Management of Scleritis in Older Adults.

Scleritis, an inflammatory disease of the eye affecting scleral tissue, presents unique challenges in the older adult population. Unlike their younger counterparts, older individuals manifest a distinct spectrum of the disease with different underlying etiologies, co-morbidities, altered immune function, and an increased risk of systemic side effects from medication choices. Addressing these complexities necessitates a comprehensive and multidisciplinary approach. Treatment of choice will depend on any underlying cause but generally involves non-steroidal anti-inflammatory drugs, systemic or local corticosteroids, and potentially disease-modifying anti-rheumatic drugs. Utilization of these therapeutic agents in older adults warrants careful consideration because of their potential side-effect profiles. This article critically examines the specific concerns for the use of these drugs in older patients and reviews the existing literature on their use in this specific cohort.

Collaborative leadership in transplantation: Blending clinical, business, and regulatory roles.

Transplantation is a high-risk, high-cost treatment for end-stage diseases and is the most strictly regulated area of healthcare in the United States. Thus, achieving success for patients and the program requires skillful and collaborative leadership. Various factors, such as outcomes, volume, and financial health, may measure the success of a transplant program. Strong collaboration between clinical and administrative leaders is key to achieving and maintaining success in those three categories. Clinical leaders of adult programs, such as medical and surgical directors, bear the primary responsibility for a program's volume, outcomes, and patient safety, while administrative directors are focused on business intelligence and regulatory compliance. This paper aims to provide readers with insights into the critical role of collaborative leadership in running a successful program, with a focus on clinical, business, and regulatory perspectives.

Direct Support Professionals: Stress and Resiliency Amidst the COVID-19 Pandemic.

This study reports on the results of an online survey of direct support professionals (DSPs) during the COVID-19 pandemic in June 2020 to measure their perceived quality of life, stressors, coping/resilience skills, and knowledge of health care rights directly related to the pandemic for the persons that they support. Specifically, we examined direct support workers' perceptions of their quality of life, levels of stress, and their self-reported resilience skills. We found that perceived stress was strongly correlated with both self-reported quality of life and resilience, but not with years of DSP experience. Moreover, while DSPs overwhelmingly knew and affirmed health care rights for people with disabilities, they were less knowledgeable about their legal rights during hospital stays.

Five-year review of ocular Neisseria gonorrhoeae infections presenting to ophthalmology departments in Greater Glasgow & Clyde, Scotland.

INTRODUCTION: As gonococcal infections continue to increase, we wanted to review the number and clinical course of recent ocular gonococcal cases presenting to ophthalmology departments in NHS Greater Glasgow and Clyde. METHODS: A 5-year retrospective review of adult ocular gonococcal cases, where the diagnosis of Neisseria gonorrhoeae was made on microbiological culture, was undertaken. RESULTS: Fifteen cases were identified (80% male). Average age was 26 years (range 17-42; median 24). Most common presenting features included purulent discharge (14/15; 93%), haemorrhagic conjunctivitis (10/15; 67%) and pre-septal cellulitis (9/15; 60%). Corneal involvement was documented in 5 (33%), with marginal ulceration in 1 (7%) but none had corneal perforation. Most common systemic treatment was IV ceftriaxone, alone or in combination with another antibiotic (6/15; 40%), followed by IM ceftriaxone, alone or in combination with another antibiotic (5/15; 33%). Median time from presentation to treatment was 1 day (0-23). All patients were referred or recommended to attend sexual health services. Seven patients (47%) attended and received complete sexually transmitted infection (STI) testing and contact tracing: 3 patients had systemic treatment initiated or changed at this visit and 1 patient had concurrent syphilis identified. CONCLUSIONS: This series confirms purulent conjunctivitis and cellulitis as the main presenting features of ocular gonococcal infection requiring hospital review. Early identification with appropriate systemic antibiotic treatment avoided corneal melting in this cohort. As concurrent STIs were identified and/or treatments changed in 4/7 (57%) following sexual health review, we recommend a shared care approach between ophthalmology, microbiology and sexual health services to effectively address all management issues.

New York Transplant Teams Versus COVID-19.

New York State, and especially New York City, were hit hard by the coronavirus disease 2019 (COVID-19) virus. While we followed its course in other parts of the world, and began preparations, there was no way we could have been prepared for the volume and severity of illness that began to overflow in our emergency departments and hospital units. We expanded intensive care units into our medical surgical units while turning conference rooms into medical surgical patient care areas. Clinicians at the bedside described war-like situations with numerous patients arresting and requiring ventilator support. Our New York consortia and organ procurement organizations met online 3 times a week and shared creative strategies to address clinical care and work processes. We would like to share strategies from what we hope was a once in a lifetime experience.

GSK3ß-SCFFBXW7α mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover.

