Ascorbic acid export from human donor lenses: Is the lens a source of ascorbic acid in the ocular humors?

In previous work, we have shown that the lens acts a reservoir of the antioxidant glutathione (GSH), capable of exporting this antioxidant into the ocular humors and potentially protecting the tissues of the eye that interface with these humors from oxidative stress. In this study, we have extended this work by examining whether the lens acts as a source of ascorbic acid (AsA) to maintain the high levels of AsA known to be present in the ocular humors either by the direct export of AsA into the humors and/or by functioning as a recycling site for AsA, via the direct uptake of oxidised ascorbate (DHA) from the humors, its regeneration to AsA in the lens and then its subsequent export back into the humors. To test this, human lenses of varying ages were cultured for 1 h under hypoxic conditions and AsA/DHA levels measured in the media and in the lens. Human lenses were also cultured in compartmentalised chambers to determine whether efflux of AsA/DHA occurs at the anterior or posterior surface. Immunohistochemistry was performed on human donor lenses and sections labelled with antibodies against GLUT1, a putative DHA uptake transporter. Vitreous humor was collected from patients undergoing vitrectomy who either had a natural clear lens, an artificial intraocular implant (IOL) or a cataractous lens, and AsA/DHA and GSH and oxidised GSH (GSSG) measured. We found that cultured human donor lenses released both AsA and DHA into the media. Culturing of lenses in a compartmentalised chamber revealed that AsA and DHA efflux occurs at both surfaces, with relatively equal amounts of AsA and DHA released from each surface. The posterior surface of the lens was shown to express the GLUT1 transporter. Analysis of vitreous samples from patients undergoing vitrectomy revealed that vitreous GSH and AsA levels were similar between the natural lens group, IOL and cataractous lens group. Taken together, while human donor lenses were shown to export AsA and DHA into the surrounding media, the amount of AsA and DHA released from donor lenses was low and not sufficient to sustain the high levels of total AsA normally present in the humors. This suggests that although the lens is not the main source for maintaining high levels of AsA in the ocular humors, the lens may help to support local AsA levels close to the lens.

Large-scale deep tissue voltage imaging with targeted-illumination confocal microscopy.

Voltage imaging with cellular specificity has been made possible by advances in genetically encoded voltage indicators. However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines the signal-to-noise ratio and induces crosstalk between cells, making reliable in vivo imaging in densely labeled tissue highly challenging. We describe a microscope that combines the distinct advantages of targeted illumination and confocal gating while also maximizing signal detection efficiency. The resulting benefits in signal-to-noise ratio and crosstalk reduction are quantified experimentally and theoretically. Our microscope provides a versatile solution for enabling high-fidelity in vivo voltage imaging at large scales and penetration depths, which we demonstrate across a wide range of imaging conditions and different genetically encoded voltage indicator classes.

The dimensional structure of the Camouflaging Autistic Traits Questionnaire (CAT-Q) and predictors of camouflaging in a representative general population sample.

OBJECTIVES: Some autistic people "camouflage" their differences by modeling neurotypical behaviors to survive in a neurotypical-dominant social world. It remains elusive whether camouflaging is unique to autism or if it entails similar experiences across human groups as part of ubiquitous impression management (IM). Here we examined camouflaging engagement and theoretical drivers in the general population, drawing on the transactional IM framework and contextualizing findings within both contemporary autism research and the past IM literature. METHODS: A large representative U.S. general population sample (N = 972) completed this survey study. We combined exploratory item factor analysis and graph analysis to triangulate the dimensional structure of the Camouflaging Autistic Traits Questionnaire (CAT-Q) and examined its correspondence with prior autism-enriched psychometric findings. We then employed hierarchical regression and elastic-net regression to identify the predictors of camouflaging, including demographic (e.g., age, gender), neurodivergence (i.e., autistic and ADHD traits), socio-motivational, and cognitive factors. RESULTS: We found a three-factor/dimensional structure of the CAT-Q in the general population, nearly identical to that found in previous autism-enriched samples. Significant socio-motivational predictors of camouflaging included greater social comparison, greater public self-consciousness, greater internalized social stigma, and greater social anxiety. These camouflaging drivers overlap with findings in recent autistic camouflaging studies and prior IM research. CONCLUSIONS: The novel psychometric and socio-motivational evidence demonstrates camouflaging as a shared social coping experience across the general population, including autistic people. This continuity guides a clearer understanding of camouflaging and has key implications for autism scholars, clinicians, and the broader clinical intersecting with social psychology research. Future research areas are mapped to elucidate how camouflaging/IM manifests and functions within person-environment transactions across social-identity and clinical groups.

