Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy on progression-free survival in early progressed follicular lymphoma before autologous stem cell transplantation: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of dose-intensified versus standard-dose salvage regimens on progression-free survival in early progressed follicular lymphoma before high-dose chemotherapy and autologous stem cell transplantation. INTRODUCTION: Despite the substantial advances in the management of follicular lymphoma, approximately 20% of patients experience progression of the disease within 2 years of induction therapy. These patients have worse outcomes, and autologous stem cell transplantation is deemed to improve outcomes in this context. Little is known about the optimal salvage regimen. INCLUSION CRITERIA: Studies must include patients ≥18 years old with early progressed follicular lymphoma who were submitted to autologous stem cell transplantation in subsequent remission. Clinical trials and observational studies will be included. METHODS: The search strategy will be carried out in MEDLINE (PubMed), Embase (Periódicos CAPES), Scopus, Web of Science, LiLACS, and the Cochrane Library. No date or language restrictions will be imposed. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis will be used. Studies should score at least 50% in accordance with the critical appraisal tool. Data will be pooled whenever possible using the random effects model. Heterogeneity will be assessed using the standard χ2 and I2 tests. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. The GRADE approach will be used to rate certainty of evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022373345.

17ß-estradiol and methylprednisolone association as a therapeutic option to modulate lung inflammation in brain-dead female rats.

Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.

Factors associated with older adults' cognitive decline 6 months after gamma-variant SARS-CoV-2 infection.

Background: Cognitive deficits are commonly reported after COVID-19 recovery, but little is known in the older population. This study aims to investigate possible cognitive damage in older adults 6 months after contracting COVID-19, as well as individual risk factors. Methods: This cross-sectional study involved 70 participants aged 60-78 with COVID-19 6 months prior and 153 healthy controls. Montreal Cognitive Assessment-Basic (MoCA-B) screened for cognitive impairment; Geriatric Depression Scale and Geriatric Anxiety Inventory screened for depression and anxiety. Data were collected on demographics and self-reports of comorbid conditions. Results: The mean age of participants was 66.97 ± 4.64 years. A higher proportion of individuals in the COVID group complained about cognitive deficits (χ2 = 3.574; p = 0.029) and presented with deficient MoCA-B scores (χ2 = 6.098, p = 0.014) compared to controls. After controlling for multiple variables, all the following factors resulted in greater odds of a deficient MoCA-B: COVID-19 6-months prior (OR, 2.44; p = 0.018), age (OR, 1.15; p < 0.001), lower income (OR, 0.36; p = 0.070), and overweight (OR, 2.83; p = 0.013). Further analysis pointed to individual characteristics in COVID-19-affected patients that could explain the severity of the cognitive decline: age (p = 0.015), lower income (p < 0.001), anxiety (p = 0.049), ageusia (p = 0.054), overweight (p < 0.001), and absence of cognitively stimulating activities (p = 0.062). Conclusion: Our study highlights a profile of cognitive risk aggravation over aging after COVID-19 infection, which is likely mitigated by wealth but worsened in the presence of overweight. Ageusia at the time of acute COVID-19, anxiety, being overweight, and absence of routine intellectual activities are risk factors for more prominent cognitive decline among those infected by COVID-19.

Peripherally Inserted Central Catheter Versus Centrally Inserted Central Catheter for In-Hospital Infusion Therapy: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the comparative effectiveness and cost-effectiveness of peripherally inserted central catheters (PICCs) compared with centrally inserted central catheters (CICCs). METHODS: Prospective cohort study was followed by an economic analysis over a 30-day time horizon. Propensity score matching was used to select hospitalized adults with similar indications for PICC or CICC. The composite outcome was device removal or replacement because of complications before the end of treatment. The economic evaluation was based on a decision tree model for cost-effectiveness analysis, with calculation of the incremental cost-effectiveness ratio (ICER) per catheter removal avoided. All costs are presented in Brazilian reais (BRL) (1 BRL = 0.1870 US dollar). RESULTS: A total of 217 patients were followed in each group; 172 (79.3%) of those receiving a PICC and 135 (62.2%) of those receiving a CICC had no device-related complication, respectively. When comparing the events leading to device removal, the risk of composite endpoint was significantly higher in the CICC group (hazard ratio 0.20; 95% CI 0.11-0.35). The cost of PICC placement was BRL 1290.98 versus BRL 467.16 for a CICC. In the base case, the ICER for placing a PICC instead of a CICC was BRL 3349.91 per removal or replacement avoided. On univariate sensitivity analyses, the model proved to be robust within an ICER range of 2500.00 to 4800.00 BRL. CONCLUSIONS: PICC placement was associated with a lower risk of complications than CICC placement. Although the cost of a PICC is higher, its use avoided complications and need for catheter replacement before the end of treatment.

