Mercury in aquatic ecosystems of two indigenous communities in the Piedmont Ecuadorian Amazon: evidence from fish, water, and sediments.

Mercury is a highly toxic element present in water, soil, air, and biota. Anthropogenic activities, such as burning fossil fuels, mining, and deforestation, contribute to the presence and mobilization of mercury between environmental compartments. Although current research on mercury pathways has advanced our understanding of the risks associated with human exposure, limited information exists for remote areas with high diversity of fauna, flora, and indigenous communities. This study aims to deepen our understanding of the presence of total mercury in water, sediments, and fish, within aquatic ecosystems of two indigenous territories: Gomataon (Waorani Nationality) and Sinangoé (Ai´Cofán Nationality) in the Ecuadorian Amazon. Our findings indicate that, for most fish (91.5%), sediment (100%) and water (95.3%) samples, mercury levels fall under international limits. For fish, no significant differences in mercury levels were detected between the two communities. However, eight species exceeded recommended global limits, and one surpassed the threshold according to Ecuadorian legislation. Piscivore and omnivore fish exhibited the highest concentrations of total mercury among trophic guilds. Only one water sample from each community's territory exceeded these limits. Total mercury in sediments exhibited greater concentrations in Gomataon than Sinangoé. Greater levels of mercury in sediments were associated with the occurrence of total organic carbon. Considering that members of the communities consume the analyzed fish, an interdisciplinary approach, including isotopic analysis, methylmercury sampling in humans, and mercury monitoring over time, is imperative for a detailed risk assessment of mercury exposure in Amazonian communities.

Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.

INTRODUCTION: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. METHODS: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw. FINDINGS: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. INTERPRETATION: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. FUNDING: Ministry of Health, Brazil.

Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial.

Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN: BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.

Vitreous diagnosis in neoplastic diseases.

Vitreous body is an intraocular structure, origin of diverse pathologies, but is also the place where cells and inflammatory mediators are released coming from several pathologic processes. These inflammatory reactions can happen in any other ocular location like choroid, retina, optic nerve, or ciliary body and vitreous humor constitutes a stagnant reservoir for these resulting substances and debris. Through the recent techniques of vitreous collecting, handling, and analysis, increasingly more sophisticated and with fewer complications, cellularity and molecules in the vitreous of challenging pathologies for the ophthalmologist can now be studied. The most usefulness for vitreous diagnosis would be the masquerade syndromes, and the best exponent in this group is the primary vitreoretinal lymphoma (PVRL), in which cytology and an IL-10/IL-6 ratio more than 1 is fundamental for the diagnosis.

Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts.

Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 and 16.5. An accumulation of autophagic vacuoles was detected in many tissues including endothelial cells and Schwann cells. Fibroblast cell lines derived from the double-deficient embryos accumulated autophagic vacuoles and the autophagy protein LC3II after amino acid starvation. Lysosomal vesicles were larger and more peripherally distributed and showed a lower specific density in Percoll gradients in double deficient when compared with control cells. Lysosomal enzyme activities, cathepsin D processing and mannose-6-phosphate receptor expression levels were not affected by the deficiency of both LAMPs. Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy. The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets. The cholesterol accumulation in LAMP-1/2 double-deficient cells could be rescued by overexpression of murine LAMP-2a, but not by LAMP-1, highlighting the more prominent role of LAMP-2. Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis.

Clinical Management of Orbital Rhabdomyosarcoma in a Referral Center in Spain.

PURPOSE: To review the systemic and ocular outcomes and long-term status of ocular rhabdomyosarcoma in pediatric patients in a tertiary center in Spain. METHODS: All patients younger than 18 years who were diagnosed as having ocular rhabdomyosarcoma and treated between 1982 and 2011 at La Paz University Hospital, Madrid, Spain, were included. Clinical presentation, management, complications, and ocular and systemic outcomes were reviewed. RESULTS: The mean age at presentation was 8 years (range: 3 months to 12.5 years). In all cases, the rhabdomyosarcoma was located primarily in the orbit. Treatment included surgical debulking and various regimens of chemotherapy and radiotherapy. All of the patients underwent surgical biopsy for diagnosis confirmation. Orbital exenteration was performed in 4 cases (28%). Twelve patients received radiotherapy. The long-term visual outcomes of the 10 patients who maintained their globe was as follows: best corrected visual acuity 20/20 to 20/40 in 6 patients (60%), 20/50 to 20/100 in 2 patients (20%), and 20/200 to no light perception in 2 patients (20%). Intraocular complications (primarily cataracts: 50%) were present in 7 patients (70%), ocular surface lesions occurred in 6 patients (60%), and orbital sequelae were found in 8 patients (80%). Local tumor recurrence was detected in 5 patients (35%) and distant metastasis occurred in 2 patients (14%). Tumor-related death occurred in 1 patient (7%). CONCLUSIONS: Orbital rhabdomyosarcoma has an excellent prognosis; nevertheless, local complications are common, including surgery-related complications. To minimize them, initial surgical planning based on individual patient characteristics and an accurate diagnosis of relapses is mandatory. The clinical presentation, management, and long-term ocular and systemic outcomes are comparable with other series published to date.

External subretinal drainage, bevacizumab, and scleral buckling for complete exudative retinal detachment after photocoagulation in retinopathy of prematurity.

