Subacute tributyltin exposure alters the development and morphology of mammary glands in association with CYP19A1 expression in female rats.

Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) related to reproductive dysfunctions. However, few studies have investigated the effects of TBT exposure on mammary gland development. Thus, we assessed whether subacute TBT exposure causes irregularities in mammary gland development. We administered TBT (100 and 1,000 ng/kg/day for 30 days) to female rats from postnatal day (PND) 25 to PND 55, and mammary gland development, morphology, inflammation, collagen deposition, and protein expression were evaluated. Abnormal mammary gland development was observed in both TBT groups. Specifically, TBT exposure reduced the number of terminal end buds (TEBs), type 1 (AB1) alveolar buds, and type 2 (AB2) alveolar buds. An increase in the lobule and differentiation (DF) 2 score was found in the mammary glands of TBT rats. TBT exposure increased mammary gland blood vessels, mast cell numbers, and collagen deposition. Additionally, both TBT rats exhibited intraductal hyperplasia and TEB-like structures. An increase in estrogen receptor alpha (ERα), progesterone receptor (PR), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) - positive cells was observed in the mammary glands of TBT rats. A strong negative correlation was observed between CYP19A1- positive cells and TEB number. In addition, CYP19A1 - positive cells were positively correlated with mammary gland TEB-like structure, ductal hyperplasia, inflammation, and collagen deposition. Thus, these data suggest that TBT exposure impairs mammary gland development through the modulation of CYP19A1 signaling pathways in female rats.

Biochemical changes and bioaccumulation of manganese in Astyanax lacustris (Teleostei: Characidae).

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris.

Differences in the impacts of muscle dysmorphia symptoms on distress between heterosexual women and homo/bisexual women.

Muscle Dysmorphia (MD) and its psychological impacts on women, especially within sexual minorities, are still relatively understudied. The objective of this study was to compare the relationship of MD symptoms and psychological distress between heterosexual women and lesbian/bisexual women. Our sample consisted of 479 Brazilian cisgender women from the community, aged between 18 and 70 years (M = 32.78; SD = 10.45). Among them, 327 (68.27 %) identified as heterosexual, 134 (27.98 %) as bisexual, and 18 (3.76 %) as lesbian. To ensure there was no bias due to measurement error, the psychometric properties of the instruments in the sample were tested, and invariance between the groups was assessed. t-tests, structural equation modeling, and latent profile analyses were conducted to comprehend the differences between the groups. The results indicated significant differences and a greater severity of MD symptoms and distress for lesbian/bisexual women. The implications of these results are discussed, emphasizing the need for further exploration of MD studies within sexual minorities.

A study on phytogenotoxicity induced by biogenic amines: cadaverine and putrescine.

Among the compounds present in necro-leachate, a liquid released during the process of decomposition of the human body, are the biogenic amines cadaverine and putrescine. Although some studies on necro-leachate have indicated a potential ecotoxicological and public health risk associated with it, the research on this type of contamination is still rather limited. This study presents information about the phytotoxic and cytogenotoxic potential of cadaverine and putrescine, evaluated separately and within a mixture. Phytotoxicity was evaluated through a germination test, the initial growth of seedlings with Lactuca sativa, and cytogenotoxicity through chromosomal aberration and micronucleus tests with Allium cepa. The L. sativa results showed a phytotoxic effect for the evaluated amines, by reducing root (> 90%) and hypocotyl (> 80%) elongation. The co-exposure of cadaverine and putrescine potentiated cytogenotoxic activity by aneugenic action in the meristematic cells of A. cepa. From this result, it is possible to infer the eco-toxicogenic potential of cadaverine and putrescine. This study not only highlights the importance of the phytotoxic and cytogenotoxic effects of these amines but also emphasizes the urgent need for further investigation into contamination originating from cemetery environments. By evaluating the risks associated with necro-leachate, this research is aimed at informing global efforts to protect ecological and public health.

