Quality of life in Brazilian medical students: a systematic review and meta-analysis

Abstract Objectives Medical training negatively impacts the quality of life of students. Assessing the well-being of medical students could guide academic policies and future research for improving the mental and physical health status of the population at risk. This study aimed to identify the influence of medical training on the quality of life of Brazilian medical students. Methods A systematic review and meta-analysis was conducted according to the Cochrane criteria and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol (PRISMA). The search was performed by two independent investigators using a predefined protocol registered on the PROSPERO database (CRD42021237926). Data were extracted from PubMed, Embase, and Biblioteca Virtual de Saúde (BVS). For quantitative synthesis, a meta-analysis was conducted to assess the mean difference in the quality of life between medical students at different stages in the academic cycle, stratified by sex. All data were analyzed using the random-effects model, with a confidence interval of 95% (95%CI). Results After evaluating the eligibility criteria, five studies were included in the meta-analysis. The data revealed that students in the pre-clinical cycle of the course exhibited higher quality of life scores in the physical (3.05 [1.48-4.62], p < 0.0001) and psychological (3.05 [0.80-5.30], p < 0.0001) domains than students in the clerkship cycle. No statistically significant differences were observed in the environmental (0.78 [-2.92-4.49], p = 0.68) or social domains (1.41 [-0.52-3.34], p = 0.15). Conclusion Our analysis revealed that the medical course is associated with decreased quality of life of medical students in the physical and psychological domains. This finding was observed in both men and women. However, these findings should be interpreted with caution given the study limitations. Registration number PROSPERO, CRD42021237926.

Levels of organic pollutants and metals/metalloids in infant formula marketed in Brazil: Risks to early-life health.

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Association between urinary concentrations of toxic metals/metalloids and oxidative stress in Brazilians living in areas affected by the Fundão dam failure.

The Fundão Dam failure has been the most significant environmental disaster in Brazil. The catastrophe released large amounts of mining waste into the environment, including toxic metals/metalloids, which are recognized to induce carcinogenic effects. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), a widely accepted oxidative stress and carcinogenesis biomarker, provide a potential tool for assessing the disaster's health implications. This study investigated the association between urinary levels of some toxic metals/metalloids and 8OHdG in Brazilian individuals living in areas affected by the Fundão dam failure. Urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) were determined using inductively coupled plasma mass spectrometry, while 8OHdG was analyzed by liquid chromatography-tandem mass spectrometry. Non-parametric bootstrap regression was used to estimate the associations between the urinary levels of toxic elements and 8OHdG. The results showed that except for Hg, urinary concentrations of all metals/metalloids analyzed here exceeded the reference ranges for the Brazilian population. The regression analysis revealed that As (0.337; CI 95%: 0.203; 0.474), Cd (0.268; CI 95%: 0.036; 0.520), and Ni (0.296; CI 950.108; 0.469) were positively associated with creatinine-adjusted urinary 8OHdG levels. Associations were not found for Hg (0.0122; CI 95%: -0.155; 0.183) and Pb (0.201; CI 95%: -0.040; 0.498). The current findings suggest that high exposure to toxic metals/metalloids might increase 8OHdG levels with potential adverse health effects. This study is the first one in which the relationship between toxic metals/metalloids and oxidative stress biomarkers is investigated in populations affected by environmental disasters. Further prospective studies are necessary to monitor exposure levels and explore additional health impacts.

Biomonitoring of polycyclic aromatic hydrocarbons in Brazilian pregnant women: Urinary levels and health risk assessment.

