Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study.

PURPOSE: Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS: We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS: Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS: Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.

Effect of Makeup Use on Depressive Symptoms: An Open, Randomized and Controlled Trial.

INTRODUCTION: Depression is one of the most disabling diseases globally, with a high disease burden that generates high direct and indirect costs. The incidence of depression is twofold higher in adult women than in men. Biological and psychosocial factors constitute the pathophysiological bases of the condition and due to the complexity of the condition, current understanding is that the "treatment strategy must be multimodal". The objective of this study was to measure the effect of introducing the frequent use of makeup on improving depressive symptoms in adult women of medium-low purchasing power METHODS: Participants with the targeted profile who did not frequently use makeup were selected and randomised to receive (test group) or not (control group) stimuli and makeup products intended for encouraging the frequent use of makeup. The Zung Depression Self-Assessment Scale was used to assess depressive symptoms, with additional assessments on self-image perception using the mirror test and salivary cortisol level. RESULTS: The results demonstrated a sustained reduction in depressive symptoms (8.3 percentage points reduction in the Average Zung Index; P < 0.05), with a significant improvement in self-image perception (25% increase in the average score obtained in the mirror test; P < 0.05) and a specific influence on salivary cortisol levels (55% reduction in salivary cortisol concentration; P < 0.05) after the first makeup application. CONCLUSION: The results show that encouraging the frequent use of makeup, a practice that can be achieved by most people and which is simple and inexpensive to implement, can contribute to effective and sustainable improvement in the well-being and mental health of a significant portion of the population.

Effect of sweetened beverages intake on salivary aspartame, insulin and alpha-amylase levels: A single-blind study.

The objective was to assess aspartame excretion in saliva and the salivary insulin, total protein (TP), and alpha-amylase (AMI) levels in response to the ingestion of sweetened beverages (sodium cyclamate, aspartame, acesulfame, and sucrose). Fifteen healthy participants were included in a single-blinded trial with the intake of Diet soft drink, Regular soft drink, Water + sweeteners, Low sucrose content (3.5 g), and Water (blank) in 5 different days. In each day, saliva was collected at T0 (fasting), T1 (15 min after test-drink intake), T2 (30 min), T3 (60 min), and T4 (120 min) for the measurement of salivary aspartame (HPLC), TP, AMI (ELISA assays) and insulin levels (chemiluminescence). Chi-square, Friedman, ANOVA and Spearman correlation tests were applied. The late-perceived sweet/sour residual flavor was reported at a frequency of 80%, 60% and 20% after ingestion of artificially sweetened drinks, beverages with sucrose, and plain water, respectively (p < 0.05). Aspartame was detected in saliva after artificially sweetened drinks intake, with highest area under the peak for the Diet soft drink (p = 0.014). No change was observed for TP and AMI levels during the 120 min. Insulin levels increased 1 h after soft-drinks ingestion (regular and diet), while the levels did not change for Low sucrose content and Water + sweeteners test-drinks. Salivary aspartame correlated with insulin levels only after Diet soft drink intake (rho ≥ 0.7; p < 0.05). As aspartame can be detected in saliva and swallowed again until completely excreted, these results contribute to the knowledge of the biological fate of artificial sweeteners and the study of health outcomes.

Association Between Frequent Use of Makeup and Presence of Depressive Symptoms-Population-Based Observational Study, Including 2400 Participants.

INTRODUCTION: The increased prevalence of depression is a global phenomenon, with an estimated 320 million cases worldwide. In Brazil, the World Health Organization (WHO) estimated that there are about 12 million cases or more, mainly among adult women with lower socioeconomic status, leading to a high consumption of health resources. Studies suggest a positive association of measures related to appearance care on depressive symptoms, but usually with no objective methodology. This study aimed to estimate the prevalence of depressive symptoms in adult Brazilian women with lower purchasing power and to verify the association between the intensity of symptoms and the use of makeup. METHODS: A national sample of 2400 cases from all regions of the country, drawn randomly from an online panel representative of the Brazilian population, was studied using an online questionnaire accessible via computer or smartphone, from which the frequency of use of makeup was surveyed, and the Zung Depressive Self-Rating Scale was applied for the inventory of symptoms. RESULTS: A prevalence of 61.4% (0.59-0.63) of depressive symptoms was identified. The association between frequent use of makeup and a lower prevalence of cases with a Zung index suggestive of mild depression was confirmed. Association between frequent use of makeup and lower intensity of depressive symptoms was also identified among cases with a Zung index suggestive of absence of depression. Additionally, an association was identified between the habit of frequent use of makeup and higher economic class as well as the younger age group. CONCLUSION: The results suggest the hypothesis that use of makeup may contribute both to a lower prevalence of mild depression and less expressive symptoms when index of absence of depression is observed.

Bioinspired Antimicrobial PLA with Nanocones on the Surface for Rapid Deactivation of Omicron SARS-CoV-2.

Bioinspired bactericidal surfaces are artificial surfaces that mimic the nanotopography of insect wings and are capable of inhibiting microbial growth by a physicomechanical mechanism. The scientific community has considered them an alternative method to design polymers with surfaces that inhibit bacterial biofilm formation, suitable for self-disinfectant medical devices. In this contribution, poly(lactic acid) (PLA) with nanocone patterns was successfully produced by a novel two-step procedure involving copper plasma deposition followed by argon plasma etching. According to reverse transcription-quantitative polymerase chain reaction tests, the bioinspired PLA nanostructures display antiviral performance to inactivate infectious Omicron severe acute respiratory syndrome coronavirus 2 particles, reducing the amount of the viral genome to less than 4% in just 15 min due to a possible combined effect of mechanical and oxidative stress. The bioinspired antiviral PLA can be suitable for designing personal protection equipment to prevent the transmission of contagious viral diseases, such as Coronavirus Disease 2019.

Omicron SARS-CoV-2 antiviral on poly(lactic acid) with nanostructured copper coating: Wear effects.

Surface modification corresponds to a set of viable technological approaches to introduce antimicrobial properties in materials that do not have such characteristics. Antimicrobial materials are important to prevent the proliferation of microorganisms and minimize the transmission of diseases caused by pathogens. Herein, poly(lactic acid) (PLA) was decorated with nanocones through copper sputtering followed by a plasma etching. Antiviral assays by Quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) show that nanostructured Cu-coated PLA has high antiviral activity against Omicron SARS-CoV-2, showing a relative reduction in the amplified RNA (78.8 ± 3.9 %). Atomic Force Microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS), and wear-resistance tests show that 20 wear cycles disrupt the surface nanocone patterns and significantly reduce the Cu content at the surface of the nanostructured Cu-coated PLA, leading to total loss of the antiviral properties of nanostructured PLA against Omicron SARS-CoV-2.

High Prevalence of a c.5979dupA Variant in the Dysferlin Gene (DYSF) in Individuals from a Semiarid Region of Brazil.

Background: Dysferlinopathies represent a group of limb girdle or distal muscular dystrophies with an autosomal-recessive inheritance pattern resulting from the presence of pathogenic variants in the dysferlin gene (DYSF). Objective: In this work, we describe a population from a small city in Brazil carrying the c.5979dupA pathogenic variant of DYSF responsible for limb girdle muscular dystrophy type 2R and distal muscular dystrophy. Methods: Genotyping analyses were performed by qPCR using customized probe complementary to the region with the duplication under analysis in the DYSF. Results: A total of 104 individuals were examined. c.5979dupA was identified in 48 (46.15%) individuals. Twenty-three (22%) were homozygotes, among whom 13 (56.5%) were female. A total of 91.3% (21) of homozygous individuals had a positive family history, and seven (30.4%) reported consanguineous marriages. Twenty-five (24%) individuals were heterozygous (25.8±16 years) for the same variant, among whom 15 (60%) were female. The mean CK level was 697 IU for homozygotes, 140.5 IU for heterozygotes and 176 IU for wild-type homo-zygotes. The weakness distribution pattern showed 17.3% of individuals with a proximal pattern, 13% with a distal pattern and 69.6% with a mixed pattern. Fatigue was present in 15 homozygotes and one heterozygote. Conclusion: The high prevalence of this variant in individuals from this small community can be explained by a possible founder effect associated with historical, geographical and cultural aspects.

Delta SARS-CoV-2 inactivation and bactericidal performance of cotton wipes decorated with TiO2/Ag nanoparticles like Brazilian heavy-fruited Myrciaria cauliflora.

The current pandemic of Coronavirus Disease 2019 (COVID-19) raised several concerns about using conventional textiles for manufacturing personal protective equipment without self-disinfecting properties since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is transmitted mainly by aerosols that can transpose cotton masks. Therefore, developing new cotton fibers with high self-disinfecting ability is essential to avoid a new pandemic due to new SARS-CoV-2 variants. Herein, we developed cotton wipes (CFs) with fibers coated by Ag, TiO2, and Ag/TiO2 hybrid nanoparticles like Brazilian heavy-fruited Myrciaria cauliflora by a sonochemical approach. Moreover, the coated CFs present high antimicrobial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), being able to inactivate infectious SARS-CoV-2 (Delta variant) by the destruction of the spike, membrane, and nucleocapsid proteins while the viral RNA is not significantly affected, according to the molecular biological findings.

Vitamin D supplementation at different doses affects the vagal component of the baroreceptor reflex and the Bezold-Jarisch reflex in eutrophic rats.

Vitamin D has been used to prevent several diseases. The 1,25 (OH) 2D3, the active form of vitamin D (VitD), participates in calcium metabolism, and has direct action in various tissues as those of the cardiovascular system binding to the VitD receptor. We investigated whether the supplementation with different doses of VitD affect or not the resting mean arterial pressure (MAP) and heart rate (HR), heart rate variability (HRV), baroreceptor and Bezold-Jarisch reflexes in eutrophic rats. Adult male Wistar rats were randomly assigned in 4 groups (Control, VitD 15, 250, and 3,750 IU/day, n = 6/group). After 3 days of supplementation, MAP and HR recordings were performed in freely moving rats. Baseline (resting) MAP, HR, and HRV showed no difference in Control and VitD groups. Nevertheless, the index of the baroreceptor reflex showed that the bradycardic component of the baroreflex evoked by a pressor dose of phenylephrine (3 µg/kg of b.w.) in bolus injection had a significant increase in rats supplemented with VitD 15 IU/day for 3 days compared to Control animals. No difference was observed in the index of the baroreflex evaluated with phenylephrine in rats treated with VitD 250 and 3,750 IU/day for 3 days in comparison to the Control group. The index of the baroreceptor reflex evaluated with an intravenous bolus injection of a depressor dose of sodium nitroprusside (30 µg/kg of b.w.) showed that the tachycardic component of the baroreflex is not different comparing all groups supplemented with VitD and Control animals. Rats supplemented with VitD 15 IU/day presented exaggerated bradycardic responses to the intravenous injection of phenylbiguanide (PBG, 5 µg/kg of b.w.) compared to Control animals, despite the similar hypotension in both groups. Higher doses of supplementation of VitD (250 and 3,750 IU/day for 3 days) abolished the hypotension and bradycardia induced by PBG. The findings suggest that the supplementation with different doses of VitD (15, 250, and 3,750 IU/day) for 3 days did not affect the resting arterial pressure, heart rate and autonomic modulation on the heart in rats. Despite that, the supplementation with a low dose of VitD (15 IU/day for 3 days) improved the sensitivity of the bradycardic component of the baroreflex, whereas higher doses of supplementation with VitD (250 and 3,750 IU/day for 3 days) were unable to cause such effect. In addition, the Bezold-Jarisch reflex responses can be affected regardless the dose of VitD (15, 250 or 3,750 IU/day) supplementation for 3 days in rats.

Questioning ZnO, Ag, and Ag/ZnO nanoparticles as antimicrobial agents for textiles: Do they guarantee total protection against bacteria and SARS-CoV-2?

Coronavirus Disease 2019 (COVID-19) occasioned global economic and health systems collapse. Also, it raised several concerns about using conventional cotton fabrics for manufacturing personal protective equipment without the antimicrobial capacity to inactivate viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its variants. Therefore, developing antimicrobial cotton fibers is crucial to avoid new global pandemics or the transmission of dangerous pathogens that remain on surfaces for long periods, especially in hospitals and medical clinics. Herein, we developed antimicrobial cotton fabrics with Ag, ZnO, and Ag/ZnO nanoparticles and evaluated their bactericidal activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), photocatalytic activity, and antiviral activity against Delta SARS-CoV-2. Although the antimicrobial fabrics are effective against these bacteria, they only reduce part of the SARS-CoV-2 virions during the first 15 min of direct contact via damage only to biological structures on the viral surface particle while the viral RNA remains intact.

1H qNMR-Based Metabolomics Discrimination of Covid-19 Severity.