The use of medications by incarcerated women: an exploratory study / O uso de medicamentos por mulheres privadas de liberdade: um estudo exploratório

Objective: To investigate the use of medicines by women deprived of their liberty in a municipality in the east of Minas Gerais. Method: The research was conducted in three stages: (I) documentary investigation, (II) analysis of medical records, and (III) application of semi-structured questionnaires. Women deprived of liberty who were part of the prison system evaluated participated in the study. The research was carried out between June 2020 and June 2021. Result: Seventeen women deprived of their liberty participated in the study, most of them black and brown (88.24%), between 30 and 49 years old (n = 9; 52.9%), and who used a total of 56 different medications, with the psychotropic class being the most prevalent (n = 28; 50%), followed by cardiovascular system drugs (n = 15; 26.8%). Conclusion: The medications most used by study participants belonged to the class of antidepressants and antiepileptics. Furthermore, the women's medical records lacked crucial information regarding medication use. These data, combined with difficulties in access, highlight the importance of complying with public policies in favor of comprehensive health care for women deprived of their liberty, especially the right to access and rational use of medicines.

Sex-Dependent Variations in Hypothalamic Fatty Acid Profile and Neuropeptides in Offspring Exposed to Maternal Obesity and High-Fat Diet.

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing n-6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation.

Sleep, Diet Quality, and Lipid Profile Assessment in NCAA Division I Acrobatics and Tumbling Student-Athletes: A Cross-Sectional Study.

OBJECTIVE: Acrobatics and Tumbling (A&T), an emerging National Collegiate Athletics Association (NCAA) sport, involves athletes with rigorous training backgrounds, usually extending from youth through early adulthood. This study examines the sleep health, diet quality, and lipid profile of A&T athletes clustered by their performance position. METHODS: Forty-two A&T athletes, clustered as tops (n = 19; age = 19.6 ± 1.0 years; body mass index [BMI] = 22.3 ± 1.7 kg/m2) and bases (n = 23; age = 19.6 ± 1.3 years; BMI = 25.7 ± 2.5 kg/m2), completed preseason sleep and diet quality (Rapid Eating Assessment for Participants-Shortened [REAP-S]) surveys. Fasting blood samples were collected for lipid analysis. Body composition was assessed via dual-energy X-ray absorptiometry. RESULTS: Most athletes (71.4%; base n = 14, top n = 16) reported insufficient sleep (≤7 hours) and "good" sleep quality (90.4%, n = 38; base n = 18, top n = 20). Average REAP-S score was 29.24 ± 3.74. Approximately 31% (n = 13) displayed at least one undesirable lipid concentration according to medical guidelines for normal levels (total cholesterol [TC] < 200 mg/dL, triglycerides [TG] < 150 mg/dL, high-density lipoprotein cholesterol [HDL-C] > 40 mg/dL, low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL). Approximately 20% exhibited elevated TC (top n = 4, base n = 4), 12.5% had elevated TG (base n = 5), 2.5% showed low HDL-C (base n = 1), and 10% presented elevated LDL-C (top n = 2, base n = 2). CONCLUSIONS: Most athletes experienced suboptimal sleep (≤7 hours/night) and 31% displayed at least one undesirable lipid concentration (elevated TC, TG, or LDL-C or reduced HDL-C). Tailoring interventions with sports dietitians is recommended, focused on increasing monounsaturated and polyunsaturated fat intake while reducing saturated fat consumption. These interventions could mitigate cardiovascular risks, improve recovery, and possibly enhance athletic performance.

Hypothalamic inflammation and the development of an obese phenotype induced by high-fat diet consumption is exacerbated in alpha7 nicotinic cholinergic receptor knockout mice.

Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

Interesterified palm oil promotes insulin resistance and altered insulin secretion and signaling in Swiss mice.

