PERK inhibition in zebrafish mimics human Wolcott-Rallison syndrome phenotypes.

Wolcott-Rallison Syndrome (WRS) is the most common cause of permanent neonatal diabetes mellitus among consanguineous families. The diabetes associated with WRS is non-autoimmune, insulin-requiring and associated with skeletal dysplasia and growth retardation. The therapeutic options for WRS patients rely on permanent insulin pumping or on invasive transplants of liver and pancreas. WRS has a well identified genetic cause: loss-of-function mutations in the gene coding for an endoplasmic reticulum kinase named PERK (protein kinase R-like ER kinase). Currently, WRS research is facilitated by cellular and rodent models with PERK ablation. While these models have unique strengths, cellular models incompletely replicate the organ/system-level complexity of WRS, and rodents have limited scalability for efficiently screening potential therapeutics. To address these challenges, we developed a new in vivo model of WRS by pharmacologically inhibiting PERK in zebrafish. This small vertebrate displays high fecundity, rapid development of organ systems and is amenable to highly efficient in vivo drug testing. PERK inhibition in zebrafish produced typical WRS phenotypes such as glucose dysregulation, skeletal defects, and impaired development. PERK inhibition in zebrafish also produced broad-spectrum WRS phenotypes such as impaired neuromuscular function, compromised cardiac function and muscular integrity. These results show that zebrafish holds potential as a versatile model to study WRS mechanisms and contribute to the identification of promising therapeutic options for WRS.

Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration.

INTRODUCTION: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies. OBJECTIVE: To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining. CASE DESCRIPTION: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE. RESULTS: The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 µm (276 µm to 292 µm) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369 µm (680 µm to 311 µm), at the twelfth year. CONCLUSIONS: Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.

Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.

Modifications in DNA repair pathways are recognized as prognostic markers and potential therapeutic targets in various cancers, including non-small cell lung cancer (NSCLC). Overexpression of ERCC1 correlates with poorer prognosis and response to platinum-based chemotherapy. As a result, there is a pressing need to discover new inhibitors of the ERCC1-XPF complex that can potentiate the efficacy of cisplatin in NSCLC. In this study, we developed a structure-based virtual screening strategy targeting the inhibition of ERCC1 and XPF interaction. Analysis of crystal structures and a library of small molecules known to act against the complex highlighted the pivotal role of Phe293 (ERCC1) in maintaining complex stability. This residue was chosen as the primary binding site for virtual screening. Using an optimized docking protocol, we screened compounds from various databases, ultimately identifying more than one hundred potential inhibitors. Their capability to amplify cisplatin-induced cytotoxicity was assessed in NSCLC H1299 cells, which exhibited the highest ERCC1 expression of all the cell lines tested. Of these, 22 compounds emerged as promising enhancers of cisplatin efficacy. Our results underscore the value of pinpointing crucial molecular characteristics in the pursuit of novel modulators of the ERCC1-XPF interaction, which could be combined with cisplatin to treat NSCLC more effectively.

Rehabilitation after cervical and lumbar spine surgery.

The total number of spine surgeries is increasing, with a variable percentage of patients remaining symptomatic and functionally impaired after surgery. Rehabilitation has been widely recommended, although its effects remain unclear due to lack of research on this matter. The aim of this comprehensive review is to resume the most recent evidence regarding postoperative rehabilitation after spine surgery and make recommendations. The effectiveness of cervical spine surgery on the outcomes is moderate to good, so most physiatrists and surgeons agree that patients benefit from a structured postoperative rehabilitation protocol and despite best timing to start rehabilitation is still unknown, most programs start 4-6 weeks after surgery. Lumbar disc surgery has shown success rates between 78% and 95% after 2 years of follow-up. Postoperative rehabilitation is widely recommended, although its absolute indication has not yet been proven. Patients should be educated to start their own postoperative rehabilitation immediately after surgery until they enroll on a rehabilitation program usually 4-6 weeks post-intervention. The rate of lumbar interbody fusion surgery is increasing, particularly in patients over 60 years, although studies report that 25-45% of patients remain symptomatic. Despite no standardized rehabilitation program has been defined, patients benefit from a cognitive-behavioral physical therapy starting immediately after surgery with psychological intervention, patient education and gradual mobilization. Formal spine rehabilitation should begin at 2-3 months postoperatively. Rehabilitation has benefits on the recovery of patients after spine surgery, but further investigation is needed to achieve a standardized rehabilitation approach.

