Retinal abnormalities in a patient with cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.

The role of mannose-binding lectin (MBL) in diabetic retinopathy: A scoping review.

Diabetes mellitus (DM) is a chronic systemic disease characterized by a multifactorial nature, which may lead to several macro and microvascular complications. Diabetic retinopathy (DR) is one of the most severe microvascular complications of DM, which can result in permanent blindness. The mechanisms involved in the pathogenesis of DR are multiple and still poorly understood. Factors such as dysregulation of vascular regeneration, oxidative and hyperosmolar stress in addition to inflammatory processes have been associated with the pathogenesis of DR. Furthermore, compelling evidence shows that components of the immune system, including the complement system, play a relevant role in the development of the disease. Studies suggest that high concentrations of mannose-binding lectin (MBL), an essential component of the complement lectin pathway, may contribute to the development of DR in patients with DM. This review provides an update on the possible role of the complement system, specifically the lectin pathway, in the pathogenesis of DR and discusses the potential of MBL as a non-invasive biomarker for both, the presence and severity of DR, in addition to its potential as a therapeutic target for intervention strategies.

Comparison of Proparacaine, Tetracaine, and Oxybuprocaine in Corneal Sensitivity Measurement.

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

Amniotic membrane transplantation for neurotrophic corneal ulcers.

PURPOSE: To evaluate the clinical results of cryopreserved amniotic membrane transplantation as a treatment option for refractory neurotrophic corneal ulcers. METHODS: This prospective study included 11 eyes of 11 patients who underwent amniotic membrane transplantation for the treatment of refractory neurotrophic corneal ulcers at Hospital de Clínicas da Universidade Federal do Paraná, in the city of Curitiba, from May 2015 to July 2021. Patients underwent different surgical techniques in which the amniotic membrane was applied with the epithelium facing upward to promote corneal re-epithelialization. RESULTS: The median age of the patients was 60 years (range, 34-82 years), and 64% were men. The predominant etiology of corneal ulcers was herpes zoster (45% of cases). Approximately one-third of the patients (27%) were chronically using hypotensive eye drops, and more than half (54%) had previously undergone penetrating corneal transplantation. At the time of amniotic membrane transplantation, 18% of the eyes had corneal melting, 9% had corneal perforation, and the others had corneal ulceration without other associated complications (73%). The time between clinical diagnosis and surgical treatment ranged from 9 days to 2 years. The corrected visual acuity was worse than 20/400 in 90% of the patients preoperatively, with improvement in 36% after 3 months of the procedure, worsening in 18% and remaining stable in 36%. Of the patients, 81% complained of preoperative pain, and 66% of them reported total symptom relief after the surgical procedure. In one month, 54.6% of the patients presented a closure of epithelial defect, and half of the total group evolved with corneal thinning. The failure rate was 45.5% of the cases. CONCLUSION: Cryopreserved amniotic membrane transplantation can be considered a good alternative for treating refractory neurotrophic corneal ulcers, as it resulted in significant improvement in pain (66%) and complete epithelial closure (60%) in many patients at 1 month postoperatively. Notably, the high failure rate highlights the need for further studies to identify patientand ulcer-related factors that may influence the outcomes of this procedure.

Correction: The route for commercial photoelectrochemical water splitting: a review of large-area devices and key upscaling challenges.

Correction for 'The route for commercial photoelectrochemical water splitting: a review of large-area devices and key upscaling challenges' by António Vilanova et al., Chem. Soc. Rev., 2024, https://doi.org/10.1039/d1cs01069g.

Authors' Response.

Dear Editor, We would like to thank Dr. Madias for his valuable comment on our original article entitled "QT interval prolongation in Takotsubo Syndrome: a frightening feature with no major prognostic impact" published in Monaldi Archives for Chest Disease on December 6, 2023...

Optical coherence tomography detection of retinal neural loss in patients with tuberous sclerosis.