Interesterified fats have been used to replace trans-fat in ultra-processed foods. However, their metabolic effects are not completely understood. Hence, this study aimed to investigate the effects related to glucose homeostasis in response to interesterified palm oil or refined palm oil intake. Four-week-old male Swiss mice were randomly divided into four experimental groups and fed the following diets for 8 weeks: a normocaloric and normolipidic diet containing refined palm oil (PO group) or interesterified palm oil (IPO group); a hypercaloric and high-fat diet containing refined PO (POHF group) or interesterified PO (IPOHF group). Metabolic parameters related to body mass, adiposity and food consumption showed no significant differences. As for glucose homeostasis parameters, interesterified palm oil diets (IPO and IPOHF) resulted in higher glucose intolerance than unmodified palm oil diets (PO and POHF). Euglycemic-hyperinsulinemic clamp assessment showed a higher endogenous glucose production in the IPO group compared with the PO group. Moreover, the IPO group showed significantly lower p-AKT protein content (in the muscle and liver tissues) when compared with the PO group. Analysis of glucose-stimulated static insulin secretion (11.1 mmol/L glucose) in isolated pancreatic islets showed a higher insulin secretion in animals fed interesterified fat diets (IPO and IPOHF) than in those fed with palm oil (PO and POHF). Interesterified palm oil, including in normolipidic diets, can impair insulin signaling in peripheral tissues and increase insulin secretion by ß-cells, characterizing insulin resistance in mice.

Dietary Intake and Menstrual Health among Acrobatics and Tumbling NCAA Division I Student-Athletes.

OBJECTIVE: Acrobatics & Tumbling (A&T) is an emerging sport in the National Collegiate Athletic Association that lacks research regarding the dietary intake and health of A&T student-athletes (A&Tsa). This study assessed the dietary intake adequacy, estimated energy availability (EA), self-reported menstrual health, and body composition of A&Tsa. METHODS: Twenty-four female A&Tsa participated during week 8 of the preseason (11 top: Age= 20.1 ± 0.9 years; BMI= 22.1 ± 1.7 kg/m2; 13 base: Age= 19.5 ± 1.3 years; BMI= 26.2 ± 2.7 kg/m2). Total energy intake (TEI) and macronutrient intakes were assessed via a paper-based 3-day dietary recall. Resting Metabolic Rate [RMR = 500 + 22 * fat-free mass (FFM)] and energy availability [EA = (TEI - exercise energy expenditure)/FFM)] were estimated; and LEAF-Q assessed menstrual health. Body composition was measured using Dual-Energy X-Ray Absorptiometry. Macronutrient intakes and EA were compared to sports nutrition recommendations (carbohydrate: 6-10 g/kg; protein: 1.2-2.0 g/kg) and the Acceptable Macronutrient Distribution Range (carbohydrate: 45-65%; protein: 10-35%; fat: 20-35%). RESULTS: TEI was 1753 ± 467 kcal (top) and 1980 ± 473.8 kcal (base). A total of 20.8% of A&Tsa failed to meet RMR with TEI, with a higher prevalence in the top (-266 ± 219.2 kcal, n = 3) vs. base (-414.3 ± 534.4 kcal, n = 2) A&Tsa. Top and base A&Tsa had both low EA (28.8 ± 13.4 kcals·FFM-1; 23.8 ± 9.5 kcals·FFM-1) and inadequate carbohydrate intake averages (4.2 ± 1.3 g/kg; 3.5 ± 1.1 g/kg, p < 0.001), respectively. A total of 17% of A&Tsa reported secondary amenorrhea, with a higher prevalence in the top (27.3%, n = 3) vs. the base (7.7%, n = 1). CONCLUSION: TEI and carbohydrate intake of the majority of A&Tsa were below recommendations. Sports dietitians should encourage and educate A&Tsa about following an adequate diet that meets energy and sports-specific macronutrient needs.

