Group mating in Cretaceous water striders.

Fossilized mating insects are irreplaceable material for comprehending the evolution of the mating behaviours and life-history traits in the deep-time record of insects as well as the potential sexual conflict. However, cases of mating pairs are particularly rare in fossil insects, especially aquatic or semi-aquatic species. Here, we report the first fossil record of a group of water striders in copulation (including three pairs and a single adult male) based on fossils from the mid-Cretaceous of northern Myanmar. The new taxon, Burmogerris gen. nov., likely represents one of the oldest cases of insects related to the marine environment, such as billabongs formed by the tides. It exhibits conspicuous dimorphism associated with sexual conflict: the male is equipped with a specialized protibial comb as a grasping apparatus, likely representing an adaptation to overcome female resistance during struggles. The paired Burmogerris show smaller males riding on the backs of the females, seemingly recording a scene of copulatory struggles between the sexes. Our discovery reveals a mating system dominated by males and sheds light on the potential sexual conflicts of Burmogerris in the Cretaceous. It indicates the mating behaviour remained stable over long-term geological time in these water-walking insects.

Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.

Cell death occurs in various circumstances, such as homeostasis, stress response, and defense, via specific pathways and mechanisms that are regulated by specific activator-induced signal transductions. Among them, Jun N-terminal kinases (JNKs) participate in various aspects, and the recent discovery of JNKs and mitochondrial protein SAB interaction in signal regulation of cell death completes our understanding of the mechanism of sustained activation of JNK (P-JNK), which leads to triggering of the machinery of cell death. This understanding will lead the investigators to discover the modulators facilitating or preventing cell death for therapeutic application in acute or chronic diseases and cancer. We discuss here the mechanism and modulators of the JNK-SAB-ROS activation loop, which is the core component of mitochondria-dependent cell death, specifically apoptosis and mitochondrial permeability transition (MPT)-driven necrosis, and which may also contribute to cell death mechanisms of ferroptosis and pyroptosis. The discussion here is based on the results and evidence discovered from liver disease models, but the JNK-SAB-ROS activation loop to sustain JNK activation is universally applicable to various disease models where mitochondria and reactive oxygen species contribute to the mechanism of disease.

Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.

Intravenous Iron Therapy: Re-administration after Prior Adverse Reaction.

BACKGROUND: Intravenous (IV) iron therapy is performed in community practices and hospitals with modern formulations when oral administration becomes impractical. Effective replacement of iron is important for the treatment of iron deficiency and anemia. Can IV iron be rechallenged in individuals with a history of adverse reactions? This review is to explore the challenge of this, when clinically indicated. METHODS: After performing a literature search, five studies (combined total sample number=1,006) for re-exposure of IV iron to individuals with a history of past reactions were identified, observed, and analyzed. Re-exposure included reactions ranging from mild to moderate and few cases of severe type. RESULTS: The majority (>80%) of IV iron rechallenges were tolerable, safe, and successful without major serious incidents. There were no reports of major reactions (severe hypersensitivity reactions or anaphylaxis) in these re-exposures. CONCLUSION: Re-administration of IV iron therapy in patients with a previous adverse reaction is plausible, with benefit and risk stratification. A rechallenge would depend on the nature and degree of the adverse reaction and use of alternative formulations. Rechallenge to a previous severe hypersensitivity reaction or anaphylaxis with the same product has not been reported in these studies. Evidence on the benefit of premedication use is conflicting and requires further studies.

A five-safes approach to a secure and scalable genomics data repository.

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a "five-safes" framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Atrial fibrillation incidence and outcomes in two cohorts of octogenarians: LiLACS NZ.

