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Copyright of HOLOS is the property of Instituto Federal do Rio Grande do norte - IFRN and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Heat stress (HT) and photoperiod affect milk production and immune status of dairy cows. The objective was to evaluate the effects of HT abatement prepartum under controlled photoperiod on hepatic metabolic gene expression and cellular immune function of periparturient Holstein cows (n = 21). Cows were dried off 46 d before expected calving date and assigned to treatments by mature equivalent milk production. The treatments were 1) HT and 2) cooling (CL), both imposed during a photoperiod of 14L:10D. Rectal temperature was measured twice daily, whereas respiration rate was measured 3 times/wk at 1500 h during the entire dry period. After calving, cows were housed in a freestall barn with cooling, and milk yield was recorded daily up to 140 d in milk. Liver samples were taken at dry off, −20, 2, and 20 d relative to calving by biopsy. Under a similar schedule, neutrophil function was determined in blood of cows on HT (n = 12) and CL (n = 9). Blood samples were taken on −46, −32, −18, 0, 14, 28, and 42 d relative to calving for measurement of metabolites and were collected twice daily from −7 to 2 d relative to calving for prolactin (PRL) analysis. The HT cows had greater concentrations of PRL at 0 d relative to calving (150 vs. 93; SEM = 11 ng/mL) and had higher afternoon rectal temperatures (39.4 vs. 39.0; SEM = 0.04°C) and elevated respiration rates (78 vs. 56; SEM = 2 breaths/min) during the prepartum period compared with CL cows. Relative to HT cows, CL cows had greater hepatic expression of PRL-R, SOCS-3, and CAV-1 mRNA. Neutrophil oxidative burst was greater in CL cows relative to HT cows at 2 d (61 vs. 42; SEM = 6%) and at 20 d (62 vs. 49; SEM = 5%) relative to calving, and phagocytosis was greater in CL cows at 20 d (47 vs. 33; SEM = 4%) relative to calving compared with HT cows. Humoral response, as measured by IgG secretion against ovalbumin challenge, was greater for CL cows at −32 d (0.44 vs. 0.33; SEM = 0.05 OD) and −21 d (0.60 vs. 0.50 ± 0.04 OD) relative to calving compared with HT cows. These results suggest that HT abatement during the dry period improved innate and acquired immune status as measured by neutrophil function and immunoglobulin secretion against ovalbumin challenge, and altered hepatic gene expression related to PRL signaling in the periparturient period or subsequent lactation. [ABSTRACT FROM AUTHOR]

Environmental factors, especially temperature and light exposure, influence the health and productivity of dairy cows during lactation, possibly via similar physiological mechanisms. For example, heat stress is a critical component of decreased milk yield during summer. However, less is known about the effect of heat stress during the dry period. The objective of this study was to evaluate the effects of heat stress prepartum under a controlled photoperiod on lactation performance and hepatic metabolic gene expression of periparturient multiparous Holstein cows (n = 16). Cows were dried off approximately 46 d before expected calving date and assigned to treatment randomly after blocking by mature equivalent milk production and parity. Treatments consisted of either heat stress (HT) or cooling (CL) with fans and sprinklers, both under a photoperiod of 14L:10D. Rectal temperature was measured twice daily during the dry period. After calving, cows were housed in a freestall barn with cooling devices, and milk yield was recorded daily up to 210 d in milk. Blood samples were taken from dry off until +42 d relative to calving for metabolites and from -2 until +2 d relative to calving for hormone analysis. Daily dry matter intake was measured from -35 to +42 d relative to calving. Liver biopsies were collected at dry off, -20, +2, and +20 d relative to calving for cows on HT (n = 5) and CL (n = 4) to measure mRNA expression of suppressors of cytokine signaling-2 (SOCS-2), insulinlike growth factor binding protein-5 (IGFBP-5), a key transcription factor in lipid biosynthesis (SREBP-1c), and enzymes of lipid metabolism (FASN, ACACA, and ACADVL) by real-time quantitative PCR. Heat stress increased rectal temperatures (39.2 vs. 38.8°C), plasma prolactin concentrations at -1 (171 vs. 79 ng/ mL) and 0 d (210 vs. 115 ng/mL) relative to calving, and decreased dry matter intake at 0 and +14 d relative to calving and 3.5% fat-corrected milk postpartum (26.1 vs. 35.4 kg/d) compared with CL cows. Relative to CL cows, hepatic mRNA expression of SOCS-2 and IGFBP-5 was downregulated in HT cows. Expression of ACADVL was upregulated in CL cows at d +2 but downregulated at d +20 relative to HT cows. Concentrations of C16:0 and cis C18:1 were greater in the milk and liver of CL cows compared with HT cows, which reflects greater lipid mobilization. These results suggest that heat-stress abatement in the dry period improves subsequent lactation, possibly via suppression of plasma prolactin surge around calving, SOCS-2 expression, and regulation of hepatic lipid metabolism. [ABSTRACT FROM AUTHOR]

Cell wall fragments from both yeast-like and mycelial forms of the dimorphic fungus Mucor rouxii were used as enzymatic preparations to study the synthesis and role of prenyl-phospho-sugars in these systems. In the presence of GDP ['4C] mannose two main products were formed. One of them was characterized as dolichol-monophosphate β-mannose on the following basis: solubility in organic solvents, behaviour upon paper chromatography, DEAF cellulose column chromatography, mild acid hydrolysis, alkali treatment, catalytic reduction and phenol degradation. The other product was identified as a glicoprotein containing a single mannose unit linked to a serine or threonine residue. It was degraded with pronase and by mild NaOH-NaBH treatment all the radioactivity was released as free mannitol. When UDP[C] glucose was employed as sugar donor two butanol soluble components were isolated. One of them (25%) was characterized as dolichol-monophosphate-ß-glucose on the basis of the same criteria as described above. The other one (75%) was neutral and was not studied in detail. Mycelial enzymes were about 40 times more active in the synthesis of the dolichol derivatives. In addition, large amounts of glycogen were detected. The role that both dolichol derivatives might play in glycoprotein biosynthesis is discussed. [ABSTRACT FROM AUTHOR]

