Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

Geometry and electronic structure of Yb(III)[CH(SiMe3)2]3 from EPR and solid-state NMR augmented by computations.

Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)[CH(SiMe3)2]3, a prototypical example, which contains notable structural features according to X-ray crystallography. Each of these techniques revealed specific information about the geometry and electronic structure of the complex. Taken together, both EPR and NMR, augmented by quantum chemical calculations, provide a detailed and complementary understanding of such paramagnetic compounds. In particular, the EPR and NMR signatures point to the presence of three-centre-two-electron Yb-γ-Me-ß-Si secondary metal-ligand interactions in this otherwise tri-coordinate metal complex, similarly to its diamagnetic Lu analogues. The electronic structure of Yb(III) can be described as a single 4f13 configuration, while an unusually large crystal-field splitting results in a thermally isolated ground Kramers doublet. Furthermore, the computational data indicate that the Yb-carbon bond contains some π-character, reminiscent of the so-called α-H agostic interaction.

Measuring skin color inequality in women's health in Northeast Brazil: Evidence from the PCSVDFMulher survey.

In this paper, we investigate whether skin color is a source of inequality in women's health by exploring the longitudinal framework of the PCSVDFMulher survey in Northeast Brazil. Specifically, we measure the skin color gradient in women's general and mental health, as well as in showing health risk behavior. We find that darker-skinned women show poorer mental health outcomes and a higher likelihood of drinking and smoking more frequently than their lighter-skinned counterparts. The skin color gradient is persistent and systematic, even when modeling different sources of unobserved heterogeneity and accounting for the existing socioeconomic inequalities and racial identity. We also find that racial identity is an important source of heterogeneous responses of women's health to skin tone.

Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Differential sensory block during labour epidural analgesia: a prospective observational study to investigate the relationship of lower and upper sensory block levels to cold, pinprick, and light touch.

PURPOSE: A zone of differential block to cold has been recently documented during labour epidural analgesia, with an upper sensory block level (USBL) and a lower sensory block level (LSBL). We aimed to determine the correlation between USBL and LSBL to cold and pinprick and sensory block level to light touch during labour epidural analgesia. METHODS: We conducted a prospective observational study in patients requesting labour epidural analgesia. We placed an epidural catheter at L2/L3 or L3/L4, followed by a programmed intermittent epidural bolus plus patient-controlled epidural analgesia regimen. We assessed the sensory block levels 140 min after administering the loading dose. The primary outcomes were the USBL and LSBL to cold and pinprick and the sensory block level to light touch. RESULTS: We studied 30 patients. The median [interquartile range (IQR)] USBL and LSBL to ice were T7 [T7-T6] and T9 [T10-T8], respectively. The median [IQR] USBL and LSBL to pinprick were T8 [T10-T6] and T10 [T12-T10], respectively. There was a strong correlation between USBL to ice and pinprick (Spearman correlation coefficient, 0.57) and between LSBL to ice and pinprick (Spearman correlation coefficient, 0.52). There was no significant correlation between sensory block level to light touch and either USBL or LSBL to ice or pinprick. CONCLUSION: We observed two sensory block levels to ice and pinprick. Further studies are required to understand if one modality-cold or pinprick-is superior to the other in assessing sensory block levels in this context. Light touch is unreliable as a modality of sensory block assessment during labour epidural analgesia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05187962); registered 12 January 2022.

