B56δ long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations.

Intrinsically disordered regions (IDR) and short linear motifs (SLiMs) play pivotal roles in the intricate signaling networks governed by phosphatases and kinases. B56δ (encoded by PPP2R5D) is a regulatory subunit of protein phosphatase 2A (PP2A) with long IDRs that harbor a substrate-mimicking SLiM and multiple phosphorylation sites. De novo missense mutations in PPP2R5D cause intellectual disabilities (ID), macrocephaly, Parkinsonism, and a broad range of neurological symptoms. Our single-particle cryo-EM structures of the PP2A-B56δ holoenzyme reveal that the long, disordered arms at the B56δ termini fold against each other and the holoenzyme core. This architecture suppresses both the phosphatase active site and the substrate-binding protein groove, thereby stabilizing the enzyme in a closed latent form with dual autoinhibition. The resulting interface spans over 190 Šand harbors unfavorable contacts, activation phosphorylation sites, and nearly all residues with ID-associated mutations. Our studies suggest that this dynamic interface is coupled to an allosteric network responsive to phosphorylation and altered globally by mutations. Furthermore, we found that ID mutations increase the holoenzyme activity and perturb the phosphorylation rates, and the severe variants significantly increase the mitotic duration and error rates compared to the normal variant.

Measurement of visual functioning following first and second eye cataract surgery using Vision-Related Activity Limitation Item Bank.

PURPOSE: This study aims to compare visual functioning (VF) after first or second eye cataract surgery using the vision-related activity limitation (VRAL) item bank. METHODS: This prospective, interventional study included 787 patients (mean age, 58.2 years) with cataract undergoing cataract surgery (first eye surgery with/out ocular comorbidity, second eye surgery with/out ocular comorbidity) at a tertiary eye care center, South India, who were administered the item bank pre- and at 6 weeks postoperatively to assess change in VF. Rasch analysis was used to estimate VF at both time points, and responsiveness to cataract surgery was calculated as effect size (ES) which was interpreted as small (≤ 0.2), moderate (0.3-0.7), and large (≥ 0.8). RESULTS: Mean best-corrected logMAR VA in surgical eye improved significantly postoperatively compared to preoperative VA (0.20 ± 0.40 vs. 1.19 ± 0.96; P < 0.0001) across all groups. Patients reported significant and large improvements in VF postoperatively across all groups: largest ES for first eye surgery without comorbidity (1.87 [95% CI, 1.61, 2.13]) and smallest for second eye without ocular comorbidity (1.55 [95% CI, 1.22, 1.88]). Compared to patients undergoing second eye surgery, first eye surgery patients reported significantly lower VF preoperatively (-0.72 ± 2.39 vs. 0.17 ± 2.34 logits; P < 0.0001), and a larger change in VF postoperatively (3.71 ± 2.33 logits vs. 4.27 ± 2.83 vs.; P = 0.004). CONCLUSIONS: Cataract surgery resulted in large and significant improvements in VF, regardless of ocular comorbidity and first or second eye surgery. The VRAL item bank is a useful tool to measure responsiveness to cataract surgery.

Social media use and vision impairment in adults between the ages of 18 and 35 years in India.

SIGNIFICANCE: Social media is used by >4.48 billion people worldwide. Despite its popularity, vision-impaired individuals struggle to use social media given visual inaccessibility of content and lack of access to Internet/Wireless-Fidelity-enabled devices. Our study explores visually impaired adult's use of social media in comparison to a control group. PURPOSE: This study aimed to report the demographic profile and patterns of social media use among adults with vision impairment (VI) aged 18 to 35 years and compare it with an age-matched normally sighted group in India. In addition, we explored barriers to use of social media among adults with VI. METHODS: Vision-impaired and normally sighted adults (controls) aged 18 to 35 years at L V Prasad Eye Institute, Hyderabad, India, answered a questionnaire about social media use (e.g., platform used). RESULTS: Four hundred twenty-two individuals (201 VI, 221 controls) participated. Normally sighted adults (98%) used social media more than the VI group (81%; p<0.001). Vision-impaired users were predominantly male (85%) and unemployed (57%; p<0.00001 for both). There was no significant difference in educational level between groups (p=0.17). Smartphones were the most popular device used (VI, 161 [99%]; control, 206 [95%]), with tablet PC/iPad being the least popular (VI, 5 [3%]; control, 12 [6%]). Adults with VI and controls commonly used WhatsApp as communication platforms, and Facebook and Twitter as networking platforms. Approximately one-third of individuals across both social media user groups reported barriers to use (VI, 48 [30%]; control, 74 [34%]; p<0.001). Vision-impaired individuals cited accessibility issues of having to rely on audio over vision to navigate social media, whereas controls reported having to share a phone. CONCLUSIONS: The proportion of social media usage among VI adults is high (81%) and is substantially higher than the 33% reported in the general Indian population. Vision-impaired adults who used social media were male with moderate VI and were less likely to be employed compared with controls.

