Efficacy of acupuncture on cancer pain: A systematic review and meta-analysis.

BACKGROUND: Pain associated with cancer is one of the greatest causes of reduced quality of life in patients. Acupuncture is one of the treatments used to address this issue, with the great advantage of having little or no side effects, especially when compared with pharmacological pain-killers. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the current evidence regarding the efficacy of acupuncture for cancer pain. SEARCH STRATEGY: Six electronic databases (PubMed, EBSCO, Cochrane Library, Scielo, b-On and Scopus) were searched for relevant articles about pain relief in cancer patients from their beginning until 2022 using MeSH terms such as "acupuncture," "electroacupuncture," "ear acupuncture," "acupuncture analgesia," ''oncological pain," and "cancer pain." INCLUSION CRITERIA: Studies included were randomized controlled trials (RCTs) where acupuncture was compared with no treatment, placebo acupuncture or usual care. DATA EXTRACTION AND ANALYSIS: Three independent reviewers participated in data extraction and evaluation of risk of bias, and a meta-analysis was conducted. The primary outcome was pain intensity, measured with the visual analog scale, numeric rating scale, or brief pain inventory. Secondary outcomes also assessed were quality of life, functionality, xerostomia, pain interference, and analgesic consumption. Results were expressed as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Sixteen RCTs with a total of 1124 participants were included in the meta-analysis, with the majority of the studies presenting a low or unclear risk of bias. Acupuncture was more effective in reducing pain than no treatment (SMD = -0.90, 95 % CI [-1.68, -0.12]), sham acupuncture (SMD = -1.10, 95 % CI [-1.59, -0.61]) or usual care (SMD = -1.16, 95 % CI [-1.38, -0.93]). CONCLUSION: The results of this study suggest that acupuncture may be an effective intervention to reduce pain associated with cancer. Despite some limitations due to the low quality and small sample size of some included studies, as well as the different types and stages of cancer, acupuncture might provide an effective and safe treatment to reduce cancer pain. Please cite this article as: Faria M, Teixeira M, Pinto MJ, Sargento P. Efficacy of acupuncture on cancer pain: A systematic review and meta-analysis. J Integr Med. 2024; Epub ahead of print.

Bedside preoperative predictors of difficult laryngeal exposure in microlaryngeal surgery.

PURPOSE: Successful microlaryngeal surgery relies on an adequate laryngeal exposure. Recognizing the likelihood of challenging exposure prior to microlaryngeal surgery may assist in selecting the appropriate surgical approach and even prompt consideration of alternative treatment options. We aim to apply the mini-Laryngoscore, a preoperative assessment tool, to our study population and incorporate novel variables to optimize the prediction model. METHODS: This single-center prospective cohort study included 80 consecutive patients undergoing elective microlaryngeal surgery, from January 1, to June 30, 2023. Each patient underwent a presurgical evaluation of 15 parameters and an intraoperative scoring of the anterior commissure visualization. These parameters were assessed for their association with difficult laryngeal exposure, using multiple logistic regression analysis. We created a novel prediction model for DLE and compared it with the existing model, the mini-Laryngoscore. RESULTS: Out of 80 patients, 24 (30%) patients had difficult laryngeal exposure, including 3 cases (3.8%) in which visualization of the anterior commissure was not possible. A large neck diameter (OR, 1.4; CI 1.1-1.9) and the presence of upper teeth (OR, 8.9; CI 1.3-62.8) were independent risk factors for a difficult laryngeal exposure, while a larger interincisors gap was the only independent protector factor (OR, 0.3; CI 0.1-0.8). The logistic regression model combining these three independent risk factors displayed a high discriminative value AUC = 0.89 (CI 0.81-0.97). The predictive performance of the mini-Laryngoscore was 0.73 (CI 0.62-0.85). CONCLUSION: Combining two parameters from the mini-Laryngoscore (upper jaw dental state and interincisors gap distance) with neck circumference measurement can accurately predict the risk of difficult laryngeal exposure.

From Suspected COVID-19 to Anti-synthetase Syndrome: A Diagnostic Challenge in the Pandemic Era.