IRF1 (Interferon Regulatory Factor-1) is the prototype of the IRF family of DNA binding transcription factors. IRF1 protein expression is regulated by transient up-regulation in response to external stimuli followed by rapid degradation via the ubiquitin-proteasome system. Here we report that DNA bound IRF1 turnover is promoted by GSK3ß (Glycogen Synthase Kinase 3ß) via phosphorylation of the T181 residue which generates a phosphodegron for the SCF (Skp-Cul-Fbox) ubiquitin E3-ligase receptor protein Fbxw7α (F-box/WD40 7). This regulated turnover is essential for IRF1 activity, as mutation of T181 results in an improperly stabilized protein that accumulates at target promoters but fails to induce RNA-Pol-II elongation and subsequent transcription of target genes. Consequently, the anti-proliferative activity of IRF1 is lost in cell lines expressing T181A mutant. Further, cell lines with dysfunctional Fbxw7 are less sensitive to IRF1 overexpression, suggesting an important co-activator function for this ligase complex. As T181 phosphorylation requires both DNA binding and RNA-Pol-II elongation, we propose that this event acts to clear 'spent' molecules of IRF1 from transcriptionally engaged target promoters.

Testing Pediatric Acuity With an iPad: Validation of "Peekaboo Vision" in Malawi and the UK.

PURPOSE: To evaluate two builds of the digital grating acuity test, "Peekaboo Vision" (PV), in young (6-60 months) populations in two hospital settings (Malawi and United Kingdom). METHODS: Study 1 evaluated PV in Blantyre, Malawi (N = 58, mean age 33 months); study 2 evaluated an updated build in Glasgow, United Kingdom (N = 60, mean age 44 months). Acuities were tested-retested with PV and Keeler Acuity Cards for Infants (KACI). Bland-Altman techniques were used to compare results and repeatability. Child engagement was compared between groups. Study 2 included test-time comparison. RESULTS: Study 1 (Malawi): The mean difference between PV and KACI was 0.02 logMAR with 95% limits of agreement (LoA) of 0.33 to 0.37 LogMAR. On test-retest, PV demonstrated 95% LoA of -0.283 to 0.198 logMAR with coefficient of repeatability (CR) 0.27. KACI demonstrated 95% LoA of -0.427 to 0.323 logMAR, and larger CR was 0.37. PV evidenced higher engagement scores than KACI (P = 0.0005). Study 2 (UK): The mean difference between PV and KACI was 0.01 logMAR; 95% LoA was -0.413 to 0.437 logMAR. Again, on test-retest, PV had narrower LoA (-0.344 to 0.320 logMAR) and lower CR (0.32) versus KACI, with LoA -0.432 to 0.407 logMAR, CR 0.42. The two tests did not differ in engagement score (P = 0.5). Test time was ∼1 minute shorter for PV (185 vs. 251 s, P = 0.0021). CONCLUSIONS: PV gives comparable results to KACI in two pediatric populations in two settings, with benefits in repeatability indices and test duration. TRANSLATIONAL RELEVANCE: Leveraging tablet technology extends reliable infant acuity testing to bedside, home, and rural settings, including areas where traditional equipment cannot be financed.

Life Outcomes and Higher Education: The Need for Longitudinal Research Using a Broad Range of Quality of Life Indicators.

Higher education is increasingly becoming an option for young adults with intellectual disability (ID). Although initial evaluations of postsecondary education for this population have been promising, a broader "quality of life" framework needs to be adopted in order to truly understand the impact of these programs. Moreover, researchers and program evaluators must collect longitudinal data that follows former students for multiple years and uses multiple measures. We conducted a pilot evaluation of the life outcomes of students who had attended at least two semesters in Kentucky's supported higher education program for students with ID, collecting data on life status and experiences using measures from the National Core Indicators-Adult Consumer Survey. The findings from this pilot study show better outcomes for young adults who participated in a postsecondary education program compared to young adults who did not, but these findings need to be considered in light of several limitations. In many respects, our data provided more new questions than answers. Recommendations for collecting and evaluating broad-based, longitudinal data to gain insight into the potential benefits of postsecondary education for people with intellectual disability are discussed.

Congregational Participation of a National Sample of Adults With Intellectual and Developmental Disabilities.

Supporting people with intellectual and developmental disabilities (IDD) to thrive requires careful consideration of multiple avenues of community involvement. Yet little attention has focused on the place of faith community participation in the lives of adults with IDD. We examined attendance at religious services using National Core Indicator data for a sample of 12,706 adults with IDD residing in 24 states. Almost half of adults (48.3%) reported attending a religious service in the past month, and more than one third (34.6%) attended 3 or more times. Religious involvement varied considerably based on a variety of individual (e.g., race, disability type, behavioral support needs, communication mode) and contextual factors (e.g., geographic locale, residential type). Moreover, monthly involvement in religious activities was much less common than participation in other community activities (i.e., exercise, entertainment, eating out, shopping). We offer recommendations for supporting the spiritual lives of adults with IDD, as well as highlight areas for future research and practice.

The Genetic Structure of Marijuana and Hemp.

Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.

Bladder calculus formation on the tip of a migrated disused ventriculoperitoneal shunt.

Bladder stones in children are rare. They generally occur in children with one or more predisposing risk factors to stone formation. In this unique case report we discuss the formation and successful endoscopic treatment of a large stone in a neuropathic bladder on the tip of a migrated VP shunt.

The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response.