Not Who You Are, But Who You Are With: Re-examining Women's Less Satisfying Sexual Debuts.

Gender differences in appraisals of first intercourse are among the largest in sexuality research, with women indicating less satisfying "sexual debuts" than men. Dispositional or "actor-level" explanations for this gender gap are pervasive, yet research has largely examined heterosexual debuts in which actor gender and partner gender are confounded. We assessed whether women's less satisfying sexual debuts are better explained by actor gender or partner gender, comparing experiences of women who debuted with men (WDM) with those of men and women who debuted with women (MDW, WDW). Retrospective accounts of sexual debut were collected from 3033 adults. At first intercourse, we found that WDW had equal physical and emotional satisfaction to MDW, and more satisfaction than WDM, suggesting satisfaction gaps owing to partner gender, not actor gender. This pattern did not extend to a comparison event (first masturbation), where WDW and WDM had similar satisfaction, but less satisfaction than MDW, suggesting an actor gender gap. To identify sources of satisfaction gaps, we probed for corresponding differences in the circumstances of sexual debut. Sexual circumstances were more strongly implicated than nonsexual ones, with relative deprivation of glans stimulation explaining relative dissatisfaction at first intercourse, but not first masturbation, and orgasm explaining it at both. Findings challenge the view that the satisfaction gap at first intercourse reflects an inherent difference between genders. Indeed, they demonstrate similarities when partner gender does not differ and suggest strategies for ensuring equal sexual satisfaction-and equal sexual rights realization-at (hetero) sexual debut.

Framing Subjective Emotion Reports as Dynamic Affective Decisions.

Self-reports remain affective science's only direct measure of subjective affective experiences. Yet, little research has sought to understand the psychological process that transforms subjective experience into self-reports. Here, we propose that by framing these self-reports as dynamic affective decisions, affective scientists may leverage the computational tools of decision-making research, sequential sampling models specifically, to better disentangle affective experience from the noisy decision processes that constitute self-report. We further outline how such an approach could help affective scientists better probe the specific mechanisms that underlie important moderators of affective experience (e.g., contextual differences, individual differences, and emotion regulation) and discuss how adopting this decision-making framework could generate insight into affective processes more broadly and facilitate reciprocal collaborations between affective and decision scientists towards a more comprehensive and integrative psychological science.

Large-scale deep tissue voltage imaging with targeted illumination confocal microscopy.

Voltage imaging with cellular specificity has been made possible by the tremendous advances in genetically encoded voltage indicators (GEVIs). However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines signal-to-noise ratio (SNR) and induces crosstalk between cells, making reliable in vivo imaging in densely labeled tissue highly challenging. We describe a microscope that combines the distinct advantages of targeted illumination and confocal gating, while also maximizing signal detection efficiency. The resulting benefits in SNR and crosstalk reduction are quantified experimentally and theoretically. Our microscope provides a versatile solution for enabling high-fidelity in vivo voltage imaging at large scales and penetration depths, which we demonstrate across a wide range of imaging conditions and different GEVI classes.

Deliberative control is more than just reactive: Insights from sequential sampling models.