Anti-synthetase syndrome (ASS), a rare immunomediated disease, is characterized by multiple signs and symptoms. Not all patients develop the entire clinical spectrum of the syndrome, as it often varies depending on the involved antibodies. In this case report, a 53-year-old non-smoking woman had complaints of fatigue and dyspnea on exertion for five weeks. The outpatient study revealed creatine kinase (CK) 351U/L, ANAs+, anti-SSa+, normal echocardiogram, and a chest X-ray suggesting imaging suspicion of SARS-CoV-2 pneumonia. Referred to the emergency department, she was hospitalized for bilateral interstitial pneumonia without respiratory failure. Three SARS-CoV-2 polymerase chain reaction tests were negative. She underwent a five-day course of dexamethasone 6mg due to suspected coronavirus disease 2019 (COVID-19) sequelae with favorable progress. About a month later, she experienced fatigue, exertional intolerance, morning cough, and Raynaud's phenomenon episodes. Anti-SARS-CoV-2 antibodies were negative, and a follow-up chest CT showed bilateral organizing pneumonia. Bronchofibroscopy and bronchoalveolar lavage with cytology suggestive of inflammatory appearance, predominantly CD8+ lymphocytes, were performed. Subsequently, positive results for anti-OJ antibodies were obtained. A diagnosis of ASS was established, and prednisolone was initiated at 60mg/day with a tapering regimen, resulting in clinical and radiological improvement. Additional therapy with azathioprine was proposed. This case is presented due to highly suggestive COVID-19 imaging changes, emphasizing the importance of a high suspicion of ASS, despite nearly exclusive pulmonary involvement, with only one isolated elevated CK value and no musculoskeletal complaints. It is also noteworthy for the association with anti-OJ antibodies, rarely identified, often presenting interstitial lung disease as an isolated manifestation.

Chitosan in the treatment of mine spoil rainwater - An approach to protect the aquatic biota.

The mining industry suppresses vegetation, exposing large soil areas in its ordinary operation. Water pollution and turbidity are caused by the carrying of solids, mainly colloidal particles, to the watercourses due to the effect of rainfall events. Therefore, the discharge of those effluents will lead to failure with watercourse quality parameters. Thus, there is a need to treat drainages (rainwaters) from the mining industry. However, using common coagulants and flocculants can result in acute or chronic ecotoxicity for aquatic biota. In this scenario, this research aimed to evaluate using a natural coagulant, the biopolymer Chitosan, to remove turbidity from mining industry spoiled water through bio-coagulation. The ecotoxicity of the natural coagulant was compared to the commonly used coagulants. For this purpose, we used synthetic rainwater (SRW) from the dispersion of fine (colloidal) particles in natural waters. Materials (water and soil) were collected in the mining area's sumps (sedimentation basins). The turbidity of the produced SRW ranged from between 500 and 4000 NTU. Jar Tests using Chitosan (CTS), polyaluminum chloride (PAC®12), and Superfloc®N100 variable doses were carried out to compare the effects of the coagulating/flocculating agents on the SRW turbidity reduction. The obtained results demonstrated the efficiency of CHS on turbidity reduction. The results were encouraging for low turbidity samples (<1000 NTU), making it possible to meet the limit parameters recommended by the Brazilian legislation. In addition, it was possible to conclude both CHS and the effluents treated with this coagulant have lower toxicity to aquatic biota than the combination of PAC®12 and Superfloc®N100.

Epidemiological trends of isolated and non-isolated central nervous system congenital malformations in live births in a middle-income setting.

OBJECTIVES: This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015. METHODS: Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004-2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00-Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00-Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained. RESULTS: 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC -1.66; 95%CI -3.09 to -0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

Necrosis of the Tongue as a Late Complication of Radiotherapy.

