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BACKGROUND: The WHO identifies climate change as the most significant threat to global health systems. Indigenous peoples, whose lives are deeply intertwined with nature, are particularly vulnerable to the impacts of these changes. OBJECTIVE: This study aimed to understand the perspectives of Indigenous stakeholders and public services managers on the interconnectedness of climate change and Indigenous health. DESIGN: A qualitative study with 22 Indigenous stakeholders and public service managers on climate change and perceived impact on Indigenous health. SETTING AND PARTICIPANTS: Indigenous stakeholders and public service managers on climate change and perceived impact on Indigenous health from Brazil. Data was collected through interviews incorporating two vignette videos depicting environmental and health scenarios. Thematic content analysis was used to analyse the data. RESULTS: The analytical process yielded six subcategories that were further grouped into three overarching thematic macro-categories: environmental degradation and climate change in the context of Indigenous peoples; environment, vulnerability and impact on Indigenous mental health; and actions and public health policies for Indigenous peoples. CONCLUSION: The perspectives of Indigenous stakeholders and public service managers on the interconnectedness of climate change and Indigenous health were deeply entrenched in their lived experiences of loss of their lands from deforestation and environmental degradation. They argued strongly for the strengthening of public health policies aimed at the Indigenous peoples, to face many challenges, especially suicide, and to have a voice in decision-making. A sensitive approach that values Indigenous peoples' connections with nature is fundamental to promote their health and well-being.

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BACKGROUND: Older people are the fastest-growing age group, with the highest risk of cognitive impairment. This study assessed the prevalence and associated factors with cognitive impairment in community-dwelling older people. METHODS: Older people were interviewed and accomplished through sociodemographic and health questionnaires. The quantitative variables were described by mean and standard deviation or median and interquartile range. The significance level adopted was 5 % (p < 0.05). The association between the quantitative variables was evaluated using the Pearson or Spearman correlation coefficients. RESULTS: The research population comprised 165 long-lived adults aged ≥80. The youngest one was 80, and the oldest one was 94 years old. The participants were 84.8 ± 3.6 years old, female (63 %) with a mean of education of 2.9 ± 1.8 years. A poor performance in the Mini-Mental State Examination (MMSE) was found in 58 (35.2 %) individuals when adjusted for educational level. After adjustment for confounding factors, body mass index (BMI) (p = 0.09), total older adults' income (up to 1 minimum wage [mw], p = 0.023; over 1 to 2 mw, p = 0.023), functional disability (Moderate dependence 75 %, p = 0.038; Moderate dependence 50 %, p = 0.081; Moderate dependence 25 %, p = 0.054), and the anxiety scale (p = 0.032), remained associated with cognitive impairment. CONCLUSIONS: This study showed that BMI, total older adults' income, functional disability, and anxiety are related to cognitive impairment in long-lived adults. This study has some limitations, such as the fact that it is a cross-sectional study, the reduced number of individuals, and the fact that there were no comparisons among different ages and populations.

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OBJECTIVE: The objective of this study is to evaluate the association of disciplinary actions by regulatory councils and unprofessional behaviour during medical graduation. METHODS: A search strategy was developed using the terms: 'physicians', 'disciplinary action', 'education', 'medical', 'undergraduate' and their synonyms, subsequently applied to the electronic databases MEDLINE, Embase, Cochrane Library, LILACs and grey literature, with searches up to November 2023. The risk of bias was assessed using the Newcastle-Ottawa scale and statistical analysis was performed using the RevMan software. RESULTS: A total of 400 studies were found in the databases, and 15 studies were selected for full-texting reading. Four studies met the inclusion criteria and were included, bringing together a total of 3341 evaluated physicians. Three studies were included in the meta-analysis, showing a greater chance of disciplinary actions among physicians who exhibited unprofessional behaviour during medical graduation (OR: 2.54; 95%CI: 1.87-3.44; I2: 0%; P < 0.0001; 3077 participants; physicians with disciplinary action: 107/323; control physicians: 222/2754). CONCLUSIONS: There is a statistically significant association between unprofessional behaviour during medical undergraduate study and subsequent disciplinary actions by Medical Councils. The tools for periodic assessments of student behaviour during undergraduate studies can be a perspective for future studies aimed at reducing disciplinary actions among physicians.

