Effects associated with exposure to the emerging contaminant octyl-methoxycinnamate (a UV-B filter) in the aquatic environment: a review.

Given the increasing concern surrounding ultraviolet (UV) radiation-induced skin damage, there has been a rise in demand for UV filters. Currently, UV-filters are considered emerging contaminants. The extensive production and use of UV filters have led to their widespread release into the aquatic environment. Thus, there is growing concern that UV filters may bioaccumulate and exhibit persistent properties within the environment, raising several safety health concerns. Octyl-methoxycinnamate (OMC) is extensively employed as a UV-B filter in the cosmetic industry. While initially designed to mitigate the adverse photobiological effects attributed to UV radiation, the safety of OMC has been questioned with some studies reporting toxic effects on environment. The aim of this review to provide an overview of the scientific information regarding the most widely used organic UV-filter (OMC), and its effects on biodiversity and aquatic environment.

Identification of an oncological clinical pathway through questionnaires to health professionals.

BACKGROUND: Clinical Pathways in Oncology can benefit patients using organized interventions to standardize and increase care efficiency. Healthcare systems should have tools to identify their oncological clinical pathways for a better institutional organization to reduce mortality rates and contain costs without compromising quality. Our objective is to determine the regional Oncology Clinical Pathway from a first basic hypothesis using questionnaires directed to healthcare professionals considered key deciders within the Pathway. METHODS: Study design consisted of data analysis of two structured region-wide questionnaires; built using available literature on Oncology Clinical Pathways, in a Portuguese Healthcare context and pre-tested in a focus group of key deciders (Physicians and nurses with management functions) from which a design was created. Queries analyzed the patients: tumor staging at service arrival; time intervals on tumor suspicion/diagnosis confirmation and diagnosis/first treatment; referral pathway; diagnostic networks and patient Follow-up. One questionnaire was sent to key deciders directly involved with Oncology patients at a Regional Hospital. 15 physicians and 18 nurses of this sample answered the questionnaire (approx. response rate = 67%). Another questionnaire sent to healthcare professionals in Primary Healthcare Centers yielded response rate 19.2%, N = 29 physicians and 46 nurses. Finally, we performed a descriptive analysis and a Cronbach Alpha reliability analysis. RESULTS: Our findings reveal: different appreciations of tumor staging at arrival in Primary Healthcare Centers and Regional Hospitals (the latter receiving more metastatic cases); approximately 4 weeks between tumor suspicion-diagnostic and divided opinions regarding diagnostic-treatment time intervals. Primary Healthcare Centers depend on private laboratories for diagnostics confirmation, while the Hospitals resolve this locally. Referral pathways indicate almost half of the patients being sent from primary healthcare centers to National Reference Hospitals instead of a Regional Hospital. Patient follow-up is developed throughout the institutions, however, is more established at Regional Hospitals. As patients advance through the Oncology Clinical Pathway and toward treatment stages the number of healthcare professionals involved reduce. CONCLUSION: Our questionnaires enable us to understand the real pathway between the different institutions involved and the main entry points of the patients into the Oncology Clinical Pathway.

The prognostic value of NRF2 in breast cancer patients: a systematic review with meta-analysis.

PURPOSE: Nuclear factor E2-related factor 2 (NRF2) is a transcription factor that plays a major role in the regulation of intracellular antioxidant response. The effect of NRF2 overexpression in many malignancies is still unclear and recent meta-analysis correlated NRF2 overexpression with poor prognosis in a variety of human cancers. However, the effect of NRF2 overexpression in breast cancer is still unclear. Thus, the main goal of this work was to clarify the role of NRF2 expression in survival and relapse of breast cancer patients by performing a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis. METHODS: The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Embase between November of 2017 and September of 2018. To be included, studies should evaluate NRF2 expression in breast cancer tissue, through immunohistochemistry and/or mRNA and had to report one or more of the following outcomes: overall survival (OS), disease-free survival (DFS), mean survival and median survival. RESULTS: For the meta-analysis, seven studies were included and NRF2 expression was correlated with OS and DFS. It was observed that compared to patients with low NRF2 expression, patients with NRF2 overexpression had poorer OS with a hazard ratio of 1.82 (95% CI 1.32-2.50; p value < 0.0001), and poorer DFS, with a hazard ratio of 1.79 (95% CI 1.07-3.01; p value = 0.03). CONCLUSIONS: These results suggest that tumours that overexpress NRF2 have a worse clinical outcome. Thus, NRF2 expression could be a marker for the prognostic of breast cancer patients and, in the future, it would be pertinent to focus on improving treatment efficacy for patients with NRF2 overexpression.

