"I can't provide what my child needs": Early feeding experiences of caregivers of children with craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) is a congenital condition that can be associated with feeding challenges in infants. As part of the larger 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program, this study described caregivers' early feeding experiences. DESIGN AND MATERIALS: US-based caregivers of 34 children with CFM participated in remote narrative interviews. Two authors completed inductive thematic analysis in an iterative process until consensus was reached. RESULTS: Caregivers' narratives outlined the inherent challenges of feeding an infant with special healthcare needs. The first theme 'Navigating Challenges and Managing Expectations' describes the distress participants experienced when they were unable to breastfeed and the negative emotional effect of switching to formula. The second theme 'Making Adaptations' outlines the methods participants tried, including breast pumps and feeding tubes. The third theme 'Accessing Support' describes participants' interactions with healthcare providers and challenges accessing feeding support. The final theme 'Growing from Adversity' recounts participants' relief once their child established a feeding pattern and the personal growth gained from their experiences. CONCLUSIONS: Caregivers reported several feeding related challenges associated with CFM, many of which negatively affected their wellbeing. Negative consequences were particularly pronounced in cases where caregivers' feeding experiences differed from their expectations. Participants identified challenges in accessing reliable feeding information and support. Despite difficult experiences, caregivers cited some positive outcomes, including increased confidence and resilience. PRACTICE IMPLICATIONS: Holistic feeding information and support for families affected by CFM should be inclusive of several feeding methods to improve care delivery, child health, and the caregiver experience.

Titanium dioxide nanotubes applied to conventional glass ionomer cement influence the expression of immunoinflammatory markers: An in vitro study.

Objectives: To assess the impact of different concentrations TiO2-nt incorporated into a glass ionomer cement on the proliferation, mitochondrial metabolism, morphology, and pro- and anti-inflammatory cytokine production of cultured fibroblasts (NIH/3T3), whether or not stimulated by lipopolysaccharides (LPS-2 µg/mL, 24 h). Methods: TiO2-nt was added to KM (Ketac Molar EasyMix™, 3 %, 5 %, 7 % in weight); unblended KM was used as the control. The analyses included: Cell proliferation assay (n = 6; 24/48/72h); Mitochondrial metabolism assay (n = 6; 24/48/72h); Confocal laser microscopy (n = 3; 24/48/72h); Determination of biomarkers (IL-1ß/IL-6/IL-10/VEGF/TNF) by using both multiplex technology (n = 6; 12/18 h) and the quantitative real-time PCR assay (q-PCR) (n = 3, 24/72/120 h). The data underwent analysis using both the Shapiro-Wilk and Levene tests, and by generalized linear models (α = 0.05). Results: It demonstrated that cell proliferation increased over time, regardless of the presence of TiO2-nt or LPS, and displayed a significant increase at 72 h; mitochondrial metabolism increased (p < 0.05), irrespective of exposure to LPS (p = 0.937); no cell morphology changes were observed; TiO2-nt reverted the impact of KM on the secreted levels of the evaluated proteins and the gene expressions in the presence of LPS (p < 0.0001). Conclusions: TiO2-nt did not adversely affect the biological behavior of fibroblastic cells cultured on GIC discs.

Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy.

BACKGROUND: Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function. This study investigates the expression profile of miR-181a/b in RPE cells and the neural retina during RP disease progression. We also evaluate how miR-181a/b downregulation, by knocking out miR-181a/b-1 cluster in RPE cells, confers therapeutic efficacy in an RP mouse model and explore the mechanisms underlying this process. RESULTS: Our findings reveal distinct expression profiles, with downregulated miR-181a/b in RPE cells suggesting a protective response and upregulated miR-181a/b in the neural retina indicating a role in disease progression. We found that miR-181a/b-2, encoded in a separate genomic cluster, compensates for miR-181a/b-1 ablation in RPE cells at late time points. The transient downregulation of miR-181a/b in RPE cells at post-natal week 6 (PW6) led to improved RPE morphology, retarded photoreceptor degeneration and decreased RPE aerobic glycolysis. CONCLUSIONS: Our study elucidates the underlying mechanisms associated with the therapeutic modulation of miR-181a/b, providing insights into the metabolic processes linked to its RPE-specific downregulation. Our data further highlights the impact of compensatory regulation between miR clusters with implications for the development of miR-based therapeutics.

A Conceptual Thematic Framework of Psychological Adjustment in Caregivers of Children with Craniofacial Microsomia.

