Presentation of the ATLETAS DA VOZ™ Conditioning Program

Objectives: To present a simple form of vocal and breathing conditioning for voice professionals based on concepts from vocal science. The vocal conditioning program called Voice Athletes Conditioning uses the principles of exercise physiology to gradually improve vocal and respiratory overload to achieve endurance, power, and flexibility. Methods: Due to our personal experience with high voice users, we synthesized a vocal conditioning program (AVCP) that combines voice science, exercise physiology, sports science and physical therapy principles. This is an 8-week program of daily vocal and breathing exercises with overload enhancement each week using different types of breathing devices and semi-occluded vocal tract exercises, designed and developed according to the specific requirements and performance of the voice professional. Reflections: Professional voice users often experience episodes of vocal fatigue that can directly affect their performance and vocal health. As with physical training for athletes, voice exercises can also contribute to improving vocal conditioning, preventing voice disorders, as well as helping to obtain better performance, greater tolerance to fatigue and shorter recovery time. Conclusions: AVCP is an approach that considers the principles of muscle training aimed objectively at the respiratory and vocal muscles, carried out with a variety of breathing devices and specific vocal exercises in search of greater performance time, less physiological stress, and shorter recovery time in the professional use of the voice.

Objetivos: Presentar una forma sencilla de acondicionamiento vocal y respiratorio para profesionales de la voz, basada en conceptos de la ciencia vocal. El programa de acondicionamiento vocal denominado Voice Athletes Conditioning utiliza los principios de la fisiología del ejercicio para mejorar gradualmente la sobrecarga vocal y respiratoria, con el fin de lograr resistencia, potencia y flexibilidad. Métodos: Debido a nuestra experiencia personal con usuarios de voz aguda, sintetizamos un programa de acondicionamiento vocal (AVCP) que combina principios de la ciencia de la voz, la fisiología del ejercicio, las ciencias del deporte y la fisioterapia. Se trata de un programa de 8 semanas de ejercicios vocales y respiratorios diarios con realce de sobrecarga cada semana utilizando diferentes tipos de dispositivos respiratorios y ejercicios semioclusivos del tracto vocal, diseñado y desarrollado de acuerdo con los requerimientos específicos y el rendimiento del profesional de la voz. Reflexiones: Los usuarios profesionales de la voz experimentan a menudo episodios de fatiga vocal que pueden afectar directamente su rendimiento y salud vocal. Al igual que ocurre con el entrenamiento físico de los deportistas, los ejercicios vocales también pueden contribuir a mejorar el acondicionamiento vocal, prevenir trastornos de la voz, además de ayudar a obtener un mejor rendimiento, una mayor tolerancia a la fatiga y un menor tiempo de recuperación. Conclusiones: El AVCP es un enfoque que considera los principios del entrenamiento muscular dirigido objetivamente a la musculatura respiratoria y vocal, realizado con diversos aparatos respiratorios y ejercicios vocales específicos en busca de un mayor tiempo de actuación, menor estrés fisiológico y menor tiempo de recuperación en el uso profesional de la voz.

Unveiling the Uncommon: A Rare Case of Group A Streptococcus Axillary Lymphadenitis With Ambiguous Presentation Leading to Multiple Misdiagnoses.

Axillary lymphadenitis in adults presents a diagnostic challenge due to its diverse etiology and variable clinical manifestations. We present a rare case of suppurative Group A Streptococcus (GAS) axillary lymphadenitis secondary to a puncture wound, emphasizing the critical importance of differential diagnosis and immediate intervention. A 36-year-old male initially presented with left axillary pain and discomfort following a traumatic injury to the left thumb. Despite multiple healthcare encounters and misdiagnoses including viral illness and shingles, the patient's condition deteriorated, manifesting as fever, edema, and erythema in the left axilla. This case underscores the paramount significance of considering lymphadenitis in patients with axillary symptoms, particularly following trauma or skin breaches. Early recognition and appropriate management are crucial to prevent grave complications such as abscess formation, thrombophlebitis, and bacteremia. Streptococcal axillary lymphadenitis should be included at the forefront of the differential diagnosis to expedite treatment and mitigate potential life-threatening consequences associated with delayed diagnosis.