Women with polycystic ovary syndrome and other causes of infertility have a higher prevalence of GSTT1 deletion.

RESEARCH QUESTION: Is GSTM1 and GSTT1 deletion associated with the development of polycystic ovary syndrome (PCOS)? DESIGN: A case-control study was designed to investigate the association between GSTM1 and GSTT1 gene polymorphisms with PCOS. Blood samples from 201 women diagnosed with infertility were taken, of which 69 women were diagnosed with PCOS. Genomic DNA was extracted, and genotyping analyses were conducted by polymerase chain reaction-based methods. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression. RESULTS: An increased risk of PCOS was found to be associated with GSTT1 null genotype (OR 4.890, 95% CI 2.261 to 9.122; P < 0.001). A strong association between GSTT1 null genotype was found with female infertility, regardless of the associated cause (OR 5.300, 95% CI 3.238 to 8.675; P < 0.001) as well as with the GSTM1 null genotype (OR 1.620, 95% CI 1.067 to 2.459; P = 0.026). A statistically significant association with the development of infertility was also found when carriers of the combined genotype GSTT1+/GSTM1+ was compared with carriers of the combined genotype GSTT1-/ GSTM1+ (OR 3.600 95% CI 1.864 to 6.956; P < 0.001). The two-way combination of GSTT1 and GSTM1 null genotypes resulted in an increased susceptibility to infertility development (OR 11.136; 95% CI 5.035 to 24.629; P < 0.001). CONCLUSIONS: Carriers of GSTT1 null genotype seem to have higher susceptibility to developing PCOS and infertility from other causes. Also, GSTT1 null genotype, alone or in association, are related with increased susceptibility to infertility development, independently of its cause. GSTM1 null genotype is only associated with all cause of infertility when the GSTT1 is null.

In vitro evaluation of potential benefits of a silica-rich thermal water (Monfortinho Thermal Water) in hyperkeratotic skin conditions.

Thermal therapy has gained popularity over the years, and Portugal is one of the richest European countries in mineral therapeutic waters. The interest in the use of these natural mineral waters (NMW) for dermatologic purposes is continuously growing but there is a lack of scientific studies supporting its health benefits. The study aims to investigate the effect of a silica-rich NMW in skin cell homeostasis using two representative cell lines of the epidermis and dermis, keratinocytes and fibroblasts, respectively, in addition to a macrophage cell line. Mouse skin fibroblasts, macrophages and human keratinocytes were exposed to culture medium prepared with NMW. Cell metabolism (MTT or resazurin assays) and cell proliferation (trypan blue exclusion dye assay) were investigated. Migration (scratch-wound assay) and senescence (ß-galactosidase activity assay) of fibroblasts were also studied. Exposure to NMW compromised the cell metabolic state of all the cell lines tested. This impairment was more pronounced in skin keratinocytes (60% reduction) relatively to skin fibroblasts (45% reduction) or macrophages (25% reduction). Proliferation of macrophages was reduced threefold upon exposure to thermal water, compared to controls. No differences were observed in migration between fibroblasts exposed to NMW and controls, while a potentiation of senescence of these cells was observed. Our results shed light in the bioactive effects of a silica-rich NMW supporting its therapeutic use. A reduction in both cell metabolism and proliferation of keratinocytes and macrophages supports the empirical clinical benefits of this NMW in hyperkeratotic conditions, such as psoriasis and atopic dermatitis.

Chemical signature and antimicrobial activity of Central Portuguese Natural Mineral Waters against selected skin pathogens.

The common therapeutic indications of Portuguese Natural Mineral Waters (NMWs) are primarily for respiratory, rheumatic and musculoskeletal systems. However, these NMWs have been increasingly sought for dermatologic purposes. Opposing to what is observed in the major European Thermal Centres, there are few scientific evidences supporting the use of Portuguese NMWs for clinical applications. The aim of this study was to characterize the antimicrobial profile of individual NMWs from the central region of Portugal and correlate the results with their physicochemical characterization. An extensive multivariate analysis (principal component analysis) was also performed to further investigate this possible correlation. Six collection strains representing skin microbiota, namely Staphylococcus aureus, Escherichia coli, Corynebacterium amycolatum, Candida albicans, Staphylococcus epidermidis and Cutibacterium acnes, were analysed, and their antimicrobial profile was determined using Clinical and Laboratory Standards Institute M07-A10, M45-A2, M11-A6 and M27-A3 microdilution methods. Different NMWs presented different antimicrobial profiles against the strains used; the physicochemical composition of NMWs seemed to be correlated with the different susceptibility profiles. Cutibacterium acnes showed a particularly high susceptibility to all NMWs belonging sulphurous/bicarbonated/sodic ionic profile, exhibiting microbial reductions up to 65%. However, due to the complex physicochemical composition of each water an overall conclusion regarding the effect of a specific ion on the growth of different microorganisms is yet to be known.

