Comparison between topical use of ketotifen and olopatadine in the treatment of allergic conjunctivitis

Purpose: To evaluate and compare the efficacy and tolerance to the topical use of 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride in the treatment of patients with allergic conjunctivitis. Methods: A masked, randomized clinical study was performed in order to compare the efficacy, safety and side effects of the use of 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride ophthalmic solutions for the alleviation of symptoms and signs in patients with allergic conjunctivitis. Thirty-four patients, fulfilling the inclusion criteria of the protocol were divided into two groups and received a flask with the masked drug, instilling one drop twice daily in each eye for 30 days. Signs and symptoms of these patients were evaluated on a visit before treatment and on five visits during the treatment (days 1, 2, 7, 14 and 30). Results: Severity of allergic conjunctivitis was the same in both studied groups. Both ketotifen and olopatadine were equivalent and efficient regarding decrease in itching, burning and lacrimation symptoms. Bulbar conjunctival hyperemia was attenuated in both groups. Evaluation of adverse reactions showed the occurrence of burning on administration of both drugs and ketotifen led to occurrence of itching. No hypersensitivity reaction to the studied drugs was observed. Conclusions: This study evidences that 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride ophthalmic solutions, when instilled twice daily for 30 days, were efficient and safe regarding alleviation of the main symptoms and signs of allergic conjunctivitis.Objetivo: Avaliar e comparar a eficácia e tolerância do uso tópico do fumarato de cetotifeno a 0,05% e cloridrato de olopatadina a 0,1% no tratamento de pacientes com conjuntivite alérgica. Método: Foi realizado estudo clínico mascarado, randomizado comparando a eficácia, segurança e os efeitos colaterais com o uso da solução oftálmica de fumarato de cetotifeno a 0,05% e cloridrato de olopatadina a 0,1% no alívio dos sintomas e sinais em pacientes com conjuntivite alérgica. Trinta e quatro pacientes obedecendo aos critérios de inclusão do protocolo receberam um frasco com a droga mascarada e instilaram uma gota duas vezes por dia em cada olho durante 30 dias. Os sintomas e sinais dos pacientes foram avaliados em uma visita pré-tratamento e cinco com tratamento (1º dia, 2º dia, 7º dia, 14º dia e 30º dia). Resultados: A gravidade da conjuntivite alérgica foi semelhante nos dois grupos do estudo. Tanto cetotifeno como a olopatadina foram equivalentes e eficazes na diminuição dos sintomas de prurido, ardor e lacrimejamento. Quanto aos sinais, a hiperemia em conjuntiva bulbar foi atenuada nos dois grupos. Na avaliação das reações adversas observou-se ardor após a administração de ambos colírios e a ocorrência de prurido no grupo do cetotifeno. Não foi observada nenhuma reação de hipersensibilidade das drogas estudadas. Conclusões: Este estudo evidencia que a solução oftálmica de fumarato de cetotifeno a 0,05% e o cloridrato de olopatadina a 0,1% quando instilados duas vezes ao dia durante 30 dias, são eficazes e seguros no alívio dos principais sintomas das conjuntivites alérgicas.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de OftalmologiaUNIFESP, EPM, Depto. de OftalmologiaSciEL

Thrips (Thysanoptera: Thripidae, Phlaeothripidae) damaging peach in Paranapanema, São Paulo State, Brazil.

Objetivando identificar as espécies de tripes associadas ao pessegueiro e as injúrias causadas, pomares das cultivares Aurora e Tropic Beauty foram monitorados semanalmente, de maio a agosto de 2005, no Distrito de Holambra II, em Paranapanema, SP. Flores e frutos de cada seis plantas por hectare foram amostrados pela técnica da batida. Foram identificadas Frankliniella occidentalis (Pergande), F. schultzei (Trybom), F. gardenia (Moulton), F. condei John, F. insularis (Franklin) e Thrips tabaci Lindeman em Thripidae, e, Haplothrips gowdeyi (Franklin) em Phlaeothripidae. F. occidentalis foi dominante compondo 55,7% do total de espécimes amostrado. Injúrias leves e severas foram registradas nos frutos. Seeking to identify thrips species associated to peach and the injuries they cause, plants of Aurora and Tropic Beauty cultivars were weekly monitored, from May to August of 2005, in Holambra II district, in Paranapanema, SP. Flowers and fruits from six plants per hectare were sampled by the hitting technique. Frankliniella occidentalis (Pergande), F. schultzei (Trybom), F. gardenia (Moulton), F. condei John, F. insularis (Franklin) and Thrips tabaci Lindeman, in Thripidae,and Haplothrips gowdeyi (Franklin), in Phlaeothripidae were identifi ed. F. occidentalis was dominant, comprising 55.7% of the total specimens sampled. Slight and severe injuries were registered in fruits.KEY WORDS: Rosaceae, thysanopteran, pest species, habitDisponível também no formato online