Over the years, humans have been continuously exposed to several compounds directly generated by industrial processes and/or present in consumed products. Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants ubiquitous in the environment and represent the main chemical pollutants in urban areas. Worldwide, studies that aim to understand the impacts of exposure to these chemicals have gained increasing prominence due to their potential toxicity profile, mainly concerning genotoxicity and carcinogenicity. Human biomonitoring (HB) is an analytical approach to monitoring population exposure to chemicals; however, these studies are still limited in Brazil. Thus, this work aimed to evaluate the exposure of Brazilian pregnant women to PAHs through HB studies. Besides, the risk characterization of this exposure was performed. For this purpose, urine samples from 358 Brazilian pregnant women were used to evaluate 11 hydroxylated metabolites of PAHs employing gas chromatography coupled to mass spectrometry. The 1OH-naphthol and 2OH-naphthol were detected in 100% of the samples and showed high levels, corresponding to 16.99 and 3.62 µg/g of creatinine, respectively. 2OH-fluorene (8.12 µg/g of creatinine) and 9OH-fluorene (1.26 µg/g of creatinine) were detected in 91% and 66% of the samples, respectively. Benzo(a)pyrene (BaP) metabolites were detected in more than 50% of the samples (0.58-1.26 µg/g of creatinine). A hazard index of 1.4 and a carcinogenic risk above 10-4 were found for BaP metabolites in the risk characterization. Therefore, our findings may indicate that exposure to PAHs poses a potential risk to pregnant women's health and a high probability of carcinogenic risk due to their exposure to BaP. Finally, this work shows the need for more in-depth studies to determine the sources of exposure and the implementation of health protection measures regarding the exposure of the Brazilian population to PAHs.

Age, gender, and 11 comorbidities as risk factors associated with COVID-19 mortality: A retrospective cohort including 1.8 million individuals.

The aim of this study was to investigate the risk factors age, gender, and 11 comorbidities for mortality attributed to COVID-19 among Brazilians. An observational, retrospective cohort study with 1,804,151 individuals was performed using the São Paulo State Statistics Portal database for COVID-19 monitoring. Multivariate binary logistic regression was conducted to estimate the influence of odds ratio (OR) for asthma, diabetes, obesity, Down's syndrome, puerperal, hematological, hepatic, neurological, pulmonary, immunological, kidney, and other diseases contributing to mortality attributed to COVID-19. An additional analysis was undertaken using age-stratified data including children, adults, and seniors. Our findings demonstrated that cardiac diseases (9.37%) and diabetes (6.26%) were the most prevalent disorders in therapeutically managed and deceased patients. Multivariate regression model found that male individuals (OR = 1.819, CI 1.783 to 1.856, p < 0.001), older age (OR per year = 1.081, CI 1.081 to 1.082, p < 0.001) and presenting comorbidities (OR varying from 1.84-5.47) were at a higher risk of death. The age-stratified analysis also indicates disparities in the impact of the comorbidities between children, adults, and seniors. Our comprehensive findings indicate the primary risk factors for mortality attributed to COVID-19 in the entire population examined, provide a broader perspective than investigations focused solely on hospitalized patients. This study may be utilized as a valuable tool for decision-making during the COVID-19 outbreak.

Risk characterization of human exposure to polycyclic aromatic hydrocarbons in vulnerable groups.

Nowadays, anthropogenic activities are a significant source of environmental pollutants at an alarming rate. Polycyclic aromatic hydrocarbons (PAHs) are widely spread and well-known mutagenic and carcinogenic legacy pollutants of public health concern. In underdeveloped countries like Brazil, limited data are available in the scientific literature on the risk assessment of exposure to PAHs, leading to a risk underestimation, especially in the vulnerable groups of the population. In the current investigation, we have measured seven PAH metabolites in healthy vulnerable groups (n = 400), including pregnant and lactating women, newborns, and children. Besides, according to the United States Environmental Protection Agency (US.EPA) guidelines, the risk characterization of this exposure was performed by calculating estimated daily intake, hazard quotient, hazard index, and cancer risk. The highest levels and detection rates for all metabolites were found in pregnant women, with 15.71 ng/mL for the ∑OH-PAHs, presumably due to the increased metabolic rate related to pregnancy. The lowest ∑OH-PAHs were detected in infants, with 2.33 ng/mL due to unmatured metabolism. When analyzing the health hazards, the non-carcinogenic risk - as a sum of all PAH metabolites, we observed a health risk (in all groups) above the limit that the US.EPA considers without significant potential health risk. Regarding cancer risks, benzo[a]pyrene levels in all the groups indicated a potential risk. In general, higher levels of potential cancer risk were observed for lactating women, which implies risks to them and their infants. Low molecular weight PAHs (naphthalene, fluorene, and phenanthrene) are associated with acute toxic effects. Their high detection rate (i.e., naphthalene: 100 %) demonstrates their extensive exposure, making these PAHs a priority for human biomonitoring. Besides, benzo[a]pyrene is carcinogenic to humans, being also important to monitor its levels since our risk assessment showed a high cancer risk to this PAH.

The influence of the co-exposure to polycyclic aromatic hydrocarbons and toxic metals on DNA damage in brazilian lactating women and their infants: A cross-sectional study using machine learning approaches.

Polycyclic aromatic hydrocarbons (PAHs) and toxic metals are widely spread pollutants of public health concern. The co-contamination of these chemicals in the environment is frequent, but relatively little is known about their combined toxicities. In this context, this study aimed to evaluate the influence of the co-exposure to PAHs and toxic metals on DNA damage in Brazilian lactating women and their infants using machine learning approaches. Data were collected from an observational, cross-sectional study with 96 lactating women and 96 infants living in two cities. The exposure to these pollutants was estimated by determining urinary levels of seven mono-hydroxylated PAH metabolites and the free form of three toxic metals. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the urine were used as the oxidative stress biomarker and set as the outcome. Individual sociodemographic factors were also collected using questionnaires. Sixteen machine learning algorithms were trained using 10-fold cross-validation to investigate the associations of urinary OH-PAHs and metals with 8-OHdG levels. This approach was also compared with models attained by multiple linear regression. The results showed that the urinary concentration of OH-PAHs was highly correlated between the mothers and their infants. Multiple linear regression did not show a statistically significant association between the contaminants and urinary 8OHdG levels. Machine learning models indicated that all investigated variables did not present predictive performance on 8-OHdG concentrations. In conclusion, PAHs and toxic metals were not associated with 8-OHdG levels in Brazilian lactating women and their infants. These novelty and originality results were achieved even after applying sophisticated statistical models to capture non-linear relationships. However, these findings should be interpreted cautiously because the exposure to the studied contaminants was considerably low, which may not reflect other populations at risk.

Recent trends in pesticides in crops: A critical review of the duality of risks-benefits and the Brazilian legislation issue.

Due to the increasing population worldwide, in recent years, an exponential increase in agricultural practices has occurred in order to attend to the growing demand for food. Unfortunately, this increase is not associated with the supply of foodstuffs free of environmental pollutants. In Brazil, agriculture is one of the most important economic pillars, making the country one of the largest consumers of pesticides around the world. The intense use of pesticides, mainly glyphosate, 2,4-D, and atrazine, constitutes an essential factor in the viability of this great agricultural productivity. Sugarcane, corn, soybean, and citrus crops consume around 66% of the total pesticides worldwide, representing 76% of the planted area. Pesticide residues have been frequently detected in food and the environment, becoming a significant concern for human health. Monitoring programs for pesticide use are essential to reduce the potential negative impacts on the environment and improve the overall efficiency and sustainability of their use. However, in Brazil, the approval status of pesticide-active ingredients is very discrepant compared to other agricultural countries. Moreover, the duality of benefits and risks of pesticide application creates an economic and toxicological conflict. In this paper, we have critically reviewed the duality of risks-benefits of the use of pesticides in agriculture and the current Brazilian legislation issues. We have also compared this flawed legislation with other countries with high economic potential. Due to the negative environmental impacts on soil and water by the high levels of pesticides, remediation techniques, sustainable agriculture, and the development of new technologies can be considered some viable alternatives to reduce the levels in these compartments. Besides, this paper includes some recommendations that can be included in the coming years.