Activating relevant responses is a key function of automatic processes in De Neys's model; however, what determines the order or magnitude of such activation is ambiguous. Focusing on recently developed sequential sampling models of choice, we argue that proactive control shapes response generation but does not cleanly fit into De Neys's automatic-deliberative distinction, highlighting the need for further model development.

Sustainable Syntheses of Paracetamol and Ibuprofen from Biorenewable ß-pinene.

Scalable processes have been developed to convert ß-pinene into 4-isopropenylcyclohexanone, which is then used as a feedstock for the divergent synthesis of sustainable versions of the common painkillers, paracetamol and ibuprofen. Both synthetic routes use Pd0 catalysed reactions to aromatize the cyclohexenyl rings of key intermediates to produce the benzenoid ring systems of both drugs. The potential of using bioderived 4-hydroxyacetophenone as a drop-in feedstock replacement to produce sustainable aromatic products is also discussed within a terpene biorefinery context.

AI and the transformation of social science research.

Careful bias management and data fidelity are key.

Motivated Categories: Social Structures Shape the Construction of Social Categories Through Attentional Mechanisms.

PUBLIC ABSTRACT: Social categories like race and gender often give rise to stereotypes and prejudice, and a great deal of research has focused on how motivations influence these biased beliefs. Here, we focus on potential biases in how these categories are even formed in the first place, suggesting that motivations can influence the very categories people use to group others. We propose that motivations to share schemas with other people and to gain resources shape people's attention to dimensions like race, gender, and age in different contexts. Specifically, people will pay attention to dimensions to the degree that the conclusions produced from using those dimensions align with their motivations. Overall, we suggest that simply examining the downstream effects of social categorization like stereotyping and prejudice is not enough, and that research should look earlier in the process at how and when we form the categories on which those stereotypes are based.

Social and moral psychology of COVID-19 across 69 countries.

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.

Coronavirus pandemic in the South Asia region: Health policy and economy trade-off.

Background: The South Asian Association for Regional Cooperation (SAARC) covers Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. We conducted a comparative analysis of the trade-off between the health policies for the prevention of COVID-19 spread and the impact of these policies on the economies and livelihoods of the South Asia populations. Methods: We analyzed COVID-19 data on epidemiology, public health and health policy, health system capacity, and macroeconomic indicators from January 2020 to March 2021 to determine temporal trends by conducting joinpoint regression analysis using average weekly percent change (AWPC). Results: Bangladesh had the highest statistically significant AWPC for new COVID-19 cases (17.0; 95% CI = 7.7-27.1, P < 0.001), followed by the Maldives (12.9; 95% CI = 5.3-21.0, P < 0.001) and India (10.0; 95% CI = 8.4-11.5, P < 0.001). The AWPC for COVID-19 deaths was significant for India (6.5; 95% CI = 4.3-8.9, P < 0.001) and Bangladesh (6.1; 95% CI = 3.7-8.5, P < 0.001). Nepal (55.79%), and India (34.91%) had the second- and third-highest increase in unemployment, while Afghanistan (6.83%) and Pakistan (16.83%) had the lowest. The rate of change of real GDP had the highest decrease for Maldives (557.51%), and India (297.03%); Pakistan (46.46%) and Bangladesh (70.80%), however, had the lowest decrease. The government response stringency index for Pakistan had a see-saw pattern with a sharp decline followed by an increase in the government health policy restrictions that approximated the test-positivity trend. Conclusions: Unlike developed economies, the South Asian developing countries experienced a trade-off between health policy and their economies during the COVID-19 pandemic. South Asian countries (Nepal and India), with extended periods of lockdowns and a mismatch between temporal trends of government response stringency index and the test-positivity or disease incidence, had higher adverse economic effects, unemployment, and burden of COVID-19. Pakistan demonstrated targeted lockdowns with a rapid see-saw pattern of government health policy response that approximated the test-positivity trend and resulted in lesser adverse economic effects, unemployment, and burden of COVID-19.

