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1.
Ophthalmol Ther ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093386

ABSTRACT

INTRODUCTION: This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. METHODS: We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. RESULTS: A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. CONCLUSION: During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

3.
S Afr Fam Pract (2004) ; 66(1): e1-e8, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39099256

ABSTRACT

BACKGROUND:  Prevention strategies for reducing cervical cancer incidence rely on informed populations, particularly those most at risk. This study assesses the knowledge and awareness of female university students towards cervical cancer, human papillomavirus (HPV) and its vaccination. METHODS:  A validated self-administered questionnaire was used in a descriptive cross-sectional study among female university students. The data were analysed with Statistical Package for Social Sciences version 26, and p  0.05 was considered significant. RESULTS:  The total participants were 190 with a mean age of 22.6 ± 4.35 years. The majority (90%) were aware of cervical cancer, and 78.9% agreed it is a terminal illness, but fewer participants knew it was associated with infection (63.7%), and that it had effective risk-reducing methods (70.5%). Only 32.6% were aware of the Pap smear test, less than half (43.2%) were aware of the cervical cancer vaccine and only 43.7% knew it was available locally. Although fewer (39.5%) considered themselves susceptible to cervical cancer, many (62.1%) would like a Pap smear test. Overall, 88.9% of the participants possessed adequate knowledge of cervical cancer, 67.9% of the HPV vaccine and only 33.7% of HPV. Ethnicity (p = 0.03), year of study (p = 0.001) and institution (p = 0.002) were all significantly associated with knowledge levels, vaccine awareness and Pap smear test awareness. CONCLUSION:  Participants showed low HPV knowledge and varying awareness levels regarding cervical cancer, HPV and HPV vaccine.Contribution: This study provides insights into female university students' knowledge and awareness gaps, highlighting the need for targeted interventions.


Subject(s)
Health Knowledge, Attitudes, Practice , Papillomavirus Infections , Papillomavirus Vaccines , Students , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Papillomavirus Vaccines/administration & dosage , Cross-Sectional Studies , Students/psychology , Students/statistics & numerical data , Young Adult , Universities , Papillomavirus Infections/prevention & control , Surveys and Questionnaires , Adult , Papanicolaou Test , Vaccination/psychology , Adolescent , Vaginal Smears/psychology , Human Papillomavirus Viruses
4.
ACS Nano ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39114914

ABSTRACT

The electrochemical CO2 reduction reaction (CO2RR) to produce methanol (CH3OH) is an attractive yet challenging approach due to a lack of selective electrocatalysts. An immobilized cobalt phthalocyanine (CoPc) molecular catalyst has emerged as a promising electrocatalyst for CH3OH synthesis, demonstrating decent activity and selectivity through a CO2-CO-CH3OH cascade reaction. However, CoPc's performance is limited by its weak binding strength toward the CO intermediate. Recent advancements in molecular modification aimed at enhancing CO intermediate binding have shown great promise in improving CO2-to-CH3OH performance. In this Perspective, we discuss the competitive binding mechanism between CO2 and CO that hinders CH3OH formation and summarize effective molecular modification strategies that can enhance both the binding of the CO intermediate and the conversion of the CO2-to-CH3OH activity. Finally, we offer future perspectives on optimization strategies to inspire further research efforts to fully unlock the potential for methanol synthesis via the CO2RR using molecular catalysts.

