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Introduction: The purpose of this study is to develop the predictive models for epidermal growth factor receptor (EGFR) mutation status and subtypes [exon 21-point mutation (L858R) and exon 19 deletion mutation (19Del)] and validate the clinical effectiveness.Methods: Total 172 patients with lung adenocarcinoma were enrolled. The analysis of variance and the least absolute shrinkage were used feature selection from plain computed tomography images. Then, radiomic score (rad-score) was calculated for the training and test cohorts. Two machine learning (ML) models with 5-fold were applied to construct the predictive models with rad-score and clinical features and evaluated by the area under the curve (AUC) of receiver operating characteristic curve. The nomogram was developed using rad-score and clinical features, then evaluated by the C-index. Finally, decision curve analysis (DCA) was performed using the best ML and nomogram models.Results: The AUC of the best ML models and the C-index of the nomogram models were 0.82, 0.73 and 0.84, 0.78 in the EGFR mutation groups, 0.83, 0.83 and 0.83, 0.80 in the L858R mutation groups, and 0.84, 0.77 and 0.85, 0.69 in the 19Del groups, respectively in the training and test cohorts. DCA showed that nomogram models have more benefits than ML models.Conclusion: We constructed two predictive models for EGFR mutation status and subtypes. The nomogram models had more clinical usefulness than ML models.

In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from the Vax1AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.

Purpose To evaluate the association between OCT-angiography (OCTA) and photopic negative response (PhNR) in open angle glaucoma (OAG) patients and assess the diagnostic accuracy of these parameters in early detection of glaucoma. Methods A total of 152 eyes were enrolled in this study, 28 eyes with mild POAG (group I), 44 eyes with moderate-severe POAG (group 2) & 80 eyes of healthy subjects (control group). Full ophthalmological examination, OCTA and PhNR measurements were underwent for all participants. RNFL, GCC thicknesses, PhNR (implicit time and amplitude) were recorded. The superficial and deep capillary plexus vessel density (SCP-VD%, DCP-VD%) were measured by using 6 × 6 mm macula OCTA scans. The peripapillary vessel density (RPC-VD %) were measured by using 4.5 × 4.5 mm optic disk head OCTA scans. Results There were reduction of the median Interquartile range (IQR) thickness of the GCC and RNFL in OAG eyes versus normal (P Conclusions OCTA vascular parameters displayed significant positive correlation with PhNR amplitude and significant negative correlation with PhNR implicit time. OCTA and PhNR parameters showed a high diagnostic accuracy for detection of glaucoma, and both may provide promising insight in early detection of glaucoma. This study was retrospectively registered on ClinicalTrials.gov (identifier, NCT05104294).

Purpose This study was conducted to explore doctors’ perceptions and understanding of the self-medication practices of people living with type 2 diabetes. Methods A qualitative research design incorporating 20 semi-structured, face-to-face interviews were conducted with doctors treating people with type 2 diabetes in Mysuru, India, between July 2019 and January 2020. All the interviews were conducted in doctors’ clinics, audio-recorded and thematically analyzed. Results Three themes were identified from these interviews- i) Doctors’ beliefs towards their patients’ use of traditional medicine and environmental factors influencing prescription practices, ii) Doctors reported little faith in traditional medicines, iii) Limited strategies implemented by doctors to overcome barriers to self-medications. Doctors reported greater belief in western medications over traditional medications and expressed concern that their patients favored traditional medications over western. Multiple factors such as social media, accessibility of healthcare facilities and pill burden influenced adherence to western medications. Also, lack of knowledge about traditional medications and trust in western medications available under government schemes have influenced prescription practices among doctors. It appears that doctors implemented strategies such as educating patients on the detrimental effects of self-medication and insisting on patients to take only western medications to achieve desired blood glucose levels when managing self-medication practices among people with diabetes. Conclusion These results suggest that doctors have limited strategies to implement to prevent self-medication practices among people with diabetes. Increasing knowledge amongst doctors about JAS medication effectiveness and thereby garnering greater trust in generic medications. In addition, efforts should be made to identify the best ways to integrate traditional and western medicine into patient-centered care delivery.

Background: Landmark artery identification in the neurovascular bundle (NVB) is important for nerve-sparing in radical prostatectomy. We aimed to investigate intraoperative angiography using indocyanine green and near-infrared fluorescence (ICG-NIRF) during robot-assisted radical prostatectomy (RARP) to identify the NVB, visualise vascularisation and haemostasis, and preserve erectile function.Methods: Retrospective, unicentric study of 91 consecutive localised prostate cancer RARP patients (stage T1/T2, prostate specific antigen Results: Ninety-one patients received intraoperative angiography. The NVB was identified in all cases, without difficulties. No ICG-related complications or allergies were observed. There was no significant difference in the SHIM score at 9 months compared with baseline (p=0.331), and erectile dysfunction returned to baseline levels in almost all patients.Conclusions: Intraoperative, real-time ICG-NIRF angiography is simple, non-invasive, and improves identification of key anatomical landmarks to optimise micropreservation of the NVB during RARP and preserve erectile function. Larger clinical studies should confirm preliminary results.

The aim of this study was to evaluate the vision-related quality of life (VR-QOL) before and after intravitreal ranibizumab injections (IVR) for central retinal vein occlusion (CRVO) and investigate subscale items of VR-QOL in detail. This multicenter, open-label, prospective study included 23 patients with treatment naïve CRVO and 22 age-matched normal controls. VR-QOL was assessed by the 25-Item Visual Function Questionnaire (VFQ-25) before and up to 12 months post-treatment. The VFQ-25 composite score and 12 subscales were compared between groups. The VFQ-25 composite scores in CRVO showed significant improvement throughout the treatment period compared with those at the baseline. The VFQ-25 composite score before and after treatment in CRVO was significantly lower than that in normal controls. The subscale items, including general health, general vision, near activities, social functioning, mental health, role difficulties, dependency, and peripheral vision, in CRVO were significantly lower than those in the normal controls even after treatment. Vision-related QOL was low in patients with CRVO before treatment and improved with IVR. Even after treatment, the values of several subscale items were lower than those in normal controls. Patients with CRVO require treatment aimed at further improving visual function as well as social and psychological care.

BackgroundWe aimed to investigate corneal densitometry and correlations with corneal morphological parameters in bilateral keratoconus (KCN) patients with unilateral Vogt's striae.MethodsOne hundred and-twelve patients (224 eyes) with bilateral KCN and unilateral Vogt's striae were enrolled in this cross-sectional contralateral eye study. Corneal densitometry and morphological parameters were measured using Pentacam HR.ResultsOur study revealed that corneal densitometry values of the anterior 0–2 mm and 2–6 mm, intermediate 0–2 mm and 2–6 mm, posterior 2–6 mm, and total cornea 2–6 mm in eyes with Vogt’s striae were significantly higher than those in eyes without Vogt's striae (P P P P P

Positively imagined activities may capture visual attention due to an increase in positive value. Increasing attention toward activities, in turn, may prove useful for clinical interventions aiming to motivate behavioral engagement. Employing a within-subject experimental design, we examined the effect of positive imagery on attention using a visual probe task with concurrent eye tracking. Adults from the general population (N = 54) imagined performing activities involving visually presented objects in a positive (focusing on the positive emotional impact) or neutral (focusing on a neutral circumstance) manner. They then completed a visual probe task using picture stimuli depicting one object per type of imagery. Positive compared to neutral imagery increased self-reported behavioral motivation and biased the direction, but not the duration, of gaze toward objects associated with the imagined activities. An exploratory analysis showed a positive association between the direction bias and depressive symptoms. Our findings build on existing literature on positive imagery as a motivational amplifier by highlighting early attention as an underlying cognitive mechanism.