Young adults with vision impairment in India: Loneliness and social networks.

PURPOSE: To examine the prevalence of loneliness and associated factors in young adults with vision impairment (VI), including quality of life (QoL) in India. METHODS: Two hundred and three VI young adults (18-35 years) and 219 age-matched non-VI (controls) adults completed the loneliness scale, WHOQOL-BREF, Social Network Index (SNI) (network diversity, people in network size and number of embedded network subscales) and questions regarding sociodemographic characteristics and independent mobility. Rasch analysis was used to validate the questionnaires and interval-level scores were generated. Generalised linear models were used to estimate independent associations of sociodemographic factors, VI characteristics, social networks and QoL with loneliness. RESULTS: The prevalence of moderate and severe loneliness in the VI group was 10% (95% CI: 6.5, 15.4) and 4.4% (95% CI: 2.0, 8.2), respectively, and higher than that of controls. The VI group had a worse loneliness score than controls (-1.66 ± 2.25 vs. -2.13 ± 1.85 logits; p = 0.03). Those with ≤12 years and >12 years of education had loneliness scores of -1.58 ± 2.45 and -1.82 ± 1.99 logits, respectively (p = 0.01). Compared with controls, the VI group reported fewer extended family members, neighbours and friends leading to significantly smaller networks and network diversity (all p < 0.001). Loneliness scores demonstrated a significant correlation with only two SNI subscales for both groups: people in network size (r = -0.28 for VI; r = -0.30 for non-VI; p < 0.001 for both) and number of embedded networks (r = -0.22 for VI; r = -0.21 for non-VI; p = 0.002 for both). Both education (ß = 0.45; p = 0.04) and QoL (ß = -0.27, p = 0.02) were predictors of loneliness. CONCLUSIONS: Loneliness was commonly experienced by young VI adults and was higher among those with lower levels of education. Loneliness decreased with the presence of a larger number of people in network, suggesting that interventions to increase social activity and participation may be valuable in young VI adults.

Long-term Outcomes in Patients Undergoing Surgery for Primary Congenital Glaucoma between 1991 and 2000: A Single-Center Database Study.

