Major clinical outcomes of melatonin use in COVID-19 patients: a systematic review

Introduction: In the context of the Sars-Cov-2 (COVID-19) pandemic, as well as other viral infections, these viruses can lead to significant morbidity and mortality. Thus, in the context of melatonin science in viral infections such as influenza and COVID-19, there is a growing realization that the regulation of melatonin pathways, both pineal and systemic, may be an important aspect of the regulation of viruses in cellular functions. Objective: It was to list the main results of clinical studies of the use of melatonin in patients infected with Sars-Cov-2 through a systematic review. Methods: The rules of the Systematic Review-PRISMA Platform. The search was carried out from December 2021 to April 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: It was found 164 articles. A total of 86 articles were fully evaluated and 30 studies were developed in a systematic review. Melatonin is known as an anti-inflammatory agent and immune modulator that may address the progressive pathophysiology of coronavirus disease 2019 (COVID-19). According to the objective and results obtained in the present study that evaluated the treatment in patients with COVID-19, the use of melatonin can help reduce thrombosis, sepsis and mortality. Furthermore, the combination of 3.0 mg oral melatonin tablets and standard care can substantially improve sleep quality and blood oxygen saturation in hospitalized patients. Clinical symptoms such as cough, dyspnea and fatigue, as well as the polymerase chain reaction (PCR) level and lung involvement in patients receiving melatonin can improve significantly. Also, the mean time of patients' hospital discharge and return to initial health was significantly shorter in patients who received melatonin compared to the control group. There was evidence of benefit of sustained-release melatonin 2 mg in therapy in patients, as well as evidence that the use of melatonin was associated with a reduced probability of a positive SARS-CoV-2 test result compared to the use of blockers of the angiotensin II receptor or angiotensin-converting enzyme inhibitors

COVID-19: Major Metabolic and Immunological Relationships in Obesity

Introduction: In the scenario of chronic non-communicable diseases, obesity stands out as a multifactorial disease that can cause several public health problems. Currently, about 30% of the world's population is overweight or obese. Estimates suggest that the prevalence of severe obesity in 2030 will be 11%, approximately twice the current prevalence. By 2025, Brazil will be in fifth place in the world ranking, with an estimated 18.0 million people. The appearance of the new coronavirus (SARS-CoV-2), which causes the disease COVID-19, has worsened the comorbidities of obesity. Objective: to explore, through a concise systematic review, the main metabolic and immunological relationships in obesity, especially in the presence of COVID-19. Methods: The present study followed a concise systematic review model (PRISMA). The search strategy was carried out in the databases PubMed, Embase, Ovid and Cochrane Library, Web of Science, and Scopus. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results: A total of 76 studies were found that were submitted to the eligibility analysis, and, after that, 15 studies of high to medium quality and with risks of bias were selected that do not compromise the scientific basis of the studies, we found that obesity is an important predictor of worsening SARS-CoV-2 pathology. There is a complex interaction between multiple metabolic, immunological and inflammatory factors that result in meta-inflammation. It has been shown that obesity causes dysfunction in the immune system, increasing susceptibility to infections and death from sepsis, and increased oxidative stress in the body. SARS-CoV-2 amplifies the inflammatory response, enabling greater propensity to alveolar thrombotic microangiopathy and pulmonary thromboembolism. Meta-inflammation and insulin resistance with hyperinsulinemia is the main baseline changes in obesity. Conclusion: In the COVID-19 scenario, obesity is an important predictor of the worsening of SARS-CoV-2 pathology, mainly due to the worsening of met inflammation

Carvedilol-loaded nanocapsules : physicochemical characterization and in vitro drug release

Carvedilol (CV) has been used for the management of heart failure, hypertension and coronary artery diseases. However, it presents low oral bioavailability (25-35%). The objective of this study was to develop carvedilol-loaded nanocapsules (NC) in order to achieve a controlled drug release aiming the development of dosage forms to be administered by alternative routes. Poly(ε-caprolactone) (PCL) and Eudragit RS100 (EUD) were evaluated as polymeric wall. Nanocapsules (CV-PCL-NC and CV-EUD-NC) were prepared by interfacial deposition of preformed polymer method and characterized according to particle size and polydispersity, zeta potential, pH, drug content, encapsulation efficiency, morphology, backscattering analysis, presence of nanocrystals and drug release profile. Thermal analysis was performed to evaluate compatibility between CV and excipients. All formulations showed nanometric diameters with low polydispersity and pH slightly acid The zeta potential was positive and negative for CV-EUD-NC and CV-PCL-NC, respectively. The drug content was close to theoretical value (0.5 mg.mL-1) for both formulations and the encapsulation efficiency was higher than 87% and 99% for CV-EUD-NC and CV-PCL-NC, respectively. Nanocapsules were spherical-shaped and their suspensions showed no significant phenomena of physical instability. Drug release was controlled by both developed formulations. However, CV-PCL-NC showed phase separation during storage and an interaction between the drug and the surfactant was evidenced by thermal analysis. This study demonstrated the feasibility to encapsulate CV in nanocapsules to achieve a controlled release rate. Further studies will be carried out to explore alternatives routes of administration using these formulations

Identity, Positioning, Brand Image and Brand Equity Comparison.

The management of marketing has as presupposition the understanding of the relations between market and consumption, as well as, the concepts related to the maximization of the results of the company. In this way, an article was elaborated in search of the understanding of the existing relations between brand identity, positioning, brand image and brand equity. In this context, qualitative-quantitative research was sought to describe the existing relationships between concepts, as well as the conceptual and managerial gaps arising from their management. As a result of this work we have the analysis of the conceptual and operational gaps of these concepts

Double-Recurrence Fibonacci Numbers and Generalizations

Let $(F_n)_{n\geq 0}$ be the Fibonacci sequence given by the recurrence $F_{n+2}=F_{n+1}+F_n$, for $n\geq 0$, where $F_0=0$ and $F_1=1$. There are several generalizations of this sequence and also several interesting identities. In this paper, we investigate a homogeneous recurrence relation that, in a way, extends the linear recurrence of the Fibonacci sequence for two variables, called {\it double-recurrence Fibonacci numbers}, given by ${F(m,n) = F(m-1, n-1)+F (m-2, n-2)}$, for $n,m\geq 2$, where $F (m, 0) = F_m$, $F (m, 1) = F_{m+1}$, $F (0, n) = F_n$ and $F (1, n) = F_{n+1}$. We exhibit a formula to calculate the values of this double recurrence, only in terms of Fibonacci numbers, such as certain identities for their sums are outlined. Finally, a general case is studied.Comment: 10 pages, 5 figures and 1 tabl