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OBJECTIVE: This review aimed to assess the utility of urinary N-acetyl-ß-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes mellitus. METHODS: The search for relevant studies was conducted across multiple databases, including PubMed (Medline), EMBASE, LILACS, CENTRAL, IBECS, and gray literature. We employed a random effects model to calculate the standardized mean difference and 95% confidence interval. Furthermore, we assessed heterogeneity using Cochrane's Q test and Higgins' I2 statistics. RESULTS: This review included a total of 16 articles involving 1669 patients, with 13 being case-control studies and three being cohorts. The meta-analysis conducted across all studies revealed significant heterogeneity. However, subgroup analysis of four studies indicated that an increase in uNAG among normoalbuminuric patients was associated with the development of macroalbuminuria (DMP = - 1.47; 95% CI = - 1.98 to 0.95; p < 0.00001; I2 = 45%). Conversely, it did not demonstrate effectiveness in predicting the development of microalbuminuria (DMP = 0.26; 95% CI = - 0.08 to 0.60; p = 0.13; I2 = 17%). CONCLUSIONS: Elevated uNAG levels in normoalbuminuric patients may indicate an increased risk for the development of macroalbuminuria, but not microalbuminuria. However, the high heterogeneity observed among the studies highlights the necessity for further research to validate these findings.

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Introduction: This study aimed to identify what indigenous university students in Brazil perceived to be important and feasible actions to protect the survival of indigenous peoples from climate change-related impacts. Methods: Concept mapping, which is a participatory mixed methodology, was conducted virtually with 20 indigenous students at two universities in Brazil. A focus prompt was developed from consultations with indigenous stakeholders and read "To protect the survival of the Indigenous Peoples from climate change, it is necessary to…". Students brainstormed 46 statements, which they then sorted into clusters based on conceptual similarity. They rated each statement for importance and feasibility. Quantitative multivariate analyses of clusters and ratings were conducted to produce multiple visual maps of perceived actionable priorities. These analyses used the Group Wisdom TM software. Results: Students agreed on 8 clusters that reflect the factors that influence the survival of indigenous peoples-preservation of lands 0.16 (SD 0.13), protection of demarcated lands 0.31 (SD 0.10), indigenous health and wellbeing 0.35 (SD 0.14), ancestral customs 0.46 (SD 0.04), global and national actions 0.61 (SD 0.13), indigenous rights 0.64 (SD 0.23), collective living 0.71 (SD 0.21), and respect 0.75 (SD 0.14). Discussion: The most actionable priorities are related to the respect for their lands and customs, educational initiatives in schools about the importance of indigenous peoples to society, guarantees for basic health rights, and culturally appropriate provision of care, with specific mention of mental healthcare. The findings aligned closely with the concept of indigenous self-determination, which is rooted in autonomy and respect for cultural diversity, and the right to make decisions that impact their lives, land, and resources.

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Background: The alarming increase in annual deforestation rates has had devastating consequences in climate change, and it is affecting Indigenous people, who depend entirely on the land for survival and has also weakened the rainforest's crucial role in stabilizing the global climate. Recognizing and respecting Indigenous people's needs and social, economic, and historical conditions influence health and healthcare. This study aimed to conduct online concept mapping workshops with university students to identify perceived important and feasible actions for improving the mental health of Indigenous people living in their territory in association with climate change. Methods: Concept mapping, a participatory mixed methodology, was conducted virtually with 20 Indigenous students at two universities in Brazil. A focus prompt was developed from consultations with Indigenous stakeholders and read-"To improve the mental health of Indigenous peoples in their territory during climate change crises, it is necessary to…." Results: University students organized 42 unique statements in 6 clusters that cover a wide range of topics: family support, 0.68 (SD 0.19); respect and understanding, 0.37 (SD 0.08); improvement actions, 0.52 (SD 0.07); public policies in favor of Indigenous people's mental health, 0.24 (0.09); health actions, 0.15 (SD 0.08); Indigenous training in health and its importance in improving mental health 0.32 (SD 0.07). Conclusion: These clusters range from community initiatives, public policies, health actions, and strengthening professional services in Indigenous communities. These all provide numerous concrete ideas for developing interventions designed to address mental health challenges associated with climate change.