OBJECTIVE: Children with craniofacial microsomia (CFM) have complex healthcare needs, resulting in evaluations and interventions from infancy onward. Yet, little is understood about families' treatment experiences or the impact of CFM on caregivers' well-being. To address this gap, the NIH-funded 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program sought to develop a conceptual thematic framework of caregiver adjustment to CFM. DESIGN: Caregivers reported on their child's medical and surgical history. Narrative interviews were conducted with US caregivers (n = 62) of children aged 3-17 years with CFM. Transcripts were inductively coded and final themes and subthemes were identified. RESULTS: Components of the framework included: 1) Diagnostic Experiences, including pregnancy and birth, initial emotional responses, communication about the diagnosis by healthcare providers, and information-seeking behaviors; 2) Child Health and Healthcare Experiences, including feeding, the child's physical health, burden of care, medical decision-making, surgical experiences, and the perceived quality of care; 3) Child Development, including cognition and behavior, educational provision, social experiences, and emotional well-being; and 4) Family Functioning, including parental well-being, relationships, coping strategies, and personal growth. Participants also identified a series of "high" and "low" points throughout their journey and shared their priorities for future research. CONCLUSIONS: Narrative interviews provided rich insight into caregivers' experiences of having a child with CFM and enabled the development of a conceptual thematic framework to guide clinical care and future research. Information gathered from this study demonstrates the need to incorporate evidence-based psychological support for families into the CFM pathway from birth onward.

Kaplan-Meier Survival Analysis: Practical Insights for Clinicians.

This article aims to provide a guide that will help healthcare professionals and clinical researchers from all fields that deal with Kaplan-Meier curves. Survival analysis methods are among the most frequently used in the medical sciences and in clinical research. Overall survival, progression free survival, time to recurrence, or any other clinically relevant parameter represented by a Kaplan-Meier curve will be discussed. We will present a practical and straightforward interpretation of these curves, setting aside intricate mathematical considerations. Our focus will be on essential concepts that interface with biological sciences and medicine in order to guarantee proficiency in one of the most popular yet frequently misunderstood methods in clinical research. Being familiar with these concepts is not only essential for designing new clinical studies but also for critically assessing and interpreting published data.

Bigger calves from doing higher resistance training volume?

We compared the effects of different calf training weekly sets on muscle size changes. Sixty-one untrained young women performed a calf training program for 6 weeks, 3 d·wk-1, with differences in the resistance training volume. The participants were randomly assigned to 1 of the 3 groups: 6-SET, 9-SET, and 12-SET calf training weekly sets. The calf raise exercise was performed in sets of 15-20 repetitions maximum. The muscle thickness measurements of medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) were taken via B-mode ultrasound. We used the sum of the three-muscle thickness as a proxy for the triceps surae (TSSUM). The 12-SET group elicited greater increases than 6-SET in LG (6-SET = +8.1% vs. 12-SET = +14.3%; P = 0.017), SOL (6-SET = +6.7% vs. 12-SET = +12.7%; P = 0.024), and TSSUM (6-SET = +6.9% vs. 12-SET = +12.0%; P = 0.005), but there was no significant difference in MG changes (6-SET = +6.6% vs. 12-SET = +9.9%; P = 0.067). There were no significant differences when comparing 9-SET vs. 6-SET and 12-SET (P ≥ 0.099). Although all groups experienced calf muscle hypertrophy, our results suggest that the higher dose range may optimize triceps surae muscle size gains.

Assessing Appearance, Speech, and Hearing (dis)Satisfaction in Individuals with Cleft Lip and/or Palate: A Contribution to General Population Norms.

BACKGROUND: Individuals with cleft lip and/or palate (CL/P) may grow up with a visible facial difference, alongside speech and/or hearing challenges. Self-perceptions are stronger predictors of psychosocial adjustment than objective assessments, highlighting the importance of patient-reported outcome measures. Previously titled the Satisfaction with Appearance (SwA) questionnaire, the Cleft Hearing, Appearance and Speech Questionnaire (CHASQ) has been used in several countries to assess patient satisfaction, guide clinical decision-making, and conduct craniofacial research, but has lacked general population norms from which to draw comparisons. The aim of this study was to contribute to the development of norms by utilising existing data collected in the United Kingdom (UK) in 2004 using the original SwA. METHODS: SwA data collected from school pupils (n = 761) aged 10-16 years were analysed across age and gender. RESULTS: Hair, Eyes and Ears received the highest ratings, while Teeth received the lowest ratings. Those who were younger, and those who were male, generally rated their appearance more favourably. Thresholds are proposed to identify young people in need of clinical monitoring (10%) and intervention (5%). DISCUSSION: This study supports the potential of the CHASQ as a clinically useful outcome measure and research tool with the ability to identify appearance concerns in relation to specific facial features, as well as overall appearance satisfaction in young people with and without CL/P. Further validation of its use in the CL/P population and other patient groups, as well as countries outside the UK would add additional weight to the CHASQ's utility.