Fenestrated-branched endovascular repair for distal thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk

Objective: To report the outcomes of fenestrated-branched endovascular repair (FBEVAR) for thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk (TAR+FET). Methods: Interrogation of prospectively maintained databases from four high-volume aortic centers identified consecutive patients treated with distal FBEVAR after prior TAR+FET between August 2013 and September 2020. The primary end point was 30-day/in-hospital mortality. Secondary end points were technical success, early clinical success, midterm survival, and freedom from reintervention. Data are presented as median (interquartile range). Results: A total of 39 patients (21 men; median age, 73 years [67-75 years]) with degenerative (n = 22) and postdissection thoracoabdominal aortic aneurysms (n = 17) (median diameter, 71 mm [61-78 mm]) were identified. Distal FBEVAR was intended in 27 patients (median interval, 9.8 months [6.2-16.6 months]), anticipated in 7, and unexpected in 5. A total of 31 patients had a two- (n = 24) or three-stage (n = 7) distal FBEVAR. Renovisceral target vessel preservation was 99.3% (145 of 146). Early primary and secondary technical success was 92% and 97%, respectively. Thirty-day mortality was 2.6% (n = 1; respiratory failure and spinal cord ischemia [SCI]). Six survivors also developed SCI, which was associated with complete (n = 4) or partial recovery (n = 2) at hospital discharge. No patients required renal replacement therapy or suffered a stroke. Early clinical success was 95%. Median follow-up was 30.5 months (23.7-49.7 months). Eleven patients required 16 late reinterventions. Estimated 3-year survival and freedom from reintervention were 84% ± 6% and 63% ± 10%, respectively. Conclusions: Distal FBEVAR after prior TAR+FET is associated with high technical success and low early mortality. The risk of SCI is significant although the majority of patients demonstrate full or partial recovery before hospital discharge. Midterm patient survival is favorable, but there remains a high requirement for late reintervention. FBEVAR represents an acceptable alternative to distal open thoracoabdominal aortic aneurysm repair

deCLUTTER²⁺ – a pipeline to analyze calcium traces in a stem cell model for ventral midbrain patterned astrocytes

Astrocytes are the most populous cell type of the human central nervous system and are essential for physiological brain function. Increasing evidence suggests multiple roles for astrocytes in Parkinson’s disease, nudging a shift in the research focus, which historically pivoted around ventral midbrain dopaminergic neurons (vmDANs). Studying human astrocytes and other cell types in vivo remains challenging. However, in vitro-reprogrammed human stem cell-based models provide a promising alternative. Here, we describe a novel protocol for astrocyte differentiation from human stem cell-derived vmDAN-generating progenitors. This protocol simulates the regionalization, gliogenic switch, radial migration and final differentiation that occur in the developing human brain. We characterized the morphological, molecular and functional features of these ventral midbrain patterned astrocytes with a broad palette of techniques and identified novel candidate midbrain-astrocyte specific markers. In addition, we developed a new pipeline for calcium imaging data analysis called deCLUTTER2+ (deconvolution of Ca2+ fluorescent patterns) that can be used to discover spontaneous or cue-dependent patterns of Ca2+ transients. Altogether, our protocol enables the characterization of the functional properties of human ventral midbrain patterned astrocytes under physiological conditions and in disease.</p

Autoantibodies in a Subgroup of Patients with Linear IgA Disease React with the NC16A Domain of BP1801