PURPOSE: To estimate the long-term surgical and visual outcomes in patients with primary congenital glaucoma (PCG) who completed at least 20 years of follow-up. DESIGN: Retrospective study. PARTICIPANTS: Two hundred twenty eyes of 121 patients undergoing surgery for PCG between January 1991 and December 2000 and who returned for a follow-up visit from January 2021 through January 2022. METHODS: Retrospective review of medical records of patients who underwent primary combined trabeculotomy-trabeculectomy (CTT) without mitomycin C as an initial procedure. Success was defined as complete when intraocular pressure (IOP) was ≥ 6 mmHg and ≤ 21 mmHg without glaucoma medication and as qualified when up to 2 glaucoma medications were required. Failure was defined as uncontrolled IOP with more than 2 glaucoma medications, need for a second IOP-lowering procedure, chronic hypotony (IOP < 6 mmHg on 2 consecutive visits), or any sight-threatening complication. A mixed-effects model using maximum likelihood estimation was used in estimation of eye-based variables and to make comparisons between different visits. Kaplan-Meier survival analysis was used to estimate the probabilities of surgical and functional successes. Cox proportional hazards regression using sandwich clustered estimation was used to evaluate risk factors for failure and poor visual outcome. MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of patients who demonstrated complete success over the 20-year follow-up. Secondary outcome measures included rate of surgical failure and need for reoperation for glaucoma, visual acuity, refractive errors, risk factors for poor outcome, and complications. RESULTS: Kaplan-Meier survival analysis revealed 1-year, 10-year, and 20-year complete success rates of 90.7%, 78.9%, and 44.5%, respectively. In univariate analysis, surgical failure was higher among patients with any additional non-glaucoma intraocular surgery. None of the clinical parameters were associated significantly with failure in multivariable analysis. Overall, the proportion of eyes with good, fair, and poor visual outcomes was 33.2%, 16.4%, and 50.4%, respectively. Myopia was seen in 68.9% eyes. Twenty-eight eyes of those who underwent primary CTT (14.4%) required second surgery for IOP control. No significant intraoperative complications occurred. Six eyes required enucleation because of painful blind eye. CONCLUSIONS: In this large cohort of patients with PCG, CTT is a useful procedure. It provides good IOP control and moderate visual recovery that remained over a 20-year follow-up after surgery. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Quality of life and psychosocial outcomes among children with metabolically healthy and unhealthy obesity.

BACKGROUND: Obesity and obesity-related morbidities are associated with poor psychosocial adjustment and health-related quality of life (HRQoL). This study aims to examine HRQoL and psychosocial outcomes in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and the effects of familial health on these outcomes. METHODS: Four hundred and six children with BMI for age ≥ 97th percentile were classified as having MHO and MUO based on the absence or presence of metabolic abnormalities. HRQoL and psychosocial outcomes were assessed using validated questionnaires such as PedsQL and DASS-21. RESULTS: There were no significant differences in HRQoL and psychosocial outcomes between children with MHO and children with MUO. Children with MUO and prior knowledge of existing metabolic conditions reported significantly lower total HRQoL (71.18 ± 17.42 vs. 75.34 ± 15.33), and higher depression (12.16 ± 11.80 vs. 8.95 ± 8.52) and stress (12.11 ± 8.21 vs. 10.04 ± 7.92) compared to children with MHO. Children with MUO who had fathers with metabolically unhealthy phenotype reported significantly lower total HRQoL (72.41 ± 15.67 vs. 76.82 ± 14.91) compared to children with MUO who had fathers with metabolically healthy phenotype. CONCLUSION: Prior knowledge of existing metabolic abnormalities was associated with poorer HRQoL and mental health in children with obesity. Paternal metabolic health status influenced HRQoL in children with MUO. IMPACT: First study that compared health-related quality of life (HRQoL) and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). No significant differences in HRQoL and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). Children with MUO who had prior knowledge of existing metabolic conditions reported lower HRQoL, higher depression and stress compared to children with MHO. Paternal metabolic health status was found to influence HRQoL in children with MUO. Mental health support intervention with paternal involvement should be provided for children with MUO.

A case study of using natural language processing to extract consumer insights from tweets in American cities for public health crises.

BACKGROUND: The COVID-19 pandemic was a "wake up" call for public health agencies. Often, these agencies are ill-prepared to communicate with target audiences clearly and effectively for community-level activations and safety operations. The obstacle is a lack of data-driven approaches to obtaining insights from local community stakeholders. Thus, this study suggests a focus on listening at local levels given the abundance of geo-marked data and presents a methodological solution to extracting consumer insights from unstructured text data for health communication. METHODS: This study demonstrates how to combine human and Natural Language Processing (NLP) machine analyses to reliably extract meaningful consumer insights from tweets about COVID and the vaccine. This case study employed Latent Dirichlet Allocation (LDA) topic modeling, Bidirectional Encoder Representations from Transformers (BERT) emotion analysis, and human textual analysis and examined 180,128 tweets scraped by Twitter Application Programming Interface's (API) keyword function from January 2020 to June 2021. The samples came from four medium-sized American cities with larger populations of people of color. RESULTS: The NLP method discovered four topic trends: "COVID Vaccines," "Politics," "Mitigation Measures," and "Community/Local Issues," and emotion changes over time. The human textual analysis profiled the discussions in the selected four markets to add some depth to our understanding of the uniqueness of the different challenges experienced. CONCLUSIONS: This study ultimately demonstrates that our method used here could efficiently reduce a large amount of community feedback (e.g., tweets, social media data) by NLP and ensure contextualization and richness with human interpretation. Recommendations on communicating vaccination are offered based on the findings: (1) the strategic objective should be empowering the public; (2) the message should have local relevance; and, (3) communication needs to be timely.