BACKGROUND: Atrial fibrillation (AF), the most common cardiac arrhythmia in the general population, has significant healthcare burden. Little is known about AF in octogenarians. OBJECTIVE: To describe the prevalence and incidence rate of AF in New Zealand (NZ) octogenarians and the risk of stroke and mortality at 5-year follow-up. DESIGN: Longitudinal Cohort Study. SETTING: Bay of Plenty and Lakes health regions of New Zealand. SUBJECTS: Eight-hundred-seventy-seven (379 indigenous Maori, 498 non-Maori) were included in the analysis. METHODS: AF, stroke/TIA events and relevant co-variates were established annually using self-report and hospital records (and ECG for AF). Cox proportional-hazards regression models were used to determine the time dependent AF risk of stroke/TIA. RESULTS: AF was present in 21% at baseline (Maori 26%, non-Maori 18%), the prevalence doubled over 5-years (Maori 50%, non-Maori 33%). 5-year AF incidence was 82.6 /1000-person years and at all times AF incidence for Maori was twice that of non-Maori. Five-year stroke/TIA prevalence was 23% (22% in Maori and 24% non- Maori), higher in those with AF than without. AF was not independently associated with 5-year new stroke/TIA; baseline systolic blood pressure was. Mortality was higher for Maori, men, those with AF and CHF and statin use was protective. In summary, AF is more prevalent in indigenous octogenarians and should have an increased focus in health care management. Further research could examine treatment in more detail to facilitate ethnic specific impact and risks and benefits of treating AF in octogenarians.

c-Jun-N Terminal Kinase-Mediated Degradation of γ-Glutamylcysteine Ligase Catalytic Subunit Inhibits GSH Recovery After Acetaminophen Treatment: Role in Sustaining JNK Activation and Liver Injury.

Aims: Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States. Liver glutathione (GSH) depletion and sustained P-JNK (c-Jun-N-terminal kinase) activation are key modulators in the mechanism leading to hepatic necrosis. GSH depletion is directly related to the consumption of GSH by APAP metabolites N-acetyl-p-benzoquinone imine (NAPQI). We previously noticed that the glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in GSH synthesis, rapidly decreased at the same time P-JNK increased. Our aims were to determine if JNK was directly responsible for decreased GCLC causing impaired recovery of GSH and if this was an important factor in determining APAP hepatotoxicity. Results: Immunoprecipitation of JNK after APAP identified binding to GCLC. Expression of a site-directed mutated canonical JNK docking site in GCLC was resistant to degradation and led to rapid restoration of GSH and inhibited sustained JNK activation. The JNK-resistant GCLC markedly protected against necrosis and alanine aminotransferase (ALT) elevation. The proteolytic loss of GCLC was abrogated by inhibition of the proteasome, ubiquitination, or calpain. Innovation: Using mutated-GCLC resistant to JNK-induced degradation, the results allowed us to identify impaired GSH recovery as an important contributor to early progression of APAP toxicity after the metabolism of APAP and initial GSH depletion had occurred. Conclusion: Activated JNK interacts directly with GCLC and leads to proteolytic degradation of GCLC. Degradation of GCLC impairs GSH recovery after APAP allowing the continued activation of JNK. Conversely, rapid recovery of GSH inhibits the sustained activation of the mitogen-activated protein (MAP) kinase cascade and dampens APAP toxicity by suppressing the continued activation of JNK. Antioxid. Redox Signal. 38, 1071-1081.

Discriminating Between Papilledema and Optic Disc Drusen Using 3D Structural Analysis of the Optic Nerve Head.