In situ study of the effect of endogenous and exogenous agents on color stability, hardness, and surface roughness of an elastomer for facial prostheses.

PURPOSE: To evaluate in situ the influence of sweat, oil, sunscreen, and disinfectant solution on the color stability, hardness, and roughness of elastomer for facial prostheses. MATERIALS AND METHODS: Standardized and intrinsically pigmented specimens remained in contact with human skin from the same person for 30 days, considering exposures (n = 36 per group), absent of exposition (Control, C); sweat and oiliness contact (SO); sweat and oiliness associated with sunscreen (SOS); 0.12% chlorhexidine digluconate immersion (CD0.12%); and all agents exposed (SOSCD). The main variables were color change (CIELab and National Standard Bureau system, NBS), Shore A hardness, and surface roughness, measured at baseline and 30 days. Qualitative analyses were performed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The data were analyzed by Kruskal-Wallis tests (color) and two-way ANOVA (hardness and roughness) with Sidak post-test (α = 0.05). RESULTS: CD0.12% (1.54 ± 0.49) and SOSCD (2.10 ± 1.03) had similar effects and caused the smallest color changes, considered mild and noticeable (NBS), respectively. SOS promoted the greatest color change (6.99 ± 1.43, NBS: large) and hardness (17.97 ± 0.56); SOS promoted intermediate roughness (3.48 ± 1.05) between SOSCD (2.25 ± 0.53), and two similar groups: C (4.46 ± 0.95), and CD0.12% (4.39 ± 1.26). The qualitative analysis showed an irregular, dense, dry, and whitish layer on the surface of the specimens exposed to sunscreen, which was reduced when in contact with 0.12% chlorhexidine digluconate. CONCLUSIONS: Endogenous and exogenous factors are capable of altering elastomer properties. The 0.12% chlorhexidine digluconate minimized the changes caused by sweat, oil, and sunscreen.

Unlocking Overexpressed Membrane Proteins to Guide Breast Cancer Precision Medicine.

Breast cancer (BC) is a prevalent form of cancer affecting women worldwide. However, the effectiveness of current BC drugs is limited by issues such as systemic toxicity, drug resistance, and severe side effects. Consequently, there is an urgent need for new therapeutic targets and improved tumor tracking methods. This study aims to address these challenges by proposing a strategy for identifying membrane proteins in tumors that can be targeted for specific BC therapy and diagnosis. The strategy involves the analyses of gene expressions in breast tumor and non-tumor tissues and other healthy tissues by using comprehensive bioinformatics analysis from The Cancer Genome Atlas (TCGA), UALCAN, TNM Plot, and LinkedOmics. By employing this strategy, we identified four transcripts (LRRC15, EFNA3, TSPAN13, and CA12) that encoded membrane proteins with an increased expression in BC tissue compared to healthy tissue. These four transcripts also demonstrated high accuracy, specificity, and accuracy in identifying tumor samples, as confirmed by the ROC curve. Additionally, tissue microarray (TMA) analysis revealed increased expressions of the four proteins in tumor tissues across all molecular subtypes compared to the adjacent breast tissue. Moreover, the analysis of human interactome data demonstrated the important roles of these proteins in various cancer-related pathways. Taken together, these findings suggest that LRRC15, EFNA3, TSPAN13, and CA12 can serve as potential biomarkers for improving cancer diagnosis screening and as suitable targets for therapy with reduced side effects and enhanced efficacy.

Primary small lymphocytic lymphoma of the breast: a rare presentation of non-Hodgkin's lymphoma.

