Genetic testing for inherited retinal degenerations: Triumphs and tribulations

Inherited retinal degenerations (IRDs) are a genotypically and phenotypically diverse group of conditions. Great strides have been made toward identifying the genetic basis for these conditions over the last 30 years—more than 270 different genes involved in syndromic and nonsyndromic forms of retinal dystrophies have now been identified. The identification of these genes and the improvement of clinical laboratory techniques have led to the identification of the genetic basis of disease in 56–76% of patients with IRDs through next generation sequencing and copy number variant analysis. Genetic testing is an essential part of clinical care for patients affected with IRDs and is required to confirm the diagnosis, understand the inheritance of the condition, and determine eligibility for gene‐specific treatments or clinical trials. Despite the success achieved in determining the genetic cause of these conditions, several challenges remain, which must be considered when providing genetic testing and genetic counseling to patients. For this reason, an integrated team of ophthalmic and genetic clinicians who are familiar with these challenges is necessary to provide optimal comprehensive care to these patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162692/2/ajmgc31835.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162692/1/ajmgc31835_am.pd

The Ophthalmic Experience: Unanticipated Primary Findings in the Era of Next Generation Sequencing

Next generation sequencing (NGS) technology, with the ability to sequence many genomic regions at once, can provide clinicians with increased information, in the form of more mutations detected. Discussions on broad testing technology have largely been focused on incidental findings, or unanticipated results related to diseases beyond the primary indication for testing. By examining multiple genes that could be responsible for the patient’s presentation, however, there is also the possibility of unexpected results that are related to the reason genetic testing was ordered. We present a case study where multiple potentially causative mutations were detected using NGS technology. This case raises questions of scientific uncertainty, and has important implications for medical management and secondary studies. Clinicians and genetic counselors should be aware of the potential for increased information to affect one’s understanding of genetic risk, and the pre‐ and post‐testing counseling process.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147171/1/jgc40588.pd

By E-Care Pharmacy Web Application, the Medicines Needed for Daily Human Life Can be Easily Delivered to Them

This project offers knowledge on creating and putting in place a pharmaceutical management system. And here, the major objective is to increase the efficacy, efficiency, and accuracy of the drug. In today's world, management is one of the most crucial organizational components. Additionally, complexity is added when management does a certain activity in any way. In other words, the availability of computers and advancements in information technology have made it possible for us to swiftly and effectively gather and communicate vast volumes of data on patient treatment. The pharmacy management system should be able to get prescriptions and non-prescription medications with the assistance of certified, trained pharmacists in order to provide patients with the medications they require. Today, many of these types of pharmacy management systems are used to better manage pharmacy-related activities

Functional Analysis of Retinitis Pigmentosa 2 (RP2) Protein Reveals Variable Pathogenic Potential of Disease-Associated Missense Variants

Genetic mutations are frequently associated with diverse phenotypic consequences, which limits the interpretation of the consequence of a variation in patients. Mutations in the retinitis pigmentosa 2 (RP2) gene are associated with X-linked RP, which is a phenotypically heterogenic form of retinal degeneration. The purpose of this study was to assess the functional consequence of disease-associated mutations in the RP2 gene using an in vivo assay. Morpholino-mediated depletion of rp2 in zebrafish resulted in perturbations in photoreceptor development and microphthalmia (small eye). Ultrastructural and immunofluorescence analyses revealed defective photoreceptor outer segment development and lack of expression of photoreceptor-specific proteins. The retinopathy phenotype could be rescued by expressing the wild-type human RP2 protein. Notably, the tested RP2 mutants exhibited variable degrees of rescue of rod versus cone photoreceptor development as well as microphthalmia. Our results suggest that RP2 plays a key role in photoreceptor development and maintenance in zebrafish and that the clinical heterogeneity associated with RP2 mutations may, in part, result from its potentially distinct functional relevance in rod versus cone photoreceptors

Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

Case Report: melioidosis - poor compliance resulting in a relapse

No abstract availabl

Impact of milk protein type on the viability and storage stability of microencapsulated Lactobacillus acidophilus using spray drying

Three different milk proteins — skim milk powder (SMP), sodium caseinate (SC) and whey protein concentrate (WPC) — were tested for their ability to stabilize microencapsulated L. acidophilus produced using spray drying. Maltodextrin (MD) was used as the primary wall material in all samples, milk protein as the secondary wall material (7:3 MD/milk protein ratio) and the simple sugars, d-glucose and trehalose were used as tertiary wall materials (8:2:2 MD/protein/sugar ratio) combinations of all wall materials were tested for their ability to enhance the microbial and techno-functional stability of microencapsulated powders. Of the optional secondary wall materials, WPC improved L. acidophilus viability, up to 70 % during drying; SMP enhanced stability by up to 59 % and SC up to 6 %. Lactose and whey protein content enhanced thermoprotection; this is possibly due to their ability to depress the glass transition and melting temperatures and to release antioxidants. The resultant L. acidophilus powders were stored for 90 days at 4 °C, 25 °C and 35 °C and the loss of viability calculated. The highest survival rates were obtained at 4 °C, inactivation rates for storage were dependent on the carrier wall material and the SMP/d-glucose powders had the lowest inactivation rates (0.013 day−1) whilst the highest was observed for the control containing only MD (0.041 day−1) and the SC-based system (0.030 day−1). Further increase in storage temperature (25 °C and 35 °C) was accompanied by increase of the inactivation rates of L. acidophilus that followed Arrhenius kinetics. In general, SMP-based formulations exhibited the highest temperature dependency whilst WPC the lowest. d-Glucose addition improved the storage stability of the probiotic powders although it was accompanied by an increase of the residual moisture, water activity and hygroscopicity, and a reduction of the glass transition temperature in the tested systems

Persistence and predictability of forward exchange arbitrage in managed rate currencies in comparison to free-floating currencies

This paper attempts to analyse whether forward exchange arbitrage in currencies of managed rate regimes behave differently from currencies of free floating regimes in the forward exchange market. For this purpose, currencies of Great Britain, the European Union, and Japan are used as proxy currencies for free floating currencies. Proxy currencies for managed rate currencies are the Sri Lankan Rupee, the Indian Rupee, the Russian Rouble and the Brazilian Real. The US dollar is used as the anchor currency for both sets of currencies. The core of the paper revolves around the pricing difference between the fundamental forward price and the market forward price. Fundamental forward price is calculated based on the interest rate differentials of the two currencies; this is in concurrence with the interest rate parity condition. Market price is based on the forward pips and the spot rate. This analysis concentrates on the persistence of mispricing availability, the availability of forward pricing differences and the predictability of the mispricing in both sets of currencies. Finally, we also test whether the current forward price can predict the future spot price based on the interest rate parity theory. We present evidence that almost all the currencies have forward rate mispricing. However, we also present evidence to prove that mispricing in free floating currencies is extremely small, while managed rate currencies offer significant mispricing that could be exploited for arbitrage purposes. We also present evidence to establish that persistence of mispricing is specific to the currency pair and cannot be clearly attributed to the exchange rate regime. This paper also finds that it is not possible to statistically forecast the mispricing in both free floating and managed rate currencies. Further, failure of interest rate parity theory to accurately forecast the future spot rate is also documented

The inheritance of educational inequality. International comparisons and fifty-year trends

This paper estimates 50-year trends in the intergenerational persistence of educational attainment for a sample of 42 nations around the globe. Large regional differences in educational persistence are documented, with Latin America displaying the highest intergenerational correlations, and the Nordic countries the lowest. We also demonstrate that the global average correlation between parent and child’s schooling has held steady at about 0.4 for the past fifty years