Impaired Visual Function in Posterior Vitreous Detachment Assessed With the Active-Learning Quantitative Contrast Sensitivity Function Test.

Introduction: To investigate whether there is visual function impairment in patients with posterior vitreous detachment (PVD) using the active-learning quantitative contrast sensitivity function test. Methods: In this cross-sectional study, contrast sensitivity was measured in eyes with PVD and eyes without PVD using the quantitative contrast sensitivity function algorithm on the Adaptive Sensory Technology platform. Outcomes included the area under the log contrast sensitivity function curve, contrast acuity, and contrast sensitivity thresholds at 1 to 18 cycles per degree (cpd). Snellen visual acuity (VA) was also measured. Mixed-effects multiple linear regression analyses were performed to evaluate the association between the presence of PVD and visual function, controlling for age and lens status. Results: The cohort comprised 232 healthy eyes of 205 participants; of these, 80 eyes of 69 patients had PVD. There was no significant association between VA and PVD presence. However, PVD was significantly associated with decreased contrast sensitivity thresholds at 1.5 cpd (ß, -0.058; P = .003) and 3 cpd (ß, -0.067; P = .004). Contrast sensitivity thresholds at lower (1 cpd) or higher (6, 12, 18 cpd) spatial frequencies did not significantly correlate with PVD presence. Even in the subgroup of symptomatic PVD eyes, VA was not significantly decreased, while quantitative contrast sensitivity function outcomes showed visual function deficits at low spatial frequencies (1.5 cpd and 3 cpd). Conclusions: Contrast sensitivity measured with the quantitative contrast sensitivity function test showed visual function deficits in eyes with PVD that would have been missed with VA testing alone. Incorporating this test in the retina clinic might offer a more comprehensive functional assessment of eyes with PVD, serving as an adjunct outcome metric in clinical decision-making.

Predictive factors for additional surgeries in drug-resistant epilepsy after mesial temporal laser interstitial thermal therapy.

We aimed to identify factors predicting additional surgical interventions in patients with drug-resistant epilepsy who continue experiencing seizures after mesial temporal laser interstitial thermal therapy (LITT). In a retrospective observational study, we analyzed consecutive patients with drug-resistant temporal epilepsy treated with mesial temporal LITT at the University of Washington between 2013-2022. The primary outcome was subsequent epilepsy surgery to improve seizure control after LITT. Logistic regression was used to assess how clinical factors and travel distance within tertiary center referral regions predict subsequent surgery occurrence. We identified 145 patients treated with mesial temporal LITT. Among the patients, 25 underwent subsequent surgeries, including 17 temporal lobectomies, 5 repeat LITT, 2 responsive neurostimulation, and 1 with deep brain stimulation. Further surgery was associated with higher Engel scores and shorter travel distance to our tertiary epilepsy center. Factors like age, sex, epilepsy duration, surgery on dominant hemisphere, and frequency of convulsive seizures were not significant. Patients who continue to have seizures after LITT are potential candidates for more surgery. Patients who must travel farther are less likely to receive follow-up surgery. Healthcare inequity presents a significant barrier in accessing epilepsy surgery, limiting the potential to achieve improved outcomes for individuals with epilepsy.

Cardiomyocyte Reduction of Hybrid/Complex N-Glycosylation in the Adult Causes Heart Failure With Reduced Ejection Fraction in the Absence of Cellular Remodeling.

BACKGROUND: Heart failure (HF) presents a massive burden to health care with a complex pathophysiology that results in HF with reduced left ventricle ejection fraction (EF) or HF with preserved EF. It has been shown that relatively modest changes in protein glycosylation, an essential posttranslational modification, are associated with clinical presentations of HF. We and others previously showed that such aberrant protein glycosylation in animal models can lead to HF. METHODS AND RESULTS: We develop and characterize a novel, tamoxifen-inducible, cardiomyocyte Mgat1 knockout mouse strain, achieved through deletion of Mgat1, alpha-1,3-mannosyl-glycoproten 2-beta-N-acetlyglucosaminyltransferase, which encodes N-acetylglucosaminyltransferase I. We investigate the role of hybrid/complex N-glycosylation in adult HFrEF pathogenesis at the ion channel, cardiomyocyte, tissue, and gross cardiac level. The data demonstrate successful reduction of N-acetylglucosaminyltransferase I activity and confirm that hybrid/complex N-glycans modulate gating of cardiomyocyte voltage-gated calcium channels. A longitudinal study shows that the tamoxifen-inducible, cardiomyocyte Mgat1 knockout mice present with significantly reduced systolic function by 28 days post induction that progresses into HFrEF by 8 weeks post induction, without significant ventricular dilation or hypertrophy. Further, there was minimal, if any, physiologic or pathophysiologic cardiomyocyte electromechanical remodeling or fibrosis observed before (10-21 days post induction) or after (90-130 days post induction) HFrEF development. CONCLUSIONS: The tamoxifen-inducible, cardiomyocyte Mgat1 knockout mouse strain created and characterized here provides a model to describe novel mechanisms and causes responsible for HFrEF onset in the adult, likely occurring primarily through tissue-level reductions in electromechanical activity in the absence of (or at least before) cardiomyocyte remodeling and fibrosis.