What are the reasons for abandonment of low vision devices prescribed in a large tertiary eye care centre?

PURPOSE: To investigate abandonment rates of near-vision low vision devices (LVDs) and factors that influence abandonment among patients attending a tertiary low vision rehabilitation centre in South India. METHODS: Two hundred and eighty-six adults with low vision completed the modified device abandonment survey 1 year following device prescription. The survey included six questions: possession of device, timing of last use, reasons for abandonment, tasks for which the device was used, payment type and change in quality of life (QoL) from device use. The primary outcome measure was abandonment. Multivariate logistic regression analysis was used to investigate factors for abandonment. RESULTS: Three hundred and twelve near-vision devices were prescribed (mean, 1.09 device per patient.) Stand magnifiers (35%) followed by hand-held magnifiers (24%) were most frequently prescribed. Mean logMAR visual acuity (Snellen) in the better-seeing eye was 0.80 (6/38). Of the prescribed near-vision devices, 22% (95% CI, 17 to 27) were abandoned. Patients who abandoned the device were significantly older than those who did not (49.3 ± 17.2 vs. 43.5 ± 18.1 years; p = 0.03). In multivariable analysis, patients reporting no change in their QoL from device use had higher odds of abandoning the device (OR: 63.97; 95% CI, 23.77 to 172.12). Device-related (31%) and psychological (30%) factors were the most frequent reasons for abandonment. Among device-related issues, the most frequent reason was that patients felt the device was too complex to use (50%) followed by being too cumbersome to use (25%). CONCLUSION: The abandonment rate for near-vision LVDs in South India was comparable with that reported in high-income countries. Patients reporting no change in their QoL had a higher likelihood of abandoning the device compared with those who reported some change. Device-related and psychological factors were the most frequent reasons for abandonment. These results can be used to develop strategies to improve compliance with use of devices.

Road to Equity in Maternal and Child Health: Honoring the Past and Blazing New Paths.

PURPOSE: This paper is a historical account of an initiative, as recalled by the authors who were directly involved, that brought to the forefront the long-standing and unjust reproductive health inequities in the United States. It is composed of three distinct but interrelated parts that together map the past, present, and future of addressing racial inequities in Maternal and Child Health. DESCRIPTION: This paper is composed of three distinct but interrelated parts that together map the past, present, and future of addressing racial inequities in Maternal and Child Health. Part I recounts the history and achievements of a Centers for Disease for Control and Prevention initiative in the 1980-90's, led by the Prematurity Research Group in the Division of Reproductive Health, Pregnancy and Infant Health Branch. This initiative stimulated a paradigm shift in how we understand and address black infant mortality and the inequities in this outcome. Part II illustrates examples of some exemplary programmatic and policy legacies that stemmed either directly or indirectly from the Centers for Disease for Control and Prevention paradigm shift. Part III provides a discussion of how effectively the current practice in Maternal and Child Health applies this paradigm to address inequities and proposes a path for accelerating Title V agencies' progress toward birth equity. ASSESSMENT: This CDC initiative was transformative in that it raised the visibility of African American researchers, moved the field from a focus on traditional epidemiologic risks such as personal health promotion and medical interventions, to include racism as a risk factor for inequitable birth outcomes. The paradigm examined the specific roles of historical and structural racism, and the racialized, contextualized, and temporal exposures that are unique to Black women's experiences in the United States. CONCLUSION: The initiative radically changed the narratives about the underlying factors contributing to inequities in birth outcomes of Black women, altered the way we currently approach addressing inequities, and holds the keys for transforming practice to a more holistic and systematic approach to building sustained organizational structures in maternal and child health that accelerate the achievement of birth equity.