PURPOSE: Tuberous Sclerosis (TS) is a rare, multisystem genetic disease caused by mutations in the TSC1 and TSC2 genes, leading to abnormalities in cell differentiation and proliferation. This study aimed to evaluate the neural integrity of individuals with TS by using Optical Coherence Tomography (OCT) to examine the peripapillary retinal nerve fiber layer (RNFL) thickness and the macular thickness in patients with TS and to compare with healthy controls. METHODS: Peripapillary and macular OCT scans (Optopol Revo NX SD OCT) were performed on 41 eyes from 22 TS patients, divided into two groups based on the presence of retinal hamartomas, and compared to 20 eyes from a control group. The average peripapillary RNFL thickness was measured for each quadrant. The macular total thickness and ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness were measured based on the Early Treatment Diabetic Retinopathy Study (ETDRS) map. All measurements were then compared between the groups and controls. RESULTS: The TS group showed significantly reduced RNFL thickness and macular thickness when compared to the control group. Specifically, patients with retinal hamartomas exhibited an even more pronounced thinning of both RNFL and macular thickness. CONCLUSIONS: These findings suggest that TS patients undergo significant changes in retinal neurodevelopment and experience axonal loss. This finding may have significant prognostic utility regarding central nervous system degeneration in TS, particularly among patients with retinal hamartomas. OCT may serve as a valuable tool for assessing axonal structural abnormalities in TS patients. TRIAL REGISTRATION NUMBER: Not applicable.

The route for commercial photoelectrochemical water splitting: a review of large-area devices and key upscaling challenges.

Green-hydrogen is considered a "key player" in the energy market for the upcoming decades. Among currently available hydrogen (H2) production processes, photoelectrochemical (PEC) water splitting has one of the lowest environmental impacts. However, it still presents prohibitively high production costs compared to more mature technologies, such as steam methane reforming. Therefore, the competitiveness of PEC water splitting must rely on its environmental and functional advantages, which are strongly linked to the reactor design, to the intrinsic properties of its components, and to their successful upscaling. This review gives special attention to the engineering aspects and categorizes PEC devices into four main types, according to the configuration of electrodes and strategies for gas separation: wired back-to-back, wireless back-to-back, wired side-by-side, and wired separated electrode membrane-free. Independently of the device architecture, the use of concentrated sunlight was found to be mandatory for achieving competitive green-H2 production. Additionally, feasible strategies for upscaling the key components of PEC devices, especially photoelectrodes, are urgently needed. In a pragmatic context, the way to move forward is to accept that PEC devices will operate close to their thermodynamic limits at large-scale, which requires a solid convergence between academics and industry. Research efforts must be redirected to: (i) build and demonstrate modular devices with a low-cost and highly recyclable embodiment; (ii) optimize thermal and power management; (iii) reduce ohmic losses; (iv) enhance the chemical stability towards a thousand hours; (v) couple solar concentrators with PEC devices; (vi) boost PEC-H2 production through the use of organic compounds; and (vii) reach consensual standardized methods for evaluating PEC devices, at both environmental and techno-economic levels. If these targets are not met in the next few years, the feasibility of PEC-H2 production and its acceptance by industry and by the general public will be seriously compromised.

Amniotic membrane transplantation for ocular surface burns / Transplante de membrana amniótica em queimaduras da superfície ocular

ABSTRACT Objective: To analyze the morphological and functional long-term outcomes of amniotic membrane transplantation after ocular surface chemical burns. Methods: This prospective study analyzed 7 patients who suffered from severe ocular surface burn and underwent amniotic membrane transplantation from 2015 to 2020 in Hospital de Clínicas - Universidade Federal do Paraná. Results: Out of the seven patients, six (85.7%) suffered unilateral burn and one (14.3%) suffered bilateral burn. Five of them had alkali burns (71.4%), one had acid burn (14.3%) and one suffered gunpowder fireworks burn (14.3%). Mean age was 29.4 years (±standard deviation 13.3, range 14.0 to 47.0 years). Mean visual acuity at first presentation was 1.83±0.79 logMAR (0.015 decimal) and mean VA after a follow-up of 1 year was 0.85±0.70 logMAR (0.141 decimal). The visual acuity significantly improved from 1.83±0.79 to 0.85±0.70 logMAR (p<0.05). Conclusion: Amniotic membrane transplantation is an effective adjunctive treatment in the management of ocular surface chemical burns with potential to improve the final vision outcome.

