Generation of stable heading representations in diverse visual scenes.

Many animals rely on an internal heading representation when navigating in varied environments1-10. How this representation is linked to the sensory cues that define different surroundings is unclear. In the fly brain, heading is represented by 'compass' neurons that innervate a ring-shaped structure known as the ellipsoid body3,11,12. Each compass neuron receives inputs from 'ring' neurons that are selective for particular visual features13-16; this combination provides an ideal substrate for the extraction of directional information from a visual scene. Here we combine two-photon calcium imaging and optogenetics in tethered flying flies with circuit modelling, and show how the correlated activity of compass and visual neurons drives plasticity17-22, which flexibly transforms two-dimensional visual cues into a stable heading representation. We also describe how this plasticity enables the fly to convert a partial heading representation, established from orienting within part of a novel setting, into a complete heading representation. Our results provide mechanistic insight into the memory-related computations that are essential for flexible navigation in varied surroundings.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Molecular Chaperonin HSP60: Current Understanding and Future Prospects.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.

The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.

Validation of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from UK Biobank.

BACKGROUND: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5-10% (termed as borderline-QRISK3 group) using the UK Biobank. METHODS: Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. RESULTS: Among 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30-1.52) with a 13.1% (95% CI, 11.7-14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010-0.017) in non-statin cohort, 0.013 (0.007-0.019) in stage 1 hypertension cohort, and 0.023 (0.018-0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3. CONCLUSIONS: Reti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY IN ASIAN POPULATIONS.

PURPOSE: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare degenerative disease that affects the peripheral retina. Reports of PEHCR in Asian patients are rare. Thus, the aim of this study was to investigate the clinical characteristics and outcomes of PEHCR in Asian patients. METHODS: A retrospective chart review of 33 eyes of 29 Asian patients with PEHCR. RESULTS: The mean age of the patients was 70 years, and 75.9% of them were women. Vitreous hemorrhage occurred in 51.5% of eyes during a mean follow-up of 43.1 months. The occurrence of vitreous hemorrhage was associated with a thicker baseline subfoveal choroid ( P = 0.001) and the male sex ( P = 0.005). Final visual acuity was less than 20/200 in 29.2% of eyes. The predictive factors for a final visual acuity worse than 20/200 included poor initial visual acuity ( P = 0.002), initial lesion involvement of more than 180° of the peripheral retina ( P = 0.03), an extension of subretinal hemorrhage to the macula ( P = 0.040), and absence of complete tumor regression ( P = 0.02). CONCLUSION: Asian PEHCR patients seem to be more frequently associated with vitreous hemorrhages, especially in male patients with thicker choroids. Although PEHCR was largely self-limiting, approximately one-third of the eyes ended up with a visual acuity of less than 20/200 with extensive lesion involvement.

BILATERAL MACULAR CHOROIDAL ABNORMALITIES WITH DRUSENOID DEPOSITS IN PATIENTS WITH UNILATERAL PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY.

PURPOSE: To investigate bilateral macular features on optical coherence tomography in patients with unilateral peripheral exudative hemorrhagic chorioretinopathy (PEHCR). METHODS: In this cross-sectional study, optical coherence tomography features of affected eyes (PEHCR group, n = 30) and unaffected contralateral eyes (contralateral group, n = 30) were investigated. Age-matched and sex-matched patients with polypoidal choroidal vasculopathy (PCV group, n = 51) and healthy controls (normal group, n = 50) were included to compare choroidal thickness, measured at six points apart from the fovea, with the PEHCR group. RESULTS: Subretinal drusenoid deposits were the most common feature in the PEHCR (20%) and contralateral (23%) groups, followed by soft drusen. Although the macular choroid was comparably thin in both the PEHCR and contralateral groups, pachyvessels were also observed. The choroids of the PEHCR group were significantly thinner than those of the normal group at the subfovea and 1-mm temporal to the fovea and considerably thinner than those of the polypoidal choroidal vasculopathy group from 3-mm nasal to 3-mm temporal to the fovea. CONCLUSION: In patients with unilateral PEHCR, bilateral choroidal thinning and drusenoid deposit accumulation were noted in the macula. The pathophysiology of PEHCR may be a rare peripheral complication of age-related macular degeneration with pathologic choroid.

Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury.

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1-13. Among these, TLR2-5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1-5, TLR8, and TLR10-13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.

Induction of Autophagy and Its Role in Peripheral Nerve Regeneration after Peripheral Nerve Injury.

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.

Ketone bodies (KBs), such as acetoacetate and ß-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

LiNi0.6Co0.2Mn0.2O2 Cathode-Solid Electrolyte Interfacial Behavior Characterization Using Novel Method Adopting Microcavity Electrode.

