In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

DENV-2 Outbreak Associated With Cosmopolitan Genotype Emergence in Western Brazilian Amazon.

Background: Dengue virus (DENV) causes an important disease and directly affects public health, being the arbovirus that presents the highest number of infections and deaths in the Western Brazilian Amazon. This virus is divided into 4 serotypes that have already circulated in the region. Methodology: Molecular characterization of a cohort containing 841 samples collected from febrile patients between 2021 and 2023 was analyzed using a commercial kit to detect the main arboviruses circulating in Brazil: Zika, DENV-1, DENV-2, DENV-3, DENV-4 and, Chikungunya. Subsequently, Sanger sequencing was performed for positive samples. Results: The cohort detected 162 positive samples, 12 for DENV-1 and 150 identified as DENV-2, indicating co-circulation of serotypes. The samples were subjected to sequencing and the analysis of the sequences that obtained good quality revealed that 5 samples belonged to the V genotype of DENV-1 and 46 were characterized as DENV-2 Cosmopolitan genotype-lineage 5. Conclusion: The results allowed us to identify for the first time the Cosmopolitan genotype in Rondônia, Brazilian Western Amazon, and its fast spread dispersion.

Dropping a bombshell: Acoustic characterization of blast fishing in Todos os Santos Bay, Brazil, and its implication for marine conservation.

Blast fishing is an illegal fishing method that not only affects fish populations and the marine ecosystem, but also local food security and local economy. Despite its effects, blast fishing continues to persist in many coastal regions around the world, including Todos os Santos Bay (BTS - Baia de Todos os Santos) in Northeastern Brazil. This study provides the first acoustic record of underwater explosions along this region. The acoustic data were collected between 2016 and 2018, from a boat-survey platform, using a portable system consisting of an HTI-90 min hydrophone (sensitivity of about -165 dB re 1 V/µPa) connected to a TASCAM DR-40 digital recorder (combined frequency response up to 30 kHz), recording at 7 m depth. The acoustic analysis was performed using both RAVEN 1.6 and MATLAB 2021a softwares. The results revealed a distinctive underwater explosion signal detected in the BTS, indicating evidence of blast fishing activities. The acoustic characterization of blast fishing in BTS provides crucial information on its occurrence and extent of this destructive practice worldwide.

Contralateral suppression in adrenal venous sampling predicts clinical and biochemical outcome in primary aldosteronism.

CONTEXT: The role for hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcome remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcome. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. Bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index (LI), aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) *100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had a worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure were significantly more frequent in the patients with CS >50% [98.41% vs. 42.86% (p < 0.001) and 41.94% vs. 0% (p < 0.001)]. CS correlated with high aldosterone at diagnosis (p < 0.001) and low postoperative aldosterone levels at 1 month (p = 0.019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs. 16.67%, p = 0.014). In multivariable analysis, a CS >50% was associated with complete biochemical cure (OR 125, 95%CI 11.904-5,000; p = 0.001) and hypertension remission (OR 12.19, 95%CI 2.074-250; p = 0.023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral PA and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.

Acoustic noise generated by TMS in typical environment and inside an MRI scanner.

BACKGROUND: The operation of a transcranial magnetic stimulation (TMS) coil produces high-intensity impulse sounds. In TMS, a magnetic field is generated by a short-duration pulse in the range of thousands of amperes in the TMS coil. When placed in a strong magnetic field, such as inside a magnetic resonance imaging (MRI) bore, the interaction of the magnetic field and the current in the TMS coil can cause strong forces on the coil casing. The strengths of these forces depend on the coil orientation in the main magnetic field (B0). Part of the energy in this process is dissipated in the form of acoustic noise. OBJECTIVE: Our objective was to measure the sound pressure levels (SPL) of TMS "click" sounds created by commercial TMS stimulators and coils in a typical environment and inside a 3-T MRI scanner and advance the knowledge of the acoustic behaviour of TMS to safely conduct TMS alone as well as concurrently with functional MRI (fMRI). METHODS: We report SPL measurements of two commercial MRI-compatible TMS systems in the 3-T B0 field of an MRI scanner and in the earth's magnetic field. Also, we present the acoustic noise measurements of four commercial TMS stimulators and three different TMS coils in a typical operational environment without the B0 field. RESULTS: The maximum peak SPL measured was 158 dB(C) inside the 3-T MRI scanner. Outside the scanner, the maximum peak SPL was 117 dB(C). Inside the scanner, the peak SPL increased by 21-45 dB(C) depending on the stimulator and the orientation of the electric field relative to the B field. CONCLUSIONS: Hearing protection is obligatory during concurrent TMS-fMRI experiments and highly recommended during any TMS experiment. The manufacturing of quieter TMS systems is encouraged to reduce the risk of hearing damage and other unwanted effects.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Própolis vermelha e ação antifúngica: potencialidades e desafios / Red própolis and antifungal activity: potentialities and challenges / Propóleo rojo y acción antifúngica: potencialidades y desafíos

Introdução: a própolis é uma composição resinosa produzida por abelhas e utilizada em suas colmeias contra microrganismos. Existem diversos tipos desse composto, sendo o de coloração vermelha o último espécime relatado na literatura. Assim, dentre suas aplicabilidades, a atividade antifúngica da própolis vermelha tem sido explorada com vistas a ampliar sua ação terapêutica. Objetivo: explorar estudos acerca da ação antifúngica da própolis vermelha, identificando suas potencialidades e desafios. Metodologia: foi realizada uma revisão integrativa nas bases de dados bibliográficos MEDLINE (via PubMed), SciELO e Google Acadêmico, complementada por uma diligência nas bases de ensaios clínicos ReBEC e Clinical Trials. Em seguida todos os estudos selecionados foram explorados para obtenção do cenário atual sobre o tema. Resultados: foram incluídos 08 estudos, sendo 01 deles um ensaio clínico. Os estudos comprovam a ação antifúngica da própolis vermelha, principalmente contra Candida spp. e Paracoccidioides brasiliensis, e evidenciam a maior potência fungicida deste composto em detrimento de outros tipos de própolis. Conclusão: a ação antifúngica da própolis vermelha mostra-se uma potencialidade em diversos estudos. Entretanto, o volume de pesquisas científicas relativas a esse tema é insuficiente e a complexidade desse composto configura-se como um desafio à sua aplicabilidade.

Introduction: propolis is a resinous composition produced by compounds and used in their hives against microorganisms. There are several types of this compound, the red one is the last specimen reported in the literature. Thus, among its applicability, the antifungal activity of red propolis has been explored as a path to expand its therapeutic action. Objective: to explore studies about the antifungal action of red propolis, identifying its potentialities and challenges. Methodology: Na integrative review was carried out in the bibliographic databases MEDLINE (via PubMed), SciELO and Google Scholar, complemented by a diligence in ReBEC and Clinical Trials databases. Then, all selected studies were explorers to obtain the current scenario on the subject. Results: 08 studies were included, which 01 of them was a clinical trial. Studies prove the antifungal action of red propolis, mainly against Candida spp. and Paracoccidioides brasiliensis, and show the greater fungicidal power of this compound compared to other types of propolis. Conclusion: the antifungal action of red propolis shows potential in several studies. However, the volume of scientific research on this theme is insufficient and the complexity of this compound represents a challenge to its applicability.

Introducción: el propóleo es una composición resinosa producida por las abejas y utilizada en sus colmenas contra los microorganismos. Existen varios tipos de este compuesto, siendo el rojo el último ejemplar reportado en la literatura. Así, entre sus posibilidades de aplicación, se ha explorado la actividad antifúngica del propóleo rojo con vistas a ampliar su acción terapéutica. Objetivo: explorar estudios sobre la acción antifúngica del propóleo rojo, identificando sus potencialidades y desafíos. Metodología: Se realizó una revisión en las bases de datos bibliográficas MEDLINE (vía PubMed), SciELO y Google Scholar, complementada con una diligencia en las bases de datos de ensayos clínicos ReBEC y Clinical Trials. Luego se exploraron todos los estudios seleccionados para obtener el escenario actual sobre el tema. Resultados: Se incluyeron 08 estudios, 01 de los cuales fue un ensayo clínico. Los estudios demuestran la acción antifúngica del propóleo rojo, principalmente contra Candida spp. y Paracoccidioides brasiliensis, y muestran el mayor poder fungicida de este compuesto en detrimento de otros tipos de propóleos. Conclusión: la acción antifúngica del propóleo rojo muestra potencial en varios estudios. Sin embargo, el volumen de investigación científica sobre este tema es insuficiente y la complejidad de este compuesto representa un desafío para su aplicabilidad.

Characterization of Sodium Alginate-Based Films Blended with Olive Leaf and Laurel Leaf Extracts Obtained by Ultrasound-Assisted Technology.

Due to environmental concerns, there is an increasing need to reduce the use of synthetic and non-renewable packaging materials to reduce waste and increase sustainability. This study aimed to characterise sodium alginate edible-based films (SA) incorporated with laurel leaf extract (LLE) and olive leaf extract (OLE) obtained by ultrasound-assisted extraction. Determination of total phenolic content, antioxidant, and antimicrobial activity was performed for the extracts and films. Also, thickness, tensile strength, elongation at break, modulus of elasticity, opacity and colour, moisture content, water vapour permeability (WVP), Fourier-transform infrared spectroscopy (FTIR) spectra, and surface morphology by scanning electron microscope (SEM) analyses were performed for the films. LLE yielded better results in terms of phenolic content (195 mg GAE/g), antioxidant (2.1 TE/g extract) and antimicrobial activity (MIC at 1% for Listeria monocytogenes and Staphylococcus aureus, and 1.8% for Enterococcus faecalis). For the films, the simultaneous incorporation of LLE 1% (w/v) and OLE 1% (w/v) resulted in a significant reduction of approximately 2 log CFU/g against S. aureus. The addition of LLE and OLE extracts also proved to improve barrier properties (lower WVP for SA films with LLE 1% + OLE 1%, 3.49 × 10-11 g m-1 s-1 Pa-1) and promoted changes in resistance and flexibility. The results demonstrated that active alginate-based films can be valuable for enhancing food preservation.

Phytotoxicity and cytogenotoxicity of pesticide mixtures: analysis of the effects of environmentally relevant concentrations on the aquatic environment.

In this study, we investigate the toxicity of commercial formulations based on glyphosate, 2,4-D, imidacloprid, and iprodione, in isolation and mixed, on Allium cepa. The mixtures consisted of combinations in the lowest (M1), intermediate (M2), and highest concentrations (M3) of each pesticide. We measured physiological (germination rate, germination speed, and radicular length) and cyto-genotoxic (mitotic index and frequency of aberrant cells) parameters. In addition, we analyzed the cell cycle progression and cell death induction by flow cytometry. When applied in isolation, the pesticides changed the parameters evaluated. M1 and M2 inhibited root length and increased the frequency of aberrant cells. Their genotoxic effect was equivalent to that of pesticides applied in isolation. Furthermore, M1 and M2 caused cell death and M2 changed the cell cycle progression. M3 had the greatest deleterious effect on A. cepa. This mixture inhibited root length and promoted an additive or synergistic effect on the mitotic index. In addition, M3 changed all parameters analyzed by flow cytometry. This research clearly demonstrates that the pesticides tested, and their mixtures, may pose a risk to non-target organisms.

Herbicide and Cytogenotoxic Activity of Inclusion Complexes of Psidium gaudichaudianum Leaf Essential Oil and ß-Caryophyllene on 2-Hydroxypropyl-ß-cyclodextrin.

The present investigation aimed to develop inclusion complexes (ICs) from Psidium gaudichaudianum (GAU) essential oil (EO) and its major compound ß-caryophyllene (ß-CAR), and to evaluate their herbicidal (against Lolium multiflorum and Bidens pilosa) and cytogenotoxic (on Lactuca sativa) activities. The ICs were obtained using 2-hydroxypropyl-ß-cyclodextrin (HPßCD) and they were prepared to avoid or reduce the volatility and degradation of GAU EO and ß-CAR. The ICs obtained showed a complexation efficiency of 91.5 and 83.9% for GAU EO and ß-CAR, respectively. The IC of GAU EO at a concentration of 3000 µg mL-1 displayed a significant effect against weed species B. pilosa and L. multiflorum. However, the ß-CAR IC at a concentration of 3000 µg mL-1 was effective only on L. multiflorum. In addition, the cytogenotoxic activity evaluation revealed that there was a reduction in the mitotic index and an increase in chromosomal abnormalities. The produced ICs were able to protect the EO and ß-CAR from volatility and degradation, with a high thermal stability, and they also enabled the solubilization of the EO and ß-CAR in water without the addition of an organic solvent. Therefore, it is possible to indicate the obtained products as potential candidates for commercial exploration since the ICs allow the complexed EO to exhibit a more stable chemical constitution than pure EO under storage conditions.

Effect of muscle length in a handgrip task on corticomotor excitability of extrinsic and intrinsic hand muscles under resting and submaximal contraction conditions.

The neurophysiological mechanisms underlying muscle force control for different wrist postures still need to be better understood. To further elucidate these mechanisms, the present study aimed to investigate the effects of wrist posture on the corticospinal excitability by transcranial magnetic stimulation (TMS) of extrinsic (flexor [FCR] and extensor carpi radialis [ECR]) and intrinsic (flexor pollicis brevis (FPB)) muscles at rest and during a submaximal handgrip strength task. Fourteen subjects (24.06 ± 2.28 years) without neurological or motor disorders were included. We assessed how the wrist posture (neutral: 0°; flexed: +45°; extended: -45°) affects maximal handgrip strength (HGSmax ) and the motor evoked potentials (MEP) amplitudes during rest and active muscle contractions. HGSmax was higher at 0° (133%) than at -45° (93.6%; p < 0.001) and +45° (73.9%; p < 0.001). MEP amplitudes were higher for the FCR at +45° (83.6%) than at -45° (45.2%; p = 0.019) and at +45° (156%; p < 0.001) and 0° (146%; p = 0.014) than at -45° (106%) at rest and active condition, respectively. Regarding the ECR, the MEP amplitudes were higher at -45° (113%) than at +45° (60.8%; p < 0.001) and 0° (72.6%; p = 0.008), and at -45° (138%) than +45° (96.7%; p = 0.007) also at rest and active conditions, respectively. In contrast, the FPB did not reveal any difference among wrist postures and conditions. Although extrinsic and intrinsic hand muscles exhibit overlapping cortical representations and partially share the same innervation, they can be modulated differently depending on the biomechanical constraints.

Analysis of brain activation and wave frequencies during a sentence completion task: a paradigm used with EEG in aphasic participants.

Aphasia is a language disorder that occurs after brain injury and directly affects an individual's communication. The incidence of stroke increases with age, and one-third of people who have had a stroke develop aphasia. The severity of aphasia changes over time and some aspects of language may improve, while others remain compromised. Battery task training strategies are used in the rehabilitation of aphasics. The idea of this research is to use electroencephalography (EEG) as a non-invasive method, of electrophysiological monitoring, with a group of aphasic patients in rehabilitation process in a prevention and rehabilitation unit of the person with disabilities of the Unified Health System (SUS), of reference in the state of Bahia-Brazil. In this study, the goal is to analyze brain activation and wave frequencies of aphasic individuals during a sentence completion task, to possibly assist health professionals with the analysis of the aphasic subject's rehabilitation and task redefinition. We adopted the functional magnetic resonance imaging (fMRI) paradigm, proposed by the American Society for Functional Neuroradiology as a reference paradigm. We applied the paradigm in the group of aphasics with preserved comprehension, right hemiparesis, and left hemisphere injured or affected by stroke. We analyzed four electrodes (F3/F4 and F7/F8) corresponding to the left/right frontal cortex. Preliminary results of this study indicate a more robust activation in the right hemisphere (average of aphasics), with a difference of approximately 14% higher in Theta and Alpha frequencies, with 8% higher in low Beta (BetaL) and with approximately 1% higher in high Beta frequency (BetaH), Gamma frequency was higher by approximately 3% in the left hemisphere of the brain. The difference in electrical activation may be revealing to us a migration of language to the non-language dominant hemisphere. We point to possible evidence suggesting that EEG may be a promising tool for monitoring the rehabilitation of the aphasic subject.

Reemergence of Dengue Virus Serotype 3, Brazil, 2023.

We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks.

SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants.

MarLe: Markerless estimation of head pose for navigated transcranial magnetic stimulation.

Navigated transcranial magnetic stimulation (nTMS) is a valuable tool for non-invasive brain stimulation. Currently, nTMS requires fixing of markers on the patient's head. Head marker displacements lead to changes in coil placement and brain stimulation inaccuracy. A markerless neuronavigation method is needed to increase the reliability of nTMS and simplify the nTMS protocol. In this study, we introduce and release MarLe, a Python markerless head tracker neuronavigation software for TMS. This novel software uses computer-vision techniques combined with low-cost cameras to estimate the head pose for neuronavigation. A coregistration algorithm, based on a closed-form solution, was designed to track the patient's head and the TMS coil referenced to the individual's brain image. We show that MarLe can estimate head pose based on real-time video processing. An intuitive pipeline was developed to connect the MarLe and nTMS neuronavigation software. MarLe achieved acceptable accuracy and stability in a mockup nTMS experiment. MarLe allows real-time tracking of the patient's head without any markers. The combination of face detection and a coregistration algorithm can overcome nTMS head marker displacement concerns. MarLe can improve reliability, simplify, and reduce the protocol time of brain intervention techniques such as nTMS.

Current Applications of Bionanocomposites in Food Processing and Packaging.

Nanotechnology advances are rapidly spreading through the food science field; however, their major application has been focused on the development of novel packaging materials reinforced with nanoparticles. Bionanocomposites are formed with a bio-based polymeric material incorporated with components at a nanoscale size. These bionanocomposites can also be applied to preparing an encapsulation system aimed at the controlled release of active compounds, which is more related to the development of novel ingredients in the food science and technology field. The fast development of this knowledge is driven by consumer demand for more natural and environmentally friendly products, which explains the preference for biodegradable materials and additives obtained from natural sources. In this review, the latest developments of bionanocomposites for food processing (encapsulation technology) and food packaging applications are gathered.