Purpose: To establish and verify a nomogram based on computed tomography (CT) radiomics analysis to predict the histological types of gastric cancer preoperatively for patients with surgical indications.Methods: A sum of 143 patients with gastric cancer in Sir Run Run Shaw Hospital from January 2019 to December 2020 (differentiated type: 46 cases; undifferentiated type: 97 cases) were included into this retrospective study, and were randomly divided into training (n=99) and test cohort (n=44). The least absolute shrinkage and selection operator(LASSO) was used for feature selection while the multivariate Logistic regression method was used for radiomics model and nomogram building. The area under curve(AUC) was used for performance evaluation in this study.Results: The radiomics model got AUCs of 0.755 (95%CI, 0.650-0.859) and 0.71 (95%CI,0.543-0.875) for histological prediction in the training and test cohorts, respectively. The radiomics nomogram based on radiomics features and Carbohydrate antigen 125 (CA125) achieved an AUC of 0.777 (95%CI:0.679-0.875) in the training cohort with 0.726 (95%CI:0.559-0.893) in the test cohort. The calibration curve of the radiomics nomogram also showed good results. The decision curve analysis(DCA) shows that the radiomics nomogram is clinically practical.Conclusion: The radiomics nomogram established and verified in this study showed good performance for the preoperative histological prediction of gastric cancer, which might contribute to the formulation of a better clinical treatment plan.

Background: to demonstrate the safety and efficacy of the intracameral use of tropicamide 0.02%/phenylephrine 0.31%/lidocaine 1% in pediatric cataract surgery, a combination widely used in adult patients but still off-label in childrenMethods: Design: two-center, prospective, observational studySetting: San Giuseppe Hospital, Milan and Meyer Children's Hospital, FlorenceStudy population: children from 0 to 4 years of age undergoing cataract surgery with or without intraocular IOL implantation, in the absence of clinically significant systemic conditions, history of ocular surgery, concurrent ocular medication, hypersensitivity to any of the substances and post-traumatic cataracts. During the surgery, patients received the combination drug after the primary access to the anterior chamber. Efficacy was evaluated by achieving an adequate mydriasis in order to perform capsulorhexis, while safety was assessed by recording vital signs (heart rate, blood pressure, respiratory rate, temperature) pre and post administration of the substance.Results: this study included 53 surgical procedures of 36 patients: 41 eyes were left aphakic while 12 eyes received primary IOL implantation. The pupil size was adequate to safely perform capsulorhexis in 52 procedures of 53. The difference in pupil enlargement was significant (6.0 ± 1.14mm, P = < 0.001). There were no notable changes in vital parameters. Conclusions: the administration of intracameral tropicamide 0.02%/phenylephrine 0.31%/lidocaine 1% in pediatric cataract surgery is effective for obtaining an adequate mydriasis without any vital parameters changes throughout the procedure.

Purpose To assess the early clinical outcomes of central hole phakic posterior chamber intraocular lens(ICL V4c) implantation for correction low and moderate myopia, and to explore the relationship among arch height, intraocular pressure(IOP), and central anterior chamber depth(ACD). Methods This retrospective clinical study included 27 patients (47 eyes)which underwent implantation of ICL V4c for correction of myopia with spherical equivalent between -1.75 D and -6.0 D, From January 2017 to December 2018. Preoperative corrected distance visual acuity (CDVA), postoperative uncorrected visual acuity (UCVA), and IOP were evaluated at one day, one week, three mouths, six mouths, and twelve months. ACD, arch height, and endothelial cell density (ECD) were evaluated at one, three and twelve months. Results At 1 year follow-up, the UCVA of 75% eyes are larger than the preoperative CDVA, and that of 25% eyes are equal to the preoperative CDVA. The postoperative UCVA of the patients was higher than the preoperative BCVA and showed a stable trend. There was no significant difference in ECD (P > 0.05). One month after surgery, the arch height was (0.77 ±0.32) mm, and decreased to (0.63 ± 0.26) mm at the one-year after surgery. ACD was (3.24±0.25) mm in the preoperative, decreased significantly to (2.05±0.39) mm at one month, and rose to (2.2± 0.39) mm at one year after surgery. There was no significant correlation between IOP and ACD and arch height at 1 month and 1 year after operation. The correlation coefficient between ACD and arch height was -0.72 at 1 month after surgery, and it was -0.71 at 1 year. One patient had visual fatigue, one patient had glare, and none of subjects developed cataract, glaucoma and decompensation of corneal endothelium. Conclusion ICL implantation is a safe, effective and stable method for the correction of low and moderate myopia, and it may be a good alternative for patients with low and moderate myopia who cannot undergo corneal refractive surgery.

Background: In Egypt, both pregabalin and tramadol misuse increased in the last decade. Although many studies have confirmed the neurotoxic effects of tramadol, those of pregabalin are understudied. Aim of the study: evaluation of the neurotoxic effects of pregabalin compared with tramadol.Material and method: Thirty male albino rats were included in this experimental study, and they were randomly allocated into three equal groups; Group I (normal saline), Group II (Tramadol addicted), and Group III (pregabalin addicted). All rats received the commenced drugs for 1 month. Open-field tests were performed on the day of scarification, and after that, cortical samples were taken for immunohistochemical analysis and quantification of dopamine receptors' gene expression.Results: The addicted groups showed a significant decrease in weight gain at the end of the study. Open-field testing showed the upper hand of controls regarding all of the tested parameters. Tramadol has a more negative impact on the locomotor parameters compared with pregabalin. Both drugs induced relatively low dopamine-1 receptors (D1Rs) expression to dopamine-2 receptors (D2Rs), mimicking the schizophrenia model.Conclusion: Both tramadol and pregabalin were associated with neurotoxic effects in male albino rats. These effects were less noticed with pregabalin. It is suggested that long-term abuse may end in psychosis.