"When I was Younger, My Story Belonged to Everyone Else": Co-production of Resources for Adults Living with Craniosynostosis.

OBJECTIVE: Despite growing recognition that congenital craniofacial conditions have lifelong implications, psychological support for adults is currently lacking. The aim of this project was to produce a series of short films about living with craniosynostosis in adulthood, alongside a psychoeducational booklet. DESIGN: The resources were developed using multiple focus groups and meetings attended by researchers, patient representatives, a leading charitable organisation, an award-winning film production company, clinicians, and other experts in the field. RESULTS: An online mixed-methods survey was developed based on prior work to request feedback on the acceptability and utility of the resources from the craniosynostosis community. While data collection to evaluate the resources is ongoing, preliminary results (n = 36) highlight an acceptability rating of 100%. CONCLUSIONS: The resources developed represent a step forward in addressing the unmet information and support needs of adults with craniosynostosis and highlight the benefits of co-production in research.

Determining Changes in Muscle Size and Architecture After Exercise Training: One Site Does Not Fit all.

ABSTRACT: Nunes, JP, Blazevich, AJ, Schoenfeld, BJ, Kassiano, W, Costa, BDV, Ribeiro, AS, Nakamura, M, Nosaka, K, and Cyrino, ES. Determining changes in muscle size and architecture after exercise training: One site does not fit all. J Strength Cond Res 38(4): 787-790, 2024-Different methods can be used to assess muscle hypertrophy, but the effects of training on regional changes in muscle size can be detected only using direct muscle measurements such as muscle thickness, cross-sectional area, or volume. Importantly, muscle size increases vary across regions within and between muscles after resistance training programs (i.e., heterogeneous, or nonuniform, muscle hypertrophy). Muscle architectural changes, including fascicle length and pennation angle, after resistance and stretch training programs are also region-specific. In this paper, we show that the literature indicates that a single-site measure of muscle shape does not properly capture the effects achieved after exercise training interventions and that conclusions concerning the magnitude of muscle adaptations can vary substantially depending on the muscle site to be examined. Thus, we propose that measurements of muscle size and architecture should be completed at multiple sites across regions between the agonist muscles within a muscle group and along the length of the muscles to provide an adequate picture of training effects.

Early Experiences of Parents of Children With Craniofacial Microsomia.

OBJECTIVE: To describe the early health care experiences of parents of children with craniofacial microsomia (CFM), a congenital diagnosis often identified at birth. DESIGN: Qualitative descriptive. SETTING: Homes of participants. PARTICIPANTS: Parents of 28 children with CFM from across the United States. METHODS: We interviewed participants (27 mothers individually and one mother and father together) via telephone or teleconference and used reflexive thematic analysis to derive themes that represented early health care experiences of parents of children with CFM. RESULTS: Participants' narratives included detailed recounting of their birth and early care experiences. We identified two overarching themes. The first overarching theme, Stressors, included four subthemes that represented difficulties related to emotional reactions and negative experiences with health care providers. The second overarching theme, Finding Strength, included four subthemes that represented participants' positive adjustment to stressors through independent information seeking about CFM, adaptive coping, positive experiences with health care providers, and drawing on external supports. CONCLUSION: Participants often described early experiences as challenging. Findings have implications for improving early care, including increasing open and supportive communication by health care professionals, expanding access to CFM information, screening for mental health concerns among parents, strengthening coping among parents, and linking families to resources such as reliable online CFM information and early intervention programs.

