Role of inflammation and oxidative stress in tissue damage associated with cystic fibrosis: CAPE as a future therapeutic strategy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

Hyperinflammation and airway surface liquid dehydration in cystic fibrosis: purinergic system as therapeutic target.

OBJECTIVE AND DESIGN: The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. MATERIALS AND METHODS: To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. CONCLUSION: We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.

Common mental disorders among medical students: systematic review and meta-analysis of Brazilian studies.

BACKGROUND: Common mental disorders (CMDs) have been correlated with consequences in different domains of life. OBJECTIVE: To summarize the prevalence rates of CMDs and factors associated with them among students at Brazilian medical schools. DESIGN AND SETTING: Systematic review and meta-analysis of studies developed in Brazilian medical schools. METHODS: In October 2021, searches were carried out in seven electronic databases, in Google Scholar and in reference lists. Observational studies reporting prevalence rates of CMDs among students at Brazilian medical schools were sought. Variables associated with CMDs arising from multivariate regression models were included in the synthesis. A meta-analysis was developed using a random-effects model and the risk of bias was assessed using an instrument developed from previous references. RESULTS: Fourteen original studies were included. The pooled prevalence rate of CMDs among undergraduate students at Brazilian medical schools was 43.3% (95% confidence interval = 38.9% to 47.6%; I2 = 87%; n = 3,927). Among the nine studies in which multivariate analyses were conducted, five showed risk associations between CMDs and medical school-related dissatisfactions, among which the desire to abandon the medical course can be highlighted (n = 3). In three studies, CMDs were associated with sleep indicators. CONCLUSION: Considering that the prevalence of CMDs among medical students is higher than in the general population, we recommend that Brazilian medical schools should give greater attention to this topic, and should enable expansion of care offerings relating to mental health. SYSTEMATIC REVIEW REGISTRATION: Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020142184).

Common mental disorders among medical students: systematic review and meta-analysis of Brazilian studies

ABSTRACT BACKGROUND: Common mental disorders (CMDs) have been correlated with consequences in different domains of life. OBJECTIVE: To summarize the prevalence rates of CMDs and factors associated with them among students at Brazilian medical schools. DESIGN AND SETTING: Systematic review and meta-analysis of studies developed in Brazilian medical schools. METHODS: In October 2021, searches were carried out in seven electronic databases, in Google Scholar and in reference lists. Observational studies reporting prevalence rates of CMDs among students at Brazilian medical schools were sought. Variables associated with CMDs arising from multivariate regression models were included in the synthesis. A meta-analysis was developed using a random-effects model and the risk of bias was assessed using an instrument developed from previous references. RESULTS: Fourteen original studies were included. The pooled prevalence rate of CMDs among undergraduate students at Brazilian medical schools was 43.3% (95% confidence interval = 38.9% to 47.6%; I2 = 87%; n = 3,927). Among the nine studies in which multivariate analyses were conducted, five showed risk associations between CMDs and medical school-related dissatisfactions, among which the desire to abandon the medical course can be highlighted (n = 3). In three studies, CMDs were associated with sleep indicators. CONCLUSION: Considering that the prevalence of CMDs among medical students is higher than in the general population, we recommend that Brazilian medical schools should give greater attention to this topic, and should enable expansion of care offerings relating to mental health. SYSTEMATIC REVIEW REGISTRATION: Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020142184).