5.
Can J Ophthalmol ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39128832

ABSTRACT

OBJECTIVE: The purpose of this study was to quantitatively analyze and compare OCT characteristics of intraretinal hyper-reflective foci (IHRF) in eyes with diabetic retinopathy (DR) versus age-related macular degeneration (AMD). DESIGN: a retrospective observational study. PARTICIPANTS: 54 treatment-naïve eyes (27 DR and 27 AMD). METHODS: The IHRF lesions in OCT B-scan were semi-automatically segmented. Mean reflectivity (MR), maximum diameter, circularity index (Cir), area, and the angle between the greatest linear dimension (GLD) and the horizontal were computed for each IHRF lesion. The presence and absence of a posterior shadow and the axial location were assessed. The MR was normalized using the vitreous and nerve fiber layer reflectance as dark and bright reference standards, respectively. RESULTS: A total of 1149 IHRF (1051 in DR and 98 in the AMD group) were identified, with a mean of 39 ± 36 lesions in DR eyes compared to only 4 ± 4 in AMD eyes (p < 0.001). The mean area of individual IHRF lesions was greater in DR eyes (1305 ± 1647 µm² vs 1031 ± 750 µm²; p = 0.016), but IHRF in AMD eyes had higher reflectivity (1.17 ± 0.14 vs 1.03 ± 0.17; p < 0.001). The angle of the GLD relative to the horizontal was greater in AMD eyes, indicating that IHRF in AMD eyes were more horizontally oriented. In AMD eyes, 88.8% of IHRF were located beneath the inner border of the outer nuclear layer (ONL), while in DR eyes, 56.9% were located there (p < 0.001). CONCLUSIONS: IHRF lesions in eyes with DR and AMD demonstrate significant differences, with IHRF in DR eyes tending to be larger and less hyper-reflective compared to AMD eyes.

6.
Lancet Reg Health Am ; 37: 100837, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39105140

ABSTRACT

Background: Most Americans believe that gun-free zones make locations more vulnerable to violent crimes, particularly active shootings. However, there is no empirical evidence regarding the impact of gun-free zones on protecting locations from violence. The objective of this study was to estimate the association between gun-free zones and active shootings. Methods: We used a pair-matched case-control study where cases were all US establishments where active shootings occurred between 2014 and 2020, and controls were randomly selected US establishments where active shootings could have but did not occur, pair-matched by establishment type, year, and county. Gun-free status of included establishments was determined via local laws, company policy, news reporting, Google Maps and posted signage, and calling establishments. Findings: Of 150 active shooting cases, 72 (48.0%) were determined to have occurred in a gun-free zone. Of 150 controls where no active shooting occurred, 92 (61.3%) were determined to be gun-free. After accounting for matched pairs, the conditional odds of an active shooting in gun-free establishments were 0.38 times those in non-gun-free establishments, with a 95% confidence interval of 0.19-0.73 (p-value = 0.0038). Several robustness analyses affirmed these findings. Interpretation: It is unlikely that gun-free zones attract active shooters; gun-free zones may be protective against active shootings. This study challenges the proposition of repealing gun-free zones based on safety concerns. Funding: This work was funded in part by the National Collaborative on Gun Violence Research and the Arnold Foundation.

7.
Perspect Behav Sci ; 47(2): 365-392, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39099743

ABSTRACT

Delay discounting, the decrease in outcome value as a function of delay to receipt, is an extensive area of research. How delays are framed (i.e., temporal framing), as well as the sign and magnitude of an outcome, produce important effects on the degree to which outcomes are discounted. Here, we examined how recent experience (i.e., order of presentation) modifies these well-known findings. Experiment 1 examined the effects of temporal framing across gains and losses. Regardless of outcome sign, the order of task presentation affected the effect of temporal framing. In particular, when typical delay frames (e.g., 1 week) preceded delays framed as actual dates (e.g., February 15), discounting was less in the date-framed task. However, when dates were followed by the delay frame, there was no difference in the degree of discounting. The experience of date-framed delays persisted or carried over to the delay-framed task. Experiment 2 examined recent experience and the magnitude effect. In particular, $10 and $100 were discounted similarly between-subjects when it was the first task completed. However, once participants completed the second magnitude task, the magnitude effect was present both within-subjects and across subjects. Furthermore, $10 was discounted more steeply when it followed $100, and $100 was discounted less steeply when it followed $10. The impact of recent experience on delay discounting has important implications for understanding mechanisms that may contribute to delay discounting. Recent experience should be considered when designing delay discounting experiments as well as when implementing interventions to reduce steep delay discounting.

9.
Can J Ophthalmol ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39033785

ABSTRACT

OBJECTIVE: To assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021. METHODS: The primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling. RESULTS: This study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42-70) and 70 (49-90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 µm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 µm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 µm (P < 0.001). CONCLUSIONS: This real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.