Introduction: Irradiation to treat head and neck cancer, causing chronic tissue damage, is associated with the development of vascular disease. Interest has risen over the effects of radiotherapy on major vessels, due to its high morbidity and mortality rate. However, small-vessel disease has been poorly studied and described. Case Report: We present a case of a patient with bilateral necrosis of the anterior third of the tongue, occurring 3 years after chemoradiotherapy treatment for squamous cell carcinoma of the floor of the mouth. Contrast-enhanced CT scan showed multiple areas of stenosis concerning both external carotid arteries and their branches, and total opacification of lingual arteries. Conservative management was performed, with auto-amputation on the fifth day, which allowed healing by secondary intention. Conclusions: Necrosis of the tongue appears as a rare late complication of radiotherapy, possibly due to its acceleration effect on the atherosclerosis process. Following small-vessel disease, one can assume a higher potential risk of major-vessel disease, highlighting the importance of a routine assessment and prophylaxis of thrombotic events.

The neuroprotective effect of traditional Chinese medicinal plants-A critical review.

Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.

The burden of inappropriate birth weight on neonatal survival in term newborns: a population-based study in a middle-income setting.

Introduction: Premature birth, perinatal asphyxia, and infections are the main causes of neonatal death. Growth deviations at birth also affect neonatal survival according to week of gestation at birth, particularly in developing countries. The purpose of this study was to verify the association between inappropriate birth weight and neonatal death in term live births. Methods: This is an observational follow-up study with all term live births from 2004 to 2013 in Sao Paulo State, Brazil. Data were retrieved with the deterministic linkage of death and birth certificates. The definition of very small for gestational age (VSGA) and very large for gestational age (VLGA) used the 10th percentile of 37 weeks and the 90th percentile of 41 weeks + 6 days, respectively, based on the Intergrowth-21st. We measured the outcome in terms of time to death and the status of each subject (death or censorship) in the neonatal period (0-27 days). Survival functions were calculated using the Kaplan-Meier method stratified according to the adequacy of birth weight into three groups (normal, very small, or very large). We used multivariate Cox regression to adjust for proportional hazard ratios (HRs). Results: The neonatal death rate during the study period was 12.03/10,000 live births. We found 1.8% newborns with VSGA and 2.7% with VLGA. The adjusted analysis showed a significant increase in mortality risk for VSGA infants (HR = 4.25; 95% CI: 3.89-4.65), independent of sex, 1-min Apgar score, and five maternal factors. Discussion: The risk of neonatal death in full-term live births was approximately four times greater in those with birth weight restriction. The development of strategies to control the factors that determine fetal growth restriction through planned and structured prenatal care can substantially reduce the risk of neonatal death in full-term live births, especially in developing countries such as Brazil.

Mortality after discharge from a public tertiary cardiovascular referral hospital.

It is critically important for stakeholders with distinct foci of attention on healthcare to understand patient evolution in the presence of an established diagnosis or with a suspected diagnosis of various diseases, specially considering death as an outcome. To study the long-term mortality of patients at a cardiovascular referral hospital. Deterministic binding (selection of pairs of registers from the hospital electronic health records and the mortality records of São Paulo state) from 2002 to 2017 was performed. Studied variables were: age, sex, hospital treatment unit where the first visit occurred (Emergency Unit, Outpatient Unit, Hospital Admissions, Diagnostics Services), treatment type, elapsed time between the first visit and death, diagnosis at first and last visits and variables related to death. Statistical Methods: descriptive, survival (with Kaplan-Meier method), correspondence and competitive risks analyses; in case of nonoccurrence of death until the end of 2017, the patients were considered alive. Statistical significance was set at values of P < .05. Median age at the first visit to the Hospital was 51.9 years. Birth locations included 4496 cities, 17.33% in São Paulo, 0.41% in Rio de Janeiro, 0.40% in Osasco, 24.04% in other cities. Sex included females (46.7%), males (44.2%), not defined (6.3%), and other (2.8%). We observed an association between diseases in ICD-10 Chapter 16 (certain conditions originating in the perinatal period) and Chapter 17 (congenital malformations, deformations, and chromosomal abnormalities), both as diagnoses and underlying causes of death, as well as between neoplasms as diagnoses and as the underlying cause of death. In this sample, there was an association between admission diagnoses and underlying causes of death, such as neoplasms, cardiovascular diseases, and congenital heart malformations. Additionally, patients who underwent a cardiac intervention had a smaller less mortality rate than those who were not operated on. There were also differences in cardiovascular mortality between distinct treatment units of the hospital ((Emergency Unit, Outpatient Unit, Hospital Admissions, Diagnostic Services).