Assessing a cut-off point for the diagnosis of abnormal uterine bleeding using the Menstrual Bleeding Questionnaire (MBQ): a validation and cultural translation study with Brazilian women

ABSTRACT BACKGROUND: Abnormal uterine bleeding (AUB) is a common condition, and the Menstrual Bleeding Questionnaire (MBQ) is used for its assessment. OBJECTIVES: To translate, assess the cut-off point for diagnosis, and explore psychometric properties of the MBQ for use in Brazilian Portuguese. DESIGN AND SETTING: Prospective cohort study including 200 women (100 with and 100 without AUB) at a tertiary referral center. METHODS: MBQ translation involved a pilot-testing phase, instrument adjustment, data collection, and back-translation. Cut-off point was obtained using receiver operating curve analysis. Menstrual patterns, impact on quality of life due to AUB, internal consistency, test-retest, responsiveness, and discriminant validity were assessed. For construct validity, the Pictorial Blood Assessment Chart (PBAC) and World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF) were applied. RESULTS: Women with AUB were older, had higher body mass indices, and had a worse quality of life during menstruation. Regarding the MBQ's psychometric variables, Cronbach's alpha coefficient was > 0.70 in all analyses, high intraclass correlation coefficient was found in both groups; no ceiling and floor effects were observed, and construct validity was demonstrated (correlation between MBQ score, PBAC score, and clinical menstrual cycle data). No difference between MBQ and PBAC scores were perceived after the test-retest. Significant differences were found between MBQ and PBAC scores before and after treatment. An MBQ score ≥ 24 was associated with a high probability of AUB; accuracy of 98%. CONCLUSION: The MBQ is a reliable questionnaire for Brazilian women. The cut-off ≥ 24 shows high accuracy to discriminate AUB.

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.

Long exposure to a mixture of endocrine disruptors prediposes the ventral prostate of rats to preneoplastic lesions.

Endocrine disruptors (ED) are compounds dispersed in the environment that modify hormone biosynthesis, affecting hormone-dependent organs such as the prostate. Studies have only focused on evaluating the effects of ED alone or in small groups and short intervals and have not adequately portrayed human exposure. Therefore, we characterized the prostate histoarchitecture of rats exposed to an ED mixture (ED Mix) mimicking human exposure. Pregnant females of the Sprague-Dawley strain were randomly distributed into two experimental groups: Control group (vehicle: corn oil, by gavage) and ED Mix group: received 32.11 mg/kg/day of the ED mixture diluted in corn oil (2 ml/kg), by gavage, from gestational day 7 (DG7) to post-natal day 21 (DPN21). After weaning at DPN22, the male pups continued to receive the complete DE mixture until they were 220 days old when they were euthanized. The ED Mix decreased the epithelial compartment, increased the fractal dimension, and decreased glandular dilation. In addition, low-grade prostatic intraepithelial neoplasia was observed in addition to regions of epithelial atrophy in the group exposed to the ED Mix. Exposure to the mixture decreased both types I and III collagen area in the stroma. We concluded that the ED Mix was able to cause alterations in the prostatic histoarchitecture and induce the appearance of preneoplastic lesions.

Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.

The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increased Let-7a and decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higher Let-7a and TNFα levels and lower Chrna7 expression, but when the cells were pre-treated with TLR4 inhibitor, Let-7a, TNFα, and Chrna7 were rescued to normal levels. Thus, the fatty acids overload trigger TNFα-induced Let-7 overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.

Dietary Fruit By-Products Improve the Physiological Status of Nile Tilapias (Oreochromis niloticus) and the Quality of Their Meat.

By-products from fruit industrialization retain nutritional and functional components; thus, they may find use in animal feeding. This study aimed to assess the effects of dietary fruit industrial by-products on the tilapias blood biochemical and oxidative parameters and on the composition and lipid peroxidation of their fillets. Four diets were supplied to the tilapias: a C-control diet, with no fruit meal, and three diets containing 5% of either acerola (ACM), apple (APM) or grape (GRM) meal. The phenolic compounds and the carotenoids in the meals and their antioxidant capacities were measured. Fish were weighed and measured for the calculation of the growth performance data, their blood was analyzed for health and oxidative status biomarkers and their fillets were analyzed for proximal composition and lipid peroxidation. Grape meal had the highest concentration of phenolics and carotenoids and the highest antioxidant activity, followed by acerola and apple meals. The productive performance was similar among the treatments. The fruit by-product diets either maintained or improved the biochemical biomarkers of health and improved the oxidative status of the fish. The fruit by-product diets increased the concentration of lipids in the fillets and slowed down the onset of the lipid peroxidation during frozen storage.