BACKGROUND AND OBJECTIVES: The distinction of papilledema from other optic nerve head (ONH) lesions mimicking papilledema, such as optic disc drusen (ODD), can be difficult in clinical practice. We aimed the following: (1) to develop a deep learning algorithm to automatically identify major structures of the ONH in 3-dimensional (3D) optical coherence tomography (OCT) scans and (2) to exploit such information to robustly differentiate among ODD, papilledema, and healthy ONHs. METHODS: This was a cross-sectional comparative study of patients from 3 sites (Singapore, Denmark, and Australia) with confirmed ODD, those with papilledema due to raised intracranial pressure, and healthy controls. Raster scans of the ONH were acquired using OCT imaging and then processed to improve deep-tissue visibility. First, a deep learning algorithm was developed to identify major ONH tissues and ODD regions. The performance of our algorithm was assessed using the Dice coefficient. Second, a classification algorithm (random forest) was designed to perform 3-class classifications (1: ODD, 2: papilledema, and 3: healthy ONHs) strictly from their drusen and prelamina swelling scores (calculated from the segmentations). To assess performance, we reported the area under the receiver operating characteristic curve for each class. RESULTS: A total of 241 patients (256 imaged ONHs, including 105 ODD, 51 papilledema, and 100 healthy ONHs) were retrospectively included in this study. Using OCT images of the ONH, our segmentation algorithm was able to isolate neural and connective tissues and ODD regions/conglomerates whenever present. This was confirmed by an averaged Dice coefficient of 0.93 ± 0.03 on the test set, corresponding to good segmentation performance. Classification was achieved with high AUCs, that is, 0.99 ± 0.001 for the detection of ODD, 0.99 ± 0.005 for the detection of papilledema, and 0.98 ± 0.01 for the detection of healthy ONHs. DISCUSSION: Our artificial intelligence approach can discriminate ODD from papilledema, strictly using a single OCT scan of the ONH. Our classification performance was very good in the studied population, with the caveat that validation in a much larger population is warranted. Our approach may have the potential to establish OCT imaging as one of the mainstays of diagnostic imaging for ONH disorders in neuro-ophthalmology, in addition to fundus photography.

Intravenous Iron Therapy: Re-administration after Prior Adverse Reaction / 가정의학회지

Background@#Intravenous (IV) iron therapy is performed in community practices and hospitals with modern formulations when oral administration becomes impractical. Effective replacement of iron is important for the treatment of iron deficiency and anemia. Can IV iron be rechallenged in individuals with a history of adverse reactions? This review is to explore the challenge of this, when clinically indicated. @*Methods@#After performing a literature search, five studies (combined total sample number=1,006) for re-exposure of IV iron to individuals with a history of past reactions were identified, observed, and analyzed. Re-exposure included reactions ranging from mild to moderate and few cases of severe type. @*Results@#The majority (>80%) of IV iron rechallenges were tolerable, safe, and successful without major serious incidents. There were no reports of major reactions (severe hypersensitivity reactions or anaphylaxis) in these re-exposures. @*Conclusion@#Re-administration of IV iron therapy in patients with a previous adverse reaction is plausible, with benefit and risk stratification. A rechallenge would depend on the nature and degree of the adverse reaction and use of alternative formulations. Rechallenge to a previous severe hypersensitivity reaction or anaphylaxis with the same product has not been reported in these studies. Evidence on the benefit of premedication use is conflicting and requires further studies.

Delivery of Radioiodine Ablation in a Patient with End-Stage Renal Disease.

This case presents a pragmatic approach to the management of a radioiodine remnant ablation patient on hemodialysis which required no pretherapeutic dosimetric measurements. Pretreatment radiation dose modeling was performed using literature values for radioiodine hemodialysis extraction efficacies to determine a safe treatment regimen including adjustment of the administered activity and hemodialysis frequency. The pretreatment modeling was subsequently verified using external and blood radiation monitoring during treatment.

Survival outcomes for patients with nasopharyngeal carcinoma in non-endemic region in the UK treated with intensity modulated based radiotherapy 65 Gy in 30 fractions ± weekly cisplatin chemotherapy.

