Spectrum of Mutations in the RPGR Gene That Are Identified in 20% of Families with X-Linked Retinitis Pigmentosa

SummaryThe RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%–15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis

Spectrum of Mutations in the RPGR Gene That Are Identified in 20% of Families with X-Linked Retinitis Pigmentosa

SummaryThe RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%–15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis

Do all bunions need surgery? An investigation of Google searches for Hallux Valgus

Introduction: Hallux valgus (HV) or a bunion is one of the most common forefoot deformities. Approximately one in four adults will develop HV with a higher prevalence in adult females. Given the high prevalence of HV along with the wide variety of non-surgical and surgical treatment options for it, we believe patients are likely turning to internet search engines for questions germane to HV. Previous orthopaedic investigations have used Google’s “People Also Ask” box to characterize frequently asked questions (FAQs) regarding total knee and hip arthroplasty. Yet, no such investigation has been conducted for HV. Using Google’s Frequently Asked Questions (FAQs), we sought to classify these questions as well as assess their levels quality and transparency.Methods: On October 9, 2022, we searched Google using these four phrases: “Hallux Valgus Treatment,” “Hallux Valgus Treatment Surgery,” “Bunion Treatment,” and “Bunion Surgery.” We refreshed search results until a minimum of 100 FAQs were produced; we extracted the sources of these 100 questions for content analysis. Information transparency was assessed using the Journal of the American Medical Association’s (JAMA) Benchmark tool, question classification was defined using the Rothwell Classification of Questions, and information quality was assessed using Brief DISCERN. This study was approved by an IRB.Results section: Our Google search returned 299 unique FAQs after removing duplicates and unrelated FAQs. The majority were classified as fact based questions (149/299, 49.8%), followed by value (92/299, 30.8%) and policy questions (58/299, 19.4%). Overall the most common topic searched was related to the evaluation of treatment or surgery (79/299, 26.4%). The frequent answer sources were medical practices (158/299, 52.8%), followed by commercial (69/299, 23.1%) and academic (38/299, 12.7%). The one-way analysis of variance revealed a significant difference in mean quality scores among the 5 source types (F= 54.49, P<.001) with medical practices averaging the worst score (12.1/30) compared to academic sources which were found to have the highest score (21.8/30).Discussion: Patients seeking online information concerning treatment options for HV appear to search Google for questions related to treatment efficacy and restrictions. The most common source type encountered by patients are small medical practices; these were found to have both poor transparency and poor quality. Our study has several limitations, JAMA benchmark and Brief DISCERN do not assess the accuracy of the information. Secondly, our study is cross-sectional in design limiting the generalizability of our findings to the time when the search was performed.Significance/Clinical Relevance: In order to increase the transparency and quality of online information regarding HV treatment, online sources should refer to established rubrics such as JAMA benchmark and Brief DISCERN when publishing online information. Physicians should be aware that patients are commonly searching for information related to the evaluation of treatments or surgeries for HV

Lessons learned and study results from HIVCore, an HIV implementation science initiative

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138261/1/jia21261.pd

Madagascar’s extraordinary biodiversity: Threats and opportunities

Madagascar's unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar's terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as themost prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar

Madagascar’s extraordinary biodiversity: Evolution, distribution, and use

Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique living laboratory for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity