Wastewater surveillance for viral pathogens: A tool for public health.

A focus on water quality has intensified globally, considering its critical role in sustaining life and ecosystems. Wastewater, reflecting societal development, profoundly impacts public health. Wastewater-based epidemiology (WBE) has emerged as a surveillance tool for detecting outbreaks early, monitoring infectious disease trends, and providing real-time insights, particularly in vulnerable communities. WBE aids in tracking pathogens, including viruses, in sewage, offering a comprehensive understanding of community health and lifestyle habits. With the rise in global COVID-19 cases, WBE has gained prominence, aiding in monitoring SARS-CoV-2 levels worldwide. Despite advancements in water treatment, poorly treated wastewater discharge remains a threat, amplifying the spread of water-, sanitation-, and hygiene (WaSH)-related diseases. WBE, serving as complementary surveillance, is pivotal for monitoring community-level viral infections. However, there is untapped potential for WBE to expand its role in public health surveillance. This review emphasizes the importance of WBE in understanding the link between viral surveillance in wastewater and public health, highlighting the need for its further integration into public health management.

Pharmacovigilance in Vaccines: Importance, Main Aspects, Perspectives, and Challenges-A Narrative Review.

Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain.

An overview on recent patents and technologies on nanoparticles for nucleic acid delivery.

INTRODUCTION: Nucleic acid-based therapeutics offer groundbreaking potential for treating genetic diseases and advancing next-generation vaccines. Despite their promise, challenges in efficient delivery persist due to the properties of nucleic acids. Nanoparticles (NPs) serve as vital carriers, facilitating effective delivery to target cells, and addressing these challenges. Understanding the global landscape of patents in this field is essential for fostering innovation and guiding decision-making for researchers, the pharmaceutical industry, and regulatory agencies. AREAS COVERED: This review provides a comprehensive overview of patent compositions, applications, and manufacturing aspects concerning NPs as nucleic acid delivery systems. It delves into temporal trends, protection locations, market dynamics, and the most influential technological domains. In this work, we provide valuable insights into the advancements and potential of NP-based nucleic acid delivery systems, with a special focus on their pivotal role in advancing cutting-edge therapeutic solutions. EXPERT OPINION: Investment in NPs for nucleic acid delivery has significantly surged in recent years. However, translating these therapies into clinical practice faces obstacles, including the need for robust clinical evidence, regulatory compliance, and streamlined manufacturing processes. To address these challenges, our review article summarizes recent advances. We aim to engage researchers worldwide in the development of these promising technologies.

Progesterone-Related Diabetes Mellitus in the Bitch: Current Knowledge, the Role of Pyometra, and Relevance in Practice.

Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant detailed information on (1) the canine estrus cycle and its impact on canine diabetes mellitus (CDM) etiology and management, (2) the role of pyometra as a further cause of insulin resistance, and (3) useful individual therapeutic and preventive strategies. PRDM is recognized due to diestrus, exogenous progestogen exposure, pregnancy, and P4-production ovarian dysfunction. Pyometra represents additional inflammatory and septic negative influence on insulin sensitivity, and its diagnosis associated with CDM is therapeutically challenging. The estrus cycle's hormone fluctuations seem to modulate peripheric insulin sensibility by influencing insulin receptor (IR) affinity and its binding capacity, as well as modulating tyrosine kinase activity. Pyometra was shown to negatively influence IR compensatory mechanisms to insulin resistance causing glucose intolerance. Spaying and pregnancy termination may cause diabetes remission in PRDM cases in a median time of 10 days (1-51). Pharmacological annulment of progesterone effects may benefit patients unable to undergo surgery; however, remission chances are virtually null. The ALIVE (Agreeing Language in Veterinary Endocrinology) project proposed new criteria for CDM diagnoses and subclinical diabetes recognition. These new concepts may increase the frequency of a PRDM diagnosis and, even more, its relevance. Spaying represents a preventive measure against pyometra and PRDM that should be individually assessed in light of its recognized benefits and harms.

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.

Distillation of essential oils: An innovative technological approach focused on productivity, quality and sustainability.

Essential oil (EO) distillation units, which are commonly installed on farms, have difficultly accessing knowledge centers. The apparent simplicity of the process hides unwanted losses and deviations that go undetected and, therefore, not corrected. This article proposes improvements to the process that are based on "4.0" technologies in order to detect and correct two important deficiencies, with an impact on the yield, quality and environmental performance. The first deficiency comprises the steam channels that are formed through green mass (channeling), are well known and are considered normal by EO producers. Without detection and correction, this negatively affects the extraction results. The second is the lack of technology that is able to automatically determine the extraction endpoint. Smart sensing, control, self-configuration and the dynamic determination of improved process parameters make up a set of actions undertaken by a smart extraction plant (50-liter capacity). Nineteen experiments using lemongrass (Cymbopogon citratus) exhibited remarkable 24% and 10% improvements in the yield and quality, respectively. Energy consumption and a more than 50% reduction in the processing complete the set of results achieved. In addition to manufacturing costs and the utilization of capacity, better sustainability indicators are positive consequences of this technological updating.

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.

Optimization and Characterization of Interspecific Hybrid Crude Palm Oil Unaué HIE OxG Nanoparticles with Vegetable By-Products as Encapsulants.

Interspecific hybrid crude palm oil (HCPO) HIE OxG derived from crossbred African oil palm (Elaeis guineensis) and American Caiaué (Elaeis oleifera) is prominent for its fatty acid and antioxidant compositions (carotenoids, tocopherols, and tocotrienols), lower production cost, and high pest resistance properties compared to crude palm oil. Biodegradable and sustainable encapsulants derived from vegetable byproducts were used to formulate HCPO nanoparticles. Nanoparticles with hybrid crude palm oil and jackfruit seed flour as a wall material (N-JSF) and with hybrid crude palm oil and jackfruit axis flour as a wall material (N-JAF) were optimized using a 22 experimental design. They exhibited nanoscale diameters (<250 nm) and were characterized based on their zeta potential, apparent viscosity, pH, color, and total carotenoid content. The nanoparticles demonstrated a monodisperse distribution, good uniformity, and stability (polydispersity index < 0.25; zeta potentials: N-JSF -19.50 ± 1.47 mV and N-JAF -12.50 ± 0.17 mV), as well as high encapsulation efficiency (%) (N-JSF 86.44 ± 0.01 and N-JAF 90.43 ± 1.34) and an optimal carotenoid retention (>85%). These nanoparticles show potential for use as sustainable and clean-label HCPO alternatives in the food industry.

RNA Combined with Nanoformulation to Advance Therapeutic Technologies.

Nucleic acid-based therapies have the potential to address numerous diseases that pose significant challenges to more traditional methods. RNA-based therapies have emerged as a promising avenue, utilizing nanoformulation treatments to target a range of pathologies. Nanoformulation offers several advantages compared to other treatment modalities, including targeted delivery, low toxicity, and bioactivity suitable for drug loading. At present, various types of nanoformulations are available, such as liposomes, polymeric nanoparticles (NPs), magnetic NPs, nanoshells, and solid lipid nanoparticles (SLNs). RNA-based therapy utilizes intracellular gene nanoparticles with messenger RNA (mRNA) emerging prominently in cancer therapy and immunotechnology against infectious diseases. The approval of mRNA-based technology opens doors for future technological advancements, particularly self-amplifying replicon RNA (repRNA). RepRNA is a novel platform in gene therapy, comprising viral RNA with a unique molecular property that enables the amplification of all encoded genetic information countless times. As a result, repRNA-based therapies have achieved significant levels of gene expression. In this context, the primary objective of this study is to furnish a comprehensive review of repRNA and its applications in nanoformulation treatments, with a specific focus on encapsulated nanoparticles. The overarching goal is to provide an extensive overview of the use of repRNA in conjunction with nanoformulations across a range of treatments and therapies.

New distance measure for comparing protein using cellular automata image.

One of the first steps in protein sequence analysis is comparing sequences to look for similarities. We propose an information theoretical distance to compare cellular automata representing protein sequences, and determine similarities. Our approach relies in a stationary Hamming distance for the evolution of the automata according to a properly chosen rule, and to build a pairwise similarity matrix and determine common ancestors among different species in a simpler and less computationally demanding computer codes when compared to other methods.