RESUMO Objetivo: Analisar os resultados morfológicos e funcionais a longo prazo do transplante de membrana amniótica após queimaduras químicas da superfície ocular. Métodos: Foi realizado um estudo prospectivo com análise de sete pacientes que sofreram queimaduras graves da superfície ocular e foram submetidos a transplante de membrana amniótica no período de 2015 a 2020 no Hospital de Clínicas da Universidade Federal do Paraná. Resultados: Dos sete pacientes, seis (85,7%) sofreram queimadura unilateral e um (14,3%) sofreu queimadura bilateral. Cinco deles sofreram queimaduras por álcali (71,4%), um por ácido (14,3%) e um por pólvora de fogo de artifício (14,3%). A média de idade foi de 29,4 anos (±desvio-padrão de 13,3, intervalo de 14,0 a 47,0 anos). A acuidade visual média na primeira apresentação foi de 1,83±0,79 logMAR (0,015 decimal) e, após 1 ano de seguimento, foi de 0,85±0,70 logMAR (0,141 decimal). A acuidade visual melhorou significativamente, de 1,83±0,79 para 0,85±0,70 logMAR (p<0,05). Conclusão: O transplante de membrana amniótica é um tratamento adjuvante eficaz no manejo de queimaduras químicas da superfície ocular com potencial para melhorar a visão final.

Amniotic membrane transplantation for neurotrophic corneal ulcers

ABSTRACT Purpose: To evaluate the clinical results of cryopreserved amniotic membrane transplantation as a treatment option for refractory neurotrophic corneal ulcers. Methods: This prospective study included 11 eyes of 11 patients who underwent amniotic membrane transplantation for the treatment of refractory neurotrophic corneal ulcers at Hospital de Clínicas da Universidade Federal do Paraná, in the city of Curitiba, from May 2015 to July 2021. Patients underwent different surgical techniques in which the amniotic membrane was applied with the epithelium facing upward to promote corneal re-epithelialization. Results: The median age of the patients was 60 years (range, 34-82 years), and 64% were men. The predominant etiology of corneal ulcers was herpes zoster (45% of cases). Approximately one-third of the patients (27%) were chronically using hypotensive eye drops, and more than half (54%) had previously undergone penetrating corneal transplantation. At the time of amniotic membrane transplantation, 18% of the eyes had corneal melting, 9% had corneal perforation, and the others had corneal ulceration without other associated complications (73%). The time between clinical diagnosis and surgical treatment ranged from 9 days to 2 years. The corrected visual acuity was worse than 20/400 in 90% of the patients preoperatively, with improvement in 36% after 3 months of the procedure, worsening in 18% and remaining stable in 36%. Of the patients, 81% complained of preoperative pain, and 66% of them reported total symptom relief after the surgical procedure. In one month, 54.6% of the patients presented a closure of epithelial defect, and half of the total group evolved with corneal thinning. The failure rate was 45.5% of the cases. Conclusion: Cryopreserved amniotic membrane transplantation can be considered a good alternative for treating refractory neurotrophic corneal ulcers, as it resulted in significant improvement in pain (66%) and complete epithelial closure (60%) in many patients at 1 month postoperatively. Notably, the high failure rate highlights the need for further studies to identify patientand ulcer-related factors that may influence the outcomes of this procedure.

QT interval prolongation in Takotsubo syndrome: a frightening feature with no major prognostic impact.

Despite the frequent and often severe repolarization abnormalities seen in Takotsubo syndrome (TTS), the underlying mechanism of life-threatening arrhythmias is incompletely understood, and the risk remains uncertain. TTS is considered a potential cause of acquired long QT syndrome; however, there is no robust evidence that QT prolongation has a major prognostic impact on these patients' outcomes. Our aim was to assess the prevalence and clinical implications of acquired long QT during TTS events and compare in-hospital and long-term outcomes between patients with and without corrected QT interval (QTc) prolongation. This is a retrospective cohort study that included 113 patients admitted to our tertiary care hospital with a diagnosis of TTS. The cohort was divided into two groups: a long QTc group (QTc≥460 milliseconds in any electrocardiogram at admission or during hospitalization) and a normal QTc group. Baseline characteristics, occurrences during hospitalization, and outcome data were obtained from the revision of medical registries and hospital visits. Of the 113 patients, 107 (94.7%) were female. The mean age was 67.6±11.7 years. QTc prolongation was found in 38%. Demographic characteristics, relevant chronic medication, prevalence of cardiovascular risk factors, and other comorbidities were similar between the groups, except for history of atrial fibrillation, which was more common in the long QTc group. Syncope was more prevalent in the long QTc group. In-hospital complications were not statistically different between patients with long and normal QTc (48.8% versus 44.2%, p=0.637), including ventricular arrhythmias and complete atrioventricular block (both 4.7% versus 1.4%, p=0.556). In-hospital mortality was 0.9%, corresponding to one patient in the long QTc group. The mean follow-up time was 4.8±3.8 years. 5-year all-cause mortality and the occurrence of the composite endpoint of major adverse cardiac and cerebrovascular events did not differ between the groups (p=0.511 and p=0.538, respectively). Our study found no association between prolonged QTc interval during TTS events and adverse prognosis, since in-hospital and long-term outcomes were similar between the groups. Our findings suggest that, although QT prolongation is usually a frightening feature on ECG, this repolarization abnormality during the acute phase has no major prognostic implications in the TTS population.