Human health risk assessment of metals in soil samples of a Brazilian city with a historic contamination complex.

Rio Grande is a city located on a narrow industrialized and urbanized Brazilian peninsula, characterized by wetlands. Due to population growth, numerous urban backfilled regions were built to expand the territorial area of the city. Currently, more than 60% of the central area of the city comes from the grounding of wetlands. The material used for the expansion of the territory had a history of contamination from metals from the tannery and textile industries (mainly Hg) and urban solid waste. In addition to past sources, the city has an active industrial complex with fertilizer, petrochemical, and grain industries. This study evaluated the risks to human health caused by metals (Hg, Fe, Ni, Cr, Cu, Pb, and Zn) in original soils and backfills, considering the oral, inhalation, and dermal routes of exposure for children and adults using the tool human health risk assessment (HHRA) proposed methodology by USEPA. A total of 63.81% of the original soil samples and 57.14% of the backfill soil samples showed a non-carcinogenic risk (HInc>1) for at least one evaluated metal. Still, approximately 10% of the samples presented carcinogenic risk when the Cr was considered in the hexavalent form. The dermal (Hg, Ni, and Cr) and oral (Fe, Cu, and Zn) exposure routes had the greatest contribution to the total risk. The non-carcinogenic risk for Hg, Cr(VI), and Pb was heterogeneously distributed between the original soils and backfills and associated with the proximity to some pollution sources. Given the complexity of historical occupation in the municipality and the increasing industrialization, both the original areas and the backfills should be included in the risk management strategy to minimize risks.

Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP. METHODS: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1ß levels. Leukocyte infiltration, myeloperoxidase presence, IL-1ß gene expression, and long-term release in lung culture (explant) were evaluated. RESULTS: Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1ß levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile. CONCLUSION: In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket.

To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.

Effects of kidney perfusion on renal stiffness and tissue fluidity measured with tomoelastography in an MRI-compatible ex vivo model.

Stiffness plays a vital role in diagnosing renal fibrosis. However, perfusion influences renal stiffness in various chronic kidney diseases. Therefore, we aimed to characterize the effect of tissue perfusion on renal stiffness and tissue fluidity measured by tomoelastography based on multifrequency magnetic resonance elastography in an ex vivo model. Five porcine kidneys were perfused ex vivo in an MRI-compatible normothermic machine perfusion setup with adjusted blood pressure in the 50/10-160/120 mmHg range. Simultaneously, renal cortical and medullary stiffness and fluidity were obtained by tomoelastography. For the cortex, a statistically significant (p < 0.001) strong positive correlation was observed between both perfusion parameters (blood pressure and resulting flow) and stiffness (r = 0.95, 0.91), as well as fluidity (r = 0.96, 0.92). For the medulla, such significant (p < 0.001) correlations were solely observed between the perfusion parameters and stiffness (r = 0.88, 0.71). Our findings demonstrate a strong perfusion dependency of renal stiffness and fluidity in an ex vivo setup. Moreover, changes in perfusion are rapidly followed by changes in renal mechanical properties-highlighting the sensitivity of tomoelastography to fluid pressure and the potential need for correcting mechanics-derived imaging biomarkers when addressing solid structures in renal tissue.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Comparison of acute kidney injury following brain death between male and female rats.

BACKGROUND: Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model. METHODS: Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. RESULTS: BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051). CONCLUSION: The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.

Ethnic/Racial Disparity in Mortality from COVID-19: Data for the Year 2020 in Brazil.

The study aimed to investigate ethnic/racial disparities in COVID-19 mortality in Brazilian federative units and their respective capitals in 2020. Population data and number of COVID-19 deaths were extracted by skin color (white, black, brown and indigenous) from all Brazilian states and their respective capitals. The mortality rate of COVID-19 by ethnicity in Brazilian states was higher between people from brown skin color, followed by indigenous and black. Only in one state, in the Federal District and in the federal capital, age-standardized mortality rates were higher among white's people. There is a high percentage of deaths from COVID-19 higher than expected among non-white individuals, especially in south-central states and capitals of the country. Mortality from COVID-19 affect ethnic-racial groups unevenly in Brazil and the number of excess deaths among non-whites was over 9000. Urgent government measures are needed to reduce the racial disparity in health indicators in Brazil.

Emissions monitoring and carcinogenic risk assessment of PM10-bounded PAHs in the air from Candiota's coal activity area, Brazil.