Rapid shift in methane carbon isotopes suggests microbial emissions drove record high atmospheric methane growth in 2020-2022.

The growth rate of the atmospheric abundance of methane (CH4) reached a record high of 15.4 ppb yr-1 between 2020 and 2022, but the mechanisms driving the accelerated CH4 growth have so far been unclear. In this work, we use measurements of the 13C:12C ratio of CH4 (expressed as δ13CCH4) from NOAA's Global Greenhouse Gas Reference Network and a box model to investigate potential drivers for the rapid CH4 growth. These measurements show that the record-high CH4 growth in 2020-2022 was accompanied by a sharp decline in δ13CCH4, indicating that the increase in CH4 abundance was mainly driven by increased emissions from microbial sources such as wetlands, waste, and agriculture. We use our box model to reject increasing fossil fuel emissions or decreasing hydroxyl radical sink as the dominant driver for increasing global methane abundance.

Diagnosis of Menopause in a Captive Sumatran Orangutan (Pongo abelii).

Humans were long thought to be the only mammal to experience menopause, the permanent cessation of reproduction followed by a long post-reproductive lifespan. More recently, evidence has been found for the existence of menopause in other long-lived mammals, including chimpanzees and gorillas. However, orangutans, which have the longest interbirth interval of any primate, have rarely been studied in this period of their lives. In this paper, we describe clinical, ultrasound, endocrine, and histological evidence consistent with a natural menopause in a captive, previously fertile, Sumatran orangutan (Pongo abelii), aged approximately 50. Consecutive serum samples showed low levels of estradiol and high levels of follicle-stimulating hormone. Transvaginal ultrasound revealed an atrophic uterus with an antero-posterior diameter of 2.36 cm, an endometrial thickness of 2 mm, and inactive ovaries. Following this female's death from a subdural hematoma, histological examination of the ovaries showed a dense stroma with corpora albicantia, in comparison to the numerous primordial follicles seen in the ovaries of a stillborn infant female orangutan. These multiple lines of evidence suggest that Sumatran orangutans can now be added to the list of mammals which undergo a true menopause, which may ensure that females' final offspring can be reared to independence.

Why does malaria transmission continue at high levels despite universal vector control? Quantifying persistent malaria transmission by Anopheles funestus in Western Province, Zambia.

BACKGROUND: Some settings continue to experience a high malaria burden despite scale-up of malaria vector control to high levels of coverage. Characterisation of persistent malaria transmission in the presence of standard control measures, also termed residual malaria transmission, to understand where and when individuals are exposed to vector biting is critical to inform refinement of prevention and control strategies. METHODS: Secondary analysis was performed using data collected during a phase III cluster randomized trial of attractive targeted sugar bait stations in Western Province, Zambia. Two seasonal cohorts of children aged 1-14 years were recruited and monitored monthly during the malaria transmission season, concurrent with entomological surveillance using a combination of human landing catch (HLC) and Centres for Disease Control (CDC) light traps at randomly selected households in study clusters. Behavioural data from cohort participants were combined with measured Anopheles funestus landing rates and sporozoite positivity to estimate the human behaviour-adjusted entomological inoculation rate (EIR). RESULTS: Behavioural data from 1237 children over 5456 child-visits in 20 entomology surveillance clusters were linked with hourly landing rates from 8131 female An. funestus trapped by HLC. Among all An. funestus tested by enzyme-linked immunosorbent assay (ELISA), 3.3% were sporozoite-positive. Mean EIR directly measured from HLC was 0.07 infectious bites per person per night (ib/p/n). When accounting for child locations over the evening and night, the mean behaviour-adjusted EIR was 0.02 ib/p/n. Children not sleeping under insecticide-treated nets (ITNs) experienced 13.6 infectious bites per person per 6 month season, 8% of which occurred outdoors, while ITN users received 1.3 infectious bites per person per 6 month season, 86% of which were received outdoors. Sleeping under an ITN can prevent approximately 90% of potential An. funestus bites among children. CONCLUSIONS: In this setting ITNs have a high personal protective efficacy owing to peak An. funestus biting occurring indoors while most individuals are asleep. However, despite high household possession of ITNs (>90%) and high individual use (>70%), children in this setting experience more than one infectious bite per person per 6 month transmission season, sufficient to maintain high malaria transmission and burden. New tools and strategies are required to reduce the malaria burden in such settings.