Prognosis of hormone-dependent breast cancer seems to be influenced by KEAP1, NRF2 and GSTM1 genetic polymorphisms.

Influence of Glutathione S-transferase Mu1 (GSTM1) has long been studied in breast cancer and GSTM1 null genotype was correlated with breast cancer risk. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a transcription factor that forms a complex with Kelch-like ECH-associated protein-1 (KEAP1). Recent studies have demonstrated that expression of these proteins is deregulated in several malignancies. Thus, in the present study we aim to distinguish GSTM1 heterozygous from wild type genotype in breast cancer patients and evaluate the presence and clinical significance of NRF2 and KEAP1 polymorphisms, alone or in association, with breast cancer prognosis, in cases confirmed to have GSTM1-present genotype. Study population consisted in 52 patients with breast cancer. Genomic DNA was extracted, GSTM1 was genotyped through multiplex PCR and gene dose was evaluated through real-time PCR. All cases were sequenced, through Sanger sequencing, for specific regions of NRF2 and KEAP1. Genotyping and clinicopathological data were correlated and statistical analysis was performed. GSTM1 wild type was identified in 1 case and 26 cases were identified as heterozygous, these data were correlated with Human Epidermal growth factor Receptor 2 (HER2) status (p value = 0.017). We also verified that most cancers diagnosed at younger ages had the presence of KEAP1 and/or NRF2 polymorphisms. The association of GSTM1 heterozygous genotype with rs1048290 and rs35652124 seems to be associated with HER2+ (p < 0.05). Our results suggest that GSTM1 * 1/0 genotype and the cumulative presence of at least one allele mutated in KEAP1 and/or NRF2 polymorphisms might be associated with worse prognosis for breast cancer patients.

UV-B Filter Octylmethoxycinnamate Induces Vasorelaxation by Ca2+ Channel Inhibition and Guanylyl Cyclase Activation in Human Umbilical Arteries.

Ultraviolet (UV) filters are chemicals widely used in personal care products (PCPs). Due to their effect as endocrine disruptor compounds (EDCs), the toxicity of UV filters is a current concern for human health. EDC exposure may be correlated to cardiovascular diseases (CVD), but to our knowledge, no studies assessed the UV filters effects as human EDCs at the vascular level. Octylmethoxycinnamate (OMC) is the world's most widely used UV-B filter, present in more than 90% of PCPs. Due to its demonstrated multiple hormonal activities in animal models, this substance is also suspected to be a human EDC. The purpose of this study was to assess the rapid/short-term effects of OMC on arterial tonus and analyse its mode of action (MOA). Using human umbilical arteries, the endocrine effects of OMC were evaluated in in vitro (cellular and organ) experiments by planar cell surface area (PCSA) and organ bath, respectively. Our data show that OMC induces a rapid/short-term smooth muscle relaxation acting through an endothelium-independent MOA, which seems to be shared with oestrogens, involving an activation of soluble guanylyl cyclase (sGC) that increases the cyclic guanosine monophosphate (cGMP) intracellular levels and an inhibition of L-type voltage-operated Ca2+ channels (L-Type VOCC).

Women's experiences, preferences and perceptions regarding vaginal products: Results from a cross-sectional web-based survey in Portugal.

OBJECTIVE: We aimed to identify Portuguese women's experiences, preferences and perceptions regarding vaginal products. METHODS: A descriptive cross-sectional study was conducted (February-May 2013) among Portuguese women (aged 18 to 65 years) using an online questionnaire. Descriptive and chi-squared statistics were applied. RESULTS: Among 2529 women, 85.4% had used vaginal products, mostly to manage vulvovaginal infections (75.3%). Gels, creams and ointments (semi-solids) were the most frequently used (82%), followed by vaginal suppositories (56.5%) and tablets/capsules (41.8%), while vaginal rings were used by 10% of women. Semi-solids were preferred as an intravaginal medication both by women who had previously used them and by women who had never used an intravaginal product, while preference for vaginal rings was higher only among women who had previously used them. Even though 87.1% of all women considered vaginal drug delivery to be advantageous, the majority preferred to use oral products. Leakage (84.8%) and insertion difficulties (58.4%) were the main problems reported for vaginal products. CONCLUSIONS: Overall, semi-solids were the most used and preferred vaginal products, while vaginal rings were highly acceptable for women who had previously used them. Although they considered the vaginal route to be more efficient and safe, many women felt it to be less appealing than the oral route, particularly due to comfort issues.