Primary Small Lymphocytic Lymphoma of the breast is a rare presentation of Non-Hodgkin's lymphoma. In this report, we present the case of primary small lymphocytic lymphoma of the breast in a 65-year-old female who presented with an abnormal breast ultrasound significant for a nodule of the right breast consistent with BI-RADS 4, indicating follow-up with ultrasound-guided biopsy for further diagnostic evaluation. The patient had no prior history of extramammary lymphoma or widespread disease. A sample of the breast mass was obtained via ultrasound-guided core needle biopsy and the pathology report revealed low-grade B-cell Lymphoma. After discussion with medical oncology and the explanation of risks, benefits and alternatives to surgery, a lumpectomy was performed, and the final pathology report of the mass revealed primary low-grade B-cell lymphocytic lymphoma of the breast. On follow up, the PET scan was unremarkable and showed no evidence of abnormal glucose metabolism or adenopathy.

High-Content Imaging-Based Assay for SARS-CoV-2-Neutralizing Antibodies.

The COVID-19 pandemic and the consequent emergence of new SARS-CoV-2 variants of concern necessitates the determination of populational serum potency against the virus. Here, we standardized and validated an imaging-based method to quantify neutralizing antibodies against lentiviral particles expressing the spike glycoprotein (pseudovirus). This method was found to efficiently quantify viral titers based on ZsGreen-positive cells and detect changes in human serum neutralization capacity induced by vaccination with up to two doses of CoronaVac, Comirnaty, or Covishield vaccines. The imaging-based protocol was also used to quantify serum potency against pseudoviruses expressing spikes from Delta, Omicron BA.1.1.529, and BA.4/5. Our results revealed increases in serum potency after one and two doses of the vaccines evaluated and demonstrated that Delta and Omicron variants escape from antibody neutralization. The method presented herein represents a valuable tool for the screening of antibodies and small molecules capable of blocking viral entry and could be used to evaluate humoral immunity developed by different populations and for vaccine development.

Unusual Presentation of Leiomyoma in the Hindfoot.

A leiomyoma is a benign smooth muscle tumor that is most commonly found in the uterus. Limited studies have reported leiomyoma of the foot, rendering it an usual finding. We present a case of a 57-year-old female patient who presented to the clinic for a painless mass on the posteromedial side of the right heel. It was diagnosed by the radiologist on MRI as a probable schwannoma. The patient underwent surgical excision of this mass which turned out to be a leiomyoma on pathology report. Although foot leiomyoma is a rare finding, leiomyoma should be listed in the differential diagnosis when evaluating foot soft tissue masses. It is difficult to confirm the diagnosis clinically and radiographically, yet a histologic evaluation can affirm the diagnosis. Surgical excision is the treatment of choice offering immediate symptomatic relief.

Behavioral and biochemical consequences after chronic exposition to the herbicide atrazine in tadpoles.

Atrazine (ATZ) is the third most sold herbicide in Brazil, occupying the seventh position between most widely used pesticides. Due to its easy outflow, low reactivity and solubility, moderate adsorption to organic matter and clay, and long soil persistence, residual herbicide can be identified after long periods following application, and its usage has been prohibited in diverse countries. Amphibians are important bioindicators to assess impact of pesticide like atrazine, due to having a partial aquatic life cycle. This study had as objective to assess the response of bullfrog (Lithobates catesbeianus) tadpoles when exposed to this herbicide. Animals were exposed for a total of 168h to following concentrations: negative control, 40 µg/L, 200 µg/L, 2000 µg/L, 20000 µg/L of ATZ. Analysis of swimming activity was performed, and biochemical profile was assessed by analysis of blood and plasma glucose levels, urea, creatinine, cholesterol, HDL, triglycerides, glutamic pyruvic transaminase (GPT), alkaline phosphatase (AP), calcium, total proteins, phenol, peroxidase and polyphenol oxidase activity. Results exhibited malnutrition, anemia, likely muscle mass loss, and hepatic damage, indicating that ATZ can lead to an increase in energy to maintain homeostasis for animal survival.

Choroidal nevus through a broader vision: Retinal imaging acquisition captured with Broad Line Fundus Imaging technology.