Retinal hamartomas at different stages in a patient with tuberous sclerosis: A OCT-SS description.

Retinal astrocytic hamartoma (RAH) is a benign glial tumor that may be present in patients with tuberous sclerosis (TS), contributing to the diagnosis of this syndrome. While hamartomas identified through indirect ophthalmoscopy are often large enough to affect vessels and optic disc anatomy, RAH not detected in previous fundoscopies may become apparent in optical coherence tomography (OCT). The purpose of this report was to describe and characterize RAH with OCT with swept-source technology (OCT-SS), aiming to establish a more comprehensive classification for these hamartomas due to their diverse presentations. Fundus examination of a 11-year-old girl revealed retinal tumors in both eyes. OCT-SS confirmed the diagnosis of TS, revealing dome-shaped hyperreflective masses at different stages of evolution. Lesion 1: maximum thickness (MT) of 336 µm and ganglion cell layer disorganization. Lesion 2: MT of 438 µm and preserved outer plexiform layer. Lesion 3: posterior shadow, MT of 1478 µm and complete rupture of retinal anatomy. Lesion 4: MT of 342 µm and preserved retinal anatomy. OCT is a noninvasive method which assists the diagnosis of subclinical lesions and clinical characterization of TS patients.

Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes-Obesity as a Crucial Player.

Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.

Effects of Low-Level Laser Therapy and Purified Natural Latex (Hevea brasiliensis) Protein on Injured Sciatic Nerve in Rodents: Morpho-Functional Analysis.

The present study analyzed the effects of low-level laser therapy (LLLT) and the purified natural latex protein (Hevea brasiliensis, F1 protein) on the morpho-function of sciatic nerve crush injuries in rats. One-hundred and eight male Wistar rats were randomly allocated to six groups (n = 18): 1. Control; 2. Exposed (nerve exposed); 3. Injury (injured nerve without treatment); 4. LLLT (injured nerve irradiated with LLLT (15 J/cm2, 780 nm)); 5. F1 (injured nerve treated with F1 protein (0.1%)); and 6. LLLT + F1 (injured nerve treated with LLLT and F1). On the 1st, 7th, 14th, and 56th days after injury, a functional sensory analysis of mechanical allodynia and mechanical hyperalgesia and a motor analysis of grip strength and gait were performed. After 3, 15, and 57 days, the animals were euthanized for morphometric/ultrastructural analyses. The treatments applied revealed improvements in morphometric/ultrastructural parameters compared to the injured group. Sensory analyses suggested that the improvements observed were associated with time progression and not influenced by the treatments. Motor analyses revealed significant improvements in grip strength from the 7th day in the LLLT group and in gait from the 56th day in all treated groups. We concluded that even though the morphological analyses showed improvements with the treatments, they did not influence sensory recovery, and LLLT improved motor recovery.

Pain interference, neuropathic-like symptoms, pain intensity, and symptoms of central sensitization negatively impact individual's disability after Chikungunya fever: cross-sectional study / Interferência da dor, sintomas do tipo neuropático, intensidade da dor e sintomas de sensibilização central afetam negativamente a capacidade funcional dos indivíduos após a febre Chicungunha: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: Particular pain features, such as pain interference, neuropathic-like symptoms, and central sensitization (CS) symptoms may be present in patients with Chikungunya fever and lead to functional limitations. The present study aimed to assess the association between pain characteristics and the disability in participants affected by Chikungunya fever in the chronic phase. METHODS: A cross-sectional study was conducted with 36 participants who filled out a sociodemographic, pain characteristics (pain interference - Brief Pain Inventory, neuropathic-like symptoms - PainDETECT Questionnaire, and CS-related signs and symptoms - Central Sensitization Inventory) and disability (Health Assessment Questionnaire) questionnaires. The Spearman correlation test (rho) verified the relationship between the outcomes. RESULTS: Most of the participants were female (77%), with a mean age of 43 years. Twenty-seven (75%) participants presented nociceptive pain and 11 (30%) had central sensitization symptoms. There was a high positive correlation between the presence of neuropathic-like symptoms and disability (rho=0.71; p<0.001) and pain intensity and disability (rho=0.76; p<0.001). A moderate positive correlation was found between the central sensitization symptoms and disability (rho=0.51; p=0.002). Moreover, there is a low positive correlation between pain interference in an individual's life and disability (rho=0.34; p=0.041). CONCLUSION: Patients in chronic phase of Chikungunya fever revealed mild pain intensity and predominance of nociceptive pain. Pain interference, neuropathic-like symptoms, and central sensitization symptoms negatively impact individual's disability after Chikungunya fever.