Educational interventions to improve prescription and dispensing of antibiotics: a systematic review.

BACKGROUND: Excessive and inappropriate antibiotic use contributes to growing antibiotic resistance, an important public-health problem. Strategies must be developed to improve antibiotic-prescribing. Our purpose is to review of educational programs aimed at improving antibiotic-prescribing by physicians and/or antibiotic-dispensing by pharmacists, in both primary-care and hospital settings. METHODS: We conducted a critical systematic search and review of the relevant literature on educational programs aimed at improving antibiotic prescribing and dispensing practice in primary-care and hospital settings, published in January 2001 through December 2011. RESULTS: We identified 78 studies for analysis, 47 in primary-care and 31 in hospital settings. The studies differed widely in design but mostly reported positive results. Outcomes measured in the reviewed studies were adherence to guidelines, total of antibiotics prescribed, or both, attitudes and behavior related to antibiotic prescribing and quality of pharmacy practice related to antibiotics. Twenty-nine studies (62%) in primary care and twenty-four (78%) in hospital setting reported positive results for all measured outcomes; fourteen studies (30%) in primary care and six (20%) in hospital setting reported positive results for some outcomes and results that were not statistically influenced by the intervention for others; only four studies in primary care and one study in hospital setting failed to report significant post-intervention improvements for all outcomes. Improvement in adherence to guidelines and decrease of total of antibiotics prescribed, after educational interventions, were observed, respectively, in 46% and 41% of all the reviewed studies. Changes in behaviour related to antibiotic-prescribing and improvement in quality of pharmacy practice was observed, respectively, in four studies and one study respectively. CONCLUSION: The results show that antibiotic use could be improved by educational interventions, being mostly used multifaceted interventions.

Exposure to UV-B filter octylmethoxycinnamate and human health effects: Focus on endocrine disruptor actions.

Human skin is the first line of photoprotection against UV radiation. However, despite having its defence mechanisms, the photoprotection that the skin exerts is not enough. To protect human skin, the inclusion of UV filters in the cosmetic industry has grown significantly as a photoprotection strategy. Octylmethoxycinnamate, also designated by octinoxate, or 2-ethylhexyl-4-methoxycinnamate (CAS number: 5466-77-3) is one of the most widely used UV-B filter in the cosmetic industry. The toxic effects of OMC have alarmed the public, but there is still no consensus in the scientific community about its use. This article aims to provide an overview of the UV filters' photoprotection, emphasizing the OMC and the possible negative effects it may have on the public health. Moreover, the current legislation will be addressed. In summary, the recommendations should be rethought to assess their risk-benefit, since the existing literature warns us to endocrine-disrupting effects of OMC. Further studies should be focus on the toxicity of OMC alone, in mixture and should consider its degradation products, to improve the knowledge of its risk assessment as EDC.

Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer.

Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.

Humulus lupulus aqueous extract and hydrolate as a potential ingredient for cosmetics: chemical characterization and in vitro antimicrobial, cytotoxicity, antioxidant and anti-inflammatory assessment.

Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, ß-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant and anti-inflammatory activities. OBJECTIVE: This work focuses on the evaluation of H. lupulus biological activities, with the aim of evaluating its potential for inclusion in cosmetic formulations. METHODS: Two distinct aqueous extracts and two hydrolates obtained via hydrodistillation were evaluated. These include the flower parts (FE, FH) and the mix of aboveground parts (ME, MH). The chemical profiles for both aqueous extracts and hydrolates were identified by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antimicrobial, antioxidant, cytotoxicity, and anti-inflammatory activity were tested in vitro using standard methods. RESULTS: Rutin was the major compound found in FE (40.041 µg mg-1 of extract) and ME (2.909 µg mg-1 of extract), while humulenol II was the most abundant compound in hydrolates (FH: 20.83%; MH: 46.80%). Furthermore, FE was able to inhibit the growth of Staphylococcus aureus and Staphylococcus epidermis with MIC values of 50% and 25% (v/v), respectively. FH showed the same effect in Staphylococcus aureus (50% v/v). FH evidenced poor antioxidant potential in DPPH scavenging test and demonstrated significant antioxidant and anti-inflammatory effects by reducing (***p < 0.001) intracellular reactive oxygen species (ROS), NO (nitric oxide) levels (***p < 0.001) and cyclooxygenase-2 (COX-2) protein expression (***p < 0.001) in lipopolysaccharide (LPS)-stimulated macrophages. Nevertheless, it is important to note that FH exhibited cytotoxicity at high concentrations in 3T3 fibroblasts and RAW 264.7 macrophages. CONCLUSION: The studied H. lupulus aqueous extracts and hydrolates revealed that FH stands out as the most promising bioactive source for cosmetic formulations. However, future research addressing antimicrobial activity is necessary to confirm its potential incorporation into dermatological and cosmetic formulations.