Toxicological and chemoprevention studies of Brazilian brown propolis from Araucaria sp.

Brazilian brown propolis (BBP) is a natural product derived predominantly from the south region of Brazil, where Araucaria forests are dominant. Despite its potential as a source of bioactive compounds with leishmanicidal, anti-inflammatory, nociceptive, and antimicrobial properties, BBP has not been comprehensively studied compared to green propolis. Therefore, this study aimed to determine the safety and chemopreventive potential of BBP. The cytotoxicity attributed to BBP was assessed using two different assays, while the Salmonella/microsome assay was employed to evaluate mutagenicity. The acute toxicity attributed to BBP was determined using a zebrafish model, while the chemopreventive potential was investigated utilizing Chinese hamster lung (V79) cell lines. Data demonstrated that BBP exerted cytotoxic effects at concentrations greater than or equal to 10 µg/ml and did not exhibit mutagenicity in Salmonella typhimurium strains TA98 and TA100. However, at the highest concentration tested (4000 µg/plate), BBP induced a significant increase in revertant colonies in S. typhimurium TA102 strain. The LC50 equivalent to 8.83 mg/L was obtained in the acute toxicity evaluation in zebrafish. BBP also showed antigenotoxic effect by significantly reducing chromosomal damage induced by the mutagen doxorubicin in V79 cell cultures at a concentration of 2.5 µg/ml. Compared to Brazilian green and red propolis, BBP exhibited greater toxicity. On the other hand, at lower concentrations, BBP displayed chemopreventive potential, which may be associated with the antioxidant capacity of the extract. These findings contribute to a better understanding of the biological properties and potential applications of BBP in treating various diseases.

High flux novel polymeric membrane for renal applications.

Biocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes used in dialysis. Oxone-mediated TEMPO-oxidized cellulose nanomaterials have been demonstrated to be excellent additives in the production and tunability of ultrafiltration and dialysis membranes. In the present study, nanocellulose ionic liquid membranes (NC-ILMs) were tested in vitro and ex vivo. An increase in flux of up to two orders of magnitude was observed with increased rejection (about 99.6%) of key proteins compared to that of polysulfone (PSf) and other commercial membranes. NC-ILMs have a sharper molecular weight cut-off than other phase inversion polymeric membranes, allowing for high throughput of urea and a uremic toxin surrogate and limited passage of proteins in dialysis applications. Superior anti-fouling properties were also observed for the NC-ILMs, including a > 5-h operation time with no systemic anticoagulation in blood samples. Finally, NC-ILMs were found to be biocompatible in rat ultrafiltration and dialysis experiments, indicating their potential clinical utility in dialysis and other blood filtration applications. These superior properties may allow for a new class of membranes for use in a wide variety of industrial applications, including the treatment of patients suffering from renal disease.

Bothrops atrox venom: Biochemical properties and cellular phenotypes of three highly toxic classes of toxins.

Snake venoms have a complex mixture of compounds that are conserved across species and act synergistically, triggering severe local and systemic effects. Identification of the toxin classes that are most damaging to cell homeostasis would be a powerful approach to focus on the main activities that underpin envenomation. Here, we focus on the venom of Bothrops atrox, snake responsible for most of the accidents in Amazon region of South America. We identified the key cytotoxic toxin fractions from B. atrox venom and mapped their biochemical properties, protein composition and cell damage. Five fractions were obtained by mass exclusion chromatography and contained either a single class of enzymatic activity (i.e., L-amino acid oxidases or Hyaluronidases) or different activities co-distributed in two or more protein fractions (e.g., Metalloproteinases, Serine Proteases, or Phospholipases A2). Only three protein fractions reduced cell viability of primary human cells. Strikingly, such activity is accompanied by disruption of cell attachment to substratum and to neighbouring cells. Such strong perturbation of morphological cell features indicates likely defects in tissue integrity in vivo. Mass spectrometry identified the main classes of toxins that contribute to these phenotypes. We provide here a strategy for the selection of key cytotoxic proteins for targeted investigation of their mechanism of action and potential synergism during snakebite envenomation. Our data highlights putative toxins (or combinations of) that may be the focus of future therapeutic interference.