OBJECTIVE: To describe the peculiarities in imaging acquisition of fourteen patients with choroidal nevus using the Broad Line Fundus Imaging (BLFI) technology. METHODS: Single-center, retrospective, cross-sectional analysis. RESULTS: All images were acquired using the BLFI technology. We have found that choroidal nevus is undetectable in the blue channel (BC) (435-500 nm) and the green channel (GC) (500-585 nm). The only visible changes are related to the drusen, which appeared in BC and GC as light focal dots, correlated to the yellowish foci in the true-color image. On the red channel (RC) (585-640 nm), all lesions revealed the same pattern: a well-defined dark spot, with enhanced contrast, allowing the better visualization, measuring, and characterization of the nevus when compared with the other color channels, including the true-color imaging. CONCLUSION: BLFI application in choroidal nevus might be helpful at presentation, refining the diagnostic reliability, and monitoring, as it allows for better detection of alterations in the lesions. The peculiarities of the choroidal nevus are better assessed when using the RC due to its longer wavelength and deeper penetration in the retina and choroid.

A polyvalent RNA vaccine reduces the immune imprinting phenotype in mice and induces neutralizing antibodies against omicron SARS-CoV-2.

Immune imprinting is now evident in COVID-19 vaccinated people. This phenomenon may impair the development of effective neutralizing antibodies against variants of concern (VoCs), mainly Omicron and its subvariants. Consequently, the boost doses with bivalent vaccines have not shown a significant gain of function regarding the neutralization of Omicron. The approach to design COVID-19 vaccines must be revised to improve the effectiveness against VoCs. Here, we took advantage of the self-amplifying characteristic of RepRNA and developed a polyvalent formulation composed of mRNA from five VoCs. LION/RepRNA Polyvalent induced neutralizing antibodies in mice previously immunized with LION/RepRNA D614G and reduced the imprinted phenotype associated with low neutralization capacity of Omicron B.1.1.529 pseudoviruses. The polyvalent vaccine can be a strategy to handle the low neutralization of Omicron VoC, despite booster doses with either monovalent or bivalent vaccines.

Aptamer-Based Recognition of Breast Tumor Cells: A New Era for Breast Cancer Diagnosis.

Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.

Use of surgical videos available on social media among retina surgeons: results of a vitreoretinal specialist survey / Uso de vídeos cirúrgicos nas mídias sociais entre cirurgiões de retina: resultados de uma pesquisa com especialista em retina

ABSTRACT Purpose: This study aimed to assess and interpret how vitreoretinal surgeons use surgical videos available on social media as complementary learning tools to improve, review, or update their abilities, considering their different levels of expertise. Methods: In this cross-sectional survey, an online survey was sent to vitreoretinal specialists and fellows. Results: This survey included 258 participants, of whom 53.88% had been in practice for >10 years (senior surgeons), 29.07% between 4 and 10 years (young surgeons), and 17.05% for <3 years (surgeons in training). Retinal surgical videos available on social media were used by 98.84% of the participants (95% confidence interval, 97.52%-100%). YouTube (91%) was the most common source of videos, and surgeons in training watched more videos on YouTube than senior surgeons. Regarding the preferred method when preparing for a procedure, 49.80% of the participants watched surgical videos available on social media, 26.27% preferred to "consult colleagues", and 18.82% preferred to seek information in scientific articles. Participants valued the most the "image quality" (88%) and presence of "surgical tips and tricks" (85%). Conclusion: Surgical videos can provide benefits in acquiring strategic skills, such as decision-making, surgical planning, and situational awareness. Retina surgeons used them as teaching aids regardless of their level of expertise, despite being relatively more valuable to surgeons in training or young surgeons.