The city of Candiota contains a great amount of coal resources. Coal activities, including coal combustion, are major releasers of polycyclic aromatic hydrocarbons (PAHs). The PAHs are considered priority air pollutants regarding their large carcinogenic potential. So, the carcinogenic risk assessment of populations living near areas with PAH sources is mandatory. This study aimed to evaluate the carcinogenic health risk of the PAH inhalation exposure of individuals living in Candiota City. A total of 158 individuals were enrolled in the study. Monitoring of PAH and meteorological parameters were carried out, and the health risk assessment was determined through the benzo(a)pyrene equivalent toxic equivalent quotient (BaP-TEQ) and the incremental lifetime cancer risk (ILCR) estimation. The coal activity area of Candiota demonstrated an annual PAH concentration of 27.7 ng/m3, PM10 concentration of 26.3 µg/m3, SO2 concentration of 9.5 µg/m3, a BaP-TEQ value of 0.3 ng/m3, and a daily inhalation of 62.4 ng/day. The comparison among seasons showed no difference in PAH concentration and BaP-TEQ. It was observed ILCR values of 2.8 × 10-6 and 2.6 × 10-6 for estimation based on reference and real values, respectively, and these levels were above the reference limit of 10-6, indicating cancer risk. Therefore, an epidemiological survey of cancer cases in the region and its relationship with environmental exposure and air pollutants levels must be required.

Multiple exposure pathways and health risk assessment of potentially harmful elements for children and adults living in a coal region in Brazil.

Energy generated by coal can contaminate the environment by releasing toxic elements, including metals. The human health risk assessment (HHRA) associated with geographic information system (GIS) tools can assist the management of contaminated areas, such as coal mining areas. The objective of the study was to carry out the assessment and spatialization of the risk to human health of potentially hazards elements (PHEs) in the soil for children and adults, from multiple exposure routes (oral, inhalation and dermal) in the Candiota mines, largest coal mining region of Brazil. The non-carcinogenic risks (HQ) of PHEs (Cu, Pb, Zn, Ni, Cr, Fe, Mn, Cd, As and Se) and carcinogenic risks of As were estimated and spatialized. The results revealed a risk for children exposure to Mn, with greatest contribution through dermal route. Mn (HQderm 72.41-96.09% and HQinh 40.84-82.52%) and Fe (HQo 43.90-81.44%) were the metals with greatest contribution to human health risk among studied population. As did not present carinogenic risk to adults. The spatial distribution of non-carcinogenic risk showed that Cr, As, Fe, Pb, Ni, Zn and Cu have higher HInc close to the coal mining areas, while Mn, Se and Cd have the highest HInc values in surrounding municipalities (Pinheiro Machado; Pedras Altas and Hulha Negra). The use of HHRA associated with GIS tools provides important elements for decision-making in the management of contaminated sites, indicating chemical elements, locations, routes of exposure and priority target populations.

Comparison of acute kidney injury following brain death between male and female rats

Abstract Background Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model. Methods Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. Results BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p< 0.0001). BD-male kidneys presented greater proximal (p= 0.0311) and distal tubule (p= 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p= 0.0060) and greater upregulation of inflammatory mediators, iNOS (p= 0.0051), and Caspase-3 (p= 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p= 0.0003), and nNOS (p= 0.0051). Conclusion The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.

What happens when Schwann cells are exposed to Mycobacterium leprae - A systematic review.

Mycobacterium leprae, the pathogen that causes human leprosy, has a unique affinity for infecting and persisting inside Schwann cells, the principal glia of the peripheral nervous system. Several studies have focused on this intricate host-pathogen interaction as an attempt to advance the current knowledge of the mechanisms governing nerve destruction and disease progression. However, during the chronic course of leprosy neuropathy, Schwann cells can respond to and internalize both live and dead M. leprae and bacilli-derived antigens, and this may result in divergent cellular pathobiological responses. This may also distinctly contribute to tissue degeneration, failure to repair, inflammatory reactions, and nerve fibrosis, hallmarks of the disease. Therefore, the present study systematically searched for published studies on M. leprae-Schwann cell interaction in vitro to summarize the findings and provide a focused discussion of Schwann cell dynamics following challenge with leprosy bacilli.

Gestational and Neonatal Outcomes in Cities in the Largest Coal Mining Region in Brazil.