RéSUMé: OBJECTIF: Une zone de bloc différentiel de réaction au froid a récemment été documentée pendant l'analgésie péridurale obstétricale, avec un niveau de bloc sensoriel supérieur (USBL, pour upper sensory block level) et un niveau de bloc sensoriel inférieur (LSBL, pour lower sensory block level). Notre objectif était de déterminer la corrélation entre l'USBL et le LSBL au contact du froid et de la piqûre et le niveau de bloc sensoriel au toucher léger pendant l'analgésie péridurale obstétricale. MéTHODE: Nous avons mené une étude observationnelle prospective chez des patient·es demandant une analgésie péridurale obstétricale. Nous avons placé un cathéter péridural au niveau L2/L3 ou L3/L4, suivi d'une administration programmée de bolus périduraux plus un régime d'analgésie péridurale contrôlée par le/la patient·e. Nous avons évalué les niveaux de bloc sensoriel 140 min après l'administration de la dose de charge. Les critères d'évaluation principaux étaient l'USBL et le LSBL en réaction au froid et à la piqûre d'épingle et le niveau de bloc sensoriel en réaction au toucher léger. RéSULTATS: Nous avons étudié 30 patient·es. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la glace étaient situés au niveau T7 [T7-T6] et T9 [T10-T8], respectivement. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la piqûre étaient localisés au niveau T8 [T10­T6] et T10 [T12­T10], respectivement. Il y avait une forte corrélation entre l'USBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,57) et entre le LSBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,52). Il n'y avait pas de corrélation significative entre le niveau de bloc sensoriel en réaction au toucher léger et l'USBL ou le LSBL en réaction à la glace ou à la piqûre. CONCLUSION: Nous avons observé deux niveaux de bloc sensoriel à la glace et à la piqûre. D'autres études sont nécessaires pour comprendre si une modalité ­ le froid ou la piqûre ­ est supérieure à l'autre pour évaluer les niveaux de bloc sensoriel dans ce contexte. Le toucher léger n'est pas fiable en tant que modalité d'évaluation du bloc sensoriel pendant l'analgésie péridurale obstétricale. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05187962); enregistré le 12 janvier 2022.

Effects of long-acting injectable progesterone supplementation at early dioestrus on pregnancy maintenance in beef and dairy recipient cattle.

We tested in the present study the hypothesis that supplementation with long-acting P4 (iP4) at different times of the initial dioestrus improves pregnancy rates in dairy and beef recipients submitted to fixed-time embryo transfer (FTET). Recipients from commercial farms had their oestrous cycle synchronized with an E2/P4-based protocol in three experiments (Exp. 1 to 3). In Exp. 1, dairy heifers (n = 76) and cows (n = 104) were randomly assigned to two experimental groups: the control group (n = 89) and the iP4D4 group (n = 91). For Exps. 2 and 3, suckled beef recipients were used. In Exp. 2, recipients were assigned to two experimental groups: Control group (n = 147) and iP4D7 group (n = 144); whereas in Exp. 3, recipients were randomly assigned to three experimental groups: Control group (n = 85), iP4-D4 group (n = 86) and iP4D7 group (n = 81). Recipients in the iP4D4 and iP4-D7 groups received an i.m. administration of 150 mg iP4, on D4 or D7 (D0 was the day of expected oestrus). On D7, all recipients were evaluated by transrectal ultrasonography and those that had a CL received a fresh or vitrified in vitro-produced embryo. In Exp. 2 and 3, the CL area was also determined by ultrasonography at the time of FTET. The pregnancy diagnosis was performed at 30 days in Exp. 1, 57 days in Exp. 2, and between 40 and 72 days of pregnancy in Exp. 3. In Exp. 1, the pregnancy rate did not differ (p > .1) between the Control group (38.2% [34/89]) and iP4D4 group (49.5% [45/91]); yet, a parity effect indicated a greater (p < .05) pregnancy rate in heifers (57.9% [44/76]) than cows (30.8% [32/104]). In Exp. 2, the pregnancy rate was greater (p < .05) in the iP4D7 group (45.0% [65/144]) than in the Control group (34.0% [50/147]). Also, a greater (p = .08) pregnancy rate was observed for recipients with a small CL (≤2.75 cm2 ) that were treated with iP4 on the day of FTET than the control recipients (46.4% [32/69] vs. 32.6% [28/86]). In Exp. 3, no significant effects (p > .1) of the treatment group or CL size were detected on pregnancy rates at days 30 and 60. In conclusion, the beneficial effects of iP4 supplementation at early dioestrus on pregnancy maintenance may vary according to the experimental conditions, but its use at the time of FTET can be used as an alternative to enhance the fertility of beef recipients in challenging conditions in commercial herds.