Due to the limitations of organic liquid electrolytes, current development is towards high performance all-solid-state lithium batteries (ASSLBs). For high performance ASSLBs, the most crucial is the high ion-conducting solid electrolyte (SE), with a focus on interface analysis between SE and active materials. In the current study, we successfully synthesized the high ion-conductive argyrodite-type (Li6PS5Cl) solid electrolyte, which has 4.8 mS cm-1 conductivity at room temperature. Additionally, the present study suggests the quantitative analysis of interfaces in ASSLBs. The measured initial discharge capacity of a single particle confined in a microcavity electrode was 1.05 nAh for LiNi0.6Co0.2Mn0.2O2 (NCM622)-Li6PS5Cl solid electrolyte materials. The initial cycle result shows the irreversible nature of active material due to the formation of the solid electrolyte interphase (SEI) layer on the surface of the active particle; further second and third cycles demonstrate high reversibility and good stability. Furthermore, the electrochemical kinetic parameters were calculated through the Tafel plot analysis. From the Tafel plot, it is seen that asymmetry increases gradually at high discharge currents and depths, which rise asymmetricity due to the increasing of the conduction barrier. However, the electrochemical parameters confirm the increasing conduction barrier with increased charge transfer resistance.

Ultrasonographic quantitative evaluation of acute and chronic renal disease using the renal cortical thickness to aorta ratio in dogs.

The renal cortical thickness (RCT) has been correlated with renal function. Previous studies have also reported that the RCT:Abdominal aorta(Ao) ratio is constant in normal dogs with various physical factors. This multi-center, retrospective, analytical study aimed to determine if there are differences between actual RCT and predicted value of RCT considering physical factors in dogs with acute or chronic renal disease. We also aimed to demonstrate whether the RCT and Ao ratio index would be useful for evaluating renal pathology. A total of 54 dogs with acute or chronic renal disease and 30 normal healthy dogs were included in this study. The RCT was measured at the center of the renal pyramid as the shortest distance perpendicular to the renal capsule from the base of the renal medullary pyramid at three points. The diameter of the Ao was measured just caudal to the branch of the left renal artery in the sagittal plane in systole. The RCT:Ao ratio of chronic kidney disease (CKD) patients was 0.50 ± 0.11 (mean ± standard deviation). The RCT:Ao ratio in normal dogs was 0.67 ± 0.07. The RCT:Ao ratio in patients with acute kidney injury (AKI) was 0.83 ± 0.05. There was a statistically significant difference between normal dogs and dogs with CKD (P < 0.001) and between normal dogs and dogs with AKI (P < 0.001). In conclusion, findings from the current study supported using the RCT:Ao ratio as a non-invasive quantitative method for characterizing kidney pathology in dogs with acute or chronic renal disease.

Beta-naphthoflavone and doxorubicin synergistically enhance apoptosis in human lung cancer cells by inducing doxorubicin accumulation, mitochondrial ROS generation, and JNK pathway signaling.

Doxorubicin is one of the most effective chemotherapeutic agents available for treating various cancers, including lung cancer-the leading cause of cancer death in both men and women. However, its clinical application has been impeded by severe adverse effects, notably cardiotoxicity. Development of cellular resistance to doxorubicin is another major obstacle that must be overcome for broader application of the drug. In the present study, we examined the therapeutic potential of beta-naphthoflavone (BNF), a synthetic derivative of a naturally occurring flavonoid, in combination with doxorubicin for the treatment of lung cancer. Among our novel observations were that BNF enhances the efficacy of doxorubicin by inducing doxorubicin accumulation, mitochondrial ROS generation, and JNK pathway signaling in lung cancer cells. These combined effects were also evident in many other cancer cell types. BNF further exhibited synergistic induction of apoptosis in lung cancer cells when combined with several other cancer drugs, including irinotecan, cisplatin, and 5-fluorouracil. Our results suggest that BNF can be developed as a promising adjuvant agent for enhancing the efficacy of doxorubicin.

Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.

Upcycling Plastic Waste into High Value-Added Carbonaceous Materials.

Even though plastic improved the human standard of living, handling the plastic waste represents an enormous challenge. It takes more than 100 years to decompose discarded or buried waste plastics. Microplastics are one of the causes of significantly pervasive environmental pollutants. The incineration of plastic waste generates toxic gases, underscoring the need for new approaches, in contrast to conventional strategies that are required for recycling plastic waste. Therefore, several studies have attempted to upcycle plastic waste into high value-added products. Converting plastic waste into carbonaceous materials is an excellent upcycling technique due to their diverse practical applications. This review summarizes various studies dealing with the upcycling of plastic waste into carbonaceous products. Further, this review discusses the applications of carbonaceous products synthesized from plastic waste including carbon fibers, absorbents for water purification, and electrodes for energy storage. Based on the findings, future directions for effective upcycling of plastic waste into carbonaceous materials are suggested.

Colonoscopy decreases mortality in colorectal cancer patients compared with fecal immunochemical test.