Evaluation of Chemotherapy Induced Peripheral Neuropathy, Sarcopenia and Fatigue in Children with Acute Lymphoblastic Leukaemia and Lymphoma in Tertiary Care Hospital, Dakshina Kannada.

Objectives: The study aims to assess the proportion and magnitude of chemotherapy-induced peripheral neuropathy (CIPN) and other common complications reported in children with acute lymphoblastic leukaemia (ALL)/ acute lymphoblastic lymphoma (LBL) undergoing chemotherapy. Material and Methods: The study included children between 5 and 18 years old with ALL/LBL undergoing chemotherapy in Tertiary Care Hospitals, Mangalore. The study was conducted using various instruments, including paediatric-modified total neuropathy scale for CIPN, handheld dynamometer for muscle strength, bioimpedance analyser for muscle mass, timed up-and-go test for physical performance, and national comprehensive cancer network (NCCN) guidelines for scoring cancer-related fatigue at 3-time points. The collected data were analysed by IBM Statistical Package for the Social Sciences version 29 using Z-scores with standard deviation for distinct ALL/LBL types. In addition, the Paired t-test compared the baseline outcome to the 3rd and 6th time points. Results: The study evaluated 25 children with ALL undergoing chemotherapy based on the UKALL 2003 protocol during their maintenance phase. The study found that 25 children experienced CIPN, with changes in sensory and pin sensibility scores at 3 and 6 months. The study found a significant change in handgrip strength, body mass index, and muscle mass at 3 months, with no significant change in physical performance over time. Fatigue scores increased from baseline to 3 months, with significant changes observed for the 7-12 years age group at 3 months but not for the 5-6 years age group at 6 months. Conclusion: Children with ALL/LBL undergoing chemotherapy experience CIPN and other side effects such as sarcopenia and fatigue. The study highlights the potential benefits of physiotherapy interventions and supportive care strategies aimed at managing the adverse effects of chemotherapy in children with ALL/LBL.

Transcriptional regulation of wound suberin deposition in potato cultivars with differential wound healing capacity.

Wounding during mechanical harvesting and post-harvest handling results in tuber desiccation and provides an entry point for pathogens resulting in substantial post​-harvest crop losses. Poor wound healing is a major culprit of these losses. Wound tissue in potato (Solanum tuberosum) tubers, and all higher plants, is composed of a large proportion of suberin that is deposited in a specialized tissue called the wound periderm. However, the genetic regulatory pathway controlling wound-induced suberization remains unknown. Here, we implicate two potato transcription factors, StMYB102 (PGSC0003DMG400011250) and StMYB74 (PGSC0003DMG400022399), as regulators of wound suberin biosynthesis and deposition. Using targeted metabolomics and transcript profiling from the wound healing tissues of two commercial potato cultivars, as well as heterologous expression, we provide evidence for the molecular-genetic basis of the differential wound suberization capacities of different potato cultivars. Our results suggest that (i) the export of suberin from the cytosol to the apoplast and ligno-suberin deposition may be limiting factors for wound suberization, (ii) StMYB74 and StMYB102 are important regulators of the wound suberization process in tubers, and (iii) polymorphisms in StMYB102 may influence cultivar-specific wound suberization capacity. These results represent an important step in understanding the regulated biosynthesis and deposition of wound suberin and provide a practical foundation for targeted breeding approaches aimed at improving potato tuber storage life.

Prevalence and predictors of metabolically healthy obesity in severely obese Asian children.