10.
Retina ; 44(8): 1441-1448, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39047131

ABSTRACT

PURPOSE: This study was designed to investigate retinal nerve fiber layer circumpapillary optical coherence tomography to determine posterior vitreous detachment (PVD) status and to develop a clinically relevant PVD grading scale based on retinal nerve fiber layer circumpapillary optical coherence tomography to determine the incidence of PVD by age and association with vitreomacular traction disorders. METHODS: Ophthalmic images and medical records of patients with retinal diseases were retrospectively analyzed by three masked graders using retinal nerve fiber layer circumpapillary optical coherence tomography and macular optical coherence tomography. Based on PVD status, eyes were categorized into five newly defined PVD stages. RESULTS: Among 2002 eyes, PVD stages were as follows: A) 25 (1.25%); B) 725 (36.21%); C-) 248 (12.39%); C+) 151 (7.54%); D) 851 (42.51%); X) 2 (0.1%). Posterior vitreous detachment was correlated with advanced age (P < 0.0001). Limited separation or partial separation between lamella within the posterior vitreous cortex (Stage B) was noted early (68% of eyes <18 years). Overall, 34% of eyes >70 years did not exhibit complete PVD. Of 75 eyes with tractional vitreoretinal disorders, 64 (85.3%) were Stage C-/C+, identifying Stage C as the high-risk "complication" stage. CONCLUSION: Imaging analyses using retinal nerve fiber layer circumpapillary optical coherence tomography and macular optical coherence tomography scans in conjunction allow rapid assessment of the PVD stage. These techniques can assist clinicians and surgeons in counseling patients and planning surgical approaches. Observations confirmed the progression of PVD through predictable stages and the progression of PVD with age.


Subject(s)
Macula Lutea , Nerve Fibers , Tomography, Optical Coherence , Vitreous Detachment , Humans , Tomography, Optical Coherence/methods , Vitreous Detachment/diagnosis , Vitreous Detachment/diagnostic imaging , Retrospective Studies , Middle Aged , Female , Male , Aged , Adult , Nerve Fibers/pathology , Macula Lutea/pathology , Macula Lutea/diagnostic imaging , Aged, 80 and over , Adolescent , Retinal Ganglion Cells/pathology , Young Adult , Child , Vitreous Body/pathology , Vitreous Body/diagnostic imaging
11.
Reprod Domest Anim ; 59(7): e14674, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39005151

ABSTRACT

Males of some species, from horses to humans, require medical help for subfertility problems. There is an urgent need for novel molecular assays that reflect spermatozoal function. In the last 25 years, studies examined RNAs in spermatozoa as a window into gene expression during their development and, more recently, for their functions in early embryo development. In clinics, more dense spermatozoa are isolated by density gradient centrifugation before use in artificial insemination to increase pregnancy rates. The objectives of the current study were to discover and quantify the microRNAs in stallion spermatozoa and identify those with differential expression levels in more dense versus less dense spermatozoa. First, spermatozoa from seven stallions were separated into more dense and less dense populations by density gradient centrifugation. Next, small RNAs were sequenced from each of the 14 RNA samples. We identified 287 different mature microRNAs within the 11,824,720 total mature miRNA reads from stallion spermatozoa. The most prevalent was miR-10a/b-5p. The less dense spermatozoa had fewer mature microRNAs and more microRNA precursor sequences than more dense spermatozoa, perhaps indicating that less dense spermatozoa are less mature. Two of the most prevalent microRNAs in more dense stallion spermatozoa were predicted to target mRNAs that encode proteins that accelerate mRNA decay. Nine microRNAs were more highly expressed in more dense spermatozoa. Three of those microRNAs were predicted to target mRNAs that encode proteins involved in protein decay. Both mRNA and protein decay are very active in late spermiogenesis but not in mature spermatozoa. The identified microRNAs may be part of the mechanism to shut down those processes. The microRNAs with greater expression in more dense spermatozoa may be useful biomarkers for spermatozoa with greater functional capabilities.