The coronavirus disease 2019 (Covid-19), which caused respiratory problems in many patients worldwide, led to more than 5 million deaths by the end of 2021. Experienced symptoms vary from mild to severe illness. Understanding the infection severity to reach a better prognosis could be useful to the clinics, and one study area to fulfill one piece of this biological puzzle is metabolomics. The metabolite profile and/or levels being monitored can help predict phenotype properties. Therefore, this study evaluated plasma metabolomes of 110 individual samples, 57 from control patients and 53 from recent positive cases of Covid-19 (IgM 98% reagent), representing mild to severe symptoms, before any clinical intervention. Polar metabolites from plasma samples were analyzed by quantitative 1H NMR. Glycerol, 3-aminoisobutyrate, formate, and glucuronate levels showed alterations in Covid-19 patients compared to those in the control group (Tukey's HSD p-value cutoff = 0.05), affecting the lactate, phenylalanine, tyrosine, and tryptophan biosynthesis and d-glutamine, d-glutamate, and glycerolipid metabolisms. These metabolic alterations show that SARS-CoV-2 infection led to disturbance in the energetic system, supporting the viral replication and corroborating with the severe clinical conditions of patients. Six polar metabolites (glycerol, acetate, 3-aminoisobutyrate, formate, glucuronate, and lactate) were revealed by PLS-DA and predicted by ROC curves and ANOVA to be potential prognostic metabolite panels for Covid-19 and considered clinically relevant for predicting infection severity due to their straight roles in the lipid and energy metabolism. Thus, metabolomics from samples of Covid-19 patients is a powerful tool for a better understanding of the disease mechanism of action and metabolic consequences of the infection in the human body and may corroborate allowing clinicians to intervene quickly according to the needs of Covid-19 patients.

Functional Characterization of Undenatured Type II Collagen Supplements: Are They Interchangeable?

Undenatured (native) type II collagen is a dietary supplement ingredient reported to support joint health in healthy individuals by providing relief from symptoms of stiffness and discomfort and improving mobility. This benefit is thought to occur through oral tolerance, a mechanism whereby the immune system distinguishes between innocuous material in the gut and potentially harmful foreign invaders. The presence of antigenic epitopes in undenatured type II collagen, but not in denatured (hydrolyzed) collagen, is thought to be the basis for the therapeutic benefits. The purpose of this study was to investigate the physicochemical and analytical characteristics of type II collagen supplements currently available on the market and to explore whether they might be sufficiently similar in their physical properties to yield similar benefits in promoting joint health. Collagen type II supplement powders (raw material) and capsules (products in the market) were examined for color, particle size, quality profiles, fatty acid profiles, electron microscopy, and were analyzed for amino acid content as well as antigenic potential via an ELISA assay. Powders labeled as undenatured type II collagen were found to have markedly different properties, including the size of collagen fibers as per electron microscopy and antigenic configuration as per the ELISA assay. As significant differences were found between products, it allows consumers and practitioners to not assume that products labeled as undenatured (native) type II collagen are interchangeable.

Potential Use of DMSA-Containing Iron Oxide Nanoparticles as Magnetic Vehicles against the COVID-19 Disease.

Iron oxide magnetic nanoparticles have been employed as potential vehicles for a large number of biomedical applications, such as drug delivery. This article describes the synthesis, characterization and in vitro cytotoxic in COVID-19 cells evaluation of DMSA superparamagnetic iron oxide magnetic nanoparticles. Magnetite (Fe3O4) nanoparticles were synthesized by co-precipitation of iron salts and coated with meso-2,3-dimercaptosuccinic acid (DMSA) molecule. Structural and morphological characterizations were performed by X-ray diffraction (XRD), Fourier transformed infrared (FT-IR), magnetic measurements (SQUID), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Our results demonstrate that the nanoparticles have a mean diameter of 12 nm in the solid-state and are superparamagnetic at room temperature. There is no toxicity of SPIONS-DMSA under the cells of patients with COVID-19. Taken together the results show that DMSA- Fe3O4 are good candidates as nanocarriers in the alternative treatment of studied cells.

Dengue-2 and Guadeloupe Mosquito Virus RNA Detected in Aedes (Stegomyia) spp. Collected in a Vehicle Impound Yard in Santo André, SP, Brazil.