The regulation of Ubiquitin (Ub) conjugates generated by the complex network of proteins that promote the mammalian DNA double-strand break (DSB) response is not fully understood. We show here that the Ub protease POH1/rpn11/PSMD14 resident in the 19S proteasome regulatory particle is required for processing poly-Ub formed in the DSB response. Proteasome activity is required to restrict tudor domain-dependent 53BP1 accumulation at sites of DNA damage. This occurs both through antagonism of RNF8/RNF168-mediated lysine 63-linked poly-Ub and through the promotion of JMJD2A retention on chromatin. Consistent with this role POH1 acts in opposition to RNF8/RNF168 to modulate end-joining DNA repair. Additionally, POH1 acts independently of 53BP1 in homologous recombination repair to promote RAD51 loading. Accordingly, POH1-deficient cells are sensitive to DNA damaging agents. These data demonstrate that proteasomal POH1 is a key de-ubiquitinating enzyme that regulates ubiquitin conjugates generated in response to damage and that several aspects of the DSB response are regulated by the proteasome.

The reproductive endocrinology of the menopausal transition.

The menopause transition is a dynamic process that begins with the first appearance of menstrual irregularity and ends with a woman's final menstrual period. As ovarian follicle numbers dwindle, the hypothalamic-pituitary-ovarian axis enters a state of compensated failure. In this state, elevated FSH is capable of maintaining relatively regular folliculogenesis and ovulation, but fertility is reduced. Eventually, this state of compensated failure cannot be sustained, and the ovary becomes unable to produce functioning follicles. Recent multicenter studies from several countries have addressed the pattern of change in hormones and a model form reproductive aging has been developed that helps explain the changes in hormone patterns and fertility that accompany menopause. Perhaps more important, the hormonal changes of the menopausal transition may be predictive of future disease risk. This review will undertake an explanation of the current literature on this topic.

The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.

Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.

Dosimetric benefits of respiratory gating: a preliminary study.

In this study, we compared the amount of lung tissue irradiated when respiratory gating was imposed during expiration with the amount of lung tissue irradiated when gating was imposed during inspiration. Our hypothesis was that the amount of lung tissue spared increased as inspiration increased. Computed tomography (CT) image data sets were acquired for 10 patients who had been diagnosed with primary bronchogenic carcinoma. Data sets were acquired during free breathing and during breath-holds at 0% tidal volume and 100% tidal volume, and, when possible, at deep inspiration, corresponding to approximately 60% vital capacity. Two treatment plans were developed on the basis of each of the gated data sets: one in which the treatment portals were those of the free-breathing plan, and the other in which the treatment portals were based on the gated planning target volumes. Dose-mass histograms of the lungs calculated at 0% tidal volume were compared to those calculated at deep inspiration and at 100% tidal volume. Data extracted from the dose-mass histograms were used to determine the most dosimetrically beneficial point to gate, the reduction in the amount of irradiated lung tissue that resulted from gating, and any disease characteristics that might predict a greater need for gating. The data showed a reduction in the mass of normal tissue irradiated when treatment portals based on the gated planning target volume were used. More normal lung tissue was spared at deep inspiration than at the other two gating points for all patients, but normal lung tissue was spared at every point in the respiratory cycle. No significant differences in the amount of irradiated tissue by disease characteristic were identified. Respiratory gating of thoracic radiation treatments can often improve the quality of the treatment plan, but it may not be possible to determine which patients may benefit from gating prior to performing the actual treatment planning.

Back pain online: a cross-sectional survey of the quality of web-based information on low back pain.

STUDY DESIGN: A cross section of Web sites accessible to the general public was surveyed. OBJECTIVE: To evaluate the quality of information on low back pain and its treatment that a "typical" patient user might access on the Internet. SUMMARY OF BACKGROUND DATA: Individuals with back pain have a desire to learn about their condition, what to expect, and what they can do about it. Web sites play a potentially useful role in providing information to help people learn about their low back pain and select the most appropriate methods of management. METHODS: A general search using popular search engines located 60 Web sites about back pain for review. A list of criteria for evaluating and scoring back pain Web sites was established using available literature and current clinical guidelines for the management of acute low back pain. The total quality score (maximum score, 38) was composed of two separate scores: one for general quality of the site (maximum score, 14) and one for site content specific to low back pain (maximum score, 24). Statistical tests, as appropriate, were used to investigate the relation between general indicators of Web site quality and total scores obtained. RESULTS: The quality of the Web sites surveyed was poor, most of them (n = 58, 97%) scoring less than half the maximum available score. The mean total score was 7.4 (range, 2-25). The mean score was 4.9 (range, 1-12) for general Web site quality and 2.4 (range, 1-13) for content specific to low back pain. Web sites providing references, sites created more recently, and sites not created for advertising purposes tended to be of better quality. CONCLUSIONS: This study highlighted the poor quality of information, particularly information about low back pain, available to "typical" patient users on the Internet. Health care professionals must have a role in evaluating existing information and in developing good-quality evidence-based Web sites. Patients with back pain should be discouraged from using the Internet as a source of information unless the Web sites they access have been evaluated and found to provide evidence-based messages.