Human blood markers of cholinergic neurotoxicity and neuropathy: A useful guide for laboratory applications.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are useful markers to assess the effects of exposure to anticholinesterase insecticides (Anti-AChE). In addition, lymphocyte neuropathy target esterase (LNTE) has been used as biomarker of neuropathic organophosphate compounds (OPs). Thus, this study evaluates the main types of circulating biomarkers related to the cholinergic system and to the neuropathy induced by OPs in standardized human samples. To achieve this objective, total protein of human plasma, erythrocytes and lymphocytes were first standardized, and then AChE, BChE and LNTE activities in human blood were evaluated in the presence of inhibitors. The acceptance criteria of the regulatory agency were respected with coefficients of regression of curves of 0.9972 for cholinesterase and 0.9956 for LNTE analyses. The wavelength established to perform cholinesterase assay was 450 nm and the time of incubation of the enzymes with inhibitors was 30 min. Differences were observed among the IC50 values regarding the in vitro inhibition of AChE, BChE and LNTE in the presence of OPs. In conclusion, the procedures demonstrated by the present work were simple, fast, inexpensive, sensitive, easy to be replicated and suitable to make conclusions about the neurotoxicity induced by Anti-AChE and neuropathic OPs.

Cryopreservation-Induced Morphological Changes in Freshwater Fish Sperm: A Systematic Review.

A systematic review was performed to summarize the scientific evidence and critically evaluate the effects of cryopreservation on sperm morphology in freshwater fish, and to assess the methodologies for sperm morphology classification. The search strategy was applied to four electronic databases (CAB Direct, Pub Med, Scopus, and ISI Web of Science). The main inclusion criteria involved studies on semen from freshwater fish subjected to the cryopreservation process and evaluation of sperm quality through morphology. The risk of bias was assessed with respect to randomization, allocation concealment, blinding, incomplete outcome data, and selective reporting. A total of 6 publications reporting sperm cryopreservation from 4 species with a total 74 fish individuals were included in this review. A high methodological variability among the results of the studies was observed due to the species-specific protocols and diversity of freshwater fish species studied. All included studies reported negative effects of cryopreservation on sperm quality, especially morphology, highlighting the increase in incidence of sperm abnormalities. However, only five studies statistically compared abnormalities between groups (fresh and cryopreserved sperm). Our results suggest the need to elaborate on a new morphological classification of fish spermatozoa, by considering the structure and physiology of fish sperm. This classification should be developed based on the sperm characterization and observing damage caused by different cryopreservation protocols.

A longitudinal analysis of the fluctuation of food stores in Belo Horizonte, Minas Gerais, Brazil.

BACKGROUND: Changes in food environments have the potential to affect consumption, nutritional status, and health, and understanding these changes is of utmost importance. This study, therefore, aimed to examine the fluctuation of food stores that sell fruits and vegetables over five years in the health promotion service area of Primary Health Care (PHC) in Belo Horizonte, Minas Gerais, Brazil. METHODS: This was an ecological study that used data from a food environment audit conducted in the realm of Brazilian PHC. Buffers of 1 mile (equivalent to 1600 m) were created around health promotion services to define food environments. All food stores and open-air food markets that sold fruits and vegetables (FV) within this buffer area were considered eligible. The data collection was performed during two periods: the baseline, in 2013, and after five years, in 2018. This study compares the fluctuation by the type of stores and according to the health vulnerability index (HVI). RESULTS: After 5 years, 35.2% of the stores were stable; 154 stores were closed, and 155 were opened. The stability was greater in low-vulnerability areas, and the fluctuation differed by type of store only for areas with high vulnerability. The number of supermarket decreased in high HVI territories; and local stores, showed greater stability when compared to specialized FV markets. CONCLUSIONS: The differences in store fluctuations according to the vulnerability of areas demonstrate the importance of food supply policies considering the local characteristics to reduce inequities of access to healthy foods.

'Scars: How Our Wounds Make Us Who We Are': Improving appearance-based stigma, conceptualisation of beauty and body esteem through a documentary.

Introduction: Those with an altered appearance as a result of injury, health condition or treatment can face stigma, which may contribute to adverse psychosocial outcomes. However, current research tends to focus on supporting individuals themselves to cope, rather than targeting societal stigma. This study aimed to reduce societal stigma towards this group, through the use of a documentary about people with scars. Methods: 146 adults completed questionnaires before and after viewing the documentary. Results: After viewing, participants had reduced self-reported intentions to behave in a stigmatising way towards those with visible differences, broader conceptualisation of beauty, and more positive body-esteem. Qualitative data also suggested further positive impacts. Conclusion: Those with visible differences (for example scars) are subject to societal stigmatisation which perpetuates psychological and social problems. Therefore, alleviating social stigma through the media, as demonstrated through the documentary in this study, may improve the lives of those living with visible differences. Lay Summary: People with an altered appearance or scars as a result of injury, health condition or treatment can face stigma, which may contribute to harmful psychological and social outcomes. However, current research tends to focus on supporting affected individuals themselves to cope, rather than targeting societal stigma. This study aimed to find out whether a documentary about people with scars was successful at reducing viewers' stigma towards this group. A group of 146 adults completed questionnaires before and after viewing the documentary. After viewing, questionnaires indicated that participants had reduced intentions to behave in a stigmatising way towards those with visible differences. Furthermore, they also viewed a broader range of appearances as beautiful and felt more positive about their own bodies. Comments and feedback from participants also suggested further positive impacts. Those with visible differences (for example scars) are subject to societal stigmatisation which can cause and worsen mental health problems. Therefore, alleviating social stigma through the media, as demonstrated through the documentary in this study, may improve the lives of those living with visible differences.