Brazil has one of the largest mineral coal reserves in the world. More than 40% of this ore is in the Candiota Mine, in the extreme south of Brazil, which was previously identified as a hotspot of environmental pollution. In addition, an important part of Brazil's population suffers from socioeconomic vulnerability. Since there is no information on unfavorable gestational and neonatal outcomes associated with these problems, we conducted a cross-sectional study with 1950 mother-child binomials, aiming to evaluate the association between these outcomes and air pollution as well as socioeconomic, demographic and health variables in seven cities in the region. Of the total births, 11.6% were preterm and 9.5% of neonates had low birth weight (<2500 g). These conditions were also associated with skin color, previous abortions, birth type and prenatal care, as well as exposure to higher levels of coarse particulate matter (PM10) during the first trimester of pregnancy. Regarding air pollutants, although the daily limits for PM10 were exceeded on less than 5% of days, the annual average overtook the values proposed by WHO. Thus, we concluded that prematurity and low birth weight in this region are related to air pollution, and to socioeconomic variables and health care.

Modulatory effects of 17ß-estradiol on acute lung inflammation after total occlusion of the descending aorta in male rats.

As a consequence of systemic inflammation caused by ischemia and reperfusion (I/R) due to aortic occlusion, the lungs can exhibit increased microvascular permeability, local release of pro-inflammatory mediators, and leukocyte infiltration. Lung tissue infiltration by activated neutrophils is followed by acute respiratory distress syndrome, which is linked to acute pulmonary microvascular damage, high mortality rates, and organ dysfunction. Previous studies have demonstrated that female sex hormones modulate the inflammatory response and that prophylactic treatment with 17ß-estradiol (E2) can prevent fatalities and preserve mesenteric perfusion and intestinal integrity after ischemia/reperfusion induced by aortic occlusion. In this study, we focused on the protective effects of estradiol after aortic ischemia/reperfusion by evaluating lung injury and endothelial alterations. Upon anesthesia and mechanical ventilation, male rats were subjected to aortic occlusion for 20 min, followed by 2 h of reperfusion. In parallel, one group of rats received a single injection of estradiol (280 µg/kg, i.v.) 30 min before ischemia. We observed increased serum concentrations of IL-1ß, IL-6 and IL-10 in the I/R rats and E2 was able to reduce them. E2 effects after 2 h of reperfusion resulted mainly in decreasing of edema, iNOS expression and preventing leukocyte infiltration. Overall, our data indicate that estradiol might be a supplementary approach to deal with systemic processes and lung deterioration.

DNA damage in Brazilian newborns admitted to NICUs - association with maternal and neonatal outcomes.

Growing evidence suggests that early-life events can predispose the newborn to a variety of health problems in postnatal life, which can lead to the need for specialized care in the neonatal intensive care unit (NICU). These events may be caused by factors intrinsically related to the mother (i.e., lifestyle, socioeconomic conditions), and this interplay between maternal exposure factors and negative outcomes in the neonate can be efficiently monitored through effect biomarkers, such as DNA damage. Thus, the present study aimed to evaluate the DNA damage and the maternal and neonatal factors associated with the genotoxic outcome using newborns admitted to the NICUs of three hospitals located in the extreme south of Brazil. A total of 81 newborns were evaluated. DNA damage was assessed using the comet assay, and according to the result obtained for the evaluated parameters (tail length, % of tail DNA and tail moment). The investigation of associated factors was performed using the bivariate and multivariate Poisson regression analysis. As a result, we observed that the tail moment was the most sensitive parameter to detect differences between variables and genetic outcomes in newborns from NICU. Birthweight and the presence of respiratory diseases were associated with greater risks of DNA damage. Furthermore, the variables family income, sex, head circumference, preterm, birthweight and the presence of respiratory and/or infectious diseases showed a significant statistical difference regarding the groups with and without DNA damage (based on the median of the parameter). While the results of this study will serve as the basis for investigating genetic damage, we encourage that similar studies should be conducted elsewhere in order to confirm these and other outcomes as associated factors with DNA damage in newborns.

Barriers and facilitators on the implementation of physical activity in Primary Health Care: A systematic review.

Barriers and facilitators influence the implementation of physical activity (PA) in Primary Health Care (PHC). This study aimed to analyze the scientific evidence on barriers and facilitators perceived by stakeholders on the implementation of PA in PHC.The search databases consisted of Web of Science, Medline, Scopus, and Lilacs. Two independent researchers reviewed the eligibility criteria and extracted and coded the information according to the Theoretical Domains Framework (TDF). The Consolidated Criteria for Reporting Qualitative Research was used to report the quality of the included studies. We analyzed 8.471 studies but included only 16. The studies identified 54 different reports on barriers and 48 on facilitators. Reports were often identified in the "environmental context and resources" domain, with 27 reports on barriers and 27 on facilitators. We found 25 reports of barriers and 16 of facilitators in the TDF domains that demonstrate professional profile characteristics. The low expectations in the professional profile for the implementation can influence the context and the organizational climate to identify more barriers than facilitators.