Subject(s)
Biomarkers , MicroRNAs , Spermatozoa , Horses , Male , Animals , Spermatozoa/physiology , Spermatozoa/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers/metabolism
12.
J Surg Orthop Adv ; 33(2): 93-96, 2024.
Article in English | MEDLINE | ID: mdl-38995065

ABSTRACT

Atherosclerotic disease in the vessels that supply the cervical spine may lead to degenerative disease. In angina pectoris (AP), atherosclerotic disease leads to coronary vessel occlusion and resulting symptoms. This study aims to determine the relationship between AP and neck pain. Analysis was focused on respondents who had a history of cervical pain disorders, adjusting for demographic, education, and mental health confounders. A total of 30,461 participated in the survey. Of 1,049 respondents, 21% reported neck pain. Mean age of the respondents was 62.6 ± 16.1 years. Nonwhite race, current everyday smokers, lower family income, hypertension, and diabetes had higher prevalence of neck pain (p < 0.05). On multivariate analysis, AP was associated with increased odds of neck pain (odds ratio [OR] = 1.42 [95% confidence interval (CI) 1.04 to 1.92], p = 0.026). AP was independently associated with 42% increased odds of having neck pain. Further study into the association of cardiovascular disease with degenerative disc disease pain should be performed. (Journal of Surgical Orthopaedic Advances 33(2):093-096, 2024).


Subject(s)
Angina Pectoris , Cervical Vertebrae , Medicare , Neck Pain , Humans , Male , Cross-Sectional Studies , Female , Middle Aged , Neck Pain/epidemiology , Aged , United States/epidemiology , Angina Pectoris/epidemiology , Intervertebral Disc Degeneration/epidemiology , Prevalence , Aged, 80 and over , Adult , Surveys and Questionnaires
13.
Transpl Infect Dis ; : e14330, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39003580

ABSTRACT

Among the post-transplantation complications that patients may encounter, the transmission of a donor-derived malignant neoplasm is uncommon but potentially life threatening. The determination of donor versus recipient origin is essential particularly in the setting of multiple transplant recipients from the donor. Advances in molecular biology now allow accurate discrimination utilizing routine tissue samples in a timely and cost-effective manner. The techniques are routinely performed in hospital molecular biology laboratories and are also available in commercial labs. The current methodologies are discussed and future possibilities are presented for clinicians caring for solid organ recipients.

14.
BMC Nephrol ; 25(1): 238, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075357

ABSTRACT

BACKGROUND: Sodium-glucose transporter-2 inhibitors (SGLT-2i) are recommended for use in patients with type 2 diabetes comorbid atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Limited reports are currently available for their use in dialysis patients. In an observational, retrospective follow-up study, we reported the clinical characteristics of chronic peritoneal dialysis (PD) patients on SGLT-2i. METHODS: We enrolled 50 diabetic chronic PD patients, and 11 continued SGLT-2i after PD treatment. We reported the patients' ultrafiltration, HbA1c, urinary tract infection episodes, and venous CO2 during follow-up and compared the differences in these factors between patients with and without SGLT-2i. RESULTS: The mean age of the patients was 65 ± 15 years, and 16 (32%) patients were female. The age, gender, heart failure, and primary kidney disease were not different between patients with and without SGLT-2i at enrollment. In an average of 31 months follow-up, patients with SGLT-2i had higher ultrafiltration (1322 ± 200 ml/day vs. 985 ± 415 ml/day, p = 0.013), hemoglobin (11.2 ± 1.7 vs. 10.2 ± 1.7 g/dl), white blood cell count (9.2 ± 3.7 vs. 7.4 ± 2.1 109/L), and a lower venous CO2 (p = 0.036). The urine amount, the overall survival, the technical survival, and the chance of UTI were not different between patients with and without SGLT2i. CONCLUSION: SGLT-2i may increase ultrafiltration volume and hemoglobin levels in chronic PD patients. SGLT-2i did not increase urinary tract infection but was linked to subclinical metabolic acidosis. WHAT WAS KNOWN: The effect of SGLT-2i in chronic PD patients is not clear? THIS STUDY ADDS: SGLT-2i is associated with increased ultrafiltration, hemoglobin, white blood cell counts, and a decreased CO2 in PD patient. POTENTIAL IMPACT: SGLT-2i may increase ultrafiltration in PD patients.