Patient factors associated with appointment non-attendance at an ophthalmology department in Aotearoa New Zealand.

AIM: Appointment non-attendance is a problem for medical outpatient clinics, which can result in interruption of continuity of care and poor health outcomes for patients. Furthermore, non-attendance creates a significant economic burden to the health sector. This study aimed to identify factors that are associated with appointment non-attendance in a large public ophthalmology clinic in Aotearoa New Zealand. METHODS: This study was a retrospective analysis of clinic non-attendance within Auckland District Health Board's (DHB) Ophthalmology Department between 1 January 2018 to 31 December 2019. Demographic data collected included: age, gender and ethnicity. Deprivation Index was calculated. Appointments were classified as new patients and follow-ups, and acute or routine. Categorical and continuous variables were analysed using logistic regression to assess likelihood of non-attendance. The research team's expertise and capacity align with the CONSIDER statement guidelines for Indigenous health and research. RESULTS: In total, 52,512 patients were scheduled to attend 227,028 outpatient visits, of which 20,580 visits (9.1%) were not attended. Median age of patients who received one or more scheduled appointments were 66.1 years (interquartile range [IQR] 46.9-77.9). Fifty-one point seven percent of patients were female. Ethnicity comprised 55.0% European, 7.9% Maori, 13.5% Pacific peoples, 20.6% Asian and 3.1% Other. Multivariate logistic regression analysis for all appointments showed that males (odds ratio [OR] 1.15 p<0.001), younger patients (OR 0.99 p<0.001), Maori (OR 2.69 p<0.001), Pacific peoples (OR 2.82 p<0.001), higher deprivation status (OR 1.06 p<0.001), new patient appointments (OR 1.61 p<0.001) and patients referred to acute clinics (OR 1.22 p<0.001) were more likely to not attend appointments. CONCLUSIONS: Maori and Pacific peoples disproportionately experience higher rates of appointment non-attendance. Further investigation of access barriers will enable Aotearoa New Zealand health strategy planning to develop targeted interventions addressing unmet patient needs of at-risk groups.

Acute intermittent porphyria: A rare cause of syndrome of inappropriate antidiuretic hormone secretion.

A 31-year-old female presented to the emergency department with abdominal pain, vomiting and constipation. Serum sodium levels were recorded at 110 mmol/L on admission, dropping to 96 mmol/L despite fluid restriction. The patient developed hallucinations and required hypertonic saline administration in critical care. Urinary sodium was detected at 149 mmol/L, consistent with syndrome of inappropriate antidiuretic hormone secretion (SiADH). Urinary porphyrins were also raised, consistent with a diagnosis of acute intermittent porphyria with SiADH as a complication.

Decoupling the Conflicting Evaluative Meanings in Automatically Activated Race-Based Associations.

Implicit measures of attitudes have classically focused on the association between a social group and generalized valence, but debate exists surrounding how these associations arise and what they can tell us about beliefs and attitudes. Here, we suggest that representations of oppression, which relate positively to implicitly measured prejudice but negatively to explicitly measured prejudice, can serve to decrease the predictive validity of implicit measures through statistical suppression. We had participants complete a Black-White implicit association test (IAT) and an IAT measuring representations of oppression, and find that oppression-related representations statistically suppress the relation between IAT scores and explicit attitudes, such that accounting for these representations increases the total amount of variance explained by implicit measures. We discuss the implications of this work both for practical matters around use of the IAT and for theoretical debates on the conceptualization of valence in implicit attitudes.

Rhegmatogenous retinal detachment presentation and surgery in uveitic eyes.