Purpose We investigated the treatment outcomes of patients with acute Vogt–Koyanagi–Harada (VKH) disease and assessed the differences between patients with no inflammation worsening and those with persistent or worsening inflammation. Potential factors responsible for eyes with low visual outcomes were also investigated.Methods We retrospectively reviewed the clinical records of patients with acute VKH disease who first visited us between 2009 and 2018 and were followed up for >300 days. Clinical characteristics, treatments, and posttreatment conditions were assessed. Patients were classified into no inflammation worsening (acute–resolved [AR]) and inflammation worsening (chronic–recurrent [CR]) groups based on conditions after 6 months from disease onset.Results This study assessed 62 eyes from 31 patients (mean age: 52.8 years). One patient was treated with topical treatment alone and showed poor visual outcomes. In total, 30 patients were treated with methylprednisolone pulse followed by the slow tapering of oral prednisolone; 73% of them developed AR and 27% CR. Although the total prednisolone dose was higher in patients with CR disease, no significant difference was noted in the final best-corrected visual acuity (BCVA). Among the patients receiving systemic steroid, five eyes had a final BCVA of ≤0.5 due to anisometropic amblyopia, diabetic maculopathy, pre-existing macular hole, epiretinal membrane, and ellipsoid zone loss. Conclusions Patients with acute VKH disease treated with corticosteroid pulse followed by the slow tapering of prednisolone appear to demonstrate good visual outcomes, including patients with CR; most eyes with low visual outcomes have pre-existing conditions that explain low vision.

PURPOSE: Pseudophakic cystoid macular edema (CME) occurs in up to 2% of uneventful cataract surgeries. This study evaluates changes in macular blood flow succeeding uneventful phacoemulsification cataract extraction among otherwise visually healthy subjects.METHODS: This prospective study included 18 eyes of 18 patients undergoing routine phacoemulsification. Optical coherence tomography angiography (OCT-A) was performed using the Angio-Retina 6x6mm protocol with the XR Avanti Angio-Vue system (Optovue Inc., Fremont, California) prior to the surgery and 4-8 weeks thereafter. Exclusion criteria included motion artifacts, segmentation errors and signal strength index (SSI) ˂40. The main outcome measure was change in flow index (FI) measured in all 4 retinal segmentation layers within an area of 1mm diameter around the foveal center.RESULTS: Following surgery, a significant increase in SSI (46.65±8.62 versus 53.12±8.07, p=0.01), superficial plexus FI (0.98±0.23 versus 1.16±0.16, p=0.02) and deep plexus FI (0.54±0.46 versus 0.93±0.39, p=0.01) was found. No significant changes were noted in the outer retina or the choriocapillaris. CONCLUSION: The study demonstrates a significant increase in FI in the superficial and deep retinal plexus following uneventful cataract surgery, with the greatest changes occurring in the latter. These findings corroborate evidence from structural imaging and support the vascular etiology of pseudophakic CME.

Purpose: To evaluate the effects of Duloxetine on anterior segment parameters and intraocular pressure(IOP) in open angle eyes.Methods: 38 eyes of 38 patients with fibromyalgia who had open or wide open angles according to the Shaffer classification. Anterior segment optic coherence tomography was performed before and after (month 3) Duloxetine treatment. IOP, central corneal thickness(CCT), corneal endothelial cell density(CECD) and anterior chamber depth(ACD) were also recorded and evaluated. Results: No statistically significant difference was determined in IOP, CCT and CECD(p > 0.05). However, a statistically significant increase was determined in both the temporal and nasal anterior chamber angle, angle opening distance, nasal trabecular-iris space area and ACD values between the baseline and month 3 (p < 0.001). Conclusion: We think that the short term use of Duloxetine does not lead to clinically significant changes despite their statistically significant effects on the anterior chamber parameters.

Purpose: The aim of this study was to describe the anatomical outcomes of Brilliant Blue G (BBG)–assisted extensive internal limiting membrane peeling (eILMp) for proliferative vitreoretinopathy (PVR) under three-dimensional (3D) visualization. Methods: This study constitutes a retrospective case series conducted in a private retina practice, of 14 consecutive patients (14 eyes) with rhegmatogenous retinal detachment (RRD) complicated by PVR who underwent pars plana vitrectomy between January 2019 and January 2020. The internal limiting membrane (ILM) was selectively stained with BBG, and perspectives were enhanced with a 3D visualization system. We peeled off the ILM beyond the vascular arcades up to the periphery. The main outcome was anatomical success, defined as persistent retinal reattachment after removal of the silicone oil tamponade.Results: Anatomic success was achieved with a single surgery in 11 of 14 (78.6%) eyes, and eventual success was achieved in all eyes. The mean patient follow-up time was 12.3 months (range, 7–16 months). The mean preoperative logMAR BCVA was 2.09 (range, 2.8–1.3), which decreased to 1.54 (range, 2.8–0.6) at the last follow-up. Conclusion: This technique allowed the creation of a cleavage plane underlying the PVR membranes that facilitated its complete ILM removal, thereby reducing the risk of recurrence of retinal detachment.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Background Recently, radiomics has been widely used in colorectal cancer, but many variable factors affect the repeatability of radiomics research. This review aims to analyze the repeatability of radiomics studies in colorectal cancer and to evaluate the current status of radiomics in the field of colorectal cancer. Methods The included studies in this review by searching from the PubMed and Embase databases. Then each study in our review was evaluated using the Radiomics Quality Score (RQS). We analyzed the factors that may affect the repeatability in the radiomics workflow and discussed the repeatability of the included studies. Results A total of 188 studies was included in this review, of which only two (2/188, 1.06%) studies controlled the influence of individual factors. In addition, the median score of RQS was 11 (out of 36), range-1 to 27. Conclusions The RQS score was moderately low, and most studies did not consider the repeatability of radiomics features, especially in terms of Intra-individual, scanners, and scanning parameters. To improve the generalization of the radiomics model, it is necessary to further control the variable factors of repeatability.

Background We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. Methods A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. Results Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p Conclusions In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

Purpose Selective IgA deficiency (IgAD) is the most common primary immunodeficiency and may be associated with autoimmune diseases such as celiac disease (CeD). Although IgAD is thought to precede CeD and autoimmunity, the association between the two conditions has not been clarified. Methods Routine techniques were used to measure serum IgA and TG2-IgA and for immunohistochemistry. Results We report two childhood cases of IgA deficiency that evolved after the diagnosis of CeD and the start of a gluten-free diet. Histology showed persistence of IgA in the intestinal mucosa. Conclusion Both children with CeD showed IgA deficiency that developed after the initiation of a gluten-free diet. This supports IgA deficiency as being an autoimmune process that develops gradually and occurs due to specific defects in immunoregulation.

Purpose: The purpose of this study is to understand the cognition and experience of oncology nurses in China when responding to a patient’s request to hasten death, to describe the obstacles that prevent their response, and to provide suggestions for dealing with the patient’s request. Methods: Researchers conducted a qualitative study that consisted of open-ended, semi-structured interviews with 18 registered nurses who had more than five years of working experience in the oncology department at a large-scale urban hospital. We analyzed these data for content and themes.Results: How to deal with patients’ requests to hasten death is a problem often encountered and handled by nurses in the Department of Oncology.Nurses have a certain understanding of the patients’ requests to hasten death. This study abstracts four themes: 1) the nurses’ cognition of the “Accelerate the process of death” ; 2) the methods they use to deal with the patients’ requests to hasten death; 3) the obstacles that prevent nurses from fulfilling the patients’ requests to hasten death; and 4) their suggestions for improvement.Conclusion: Nurses have a deep understanding of the real thoughts of patients who make a death request, and they hope to provide the corresponding psychological support and physical care. However, the lack of relevant knowledge, policy support, and cooperation of patients’ families are obstacles that prevent them from taking action. Therefore, increasing relevant training for nurses, encouraging multi-department cooperation, and developing standardized nursing processes may lay a foundation for oncology nurses to better undertake and guide such conversations.