Decision Support Frameworks in Public Health Emergencies: A Systematic Review of Dynamic Models in Complex Contexts.

Public health emergencies are extraordinary events of disease spread, with health, economic, and social consequences, which require coordinated actions by governments and society. This work aims to analyze scopes, application possibilities, challenges, and gaps of decision support frameworks in PHE management, using the components of the Health Emergency and Disaster Risk Management Framework (H-EDRM) and the Preparedness, Prevention, Response and Recovery Model (PPRR Model), providing guidelines for the development of new models. A systematic literature review was carried out using the Web of Science, Scopus, and Pubmed knowledge databases on studies published between 2016 and 2023, and thirty-six articles were selected. The outcomes show a concentration of frameworks on short-term emergency response operations, with a limited emphasis on the political and strategic components that drive actors and responsibilities. Management prioritizes monitoring, evaluation, and information management frameworks. However, the models need to overcome the challenges of multisectoral and interdisciplinary action, different levels of decisions and actors, data sharing, and development of common platforms of evidence for decisions fitted to the various emergencies.

Edible and essential oils nanoparticles in food: a review on the production, characterization, application, stability, and market scenario.

The application of oils in the food industry is challenging, owing to their inherent factors such as oxidation. Therefore, new technologies, such as nanoencapsulation, are being developed. Among the nanoencapsulated oils, essential oils (EO) and edible oils stand out for their high consumer demand. This review analyzes the production, characterization, stability, and market scenario of edible and EO nanoparticles applied in foods. Homogenization was found to be the most common technique for producing oil nanoparticles. Different encapsulants were used, and Tween 80 was the main emulsifier. Approximately 80% of the nanoparticles were smaller than 200 nm, and the polydispersibility index and zeta potential values were satisfactory, mainly for nanoparticles containing EO, whereas encapsulation efficiency varied based on the technique and the type of oil used. Oil nanoparticles were mainly applied on meat products. The temperatures and times used in the stability tests of foods containing oil nanoparticles varied depending on the food matrix, especially in microbiological and physicochemical analyses. Only one product with nanoencapsulated oil in its composition was found in the market. Oil nanoparticles have great potential in the development of innovative, economically viable, and sustainable techniques for producing new food products that are high in nutrition value.

Long-term monitoring of COVID-19 prevalence in raw and treated wastewater in Salvador, the largest capital of the Brazilian Northeast.

Wastewater-based epidemiology (WBE) becomes an interesting epidemiological approach to monitoring the prevalence of SARS-CoV-2 broadly and non-invasively. Herein, we employ for the first time WBE, associated or not with the PEG 8000 precipitation method, for the detection of SARS-CoV-2 in samples of raw or treated wastewater from 22 municipal wastewater treatment stations (WWTPs) located in Salvador, the fourth most populous city in Brazil. Our results demonstrate the success of the application of WBE for detecting SARS-CoV-2 in both types of evaluated samples, regardless of the usage of PEG 8000 concentration procedure. Further, an increase in SARS-CoV-2 positivity rate was observed in samples collected in months that presented the highest number of confirmed COVID-19 cases (May/2021, June/2021 and January/2022). While PEG 8000 concentration step was found to significantly increase the positivity rate in treated wastewater samples (p < 0.005), a strong positive correlation (r: 0.84; p < 0.002) between non-concentrated raw wastewater samples with the number of new cases of COVID-19 (April/2021-February/2022) was observed. In general, the present results reinforce the efficiency of WBE approach to monitoring the presence of SARS-CoV-2 in either low- or high-capacity WWTPs. The successful usage of WBE even in raw wastewater samples makes it an interesting low-cost tool for epidemiological surveillance.

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.

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.

Dengue as a Disease Threatening Global Health: A Narrative Review Focusing on Latin America and Brazil.