The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin.

Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety/toxicity profile that has been studied in several types of cancer. It is currently in four phase I/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.

Fighting Multidrug Resistance with Ruthenium-Cyclopentadienyl Compounds: Unveiling the Mechanism of P-gp Inhibition.

The search for more effective and selective drugs to overcome cancer multidrug resistance is urgent. As such, a new series of ruthenium-cyclopentadienyl ("RuCp") compounds with the general formula [Ru(η5-C5H4R)(4,4'-R'-2,2'-bipy)(PPh3)] were prepared and fully characterized. All compounds were evaluated toward non-small cell lung cancer cells with different degrees of cisplatin sensitivity (A549, NCI-H2228, Calu-3, and NCI-H1975), showing better cytotoxicity than the first-line chemotherapeutic drug cisplatin. Compounds 2 and 3 (R' = -OCH3; R = CHO (2) or CH2OH (3)) further inhibited the activity of P-gp and MRP1 efflux pumps by impairing their catalytic activity. Molecular docking calculations identified the R-site P-gp pocket as the preferred one, which was further validated using site-directed mutagenesis experiments in P-gp. Altogether, our results unveil the first direct evidence of the interaction between P-gp and "RuCp" compounds in the modulation of P-gp activity and establish them as valuable candidates to circumvent cancer MDR.

The ideal patient positioning in spine surgery: a preventive strategy.

Patient positioning on the surgical table is a critical step in every spine surgery. The most common surgical positions in spine surgery are supine, prone and lateral decubitus. There are countless lesions that can occur during spine surgery due to patient mispositioning. Ulnar nerve and brachial plexus injuries are the most common nerve lesions seen in malpositioned patients. Devastating complications due to increased intraocular pressure or excessive abdominal pressure can also occur in prone decubitus and are real concerns that the surgical team must be aware of. All members of the surgical team (including surgeons, anesthesiologists and nurses) should know how to correctly position the patient, identify possible positioning errors and know how to avoid them in order to prevent postoperative morbidity. This work pretends to do a review of the most common positions during spine surgery, alert to errors that can happen during the procedure and how to avoid them.

The Dietary Isothiocyanate Erucin Reduces Kidney Cell Motility by Disturbing Tubulin Polymerization.

SCOPE: Epidemiological evidence associates the consumption of cruciferous vegetables with reduced risk of several cancers, including renal cell carcinoma. Erucin can be generated by in vivo reduction of sulforaphane or by enzymatic hydrolysis of glucoerucin. Contrarily to sulforaphane, only limited studies have addressed the anticancer properties of erucin. This study aims at evaluating the impact of erucin on renal cell biology. METHODS AND RESULTS: The effects of erucin were assessed in 786-O and Vero-E6 cells, representative of human renal cancer and non- cancer kidney cells, respectively. Erucin induced a concentration-dependent decrease in cell viability and cell cycle arrest at G2/Mitosis. In Vero-E6 cells erucin modestly reduced intracellular reactive oxygen species levels while in 786-O no effects were detected. After erucin treatment, both cell lines revealed altered morphology, with a concentration-dependent change from an elongated shape towards a smaller round conformation. Moreover, erucin affected cell adhesion and strongly altered the tubulin network structure and specifically microtubule polymerization. These results are in line with the observed decrease in collective and single cell migration and G2/Mitosis arrest. CONCLUSIONS: Overall, erucin may have a beneficial impact in reducing the motility of renal cancer cells. Our results contribute to explore possible dietary approaches for secondary/tertiary renal cancer chemoprevention.

MnTnHex-2-PyP5+ Displays Anticancer Properties and Enhances Cisplatin Effects in Non-Small Cell Lung Cancer Cells.