RESUMO Objetivo: Avaliar e interpretar como os cirurgiões vitreorretinianos utilizam os vídeos cirúrgicos disponíveis nas mídias sociais como ferramentas complementares de aprendizagem para melhorar, revisar ou atualizar suas habilidades, considerando seus diferentes níveis de especialização. Métodos: Nesta pesquisa transversal, um survey online foi enviado à especialistas e aprendizes na área vítreo-retiniana. Resultados: Esta pesquisa incluiu 258 participantes, dos quais 53,88% atuavam há mais de 10 anos (cirurgiões seniores), 29,07% entre 4 e 10 anos (cirurgiões jovens) e 17,05% há menos de 3 anos (cirurgiões em treinamento). Vídeos cirúrgicos de retina nas mídias sociais foram usados por 98,84% dos participantes (intervalo de confiança de 95%, 97,52%-100%). A fonte mais comum de acesso aos vídeos foi o YouTube (91%), e o grupo de cirurgiões com menos de 3 anos de experiência assistiu mais vídeos no YouTube em comparação aos cirurgiões seniores. Assistir a vídeos cirúrgicos nas redes sociais foi o método preferido na preparação para um procedimento para 49,80% dos participantes versus 26,27% que preferiram "consultar colegas" e 18,82% que preferiram buscar informações em artigos científicos. A "qualidade de imagem" (88%) e a presença de "dicas e truques cirúrgicos" (85%) foram as características dos vídeos mais valorizadas pelos participantes. Conclusão: O uso de vídeos cirúrgicos pode trazer benefícios na aquisição de habilidades estratégicas, como tomada de decisão, planejamento cirúrgico e consciência situacional. Sua aplicação como auxiliar de ensino foi utilizada por cirurgiões de retina independentemente de seu nível de especialização, apesar de ser relativamente mais valioso para cirurgiões em formação ou com menos de 10 anos de experiência.

Telementoring versus face-to-face mentoring in the training of scleral fixation surgery of intraocular lenses.

PURPOSE: To assess telementoring as a complementary tool for surgical training of a scleral fixation technique. DESIGN: Randomized, controlled, two-arm, blinded clinical trial. METHODS: Using a 3D visualization system, 132 participants were randomized in order of enrollment into traditional face-to-face mentoring (n = 66) and telementoring (n = 66). A single surgeon mentored all participants in the 2 groups. The procedure was performed in a model suitable for training in intraocular lens fixation SimulEYE® (INSEYET, WESTLAKE VILLAGE, CA, USA). In the telementoring group, the images captured on a local computer were sent to a second computer located in another room through a teleconferencing platform in real-time. Nine steps of the recorded procedure were evaluated and scored by two masked independent surgeons experienced in the technique. MAIN OUTCOMES MEASURES: The primary outcomes evaluated were the global score (the sum of each score on the rubric), surgical failure, and surgical time (in seconds). RESULTS: Surgical success was achieved in 98.5% in the face-to-face group and in 95.5% in the telementoring group (p-value = 0.619). Minimal technical problems were reported in 8 procedures in the telementoring group (12%), without interfering with the surgical result, and completion of the procedure. CONCLUSIONS: Telementoring is an encouraging educational tool that can overcome geographical barriers to ease the transfer of abilities and knowledge. We lack evidence in terms of group differences for superiority comparing face-to-face and telementoring, in addition to presenting comparable results regarding surgical success and failure. More studies are needed to explore the impact of telementoring in other ophthalmological surgeries. TRIAL REGISTRATION: The Federal University of São Paulo institution's Research Ethics Committee reviewed and approved this study protocol (approval number, 5.383.484).

High-Resolution Manometry Contributions to the Physiology of Phonation

High-resolution manometry (HRM) is a motility diagnostic system that measures intraluminal pressure of the gastrointestinal tract using a series of closely spaced pressure sensors. The topographic plot generated by HRM software makes it possible to visualize phonation pressures at the pharynx, UES, and body of the esophagus in real time, indicating pressure intensity by color, which permits easy data interpretation. It has been largely used for swallowing study and dysphagia diagnosis. Due to the proximity of the pharyngoesophageal and laryngeal structures, this technology instigated voice researchers. Despite the few studies published so far, high-resolution manometry has yet proven to be an extremely useful tool in obtaining entire pharyngoesophageal segment pressure measurements during phonation. It also allows natural voice production not interfering with the mouth area. HRM data already brought light to subglottic pressure, vertical laryngeal excursion, cricopharyngeal muscle activation, air flow, muscle tension associated with vocalization and pressure variations associated with different phonatory stimuli.

La manometría de alta resolución (HRM, por sus siglas en inglés) es un sistema de diagnóstico de motilidad que mide la presión intraluminal del tracto gastrointestinal mediante una serie de sensores de presión dispuestos de manera cercana. El gráfico topográfico generado por el software de HRM permite visualizar las presiones de fonación en la faringe, el EEI y el cuerpo del esófago en tiempo real, indicando la intensidad de la presión mediante colores que facilitan la interpretación de los datos. Ha sido ampliamente utilizado para el estudio de la deglución y el diagnóstico de la disfagia. Debido a la proximidad de las estructuras faringoesofágicas y laríngeas, esta tecnología ha despertado el interés de los investigadores en voz. A pesar de los pocos estudios publicados hasta ahora, la manometría de alta resolución ha demostrado ser una herramienta extremadamente útil para obtener mediciones de presión de todo el segmento faringoesofágico durante la fonación. Además, permite la producción natural de la voz sin interferir en el área de la boca. Los datos de HRM ya han arrojado luz sobre la presión subglótica, la excursión laríngea vertical, la activación del músculo cricofaríngeo, el flujo de aire, la tensión muscular asociada con la vocalización y las variaciones de presión asociadas con diferentes estímulos fonatorios.

Synthesis of new non-natural L-glycosidic flavonoid derivatives and their evaluation as inhibitors of Trypanosoma cruzi ecto-nucleoside triphosphate diphosphohydrolase 1 (TcNTPDase1).

Trypanosoma cruzi is the pathogen of Chagas disease, a neglected tropical disease that affects more than 6 million people worldwide. There are no vaccines to prevent infection, and the therapeutic arsenal is very minimal and toxic. The unique E-NTPDase of T. cruzi (TcNTPDase1) plays essential roles in adhesion and infection and is a virulence factor. Quercetin is a flavonoid with antimicrobial, antiviral, and antitumor activities. Its potential as a partial inhibitor of NTPDases has also been demonstrated. In this work, we synthesized the non-natural L-glycoside derivatives of quercetin and evaluated them as inhibitors of recombinant TcNTPDase1 (rTcNTPDase1). These compounds, and quercetin and miquelianin, a natural quercetin derivative, were also tested. Compound 16 showed the most significant inhibitory effect (94%). Quercetin, miquelianin, and compound 14 showed inhibition close to 50%. We thoroughly investigated the inhibitory effect of 16. Our data suggested a competitive inhibition with a Ki of 8.39 µM (± 0.90). To better understand the interaction of compound 16 and rTcNTPDase1, we performed molecular dynamics simulations of the enzyme and docking analyses with the compounds. Our predictions show that compound 16 binds to the enzyme's catalytic site and interacts with important residues for NTPDase activity. As an inhibitor of a critical T. cruzi enzyme, (16) could be helpful as a starting point in the developing of a future treatment for Chagas disease. Furthermore, the discovery of (16) as an inhibitor of TcNTPDase1 may open new avenues in the study and development of new inhibitors of E-NTPDases.

Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.

Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.

A randomized clinical trial to evaluate the efficacy of L-carnitine L-tartrate to modulate the effects of SARS-CoV-2 infection.