Immobilization of Horseradish Peroxidase on Ca Alginate-Starch Hybrid Support: Biocatalytic Properties and Application in Biodegradation of Phenol Red Dye.

In this study, horseradish peroxidase was extracted, purified, and immobilized on a calcium alginate-starch hybrid support by covalent bonding and entrapment. The immobilized HRP was used for the biodegradation of phenol red dye. A 3.74-fold purification was observed after precipitation with ammonium sulfate and dialysis. An immobilization yield of 88.33%, efficiency of 56.89%, and activity recovery of 50.26% were found. The optimum pH and temperature values for immobilized and free HRP were 5.0 and 50 °C and 6.5 and 60 °C, respectively. The immobilized HRP showed better thermal stability than its free form, resulting in a considerable increase in half-life time (t1/2) and deactivation energy (Ed). The immobilized HRP maintained 93.71% of its initial activity after 45 days of storage at 4 °C. Regarding the biodegradation of phenol red, immobilized HRP resulted in 63.57% degradation after 90 min. After 10 cycles of reuse, the immobilized HRP was able to maintain 43.06% of its initial biodegradative capacity and 42.36% of its enzymatic activity. At the end of 15 application cycles, a biodegradation rate of 8.34% was observed. In conclusion, the results demonstrate that the immobilized HRP is a promising option for use as an industrial biocatalyst in various biotechnological applications.

Availability and price of fruits and vegetables in the surroundings of food and nutrition public establishments.

BACKGROUND: Inequalities of access to healthy food reinforce the need to strengthen public policies on Food and Nutritional Security. In this context, Food and Nutrition Public Establishments, which are public spaces for distribution and commercialization of healthy foods, stand out. However, in middle-income countries there is little monitoring of the impacts of public policies on food environments, which are fundamental for strengthening these actions. Thus, the purpose of the study was to evaluate the availability and price of fruits and vegetables in areas with and without Food and Nutrition Public Establishments. METHODOLOGY: A cross-sectional study carried out in Belo Horizonte, Brazil. Audits were conducted in the retail food environment of a representative sample of Food and Nutrition Public Establishments (n = 10) and corresponding census sectors, without Food and Nutrition Public Establishments (n = 10). Information was collected on the availability and price of the most consumed fruits and vegetables in Belo Horizonte. The food retailers were grouped into fresh food retailers and mixed food retailers. The Chi-Square test was used to compare the availability of fruits and vegetables between areas. The Mann Whitney test was used to compare the prices of fruit and vegetables and the price differences between fresh food retailers and mixed food retailers between areas. RESULTS: 148 food retailers were audited, including 17 Food and Nutrition Public Establishments. In fresh food retailers, the availability of vegetables was higher in areas with Food and Nutrition Public Establishments (p = 0.024). In mixed food retailers there was low availability of fruit and vegetables in both areas (34.0% vs. 26.2%; p>0.05). The price difference between fresh food retailers and mixed food retailers differed significantly between areas (p<0.001). In general, fresh food retailers had lower prices than mixed food retailers only in areas with Food and Nutrition Public Establishments. CONCLUSIONS: The presence of Food and Nutrition Public Establishments was associated with the availability of vegetables, and with lower prices in fresh food retailers compared with mixed food retailers. Monitoring and understanding the impacts of public policies on the food environment are essential to register trends and provide relevant information to civil society and government authorities.

Food and nutrition public establishments: assessment of the food environment.