The manganese(III) porphyrin MnTnHex-2-PyP5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for lung cancer, hardly any information is available. Thus, the present work aims to fill this gap and reports the effects of MnTnHex in non-small cell lung cancer (NSCLC) cells, more specifically, A549 and H1975 cells, in vitro. Both cell lines were initially characterized in terms of innate levels of catalase, glutathione peroxidase 1, and peroxiredoxins 1 and 2. To assess the effect of MnTnHex in NSCLC, alone or in combination with cisplatin, endpoints related to the cell viability, cell cycle distribution, cell motility, and characterization of the volatile carbonyl compounds (VCCs) generated in the extracellular medium (i.e., exometabolome) were addressed. The results show that MnTnHex as a single drug markedly reduced the viability of both NSCLC cell lines, with some IC50 values reaching sub-micromolar levels. This redox-active drug also altered the cell cycle distribution, induced cell death, and increased the cytotoxicity pattern of cisplatin. MnTnHex also reduced collective cell migration. Finally, the metabolomics study revealed an increase in the levels of a few VCCs associated with oxidative stress in MnTnHex-treated cells. Altogether these results suggest the therapeutic potential of MnTnHex to be further explored, either alone or in combination therapy with cisplatin, in NSCLC.

An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava.

Kava (Piper methysticum) has been widely consumed for many years in the South Pacific Islands and displays psychoactive properties, especially soothing and calming effects. This plant has been used in Western countries as a natural anxiolytic in recent decades. Kava has also been used to treat symptoms associated with depression, menopause, insomnia, and convulsions, among others. Along with its putative beneficial health effects, kava has been associated with liver injury and other toxic effects, including skin toxicity in heavy consumers, possibly related to its metabolic profile or interference in the metabolism of other xenobiotics. Kava extracts and kavalactones generally displayed negative results in genetic toxicology assays although there is sufficient evidence for carcinogenicity in experimental animals, most likely through a non-genotoxic mode of action. Nevertheless, the chemotherapeutic/chemopreventive potential of kava against cancer has also been suggested. Both in vitro and in vivo studies have evaluated the effects of flavokavains, kavalactones and/or kava extracts in different cancer models, showing the induction of apoptosis, cell cycle arrest and other antiproliferative effects in several types of cancer, including breast, prostate, bladder, and lung. Overall, in this scoping review, several aspects of kava efficacy and safety are discussed and some pertinent issues related to kava consumption are identified.

Novel US-CpHMD Protocol to Study the Protonation-Dependent Mechanism of the ATP/ADP Carrier.

We have designed a protocol combining constant-pH molecular dynamics (CpHMD) simulations with an umbrella sampling (US) scheme (US-CpHMD) to study the mechanism of ADP/ATP transport (import and export) by their inner mitochondrial membrane carrier protein [ADP/ATP carrier (AAC)]. The US scheme helped overcome the limitations of sampling the slow kinetics involved in these substrates' transport, while CpHMD simulations provided an unprecedented realism by correctly capturing the associated protonation changes. The import of anionic substrates along the mitochondrial membrane has a strong energetic disadvantage due to a smaller substrate concentration and an unfavorable membrane potential. These limitations may have created an evolutionary pressure on AAC to develop specific features benefiting the import of ADP. In our work, the potential of mean force profiles showed a clear selectivity in the import of ADP compared to ATP, while in the export, no selectivity was observed. We also observed that AAC sequestered both substrates at longer distances in the import compared to the export process. Furthermore, only in the import process do we observe transient protonation of both substrates when going through the AAC cavity, which is an important advantage to counteract the unfavorable mitochondrial membrane potential. Finally, we observed a substrate-induced disruption of the matrix salt-bridge network, which can promote the conformational transition (from the C- to M-state) required to complete the import process. This work unraveled several important structural features where the complex electrostatic interactions were pivotal to interpreting the protein function and illustrated the potential of applying the US-CpHMD protocol to other transport processes involving membrane proteins.

Ovarian steroid cell tumour inducing virilisation in a postmenopausal woman.

Hyperandrogenism with virilisation de novo in postmenopausal women is exceedingly rare, with aetiology oscillating between ovarian tumours, adrenal tumours, ovarian hyperthecosis and, less frequently, Cushing's syndrome. We report a case of a postmenopausal woman in her late 60s, referred from her primary healthcare physician to a gynaecology appointment due to hirsutism and vasomotor symptoms. At physical examination, clitoromegaly was also identified. Blood tests revealed severe hyperandrogenemia, with total testosterone above 200 ng/dL, but transvaginal ultrasound and abdominal CT were unremarkable. Three months later, abdominal CT was repeated, revealing a moderate heterogeneous enhancement with 18 mm on the left ovary, which was confirmed by transvaginal ultrasound. Total laparoscopic hysterectomy with bilateral adnexectomy was performed. Histopathological examination reported an ovarian steroid cell tumour not otherwise specified on the left ovary and bilateral ovarian hyperthecosis. Two months later, the patient had normal total testosterone and the hirsutism complaints were completely absent.

