Validation-based insertional mutagenesis (VBIM) technology identifies adenomatous polypossis coli (APC) like protein (ALP) as a novel negative regulator of NF-κB

Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States. The nuclear factor κB (NF-κB) is an important family of transcription factors whose aberrant activation has been found in many types of cancer, including CRC. Therefore, understanding the regulation of NF-κB is of ultimate importance for cancer therapy. Using a novel validation-based insertional mutagenesis (VBIM) strategy, our lab has identified the novel adenomatous polyposis coli (APC) like protein (ALP) gene as a negative regulator of NF-κB. Preliminary studies from our lab demonstrated that overexpression of ALP led to decreased NF-κB activity by κB reporter assay and electrophoresis mobility gel shift assay (EMSA). The current project aims to further evaluate the role of ALP in the regulation of NF-κB signaling in CRC cells. We found that overexpression of ALP in human CRC HT29 cells greatly reduced both the number and the size of colonies that were formed in a soft agar assay. ALP overexpression also decreased the cell growth rate and cell migration ability, while shRNA mediated knockdown of ALP showed opposite effects, confirming that ALP is a tumor suppressor in CRC HT29 cells. Overexpression of ALP led to decreased NF-κB activity by κB reporter assay and condition media assay in CRC HT29 cells. Furthermore, immunohistochemical analysis with human colon vii tissues revealed that there is a gradual loss of ALP protein with tumor progression. We also found that ALP predominantly localizes in the cytoplasm, and binds to the p65 subunit of NF-κB, and might be functioning downstream of IκB kinase (IKK). In summary, in this study, we provide evidence regarding the tumor suppressor role of ALP in CRC by functioning as novel negative regulator of NF-κB. This discovery could lead to the establishment of ALP as a potential biomarker and therapeutic target in CRC

Evidence Based National Framework for Undergraduate Nursing Education in Sri Lanka

In Sri Lanka, nursing education is moving from diplomanursing certificate to a university bachelor degree. In thistransitional stage, the development of an evidence based nationallevel framework for undergraduate nursing education is acrucially important step to improve nursing education andnursing service in Sri Lanka. The overall purpose of this PhDresearch study was to develop an evidence-based nationalframework for undergraduate nursing education in Sri Lanka.MethodMy PhD research study has involved conducting criticalreviews of literature, two systematic reviews, developing a draftconceptual framework, testing its appropriateness and feasibilitywith key stakeholders via focus group discussions in Sri Lanka,and formulating the final national framework for nursingeducation in Sri Lanka.ResultsThe systematic reviews revealed that the evidence regardingthe effectiveness and appropriateness of undergraduate nursingcurricula is notably weak and direct transfer of the curriculummodel from one country to another is not appropriate withoutfirst assessing the cultural context of both countries. Theconceptual framework, which was developed using the finding ofsystematic reviews and literature reviews, consists of widelyrecognized nursing concepts in international and local contexts.However, some concepts cannot be directly applicable because ofcultural and economic impediments.DiscussionThis study identified several factors that shape the approachto nursing education in Sri Lanka. These factors include:Western influence; Sri Lanka’s cultural influence; the currenthealthcare system and demand for healthcare; nursing systemsand regulation; medical dominance; financial support; and SriLanka’s education system. All of these factors influence theconceptualization of nursing and educational strategies needed toeffectively and appropriately prepare nurses in Sri Lanka. Thisstudy proposes seven recommendations to support theimplementation of the study findings into practice in Sri Lanka

Erosion mitigation of lignosulfonate treated unstable soils

Highly unstable soils are common in many parts of the world. In recent years, traditional chemical admixtures such as cement, lime and fly ash were used for stabilising these soils. However, not all chemical stabilisers are readily acceptable due to stringent occupational health and safety issues and invariable change of soil pH that often limits the scope of vegetation plus imposing a threat to ground water pollution. However, recent research shows that lignosulfonate, an environmentally sustainable admixture, can stabilise unstable and erodible soils without causing adverse effects on the environment. This paper presents the results of a laboratory investigation and model predictions on the internal erosion behaviour of an unstable soil stabilised by lignosulfonate. Test results reveal that the erosion parameters such as the critical shear stress and coefficient of soil erosion were improved with the increased amount of lignosulfonate. A theoretical model has also been developed to capture the internal erosion behaviour of soil based on the law of conservation of energy. The stabilization of the soil particles by lignosulfonate treatment is characterized by the increased strain energy required to break the inter-particle bonds. The model predictions capture the internal erosion behaviour of lignosulfonate treated soil similar to the laboratory experiments

Awareness study of Pharmacovigilance among the health care professionals (nursing staff) at tertiary care hospital, Solapur, Maharashtra, India