Urinary levels of 30 metal/metalloids in the Brazilian southeast population: Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The assessment of risks associated with environmental exposure to metals/metalloids requires well-established reference values for each population since it varies considerably according to distinct local/regional characteristics. However, very few studies establish baseline values for these elements (essential and toxic) in large population groups, especially in Latin American countries. This study was aimed at establishing urinary reference levels of 30 metals/metalloids: aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cerium (Ce), cesium (Cs), chromium (Cr), cobalt (Co), copper (Cu), lanthanum (La), lead (Pb), lithium (Li), strontium (Sr), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), platinum (Pt), rubidium (Rb), selenium (Se), silver (Ag), tin (Sn), tellurium (Te), thallium (Tl), thorium (Th), tungsten (W), uranium (U) and zinc (Zn) in a Brazilian southeast adult population. This pilot study is a cross-sectional analysis conducted with the first wave of the ELSA-Brasil cohort (baseline examination). A total of 996 adults (45.5% men, N = 453, mean age: 50.5, and 54.5% women, N = 543, mean age: 50.6) were included in the study. Sample analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Percentiles (2.5, 10, 25, 50, 75, 95 (CI95%), and 97.5) of each element (µg/g of creatinine) in the study are presented according to sex. Moreover, differences in the mean metal/metalloid urinary levels according to age, education, smoking, and alcohol intake are also presented. Finally, median found values were compared to established values of large human biomonitoring surveys previously conducted in North America and France. This is the first comprehensive and systematic human biomonitoring study that established population reference ranges for 30 (essential and/or toxic elements) in a Brazilian population group.

Magnetic restricted-access carbon nanotubes for SPME to determine cannabinoids in plasma samples by UHPLC-MS/MS.

This manuscript describes the development of magnetic restricted-access carbon nanotubes (M-RACNTs) for use as SPME sorbent to determine cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in human plasma samples by UHPLC-MS/MS. The adsorptive phase was immobilized on an SPME device by electromagnetic interactions between the M-RACNTs and a cylindrical neodymium magnet (3-mm diameter x 8-mm height) attached to a stainless-steel rod (3-mm diameter x 40-mm height). The M-RACNTs were synthesized by incorporating Fe3O4 magnetic nanoparticles (MNPs) into commercial carbon nanotubes (CNTs); then the surface of the resulting sorbent was further coated with a layer of bovine serum albumin (BSA). Characterization techniques (SEM, FTIR, and Zeta potential) confirmed the presence of both MNPs and BSA layer dispersed through the structure of the CNTs. The M-RACNTs presented adequate sorption capacity, stable physical/chemical characteristics, and appropriate magnetic properties. Protein exclusion capacity (about 98.5%) was attributed to the chemical diffusion barrier created by the BSA network at the outer surface of the sorbent. The SPME parameters (sample pH, equilibrium time, and desorption conditions) were optimized by design of experiments (fraction factorial planning). The method (validated according to the FDA guidelines) presented adequate selectivity and linearity (coefficient of determination higher than 0.99) at concentrations ranging from the lower limit of quantification (LLOQ) (10 ng mL-1) to the upper limit of quantification (ULOQ) (300 ng mL-1) for both CBD and THC. Precision and accuracy varied from 4.47 to 19.84% (LLOQ) and -6.90 to 17.78% (LLOQ), respectively. Carry-over and matrix effect were not significant. The method was successfully applied to determine plasmatic CBD levels in healthy volunteers attending a single session of oral drug administration and THC levels in frequent cannabis smokers.

Quality of life in Brazilian medical students: A systematic review and meta-analysis.

INTRODUCTION: Medical training negatively impacts the quality of life of students. Assessing the well-being of medical students might guide academic policies and future research for improving mental and physical health status of the population at risk. OBJECTIVES: This study aimed to identify the influence of medical training on the quality of life of Brazilian medical students. METHOD: A systematic review and meta-analysis was conducted according to the Cochrane criteria and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. The search was performed by two independent investigators using a predefined protocol registered in PROSPERO (CRD42021237926). Data were extracted from PubMed, EMBASE, and Biblioteca Virtual de Saúde. For quantitative synthesis, a meta-analysis was conducted to assess the mean difference in the quality of life between medical students of different academic cycles stratified by sex. All data were analyzed using the random-effects model, with a confidence interval of 95%. RESULTS: After evaluating the eligibility criteria, five studies were included in the meta-analysis. The data revealed that students in the pre-clinical cyclee of the course exhibited higher quality of life scores in the physical (3.05 [1.48, 4.62], p< 0.0001) and psychological (3.05 [0.80, 5.30], p< 0.0001) domains than students in the clerkship cycle. No statistically significant difference was observed in the environmental (0.78 [-2.92, 4.49], p= 0.68]) and social domains (1.41 [-0.52, 3.34], p= 0.15). CONCLUSION: Our analysis revealed that the medical course is associated with a decreased quality of life in the physical and psychological domains of medical students. This finding was observed in both men and women. However, these findings should be interpreted with caution given the limitations of this study.