Adenomyosis in a uterine horn of a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.

A 37-year-old woman with a previous diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome at 18 years of age was referred from a primary healthcare physician to a gynaecology appointment in our centre. She presented with a 2-year worsening pelvic pain and dyspareunia, symptoms that were previously absent and, at the time, with inadequate relief with oral analgesia. Physical examination showed absent uterine cervix and hypoplastic superior vagina. Transvaginal ultrasound and MRI suggested the presence of an hypoplasic uterus in left rotation. Laparoscopically, two asymmetric rudimentary horns were found, united by a fibrous central band, with an enlarged and congestive left horn. The three structures were removed as a whole. Histopathological examination reported the presence of multiple adenomyotic foci along the full thickness of the left rudimentary horn. The patient had an uneventful postoperative recovery and full remission of her symptoms.

Improved Clinical Outcomes After Lateralized Reverse Shoulder Arthroplasty: A Systematic Review.

BACKGROUND: Lateralized reverse shoulder arthroplasty (RSA) has emerged as an attempt to improve on some of the drawbacks of conventional RSA, such as glenoid notching and decrease in ROM. Although this new design is being used in clinical practice, the evidence is mostly limited to case series and has not been systematically reviewed. QUESTIONS/PURPOSES: (1) How much did patient-reported outcome measures (PROMs) and ROM improve among patients who receive a lateralized RSA implant? (2) What proportion of shoulders experience complications, revision surgery, or scapular notching? METHODS: The PubMed and EMBASE databases were searched from database inception to January 31, 2020. We included clinical studies that reported the PROMs and/or ROM of patients with insufficient rotator cuffs undergoing RSA with a lateralized implant. All other types of studies and those including patients with fractures, instability or escape, infection, rheumatologic disease, neurologic disease, or revision surgeries as an indication for RSA were excluded. PROMs and ROM were collected and are reported as mean values and ranges. Complications, revision surgery, and scapular notching are presented as proportions. The percentage of the mean change relative to the minimum clinically important difference (MCID) was calculated using the anchor-based value for each outcome. The Methodological Index for Non-randomized Studies (MINORS) was used to assess study quality. The initial search yielded 678 studies; 61 full-text articles were analyzed according to our eligibility criteria. After a detailed analysis, we included nine studies that evaluated 1670 patients (68% of whom [1130] were women) with a mean age of 71.8 ± 0.6 years. The mean follow-up period was 41.1 ± 5.6 months. The mean MINORS score was 12 ± 4. RESULTS: Active ROM improved for forward flexion (mean change 47° to 82°; MCID 12°), abduction (mean change 43° to 80°; MCID 7°), external rotation (mean change 8° to 39°; MCID 3°), and internal rotation (mean change -2 to 1 points). PROM scores also improved, including the American Shoulder and Elbow Surgeons score (mean change 20 to 50; MCID 20.9 points), Constant score (mean change 28 to 40; MCID 5.7 points), Simple Shoulder Test score (mean change 3 to 7; MCID 2.4 points), and VAS score (mean change -1.8 to -4.9; MCID -1.6 points). The proportion of shoulders with complications ranged from 0% (0 of 44) to 21% (30 of 140), and the proportion of shoulders with scapular notching ranged from 0% (0 of 76) to 29% (41 of 140). The proportion of patients undergoing revision ranged from 0% (0 of 44) to 13% (10 of 76) at short-term follow-up. CONCLUSION: Lateralized RSA is a reasonable alternative to medialized implants for patients with rotator cuff insufficiency because it might reduce the likelihood of scapular notching without apparently compromising PROMs or ROM. More studies are required to determine whether there is a direct correlation between the amount of lateralization and PROMs or ROM.

The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells.

Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.

A narrative review of the migration and invasion features of non-small cell lung cancer cells upon xenobiotic exposure: insights from in vitro studies.

