Squamous cell carcinoma of the palm in Nigeria

Objective: To document six cases of squamous cell carcinoma (SCC) of the palm. Materials and Methods: A review of patients’ records seen from 1986 to 1998, at the Plastic Surgical Unit of the National Orthopaedic Hospital, Enugu was undertaken. The accumulated data were analyzed with the reference to those diagnosed as SCCs. Results: Four males and two females with a mean age of 61.3 years were afflicted with SCC of the palm. All but one of these patients farmed. There were long delays before presentation, and extents of the lesions reflected that. Conclusion: The Public health education is indicated in our community, if the patients are to recognize the nature of this lesion and report early.Keywords: Health education, Nigerians, palm, squamous cell carcinom

Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection

Background: Gonorrhea is a sexually transmitted infection of global concern. We investigated whole genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management. / Methods: Between May-November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, UK, underwent WGS. Reports listing sequences within 20 single nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1 2016 to November 15 2018 were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. WGS reports were reviewed to identify additional cases within ≤6 SNPs and verified for PN concordance. / Results: 380 isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within ≤6 SNPs; examination of these cases’ PN data identified seven partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had ≤4 SNP differences. WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections. / Conclusions: WGS could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding

Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery

RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications

ESPACOMP Medication Adherence Reporting Guidelines (EMERGE): a reactive-Delphi study protocol

INTRODUCTION: Medication adherence is fundamental to achieving optimal patient outcomes. Reporting research on medication adherence suffers from some issues—including conceptualisation, measurement and data analysis—that thwart its advancement. Using the ABC taxonomy for medication adherence as the conceptual basis, a steering committee of members of the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) launched an initiative to develop ESPACOMP Medication Adherence Reporting Guidelines (EMERGE). This paper is a protocol for a Delphi study that aims to build consensus among a group of topic experts regarding an item list that will support developing EMERGE. METHODS AND ANALYSIS: This study uses a reactive-Delphi design where a group of topic experts will be asked to rate the relevance and clarity of an initial list of items, in addition to suggesting further items and/or modifications of the initial items. The initial item list, generated by the EMERGE steering committee through a structured process, consists of 26 items distributed in 2 sections: 4 items representing the taxonomy-based minimum reporting criteria, and 22 items organised according to the common reporting sections. A purposive sample of experts will be selected from relevant disciplines and diverse geographical locations. Consensus will be achieved through predefined decision rules to keep, delete or modify the items. An iterative process of online survey rounds will be carried out until consensus is reached. ETHICS AND DISSEMINATION: An ethics approval was not required for the study according to the Swiss federal act on research involving human beings. The participating experts will be asked to give an informed consent. The results of this Delphi study will feed into EMERGE, which will be disseminated through peer-reviewed publications and presentations at conferences. Additionally, the steering committee will encourage their endorsement by registering the guidelines at the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network and other relevant organisations