Linear IgA disease is an autoimmune subepidermal blistering disease characterized by IgA deposits at the cutaneous basement membrane zone. IgA antibodies from linear IgA disease sera react with antigens of 97 kDa (LABD97) and 120 kDa (LAD-1), both of which appear to be fragments of the extracellular domain of bullous pemphigoid 180 (type XVII collagen). The aim of this study was to determine whether linear IgA disease sera react with the immunodominant region of BP180 (NC16A domain), which is a major target of IgG autoanti-bodies produced by patients with bullous pemphigoid. Indeed, 11 of 50 linear IgA disease sera were found to contain IgA autoantibodies that recognized a recombinant form of NC16A by immunoblotting. The same sera also reacted with NC16A by enzyme-linked immunosorbent assay. An epitope mapping analysis uncovered four linear IgA disease-associated epitopes located within the 45 amino acid N-terminal stretch of NC16A, all of which were previously identified as antigenic sites targeted by bullous pemphigoid autoantibodies. Eight of the linear IgA disease sera that were reactive with NC16A also recognized LAD-1 secreted by the SCC-25 cell line, and five sera recognized BP180 extracted from keratinocytes. Linear IgA disease sera depleted of reactivity to NC16A by immunoadsorption continued to react with both the LAD-1 antigen and BP180 by immunoblotting and with the basement membrane zone by indirect immunofluorescence microscopy. Our results demonstrate that IgA autoantibodies from a subset of linear IgA disease patients react with the same sites on BP180 that are targeted by IgG autoantibodies in bullous pemphigoid

Genetic study of atypical femoral fractures using exome sequencing in three affected sisters and three unrelated patients

Objectives: Atypical femoral fractures (AFF) are rare, often related to long-term bisphosphonate (BPs) tre- atment. Their pathogenic mechanisms are not precisely known and there is no evidence to identify patients with a high risk of AFF. The aim of this work is to study the genetic bases of AFFs. Material and methods: Whole-exome sequencing was carried out on 3 sisters and 3 unrelated additional patients, all treated with BPs for more than 5 years. Low frequency, potentially pathogenic variants sha- red by the 3 sisters, were selected, were selected and a network of gene and protein interactions was constructed with the data found. Results: We identified 37 rare variants (in 34 genes) shared by the 3 sisters, some not previously descri- bed. The most striking variant was the p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophos- phate synthase (encoded by the GGPS1 gene), from the mevalonate pathway and essential for osteoclast function. Another noteworthy finding was two mutations (one in the 3 sisters and one in an unrelated patient) in the CYP1A1 gene, involved in the metabolism of steroids. We identified other variants that could also be involved in the susceptibility to AFFs or in the underlying osteoporotic phenotype, such as those present in the SYDE2, NGEF, COG4 and FN1 genes. Conclusions: Our data are compatible with a model where the accumulation of susceptibility variants could participate in the genetic basis of AFFs

LRP10 and α-synuclein transmission in Lewy body diseases

Autosomal dominant variants in LRP10 have been identified in patients with Lewy body diseases (LBDs), including Parkinson's disease (PD), Parkinson's disease-dementia (PDD), and dementia with Lewy bodies (DLB). Nevertheless, there is little mechanistic insight into the role of LRP10 in disease pathogenesis. In the brains of control individuals, LRP10 is typically expressed in non-neuronal cells like astrocytes and neurovasculature, but in idiopathic and genetic cases of PD, PDD, and DLB, it is also present in α-synuclein-positive neuronal Lewy bodies. These observations raise the questions of what leads to the accumulation of LRP10 in Lewy bodies and whether a possible interaction between LRP10 and α-synuclein plays a role in disease pathogenesis. Here, we demonstrate that wild-type LRP10 is secreted via extracellular vesicles (EVs) and can be internalised via clathrin-dependent endocytosis. Additionally, we show that LRP10 secretion is highly sensitive to autophagy inhibition, which induces the formation of atypical LRP10 vesicular structures in neurons in human-induced pluripotent stem cells (iPSC)-derived brain organoids. Furthermore, we show that LRP10 overexpression leads to a strong induction of monomeric α-synuclein secretion, together with time-dependent, stress-sensitive changes in intracellular α-synuclein levels. Interestingly, patient-derived astrocytes carrying the c.1424 + 5G &gt; A LRP10 variant secrete aberrant high-molecular-weight species of LRP10 in EV-free media fractions. Finally, we show that this truncated patient-derived LRP10 protein species (LRP10splice) binds to wild-type LRP10, reduces LRP10 wild-type levels, and antagonises the effect of LRP10 on α-synuclein levels and distribution. Together, this work provides initial evidence for a possible functional role of LRP10 in LBDs by modulating intra- and extracellular α-synuclein levels, and pathogenic mechanisms linked to the disease-associated c.1424 + 5G &gt; A LRP10 variant, pointing towards potentially important disease mechanisms in LBDs.</p