Lung cancer (LC) is the leading cause of cancer deaths worldwide, being non-small lung cancer (NSCLC) sub-types the most prevalent. Since most LC cases are only detected during the last stage of the disease the high mortality rate is strongly associated with metastases. For this reason, the migratory and invasive capacity of these cancer cells as well as the mechanisms involved have long been studied to uncover novel strategies to prevent metastases and improve the patients' prognosis. This narrative review provides an overview of the main in vitro migration and invasion assays employed in NSCLC research. While several methods have been developed, experiments using conventional cell culture models prevailed, specifically the wound-healing and the transwell migration and invasion assays. Moreover, it is provided herewith a summary of the available information concerning chemical contaminants that may promote the migratory/invasive properties of NSCLC cells in vitro, shedding some light on possible LC risk factors. Most of the reported agents with pro-migration/invasion effects derive from cigarette smoking [e.g., Benzo(a)pyrene and cadmium] and air pollution. This review further presents several studies in which different dietary/plant-derived compounds demonstrated to impair migration/invasion processes in NSCLC cells in vitro. These chemicals that have been proposed as anti-migratory consisted mainly of natural bioactive substances, including polyphenols non-flavonoids, flavonoids, bibenzyls, terpenes, alkaloids, and steroids. Some of these compounds may eventually represent novel therapeutic strategies to be considered in the future to prevent metastasis formation in LC, which highlights the need for additional in vitro methodologies that more closely resemble the in vivo tumor microenvironment and cancer cell interactions. These studies along with adequate in vivo models should be further explored as proof of concept for the most promising compounds.

Confiabilidade da baropodometria na avaliação do equilíbrio de indivíduos com deficiência visual / Reliability of baropodometry in assessing the balance of individuals with visual impairment

Indivíduos com deficiência visual podem apresentar déficits de equilíbrio e existem diversos métodos capazes de avalia-lo, sendo a baropodometria um método em expansão, porém com escassez de estudos que abordem suas medidas psicométricas e avaliações padronizados. Objetivo: Avaliar a confiabilidade relativa e absoluta da baropodometria em um protocolo de avaliação de equilíbrio para pessoas com deficiência visual. Método: Estudo observacional, de corte transversal, com 38 indivíduos, de ambos os sexos, com e sem diagnóstico de deficiência visual, sendo alocados: grupo controle (GCO) (n= 13) composto por indivíduos sem deficiência visual, grupo baixa visão (GBV) (n= 15), grupo cegueira (GCE) (n= 10) e posteriormente realizada a junção do GBV e GCE, compondo o grupo deficiência visual (GDV) (n= 25). Para avaliar a confiabilidade da baropodometria, utilizou-se o método teste e reteste, com um intervalo de sete dias. Os indivíduos foram avaliados em três condições, apoio bipodal, apoio unipodal direito e apoio unipodal esquerdo considerando as variáveis área, amplitude e velocidade média anteroposterior e laterolateral. Para confiabilidade relativa foi utilizado o Coeficiente de Correlação Intraclasse (CCI) e para a confiabilidade absoluta o erro padrão da medida (EPM). Resultados: Em relação a confiabilidade relativa, os CCIs das variáveis da baropodometria variaram de baixo a muito alto em todos os grupos, com melhor confiabilidade nas condições de apoios unipodais e maior índice no GCE. Na confiabilidade absoluta, 14 variáveis apresentaram boa confiabilidade. Conclusão: A baropodometria apresenta-se como um método confiável, porém deve-se ter cautela na escolha do posicionamento e da variável a ser analisada.

Individuals with visual impairment may have balance deficits and there are several methods capable of evaluating it, and baropodometry is an expanding method, but with a lack of studies that address its psychometric measures and standardized assessments. Objective: To assess the relative and absolute reliability of baropodometry in a balance assessment protocol for visually impaired people. Methods: Observational, cross-sectional study, with 38, of both sexes, with and without a diagnosis of visual impairment, were included in three groups: control group (CG) (n= 13) composed of individuals without visual impairment, low vision group (LVG) (n= 15), blindness group (BG) (n= 10) and subsequently the LVG and BG were joined, making up the group visual impairment (VIG) (n= 25). To evaluate the reliability of baropodometry, the test and retest method was used, with an interval of seven days. The individuals were evaluated in three conditions, support bipedal, right unipodal support and left unipodal support considering the variables area, amplitude and mean anteroposterior and laterolateral speed. For relative reliability, the Intraclass Correlation Coefficient (ICC) was used and for absolute reliability the standard error of measurement (SEM). Results: Regarding the relative reliability, the ICCs of the baropodometry variables varied from low to very high in all groups, with better reliability in the conditions of unipodal supports and a higher index in the BG. In absolute reliability, 14 variables showed good reliability. Conclusion: Baropodometry is a reliable method, however, care must be taken when choosing the position and the variable to be analyzed.