This article aims to assess the community food environment around areas with and without Food and Nutrition Public Establishments (FNPE). Cross-sectional study carried out in Belo Horizonte, Brazil. The unit of analysis was the buffer (500m) around the FNPE and the census tracts without FNPE. The investigated establishments should market food for consumption at home and be located within the buffer of the areas with and without FNPE. Data collection performed by direct observation (active search) in August to October 2019. Data collected were location and type of commercial establishments, the density of the establishments was calculated. Descriptive analysis, spatial distribution (Kernel estimator) and Nearest Neighbor analysis were performed. Of the evaluated establishments, 60.5% were in the areas without FNPE and 39.6% in the areas with FNPE, showing a random distribution pattern. Of these, 24.2% were convenience stores and bakeries, 21.0% butcher stores, and 19.0% street markets. Seven FNPE were close to commercial establishments. There were fewer establishments around the FNPE, with convenience stores and bakeries predominating.

Food and nutrition public establishments: assessment of the food environment / Equipamentos públicos de segurança alimentar e nutricional: avaliação do ambiente alimentar

Abstract This article aims to assess the community food environment around areas with and without Food and Nutrition Public Establishments (FNPE). Cross-sectional study carried out in Belo Horizonte, Brazil. The unit of analysis was the buffer (500m) around the FNPE and the census tracts without FNPE. The investigated establishments should market food for consumption at home and be located within the buffer of the areas with and without FNPE. Data collection performed by direct observation (active search) in August to October 2019. Data collected were location and type of commercial establishments, the density of the establishments was calculated. Descriptive analysis, spatial distribution (Kernel estimator) and Nearest Neighbor analysis were performed. Of the evaluated establishments, 60.5% were in the areas without FNPE and 39.6% in the areas with FNPE, showing a random distribution pattern. Of these, 24.2% were convenience stores and bakeries, 21.0% butcher stores, and 19.0% street markets. Seven FNPE were close to commercial establishments. There were fewer establishments around the FNPE, with convenience stores and bakeries predominating.

Resumo O objetivo deste artigo é avaliar o ambiente alimentar comunitário de áreas com e sem estabelecimentos públicos de segurança alimentar e nutricional (EPSAN). Estudo transversal realizado em Belo Horizonte, Brasil. Unidade de análise foi o buffer (500m) no entorno dos EPSAN e dos setores censitários sem EPSAN. Os estabelecimentos investigados deveriam comercializar alimentos para consumo no domicílio e localizar-se dentro do buffer das áreas com e sem EPSAN. Coleta de dados realizada por observação direta (busca ativa) de agosto a outubro de 2019. Os dados coletados foram localização e tipo dos estabelecimentos comerciais, e também foi calculada a densidade dos estabelecimentos. Foram feitas análise descritiva, distribuição espacial (estimador de Kernel) e análise do vizinho mais próximo. Dos estabelecimentos avaliados, 60,5% estavam nas áreas sem EPSAN, e 39,6% nas áreas com EPSAN, apresentando padrão de distribuição aleatório. Desses, 24,2% eram lojas de conveniência e padarias, 21,0% açougues e 19,0% feiras-livres. Sete EPSAN encontravam-se próximos aos estabelecimentos comerciais. Havia menor número de estabelecimentos no entorno dos EPSAN, com predominância de lojas de conveniência e padaria.

A novel pathogenic CRB1 variant presenting as Leber Congenital Amaurosis 8 and evaluation of gene editing feasibility.

INTRODUCTION: Leber Congenital Amaurosis (LCA) is an inherited retinal disease that presents in infancy with severely decreased vision, nystagmus, and extinguished electroretinography findings. LCA8 is linked to variants in the Crumbs homolog 1 (CRB1) gene. CASE DESCRIPTION: We report a novel CRB1 variant in a 14-year-old male presenting with nystagmus, worsening vision, and inability to fixate on toys in his infancy. Color fundus photography revealed nummular pigments in the macula and periphery. Imaging studies revealed thickened retina on standard domain optical coherence tomography and widespread atrophy of the retinal pigment epithelium on autofluorescence. Full-field electroretinography revealed extinguished scotopic and significantly reduced photopic responses. Genetic testing demonstrated a novel homozygous variant, c.3057 T > A; p.(Tyr1019Ter), in the CRB1 gene. This variant is not currently amenable to base editing, however, in silico analysis revealed several potential prime editing strategies for correction. CONCLUSION: This case presentation is consistent with LCA8, suggesting pathogenicity of this novel variant and expanding our knowledge of disease-causing CRB1 variants.

Neurological syndromes and potential triggers associated with antibodies to neuronal surface antigens.

BACKGROUND: Autoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. METHODS: We described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. RESULTS: We identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. CONCLUSION: We identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.