The Ergonomic Evaluation of Attendings and Trainees Across the Vitreoretinal Service as Measured by a Wearable Device.

BACKGROUND AND OBJECTIVE: A cross-sectional prospective study to examine ergonomic differences in vitreoretinal settings: surgery, clinic, and dedicated procedure clinic. PATIENTS AND METHODS: Three vitreoretinal surgeons, three fellows, and one resident at a tertiary eye care facility. Participants wore an Upright Go 2 posture device and posture was recorded in each setting between July 1 to August 31, 2023. RESULTS: Time in upright and poor postures was tracked. Significant differences were found in postural score for attendings between work settings (P < 0.01). Trainees showed no significant difference between settings. Poor posture in surgery was linked to microscope use and scleral buckle placement; in the clinic, it was associated with pan-retinal photocoagulation and injection minutes; in procedure clinic, it was ophthalmologist-dependent and those performing injections. CONCLUSIONS: Ergonomic considerations are crucial in vitreoretinal practice. Attendings and trainees should focus on posture in surgery and clinic settings to enhance career longevity. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Improved Visual Outcomes With Dedicated Retina Call Block Time in Primary Retinal Detachment Repair.

BACKGROUND AND OBJECTIVE: To investigate visual outcomes for macula-off rhegmatogenous retinal detachments (RRD) compared to macula-on RRDs based on duration from diagnosis to surgical repair performed by a single surgeon with access to a retina call block system. PATIENTS AND METHODS: A case-control study reviewing the visual acuity (VA) after surgical repair in consecutive macula-off (n = 127) and maculaon (n = 63) RRD comparison eyes that underwent primary RRD repair performed by a single surgeon with dedicated retina call block time. RESULTS: Our results revealed significantly improved VA in macula-off RRD eyes repaired within 3 days of diagnosis at 3, 6, and 12 months/last follow-up, and that duration from diagnosis to surgery is a predictor of VA at 3- and 12-month/last follow-up postoperative visits. CONCLUSION: Our findings support the use of mechanisms that improve access to operating room time, such as a retina call block system, to expedite surgical repair access. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Evaluating trends in damage to attractive targeted sugar baits (ATSBs) deployed during the second year of a two-year Phase III trial in Western Zambia.

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) are a proposed new vector control tool for malaria that contain sugar and an ingestion toxicant, and are designed to attract and kill sugar-feeding mosquitoes. During a two-arm cluster randomized Phase III trial conducted in Zambia to test the efficacy of ATSB stations on malaria incidence, ATSB stations deployed on eligible household structures within intervention clusters were routinely monitored to ensure their good physical condition and high coverage. This study investigates trends in prevalence and rate of damage to ATSB stations during year 2 of the two-year trial. METHODS: The analysis was conducted using monitoring data collected in year 2, which included types of damage observed, location, and date of removal and/or replacement of ATSB stations. The study evaluated temporal trends in the prevalence of overall damage and different damage types among 68,299 ATSB stations deployed. A profile of all ATSB stations installed on each structure was constructed, and spatial analyses conducted on overall damage and different damage types observed on 18,890 structures. Mixed effects regression analyses were conducted to investigate drivers of damage to ATSB stations on these structures. RESULTS: Prevalence of overall damage and different damage types was temporally and spatially heterogeneous. Among damaged ATSB stations observed during monitoring, tears and mold had the highest prevalences on average, with tears maintaining above 50.0% prevalence through most of the monitoring period, while mold prevalence increased steadily during the first few months, peaking in February. Overall, 45.6% of structures had at least one damaged ATSB station, however this varied spatially across the trial site. Both structure characteristics and environmental factors significantly impacted the odds and rate of damage to ATSB stations on structures, including: ATSB stations' level of protection from rainfall and sunshine; roof and wall material of the structure; night-time temperature; rainfall; enhanced vegetation index, and land cover. CONCLUSION: Damage to ATSB stations in this setting was common and was temporally and spatially heterogeneous. This has implications on operational feasibility, sustainability, and cost of future deployment. Further research is required to understand the mechanisms of damage, and to minimize prevalence and rate of damage to ATSB stations.