In 2018-2019, we conducted mosquito collections in a municipal vehicle impound yard, which is 10 km from the Serra do Mar Environmental Protection Area in Santo André, SP, Brazil. Our aim is to study arboviruses in the impound yard, to understand the transmission of arboviruses in an urban environment in Brazil. We captured the mosquitoes using human-landing catches and processed them for arbovirus detection by conventional and quantitative RT-PCR assays. We captured two mosquito species, Aedes aegypti (73 total specimens; 18 females and 55 males) and Ae. albopictus (34 specimens; 27 females and 7 males). The minimum infection rate for DENV-2 was 11.5 per 1000 (CI95%: 1-33.9). The detection of DENV-2 RNA in an Ae. albopictus female suggests that this virus might occur in high infection rates in the sampled mosquito population and is endemic in the urban areas of Santo André. In addition, Guadeloupe mosquito virus RNA was detected in an Ae. aegypti female. To our knowledge, this was the first detection of the Guadeloupe mosquito virus in Brazil.

Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients.

In tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(-ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90-91 and 160-161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.

Cotton Fabrics Decorated with Antimicrobial Ag-Coated TiO2 Nanoparticles Are Unable to Fully and Rapidly Eradicate SARS-CoV-2.

The successful development of multifunctional cotton fabrics with antimicrobial and antiviral activities is essential to prevent the proliferation of microorganisms and transmission of coronavirus virions today, especially with the emergence of new variants of SARS-CoV-2. In this work, we developed antimicrobial cotton fabrics with Ag/TiO2 nanoparticles synthesized via sonochemistry. Here, we show that more than 50% of infectious SARS-CoV-2 remain active after prolonged direct contact self-disinfecting materials capable of inhibiting the proliferation of Escherichia coli and Staphylococcus aureus. The findings bring several epidemiologic worries about using silver and TiO2 as self-disinfecting nanostructured agents to prevent coronavirus transmission.

Relationship between polypharmacy, xerostomia, gustatory sensitivity, and swallowing complaints in the elderly: A multidisciplinary approach.

Oral dysfunctions are common in the elderly but the literature lacks a multidisciplinary approach on the relationship between polypharmacy, saliva flow, xerostomia, taste, and swallowing complaints. This cross-sectional study included 204 non-institutionalized elderly (>60 years; 123 women/81 men), free of severe disabilities and non-alcohol/tobacco consumers, from whom specific pharmacological therapies were evaluated, as well xerostomia (Xerostomia Inventory-XI) and swallowing complaints (EAT-10 questionnaire), salivary flow rate and gustatory sensitivity. Statistical analysis included Chi-square, Mann-Whitney, Two-way ANCOVA, and linear multiple regression. Polypharmacy (≥5 drugs daily), hyposalivation, and severe taste dysfunction were found in 18, 46, and 10% of the participants, respectively. Polypharmacy was related with xerostomia (p = .041) and swallowing complaints (p < .001; power = 94%), but not with taste dysfunction. Dry mouth complaint and higher risk of swallowing disorders were found in 50 and 12% of the elderly, respectively, and angiotensin-converting enzyme (ACE) inhibitors users (n = 36) showed higher EAT-10 scores (p = .038). Regression models showed that stimulated salivary flow rate was dependent on gender and diuretic use, while xerostomia scores were dependent on the number of medications and unstimulated saliva flow (p < .001). In conclusion, the results draw attention to the high frequency of oral and maxillofacial dysfunctions found in non-institutionalized elderly, especially polypharmacy, xerostomia and swallowing complaints, and the side effects of drugs that can disturb the oral functions, the acceptance of food, and the adherence to oral therapies.

PYGM mRNA expression in McArdle disease: Demographic, clinical, morphological and genetic features.

INTRODUCTION: McArdle disease presents clinical and genetic heterogeneity. There is no obvious association between genotype and phenotype. PYGM (muscle glycogen phosphorylase gene) mRNA expression and its association with clinical, morphological, and genetic aspects of the disease as a set have not been studied previously. METHODS: We investigated genetic variation in PYGM considering the number of PTCs (premature termination codon) per sample and compared mRNA expression in skeletal muscle samples from 15 patients with McArdle disease and 16 controls to PTCs number and different aspects of the disease. RESULTS: The main variant found was c.148C>T (PTC-premature termination codon). Patients with two PTCs showed 42% mRNA expression compared to the control group. Most cases showed an inversely proportional relation among PTCs and mRNA expression. Association between mRNA expression and other aspects of the disease showed no statistically significant difference (p> 0.05). DISCUSSION: mRNA expression is not useful as a predictor factor for the prognosis and severity of the disease. Different mechanisms as post-transcriptional events, epigenetics factors or protein function may be involved.