No presente texto discutimos como palavras polissêmicas e homônimas são acessadas e qual o papel do contexto durante a etapa de acesso. Trabalhos clássicos como Swinney (1979) e Tanenhaus et al. (1979) defendem a hipótese do acesso múltiplo, para a qual o contexto age apenas tardiamente no acesso lexical de palavras ambíguas. Já Tabossi e Zardon (1993) e Simpson (1994) defendem a hipótese do acesso seletivo, segundo a qual apenas o sentido especificado pelo contexto é acessado na leitura de uma palavra ambígua. Para verificar a validade dessas hipóteses no acesso a palavras polissêmicas e homônimas realizamos três experimentos de cross-modal priming. Os resultados corroboram a hipótese do acesso múltiplo. No que concerne à relação entre polissemia e homonímia, nossos achados fornecem evidências para a hipótese de que palavras polissêmicas e homônimas são acessadas da mesma forma, mesmo que haja mais sentidos diacronicamente associados às polissemias

In an effort to improve the efficiency of dairy cattle production, the University of Florida provides producers with information, support and leadership for the continued economic development and sustainability of the dairy industry. Dietary supplementation of lipids allowed for improved production and reproductive performance of dairy cows, especially during the summer. Other contributions in nutrition include use of citrus pulp as an energy source and DCAD diets for cows in the transition period and the realization of the importance of mineral nutrition in the summer. A greater understanding of the physiology and endocrinology of the estrous cycle and ovarian function has led to the development of reproductive management tools for synchronizing estrus for timed insemination. In addition, pioneering work led to the discovery of interferon-tau as the key protein involved in maternal recognition of pregnancy. Shortening of the dry period increased milk income and reduced the incidence of disorders associated with transition cows as they initiate a new lactation. Studies with bST in lactating cows helped with its promotion and utilization to increase milk yield and allowed for increased profit margins of dairy enterprises. Realization that heat stress reduced the establishment and maintenance of pregnancy and lowered milk production led to studies to improve the ability of lactating cows to regulate their body temperature. These efforts included improving housing conditions through the use of shade, fans, sprinklers, water application rates, and cooling ponds and identification of the "slick hair" gene involved in thermoregulation. Incorporation of timed artificial insemination to eliminate heat detection and utilization of timed embryo transfer to bypass the sensitivity of early embryos to elevated temperature are management strategies used by producers to increase pregnancy rates in the summer. The Dairy Science program continues to improve dairy cattle efficiency while maximizing milk production and developing solutions for the changing needs of the dairy industry. [ABSTRACT FROM AUTHOR]

The objective was to evaluate how dietary fat sources enriched with oleic, trans-octadecenoic, linoleic, or linolenic acids affected the plasma and liver fatty acid profiles of Holstein heifers (n = 22) and cows (n = 32) during the summer season. Fat supplements were the following: 1) sunflower oil (SFO - Trisun, Humko Oil, 80% C18:1), 2) Ca salt of trans-octadecenoic acids (TRANS- EnerG TR, Virtus Nutrition, 57% trans 6-12), 3) Ca salt of vegetable oils (MEGRMegalac- R, Church & Dwight Co, 30% C18:2), and 4) linseed oil (LSO- Archer Daniels Midland, 56% C18:3 and 16% C18:2). Supplemental fats were fed at 1.35% of dietary DM beginning at 29 d prior to expected calving date. After calving, fats were fed at 1.5% (oils) and 1.75% (Ca salts) of dietary DM for 15 wk. Three blood samples collected on a Monday-Wednesday-Friday schedule between 21 and 28 DIM were analyzed for fatty acids using gas chromatography. Liver samples were taken via biopsy on 2, 14±2, and 28±2 DIM, immediately frozen in liquid nitrogen and kept at -800C for fatty acid analysis. Feeding high oleic sunflower oil did not affect the C18:1 concentrations of plasma (12.35%) or liver (21.8%). Cows fed TRANS fats had greater concentrations of plasma C18:1 trans isomers in liver tissue (1.0, 1.4, 1.0, and 1.0% for diets 1, 2, 3, and 4, respectively). Concentrations of C18:2 were greater in cows fed MEGR (44.4%) compared to cows fed LSO (41.8%) but were not different from that of cows fed SFO (43.4%) or TRANS (45.2%). Cis-9, trans-11 CLA was greater in plasma (0.13, 0.13, 0.16, and 0.14%) and liver (0.41, 0.43, 0.50, and 0.47%) of cows fed MEGR compared to those fed SFO or TRANS. Cows fed LSO had greater concentrations of C18:3 (2.4, 2.5, 2.3, and 4.9%; 0.9, 0.9, 1.0, and 1.4%) and C20:5 (0.5, 0.5, 0.5, and 0.7%; 0.6, 0.6, 0.5, and 0.9%) in plasma and liver, respectively. Feeding dietary fats enriched with particular fatty acids resulted in increased concentrations of those fatty acids in the plasma and liver. [ABSTRACT FROM AUTHOR]