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Background: Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer. Methods: We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201. Findings: We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity. Interpretation: Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance. Funding: There was no funding source for this study.

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Background: The increase in life expectancy and in the number of individuals over 60 years old brings new demands to health professionals and services based on the physiological changes that occur in this population. The aging process results in changes in body composition, increasing body fat and reducing muscle mass, in addition to a reduction in bone mass. Aim: The aim of this study was to examine the effect of whey protein and vitamin D supplementation on body composition and skeletal muscle in older adults living in long-term care facilities. Methods: This study is a double-blind randomized controlled trial. Thirty older adults (>60 years old) were randomized and allocated in three groups: group receiving resistance training and supplementation receiving resistance training, whey protein and vitamin D; group received resistance and placebo training receiving resistance training and placebo, and control group without any intervention. Body composition was measured by dual-energy X-ray absorptiometry at baseline, 12 weeks, and 24 weeks. Results: The mean age was 74.87 (± 8.14) years. A significant difference (p = 0.042) was observed between the group receiving resistance training and supplementation and control groups in relation to lean mass increase (kg) at 24 weeks. After 24 weeks of intervention, there was a significant increase in Relative index of muscle mass for the two groups that underwent resistance training, group received resistance and placebo training (p = 0.042) and group receiving resistance training and supplementation (p = 0.045), in relation to the control. Conclusion: Combined supplementation of whey protein and vitamin D with resistance training can significantly improve lean mass, total mass, and relative index of muscle mass in institutionalized older adults.

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Background: Endometriosis is a clinical condition associated with genetic, endocrine, and immunological factors, present in 6 to 10% of women of reproductive age. Currently, the human microbiota has been studied and associated with the evolution of diseases due to its influence on pathogenesis, indicating that changes in the colonization of microorganisms in the genitourinary and gastrointestinal systems can promote physiological changes that can trigger inflammatory and immunological processes and hormonal dysregulation, which can be linked to endometriosis. Thus, this systematic review and meta-analysis evaluated microbiota changes in women with endometriosis. Methods: The following electronic databases were searched up to April 2022: Medline, Embase, Web of Science, Cochrane Library, and gray literature (Google Scholar), using the keywords "dysbiosis", "microbiome" and "endometriosis", combined with their synonyms. The observational studies conducted with women diagnosed with endometriosis and women without endometriosis as controls were included. For the analyses, a standard mean difference with a 95% confidence interval was used using RevMan software (version 5.4), and for methodological quality assessment, the Newcastle-Ottawa scale was used. Results: A total of 16 studies were found in the literature assessing the composition of the microbiota in women with endometriosis, and no significant difference were found for changes in alpha diversity analysis in gut microbiota (SMD = -0.28; 95% CI = -0.70 to 0.14; P = 0.19; I2 = 52%; four studies, 357 participants) or vaginal microbiota (SMD = -0.68; 95% CI = -1.72 to 0.35; P = 0.19; I2 = 66%; two studies, 49 participants). Conclusion: In intestinal and vaginal samples from women with endometriosis, alpha-diversity did not present a significant difference when compared to the control population. However, each study individually showed a possible relationship between the female microbiota and endometriosis. This trial is registered with CRD42021260972.

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INTRODUCTION: Cisplatin-based chemotherapy is the standard cancer therapy; however, this treatment causes depletion of ovarian follicles in women of reproductive age. Adjuvant treatment with melatonin can protect the ovaries from oxidative stress, reducing the side effects of chemotherapy. The objective was to evaluate the effects of the use of melatonin on the ovarian follicles of mice treated with cisplatin. METHODOLOGY: A systematic review was performed. The search strategy used the terms: "cisplatin", "melatonin," and "ovarian". MEDLINE EMBASE, Cochrane Library, and gray literature (Google Scholar) were used as databases. The search was limited to experimental studies, performed on animals, with no language restrictions. RESULTS: The search identified 30 studies and 5 primary studies, published between 2016 and 2021, and met the inclusion criteria, with a total of 115 mice. For the p-FOX3a/FOXO3a pathway, the meta-analysis showed a standard mean difference (SMD) of -4.79 (95% CI -6.16 to -3.42; P < 0.00001, two studies, 38 mice; I2 = 0%). For the p-PTEN pathway, the meta-analysis showed an SMD of -1.65 (95% CI -2.71 to -0.59; P = 0.002, two studies, 38 mice; I2 = 47%). CONCLUSION: Melatonin variation in efficacy varies according to the dose used in mice previously exposed to cisplatin. However, melatonin was able to alter the p-PTEN and p-FOX3a/FOXO3a pathways.