Purpose To predict the change of retinal sensitivity using optical coherence tomography (OCT) parameters in eyes with central serous chorioretinopathy (CSC). Methods Twenty-three eyes of 23 patients with CSC were enrolled. Retinal sensitivity was measured twice with a microperimetry in all examined eyes. OCT measurement was simultaneously conducted. The relationship between retinal sensitivities and the thicknesses of i) retinal nerve fiver layer + ganglion cell layer (RNFL+GCL), ii) inner nuclear layer (INL) iii) outer nuclear layer (ONL) and iV) serous retinal detachment height (SRDH) were investigated in a point-wise manner. We also investigated the association between the change of retinal sensitivity and OCT parameters at baseline. Results The mean age of participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p

Purpose To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination. Methods In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging. Results Fifteen eyes of VO (14 patients) after COVID-19 vaccinations were identified. The median time between vaccination and symptoms onset was 14 days (range 7–42 days). The mean best-corrected visual acuity (BCVA) was 20/55 with a range of 20/20 to 20/200. Eleven of 15 eyes (73.3%) had visual acuity improvement after intravitreal treatment at 60–90 days (range, 45–105 days) from the presentation. Four of 5 cases without systemic risk factors for VO had a mean BCVA > 20/32 at presentation and > 20/25 at the latest evaluation. Between May 1 and October 31, 2021, a temporal association was found between the 15 reported cases and COVID-19 vaccination out of a total of 29 VO (p = 0.05). The incidence of VO was higher in the considered period compared to the equivalent 6-month period in 2019 (1.17% vs 0.52%, respectively; p = 0.0134). Conclusions Retinal vascular occlusion with different grades of severity are reported in temporal association with COVID-19 vaccination. The exact pathogenic mechanism needs to be further studied. No certain causal relationship can be established from this case series.

Maintaining object correspondence among multiple moving objects is an essential task of the perceptual system in many everyday life activities. A substantial body of research has confirmed that observers are able to track multiple target objects amongst identical distractors based only on their spatiotemporal information. However, naturalistic tasks typically involve the integration of information from more than one modality, and there is limited research investigating whether auditory and audio-visual cues improve tracking. In two experiments, we asked participants to track either five target objects or three versus five target objects amongst similarly indistinguishable distractor objects for 14 s. During the tracking interval, the target objects bounced occasionally against the boundary of a centralised orange circle. A visual cue, an auditory cue, neither or both coincided with these collisions. Following the motion interval, the participants were asked to indicate all target objects. Across both experiments and both set sizes, our results indicated that visual and auditory cues increased tracking accuracy although visual cues were more effective than auditory cues. Audio-visual cues, however, did not increase tracking performance beyond the level of purely visual cues for both high and low load conditions. We discuss the theoretical implications of our findings for multiple object tracking as well as for the principles of multisensory integration.

The inability to meet the desired outcomes of anticancer treatment and decrease in treatment success of bacterial and fungal infections accelerated research in these areas. Our research group has conducted numerous studies, especially on benzimidazole ring systems' antiproliferative and antimicrobial activities. In this study, the antiproliferative activity of benzimidazole compounds was tested against A549, A498, HeLa, A375, and HepG2 cancer cell lines by MTT assay. All compounds exhibited good to potent antiproliferative activity against all tested cancer cell lines. Compounds 6-chloro-2-(4-fluorobenzyl)-1H-benzo[d] imidazole (30) and 6-chloro-2-phenethyl-1H-benzo[d]imidazole (46) were especially active against HeLa and A375 cancer cell lines with IC50 values in the range of 0.02-0.04 mu M. In contrast, compounds 6-chloro-2-((p-tolyloxy)methyl)-1H-benzo[d] imidazole (67) and 5(6)-chloro-2-((4-hydroxyphenoxy)methyl)-1H-benzimidazole (68) were active against A549 and A498 cancer cell lines with an IC50 value of 0.08 mu M. These compounds (30, 46, 67, and 68) were less toxic to normal human cells than the positive control compound methotrexate, which was screened to determine its toxicity against normal cell lines (HEK293). In the second part of the study, all compounds were tested to demonstrate their antimicrobial properties. All compounds exhibited moderate activity against all tested bacteria and fungi. However, some phenoxy methyl derivatives 5-chloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d]imidazole (69) and 5,6-dichloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d] imidazole and (74) were most active against Candida (

Concomitant vitamin D deficiency (VDD) is speculated to aggravate diabetic macular edema (DME). We aimed to determine the effect of hypovitaminosis D correction on the outcome of treatment with intravitreal bevacizumab (IVB) in DME eyes.In this randomized clinical trial, 83 eyes of 83 patients with DME were recruited and divided into three groups: normal vitamin D levels + IVB administration (Group 1), vitamin D insufficient/deficient + IVB administration (Group 2), and vitamin D insufficient/deficient + IVB administration + oral vitamin D supplementation (Group 3). Participants were followed for 6 months after the intervention. Visual (corrected distance visual acuity, CDVA) and anatomical (central macular thickness, CMT) outcomes of intervention were evaluated 1, 3, and 6 months after three monthly loading doses of IVB were given. Serum vitamin D levels were measured 1 and 6 months after the third IVB administration.A total of 29, 26, and 28 eyes were enrolled in groups 1, 2, and 3, respectively. In months 1, 3, and 6, after the three basic loading doses of IVB, visual acuity and CMT improved in all three groups, but improvements (both functional and anatomical) in groups 1 and 3 in month 6 were more significant than in group 2 (mean CDVA LogMAR changes: - 0.18 ± 0.03, - 0.14 ± 0.05, and - 0.2 ± 0.06; mean CMT reductions: - 82.24 ± 11.43, - 66.62 ± 14.34, and - 86.14 ± 18.36, in groups 1, 2, and 3, respectively; p 0.001). The mean number of IVB injections during follow-up was 5.33 (range 4-7), which did not differ between the groups.Correction of vitamin D deficiency in DME patients with type 2 diabetes and vitamin D deficiency, in addition to IVB injections, may play a role in improving CDVA and CMT. However, this beneficial effect seems to be delayed by several months.Iranian Registry of Clinical Trials (IRCT), IRCT20200407046978N1, registered on April 11, 2020, retrospectively registered ( https://en.irct.ir/trial/46999 ).