BACKGROUND AND AIM: Colonoscopy and fecal immunochemical test (FIT) are commonly used screening methods for the detection of colorectal cancer (CRC), but their effects on survival have not been compared. We compared survival outcomes in patients with CRC according to the exposure history to colonoscopy or FIT before diagnosis of CRC. METHODS: We performed a nationwide population-based retrospective cohort study using Korean national-insurance claims data. In total, 24 875 patients with CRC diagnosed in 2012 were included. The patients were divided into three groups in terms of examinations performed during the 10 years prior to CRC diagnosis: the colonoscopy group, the FIT group, and the never-screened group. Survival outcomes were compared among the three groups. The colonoscopy group and FIT group were matched using propensity score-matching method. RESULTS: The cohort consisted of 9619 patients in the colonoscopy group, 6936 patients in the FIT group, and 8320 patients in the never-screened group. The 5-year overall survival rates were 74.1% in the colonoscopy group, 65.9% in the FIT group, and 59.6% in the never-screened group (P < 0.001). The adjusted hazard ratios for death were 0.56 (95% confidence interval [CI], 0.53-0.59) in the colonoscopy group and 0.78 (95% CI, 0.74-0.82) in the FIT group compared with the never-screened group. In the matched cohort, the adjusted hazard ratios for death was 0.76 (95% CI, 0.72-0.81) in the colonoscopy group compared with the FIT group. CONCLUSION: Colonoscopy is a more effective method for reducing mortality in patients with CRC compared with FIT.

Retinal photograph-based deep learning predicts biological age, and stratifies morbidity and mortality risk.

BACKGROUND: ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). OBJECTIVE: we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. METHODS: we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). RESULTS: in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42-1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69-3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31-1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14-1.69]) and 18% (HR = 1.18 [1.10-1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). CONCLUSIONS: the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.

Clinical features, treatment factors, and long-term outcomes of optic disc pit maculopathy.

PURPOSE: To assess the clinical features, treatment factors, and long-term visual and anatomical outcomes of optic disc pit maculopathy (ODPM) in Korean patients. METHODS: Consecutive patients diagnosed between January 2000 and September 2020 were retrospectively reviewed. The primary outcome was best-corrected visual acuity (BCVA) and anatomical changes (determined by macular thickness reduction and fluid resorption). Secondary outcomes included factors associated with poor visual outcomes (> 3-line decrease or < 20/200 vision). RESULTS: Of the 24 eyes (24 patients, mean age, 42.8 years) in this study, two peak incidence groups were noted: children younger than 14 years (six patients; mean age, 9.7 years) and middle-aged adults (18 patients; 53.8 years). There were no significant differences between groups in terms of clinical features, treatment, and outcomes (P > 0.05). The primary treatment involved immediate (7 eyes) or delayed (9) vitrectomy, laser only (2), or observation only (6). Good (50%) or partial (33%) anatomical response was noted in most cases at the final follow-up (P > 0.05). However, regression analyses showed that poor visual outcomes were associated with low preoperative BCVA (OR, 8.73; 95%CI, 1.34-56.85; P = 0.023) and delayed vitrectomy (OR, 13.00; 95%CI, 1.70-99.38; P = 0.013), while presence of intraretinal fluid in the inner and outer layers reduced the risk (OR, 0.086; 95%CI, 0.01-0.88; P = 0.039). CONCLUSION: Patients with ODPM may have two peak incidence groups with similar clinical features and treatment outcomes, supporting the idea of heterogeneous mechanisms triggering fluid accumulation. Although the primary treatment choice may not impact long-term anatomical outcomes, delayed vitrectomy may be associated with poorer visual outcomes.

Clinical Characteristics of recurrent intraocular lens dislocation after scleral-fixated sutured intraocular lens and long-term outcomes of intraocular lens re-fixation.

PURPOSE: This study aimed to investigate the clinical characteristics of patients with recurrent intraocular lens (IOL) dislocation after scleral-fixated sutured IOL implantation and evaluate the long-term outcomes of scleral re-fixation of IOL. METHODS: The medical records of patients who underwent surgery for IOL dislocation between January 2011 and January 2021 were reviewed. The study included 164 patients (male: 131, female: 33) (176 eyes). Patient demographics, preoperative, intraoperative and postoperative data, and the ocular and systemic conditions associated with IOL re-dislocation were analyzed. RESULTS: The study included 176 consecutive cases of scleral-fixated sutured IOL. Twenty-six eyes (14.8%) showed re-dislocation of IOL after the initial IOL scleral fixation and underwent reoperation (mean 75.5 ± 62.5 months after the first surgery); three (11.5%) of them required a third surgery. Younger adults (aged less than 40 years), and patients who underwent IOL scleral fixation in complicated cataract surgery or aphakic state had a higher risk of re-dislocation. Diabetes mellitus (DM) was the only statistically significantly higher risk factor in the re-dislocated group (p = 0.041). The complication rate with scleral re-fixation was higher than that in the non-re-dislocated group. No statistically significant differences were observed, except for vitreous hemorrhage (p = 0.024). CONCLUSIONS: Caution should be exercised when performing sutured scleral fixation of IOL in younger patients, cases of complicated cataract surgery and aphakia, and patients with DM to prevent IOL re-dislocation. Scleral-fixated sutured IOL in eyes with recurrent IOL dislocation seems to be a safe and effective procedure with a relatively low complication rate.