Background: Nasopharyngeal carcinoma (NPC) is rare in the UK. The aim of the current study was to investigate survival outcomes for patients with NPC treated with (chemo)radiotherapy using 65 Gy in 30 fractions in a non-endemic region. Materials and methods: All consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis. Results: Median age was 59 years (range:19-81). The majority of patients had stage III disease (66.1%). Induction chemotherapy was given in 21% of patients and 82.3% of patients received concomitant systemic therapy. All patients were treated with 65 Gy in 30 fractions. There was disease recurrence in 17.4% patients. The 5-year disease-free, disease-specific and overall survival were 81.9%, 79.2% and 76.4%, respectively. On univariate analysis, disease recurrence was associated with N-stage (p = 0.047) and overall stage group (p = 0.023). Conclusion: To the best of authors' knowledge, this is the first report of the use of 65 Gy in 30 fractions of radiotherapy ± weekly cisplatin chemotherapy in NPC in a real-world setting. Our results are comparable to that from other non-endemic regions of the world using different dose fractionation of (chemo)radiotherapy. Future randomised control trials are warranted to compare various dose fractionations in these settings.

Dissolved trace element concentrations and fluxes in the Irrawaddy, Salween, Sittaung and Kaladan Rivers.

The Irrawaddy (Ayeyarwaddy) and Salween (Thanlwin) globally rank among the largest rivers for supplying dissolved and particulate material to the ocean. Along with the Sittaung and Kaladan rivers they have societal importance to Myanmar in terms water sources and food production. Despite their importance for global biogeochemical cycles and the ~50 million people who live in their catchments, the chemistry of these rivers is poorly known. This study presents a comprehensive survey of dissolved (<0.22 µm) trace element concentrations (Sr, Fe, Al, Ba, Mn, V, Rb, Cu, Zn, As, Li, Ni, Mo, Cr, U, Pb, Sb, Co, Cs, Tl and Cd) at 38 locations within these river catchments, spanning a period of 2 years. The results highlight the global importance of the Irrawaddy and Salween rivers for trace element global biogeochemical cycles; contributing between 1 and 17 % of global dissolved riverine fluxes to the land-ocean interface for the studied elements. Area normalized dissolved fluxes in these catchments are ~2 to 10 times higher than global average values for most elements, consistent with high rates of chemical weathering. In general, anthropogenic activities have yet to significantly perturb dissolved trace element fluxes in these river systems. The presented dataset should therefore serve as a useful 'natural' baseline, against which future perturbations driven by climate change and/or the development of Myanmar's mining industry could be assessed. Exceptions to this include As in the Sittaung River and Sb, Zn, Pb and As in the Salween River, which may already be significantly impacted by anthropogenic inputs. The former represents a water quality issue of concern for public health, and so constraining the exact sources of As in the Sittaung River should be considered a priority for future research.

Serum anion gap revisited: a verified reference interval for contemporary use.

BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. AIMS: To determine the reference interval for AG based on current laboratory techniques. METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+ ] - [Cl- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. RESULTS: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L. CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders.

Digital Gonioscopy Based on Three-dimensional Anterior-Segment OCT: An International Multicenter Study.

PURPOSE: To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. DESIGN: International, cross-sectional, multicenter study. PARTICIPANTS: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). METHODS: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. MAIN OUTCOME MEASURES: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. RESULTS: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level. CONCLUSIONS: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

Genetic Markers PLEKHA7, ABCC5, and KALRN Are Not Associated With the Progression of Primary Angle Closure Glaucoma (PACG) in Malays.