Purpose: The aim of this study was to investigate the prevalance of congenital optic disc (OD) anomalies in Turkey. Methods: The 11149 eyes of 5583 patients were screened for OD anomalies. All patients were underwent a complete ophthalmic examination including best corrected visual acuity, refraction, spherical equivalent, slit lamp biomicroscopy, intraocular pressure measurements, dilated stereoscopic fundus examination. Data analyses were performed by using SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL, United States).Results: 11149 eyes of 5583 participants were screened. Of the 5583 participants who underwent OD examination, 186 (3,3%) were found to be abnormal. 266 of 11149 (2,38%) eyes were found OD anomalies. 98 (52,7%) were female, 88 (47,3%) were male and the mean of age was 44,05±15,73 years. The prevalence of all congenital OD anomalies was found 3,3%. The tilted disc was the most common anomaly and was found at least one eye in 46 patients (75 eyes) and 0.82% of all screened patients. Peripapillary myelinated nerve fibres was the second common anomaly and was found at least one eye in 29 subjects (35 eyes) and 0,51% of all screened subjects. Peripapillary atrophy was the third common anormality, and was found in at least one eye in 24 patients (37 eyes) and 0,42% of all screened subjects.Conclusion: To our knowledge, this is the first study that the prevalences of all congenital optic disc anomalies from Turkey. The prevalence of congenital optic disc anomalies is higher than in other countries.

Background: To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families.Methods: In our study, we screened 425 potential eye disease-related genes of the proband of a three-generation Chinese family diagnosed with microphthalmos using next-generation sequencing-based target capture sequencing. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation.Results: We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, PXDN c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and CRYBB2 c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation.Conclusions: The three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early presymptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

As prodrugs series of new sartan-derived molecules were designed, synthesized, and evaluated. Most of the synthesized compounds could decrease blood pressure efficiently in spontaneously hypertensive rats. It could be ratiocinated that the original drugs could be released from the prodrugs exactly at the connecting position catalyzed by the hydrolyzation enzymes. The maximal response of mean blood pressure (MBP) lowered 70.2 ± 5.0 mmHg (compound 1) and 61.2 ± 1.0 mmHg (compound 4) at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan and were similar with Telmisartan. Pharmacokinetics test results of 1 were consistent with its anti-hypertension effects in vivo. The safety of new compounds was confirmed by the influence on the rats’ heart rates and other symptoms which couldn’t been observed during whole process. Thence, compounds 1 and 4 may be considered as potential antihypertension drug candidates.

Purpose: To determine the status of sub-specialization among Nigerian ophthalmologists as well as their dispositions and barriers against sub-specialization with a view to providing valuable information for the purpose of human resources for eye care planning thereby providing useful insight into the future of ophthalmic practice in Nigeria. Methods: This was a web-based, cross-sectional study conducted among Ophthalmologists in Nigeria. An online questionnaire was distributed through e-mails using Qualtrics software (Qualtrics, Provo, UT, USA). Information concerning socio-demographic characteristics, type of practice, location of practice, years of practice, status and disposition to sub-specialization as well as barriers to sub-specialization were obtained through the questionnaire.Results: two hundred and four Nigerian Ophthalmologists participated in the study out of which 118 (57.8%) were females. One hundred and ten (54.0%) respondents had undergone sub-specialty training. The sub-specialties with the highest number of patronage was Paediatric Ophthalmology and Strabismus (14.2%). Respondents older than 46 years were three times more likely to have undergone subspecialty training compared to respondents who were aged 46 years and below [odds ratio (OR) = 3.01, 95% Confidence interval (CI) = 1.33 – 6.83, p = 0.01]. The main barriers to the availability and uptake of sub-specialty services as well as the challenges of sub-specialty services at the centres with established sub-specialty practice were non-availability/inadequate trained specialist and inadequate equipment. Conclusion: Nigerian Ophthalmologists are well disposed to sub-specialization although the extent of sub-specialization among them was a little above average. The main barriers to the availability and uptake of sub-specialty services as well as the challenges of sub-specialty services at the centres with established sub-specialty practice in this study were non-availability/inadequate trained specialist and inadequate equipment.

Purpose:Ultra-thin strut polymer-free sirolimus eluting stent (UPF-SES) have two novel characteristics, ultra-thin strut and polymer-free coating, which have the potential to achieve early re-endotherialization. However, a little is known whether early vascular healing of UPF-SES can be achieved in patients with acute coronary syndrome (ACS).The aim of this study was to evaluate the vascular healing after an implantation of UPF-SES in patients with ACS using optical coherence tomography (OCT) at 3 months after the stent implantation. Methods:From September 2020 and January 2021, a total of 31 consecutive patients presenting with ACS who underwent OCT examinations at the initial percutaneous coronary intervention (PCI) and 3-month follow-up were enrolled in the USUI-ACS study. The endpoints of this study were neointimal strut coverage, malapposition, and mean neointimal hyperplasia (NIH) thickness at 3-month follow-up.Results:Over a mean follow-up of 91 days after the initial PCI, the follow-up OCT was examined. The median percentage of covered struts was 98.4% and malapposed struts 0%, and the mean NIH thickness was 60μm.Conclusions:UPF-SES exhibited an excellent early vascular healing at 3-months in patients with ACS.

Purpose To verify the correct decision-making procedure on performing an intravitreal injection by investigating the in vivo wound morphology and evolution of 22-gauge wounds after dexamethasone oblique injection with anterior segment optical coherence tomography (OCT). Design Prospective, observational consecutive case series. Methods Subjects underwent a dexamethasone injection at University Eye Clinic of Turin. All the injections have been performed in an oblique (aka beveled or angled) fashion. Patients were divided according to the number of injections already performed with dexamethasone. Group 1 consisted of patients at the first injection, group 2 of patients at a second or more injection always in the same quadrant, and group 3 of patients at the second or more injection in a different quadrant. The incisions were imaged with the Heidelberg SPECTRALIS OCT device on postoperative days 1, 8, and 15. The main outcome measure was wound structure/characteristics (e.g., presence of gaping) as evaluated with OCT. Surgical and ocular parameters were also recorded. Results Thirty-three consecutive patients were investigated. OCT demonstrated closed wounds in all eyes on postoperative days 1, 8, and 15. In all patients, the external (entry) side of the incision was seen as a gape; however, the rest of the wound was closed. No complications were recorded in the different patients during the follow-up. In patients of group 1, we identified the scleral pathway in 10 eyes at day 1. At 8 days in 9 of 10 eyes, the sclera had returned to its restitutio ad integrum. In patients of group 2, the scleral pathway was recognizable on the first day of control; in 7 patients, this was accompanied by the presence of intrascleral edema with peri-wound fluid. At the 8-day checkup, 3 eyes still showed signs attributable to the intrascleral pathway accompanied by peri-wound edema. In group 3, it was possible to identify the intrascleral pathway in 8 patients. There were no signs of intrascleral peri-wound edema or other anatomical changes in 9 patients as early as the first day. In the 8-day follow-up, the signs of scleral edema were absent in the single patient who presented them. At 15 days, there were no signs of scleral pathway in all eyes analyzed. Conclusions Speaking of intravitreal injections of slow-release dexamethasone, the technique that involves moving the conjunctiva and a beveled or angled sclerotomy after a careful choice of the injection site, paying attention to vary the quadrant involved with each puncture, reduces the number of days of closure of the sclera via and the scleral damage, thus protecting the patient from complications. For the future, it is hoped that the operating microscope and intraoperative OCT will be used on every occasion.