Arboviruses constitute the largest known group of viruses. These viruses are the etiological agents of pathologies known as arboviruses, with dengue being one of the most prevalent. Dengue has resulted in important socioeconomic burdens placed on different countries around the world, including those in Latin America, especially Brazil. Thus, this work intends to carry out a narrative-based review of the literature, conducted using a study of the secondary data developed through a survey of scientific literature databases, and to present the situation of dengue, particularly its distribution in these localities. Our findings from the literature demonstrate the difficulties that managers face in controlling the spread of and planning a response against dengue, pointing to the high cost of the disease for public coffers, rendering the resources that are already limited even scarcer. This can be associated with the different factors that affect the spread of the disease, including ecological, environmental, and social factors. Thus, in order to combat the disease, it is expected that targeted and properly coordinated public policies need to be adopted not only in specific localities, but also globally.

Hereditary hemochromatosis beyond hyperferritinemia: Clinical and laboratory investigation of the patient's profile submitted to phlebotomy in two reference centers in southern Brazil.

Hereditary Hemochromatosis is a disorder characterized by iron deposition in several organs and hyperferritinemia. The most studied variants are linked to the HFE gene. In Brazil, surveys that characterize this population are scarce, with no sampling in the state of Rio Grande do Sul. Our objective is to carry out a data collection focusing on the profile of this population and the influence of the most frequently HFE variants. Two centers were enrolled: Hospital de Clínicas de Porto Alegre and Hospital São Vicente de Paulo. Patients with hyperferritinemia and undergoing phlebotomy were invited. Clinical data were collected, including HFE investigation. Among the descriptive data, the allele frequency of the C282Y variant (0.252) stands out, which differs from the national scenario. Systemic arterial hypertension was the most cited comorbidity. Differences between centers were observed, highlighting higher frequency of H63D cases in HSVP (p<0.01). Genotypes were stratified according to deleterious effect of C282Y variant. Higher transferrin saturation and number of phlebotomies were observed in the C282Y/C282Y cases (p<0.001). Positive family history for hyperferritinemia was more prevalent in compound heterozygotes (p<0.01). The results presented confirm the importance of encouraging such studies and reiterate the need for greater attention to this population.

Extraction of Antioxidant Compounds from Brazilian Green Propolis Using Ultrasound-Assisted Associated with Low- and High-Pressure Extraction Methods.

The demand for bee products has been growing, especially regarding their application in complementary medicine. Apis mellifera bees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate produce green propolis. Among the examples of bioactivity of this matrix are antioxidant, antimicrobial, and antiviral actions. This work aimed to verify the impact of the experimental conditions applied in low- and high-pressure extractions of green propolis, using sonication (60 kHz) as pretreatment to determine the antioxidant profile in the extracts. Total flavonoid content (18.82 ± 1.15-50.47 ± 0.77 mgQE·g-1), total phenolic compounds (194.12 ± 3.40-439.05 ± 0.90 mgGAE·g-1) and antioxidant capacity by DPPH (33.86 ± 1.99-201.29 ± 0.31 µg·mL-1) of the twelve green propolis extracts were determined. By means of HPLC-DAD, it was possible to quantify nine of the fifteen compounds analyzed. The results highlighted formononetin (4.76 ± 0.16-14.80 ± 0.02 mg·g-1) and p-coumaric acid (

Myocardial infarction or myocarditis? A case report and review of a myocardial adverse event associated with mRNA vaccine.

A 23-year-old man started with chest pain 8 h after his first Pfizer-BioNTech COVID-19 vaccination. ECG evaluation showed sinus tachycardia with ST-segment elevation in D1, AVL, V5, and V6, the findings compatible with acute subepicardial myocardial damage. However, cardiac MRI documented myocardial fibrosis, with cardiac late enhancement non-ischemic pattern with diffuse edema. He had no other symptoms to suggest another etiology than the vaccination. The patient was hospitalized and received corticosteroid (prednisolone) daily. Then, 2 weeks after hospitalization, all laboratory parameters and ECG were normal and the patient was discharged from the hospital. The patient had a history of Wolf-Parkinson White that was corrected with ablation when he was 11 years old. This report calls attention to myocardial adverse reaction risk for mRNA COVID-19 vaccines for people with a previous cardiac disease history.