Subject(s)
Peritoneal Dialysis , Sodium-Glucose Transporter 2 Inhibitors , Humans , Female , Male , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Aged , Retrospective Studies , Middle Aged , Follow-Up Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/metabolism , Urinary Tract Infections , Ultrafiltration , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complications
15.
Health Policy Plan ; 39(7): 652-660, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39001892

ABSTRACT

Zimbabwe has received substantial external assistance for health since the early 2000s, including funding earmarked for, or framed as, health systems strengthening (HSS). This study sought to examine whether external assistance has strengthened the health system (i.e. enabled comprehensive changes to health system performance drivers) or has just supported the health system (by increasing inputs and improving service coverage in the short term). Between August and October 2022, we conducted in-depth key informant interviews with 18 individuals and reviewed documents to understand: (1) whether external funding has supported or strengthened Zimbabwe's health system since the 2000s; (2) whether the experience of COVID-19 fosters a re-examination of what had been considered as HSS during the pre-pandemic era; and (3) areas to be reconsidered for HSS post COVID-19. Our findings suggest that external funders have supported Zimbabwe to control major epidemics and avert health system collapse. However, the COVID-19 pandemic showed that supporting the health system is not the same as strengthening it, as it became apparent at that time that the health sector is plagued with several system-wide bottlenecks. External funding is fragile and highly unsustainable, which reinforces the oft-ignored reality that HSS is a sovereign mandate of country-level authorities, and one that falls outside the core interests of external funders. The key positive lesson from the pandemic is that Zimbabwe is capable of raising domestic resources to fund HSS. However, there is no guarantee that such funding will be maintained. There is a need, then, to reconsider government's stewardship for HSS. External funders need to re-examine whether their funding really strengthens the national health system or just supports the country to provide basic services in their areas of interest.


Subject(s)
COVID-19 , Delivery of Health Care , Zimbabwe , Humans , COVID-19/epidemiology , Delivery of Health Care/organization & administration , Pandemics , SARS-CoV-2
16.
Chem Commun (Camb) ; 60(62): 8039-8042, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38988236

ABSTRACT

Studying the interactions between CO2 sorbents and electrocatalysts for the electrochemical CO2 reduction reaction (e-CO2RR) can offer viable strategies to advance the development of the Reactive Capture of CO2 (RCC). In this report we studied the effect of amines on the performance of the [Co(PDI-Py)] catalyst for the e-CO2RR. The presence of amines shifts the onset potential for the e-CO2RR more positive and increases the catalytic activity while maintaining the high Faradaic efficiency (≥90%) for CO production.

17.
Res Sq ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38946950

ABSTRACT

Background: The research community has historically failed to enroll diverse groups of participants in dementia clinical trials. A unique aspect of dementia care research is the requirement of a study partner, who can attest to the care recipient's clinical and functional capacity. The aim of this study is to assess racial and ethnic differences and the importance of various trial considerations among dementia caregivers, in their decision to participate in clinical research as study partners. Method: We embedded a vignette about a hypothetical dementia clinical trial in a nationally representative survey of U.S. dementia caregivers, oversampling non-Hispanic Black and Hispanic caregivers. Dementia caregivers were asked about their willingness to participate in the trial with their care recipient and rated the importance of nine considerations in hypothetical decisions to participate. Caregiver demographic characteristics were analyzed as predictors of trial participation in a base demographic model. In a second reasons model caregiver demographic characteristics and the rated importance of the nine considerations were separately analyzed as predictors; both models used survey-weighted logistic regression. Result: The sample consisted of 610 dementia caregivers, including 156 non-Hispanic Black and 122 Hispanic caregiver participants. In the base demographic model, hypothetical trial participation was negatively associated with older caregiver age (OR (odds ratio) = 0.72, p = < 0.001). In the reasons model, the rated importance of a social responsibility to help others by participating in research was significantly associated with participation (OR = 1.56, p = 0.049), while the importance of the possibility of the care recipient experiencing serious side effects was negatively associated with participation (OR = 0.51, p = 0.003). In both models there was no significant difference in hypothetical participation between non-Hispanic Black and non-Hispanic White caregivers, or between Hispanic and non-Hispanic White caregivers. Conclusion: Hispanic and non-Hispanic Black dementia caregivers were not less likely than non-Hispanic White dementia caregivers to participate in a hypothetical dementia clinical trial. Our study suggests that failures to recruit diverse populations in dementia clinical research are not attributable to less willingness among members of underrepresented groups but may instead reflect structural barriers and historic exclusion from trial participation.