Temporal Trend, Causes, and Timing of Neonatal Mortality of Moderate and Late Preterm Infants in São Paulo State, Brazil: A Population-Based Study.

Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

Congenital diaphragmatic hernia in a middle-income country: Persistent high lethality during a 12-year period.

BACKGROUND: In high- and middle-income countries, mortality associated to congenital diaphragmatic hernia (CDH) is high and variable. In Brazil, data is scarce regarding the prevalence, mortality, and lethality of CDH. This study aimed to analyze, in São Paulo state of Brazil, the temporal trends of prevalence, neonatal mortality and lethality of CDH and identify the time to CDH-associated neonatal death. METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥400g, from mothers residing in São Paulo State, Brazil, during 2004-2015. CDH definition and its subgroups classification were based on ICD-10 codes reported in the death and/or live birth certificates. CDH-associated neonatal death was defined as death up to 27 days after birth of infants with CDH. CDH prevalence, neonatal mortality and lethality were calculated and their annual percent change (APC) with 95% confidence intervals (95%CI) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that CDH-associated neonatal death occurred. RESULTS: CDH prevalence was 1.67 per 10,000 live births, with a significant increase throughout the period (APC 2.55; 95%CI 1.30 to 3.83). CDH neonatal mortality also increased over the time (APC 2.09; 95%CI 0.27 to 3.94), while the lethality was 78.78% and remained stationary. For isolated CDH, CDH associated to non-chromosomal anomalies and CDH associated to chromosomal anomalies the lethality was, respectively, 72.25%, 91.06% and 97.96%, during the study period. For CDH as a whole and for all subgroups, 50% of deaths occurred within the first day after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, CDH prevalence and neonatal mortality showed a significant increase, while lethality remained stable, yet very high, compared to rates reported in high income countries.

Temporal Trend and Risk Factors for Respiratory Distress Syndrome-Associated Neonatal Mortality in Preterm Infants: A Population-Based Study in a Middle-Income Country.

OBJECTIVE: This article aimed to report a temporal series of respiratory distress syndrome (RDS)-associated neonatal mortality rates in preterm live births in São Paulo state, Brazil, and to identify social, maternal, and neonatal characteristics associated with these deaths. STUDY DESIGN: This is a population-based study of all live births with gestational age (GA) between 22 and 36 weeks, birth weight ≥400 g, without congenital anomalies from mothers living in São Paulo state during 2004 to 2015. RDS-associated neonatal mortality was defined as death up to 27 days after birth with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality rate (annual percent change [APC] with 95% confidence intervals [95% CIs]) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that the RDS-associated neonatal death occurred. Poisson's regression model compared social maternal and neonatal characteristics between preterm live births that survived the neonatal period and those with RDS-associated neonatal deaths, with results expressed in incidence rate ratio and 95% CI. RESULTS: A total of 645,276 preterm live births were included in the study, of which 612,110 survived and 11,078 had RDS-associated neonatal deaths. RDS-associated neonatal mortality rate was 17.17 per thousand preterm live births, with a decreasing annual trend (APC: -6.50%; 95% CI: -9.11 to -3.82%). The median time of these deaths was 48 hours after birth. The following risk factors for RDS-associated neonatal death were identified: maternal schooling ≤7 years (1.18; 1.09-1.29), zero to three prenatal care visits (1.25; 1.18-1.32), multiple pregnancy (1.24; 1.16-1.33), vaginal delivery (1.29; 1.22-1.36), GA 22 to 27 weeks (106.35; 98.36-114.98), GA 28 to 31 weeks (20.12; 18.62-21.73), male sex (1.16; 1.10-1.22), and 5-minute Apgar scores of 0 to 3 (6.74; 6.08-7.47) and 4 to 6 (3.97; 3.72-4.23). CONCLUSION: During the study period, RDS-associated neonatal mortality rates showed significant reduction. The relationship between RDS-associated neonatal deaths and social, maternal, and neonatal factors suggests the need for perinatal strategies to reduce prematurity and to improve the initial management of preterm infants. KEY POINTS: · RDS is associated with preterm live births.. · Impact of RDS-associated neonatal mortality in middle-income countries is scarce.. · Qualified perinatal care can reduce RDS-associated neonatal mortality..