Introduction PLEKHA7, ABCC5, and KALRN have been identified as susceptible genetic markers related to glaucoma. We aimed to investigate the association between the identified susceptible genetic markers PLEKHA7 rs11024102, ABCC5 rs17217796, and KALRN rs1392912 in the progression of primary angle-closure glaucoma (PACG) in Malay patients. Methods For this study, 163 Malay patients with PACG were recruited from April 2015 to April 2017 at Hospital Universiti Sains Malaysia and Hospital Raja Perempuan Zainab II, Kota Bharu. Venesection was performed. DNA was extracted using a commercial DNA extraction kit. The primer was optimized for rs11024102, rs17217796, and rs1392912 of the PLEKHA7, ABCC5, and KALRN genes, respectively. Polymerase chain reaction (PCR) was performed, and PCR products were purified. A DNA sequencer was used to identify polymorphisms. Progression was based on the agreement between the Advanced Glaucoma Intervention Study scoring system and the Hodapp-Parrish and Anderson staging system. The scoring was conducted on two reliable consecutive Humphrey visual fields (HVFs) during the recruitment period and two baseline HVFs obtained when the diagnosis was made. Based on the scoring, patients were grouped into progressed and non-progressed. A chi-square test was used to analyze the association between the genetic markers and the progression of PACG. Results One hundred and sixty-three Malay patients with PACG (58 men and 105 women) were recruited. Twenty-nine patients (18%) had visual field progression of PACG after a mean (SD) follow-up of 6.0 (1.0) years. The minor allele frequencies for PLEKHA7 rs11024102 (G/A), ABCC5 rs17217796 (C/G), and KALRN rs1392912 (A/G) were 0.44, 0.08, and 0.48, respectively. We found that rs11024102 (p=0.828), rs17217796 (p=0.865), and rs1392912 (p=0.684) were not associated with PACG progression in the Malay patients. Conclusion Although PLEKHA7 and ABCC5 were found to be genetic markers associated with the risk of PACG, they played no roles in PACG progression in the Malay population. Moreover, KALRN was not significantly associated with PACG progression. Other susceptible genetic markers may be responsible for PACG progression.

Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12-15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.

Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality among patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: There are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This systematic review and meta-analysis aimed to study the in-hospital mortality among COVID-19 patients who were on ACEIs/ARBs as compared to those not on ACEIs/ARBs. METHODS: We searched PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEIs/ARBs and reported the in-hospital mortality outcomes of COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was the in-hospital mortality of COVID-19 patients who were on ACEIs/ARBs compared with those not on ACEIs/ARBs. RESULTS: Of the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies involving only patients with hypertension. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, no significant difference was observed in the in-hospital mortality between patients on ACEIs/ARBs and those not on ACEIs/ARBs (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.75-1.50; p = 0.73). Further sensitivity analysis in the hypertension group and the all-comers group showed similar results (OR 0.88, 95% CI 0.58-1.32; p = 0.53 and OR 1.85, 95% CI 1.00-3.43; p = 0.05, respectively). CONCLUSION: We observed that ACEIs/ARBs had no significant impact on the in-hospital mortality of COVID-19 patients and can be used safely in patients with indications.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

DeshadowGAN: A Deep Learning Approach to Remove Shadows from Optical Coherence Tomography Images.

Purpose: To remove blood vessel shadows from optical coherence tomography (OCT) images of the optic nerve head (ONH). Methods: Volume scans consisting of 97 horizontal B-scans were acquired through the center of the ONH using a commercial OCT device for both eyes of 13 subjects. A custom generative adversarial network (named DeshadowGAN) was designed and trained with 2328 B-scans in order to remove blood vessel shadows in unseen B-scans. Image quality was assessed qualitatively (for artifacts) and quantitatively using the intralayer contrast-a measure of shadow visibility ranging from 0 (shadow-free) to 1 (strong shadow). This was computed in the retinal nerve fiber layer (RNFL), the inner plexiform layer (IPL), the photoreceptor (PR) layer, and the retinal pigment epithelium (RPE) layer. The performance of DeshadowGAN was also compared with that of compensation, the standard for shadow removal. Results: DeshadowGAN decreased the intralayer contrast in all tissue layers. On average, the intralayer contrast decreased by 33.7 ± 6.81%, 28.8 ± 10.4%, 35.9 ± 13.0%, and 43.0 ± 19.5% for the RNFL, IPL, PR layer, and RPE layer, respectively, indicating successful shadow removal across all depths. Output images were also free from artifacts commonly observed with compensation. Conclusions: DeshadowGAN significantly corrected blood vessel shadows in OCT images of the ONH. Our algorithm may be considered as a preprocessing step to improve the performance of a wide range of algorithms including those currently being used for OCT segmentation, denoising, and classification. Translational Relevance: DeshadowGAN could be integrated to existing OCT devices to improve the diagnosis and prognosis of ocular pathologies.