CYP19A1 TC/CC Polymorphism, along with Deletion of GSTM1 and GSTT1 Genes, Strongly Influences Female Infertility Risk.

Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with established infertility and 161 fertile female controls was performed, and statistical associations were analyzed. For carriers of GSTM1 null genotype along with CYP19A1 C allele, there is a significant association with female infertility risk (OR 7.023; 95% CI (3.627-13.601; p < 0.001), and, also for carriers of GSTT1 null genotype along with the CYP19A1 TC/CC genotype (OR 24.150; 95% CI (11.148-52.317; p < 0.001). A positive association with female infertility risk for carriers of the C allele in CYP19A1 and null genotypes in GTSM1 (OR 11.979; 95% CI (4.570-31.400; p < 0.001) or GSTT1 (OR 13.169; 95% CI (4.518-38.380; p < 0.001) was found. When both GSTs are deleted, the risk of developing female infertility is significant, independently of the CYP19A1 genotype; when all the presumed high-risk genotypes are present, we found a significant association with female infertility risk (OR 47,914; 95% CI (14,051-163,393; p < 0.001).

Cell-Free DNA as a New Biomarker of IVF Success, Independent of Any Infertility Factor, Including Endometriosis.

Cell-free DNA fragments detected in blood and in other biological fluids are released from apoptotic/necrotic cells. In this study, we analyzed cfDNA levels in follicular fluid (FF) samples from patients with infertility. Samples were collected from 178 infertile women and cfDNA was extracted and quantified by qPCR, using ALU115 and ALU247 primers, and statistical correlations were performed. We found that cfDNA concentration was significantly higher in FF pools from women aged 35 and over than in women under 35 years of age (p = 0.017). We also found that q247 cfDNA levels were significantly higher in women with an associated female factor, such as endometriosis, PCOS and POF, compared with women with no specific cause of infertility (p = 0.033). The concentration of cfDNA did not vary significantly in each group of women with an associated female factor. The concentration of cfDNA was significantly higher in the FF of women that obtained embryos with a high fragmentation rate, compared to embryos with a low fragmentation rate (p = 0.007). Finally, we found that women who did not become pregnant during IVF treatments had higher q247 cfDNA levels (p = 0.043). The quantification of cfDNA could be an important biomarker of follicular micro-environment quality to predict embryo quality and the success of IVF, making them more specific and effective.

UV-B Filter Octylmethoxycinnamate Is a Modulator of the Serotonin and Histamine Receptors in Human Umbilical Arteries.

Every day, people use personal care products containing UV filters. Although their use initially showed a protective role, toxicity is a concern for human health as several UV filters are endocrine-disrupting chemicals (EDCs). Exposure to EDCs may induce cardiovascular diseases and can affect the health of sensitive people, such as pregnant women. Currently, the world's most widely used UV-B filter is octylmethoxycinnamate (OMC), an EDC. However, the disruptive effects on pregnant women are little known. The present work proposed to understand how long-term exposure to OMC affects vascular homeostasis. Endothelium-denuded human umbilical artery (HUA) rings were incubated in an organ bath system. Long-term effects of exposure to OMC (0.001-50 µmol/L) were evaluated on the contractile responses of HUA to the application of the contractile agents, serotonin (5-HT) and histamine (Hist). To investigate in more detail the vascular mode of action of OMC, through which it impairs the vascular homeostasis of HUA, the activity and expression of different 5-HT and Hist-receptors involved in contractility processes were studied. Our findings pointed out an increase in the reactivity of HUA to 5-HT and Hist due to OMC exposure. These alterations in reactivity may be precursors of preeclampsia development and/or gestational hypertension.

The Effects of the COVID-19 Pandemic in Oncology Patient Management.