BACKGROUND: Obese individuals who have little or no metabolic syndrome components are proposed to be "metabolically healthy obese (MHO)". This study aim to evaluate the prevalence of MHO and examine the predictors associated with MHO in a multi-ethnic Asian cohort of severely obese children. METHODS: This study included a cross-sectional cohort of 406 Chinese, Malay and Indian children aged 5-20 years old with BMI for age ≥ 97th percentile. Metabolic syndrome (MS) and metabolic health (MH) definitions based on the presence or absence of metabolic abnormalities (High triglycerides, low HDL cholesterol, elevated blood pressure and high glucose) were used to define MHO in the cohort. RESULTS: The prevalence of MHO is 63.5% by MS definition and 22.4% by MH definition. Maternal healthy metabolic status (OR: 2.47), age (OR: 0.83, 0.80), paternal obesity (OR: 0.48, 0.53), Malay (OR: 1.97) and Indian ethnicity (OR: 6.38, 3.21) (compared to Chinese ethnicity) are independent predictors for MHO phenotype based on different MHO definitions. CONCLUSIONS: Adiposity measures are not associated with MHO phenotype, but instead younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype in a multi-ethnic Asian cohort of severely obese children. IMPACT: The prevalence of metabolically healthy obese (MHO) in our multi-ethnic Asian cohort of severely obese children is 63.5% and 22.4%, respectively, based on different MHO definitions. Adiposity measures are not associated with the MHO phenotype. There are other factors that contribute to the metabolic phenotype in obese individuals. Younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype. Parental influence is important in predicting metabolic health in obese individuals.

Life in lockdown: impact of COVID-19 lockdown measures on the lives of visually impaired school-age children and their families in India.

PURPOSE: The COVID-19 outbreak has adversely impacted all societal domains including education. Home confinement, school closures and distance learning impacted children's, teachers' and parents' lives worldwide. In this study, we aimed to examine the impact of the COVID-19 lockdown on the lives, including education, of school-age children with vision impairment (VI) and their parents in India. METHODS: Primary and secondary school children with VI were recruited from the Institute for Vision Rehabilitation, L V Prasad Eye Institute, Hyderabad, India. A qualitative research methodology, utilising a self-constructed questionnaire with open and closed questions and stem and leaf design, was employed to explore the experiences of school closure and its impact on education and attending online classes during the COVID-19 lockdown. Textual data from responses to the questions were analysed using content analysis to identify themes pertinent to the cohort studied. RESULTS: Forty eight child-parent dyads were included. The median age of children was 10 years (range, 7-19 years) and 60% were male. Inherited retinal disorders were the major cause of VI (40%). Best spectacle corrected visual acuity (better eye) ranged from 0.30 to 2.09 logMAR (6/12 to 6/750). Six major themes were identified: (1) accessibility of technology (online learning and technology); (2) parental beliefs/concerns (harmful effects of technology, prioritisation of normally sighted children, online classes considered a distraction); (3) support (peers, parents, teachers, private tuition); (4) socialisation and physical activity; (5) socioeconomic status and (6) near vision. CONCLUSIONS: This study provides an understanding of the adverse impact of lockdown on the lives of children with VI and their parents, especially related to education in India. The study identified critical factors that affect online learning and the participation of children with VI in these sessions. Policymakers and educators should implement effective measures for supporting online classes.

Factors affecting quality of life in keratoconus.

PURPOSE: To identify the factors affecting the quality of life (QoL) in adults with keratoconus, using the disease-specific Keratoconus Outcomes Research Questionnaire (KORQ). METHODS: In this cross-sectional study, 574 patients with keratoconus completed the 29-item KORQ (18-item activity limitations and 11-item symptoms subscales) and demographic information. Based on mean corneal curvature to grade keratoconus severity, participants were categorised into four groups: mild <48 dioptres [D]; moderate: 48 to 53 D; advanced: 54 to 55 D and severe: >55D. Rasch analysis was used to assess the psychometric properties and to score the KORQ. Multivariable regression was performed to determine the independent impact of age, sex, laterality, severity and duration of keratoconus, education, employment status and mode of treatment for keratoconus on activity limitations and symptoms. RESULTS: Mean (SD) age was 24.5 (5.1) years. 304 (53%), 160 (28%), 26 (4%) and 84 (15%) belonged to keratoconus groups 1, 2, 3 and 4, respectively. Rasch analysis demonstrated the 'activity limitations' and 'symptoms' KORQ subscales to possess good psychometric properties. Statistically significant associations were found between activity limitation score and the following measures: visual acuity (VA) in the better-seeing eye (r = -0.10, p = 0.01); VA in the worse-seeing eye (r = -0.09, p = 0.04) and ocular aberrations (r = -0.13, p = 0.008) in the worse-seeing eye. Statistically significant associations were also found between symptoms score and mean corneal curvature in the better-seeing eye (r = -0.10, p = 0.02). In regression models, female sex was associated with 21% worse symptom score than male (ß = -0.33, 95% CI, -0.09, -0.59, p = 0.01) and working people experienced clinically and statistically significantly greater trouble from symptoms compared to those not working (ß =0.44, 95% CI, 0.17, 0.70, p = 0.001). CONCLUSIONS: People with keratoconus have poorer QoL in terms of activity limitations if they have poorer VA and greater wavefront aberrations, and in terms of symptoms if they are female and employed.