18.
Br J Pharmacol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978389

ABSTRACT

BACKGROUND AND PURPOSE: Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady-state binding affinities of various neurosteroids for specific sites on the GABAA receptor. EXPERIMENTAL APPROACH: Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17-methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC-α1GABAAR, a chimeric receptor containing transmembrane domains of the α1-GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions. KEY RESULTS: Allopregnanolone (3α-OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi-allopregnanolone (3ß-OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site-specific probe for the intersubunit site. The affinity and site-specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites. CONCLUSIONS AND IMPLICATIONS: The affinity and specificity of neurosteroid binding to two sites in the ELIC-α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate-reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.

19.
Eye (Lond) ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033242

ABSTRACT

OBJECTIVE: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses. METHODS: Meta-analyses of randomized controlled trials with binary outcomes published in a journal classified as 'Ophthalmology' according to the Journal Citation Report or an Ophthalmology-related Cochrane Review were included. An iterative process determined the FI of each meta-analysis. Multivariable linear regression modeling evaluated the relationship between the FI and potential predictive factors in statistically significant and non-significant meta-analyses. RESULTS: 175 meta-analyses were included. The median FI was 6 (Q1-Q3: 3-12). This meant that moving 6 outcomes from one group to another would reverse the study's findings. The FI was 1 for 18 (10.2%) of the included meta-analyses and was ≤5 for 75 (42.4%) of the included meta-analyses. The number of events (p < 0.001) and the p-value (p < 0.001) were the best predictors of the FI in both significant and non-significant meta-analyses. CONCLUSION: The statistical significance of meta-analyses in ophthalmology often hinges on the outcome of a few patients. The number of events and the p-value are the most important factors in determining the fragility of the evidence. The FI is an easily interpretable measure that can supplement the reader's understanding of the strength of the evidence being presented. PROSPERO REGISTRATION: CRD42022377589.

20.
Article in English | MEDLINE | ID: mdl-39033348

ABSTRACT

PURPOSE: The purpose of this retrospective review was to determine the prevalence of osteochondral lesions (OCLs) of the lateral talar dome in patients with anterior ankle impingement with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament. METHODS: Retrospective chart review identified 40 patients who underwent anterior ankle arthroscopy for the management of anterior ankle impingement. Clinical outcomes assessed included pre- and postoperative foot and ankle outcome score (FAOS), visual analogue scale (VAS), complications, failures, secondary surgical procedures, return-to-work data and return-to-sport data. RESULTS: Thirty-two patients with a mean follow-up time of 29.3 ± 10.4 months were included. The hypertrophic distal fascicle of the anterior tibio-fibular ligament was hypertrophic in 29 patients (90.6%), with a mean thickness of 2.5 ± 0.4 mm on MRI. There were 22 OCLs of the lateral talar dome (75.9%) with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament visualized during arthroscopy. The international cartilage repair society gradings of the lesions included 3 (13.6%) grade I lesions, 15 (68.1%) grade II lesions, 3 (13.6%) grade III lesions, and 1 (4.6%) grade IV lesion. There was a statistically significant improvement in mean FAOS and VAS scores from preoperative to postoperative (p < 0.001). No cases of syndesmotic instability were observed following resection of hypertrophic distal fascicle of the anterior tibio-fibular ligament. CONCLUSION: This retrospective case series demonstrated that a hypertrophic distal fascicle of the anterior tibio-fibular ligament was associated with an OCL of the lateral talar dome identified during arthroscopic evaluation. In addition, preoperative MRI demonstrated poor sensitivity for the detection of these OCLs. Heightened awareness is warranted for potential lateral talar dome OCLs in patients presenting with anterolateral ankle impingement with a hypertrophic ATiFLdf identified on preoperative MRI in the absence of an associated OCLs. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

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