Community acceptance of a novel malaria intervention, Attractive Targeted Sugar Baits, in the Zambia phase III trial.

BACKGROUND: Community acceptance is an important criterion to assess in community trials, particularly for new tools that require high coverage and use by a target population. Installed on exterior walls of household structures, the attractive targeted sugar bait (ATSB) is a new vector control tool designed to attract and kill mosquitoes. ATSBs were evaluated in Western Zambia during a two-year cluster randomized controlled trial to assess the efficacy of ATSBs in reducing malaria transmission. Community acceptance of ATSBs was critical for successful trial implementation. METHODS: A community engagement strategy outlined activities and key messages to promote acceptance. Annual cross-sectional surveys, conducted during the peak transmission period, assessed households for presence of ATSBs as well as perceived benefits, concerns, and willingness to use ATSBs. Sixteen focus group discussions and 16 in-depth interviews, conducted at the end of each ATSB station deployment period, obtained a range of perceptions and household experiences with ATSB stations, as well as ITN use in the context of ATSB deployment. RESULTS: Methods used during the study to promote acceptance and continued use of ATSBs were effective in achieving greater than 90% coverage, a high (greater than 70%) level of perceived benefits, and fewer than 10% of households reporting safety concerns. Common facilitators of acceptance included the desire for protection against malaria and reduction of mosquitoes, trust in health initiatives, and understanding of the product. Common barriers to acceptance included misconceptions of product impact on mosquitoes, continued cases of malaria, association with satanism, and damage to household structures. DISCUSSION: Future use of the ATSB intervention will likely require activities that foster community acceptance before, during, and after the intervention is introduced. Additional research may be needed to understand the impact of different levels of community engagement on ATSB station coverage, ATSB station perception, and ITN use. CONCLUSION: There was high acceptance of ATSB stations during the trial in Western Zambia. Continuous and intense community engagement efforts contributed to sustained ATSB coverage and trust in the product. Acceptance of ATSBs during programmatic delivery requires further research.

Full-Thickness Macular Hole in a Pediatric Patient With Normal Vision.

A 17-year-old boy presented with a full-thickness macular hole, with 20/20 vision with eccentric fixation in the left eye. Examination of the left eye showed a large macular hole with a base diameter measuring 1,680 µm and temporal macular and mid-peripheral retinal atrophy on ultra-high-definition optical coherence tomography (OCT) scans. Microperimetry showed eccentric fixation with good nasal sensitivity. A 12 x 12-mm extended-field swept-source OCT angiogram showed flow loss in the temporal macula, with slight reduction noted in the choriocapillaris. Given excellent visual acuity, good tolerance by the patient, and large atrophic hole, the decision was made for observation rather than surgery. [Ophthalmic Surg Lasers Imaging Retina 2024;55:607-612.].

Atypical Central Retinal Vein Occlusion in an Older Man With Multiple Myeloma: A Case Report.

This report aims to describe the clinical presentation of a patient with an atypical central retinal vein occlusion (CRVO) in the setting of multiple myeloma. The patient was a 72-year-old man with an extensive hematologic-oncologic history and cardiovascular risk factors who presented with new-onset blurry vision and visual acuity (VA) of 20/40 in the left eye. The VA worsened to 20/60 two months after the initial presentation. By the 6-month follow-up visit, a series of three intravitreal bevacizumab injections for macular edema improved VA from 20/60 to 20/40. This case demonstrates the importance of fluorescein angiography in diagnosing a CRVO and exemplifies an atypical presentation on exam and imaging studies. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Nondiabetic Vitreous Hemorrhage: A Review of Management Strategy and Outcomes.