Neuromuscular Complications of Statin Therapy.

PURPOSE OF REVIEW: This review provides an overview of neuromuscular side effects associated with statin use, their diagnosis, and treatment. RECENT FINDINGS: The discovery of anti-HMGCR antibodies led to a better understanding of clinical aspects of statin-associated anti-HMGCR myopathy and its treatment. Statins are widely prescribed medications with well-established benefits in the treatment of cardiovascular diseases and stroke. Adherence to statins is influenced by development of side effects, especially muscle related. There is wide range of neuromuscular side effects associated with statin therapy. Documented neuromuscular side effects include asymptomatic elevation of muscle enzymes, mild-moderate myalgias and cramps, toxic and immune-mediated severe necrotizing myopathy, and rare cases of rhabdomyolysis. In addition, statins can lead to unmasking or triggering of underlying muscle and neuromuscular junction disorders. This article identifies the risk factors and provides a review of neuromuscular side effects associated with statin use, their diagnosis and treatment.

A Pilot Trial Examining the Merits of Combining Amantadine and Repetitive Transcranial Magnetic Stimulation as an Intervention for Persons With Disordered Consciousness After TBI.

OBJECTIVE: Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. PARTICIPANTS: Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). DESIGN: Alternate treatment-order, within-subject, baseline-controlled trial. MAIN MEASURES: For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. RESULTS: Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. CONCLUSIONS: For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

Tryptophan 32 mediates SOD1 toxicity in a in vivo motor neuron model of ALS and is a promising target for small molecule therapeutics.

SOD1 misfolding, toxic gain of function, and spread are proposed as a pathological basis of amyotrophic lateral sclerosis (ALS), but the nature of SOD1 toxicity has been difficult to elucidate. Uniquely in SOD1 proteins from humans and other primates, and rarely in other species, a tryptophan residue at position 32 (W32) is predicted to be solvent exposed and to participate in SOD1 misfolding. We hypothesized that W32 is influential in SOD1 acquiring toxicity, as it is known to be important in template-directed misfolding. We tested if W32 contributes to SOD1 cytotoxicity and if it is an appropriate drug target to ameliorate ALS-like neuromuscular deficits in a zebrafish model of motor neuron axon morphology and function (swimming). Embryos injected with human SOD1 variant with W32 substituted for a serine (SOD1W32S) had reduced motor neuron axonopathy and motor deficits compared to those injected with wildtype or disease-associated SOD1. A library of FDA-approved small molecules was ranked with virtual screening based on predicted binding to W32, and subsequently filtered for analogues using a pharmacophore model based on molecular features of the uracil moiety of a small molecule previously predicted to interact with W32 (5'-fluorouridine or 5'-FUrd). Along with testing 5'-FUrd and uridine, a lead candidate from this list was selected based on its lower toxicity and improved blood brain barrier penetrance; telbivudine significantly rescued SOD1 toxicity in a dose-dependent manner. The mechanisms whereby the small molecules ameliorated motor neuron phenotypes were specifically mediated through human SOD1 and its residue W32, because these therapeutics had no measurable impact on the effects of UBQLN4D90A, EtOH, or tryptophan-deficient human SOD1W32S. By substituting W32 for a more evolutionarily conserved residue (serine), we confirmed the significant influence of W32 on human SOD1 toxicity to motor neuron morphology and function; further, we performed pharmaceutical targeting of the W32 residue for rescuing SOD1 toxicity. This unique residue offers future novel insights into SOD1 stability and toxic gain of function, and therefore poses an potential target for drug therapy.