Genome-wide Association Study Identifies Novel Risk Loci for Apical Periodontitis.

INTRODUCTION: Apical periodontitis (AP) is a common consequence of root canal infection leading to periapical bone resorption. Microbial and host genetic factors and their interactions have been shown to play a role in AP development and progression. Variations in a few genes have been reported in association with AP; however, the lack of genome-wide studies has hindered progress in understanding the molecular mechanisms involved. Here, we report the first genome-wide association study of AP in a large and well-characterized population. METHODS: Male and female adults (n = 932) presenting with deep caries and AP (cases), or deep caries without AP (controls) were included. Genotyping was performed using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGA). Single-variant association testing was performed adjusting for sex and 5 principal components. Subphenotype association testing, analyses of genetically regulated gene expression, polygenic risk score, and phenome-wide association (PheWAS) analyses were also conducted. RESULTS: Eight loci reached near genome-wide significant association with AP (P < 5 × 10-6); gene-focused analyses replicated 3 previously reported associations (P < 8.9 × 10-5). Sex-specific and subphenotype-specific analyses revealed additional significant associations with variants genome-wide. Functionally oriented gene-based analyses revealed 8 genes significantly associated with AP (P < 5 × 10-5), and PheWAS analysis revealed 33 phecodes associated with AP risk score (P < 3.08 × 10-5). CONCLUSIONS: This study identified novel genes/loci contributing to AP and specific contributions to AP risk in men and women. Importantly, we identified additional systemic conditions significantly associated with AP risk. Our findings provide strong evidence for host-mediated effects on AP susceptibility.

Assessing a cut-off point for the diagnosis of abnormal uterine bleeding using the Menstrual Bleeding Questionnaire (MBQ): a validation and cultural translation study with Brazilian women.

BACKGROUND: Abnormal uterine bleeding (AUB) is a common condition, and the Menstrual Bleeding Questionnaire (MBQ) is used for its assessment. OBJECTIVES: To translate, assess the cut-off point for diagnosis, and explore psychometric properties of the MBQ for use in Brazilian Portuguese. DESIGN AND SETTING: Prospective cohort study including 200 women (100 with and 100 without AUB) at a tertiary referral center. METHODS: MBQ translation involved a pilot-testing phase, instrument adjustment, data collection, and back-translation. Cut-off point was obtained using receiver operating curve analysis. Menstrual patterns, impact on quality of life due to AUB, internal consistency, test-retest, responsiveness, and discriminant validity were assessed. For construct validity, the Pictorial Blood Assessment Chart (PBAC) and World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF) were applied. RESULTS: Women with AUB were older, had higher body mass indices, and had a worse quality of life during menstruation. Regarding the MBQ's psychometric variables, Cronbach's alpha coefficient was > 0.70 in all analyses, high intraclass correlation coefficient was found in both groups; no ceiling and floor effects were observed, and construct validity was demonstrated (correlation between MBQ score, PBAC score, and clinical menstrual cycle data). No difference between MBQ and PBAC scores were perceived after the test-retest. Significant differences were found between MBQ and PBAC scores before and after treatment. An MBQ score ≥ 24 was associated with a high probability of AUB; accuracy of 98%. CONCLUSION: The MBQ is a reliable questionnaire for Brazilian women. The cut-off ≥ 24 shows high accuracy to discriminate AUB.