Vitreous hemorrhage involves blood leakage into or around the vitreous cavity, which presents complex management decisions. Treatment options for nondiabetic vitreous hemorrhage (NDVH) traditionally include observation or early vitrectomy. Traditional guidelines have long emphasized an initial period of cautious observation. This systematic review shows that a significant portion (∼62% to 75%) of NDVH patients present a retinal tear and/or detachment upon initial presentation. B-scan ultrasonography, the primary diagnostic tool, exhibits variable sensitivities and may miss approximately half (46.4%) of underlying tears or detachments. Only 25% of observed NDVH cases clear spontaneously, while the remaining will ultimately require vitrectomy due to nonclearance (45%) or sight-threatening complications (30%). Patients under observation experience visual deficits as hemorrhage clears slowly, challenging the efficacy of traditional guidelines favoring observation. While there is no clear guideline concerning the management of NDVH, our findings suggest that early vitrectomy for severe NDVH may be the safest and most appropriate approach, provided the patient accepts procedural risks like cataract development. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Widefield Swept-Source OCTA Findings in HELLP Syndrome: Choroidal Infarcts.

PURPOSE: Pre-eclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome have been previously implicated with ophthalmic complications including serous retinal detachments and disorders of the choroidal vasculature. Herein, we report a case of macular serous detachment associated with HELLP syndrome in which wide field swept-source optical coherence tomography angiography (WF SS-OCTA) was used. METHODS: Retrospective case report of a patient who developed HELLP syndrome. The patient underwent multimodal retinal imaging and wide field swept-source OCT angiography (WF SS-OCTA) (PLEX® Elite 9000, Carl Zeiss Meditec Inc.). RESULTS: A 36-year-old female patient diagnosed with HELLP syndrome presented with bilateral blurry vision. At presentation, dilated fundus exam revealed localized subretinal fluid in the macula. WF SS-OCTA showed areas of peripapillary and subfoveal flow signal attenuation in the choroid OD, consistent with choroidal infarction. CONCLUSIONS: These findings support the hypothesis that HELLP syndrome is associated with vascular changes that lead to choroidal dysfunction and subsequent serous retinal detachments. Furthermore, this case highlights a role for the non-invasive WF SS-OCTA technology in diagnosing and further characterizing the pathophysiology without the use of dye-based angiography.

Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia.

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Heads-up 3-Dimensional Visualization to Enhance Video Endoscopy During Vitreoretinal Surgery.

Purpose: To describe 2 cases in which video endoscopy was combined with heads-up 3-dimensional (3D) visualization. Methods: The imaging modalities of the heads-up 3D visualization system and video endoscopy were combined by converting the endoscope's S-Video output into a high-definition multimedia interface. The technique was used in 2 cases that included lens dislocation and endophthalmitis. Results: In the 2 cases, the heads-up split-screen view simplified the surgical setup. Simultaneously viewing the endoscopic image and widefield 3D image anecdotally appeared to improve ergonomics, help keep the probe oriented, and assist in guiding surgical movements endoscopically. Conclusions: These cases show the advantages of a heads-up 3D system to simultaneously view endoscopic and widefield images during ophthalmic endoscopy in vitreoretinal surgery.

National genomic profiling of Plasmodium falciparum antimalarial resistance in Zambian children participating in the 2018 Malaria Indicator Survey.

The emergence of antimalarial drug resistance is a major threat to malaria control and elimination. Using whole genome sequencing of 282 P. falciparum samples collected during the 2018 Zambia National Malaria Indicator Survey, we determined the prevalence and spatial distribution of known and candidate antimalarial drug resistance mutations. High levels of genotypic resistance were found across Zambia to pyrimethamine, with over 94% (n=266) of samples having the Pfdhfr triple mutant (N51I, C59R, and S108N), and sulfadoxine, with over 84% (n=238) having the Pfdhps double mutant (A437G and K540E). In northern Zambia, 5.3% (n=15) of samples also harbored the Pfdhps A581G mutation. Although 29 mutations were identified in Pfkelch13, these mutations were present at low frequency (<2.5%), and only three were WHO-validated artemisinin partial resistance mutations: P441L (n=1, 0.35%), V568M (n=2, 0.7%) and R622T (n=1, 0.35%). Notably, 91 (32%) of samples carried the E431K mutation in the Pfatpase6 gene, which is associated with artemisinin resistance. No specimens carried any known mutations associated with chloroquine resistance in the Pfcrt gene (codons 72-76). P. falciparum strains circulating in Zambia were highly resistant to sulfadoxine and pyrimethamine but remained susceptible to chloroquine and artemisinin. Despite this encouraging finding, early genetic signs of developing artemisinin resistance highlight the urgent need for continued vigilance and expanded routine genomic surveillance to monitor these changes.