PurposeMyopic glaucoma patients display a considerable risk of complications following antiglaucomatous filtering surgery, e.g., trabeculectomy. Canaloplasty with mitomycin C may reduce this risk by avoiding massive overfiltration.MethodsWe performed retrospective analysis of 31 eyes with myopia that underwent canaloplasty modified with mitomycin C in a consecutive single-surgeon case series. Annual data and success rates were analysed. Twenty-three myopic eyes that had received conventional trabeculectomy with mitomycin C were recorded as a comparison.ResultsThe 31 eyes with a follow-up of 40 ± 26 months after canaloplasty had a mean spherical equivalent of − 8.4 ± 4.5 dioptres. Intraocular pressure decreased from 32.3 ± 9.6 mmHg (range: 17 to 58) to 16.8 ± 8.1 mmHg (range: 5 to 44) 1 year after surgery (− 46%;p p 20%) were 83% after 1 year and 61% at the 2nd and 3rd years. In 5 eyes (16%), early ocular hypotony (≤ 5 mmHg) was observed. Two eyes (7%) showed transient choroidal detachment and swelling. The 23 eyes that had received trabeculectomy had success rates (Criterion B) of 91% at the 1st and 86% at the 2nd and 3rd years. Hypotony occurred in 10 eyes (44%), and 4 eyes (17%) showed choroidal detachment or macular folds.ConclusionsPostoperative complications related to overfiltration were less frequent after canaloplasty with mitomycin C. Midterm data proved good efficacy. Pressure reduction, success rates and rates of medication free patients were significantly higher in trabeculectomy compared to modified canaloplasty with mitomycin C.

Purpose To evaluate the dynamics of Bruch’s membrane opening-based morphometrics of the optic nerve head (ONH) using spectral-domain optical coherence tomography (SD-OCT) during the first week after glaucoma surgery by trabeculectomy with mitomycin C. Methods Prospective, longitudinal analysis of 25 eyes of 25 patients treated by trabeculectomy. Twenty-four eyes had evaluable postoperative SD-OCT examinations. Bruch’s membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness were analyzed at baseline before surgery, 1 day, 2 to 3 days, and 1 week after surgery. Changes compared to baseline were correlated to intraocular pressure (IOP). Results One day after surgery, the mean BMO-MRW changed by + 26.17 µm, p = 0.001 (mean IOP reduction by 17.01 mmHg). This increase persisted on day 2–3 with a mean increase of BMO-MRW of + 25.33 µm, p = 0.001 (mean IOP reduction by 20.46 mmHg) and by week 1 with a mean BMO-MRW increase of + 33.17 µm, p ρ = 0.656, p = 0.003) and d2–3 (Spearman’s rho ρ = 0.479, p = 0.038). There was no statistically significant correlation found between the IOP and the increase in BMO-MRW in week 1. RNFL thickness showed no significant changes at day 1 as well as days 2–3 (p ≥ 0.078, respectively). It showed a small but significant increase in week 1 by 3.94 µm, p = 0.015. Conclusions Structural reversal of disc cupping in BMO-MRW occurs as early as 1 day after trabeculectomy and correlates to the extent of the IOP reduction. During the whole first week after surgery, a strong increase in BMO-MRW can be noted. The changes in BMO-based parameters need to be considered when evaluating patients’ longitudinal follow-up.

G protein-coupled receptors (GPCRs) are cell-surface receptors that respond to various stimuli to induce signalling pathways across cell membranes. Recent progress has yielded atomic structures of key intermediates1,2 and roles for lipids in signalling3,4. However, capturing signalling events of a wild-type receptor in real time, across a native membrane to its downstream effectors, has remained elusive. Here we probe the archetypal class A GPCR, rhodopsin, directly from fragments of native disc membranes using mass spectrometry. We monitor real-time photoconversion of dark-adapted rhodopsin to opsin, delineating retinal isomerization and hydrolysis steps, and further showing that the reaction is significantly slower in its native membrane than in detergent micelles. Considering the lipids ejected with rhodopsin, we demonstrate that opsin can be regenerated in membranes through photoisomerized retinal–lipid conjugates, and we provide evidence for increased association of rhodopsin with unsaturated long-chain phosphatidylcholine during signalling. Capturing the secondary steps of the signalling cascade, we monitor light activation of transducin (Gt) through loss of GDP to generate an intermediate apo-trimeric G protein, and observe Gαt•GTP subunits interacting with PDE6 to hydrolyse cyclic GMP. We also show how rhodopsin-targeting compounds either stimulate or dampen signalling through rhodopsin–opsin and transducin signalling pathways. Our results not only reveal the effect of native lipids on rhodopsin signalling and regeneration but also enable us to propose a paradigm for GPCR drug discovery in native membrane environments.

Background Health providers are under unprecedented pressures to perform in the COVID-19 health crisis and under unprecedented risks. We initiated a large mixed-method survey of health professionals in five large metropolitan areas in Brazil to document the risks and needs of health professionals. To initiate the study, we conducted formative research. Methods We conducted 77 open-ended semi-structured interviews online in a convenience sample of physicians, nurses, nurse technicians, and physiotherapists in Belem, Fortaleza, Porto Alegre, Recife, and São Paulo, Brazil. Design, data collection, and analysis were informed by Rapid Ethnographic Analysis (REA). Results Responses are organized into three themes that emerged in the interviews: the lack of preparation – both locally and nationally—for the pandemic and its effects on staffing and training; the overlap of personal, family, and professional risk and consequences; and inadequately addressed anxiety and suffering among health staff. Conclusions Our respondents were unprepared for the epidemic, especially the institutional sequelae and psychological cost. These consequences were exacerbated by both lack of leadership and sweeping changes undercutting the Brazilian health system noted by almost all participants.

Background: ALCAPA is a rare disease. The sinus pouch technique reported in transposition of the great arteries has not been reported to be applied to ALCAPA, but it was a useful method. Case presentation: A five-month-old girl, weighing 5.3 kg, diagnosed ALCAPA underwent emergency surgery. The left coronary artery (LCA) originated from the posterior pulmonary artery (PA), and the left main trunk (LMT) was very short (1.5 mm), with moderate level of mitral valve regurgitation (MR). Because of the low height from the orifice to the pulmonary valve(Pv), it was necessary to avoid the tunneling technique due to concerns about adverse effects on the Pv. The sinus pouch technique was chosen because of its simplicity and low risk of stenosis due to coronary artery bending, especially in cases with short LMT. Conclusion: We report a case of infantile ALCAPA with good results using this technique.

Background To investigate the efficacy of injecting suprachoroidal triamcinolone acetonide (SCTA) plus intravitreal bevacizumab (IVB) into patients with center-involving diabetic macular edema (CI-DME). Methods In this phase 2/3 randomized controlled pilot trial, sixty-six eyes with CI-DME and best-corrected visual acuity (BCVA) of at most 20/50 Snellen chart were randomly assigned into two groups. Monotherapy arm received sham injection plus 3 monthly IVB doses and combination arm received a single dose of SCTA and 3 monthly IVB doses. The mean improvements in BCVA and Central subfield thickness (CST), over the three-month was considered the main efficacy outcomes. Results The mean BCVA improvements were obtained respectively as − 0.20 ± 0.20 log [minimum angle of resolution (MAR)] (P = 0.004) and 0.37 ± 0.24 log MAR (P ) in monotherapy and combination arms [between-group analysis (P = 0.014)]. Significant improvements were also observed in CST (P = 0.019) in the combination arm compared to the other. No adverse events (elevated intraocular pressure, cataract) were observed in any of the study arms. Conclusion Significant improvements in BCVA and retinal anatomical outcomes demonstrated the additive effects of SCTA to those of anti-vascular endothelial growth factors with no short-term side effects and this combination appears to be a promising option in the management of patients with CI-DME. Trial registration The trial was registered in Iranian Registry of Clinical Trials (IRCT20200314046761N1).

Background Techniques used to suture the rectus muscle to the implant can influence the implant-related complications which is still a major problem following retinoblastoma enucleation. The goals of this work were to report the efficacy among patients with retinoblastoma who underwent enucleation followed by porous implant placement with the rectus muscles sutured with 5–0 polyester suture. Methods This was a retrospective study of consecutive patients with retinoblastoma who underwent primary enucleation and porous implant placement with the rectus muscles tagged and sutured to the implant with polyester 5–0 suture. All the patients were followed up for a minimum of 2 years. The main outcome measure was implant exposure. The secondary efficacy measures were other implant-related complications. Results Between May 2016 and December 2018, a total of 120 patients (120 eyes) underwent primary enucleation and porous implant placement were included. Postoperatively, 10/120 (8.3%) eyes developed exposure or conjunctival granuloma. Exposure was the most common postoperative complication (7/10, 70.0%). There were no cases of implant extrusion, migration, or infection. Conclusions Polyester 5–0 sutures are successful in patients with retinoblastoma who underwent enucleation followed by porous implant placement. Complications are minimal. Polyester 5–0 sutures were not associated with unacceptable complications in this pediatric population.

Objective The purpose of this study was to investigate the efficacy of Kinesio taping (KT) combined with multi-angle isometric resistance training for cervical spondylosis. Methods Sixty-one patients were divided into two groups by random number table method. Both groups were given multi-angle isometric training, the patients in the observation group were supplemented with Kinesio taping. Before and after treatment, the symptoms of cervical spine function were evaluated in two groups by visual analogue scale (VAS), cervical dysfunction index (NDI), cervical range of motion and muscle stiffness. Results After 3 weeks of treatment, VAS, NDI scores and the cervical range of motion were significantly better than before (P P Conclusion Kinesio taping combined with multi-angle isometric resistance training can further alleviate the clinical symptoms and correct the neck abnormal posture. But its effects on the range of cervical motion remain uncertain.

Purpose: Theta Burst Stimulation can influence adult neuro-visual response in imbalanced visual pathways, possibly by influencing cortical excitability. Our objective was to compare suppressive imbalance (SI) and visual acuity (VA) after applying repetitive Transcranial Magnetic Stimulation (TMS) between groups of subjects with normal binocular vision, visual asymmetry and amblyopia. Methods: Thirty – five volunteers between 19 and 51 years of age, were split into three groups: 6 volunteers with asymmetric VA (group A); 19 amblyopes (group B); and 10 subjects with normal binocular vision (group C). VA and SI of all groups were evaluated before and after a single session of continuous theta-burst stimulation (cTBS) or placebo stimulation over the right occipital cortex. Results: In both groups A and B we found a significant VA improvement in the non-dominant eye after cTBS (p=0.04 and p=0.01, respectively). In SI evaluation, group A and group B also revealed a significant improvement after the cTBS session (p=0.03 and p=0.01, respectively).Finally, in the group of volunteers with normal binocular vision and for placebo groups A and B, there were no significant differences in VA and SI after cTBS. Conclusions: Amblyopic and visually asymmetric individuals improved VA and SI of the non-dominant eye after cTBS when compared to baseline and to placebo stimulation. These enhancements were not found in the group of volunteers with normal binocular vision. We can therefore reasonably assume that cTBS may interfere with the visual system of subjects that present some kind of asymmetry, possibly by improving neuronal imbalances.

Body gaze behavior is assumed to be a key feature of sexual objectification. However, there are few self-report gaze measures available and none capturing behavior which seeks to invite body gaze from others. Across two studies, we used existing self-report instruments and measurement of eye movements to validate a new self-report scale to measure pervasive body gaze behavior and body gaze provocation behavior in heterosexual women and men. In Study 1, participants (N = 1021) completed a survey with newly created items related to pervasive body gaze and body gaze provocation behavior. Participants also completed preexisting measures of body attitudes, sexual assault attitudes, pornography use, and relationship status. Exploratory and confirmatory factor analyses across independent samples suggested a 12-item scale for men and women to separately measure pervasive body gaze (5 items) and body gaze provocation (7 items) toward the opposite sex. The two scales yielded excellent internal consistency estimates (.86–.89) and promising convergent validity via positive correlations with body and sexual attitudes. In Study 2, a subsample (N = 167) of participants from Study 1 completed an eye-tracking task to capture their gaze behavior toward matched images of partially and fully dressed female and male subjects. Men exhibited body-biased gaze behavior toward all the female imagery, whereas women exhibited head-biased gaze behavior toward fully clothed male imagery. Importantly, self-reported body gaze correlated positively with some aspects of objectively measured body gaze behavior. Both scales showed good test–retest reliability and were positively correlated with sexual assault attitudes.

Atrophic (“dry”) form of age-related macular degeneration (AMD) is a leading cause of vision loss characterized by macular retinal pigment epithelium (RPE) and the ensuing photoreceptor degeneration. cGAS-STING signaling is a key cytosolic DNA sensor system in innate immunity and have recently been shown promotes RPE degeneration. However, expression regulation and therapeutic potential of cGAS and STING are not explored in retina under dry AMD pathogenic conditions. Our analysis shows upregulated STING RNA and increased chromatin accessibility around cGAS and STING promoters in macular retinas from dry AMD patients. cGAS-STING activation was detected in oxidative stress-induced mouse retina degeneration, accompanied with cytosolic leakage of damaged DNA in photoreceptors. Pharmaceutical or genetic approaches indicates STING promotes retina inflammation and degeneration upon oxidative damage. Drug screening reveals that BRD4 inhibitor JQ1 reduces cGAS-STING activation, inflammation and photoreceptor degeneration in the injured retina. BRD4 inhibition epigenetically suppresses STING transcription, and promotes autophagy-dependent cytosolic DNA clearance. Together, our results show that activation of cGAS-STING in retina may present pivotal innate immunity response in GA pathogenesis, whereas inhibition of cGAS-STING signaling by JQ1 could serve as a potential therapeutic strategy.