BACKGROUND/AIMS: To explore the occurrence, uveitis activity, features, rate of proliferative vitreoretinopathy (PVR) and outcomes following rhegmatogenous retinal detachment (RRD) in a large tertiary referral uveitis service. METHODS: Retrospective analysis of subjects attending between 2008 and 2019. Multivariate analysis of risk factors for RRD was calculated. Nelson-Aalen plots were used to demonstrate cumulative risk of RRD. Outcomes of RRD surgery and prognostic indicators were analysed. RESULTS: Two thousand four hundred and forty-seven (2447) subjects (3516 eyes) with uveitis included. The mean follow-up was 5.7 years (19 767 eye-years); 56 eyes developed a RRD (1.6%). Thirty-two eyes had surgery in our unit. Risk factors for RRD were posterior uveitis or panuveitis (HR 3.386, p<0.001), male gender (HR 2.045, p=0.029) and infectious aetiology (HR 1.942, p=0.044). PVR was present in six (18.8%) eyes at presentation, and a further four (12.5%) developed it after the primary surgery. Final follow-up data showed 16 (50%) moderate or severe visual loss, although 29 (90.6%) had anatomical reattachment without oil in situ. CONCLUSIONS: There is a high rate of RRD in uveitis eyes. This is accompanied by high rates of PVR and redetachment. Anatomical success was high, but visual outcomes remain unpredictable.

Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment.

BACKGROUND/OBJECTIVES: Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes. SUBJECTS/METHODS: Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival. RESULTS: Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Maori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%. CONCLUSION: In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.

Geographic access to eye health services in Aotearoa New Zealand: which communities are being left behind?

CLINICAL RELEVANCE: Efforts to provide accessible eye care must consider the extent to which travel-distance may be a barrier for some communities. BACKGROUND: This study aimed to determine the distribution of - and geographic access to - eye health services in Aotearoa New Zealand. We further sought to identify communities who might benefit from provision of eye health services that were more geographically accessible. METHODS: We obtained addresses of optometry and ophthalmology clinics from regulatory bodies and augmented this with online searches. Address locators were created using a Land Information dataset and geocoded using ArcGIS 10.6. A national population was derived using Statistics New Zealand's Integrated Data Infrastructure. We generated population-weighted centroids of each of New Zealand's 50,938 meshblocks and calculated the travel distance along the road network between each clinic and population (meshblock centroid). The proportion of the population living >50 km from each clinic type was calculated; as was the median, inter-quartile range and maximum distance across area-level deprivation quintiles in each district. RESULTS: A national population of 4.88 million was identified, as were addresses for 344 optometry, 46 public ophthalmology and 90 private ophthalmology clinics. Nationally and within each district, travel distance to optometry was shorter than to either type of ophthalmology clinic. The region of Northland - with a high proportion of the population Maori and in the highest quintile of area-level deprivation - had the furthest average distance to travel to optometry and public ophthalmology, while the West Coast region on the South Island had the farthest to travel to private ophthalmology. Several communities were identified where longer distances intersected with higher area-level deprivation. CONCLUSION: Most New Zealanders live within 10 km of eye health services. However, to achieve equitable eye health, strategies are required that make affordable eye health services accessible to communities for whom large travel distances intersect with high deprivation.

Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers.

This pilot study examined the associations among functional connectivity in the salience, central executive, and default mode networks, and neurocognition in pediatric brain tumor survivors and healthy children. Thirteen pediatric brain tumor survivors (9 boys, M = 12.76 years) and 10 healthy children (6 boys, M = 12.70 years) completed magnetic resonance imaging (MRI) and assessment of processing speed and executive function. Pediatric brain tumor survivors performed more poorly than healthy children on measures of processing speed, divided attention, and working memory; parent ratings of day-to-day executive function did not differ significantly by group, though both pediatric brain tumor survivors who underwent only surgical resection and healthy children were rated by parents as having difficulties approaching a standard deviation above the normative mean. Connectivity was lower in the salience network and greater in the default mode network in pediatric brain tumor survivors. Cross-method correlations showed that increased salience network and default mode network connectivity were associated with better task performance and parent-rated executive skills and higher central executive network connectivity with poorer parent-rated executive skills. This perhaps reflects an adaptive pattern of hyperconnectivity in pediatric brain tumor survivors.