Psychometric Properties of an Indian Translation of the Vision-related Activity Limitation Item Bank in Cataract.

SIGNIFICANCE: The Indian translated and culturally adapted version of the vision-related activity limitation (VRAL) item bank is a validated instrument to assess the difficulty in performing daily activities by cataract patients and can also be used to capture self-reported changes in ability to perform daily activities after cataract surgery. PURPOSE: The purpose of this study was to document (a) translation, cross-cultural adaptation of VRAL item bank into an Indian language, and (b) its validation using Rasch analysis in a South Indian cataract population. METHODS: At the first stage, a translated Indian version of VRAL item bank was produced using recommended procedures. At the second stage, Rasch analysis was performed to investigate its psychometric properties in 787 cataract patients (mean age, 58.2 years; mean ± SD visual acuity [logMAR], 1.19 ± 0.96 at baseline in eye for surgery) including comparison with the original version. RESULTS: Post-translation equivalence of meaning was achieved, but some English phrases required cross-cultural adaptation. Subsequently, all items were appropriate for the Indian culture, and VRAL item bank demonstrated excellent measurement precision (7.39). Dimensionality assessment suggested that VRAL construct may contain other dimensions such as self-care and visual search, and mobility. Self-care and visual search formed a unidimensional measure but was highly correlated with main VRAL dimension, and the removal of its items weakened precision of the main VRAL dimension measurement. Taken together, evidence favored retaining self-care and visual search items in a larger VRAL item bank. Mobility subscale lacked adequate measurement precision, so it was not examined further; again, items were retained in VRAL scale because they strengthened its measurement properties. Majority of items (99%) did not demonstrate notable differential item functioning (>1.0 logit) by presenting visual acuity (median, 0.20 logMAR) in the better-seeing eye. CONCLUSIONS: Items in the translated Indian VRAL item bank measure the same construct as the English version and fulfilled the psychometric requirements for use in cataract patients.

Randomized Trial of Tablet Computers for Education and Learning in Children and Young People with Low Vision.

SIGNIFICANCE: Mobile devices such as tablet computers have become widely available as mainstream devices and are also used in some schools, but there is an absence of robust information regarding the efficacy of any optical/electronic low vision device or tablet computer in supporting education of young people with low vision. PURPOSE: A randomized controlled trial (RCT) is needed to measure the impact of tablet computers on education, specifically on independent access to educational material, in children and young people with low vision. We conducted a pilot RCT to determine the feasibility of conducting a full-scale trial. METHODS: This was a randomized multicenter pilot trial across two sites in the United Kingdom and one site in India. Forty children and young people aged 10 to 18 years with low vision (best-corrected visual acuity for distance between <20/60 [0.48 logMAR] and 20/400 [1.30 logMAR] in the better eye) in the United Kingdom (n = 20) and India (n = 20) were randomized to two parallel arms, with a 1:1 allocation ratio, to control (n = 20) or intervention (n = 20). Control group participants received standard low vision care. The intervention group received a tablet computer (iPad) with low vision applications and instruction in its use, including accessibility features. Four primary outcomes included (1) 6-month recruitment rate, (2) retention of participants for 3 months, (3) acceptance/usage of device, and (4) accessibility of device. RESULTS: Nineteen participants (95%) enrolled within 6 months in the United Kingdom, and 20 participants (100%), in India. Retention at 3 months was 85% (n = 17) in the United Kingdom and 95% (n = 19) in India. More than one half of participants reported using a tablet computer at school at least once every day. The majority (90%) found it easily accessible. CONCLUSIONS: This study demonstrated that it is feasible to recruit children and young people with low vision into an international multicenter RCT of electronic assistive technology. Regardless of geographical location, children and young people with low vision reported using tablet computers at least once a day at school and accessed them easily.