International audience; Soon after the onset of the COVID-19 pandemic, the French government decided to still hold the first round of the 2020 municipal elections as scheduled on March 15. What was the impact of these elections on the spread of COVID-19 in France? Answering this question leads to intricate econometric issues as omitted variables may drive both epidemiological dynamics and electoral turnout, and as a national lockdown was imposed at almost the same time as the elections. In order to disentangle the effect of the elections from that of confounding factors, we first predict each department’s epidemiological dynamics using information up to the election. We then take advantage of differences in electoral turnout across departments to identify the impact of the election on prediction errors in hospitalizations. We report a detrimental effect of the first round of the election on hospitalizations in locations that were already at relatively advanced stages of the epidemic. Estimates suggest that the elections accounted for at least 3,000 hospitalizations, or 11% of all hospitalizations by the end of March. Given the sizable health cost of holding elections during an epidemic, promoting ways of voting that reduce exposure to COVID-19 is key until the pandemic shows signs of abating.

Axons of adult neurons in the mammalian central nervous system generally fail to regenerate by themselves, and few if any therapeutic options exist to reverse this situation. Due to a weak intrinsic potential for axon growth and the presence of strong extrinsic inhibitors, retinal ganglion cells (RGCs) cannot regenerate their axons spontaneously after optic nerve injury and eventually undergo apoptosis, resulting in permanent visual dysfunction. Regarding the extracellular environment, research to date has generally focused on glial cells and inflammatory cells, while few studies have discussed the potentially significant role of interneurons that make direct connections with RGCs as part of the complex retinal circuitry. In this study, we provide a novel angle to summarize these extracellular influences following optic nerve injury as “intercellular interactions” with RGCs and classify these interactions as synaptic and non-synaptic. By discussing current knowledge of non-synaptic (glial cells and inflammatory cells) and synaptic (mostly amacrine cells and bipolar cells) interactions, we hope to accentuate the previously neglected but significant effects of pre-synaptic interneurons and bring unique insights into future pursuit of optic nerve regeneration and visual function recovery.

Introduction Uveitic glaucoma remains challenging despite medical and surgical advancements and can potentially lead to blindness if left uncontrolled. Conservative alternatives as well as microinvasive surgeries can postpone the necessity of a highly invasive intervention. However, such procedures are still necessary to treat some refractive glaucoma cases. Since previous studies have reported excellent results following the primary implantation of glaucoma drainage devices, it was our study’s aim to evaluate long-term results following a Baerveldt 250 implantation in highly complex and surgically burdened uveitic glaucoma eyes (UG) and compare these to a similar population suffering from other forms of glaucoma (OFG). Material and methods We performed a retrospective analysis of all eyes (UG vs. OFG) following a Baerveldt 250 implant between 2013 and 2019. Efficacy parameters as well as post-operative complication data were extracted from our electronic data system for statistical analysis. Results A total of 62 eyes were included in our study (24 UG and 38 OFG). UG baseline mean IOP was 35.04 mmHg (± 11.85 mmHg) with 3.08 (± 1.13) topical agents, and OFG was 32.63 mmHg (± 7.74 mmHg) with 2.68 (± 1.28) topical agents. A majority of eyes also required systemic acetazolamide (UG: 79% OFG: 87%) and had undergone at least one glaucoma-related operation prior to the Baerveldt 250 implant ((UG: 1.21 (± 0.66)), OFG: 1.74 (± 1.33)). At the median follow-up period (UG 592, OFG 764 days), 52.5%/32.5% of UG/OFG cases showed qualified success (IOP below 21 mmHg with either topical or/and systemic medication), 15%/30% no longer required topical medication, and 47.5% /47.5% were free of acetazolamide systemically. Moreover, 75%/72.5% of eyes experienced no further pressure-related surgical event. Although sight-threatening complications such as corneal and macular edema were reported in both groups, most either maintained or improved their visual acuity at the last follow-up (58.33%/57.89%). Conclusion The Baerveldt 250 implant is shown to be both effective and safe for advanced glaucoma cases in uveitis and other forms. No further glaucoma-related surgery is required in the majority of eyes in either group within a follow-up period of almost 2 years. Despite sight-threatening complications such as macular and corneal edema, visual acuity can be either maintained or improved in most eyes.

Question: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions?Target population: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection.Recommendation:Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

Development of Bruton’s tyrosine kinase (BTK) inhibitors is of great value and significance in the treatment of B-cell malignancies and autoimmune diseases. Herein, a novel class of pyrazolopyrimidine-based BTK inhibitors were designed and evaluated in mantle cell lymphoma (MCL) cell lines. We demonstrated that target compounds had made great progress in improvement of antiproliferative activity compared to lead compound. Compounds 13c, 13g, 13h, 13l, 13n and 13o demonstrated effectively antiproliferative activity in MCL cells lines with single-digit micromolar potency. Furthermore, compound 13l specifically disturbed mitochondrial membrane potential and increased reactive oxygen species level in Z138 cells in a dose-dependent manner. 13l induced cell apoptosis through the caspase 3- mediated apoptotic pathway in Z138 cells. Overall, this study provides valuable lead compounds for developing antitumor agents.

Background: Autism spectrum disorder (ASD) is a highly heritable, genetically complex neurodevelopmental disorder. Genetic liability is often expressed among relatives through subclinical, genetically meaningful traits, or endophenotypes. Studies of parents of individuals with ASD suggest important differences from controls in language-related skills in particular, including evidence that such differences may emerge in childhood, that may serve as early markers of genetic liability to ASD. This study investigated whether developmental academic profiles may be evident among clinically unaffected siblings of individuals with ASD, and possibly constitute developmental endophenotypic markers of ASD genetic risk among relatives. Methods: Longitudinal, archival academic testing records were studied to characterize developmental profiles in the domains of language, reading, and math, among clinically unaffected siblings of individuals with ASD. Relationships were explored between siblings’ childhood academic profiles and subclinical ASD-related traits, and the familiality of such traits. Results: Results revealed relatively lower performance in language-related academic skills among siblings of individuals with ASD, mirroring patterns previously reported among parents. Relationships were detected between siblings’ academic performance patterns and subclinical ASD-related traits in themselves and their parents, and with symptom severity in their sibling with ASD. Language phenotypes were associated in mother-sibling dyads, and rigidity and math performance associated in father-child dyads. Limitations: Data from this study represent a relatively small and racially homogenous group of siblings of individuals with ASD, and as such, replication in a larger more diverse sample should be completed to increase generalizability. Conclusions: Distinctive profiles of academic development were evident in siblings in language-related skills, mirroring prior findings in parents, suggesting specific and subtle phenotypes that may represent early-emerging indicators of genetic liability to ASD and are measurable in first-degree relatives using standardized academic testing. Results also suggest differential intergenerational transmission of ASD-related traits between mothers and fathers.

Target populationThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).Question (Q1):In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Recommendation:Level III: Adult patients with pGBM might derive benefit in treatment with TMZ especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohypothermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.Question (Q2):In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Recommendation:Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a suggestion about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.Question (Q3):In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Recommendation:Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Level III: Other cytotoxic therapies like perillyl acohol and ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.Question (Q4):In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Recommendation:Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.Question (Q5):In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Recommendation:Level III: Oncolytic virotherapy is not suggested in patients with pGBM.