Hydroethanolic extracts from Bauhinia guianensis: a study on acute toxicity in Zebrafish embryos and adults.

CONTEXT: The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes. OBJECTIVE: The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations. MATERIALS AND METHODS: Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h. RESULTS: HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg. CONCLUSIONS: The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.

Existential meaning, spiritual unconscious and spirituality in Viktor Frankl.

There is robust evidence to support the relationship between spirituality and mental health, but the mechanisms of this association are not well-understood. The existential meaning provided by spirituality may be one of these mechanisms. This was the central theme of Viktor Frankl's psychology, which he explained using the notion of the spiritual unconscious. Thus, we sought to explain how Frankl understands this spiritual unconscious and the two pieces of evidence he presents for its existence: the phenomenological description of responsible action and the analysis of dreams. Lastly, we discuss his contribution to the current understanding of the relationship between having an overarching purpose and/or religious meaning and improvement in mental health.

Anesthetic management of patients with class 3 obesity undergoing elective Cesarean delivery: a single-centre historical cohort study.

PURPOSE: The preferred neuraxial anesthetic technique for patients with class 3 obesity undergoing elective Cesarean delivery is still under debate. We aimed to describe the anesthetic technique used in our tertiary institution across body mass index (BMI) groups and different surgical incisions. METHOD: In this historical cohort study, we reviewed medical records of patients with a BMI ≥ 40 kg·m-2 undergoing elective Cesarean delivery between July 2014 and December 2020. We collected data on patient characteristics, anesthetic and surgical technique, and procedural times. For data analysis, we stratified patients by BMI into three different groups: 40.0-49.9 kg·m-2, 50.0-59.9 kg·m-2, and ≥ 60.0 kg·m-2. RESULTS: We included 396 deliveries, distributed as follows: 258 with a BMI 40.0-49.9 kg·m-2, 112 with a BMI 50.0-59.9 kg·m-2, and 26 with a BMI ≥ 60.0 kg·m-2. For patients with a BMI 40.0-49.9 kg·m-2, the anesthetic technique of first choice was predominantly spinal anesthesia (71%), whereas for those with a BMI ≥ 60.0 kg·m-2, spinal anesthesia was never used as the anesthetic of first choice. With regard to the surgical incision, spinal anesthesia was almost exclusively used for patients undergoing Pfannenstiel incision and was rarely used for a higher supra- or infraumbilical transverse or midline incision. The overall incidence of general anesthesia was low (7/396, 1.8%). Anesthetic time, surgical time, and operating room time increased almost twofold in patients with a BMI ≥ 60.0 kg·m-2 compared with those with a BMI of 40.0-49.9 kg·m-2. CONCLUSION: Neuraxial anesthesia was successfully used in approximately 98% of patients with class 3 obesity undergoing elective Cesarean delivery. The choice of regional anesthesia technique varied with increasing BMI and with the planned surgical incision. Procedural times increased with increasing BMI. This information should prove useful for comparing anesthetic choices and outcomes in this challenging population.