Clusters of preterm live births and respiratory distress syndrome-associated neonatal deaths: spatial distribution and cooccurrence patterns.

BACKGROUND: Prematurity and respiratory distress syndrome (RDS) are strongly associated. RDS continues to be an important contributor to neonatal mortality in low- and middle-income countries. This study aimed to identify clusters of preterm live births and RDS-associated neonatal deaths, and their cooccurrence pattern in São Paulo State, Brazil, between 2004 and 2015.  METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥ 400 g, without congenital anomalies from mothers living in São Paulo State, Brazil, during 2004-2015. RDS-associated neonatal mortality was defined as deaths < 28 days with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality and preterm live births rates per municipality were submitted to first- and second-order spatial analysis before and after smoothing using local Bayes estimates. Spearman test was applied to identify the correlation pattern between both rates. RESULTS: Six hundred forty-five thousand two hundred seventy-six preterm live births and 11,078 RDS-associated neonatal deaths in São Paulo State, Brazil, during the study period were analyzed. After smoothing, a non-random spatial distribution of preterm live births rate (I = 0.78; p = 0.001) and RDS-associated neonatal mortality rate (I = 0.73; p = 0.001) was identified. LISA maps confirmed clusters for both, with a negative correlation (r = -0.24; p = 0.0000). Clusters of high RDS-associated neonatal mortality rates overlapping with clusters of low preterm live births rates were detected. CONCLUSIONS: Asymmetric cluster distribution of preterm live births and RDS-associated neonatal deaths may be helpful to indicate areas for perinatal healthcare improvement.

Systematic review and meta-analysis of the prevalence of coronavirus: One health approach for a global strategy.

Coronaviruses have been responsible for major epidemic crises in 2003 with SARS-CoV-1, in 2012 with MERS-CoV and in 2019 with SARS-CoV-2 (COVID-19), causing serious atypical pneumonia in humans. We intend, with this systematic analysis and meta-analysis, to clarify the prevalence of the various strains of coronavirus in different animal species. For this purpose, we carried out an electronic survey using Pubmed's Veterinary Science search tool to conduct a systematic assessment of published studies reporting the prevalence of different strains of coronavirus in different animal species between 2015 and 2020. We conducted different analysis to assess sensitivity, publication bias, and heterogeneity, using random effect. The final meta-analysis included 42 studies for systematic review and 29 in the meta-analysis. For the geographic regions with a prevalence greater than or equal to 0.20 (Forest plot overall; prevalence = 0.20, p < 0.01, Q = 10,476.22 and I2 = 100%), the most commonly detected viruses were: enteric coronavirus (ECoV), pigeon-dominant coronavirus, (PdCoV), Avian coronavirus M41, Avian coronavirus C46, Avian coronavirus A99, Avian coronavirus JMK, MERS-CoV, Bovine coronavirus, Ro-BatCoV GCCDC1, Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gamacoronavirus and human coronaviruses (HCoVs). The wide presence of different strains of coronavirus in different animal species on all continents demonstrates the great biodiversity and ubiquity of these viruses. The most recent epidemiological crises caused by coronavirus demonstrates our unpreparedness to anticipate and mitigate emerging risks, as well as the need to implement new epidemiological surveillance programs for viruses. Combined with the need to create advanced training courses in One Health, this is paramount in order to ensure greater effectiveness in fighting the next pandemics.

Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY: This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS: Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3ß). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. RESULTS: Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3ß inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS: The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

Clusters of cause specific neonatal mortality and its association with per capita gross domestic product: A structured spatial analytical approach.