RESUMO JUSTIFICATIVA E OBJETIVOS: Características particulares da dor, como interferência da dor, sintomas do tipo neuropático e sintomas de sensibilização central (SC), podem estar presentes em pacientes com febre Chicungunha e levar a limitações funcionais. O presente estudo teve como objetivo avaliar a correlação entre as características da dor e a capacidade funcional em participantes acometidos pela febre Chicungunha na fase crônica. MÉTODOS: Foi realizado um estudo transversal com 36 participantes que preencheram questionários sociodemográficos, de características de dor (interferência da dor - Inventário Breve de Dor, sintomas do tipo neuropático - questionário PainDETECT, e sinais e sintomas relacionados à SC - Inventário de Sensibilização Central) e de capacidade funcional (Health Assessment Questionnaire). O teste de correlação de Spearman (rho) verificou a relação entre os desfechos. RESULTADOS: A maioria dos participantes era do sexo feminino (77%), com média de idade de 43 anos. Vinte e sete (75%) participantes apresentaram dor nociceptiva e 11 (30%) apresentaram sintomas de sensibilização central. Houve alta correlação positiva entre a presença de sintomas do tipo neuropático e capacidade funcional (rho=0,71; p<0,001) e intensidade da dor e capacidade funcional (rho=0,76; p<0,001). Foi encontrada uma correlação positiva moderada entre os sintomas de sensibilização central e a capacidade funcional (rho=0,51; p=0,002). Além disso, há uma correlação positiva baixa entre a interferência da dor na vida do indivíduo e a capacidade funcional (rho=0,34; p=0,041). CONCLUSÃO: Pacientes em fase crônica da febre Chicungunha apresentaram intensidade de dor leve e predominância de dor nociceptiva. A interferência da dor, os sintomas do tipo neuropático e os sintomas de sensibilização central afetam negativamente a capacidade funcional do indivíduo após a febre Chicungunha.

Emergency coronary angiography in a 90-plus population: outcomes at 5-year follow-up.

Elderly people represent a vulnerable and increasing population presenting with acute coronary syndrome (ACS). Our goal was to evaluate a group of very old patients who underwent emergency coronary angiography (CA). We retrospectively analyzed a group of very old patients (≥90 years old) who underwent emergency CA from 2008 to 2020. Survival and major adverse cardiovascular events (MACE) (a composite of all-cause death, ischemic stroke, ACS, or hospitalization for acute heart failure) were compared with an aged-matched control population with ACS not submitted to emergency CA. A total of 34 patients were enrolled, 56% of whom were female, with a median age of 92 years old. Almost all patients had ST elevation-ACS. In CA, 65% had multivessel disease, and coronary intervention was performed in 71%. More than one-third evolved in Killip class III/IV, and 70% had left ventricular dysfunction. Regarding mortality, 38% of patients died in the index event versus 25% in the aged-matched control group (p=0.319). During 5 years of follow-up, there was no significant difference in mortality between the 2 groups (Log-rank=0.403) and more than 50% of patients died in 2 years. Comparing MACE occurrence, both groups were similar (Log-rank=0.662), with more than 80% having at least one event in 5 years. Very old patients submitted to emergency CA had a high rate of multivessel disease and left ventricular dysfunction, in-hospital and follow-up mortality, and MACE. Compared to an aged-matched control group not submitted to emergency CA, they showed no survival or MACE benefit during a 5-year follow-up.

Vimentin epigenetic deregulation in Bladder Cancer associates with acquisition of invasive and metastatic phenotype through epithelial-to-mesenchymal transition.