BACKGROUND: Total serous retinal detachment after laser photocoagulation for retinopathy of prematurity is an infrequent type of retinal detachment in preterm babies. PURPOSE: To describe the successful outcome for treatment by scleral drainage, bevacizumab, and scleral buckling for complete serous exudative retinal detachment in a patient with retinopathy of prematurity. METHODS: A preterm baby with primary pulmonary hypertension under treatment with sildenafil developed a total (retrolental) serous retinal detachment after photocoagulation for threshold retinopathy. The dense subretinal fluid was externally drained using a bent needle with an infusion placed in the anterior chamber. Additional bevacizumab and scleral buckling helped to control the plus disease and subretinal leakage. RESULTS: Retinal apposition was obtained with the described approach. CONCLUSION: Total serous retinal detachment is a rare but severe visual complication in retinopathy of prematurity. The described technique may restore the retinae immediately in a visually critical period.

Adalimumab therapy for refractory childhood uveitis.

PURPOSE: To report the results of adalimumab therapy in a cohort of children with refractory noninfectious uveitis. METHODS: The medical records of patients diagnosed with uveitis and treated with biweekly adalimumab injections for a period of at least 3 months at the University Hospital of La Paz from 2007-2012 were retrospectively reviewed. Improvement in inflammatory activity was graded according to grading schema of the Standardization of Uveitis Nomenclature Working Group. RESULTS: A total of 15 patients participated in the study (12 girls; mean patient age, 12 years). Diagnoses included juvenile idiopathic arthritis in 10 patients, idiopathic uveitis in 4, and familial juvenile systemic granulomatosis or Blau syndrome in 1. Mean follow-up was 32 months (median, 36; range, 15-58 months). Improvement in inflammatory activity was initially observed in 12 (86%) of 14 children, with a mean time to achieve response of 6 weeks (median, 4; range, 1-18). Treatment was effective in 9 patients (60%), mildly effective in 2 (13%), ineffective in 2 (13%), and resulted in worsening in 2 (13%). In the juvenile idiopathic arthritis patients, response was effective in 6 cases (60%), mildly effective in 2 (20%), and ineffective in 2 (20%). Adalimumab therapy was discontinued in 4 patients. CONCLUSIONS: Adalimumab was effective in most patients in the initial control of acute inflammatory activity in children with refractory uveitis, although therapy appears to become less effective in the long term.

Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report.

INTRODUCTION: Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. CASE PRESENTATION: A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. CONCLUSIONS: Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be achieved in patients with this malignant tumor.

Índice Manchester de incapacidade associada ao pé doloroso no idoso: tradução, adaptação cultural e validação para a língua portuguesa / Manchester foot pain associated disability index in the feet of elderly people: cultural adaptation, validation, and translation into the portuguese language

OBJETIVO: O objetivo do estudo foi realizar a tradução e a adaptação e estudar as propriedades das medidas: reprodutibilidade, validade e consistência interna do índice Manchester de incapacidade associada ao pé doloroso no idoso (MFPDI) para a língua portuguesa. MÉTODOS: O MFPDI foi traduzido e adaptado culturalmente para uma população de idosos, residentes na cidade de São Paulo. Foram avaliados 85 pacientes ambulatoriais com idade de 60 anos ou mais, de ambos os sexos, que apresentavam dor nos pés de 30 mm ou mais na escala analógica visual de dor (EVA). Os pacientes foram submetidos ao MFPDI por três vezes, visto que na primeira vez cada paciente foi avaliado pelos entrevistadores 1 e 2 no mesmo dia, e no período máximo de 15 dias cada paciente foi, novamente, avaliado pelo entrevistador 1 para realizar a fase de reprodutibilidade. Para verificar a validade, foram colhidas medidas sociodemográficas, morfológicas e valores da escala analógica visual. E para a consistência interna foi aplicado o alfa de Cronbach, a fim de verificar a confiabilidade das respostas nas três entrevistas. RESULTADOS: Ao utilizar o processo metodológico, foi possível observar que a população ambulatorial entrevistada apresentou incapacidade funcional associada ao pé doloroso. A consistência interna foi alta (alfa de Cronbach = 0,80) entre as entrevistas. A validade foi obtida comparando-se o MFPDI com a EVA, sendo possível observar que, apesar de baixa, a correlação foi significante (p < 0,001). CONLUSÃO: Com o processo de tradução e adaptação cultural do MFPDI demonstraram-se as propriedades de medida de reprodutibilidade, validade e consistência interna.

OBJECTIVE: This work aimed to translate into Portuguese, make adaptations, and study the reproducibility, validation and internal consistency of the parameters of the "Manchester Foot-Pain Disability Index". METHODS: The MFPDI was translated and culturally adapted in a population of eighty-five (85) elderly people, living in the city of São Paulo, seen at the outpatient clinics of the .Instituto de Geriatria e Gerontologia of the Escola Paulista de Medicina. The patients had at least 60 years-old, of either sex, displaying foot pain of at least 30 mm on a visual analog scale (VAS). Patients were evaluated by 3 times by the MFPDI, in such a way that on the first time each patient was evaluated by the interviewers 1 and 2 at the same day; to assess reproducibility, within the next 15 days each patient was evaluated again by the interviewer 1. Validation was verified by checking for social and demographic data, as well as morphological and VAS values. Internal consistency was checked by means of the Cronbach alpha, assessing reproducibility of the answers in the three interviews. RESULTS: The MFPDI index demonstrated that this population presented functional inability associated to foot pain. The internal consistency between interviews was high (Alpha of Cronbach = 0.80). Though presenting a weak correlation, there was a significant validity comparing MFPDI and the VAS (p < 0.001). CONCLUSION: The translation and cultural adaptation of the MFPDI provide a reproducible, consistent and valuable tool to evaluate foot pain.