BACKGROUND: Infant mortality rate is a measure of population health and neonatal mortality account for great proportion of these deaths. Underdevelopment might be associated to higher neonatal mortality risk due to assistant related factors. Spatial and temporal distribution of mortality help identifying and developing strategies for interventions. OBJECTIVE: To investigate the cluster areas of asphyxia-associated neonatal mortality and to explore its association with per capita gross domestic product (GDP) in São Paulo State (SP), Brazil. METHODS: Ecological study including live births residents in SP from 2004-2013. Neonatal deaths (0-27 days) with perinatal asphyxia were defined as intrauterine hypoxia, birth asphyxia or meconium aspiration syndrome written in any line of the Death Certificate. Geoprocessing analytical approach included detection of first order effects through quintiles and spatial moving average maps, followed by second order effects by global and local spatial autocorrelation (Moran and LISA, respectively) before and after smoothing with local Bayesian estimates. Finally, Spearman correlation was applied between asphyxia-associated neonatal mortality and mean per capita GDP rates for the municipalities with significant LISA. RESULTS: There were 6,713 asphyxia-associated neonatal deaths among 5,949,267 live births (rate: 1.13/1000) in SP. Spatial moving average maps showed a non-random distribution among municipalities, with presence of clusters (I = 0.048; p = 0.023). LISA map identified clusters of asphyxia-associated neonatal mortality in the south, southeast and northwest. After applying local Bayes estimates, clusters were more pronounced (I = 0.589; p = 0.001). There was a partial overlap of the areas of higher asphyxia-associated neonatal mortality and lower mean per capita GDP. CONCLUSIONS: Spatial analysis identified cluster areas of high asphyxia-associated neonatal mortality and low per capita GDP rates, with a significant negative correlation. This optimized, structured, and hierarchical approach to identify high-risk areas of cause-specific neonatal mortality may be helpful for guiding public health efforts to decrease neonatal mortality.

Operational Challenges in the Use of Structured Secondary Data for Health Research.

Background: In Brazil, secondary data for epidemiology are largely available. However, they are insufficiently prepared for use in research, even when it comes to structured data since they were often designed for other purposes. To date, few publications focus on the process of preparing secondary data. The present findings can help in orienting future research projects that are based on secondary data. Objective: Describe the steps in the process of ensuring the adequacy of a secondary data set for a specific use and to identify the challenges of this process. Methods: The present study is qualitative and reports methodological issues about secondary data use. The study material was comprised of 6,059,454 live births and 73,735 infant death records from 2004 to 2013 of children whose mothers resided in the State of São Paulo - Brazil. The challenges and description of the procedures to ensure data adequacy were undertaken in 6 steps: (1) problem understanding, (2) resource planning, (3) data understanding, (4) data preparation, (5) data validation and (6) data distribution. For each step, procedures, and challenges encountered, and the actions to cope with them and partial results were described. To identify the most labor-intensive tasks in this process, the steps were assessed by adding the number of procedures, challenges, and coping actions. The highest values were assumed to indicate the most critical steps. Results: In total, 22 procedures and 23 actions were needed to deal with the 27 challenges encountered along the process of ensuring the adequacy of the study material for the intended use. The final product was an organized database for a historical cohort study suitable for the intended use. Data understanding and data preparation were identified as the most critical steps, accounting for about 70% of the challenges observed for data using. Conclusion: Significant challenges were encountered in the process of ensuring the adequacy of secondary health data for research use, mainly in the data understanding and data preparation steps. The use of the described steps to approach structured secondary data and the knowledge of the potential challenges along the process may contribute to planning health research.

Critical Review of Lipid-Based Nanoparticles as Carriers of Neuroprotective Drugs and Extracts.

The biggest obstacle to the treatment of diseases that affect the central nervous system (CNS) is the passage of drugs across the blood-brain barrier (BBB), a physical barrier that regulates the entry of substances into the brain and ensures the homeostasis of the CNS. This review summarizes current research on lipid-based nanoparticles for the nanoencapsulation of neuroprotective compounds. A survey of studies on nanoemulsions (NEs), nanoliposomes/nanophytosomes and solid lipid nanoparticles (SLNs)/nanostructured lipid carriers (NLCs) was carried out and is discussed herein, with particular emphasis upon their unique characteristics, the most important parameters influencing the formulation of each one, and examples of neuroprotective compounds/extracts nanoencapsulated using these nanoparticles. Gastrointestinal absorption is also discussed, as it may pose some obstacles for the absorption of free and nanoencapsulated neuroprotective compounds into the bloodstream, consequently hampering drug concentration in the brain. The transport mechanisms through which compounds or nanoparticles may cross BBB into the brain parenchyma, and the potential to increase drug bioavailability, are also discussed. Additionally, factors contributing to BBB disruption and neurodegeneration are described. Finally, the advantages of, and obstacles to, conventional and unconventional routes of administration to deliver nanoencapsulated neuroprotective drugs to the brain are also discussed, taking into account the avoidance of first-pass metabolism, onset of action, ability to bypass the BBB and concentration of the drug in the brain.

Interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi in multicomponent mixtures towards cholinesterase inhibition and ROS scavenging.

This study gives new insights to understand the type of interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi, two Chinese medicinal plants with well documented neuroprotective effects, on three targets in Alzheimer's disease (AD): acetylcholinesterase (AChE) and butyrylcholnesterase (BuChE) inhibition and hydrogen peroxide scavenging. Individual samples, binary mixtures with different proportions of both plant species, and also a commercial multicomponent combination containing both plants together with unroasted Coffea arabica L. and quercetin-3-O-rutinoside were used to perform this in vitro evaluation. Sample phenolic profiles were also determined by HPLC-DAD, showing the presence of several flavonoid glycosides, phenolic acids and a methylxanthine. In order to investigate the possible synergism/antagonism interaction, data obtained were analyzed by CompuSyn software. The results showed that G. biloba and S. baicalensis alone display better activities than in mixtures, most of the interactions exhibiting different degrees of antagonism. A slight synergism interaction was only observed for the commercial multicomponent mixture tested against H2O2. Further analysis was carried out to understand which compounds could be responsible for the antagonistic interaction. Seventeen single pure compounds present in all extracts were tested against AChE inhibition, most of them displaying weak or no activity. Only caffeine had a remarkable activity. Five different binary and quaternary mixture compositions were design to deepen the interaction between these compounds, revealing mainly phenolic acid-flavonoid, flavonoid-flavonoid and methylxanthine-flavonoid-phenolic acid antagonistic interactions. These results clearly show that, for the targets evaluated, there is no potentiation of the neuroprotective effect by combining S. baicalensis and G. biloba extracts.

Neonatal mortality associated with perinatal asphyxia: a population-based study in a middle-income country.

BACKGROUND: It is challenging to decrease neonatal mortality in middle-income countries, where perinatal asphyxia is an important cause of death. This study aims to analyze the annual trend of neonatal mortality with perinatal asphyxia according to gestational age in São Paulo State, Brazil, during a 10-year period and to verify demographic, maternal and neonatal characteristics associated with these deaths. METHODS: Population-based study of neonatal deaths associated with perinatal asphyxia from 0 to 27 days in São Paulo State, Brazil, from 2004 to 2013. Perinatal asphyxia was considered as associated to death if intrauterine hypoxia, birth asphyxia or neonatal aspiration of meconium were noted in any line of the Death Certificate according to ICD-10. Poisson Regression was applied to analyze the annual trend of neonatal mortality rate according to gestational age. Kaplan-Meier curve was used to assess age at death during the 10-year study period. Hazard ratio of death during the neonatal period according to gestational age was analyzed by Cox regression adjusted by year of birth and selected epidemiological factors. RESULTS: Among 74,002 infant deaths in São Paulo State, 6648 (9%) neonatal deaths with perinatal asphyxia were studied. Neonatal mortality rate with perinatal asphyxia fell from 1.38‰ in 2004 to 0.95‰ in 2013 (p = 0.002). Reduction started in 2008 for neonates with 32-41 weeks, in 2009 for 28-31 weeks, and in 2011 for 22-27 weeks. Median time until 50% of deaths occurred was 25.3 h (95%CI: 24.0; 27.2). Variables independently associated with higher risk of death were < 7 prenatal visits, 1st minute Apgar score 0-3, and death at the same place of birth. Cesarean delivery compared to vaginal was protective against death with perinatal asphyxia for infants at 28-36 weeks. CONCLUSIONS: There was an expressive reduction in neonatal mortality rates associated with perinatal asphyxia during this 10-year period in São Paulo State, Brazil. Variables associated with these deaths highlight the need of public health policies to improve quality of regionalized perinatal care.