like Alzheimer’s disease

Utilizing and Controlling Water Resources in the Islamic Jurisprudence: A Contrastive Study

تعددت البحوث حول المياه التي هي أحد الموارد الطبيعية لما لها من أهمية في حياة الانسان ولأهمية ذلك وبسبب الاستخدام غير المشروع&nbsp; وبسبب الاستغلال والتصرف غير المسؤول للموارد المائية الذي يكشف بشكل وبآخر عن حرمان الكثير من تلك الموارد انعقد البحث في دراسة موقف الفقه الإسلامي من استغلال تلك الموارد والتصرف فيها وبيان الأحكام المترتبة على ذلك من حيث الحكم التكليفي والوضعي ودراسة الأحاديث دراسة تحليلية استدلالية وبيان آراء فقهاء المذاهب الإسلامية (الإمامية والحنفية والمالكية والشافعية والحنابلة) التي اتفقت فيها كلمات الفقهاء على حرمة استغلال تلك الموارد بشكل غير مشروع&nbsp; لضمان حقوق الآخرين ودراسة الروايات الواردة في&nbsp; تنظيم الموارد المائية والاستفادة منها بالشكل الذي يضمن الحق العام للجميع .Many researches have been conducted concerning the importance of water in the life of man. The significance of the current study is to clarify the importance of water and the misuse of its resources. The exploitation of water resources illegally leads to deprivation of many communities from potable water. On light of this data, the study has been conducted, entitled, The status of Islamic jurisprudence in exploitation of water resources. The study aims at exploring the legislative verdict in Islam toward the misuse of water. Moreover, the study moves on to discuss the issue from various Islamic doctrines (Imami, Hanafi, Shafee and Hanbali). Which agree to classify the misuse of water resources as taboo, in order to guarantee the right of all people in community to benefit from water

Septic coronary embolism – A case report

The embolization represents one of the most dreadful complications of infective endocarditis; however, coronary embolism is a rare entity with an incidence of 2.9%. The definite line of management is rather ambiguous in published literatures. We reported an urgent coronary revascularization with double valve replacement due to infective endocarditis with large vegetation complicated by coronary embolism and acute coronary syndrome