TIP60-miR-22 axis as a prognostic marker of breast cancer progression

MicroRNAs (miRNAs) are 22- to 24-nucleotide, small, non-coding RNAs that bind to the 3′UTR of target genes to control gene expression. Consequently, their dysregulation contributes to many diseases, including diabetes and cancer. miR-22 is up-regulated in numerous metastatic cancers and recent studies have suggested a role for miR-22 in promoting stemness and metastasis. TIP60 is a lysine acetyl-transferase reported to be down-regulated in cancer but the molecular mechanism of this reduction is still unclear. In this study, we identify TIP60 as a target of miR-22. We show a negative correlation in the expression of TIP60 and miR-22 in breast cancer patients, and show that low levels of TIP60 and high levels of miR-22 are associated with poor overall survival. Furthermore, pathway analysis using high miR-22/low TIP60 and low miR-22/high TIP60 breast cancer patient datasets suggests association of TIP60/miR-22 with epithelial-mesenchymal transition (EMT), a key alteration in progression of cancer cells. We show that blocking endogenous miR-22 can restore TIP60 levels, which in turn decreases the migration and invasion capacity of metastatic breast cancer cell line. These results provide mechanistic insight into TIP60 regulation and evidence for the utility of the combination of TIP60 and miR-22 as prognostic indicator of breast cancer progression.     

Prosthetic rehabilitation after orbital exenteration: A case series

Orbital exenteration is executed by the ophthalmic surgeon to treat various neoplasms or non-malignant diseases. But it leads to several functional, esthetic and psychological problems for the patients. Orbital prosthesis is a good alternative for cosmetic and psychological rehabilitation, if reconstructive surgery is not possible or not desired by the patient. In the following article, different materials and retentive aids for fabrication of an orbital prosthesis given in the literature along with few novel methods have been discussed for four patients who underwent orbital exenteration. Factors that an ophthalmic surgeon should consider during surgery, which may later on help the prosthodontist to obtain good cosmetic results, are also discussed briefly. Remarkable results can be obtained if both work as a team for one common goal i.e. improvement of quality of life of the patient after orbital exenteration.     

Assessing the effect of introducing a new method into family planning programs in India, Peru, and Rwanda

ABSTRACT: BACKGROUND: Introducing a new method into family planning programs requires careful attention to ensure it meets an actual need and has a positive effect on program goals. The Standard Days Method(R) is a fertility awareness-based method of family planning that is being introduced into family planning programs in countries around the world. It is different from other methods offered by programs, and may bring new couples into family planning, and increase contraceptive prevalence. The study assesses the effect on contraceptive use and prevalence of Introducing Standard Days Method into existing family planning services in whole regions of India, Peru, and Rwanda. METHODS: In collaboration with the Ministry of Health, health providers were given a contraceptive update on all methods, then trained in counseling on Standard Days Method. Efforts were made to promote demand in the context of informed choice. Routine monthly service statistics in control and intervention areas were used to assess the effect of Standard Days Method introduction at the clinic level; baseline and endline household-based surveys were undertaken to obtain results at the community level (n > 3400 women at endline). RESULTS: Demand for the method is evident in countries with different levels of contraceptive prevalence. The method attracts couples new to family planning, and introducing it into services may increase overall contraceptive prevalence. CONCLUSIONS: Introducing Standard Days Method into existing family planning has the potential of benefiting men and women in diverse settings and populations. This study illustrates the critical role of evidence in scaling up a health innovation.     

Utility-Fuzzy-Taguchi based hybrid approach in investment casting process

In this paper, the use of the Utility-Fuzzy-Taguchi based hybrid approach in investment casting process for optimizing multiple quality characteristics of wax patterns has been conceptualized. Selection of an appropriate orthogonal array, preference scale construction followed by preference values, generation of multi-performance index (MPI) by fuzzy logic, analysis of means and analysis of variance are employed to study the performance characteristics of the process. The control factors considered are injection temperature, injection pressure and injection time, whereas linear shrinkage, surface roughness and penetration are the corresponding responses. The optimal setting obtained by the proposed method is validated by confirmatory experiments. This concludes the application feasibility of the proposed method for parametric optimizations in investment casting process. Further, the result of the aforementioned optimization technique has been compared with that of Utility-Taguchi technique. It is found that the optimal condition for both is same, while the most influential process parameter is different in both cases due to employment of random selection of weights in Utility-Taguchi method.     

Treatment of overactive bladder in the aging population: focus on darifenacin

Anticholinergics are commonly used in primary and secondary care settings for the treatment of overactive bladder syndrome. The number of anticholinergic drugs available on the market is increasing and various studies, both observational and randomized controlled trials, have evaluated effectiveness of the different preparations available. When anticholinergic therapy is prescribed, there is still uncertainty about which anticholinergic drugs are most effective, at which dose, and by which route of administration. There is also uncertainty about the role of anticholinergic drugs in different patient groups, particularly in the elderly. The rationale for using anticholinergic drugs in the treatment of overactive bladder syndrome is to block the parasympathetic acetylcholine pathway and thus abolish or reduce the intensity of detrusor muscle contraction. There are currently five recognized subtypes of muscarinic receptor; the M₁, M₂, and M₃ subtypes are of interest in bladder activity. Muscarinic receptors are found in other parts of the body, eg, in the gut, salivary glands, tear ducts. Side effects associated with non-selective antimuscarinics can be particularly distressing in the elderly. The development of bladder selective M₃ specific antagonists has the advantage of providing increased efficacy with minimal side effects. Darifenacin is one such preparation. The aim of this review is to assess the pharmacology, interactions and the safety and tolerability of darifenacin in the treatment of overactive bladder in the elderly population with particular reference to clinical trial data available.