Missed Tillaux Fracture and Syndesmosis Injury in Adult: Arthroscopic Assisted Reduction and Fixation / Fratura de Tillaux não percebida e lesão por sindesmose em adultos: Redução e fixação artroscópica assistida

Abstract Tillaux fractures are fractures of the lateral margin of the distal tibia, usually reported in children between 12 and 14 years old. As intraarticular fractures, they require anatomic reduction and fixation to avoid posttraumatic complications. Since the injury mechanism is external rotation of the foot on the leg, these injuries are commonly associated with other fractures or ligamentous lesions. Currently, arthroscopy is being increasingly used to assist and improve surgical treatment of ankle fractures. The authors describe a 12-month follow-up of a rare case of a missed Tillaux fracture associated with syndesmosis injury in a 76-year-old polytrauma patient, successfully treated by arthroscopically-assisted reduction and internal fixation.

Resumo As fraturas de Tillaux são fraturas da margem lateral da tíbia distal, geralmente relatadas em crianças entre 12 e 14 anos. Como fraturas intra-articulares, requerem redução e fixação anatômica para evitar complicações pós-traumáticas. Como o mecanismo de lesão é a rotação externa do pé na perna, essas lesões são comumente associadas a outras fraturas ou lesões ligamentares. Atualmente, a artroscopia está sendo cada vez mais utilizada para auxiliar e melhorar o tratamento cirúrgico das fraturas do tornozelo. Os autores descrevem um acompanhamento de 12 meses de um caso raro de uma fratura não percebida de Tillaux associada a lesão por sindesmose em um paciente de politrauma com 76 anos de idade, tratado com sucesso por redução e fixação interna assistida por artroscopia.

Foreign Body in the Eustachian Tube: A Challenging Diagnosis and Management.

Foreign bodies in the external ear are very common. The same cannot be said about foreign bodies in the Eustachian tube (ET). We report the case of a 63-year-old woman with a history of painless left side otorrhea and hearing loss. She reported a left ear surgery when she was 30-year-old but she did not know the diagnosis that was made at that time neither the kind of surgery performed. Otoscopic examination revealed an inferior perforation of the eardrum. Audiologic evaluation demonstrated a unilateral, moderate-severe mixed hearing loss. Computed tomography scan showed, in left ear, a soft tissue density filling the middle ear cavity and a foreign body in ET. The patient underwent middle ear exploration which required endoscopic assistance to visualize and remove the foreign body. It appeared to be a stapes prothesis of Robinson type. The displacement of a stapes prosthesis to the ET has not been reported in the literature. Surgeries in this region are challenging. This case highlights the importance of the integration of endoscopy into otologic surgery.

Genetic toxicology and toxicokinetics of arecoline and related areca nut compounds: an updated review.

Areca nut (AN) is consumed by more than 600 million of individuals, particularly in some regions of South Asia, East Africa, and tropical Pacific, being classified as carcinogenic to humans. The most popular way of exposure consists of chewing a mixture of AN with betel leaf, slaked lime, and other ingredients that may also contain tobacco named betel quid (BQ). Arecoline is the principal active compound of AN, and, therefore, has been systematically studied over the years in several in vitro and in vivo genotoxicity endpoints. However, much of this information is dispersed, justifying the interest of an updated and comprehensive review article on this topic. In this sense, it is thus pertinent to describe and integrate the genetic toxicology data available as well as to address key toxicokinetics aspects of arecoline. This review also provides information on the effects induced by arecoline metabolites and related compounds, including other major AN alkaloids and nitrosation derivatives. The complexity of the chemicals involved renders this issue a challenge in genetic toxicology. Overall, positive results in several endpoints have been reported, some of them suggesting a key role for arecoline metabolites. Nevertheless, some negative genotoxicity findings for this alkaloid in short-term assays have also been reported in the literature. Finally, this article also collates information on the potential mechanisms of arecoline-induced genotoxicity, and suggests further approaches to tackle this important toxicological issue.