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BACKGROUND: Human colostrum has been used in a number of investigations when preterm human infants cannot, for any reason, breastfeed directly from their mothers. One of the growing fields in these investigations is colostrum therapy, which consists of exposing the oropharyngeal mucosa of these preterm newborns to small amounts of raw colostrum. RESEARCH AIM: To critically review the scientific evidence about colostrum therapy in premature infants and to explore its influences on the immune system. METHODS: This systematic review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement). The following databases were searched for potentially eligible studies up to March 10, 2021: Medline, Scopus, Web of Science, Cochrane Library, Embase. Two reviewers independently screened all titles, abstracts, and full texts for eligibility. RESULTS: A total of 12 studies with 996 participants were included. A significant difference in lactoferrin levels in the urine was found (SMD 0.70; 95% CI [0.03,1.36]; p = .04; I² = 65% two studies, 112 participants, very low-quality evidence). CONCLUSION: Colostrum seems to result in increasing lactoferrin levels in the urine of premature newborns after 1 week of intervention. CLINICAL TRIAL REGISTRATION: The study was registered at PROSPERO with the number CRD42017073624, submitted on August 9, 2017.

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OBJECTIVES: To evaluate the levels of salivary cortisol in adults and children diagnosed with bruxism. METHODS: A search strategy was developed using the following terms: "cortisol", "bruxism" and "sleep bruxism". These were searched in databases: Medline, Embase, Scopus, Cochrane, Web of Science, LILACS and gray literature, for studies published until May 2020. RESULTS: We obtained a total of six primary studies, involving 854 participants, who met the criteria and were included in the present study. The analysis cortisol levels shows a significant difference favourable to the control group 1.10 (95% CI: 0.68-1.53), showing that patients with bruxism have higher values of salivary cortisol. Heterogeneity of I²â€¯= 4% (P = .31). CONCLUSIONS: It was concluded that despite the different methodologies adopted for the collection and analysis of salivary content, this review found significant results of higher levels of salivary cortisol in adult patients with bruxism.

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The objective of this study was to analyze the available evidence of systematic reviews that evaluated the efficacy of antenatal corticosteroids in order to contribute to a reduction in magnitude and transcendence of respiratory distress syndrome of the newborn (RDS). Thus, an overview was conducted including all systematic reviews of randomized controlled trials (RCTs) that evaluated women who received corticosteroid treatment during pregnancy to prevent RDS. Therefore, a search strategy was developed using the terms "respiratory distress syndrome, newborn," "corticosteroids," "perinatal death," "neonatal death," "neonate," and "pregnancy." The electronic databases searched were MEDLINE, EMBASE, Cochrane Library, LILACS, and Google Scholar, for studies published until June 2020. We identified 354 references, 38 of which were relevant after the initial screening. Ten systematic reviews met the inclusion criteria. For RDS, 1522 cases occurred in the control group composed of 8716 participants, while in the intervention group was 1088 in 8740 participants (RR = 0.67, 95% CI 0.60-0.75). For neonatal death, 343 cases occurred in 5248 participants of the control group, while in the intervention group, there were 227 cases in 5246 participants (RR = 0.66, 95% CI 0.56-0.78). For perinatal death, there were 344 cases in 3345 participants in the control group, while in the intervention group, the number of cases was 264 in 3384 participants (RR = 0.72, 95% CI 0.58-0.89). Thus, the use of corticosteroids during pregnancy in women at risk of preterm birth is effective for the prevention of RDS in neonates and reducing the number of neonatal and perinatal deaths in preterm. PROSPERO protocol no: CRD42017074604.

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To map and assess evidence regarding use of the levonorgestrel-releasing intrauterine system (LNG-IUS) and its association with breast cancer, we conducted a systematic review and meta-analysis. A search strategy was developed using the terms "Levonorgestrel-releasing," "LNG-IUS," "intrauterine system," and "breast cancer. The electronic databases searched were MEDLINE, Embase, Cochrane Library, Latin American & Caribbean Health Sciences Literature, and Google Scholar for studies published until August 2020. We included observational studies: prospective or retrospective cohort, case-control, and cross-sectional. A total of 494 studies were identified, 294 studies were evaluated by title and abstract, and 262 were excluded because they did not meet the inclusion criteria. A total of 32 studies were read in full, and 24 were excluded. Thus, eight studies were included in the systematic review. The meta-analysis included four studies (two cohort and two case-control studies). Two subgroup analyses were performed for different study designs. The estimated relative risk for the two cohort studies (144,996 cases), with moderate-quality evidence, was 0.93 (95% confidence interval [CI], 0.840-1.03). The odds ratio estimated for the two case-control studies (5556 cases and 35987 controls), with moderate-quality evidence, was 1.07 (95% CI, 0.91-1.26). Evidence of an increased risk of breast cancer was not observed in levonorgestrel-releasing intrauterine system users.

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According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD - 0.57, 95%CI - 0.97 to - 0.18) and waist circumference (MD - 2.95 cm, 95%CI - 4.93 to - 0.97). Exercise did not have an effect on BMI (MD - 0.23 kg/m2, 95%CI - 0.73 to 0.27), weight (MD - 0.06 kg, 95%CI - 1.46 to 1.34), or HDL (SMD 0.26, 95%CI - 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581).

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BACKGROUND: The decline in postmenopausal serum estrogen concentration results in several changes in the vulvovaginal and vesicourethral areas, resulting in the genitourinary syndrome of menopause, including symptoms such as vaginal atrophy. AIM: To evaluate the effects of hyaluronic acid in vaginal atrophy. METHODS: A search strategy was developed using the following terms: "Hyaluronic Acid vaginal gel," "vaginal estrogens," "Vaginitis, Atrophic," and "Postmenopause." This strategy was used in major databases such as MEDLINE, EMBASE, Scopus, Cochrane library, Web of Science, Virtual Health Library (BVS), Congress Abstracts, and Gray Literature (Google Scholar and British Library) for studies published until June 2020. OUTCOMES: A systematic review was carried out to assess the results of atrophic vaginitis/vaginal dryness, dyspareunia, vaginal pH, and cell maturation of the studies found by the search strategy. RESULTS: A total of 833 studies were identified, 528 studies were directed for reading titles and abstracts, and 515 were excluded for not meeting the selection criteria. A total of 13 studies were selected for reading the full text. 5 primary studies involving 335 women met the criteria and were included. The studies were published between the years 2011 and 2017. It was not possible to perform meta-analysis owing to the substantial heterogeneity present in the studies. The results presented suggest that treatment with hyaluronic acid, when compared with the use of estrogens, does not present a significant difference in the results obtained for the outcomes: epithelial atrophy, vaginal pH, dyspareunia, and cell maturation. CLINICAL TRANSLATION: Hyaluronic acid appears to be an alternative to non-hormonal treatments for the signs of vaginal atrophy and dyspareunia. STRENGTHS & LIMITATIONS: The analysis of the studies in this systemic review suggests that hyaluronic acid has efficacy similar to vaginal estrogens for the treatment of the signs of vaginal atrophy and dyspareunia. However, the included studies measured the data in different ways, causing the performance of meta-analysis to be impaired. CONCLUSION: The comparisons presented suggest that hyaluronic acid has a profile of efficacy, safety, and tolerability comparable with vaginal estrogens for the treatment of symptoms of vaginal atrophy. It is a possible alternative for women who cannot use hormonal treatment. dos Santos CCM, Uggioni MLR, Colonetti T, et al. Hyaluronic Acid in Postmenopause Vaginal Atrophy: A Systematic Review. J Sex Med 2021;18:156-166.

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Bipolar disorder (BD) is a mood psychiatric disorder described by changes between depressive, hypomanic, or manic episodes. The aimed of the present study was evaluated possible changes in the AA pathway in BD through a systematic review of observational studies. A search in the electronic databases was proceeded, on Cochrane Library, MEDLINE, EMBASE, PsycINFO, Google Scholar and the British Library for studies published until August 2020. A search strategy was developed using the terms: "Bipolar Disorder" and "Phospholipase A2" or "Arachidonic Acids" or "Cyclooxygenase 2" or "Prostaglandins E" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). Seven primary studies were included in the systematic review, with a total of 246 BD patients, 20 depression patients, and 425 heathy controls (HC). The studies showed contradictory results in the AA and PLA2, no primary articles with COX and PGE2 assessments were included in this review. According to the Newcastle-Ottawa quality score scale (NOS), our systematic review presented high quality. The investigation of the inflammatory pathway of AA still needs further investigation and evidence, given the growing number of studies suggesting the efficacy of anti-inflammatory drugs as adjunctive therapy in the pharmacological treatment of BD.

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BACKGROUND: Bipolar Disorder (BD) is a chronic psychiatric disorder characterized by mood disturbances that include depressive, manic, and hypomanic episodes. Despite the severity of the symptoms, there is still a gap in the literature on the precise neurobiology and treatment of BD. The investigations of inflammatory changes in BD has increased in the last decade, evincing the importance of its role in the pathophysiology of the disorder. The present study aimed to investigate the inflammatory role in BD, through the evaluation of biomarkers and their relation to biological rhythms. METHODS: It was conducted a case-control study that included 36 BD and 46 healthy controls (HC). The Cyclooxygenase 2 (COX-2) enzyme, Arachidonic Acid (AA), interleukins (IL) IL-4, IL-5, IL-6, IL-10, IL-33, and Tumor Necrosis Factor Alpha (TNF-α) in the serum of individuals. It also was administered the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) to the BD and healthy control groups. RESULTS: The results indicated that the individuals with BD showed increased COX-2, AA, IL-6, and TNF-α levels in comparison to the HC without psychiatric disorders, as well as significant commitments in all domains evaluated by BRIAN. LIMITATIONS: Uncontrolled pharmacotherapy used by the included bipolar participants, which had important effects on participants' inflammatory systems and the lack of cases with bipolar manic episodes. CONCLUSIONS: The results of the present study reaffirm that inflammation has an important role in BD, as well as the significant changes in biological rhythms. It is still necessary to better characterize the inflammatory pathway of AA.

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BACKGROUND: Treatment-resistant depression (TRD) denotes the therapeutic failure of at least two evidence-based, dose-based, and time-appropriate treatment regiments for major depressive disorder (MDD). Studies have suggested that alterations in proinflammatory cytokines play an important role in the pathophysiology of TRD, as well as a significant relationship between the number of failed treatment and the levels of tumor necrosis factor-alpha (TNF-α). OBJECTIVE: Performed a systematic review and meta-analysis to evaluate the potential effect of the TNF-inhibitor Infliximab adjunct treatment in MDD, through randomized controlled trials (RCT). METHODS: A search in the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO, Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published until April 2019. A search strategy was developed using the terms: "Mood disorder" OR "Depressive Disorder" OR "Bipolar disorder" AND "Infliximab" OR "tumor necrosis factor antagonist" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). The therapeutic effects of adjunctive treatment with Infliximab were analyzed. The meta-analysis was performed including the results of the Hamilton Scale for Depression (HAM-D). RESULTS: Four primary studies were included in the systematic review, with a total of 152 patients. The meta-analysis did not show a statistically significant effect of Infliximab as an adjuvant treatment for TRD. LIMITATIONS: Articles in this meta-analysis originate from the same country. The main treatments used were different among the included studies. CONCLUSION: Infliximab was not efficient in reducing depressive symptoms according to the HAM-D, only when the patients already had increased inflammatory genes, including TNF and C-reactive protein (CRP).

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