The COVID-19 pandemic has changed the way cancer patients should be managed. Using published literature on best practices on oncology patient management, we developed checklists to establish which recommendations were followed and differences between healthcare staff and institutions in a local health unit (overseeing two regional hospitals and 14 primary Healthcare Centers) in an interior region in Portugal. Checklists were delivered and completed by 15 physicians, 18 nurses and 5 pharmacists working at the Hospitals, and 29 physicians and 46 nurses from primary healthcare centers. Hospital staff do not show statistically significant differences regarding most proposed recommendations for the oncology clinical pathway, human resources, treatments, patient management and service management. Primary healthcare centers seem to follow a similar trend. As a local health unit, general recommendations for Oncology Patient Management show statistically significantly different values on education of suspected cases, identification, isolation procedures and samples collection; extension of work schedules; and education on cancer patient and COVID-19 positive referral procedures. All the checklists indicated good-to-high internal consistency. Our analysis showed cohesive work between groups regarding control and prevention of sources of infection; therefore, it is considered the highest priority to ensure that all other services, including oncology, continue functioning. Patient management measures such as adjustments in treatments, analysis, patient care, referrals and emergencies were not ranked higher by responders.

Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) represents one of the leading causes of anovulatory infertility and affects 5% to 20% of women worldwide. Until today, both the subsequent etiology and pathophysiology of PCOS remain unclear, and patients with PCOS that undergo assisted reproductive techniques (ART) might present a poor to exaggerated response, low oocyte quality, ovarian hyperstimulation syndrome, as well as changes in the follicular fluid metabolites pattern. These abnormalities originate a decrease of Metaphase II (MII) oocytes and decreased rates for fertilization, cleavage, implantation, blastocyst conversion, poor egg to follicle ratio, and increased miscarriages. Focus on obtaining high-quality embryos has been taken into more consideration over the years. Nowadays, the use of metabolomic analysis in the quantification of proteins and peptides in biological matrices might predict, with more accuracy, the success in assisted reproductive technology. In this article, we review the use of human follicular fluid as the matrix in metabolomic analysis for diagnostic and ART predictor of success for PCOS patients.

Volatilomics as an Emerging Strategy to Determine Potential Biomarkers of Female Infertility: A Pilot Study.

Due to its high prevalence, infertility has become a prominent public health issue, posing a significant challenge to modern reproductive medicine. Some clinical conditions that lead to female infertility include polycystic ovary syndrome (PCOS), endometriosis, and premature ovarian failure (POF). Follicular fluid (FF) is the biological matrix that has the most contact with the oocyte and can, therefore, be used as a predictor of its quality. Volatilomics has emerged as a non-invasive, straightforward, affordable, and simple method for characterizing various diseases and determining the effectiveness of their current therapies. In order to find potential biomarkers of infertility, this study set out to determine the volatomic pattern of the follicular fluid from patients with PCOS, endometriosis, and POF. The chromatographic data integration was performed through solid-phase microextraction (SPME), followed by gas chromatography-mass spectrometry (GC-MS). The findings pointed to specific metabolite patterns as potential biomarkers for the studied diseases. These open the door for further research into the relevant metabolomic pathways to enhance infertility knowledge and diagnostic tools. An extended investigation may, however, produce a new mechanistic understanding of the pathophysiology of the diseases.

Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population.

Glutathione S-transferases are a superfamily of multifunctional enzymes that play a key role in Phase II metabolism, detoxifying therapeutic drugs, and various carcinogens by conjugation with glutathione. We undertook a case-control study in Central-Eastern Portuguese population to evaluate the association of null genotype in GSTM1 and GSTT1 along with the polymorphism in GSTP1 (A/G) and susceptibility to breast cancer. The population sample consisted of 85 patients with histological diagnosis of breast cancer and 102 healthy women. Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR-based methods. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. We found a increased breast cancer risk associated with GSTM1 null genotype (OR = 3.597; 95% CI = 1.849-6.999; P = 0.0001) and GSTT1 (OR = 2.592; 95% CI = 1.432-4.690; P = 0.002), but the presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The two-way combination of GSTM1 and GTTT1 null genotypes resulted in 8-fold increase for breast cancer risk (OR = 8.287; 95% CI = 3.124-21.980; P = 0.0001) and the three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in 5-fold increase for breast cancer risk (OR = 5.040; 95% CI = 1.392-18.248; P = 0.016). Our results suggest that GSTM1 and GSTT1 null genotype alone, both combined or combined with GSTP1 valine alleles, are associated with higher susceptibility to breast cancer development.