Introduction: L-carnitine (LC) has been associated with inflammatory mediator reduction and with downregulating the angiotensin-converting enzyme-2 (ACE2) receptor, which is the target of SARS-CoV-2 attachment. Methods: This pilot phase 2 randomized, double-blind placebo-controlled trial contained two cohorts. Cohort 1 comprised 101 individuals with negative RT-PCR SARS-CoV-2 test results who cohabitated with an individual diagnosed with SARS-CoV-2 infection. Cohort 2 comprised 122 individuals with positive SARS-CoV-2 RT-PCR test results who were asymptomatic or had mild COVID-19 pneumonia symptoms. Participants in each cohort were randomized 1:1 to receive either 2 g elemental oral LC supplementation or placebo daily for 21 days. Primary endpoints included adverse events, SARS-CoV-2 infection incidence in Cohort 1, and disease progressions in Cohort 2. Secondary endpoints included between-group laboratory profile comparisons and Cohort 2 ACE1/ACE2 plasma levels. Disease progression was compared between the Cohort 2 groups using chest computed tomography. Results: In Cohort 1, two SARS-CoV-2 infections occurred in each group. The common adverse events included headache, dyspnea, and tiredness. In Cohort 2, platelet counts were elevated, and fibrinogen levels reduced in the LC group compared with those of the placebo group. Conclusion: Our study showed that LC was well-tolerated and suggests it modulates coagulation pathways. Furthermore, chest computed tomography images of the Cohort 2 LC group showed significant lung lesion improvement, suggesting that LC may slow COVID-19 progression.

Oxidation of whey protein isolate after thermal convection and microwave heating and freeze-drying: Correlation among physicochemical and NIR spectroscopy analyses.

This study investigated the oxidative susceptibility of whey protein isolate (WPI) dispersions treated by microwave or thermal convection before freeze-drying. WPI (20 mg protein/mL) in distilled water (DW) was heated at 63 ± 2 °C for 30 min by microwave (WPI-MW) or convection heating (WPI-CH) and freeze-dried. Untreated WPI (WPI-C), WPI solubilized in DW and freeze-dried (WPI-FD), and WPI solubilized in DW, heated at 98 ± 2 °C for 2 min and freeze-dried (WPI-B) were also evaluated. Structural changes (turbidity, ζ potential, SDS-PAGE, and near-infrared spectroscopy (NIR)) and protein oxidation (dityrosine, protein carbonylation, and SH groups) were investigated. WPI-FD showed alterations compared to WPI-C, mainly concerning carbonyl groups. Microwave heating increased carbonyl groups and dityrosine formation compared to conventional heating. NIR spectrum indicated changes related to the formation of carbonyl groups and PCA analysis allowed us to distinguish the samples according to carbonyl group content. The results suggest that NIR may contribute to monitoring oxidative changes in proteins resulting from processing.

An Overview of the Conventional and Novel Methods Employed for SARS-CoV-2 Neutralizing Antibody Measurement.

SARS-CoV-2 is the etiological agent of the coronavirus disease-19 (COVID-19) and is responsible for the pandemic that started in 2020. The virus enters the host cell through the interaction of its spike glycoprotein with the angiotensin converting enzyme-2 (ACE2) on the host cell's surface. Antibodies present an important role during the infection and pathogenesis due to many reasons, including the neutralization of viruses by binding to different spike epitopes. Therefore, measuring the neutralizing antibody titers in the whole population is important for COVID-19's epidemiology. Different methods are described in the literature, and some have been used to validate the main vaccines used worldwide. In this review, we discuss the main methods used to quantify neutralizing antibody titers, their advantages and limitations, as well as new approaches to determineACE2/spike blockage by antibodies.

Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms.

Background: Lipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain. Methods: Mice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (0.1, 1, or 10ng/animal) or vehicle (ethanol 3.2% in saline) administration. Pain-like behavior, inflammation, and dosages were performed to assess the effects of LXA4 in vivo. Results: LXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 improved antioxidant parameters [reduced glutathione (GSH) and 2,2-azino-bis 3-ethylbenzothiazoline-6-sulfonate (ABTS) levels, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and Nrf2 protein expression], reducing reactive oxygen species (ROS) fluorescent detection induced by TiO2 in synovial fluid leukocytes. We observed an increase of lipoxin receptor (ALX/FPR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2-induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons. Conclusion: LXA4 might target recruited leukocytes and primary afferent nociceptive neurons to exert analgesic and anti-inflammatory activities in a model resembling what is observed in patients with prosthesis inflammation.