Background: Early detection of adverse drug reaction is one step towards the prevention of ADRs. Foundation of Pharmacovigilance is spontaneous reporting which is minimal in India. Among the all health care professionals, nurses are caregivers at bedside. Improvement in knowledge and practice of adverse drug reaction reporting among nurses will definitely increases spontaneous reporting. In this study, knowledge, attitude and practice of nursing staff about pharmacovigilance was evaluated.Methods: It was prospective, cross-sectional, observational, questionnaire-based study among the nurses of the tertiary care hospital Solapur. A questionnaire evaluating knowledge, attitude and practice was distributed among nursing staff and filled questionnaire were collected back and analyzed by microsoft excel 2013.Results: Response rate of our study was 44.88%.  38.61% doctors were knowing meaning of pharmacovigilance while 61.38% participants knew that all drugs available in market are not safe. Taking proper medication history before prescribing drugs was considered important by 92.57% participants. 79.70% participants were aware about Pharmacovigilance program of India. 64.35% doctors answered correctly to elements which are mandatory to record. Only 24.75% participants were knowing the basis that pharmcovigilance provides for.Conclusions: Nursing staff of tertiary care hospital, Solapur had very appreciable and positive attitude towards pharmacovigilance but there is a need for improvement in knowledge and practice of ADR reporting

Hemovigilance: a momentous step to blood safety

Hemovigilance is a series of monitoring procedures that cover the entire transfusion chain, from blood and its component collection to recipient follow-up, collecting and collecting information about unexpected or adverse effects resulting from the therapeutic use of unstable blood products. It is designed to be evaluated, and to prevent their occurrence and recurrence. The Haemovigilance program in developed countries is associated with IHN and has voluntary reporting requirements. In France, Germany and Switzerland, the hemodynamic system is regulated by supervisors. It is one of the blood manufacturers in Japan, Singapore and South Africa. In the Netherlands and the United Kingdom within the Medical Society; in Canada, regulated by health authorities. Intensive blood exercise program to ensure patient safety and promote public health begins on December 10, 2012 in Phase 1 in collaboration with National Institute of Biological Sciences under MOHFW for the first time in India it was done. HvPI is responding very well, as most medical colleges and laboratories have already registered and are beginning to provide data on side effects. The HvPI Unit produces educational materials in the form of publishing the Haemovigilance newsletter, information, education and communication (IEC) literature, and conducts an academic CME and awareness program on Haemovigilance throughout the year in India. The provocation is to understand not only the feedback of the internet, but even the sociology of human networks. Guaranteeing the reliability, responsiveness, and feedback of each alert is also important. Blood products are an important area of PvPI for reporting and recording post-transfusion ADRs of blood / blood products. To work efficiently, a lean mechanism and proper coordination with standardized tools at all levels is needed

Microfilaria in malignant pleural effusion: an unusual incidental finding or causative association?

Lymphatic filariasis is common in tropical countries and is endemic in India. Filaria has a wide spectrum of presentation. Filarial lung involvement is usually in the form of tropical pulmonary eosinophilia with pulmonary infiltrates and peripheral eosinophilia. Filariasis presenting with pleural effusion is an unusual presentation. Malignancy in association with filarial pleural effusion is extremely rare and its role in tumorigenesis is controversial. In this context, we hereby report a case of 60 year old male, chronic smoker, who presented with left sided chest pain, cough, breathlessness, generalized weakness and swelling over left infrascapular region. Pleural fluid cytology repeated thrice due to degenerative changes, finally revealed malignant cells along with microfilaria. FNAC from left infrascapular swelling showed cytological features suggestive of metastatic deposits of Adenocarcinoma

Effect of Dentin Biomodification Delivered by Experimental Acidic and Neutral Primers on Resin Adhesion

Objectives Proanthocyanidins (PACs) are biocompounds mimicking native collagen cross-links. The effective and practical delivery of any biocompound is pivotal for clinical usage. The aim was to investigate the dentin biomodification and effective formation of dentin–resin biointerfaces of two highly bioactive PAC-rich extracts, Vitis vinifera (Vv) and Camellia sinensis (Cs), delivered using neutral (NP) or acidic (AP) rinse-out primer approaches. Methods The depth of dentin demineralization (optical profilometry), dentin biomodification (apparent modulus of elasticity, collagen auto-fluorescence) and properties of dentin–resin interfaces (microtensile bond strength - μTBS, and micro-permeability) were investigated. NP consisted of either 15% Vv or Cs applied for 60 s after surface etching; while AP contained 15% Vv or Cs in either 35% glycolic acid or tartaric acid applied for 30 s or 60 s. Data were analyzed using ANOVA and post-hoc tests (α = 0.05). Results The depth of demineralization was statistically higher when applied for 60 s, regardless of rinse-out primer approach (p \u3c 0.001). Compared to the AP strategy, NP exhibited statistically higher apparent modulus of elasticity, regardless of PAC extract (p \u3c 0.001). Highest μTBS were obtained for NPVv, which were statistically similar to APGAVv, when applied for 60 s (p \u3c 0.001); both resulted in a dramatic decrease of the interfacial permeability. NPCs group showed the lowest μTBS (p \u3c 0.001). Conclusions A combination of high bond strength and low micro-permeability can be accomplished using glycolic acid with the mid- and high-PAC oligomer enriched extract (Vv). Cs extract containing mostly catechins and dimeric PACs, was found unsuitable for resin-dentin adhesion despite exhibiting high initial dentin biomodification. Clinical significance This study provides a new conceptual delivery of PAC-mediated dentin biomodification and conservative dentin surface etching using rinse-out primers. The strategy requires a specific combination of PAC source, α-hydroxy acid, and application time