Current advances and applications of online sample preparation techniques for miniaturized liquid chromatography systems.

Miniaturized liquid chromatography (LC) has been recognized as one of the most important analytical methods in several research fields. Reduced analytical work-scale provides superior chromatographic resolution and decreases sample and organic solvent consumption. However, frequent clogging of tubing connections and use of small sample volumes are significant limitations when high throughput and sensitive analyses are required. Effective sample preparation could help to overcome these limitations. Online coupling of sample preparation techniques (such as column switching and in-tube solid-phase microextraction) with these miniaturized systems may result in more sensitive and reproducible analyses, improving analytical efficiency. This review describes the most common online miniaturized LC configurations, and the main applications of current online sample preparation techniques coupled to miniaturized LC systems in the bioanalytical, omics, and environmental areas. Relevant features, and challenges of these systems, and innovative sorbents, including restricted access materials, monoliths, and immunosorbents is also discussed.

Pipette tip micro-solid phase extraction (octyl-functionalized hybrid silica monolith) and ultra-high-performance liquid chromatography-tandem mass spectrometry to determine cannabidiol and tetrahydrocannabinol in plasma samples.

This manuscript describes the development of an innovative method to determine cannabinoids (cannabidiol and tetrahydrocannabinol) in human plasma samples by pipette tip micro-solid phase extraction and liquid chromatography-mass spectrometry/mass spectromtery. An octyl-functionalized hybrid silica monolith, which had been synthesized and characterized, was used as a selective stationary phase. The octyl-functionalized hybrid silica monoliths presented high permeability and adequate mechanical strength. The micro-solid phase extraction variables (sample pH, draw-eject cycles, solvent for phase clean-up, and desorption conditions) were investigated to improve not only the selectivity but also the sorption capacity. The method was linear at concentrations ranging from the lower limit of quantification (10.00 ng/mL) to the upper limit of quantification (150.0 ng/mL). The lack of fit and homoscedasticity tests, as well as the determination coefficients (r2 greater than 0.995), certified that linearity was adequate. The precision assays presented coefficient of variation values lower than 15%, and the accuracy tests provided relative error values ranging from 3.2 to 14%. Neither significant carry-over nor matrix effects were detected. Therefore, the pipette tip micro-solid phase extraction/liquid chromatography-mass spectrometry/mass spectrometry method has demonstrated to be adequate to determine cannabidiol and tetrahydrocannabinol simultaneously in plasma samples for therapeutic drug monitoring of patients undergoing treatment with cannabinoids.

Restricted access carbon nanotube for microextraction by packed sorbent to determine antipsychotics in plasma samples by high-performance liquid chromatography-tandem mass spectrometry.

This manuscript describes the development of the restricted access carbon nanotube (RACNT) as a selective stationary phase for microextraction by packed sorbent (MEPS) to determine antipsychotics (chlorpromazine, clozapine, olanzapine, and quetiapine) in untreated plasma samples from schizophrenic patients by ultra-high liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The synthesis was achieved by chemically covering commercial multi-walled carbon nanotubes with bovine serum albumin (BSA) to subsequently pack the material in a polyethylene conical tube (1000 µL). The RACNTs' sorbents were able to exclude about 97% of the plasma proteins, maintaining the same performance for about 100 assays. The MEPS variables (sample pH, draw-eject cycles, desorption and phase cleanup) were evaluated to improve sensibility and selectivity. The MEPS/UHPLC-MS/MS method was linear at concentrations ranging from the lower limit of quantification (10.0 ng mL-1) to the upper limit of quantification (200-700 ng mL-1) with coefficients of determinations higher than 0.99. The precision assays presented relative standard deviation (RSD) values lower than 13%, and the accuracy assays presented relative error (RE) values that ranged from - 8.01 to 11.53%. Neither significant matrix effects nor carryover was observed. The developed method was successfully applied to determine antipsychotics drugs for therapeutic drug monitoring of schizophrenic patients.