The objective was to evaluate how dietary fat sources of oleic, transoctadecenoic, linoleic, or linolenic acids affected bST, IGF-1, and PGF metabolite (PGFM) concentrations in plasma of Holstein heifers (n = 22) and cows (n = 32) during the summer season. Fat supplements were the following: 1) sunflower oil (SFO; Trisun, Humko Oil, 80% C18:1), 2) Ca salt of trans-octadecenoic acids (TRANS; EnerG TR, Virtus Nutrition, 57% trans 6-12 C18:1), 3) Ca salt of vegetable oils (MEGR; Megalac-R, Church & Dwight Co, 30% C18:2), and 4) linseed oil (LSO- Archer Daniels Midland, 56% C18:3 and 16% C18:2). Supplemental fats were fed at 1.35% of dietary DM beginning at 29 d prior to expected calving date. After calving, fats were fed at 1.5% (oils) and 1.75% (Ca salts) of dietary DM for 15 wk. Blood samples were taken thrice weekly during 7 wk for measurement of IGF-1 and bST and for the first 14 DIM for PGFM. Mean concentrations of plasma IGF-1 tended to be greater (P = 0.08) in heifers compared to cows (135 vs. 124 ng/ml) but did not differ among treatment groups (122, 135, 124, and 137 ng/ml for diets 1, 2, 3, and 4 respectively). Concentrations of IGF-1 increased at a faster rate for animals fed polyunsaturated fats compared to those fed monounsaturated fats. Mean concentrations of bST were not different among treatments. Plasma concentrations of bST decreased from 7.0 to 4.1 ng/ml over DIM for primiparous cows except those fed MEGR, which increased from 7.3 to 8.3 ng/ml. For multiparous cows, bST concentrations also decreased over time but those fed MEGR decreased at a faster rate (treatment by parity by DIM interaction). Cows fed TRANS had a higher initial plasma concentration of PGFM (4065 vs. 2408 ng/ml) and decreased at a faster rate than cows fed SFO but both reached baseline by 9 DIM. The PGFM concentrations of cows fed MEGR decreased at a slower rate compared to cows fed LSO, reaching baseline 2 d later. Dietary fatty acids alter hormonal status of lactating dairy cows. [ABSTRACT FROM AUTHOR]

Heat stress during the dry period negatively affects hepatic metabolism and cellular immune function during the transition period, and milk production in the subsequent lactation. However, the cellular mechanisms involved in the depressed mammary gland function remain unknown. The objective of the present study was to determine the effect of heat stress during the dry period on various indices of mammary gland development of multiparous cows. Cows were dried off approximately 46 d before expected calving and randomly assigned to 2 treatments, heat stress (HT, n = 15) or cooling (CL, n = 14), based on mature equivalent milk production. Cows in the CL treatment were provided with sprinklers and fans that came on when ambient temperatures reached 21.1°C, whereas HT cows were housed in the same barn without fans and sprinklers. After parturition, all cows were housed in a freestall barn with cooling. Rectal temperatures were measured twice daily (0730 and 1430 h) and respiration rates recorded at 1500 h on a Monday-Wednesday-Friday schedule from dry off to calving. Milk yield and composition were recorded daily up to 280 d in milk. Daily dry matter intake was measured from dry off to 42 d relative to calving. Mammary biopsies were collected at dry off, -20, 2, and 20 d relative to calving from a subset of cows (HT, n = 7; CL, n = 7). Labeling with Ki67 antigen and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling were used to evaluate mammary cell proliferation and apoptosis, respectively. The average temperature-humidity index during the dry period was 76.6 and not different between treatments. Heat-stressed cows had higher rectal temperatures in the morning (38.8 vs. 38.6°C) and afternoon (39.4 vs. 39.0°C), greater respiration rates (78.4 vs. 45.6 breath/min), and decreased dry matter intake (8.9 vs. 10.6 kg/d) when dry compared with CL cows. Relative to HT cows, CL cows had greater milk production (28.9 vs. 33.9 kg/d), lower milk protein concentration (3.01 vs. 2.87%), and tended to have lower somatic cell score (3.35 vs. 2.94) through 280 d in milk. Heat stress during the dry period decreased mammary cell proliferation rate (1.0 vs. 3.3%) at -20 d relative to calving compared with CL cows. Mammary cell apoptosis was not affected by prepartum heat stress. We conclude that heat stress during the dry period compromises mammary gland development before parturition, which decreases milk yield in the next lactation. [ABSTRACT FROM AUTHOR]

Dietary sources of fatty acids were evaluated for their influence on oocyte quality and follicular development using 54 lactating cows in summer. Fat supplements were 1) sunflower oil (80% cis 18:1), 2) Ca salt of transoctadecenoic acids (57% trans 18:1), 3) Ca salt of vegetable oils (30% 18:2), and 4) linseed oil (56% 18:3 and 16% 18:2). Fats were fed at 1.35% of dietary dry matter beginning at 5 wk prior to expected calving date and at 1.5% (oils} and 1.75% (Ca salts) of dietary dry matter for 15 wk after parturition. Four days following a programmed induced ovulation, 5 transvaginal oocyte aspirations were performed 3 or 4 d apart. Three days after the last aspiration, PGF2α was injected, followed 3 d later by a GnRH injection and a timed artificial insemination (d 0) 16 to 20 h later. For the first 4 aspirations, oocytes grading 1 or 2 were used for in vitro embryo production. Total cell number and the proportion of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive blastomeres were analyzed at d 8. At the fifth aspiration, the occurrence of metaphase II, group II caspase activity, and TUNEL labeling were determined after oocyte maturation. A total of 1,011 oocytes were collected. The proportion of oocytes with high caspase activity was greater for grade 3 compared with grades 1 and 2 (37.5 vs. 1.54 and 1.61%). Feeding polyunsaturated fatty acids, as compared with monosaturated fatty acids, failed to affect oocyte quality, as demonstrated by subsequent embryo development. Cows fed 18:2- or 18:3-enriched diets had a larger preovulatory follicle at insemination and subsequent volume of the corpus luteum compared with those fed cis 18:1 or trans 18:1 diets (!6.8, 16.2 vs. 15.0, 14.9 ± 0.7 mm; 7,323, 8,208 vs. 6,033, 5,495 ± 644 mm³, respectively). The previously documented benefits of polyunsaturated fatty acids on reproductive performance appear to reflect actions at alternative biological windows in lactating dairy cows. [ABSTRACT FROM AUTHOR]

Heat stress (HT) during the dry period compromises mammary gland development, decreases future milk production, and impairs the immune status of dairy cows. Our objective was to evaluate the effect of cooling HT cows during the dry period on gene expression of the mammary gland and peripheral blood mononuclear cells (PBMC). Cows were dried off 46 d before their expected calving and assigned to 2 treatments, HT or cooling (CL). Cows in the CL group were cooled with sprinklers and fans whereas HT cows were not. After parturition, all cows were housed in a freestall barn with cooling. The PBMC were isolated at dry-off and at -20, 2, and 20 d relative to calving from a subset of cows (HT, n = 9; CL, n = 10), and mammary biopsies were taken at the same intervals (HT, n = 7; CL, n = 6) for RNA extraction. Gene expression was assessed using a custom multiplex gene expression assay based on traditional reverse transcription-PCR. Genes involved in prolactin (PRL) signaling [PRL receptor long form, PRL receptor short form, suppressor of cytokine signaling (SOCS)2, SOCS3, IGF2, IGF binding protein 5, and cyclin D1], fatty acid metabolism (acetyl-CoA carboxylase a (ACACA) and lipoprotein lipase (LPL)], and IGF1 were evaluated in mammary tissue, and genes related to fatty acid metabolism [ACACA, fatty acid synthase (FASN), and LPL], cytokine production [IL6, IL8, and tumor necrosis factor (TNF)], and IGF1 were evaluated in PBMC. No differences were observed in PRL signaling or fatty acid metabolism gene expression in the mammary gland. In PBMC, HT cows had greater mRNA expression of IGF1 and TNF during the transition period relative to CL and upregulated IL8 and downregulated FASN mRNA expression at 2 d relative to calving. We conclude that cooling HT cows during the dry period alters expression of genes involved in cytokine production and lipid metabolism in PBMC. [ABSTRACT FROM AUTHOR]

The objectives of this retrospective observational study were to investigate the association between BCS at 21 d before calving with prepartum and postpartum DMI, energy balance (EB), and milk yield. Data from 427 multigravid cows from 11 different experiments conducted at the University of Florida (Gainesville, FL) were used. Cows were classified according to their BCS at 21 d before calving as fat (BCS ≥ 4.00; n = 83), moderate (BCS = 3.25-3.75; n = 287), and thin (BCS ≤ 3.00; n = 57). Daily DMI from -21 to -1 and from +1 to +28 DIM was individually recorded. Energy balance was calculated as the difference between net energy for lactation consumed and required. Dry matter intake in fat cows was lower than that in moderate and thin cows both prepartum (fat = 9.97 ± 0.21, moderate = 11.15 ± 0.14, and thin = 11.92 ± 0.22 kg/d) and postpartum (fat = 14.35 ± 0.49, moderate = 15.47 ± 0.38, and thin = 16.09 ± 0.47 kg/d). Dry matter intake was also lower for moderate cows compared with thin cows prepartum, but not postpartum. Energy balance in fat cows was lower than in moderate and thin cows both prepartum (fat = -4.16 ± 0.61, moderate = -1.20 ± 0.56, and thin = 0.88 ± 0.62 Mcal/d) and postpartum (fat = -12.77 ± 0.50, moderate = -10.13 ± 0.29, and thin = -6.14 ± 0.51 Mcal/d). Energy balance was also lower for moderate cows compared with thin cows both prepartum and postpartum. There was a quadratic association between BCS at 21 d before calving and milk yield. Increasing BCS from 2.5 to 3.5 was associated with an increase in daily milk yield of 6.0 kg and 28 d cumulative milk of 147 kg. Increasing BCS from 3.5 to 4.5 was associated with a decrease in daily milk yield of 4.4 kg and 28 d cumulative milk of 116 kg. In summary, a moderate BCS at 21 d before calving was associated with intermediate DMI and EB pre- and postpartum but greater milk yield compared with thinner and fatter cows. Our findings indicate that a moderate BCS is ideal for ensuring a successful lactation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This work assessed the influence of the amount of dentifrice and fluoride (F) concentration in the product on the pH and inorganic components of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated with suspensions of fluoride dentifrices containing 550 or 1100 ppm of F (550 F or 1100 F, respectively) administered at comparable intensities: (i-1) 550 F/0.08 g or 1100 F/0.04 g; (i-2) 550 F/0.16 g or 1100 F/0.08 g; and (i-3) 550 F/0.32 g or 1100 F/0.16 g. A placebo dentifrice (without NaF, 0.32 g) was used as a negative control. After the last treatment, the biofilm pH was measured and the F, calcium (Ca), and phosphorus (P) concentrations were determined. Data were subjected to an ANOVA/Kruskal-Wallis test, and a Student-Newman-Keuls test. The highest biofilm pH and F concentrations (biomass and fluid) were observed for 1100 F at i-3. Overall, 1100 F resulted in F levels similar to 550 F for i-1 and i-2. In addition, 550 F applied at i-2 and i-3 led to higher F in the biomass/fluid compared to 1100 F applied at i-1 and i-2, respectively. In biomass, the lowest Ca concentrations were observed for 1100 F at i-3. The conclusion drawn is that the treatment intensity holds greater significance as a parameter compared to the concentration of F or the amount of dentifrice when considered individually.

The connection between contextuality and graph theory has paved the way for numerous advancements in the field. One notable development is the realization that sets of probability distributions in many contextuality scenarios can be effectively described using well-established convex sets from graph theory. This geometric approach allows for a beautiful characterization of these sets. The application of geometry is not limited to the description of contextuality sets alone; it also plays a crucial role in defining contextuality quantifiers based on geometric distances. These quantifiers are particularly significant in the context of the resource theory of contextuality, which emerged following the recognition of contextuality as a valuable resource for quantum computation. In this paper, we provide a comprehensive review of the geometric aspects of contextuality. Additionally, we use this geometry to define several quantifiers, offering the advantage of applicability to other approaches to contextuality where previously defined quantifiers may not be suitable. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

This study aimed to evaluate and monitor pesticides in groundwater of the Serra Geral aquifer, located in the Paraná Basin 3 (southern Brazil), using Liquid Chromatography coupled with a Quadrupole-Time-of-Flight Mass Spectrometer (LC-QTOF MS). A total of 117 samples, collected in three different moments, were analyzed over 36 months. Groundwater samples from 35 wells and four surface water points were monitored in each sampling campaign. A pesticide screening methodology was proposed with the tentative identification of 1607 pesticides and pesticide metabolites. The application of the proposed methodology resulted in the verification of 29 pesticides and pesticide metabolites, 7 as confirmed analytes and 22 as suspect compounds. (Q)SAR in silico predictions and GUS index calculation provided data on the potential environmental risk of the identified compounds, with eight endpoints considered. After in silico predictions, an alternative hybrid multicriteria method was applied, combining the weighting of endpoints of fuzzy AHP and micropollutants classification by environmental risk using ELECTRE. The fuzzy AHP results indicated the greatest importance of mutagenicity among the eight evaluated indicators, while the scarce influence of the physicochemical properties on the environmental risk suggested their exclusion from the model. Accordingly, the ELECTRE results highlighted the prevalence of thiamethoxam and carbendazim as the most dangerous for the environment. The application of the proposed method enabled the selection of the compounds that must be monitored, considering mutagenicity and toxicity predictions for environmental risk analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We aimed to characterize and investigate the antibacterial potential of the native stingless bees geopropolis volatile oils (VO) for the search of potentially new bioactive compounds. Geopropolis samples from Melipona bicolor schencki, M. compressipes manaosensis, M. fasciculata, M. quadrifasciata, M. marginata and M. seminigra merrillae were collected from hives in South Brazil. VO were obtained by hydrodistillation and characterised by gas chromatography coupled to mass spectrometry (GC/MS). Antimicrobial activity was assessed by microplate dilution method. The lowest MIC against cell walled bacteria was 219±0 μg mL -1 from M. quadrifasciata geopropolis VO with Staphylococcus aureus. The M. b. schencki geopropolis VO minimal inhibition concentration (MIC) was 424±0 μg mL -1 against all the mycoplasma strains evaluated. Fractionation resulted in the reduction of 50 % of the MIC value from the original oil. However, its compounds' synergism seems to be essential to this activity. Antibiofilm assays demonstrated 15.25 % eradication activity and 13.20 % inhibition of biofilm formation after 24 h for one subfraction at 2× its MIC as the best results found. This may be one of the essential mechanisms by which geopropolis VOs perform their antimicrobial activity., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: To compare the live birth rates (LBRs) in modified natural and programmed single blastocyst frozen embryo transfer (FET) cycles., Design: Retrospective cohort study., Setting: University-affiliated fertility practice., Patient(s): Patients who underwent single blastocyst FETs between January 2014 and December 2019. A total of 15,034 FET cycles from 9,092 patients were reviewed; 1,186 modified natural and 5,496 programmed FET cycles from 4,532 patients met the inclusion criteria for analysis., Intervention(s): No intervention., Main Outcome Measure(s): The primary outcome measure was the LBR., Result(s): There was no difference in live birth after programmed cycles using intramuscular (IM) progesterone or a combination of vaginal progesterone and IM progesterone compared with that after modified natural cycles (adjusted relative risks, 0.94 [95% confidence interval {CI}, 0.85-1.04] and 0.91 [95% CI, 0.82-1.02], respectively). The relative risk of live birth decreased in programmed cycles that used exclusively vaginal progesterone compared with that in modified natural cycles (adjusted relative risk, 0.77 [95% CI, 0.69-0.86])., Conclusion(s): The LBR decreased in programmed cycles that used only vaginal progesterone. However, no difference in the LBRs existed between modified natural and programmed cycles if programmed cycles used either IM progesterone or a combination of IM and vaginal progesterone protocols. This study demonstrates that modified natural FET cycles and optimized programmed FET cycles have equivalent LBRs., (Published by Elsevier Inc.)

Glycogen synthase kinase 3 (GSK3) remains a therapeutic target of interest for diverse clinical indications. However, one hurdle in the development of small molecule GSK3 inhibitors has been safety concerns related to pan-inhibition of both GSK3 paralogs, leading to activation of the Wnt/β-catenin pathway and potential for aberrant cell proliferation. Development of GSK3α or GSK3β paralog-selective inhibitors that could offer an improved safety profile has been reported but further advancement has been hampered by the lack of structural information for GSK3α. Here we report for the first time the crystal structure for GSK3α, both in apo form and bound to a paralog-selective inhibitor. Taking advantage of this new structural information, we describe the design and in vitro testing of novel compounds with up to ∼37-fold selectivity for GSK3α over GSK3β with favorable drug-like properties. Furthermore, using chemoproteomics, we confirm that acute inhibition of GSK3α can lower tau phosphorylation at disease-relevant sites in vivo, with a high degree of selectivity over GSK3β and other kinases. Altogether, our studies advance prior efforts to develop GSK3 inhibitors by describing GSK3α structure and novel GSK3α inhibitors with improved selectivity, potency, and activity in disease-relevant systems.

Crossing and developing inbred lines have been promising options for guava breeding programs. The purpose of this study was to evaluate the genetic divergence among genotypes of S 1 inbred guava families by means of the Gower's technique and the Ward-MLM methodology, to verify the correlation and relative contribution of traits, as well as to identify descriptors with minimum efficiency for this species. The experiment was implemented at the Estação Experimental da Ilha Barra do Pomba, in the municipality of Itaocara, RJ, Brazil. A randomized block design with 18 inbred families, three replicates, and ten plants per plot was used for the experimental design. After 19 months from the planting of the experiment, the 61 earliest and most productive genotypes (individual plants) were evaluated. For this purpose, 29 descriptors were evaluated, of which fifteen were qualitative and fourteen, quantitative. The characteristics required to obtain the distance matrix were analyzed based on the Gower algorithm, and a comparative cluster between the dendrograms of the morphoagronomic variables was achieved from this matrix. Lastly, the Ward-MLM procedure was applied to form the clusters of inbred families. By using all 29 descriptors, greater efficiency was achieved in cluster discrimination. Hence, according to the results identified, it is not possible to indicate minimum descriptors for the culture. Using the Ward-MLM method, the descriptors that most contributed to the divergence among the genotypes were fruit flesh mass, fruit weight, fruit diameter, fruit flesh thickness, fruit placental mass, and fruit length. The most divergent genotypes can be recommended for further crosses or self-pollinations to develop new lines in the guava breeding program of UENF., (© 2022. The Author(s).)

Objectives: The objective of this study was to evaluate the impact of a telehealth intervention on metabolic outcomes and self-perceptions of the patients regarding their management of diabetes during the COVID-19 pandemic., Methods: This is a non-blind randomized controlled clinical trial to assess a telehealth intervention. We included adults with diabetes mellitus. The outcomes assessed were the level of HbA1c, lipid profile, blood pressure levels, weight, body mass index and self-perceptions about diabetes management., Results: A total of 150 individuals with diabetes participated in the study and at the end of telehealth intervention there were no changes in the patient's HbA1c levels between intervention and control groups for neither type 1 (8.1% vs. 8.6%; p = 0.11) nor type 2 diabetes (8.6% vs. 9.0%; p = 0.09), respectively. From the rest of the metabolic profile, triglyceride levels from type 1 diabetes group was the only variable that demonstrated improvement with telehealth intervention (66.5% intervention group vs. 86.5% control group; p = 0.05)., Conclusions: After 4 months of telehealth intervention, no statistically significant results were observed in HbA1c nor in secondary outcomes (with the exception of triglycerides for the type 1 diabetes group)., Competing Interests: Conflicts of interest There is no conflict of interest to declare., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to evaluate the expression of several cell membrane markers in oral squamous cell carcinomas (OSCC) and to examine their prognostic influence., Study Design: We analyzed the immunohistochemical expression of claudin-1 (CLDN-1), claudin-4 (CLDN-4), claudin-5 (CLDN-5), claudin-7 (CLDN-7), occludin (OCLN), and E-cadherin (CDHE) in 60 patients with OSCC treated in a central hospital Center of Oporto. The prognostic significance of these biomarkers in cancer-specific survival and recurrence-free survival were evaluated using multivariate analysis., Results: Claudin-1 was observed in the membrane of tumor cells in 51 cases (89.5%), CLDN-4 in 36 cases (63.2%), and CLDN-7 in 48 cases (80%). Claudin-5 was detected in the cytoplasm of tumor cells in 46 cases (78%) and OCLN in 40 cases (70.2%). In a multivariate analysis, the combined evaluation of OCLN and CLDN-1 revealed a significant and independent association with cancer-specific survival and recurrence-free survival. We found a low extent score for OCLN and a high intensity score for CLDN-1, presenting the hazard ratios of 15.48 (P = .014) and 9.446 (P = .012), respectively., Conclusion: The CLDN-1 and OCLN proteins could be involved in tumor progression of OSCC. Their combined deregulated expression showed an adverse effect on survival and therefore they could be regarded as important prognostic biomarkers in OSCC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A simple and straightforward QuEChERS extraction method was proposed for the simultaneous determination of atrazine (ATZ), desethylatrazine (DEA), desisopropylatrazine (DIA), carbaryl (CBL), carbendazim (CBD), and diuron (DIU) in soil with high agricultural activity from southeastern Brazil, using high-performance liquid chromatography-diode-array detection/fluorescence detection. Screening studies carried out by 2 4 factorial design indicate better recoveries when less sample (1.0 g) and the volume of solvent (2.0 mL of ACN) were applied, compared to the original QuEChERS method. Furthermore, interactions between factors were not negligible in the experimental set, except for ATZ and DIU, in which only water volume influenced their recovery. The influence of the type (primary secondary amine (PSA), C18, and Florisil) and the sorbent amount ratio to the compounds' concentration were also considered. PSA (25 mg) was selected as the best sorbent without losing analytical response. The limits of quantification (LOQ) were estimated to be 5.0 to 15 µg kg -1 in the soil matrix. Analytical performances were consistent with linearity (R 2  ≥ 0.998), recovery from 74.7 to 108%, and relative standard deviations (RSD) between 2.6 and 20.2%. Robustness was assessed by fractional factorial Plackett-Burman design. The method is recommended for chemicals that are soluble in water, and it was successfully applied in the analysis of real soil samples containing the analytes in the range of μg kg -1 , proving to be suitable for the study of soils strongly impacted by agricultural activity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The association between type 1 diabetes and mental health disorders could be exacerbated in a stressful environment. This study aimed to evaluate the feasibility of a teleguided intervention on emotional disorders in patients with type 1 diabetes during the COVID-19 outbreak. This study was performed during the social distancing period in the COVID-19 outbreak in Brazil. Individuals with type 1 diabetes aged ≥ 18 years were selected to receive a teleguided multidisciplinary intervention or the usual care plus an educational website access. The proposed intervention aimed addressing aspects of mental health, diabetes care and lifestyle habits during the pandemic. The feasibility outcome included the assessment of recruitment capability and adherence to the proposed intervention. Moreover, we evaluated the presence of positive screening for emotional disorders (Self Report Questionnaire 20) after a 16-week intervention, patients' perceptions of pandemic-related changes, diabetes-related emotional distress, eating disorders, and sleep disorders. Data were analyzed with the intent-to-treat principle. Fifty-eight individuals (mean age, 43.8 ± 13.6 years) were included (intervention group, n = 29; control group, n = 29). At the end of the study, a total of 5 participants withdrew from the study in the intervention group compared to only 1 in the control group. Participants who dropout from the study had similar mean age, sex and income to those who remained in the study. The analysis of mental health disorders was not different between the groups at the follow up: a positive screening result was found in 48.3% and 34.5% of participants in the intervention and control groups, respectively (P = 0.29). The intervention group felt more supported in their diabetes care during the social distancing period (82.8% vs. 48.3% in the control group, P < 0.01). Our study identified a disproportionate higher number of withdrawals in the intervention group when compared to the control group. This difference may have compromised the power of the study for the proposed assessments and should be reevaluated in future studies.Trial registration: ClinicalTrials.gov (NCT04344210). Date of registration: 14/04/2020., (© 2022. The Author(s).)

Our aim was to evaluate the expression of biomarkers, CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin in oral leukoplakias (OL) and to assess their potential for prediction of malignant transformation (MT). We analyzed the expression of CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin by immunohistochemistry in 52 OL, comprised of 41 low-grade (LG) dysplasia and 11 high-grade (HG) cases. Twelve healthy normal tissues (NT) were also included. Univariate and multivariate analysis were performed to evaluate any association with MT. Variable expression among the studied markers was observed, with a significant increase of high expression from NT to LG and HG cases in CD44v6 (p = 0.002), P53 (p = 0.002), P73 (p = 0.043), and podoplanin (p < 0.001). In multivariate analysis, cases with high podoplanin score showed a significant increased risk of MT (HR of 10.148 (95% CI of 1.503−68.532; p = 0.017). Furthermore, podoplanin combined with binary dysplasia grade obtained a HR of 10.238 (95% CI of 2.06−50.889; p = 0.004). To conclude, CD44v6, p53, p73, and podoplanin showed an increasing expression along the natural history of oral carcinogenesis. Podoplanin expression independently or combined with dysplasia grade could be useful predictive markers of MT in OL.

The association between type 1 diabetes and mental health disorders could be exacerbated in a stressful environment. This study aimed to evaluate the effectiveness of a teleguided intervention on emotional disorders in patients with type 1 diabetes during the COVID-19 outbreak. An open-label clinical trial was performed during the social distancing period in the COVID-19 outbreak in Brazil. Individuals with type 1 diabetes aged ≥ 18 years were randomized to receive a teleguided multidisciplinary intervention or the usual care plus an educational website access. The primary outcome was a positive screening for emotional disorders (Self Report Questionnaire 20) after a 16-week intervention. Secondary outcomes included evaluation of patients' perceptions of pandemic-related changes, diabetes-related emotional distress, eating disorders, and sleep disorders. Data were analyzed with the intent-to-treat principle. Fifty-eight individuals (mean age, 43.8 ± 13.6 years) were included (intervention group, n = 29; control group, n = 29). The primary outcome was not different between the groups. The intervention group felt more supported in their diabetes care during the social distancing period (82.8% vs. 48.3% in the control group, P < 0.01). Both groups reported a similar self-perceived worsening of physical activity habits and mental health during the outbreak. There was no benefit to using the telehealth strategy proposed for emotional disorders in patients with type 1 diabetes during the COVID-19 outbreak. Further studies are needed to determine the impact on metabolic parameters and to understand why it is so difficult to emotionally support these patients.Trail Registration: ClinicalTrials.gov (NCT04344210), 14/04/2020., (© 2022. The Author(s).)

Purpose of Review: The use of renal tumor biopsy (RTB) for small renal masses (SRMs) in daily practice, although safe and accurate, is unusual. Considering the large number of benign tumors in patients with renal masses < 4 cm, some patients with benign tumors are directly referred for surgery instead. This study aimed to report the diagnostic rates of RTB, determine the concordance with surgical pathology, and assess the number of procedures that could have been avoided. We retrospectively studied 255 patients who underwent RTB at our institution in 2010-2019. Of them, 73 were excluded from the analysis (exclusion criteria: > 4 cm, cystic lesion, missing data). The remaining 182 with undetermined SRMs ≤ 4 cm underwent RTB under computed tomography guidance., Recent Findings: Biopsies were diagnostic in 154/182 (84.6%) cases. Of the non-diagnostic biopsies, 11 were diagnostic when repeated. When RTB was performed of all undetermined SRMs, active treatment (surgery or cryotherapy) was avoided in 50/182 patients (27.5%) because of a benign diagnosis, while 9/182 patients (4.9%) underwent surveillance after a shared multidisciplinary decision. The overall diagnostic rate was 90.6%. All adverse events (approximately 4%) were Clavien-Dindo grade I and did not require active treatment. RTB histology results and nuclear grade were highly concordant with the final pathology (96% and 86.6%, respectively). On univariate logistic regression analysis, male sex was the only contributing factor of diagnostic biopsy. RTB of SRMs should be performed more frequently as part of a multidisciplinary decision-making process since it avoided unnecessary surgical treatment in 1 of 3 patients in our institution., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Odontogenic cysts and tumours of the jaws represent one of the most prevalent groups of oral-maxillofacial lesions. We aimed to evaluate the clinical and pathological characteristics of a cohort of odontogenic cysts (OC) and odontogenic tumours (OT) of the jaws in a Portuguese population., Material and Methods: This observational retrospective study analysed patients diagnosed with either an OC or OT of the jaws at a central hospital of Oporto, Portugal, between 1988 and 2006. Data collected from patients' files included demographic, clinical, radiological and histopathological information. Recurrence was evaluated using univariate and multivariate analysis., Results: The sample consisted of 397 patients, 231 males (58.2%) and 166 females (41.8%), with a mean-age of 36.7±17 years. Twenty-seven patients (6.8%) presented with more than one lesion providing a total of 433 lesions. There were 396 (91.5%) OC, mostly represented by radicular cysts (n=257;59.4%), dentigerous cysts (n=79;18.2%), or odontogenic keratocysts (n=50;11.5%). There were 37 (8.5%) OT, mostly represented by ameloblastomas (n=16;3.7%), and odontomas (n=9;2.1%). The most common initial clinical manifestation was swelling (n=224;51.7%). Recurrence was observed in 30 cases (6.9%), mostly in ameloblastomas (n=6;37.5%) and odontogenic keratocysts (n=12;24%). In the multivariate analysis the diagnosis classification of the lesion was the only independent and significant variable related with the recurrence (P=0.04)., Conclusions: Radicular cysts were the most commonly occurring type of OC and ameloblastomas the most commonly occurring OT. Amelobastomas and odontogenic keratocysts were the lesions with the highest rates of recurrence. This large sample provides useful information about the frequency profile and characteristics of OC and OT over a period of 18 years, allowing valuable comparison with data from other countries.

Purpose of Review: To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition - "MIC" - and a new optimal surgical definition: the "Novel TRIFECTA" (NT) concept. We sought to strengthen the PN evidence and to test the NT's performance., Recent Findings: The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

Structural analysis of the known NIK inhibitor 3 bound to the kinase domain of TTBK1 led to the design and synthesis of a novel class of azaindazole TTBK1 inhibitors exemplified by 8 (cell IC 50 : 571 nM). Systematic optimization of this series of analogs led to the discovery of 31 , a potent (cell IC 50 : 315 nM) and selective TTBK inhibitor with suitable CNS penetration (rat K p,uu : 0.32) for in vivo proof of pharmacology studies. The ability of 31 to inhibit tau phosphorylation at the disease-relevant Ser 422 epitope was demonstrated in both a mouse hypothermia and a rat developmental model and provided evidence that modulation of this target may be relevant in the treatment of Alzheimer's disease and other tauopathies.

Here we describe a successful mechanical thrombectomy (MT) for acute large vessel occlusion in stroke treatment with one passage (thrombolysis in cerebral infarction, TICI 3). Immediately after the withdrawing of the stent retriever, a narrowing of the middle cerebral artery was diagnosed. The rate of vasospasms during this procedure can be as higher as 41% (range from 6-41%). Here we describe our protocol when a narrowing of the artery is visualized after a stent retriever is withdrawn. A patient presented in our emergency room with National Institute of Health Stroke Scale (NIHSS) of 21, Alberta Stroke Program Early CT Score (ASPECTS) 8, computed tomography angiography revealed occlusion of the M1 segment and MT was indicated. One passage TICI Ⅲ was achieved. After that, the image showed a narrowing of the artery. We present one case of a spasm after stent retriever technique for MT, we injected vasodilator and the artery became normal in a few minutes differentiating between atheromatous stenosis and vasospasm. We present a technical note that can help to make the differentiation of vasospasm or atheromatous disease after MT with the stent retriever technique.

Bovine alphaherpesvirus 2 (BoHV-2) - the agent of bovine herpetic mamillitis (BHM) - is related to Human alphaherpesviruses 1 and 2 (HHV-1, HHV-2) and, as such, has been proposed as a model for vaccine and drug testing. We herein investigated the anti-viral activity in vitro against BoHV-2 of three anti-herpetic drugs: Cidofovir (CDV), Fanciclovir (FAM), Foscarnet (PFA), and diphenyl disselenide (Ph 2 Se 2 ) , a compound that has showed activity against HHV-2. Plaque reduction assays (PRA) revealed a significant reduction in viral plaques (p < 0.05) in cells treated with Ph 2 Se 2 (79.7% reduction) or CDV (62.8%). FAM treatment resulted in a slight decrease in plaque number (22.9%, p < 0.05); PFA showed no activity. The effects of Ph 2 Se 2 and CDV, alone or in combination, were investigated in ewes inoculated with BoHV-2 transdermally and submitted to daily topic treatment. Virus inoculated ewes developed lesions progressing through the stages of hyperemia, large papules or depressed dark areas, followed by scab formation. Treatment with Ph 2 Se 2 resulted in reduction in clinical score from day 10 pi onwards (P < 0.05), shortening of clinical course and reduction in duration of virus shedding (P < 0.05) compared to untreated controls. Combined treatment (Ph 2 Se 2  + CDV) and CDV alone, also led to clinical improvement (P < 0.05), yet less pronounced and delayed. These results are promising towards the use of Ph 2 Se 2 , alone or in combination with anti-herpetic drugs, in the treatment of udder and teat lesions produced by BoHV-2 in dairy cows., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In patients with diabetes, the prevalence of depression and anxiety symptoms is about two to four times greater than in the general population. The association between diabetes and mental health disorders could be exacerbated in a stressful environment, and psychological distress could increase depressive symptoms and cause adverse diabetes outcomes., Objectives: To assess the prevalence of mental health disorders in patients with diabetes during the social distancing period due to COVID-19 pandemic., Methods: This is a cross-sectional study developed to assess the impact of social distancing on a cohort of adults with type 1 (n = 52) and type 2 diabetes (n = 68) in Brazil. Inclusion criteria involved having an HbA1c test collected in the past 3 months and having a valid telephone number in electronic medical records. The primary outcome was the prevalence of minor psychiatric disorders, assessed by survey (SRQ-20). Secondary outcomes included the prevalence of diabetes related emotional distress, eating and sleeping disorders, all assessed by validated surveys at the moment of the study. Statistical analyses included unpaired t -test for continuous variables and χ 2 test for categorical variables., Results: Overall (n = 120), participants had a mean age of 54.8 ± 14.4 years-old, and HbA1c of 9.0 ± 1.6% (75 ± 17.5 mmol/mol); 93% of patients showed signs of current mental suffering based on the surveys measured. Almost 43% of patients showed evidence of significant psychological distress, with a significant greater tendency in patients with type 2 diabetes. The presence of diabetes related emotional distress was found in 29.2% of patients; eating disorders in 75.8%; and moderate/severe sleeping disorders in 77.5%., Conclusions: We found a high prevalence of evidence of psychological distress among patients with diabetes during the COVID-19 pandemic and this highlights the need for mental health access and support for patients with type 1 and type 2 diabetes., Competing Interests: Competing interestsThere is no conflict of interest to declare., (© The Author(s) 2020.)