Bladder cancer (BlCa) is the ninth most common cancer worldwide, associated with significant morbidity and mortality. Thus, understand the biological mechanisms underlying tumour progression is of great clinical significance. Vimentin (VIM) is (over)expressed in several carcinomas, putatively in association with EMT. We have previously found that VIM promoter methylation accurately identified BlCa and VIM expression associated with unfavourable prognosis. Herein, we sought to investigate VIM expression regulation and its role in malignant transformation of BlCa. Analysis of tissue samples disclosed higher VIM transcript, protein, and methylation levels in BlCa compared with normal urothelium. VIM protein and transcript levels significantly increased from non-muscle invasive (NMIBC) to muscle-invasive (MIBC) cases and to BlCa metastases. Inverse correlation between epithelial CDH1 and VIM, and a positive correlation between mesenchymal CDH2 and VIM were also observed. In BlCa cell lines, exposure to demethylating agent increased VIM protein, with concomitant decrease in VIM methylation. Moreover, exposure to histone deacetylases pan-inhibitor increased the deposit of active post-translational marks (PTMs) across VIM promoter. In primary normal urothelium cells, lower levels of active PTMs with concomitant higher levels of repressive marks deposit were observed. Finally, VIM knockdown in UMUC3 cell line increased epithelial-like features and decreased migration and invasion in vitro, decreasing tumour size and angiogenesis in vivo. We demonstrated that VIM promoter is epigenetically regulated in normal and neoplastic urothelium, which determine a VIM switch associated with EMT and acquisition of invasive and metastatic properties. These findings might allow for development of new, epigenetic-based, therapeutic strategies for BlCa.

Spontaneous coronary artery dissection: Ten years' experience of a tertiary center.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) represents 1-4% of all acute coronary syndromes (ACS), and is a particularly important cause among young women and individuals with few cardiovascular risk factors. OBJECTIVES: To characterize clinical background, therapeutic management and clinical outcomes in a SCAD population. METHODS: We retrospectively analyzed all consecutive patients diagnosed with SCAD at a tertiary center between August 2009 and May 2020, with a median follow-up of 40 months (IQR 14-95 months). SCAD was classified according to the Saw angiographic SCAD classification. RESULTS: A total of 36 patients were included, 94% female, mean age 51 years (±11 years). A trigger was only detected in 8% and associated conditions in 31% of patients, mainly inflammatory or autoimmune systemic diseases and migraine. Most patients had non-ST-elevation ACS and 33% presented with ST-elevation ACS. The most frequent culprit lesion was the left anterior descending (LAD) artery (67%); mid to distal segments were the most affected (94%) and type 2 dissection the most prevalent (60%). Almost all patients were successfully medically managed, with only four undergoing percutaneous intervention. During follow-up, ischemic events recurred in 15% of patients and no patient died. Patients with type 2 dissection exhibited lower risk of recurrence compared to type 1 (p=0.049, OR=0.13). CONCLUSION: SCAD patients were mainly young or middle-aged women; the LAD artery was the most affected vessel and type 2 dissection the most prevalent. This report showed for the first time a correlation between type 2 SCAD and lower risk of recurrence.

Maternal immune activation induces autism-like behavior and reduces brain-derived neurotrophic factor levels in the hippocampus and offspring cortex of C57BL/6 mice.

Prenatal factors such as viral or bacterial infections occurring mainly during the first trimesters of pregnancy can increase the incidence of autism spectrum disorder (ASD) in children. In an animal model, it is already known that maternal immune activation (MIA) induces autistic-like behavior. However, it is unclear whether this behavior presents itself in young animals. In this preclinical experimental study, we investigated in the offspring of C57BL/6 female mice submitted to MIA with lipopolysaccharide (LPS), typically altered behaviors in ASD, such as social interaction and stereotyped self-grooming movement, as well as the levels of the brain-derived neurotrophic factor (BDNF) and interleukin 17A (IL-17A) in the hippocampus and cortex, at 28 and 60 days. Adult animals aged 60 days, offspring of females submitted to MIA, showed a decrease in the time of social interaction and an increase in the number of self-cleaning movements. In the hippocampus of the offspring of females submitted to MIA, a decrease in BDNF levels was found at 28 days and 60 days of life, and a decrease in IL-17A levels only at 60 days. The levels of BDNF and IL-17A did not change in the cortex of the offspring of mice submitted to MIA at the evaluated times. Young animals aged 28 days still showed typical behavior, without social deficits and stereotyped movements that characterize ASD, which suggests that at this age it is still not possible to observe the repercussions of MIA in this model. In the neurochemical issues of the hippocampal region, impairment of BDNF levels has already been demonstrated, which may be an important factor for the observation of ASD-like behaviors in adult mice at 60 days.