RéSUMé: OBJECTIF: La technique d'anesthésie neuraxiale préférée pour les patientes atteintes d'obésité de classe 3 bénéficiant d'un accouchement par césarienne programmée n'a pas encore été déterminée. Nous avons cherché à décrire la technique d'anesthésie utilisée dans notre établissement d'enseignement supérieur à travers les groupes d'indice de masse corporelle (IMC) et les différentes incisions chirurgicales. MéTHODE: Dans cette étude de cohorte historique, nous avons examiné les dossiers médicaux de patientes ayant un IMC ≥ 40 kg·m­2 ayant bénéficié d'un accouchement par césarienne programmée entre juillet 2014 et décembre 2020. Nous avons recueilli des données sur les caractéristiques des patientes, la technique anesthésique et chirurgicale et les délais de procédure. Pour l'analyse des données, nous avons stratifié les patientes par IMC en trois groupes différents, soit : 40,0­49,9 kg·m­2, 50,0­59,9 kg·m­2, et ≥ 60,0 kg·m­2. RéSULTATS: Nous avons inclus 396 accouchements, répartis comme suit : 258 pour un IMC de 40,0 à 49,9 kg·m­2, 112 pour un IMC de 50,0 à 59,9 kg·m­2, et 26 pour un IMC ≥ 60,0 kg·m­2. Pour les patientes ayant un IMC de 40,0 à 49,9 kg·m­2, la technique anesthésique de premier choix était principalement la rachianesthésie (71 %), alors que pour celles dont l'IMC ≥ de 60,0 kg·m­2, la rachianesthésie n'a jamais été utilisée comme modalité anesthésique de premier choix. En ce qui concerne l'incision chirurgicale, la rachianesthésie était presque exclusivement utilisée pour les patientes bénéficiant d'une incision de Pfannenstiel et était rarement utilisée pour une incision transversale ou médiane supra- ou infra-ombilicale supérieure. L'incidence globale d'anesthésie générale était faible (7/396, 1,8 %). Le temps d'anesthésie, le temps chirurgical et le temps passé en salle d'opération ont presque doublé chez les patientes ayant un IMC ≥ 60,0 kg·m­2 par rapport à celles ayant un IMC de 40,0 à 49,9 kg·m­2. CONCLUSION: L'anesthésie neuraxiale a été utilisée avec succès chez environ 98 % des patientes atteintes d'obésité de classe 3 bénéficiant d'un accouchement par césarienne programmée. Le choix de la technique d'anesthésie régionale variait en fonction de l'augmentation de l'IMC et de l'incision chirurgicale prévue. Les temps procéduraux augmentaient avec l'augmentation de l'IMC. Ces informations devraient s'avérer utiles pour comparer les choix et les issues en matière d'anesthésie dans cette population difficile.

Anti-inflammatory potential of baicalein combined with silk fibroin protein in a zebrafish model (Danio rerio).

Baicalein (BA) is a flavonoid with wide-ranging pharmacological activity. However, its biological evaluation is hampered by its low solubility in aqueous medium, making forms of incorporation that improve its solubility necessary. In the present study, BA was combined with a solution of silk fibroin protein (SF), a biomaterial used too as a drug carrier, to evaluate the anti-inflammatory potential of this combination, in vivo, in an experimental model, zebrafish (Danio rerio). Baicalein-silk fibroin (BASF) improved the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging rate (95%) in comparison with BA in solution. The acute toxicity study and histopathological analysis in zebrafish showed that BASF has low cytotoxic potential, except for the maxim dose of 2000 mg/kg. The use of BA in combination with SF enhanced the anti-inflammatory effect of flavonoids by inducing inflammatory peritoneal edema through carrageenan and achieved 77.6% inhibition of abdominal edema at a dose of 75 mg/kg. The results showed that the BASF, significantly increases the bioavailability and therapeutic effect of flavonoids and several results observed in this study may help in the development of new drugs.

Phytocompounds from Amazonian Plant Species against Acute Kidney Injury: Potential Nephroprotective Effects.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury-caused by several factors, including ischemia, toxins, and inflammation-has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. This article is a brief review of phytocompounds with potential nephroprotective effects against acute kidney injury (AKI). The classes of Amazonian plant compounds with significant biological activity most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids, and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although with insufficiently explored potential, mainly in the face of AKI, a clinical condition with high morbidity and mortality.

Anti-Melanogenic Potential of Natural and Synthetic Substances: Application in Zebrafish Model.

Melanogenesis is a biosynthetic pathway for the formation of the pigment melanin in human skin. A key enzyme in the process of pigmentation through melanin is tyrosinase, which catalyzes the first and only limiting step in melanogenesis. Since the discovery of its methanogenic properties, tyrosinase has been the focus of research related to the anti-melanogenesis. In addition to developing more effective and commercially safe inhibitors, more studies are required to better understand the mechanisms involved in the skin depigmentation process. However, in vivo assays are necessary to develop and validate new drugs or molecules for this purpose, and to accomplish this, zebrafish has been identified as a model organism for in vivo application. In addition, such model would allow tracking and studying the depigmenting activity of many bioactive compounds, important to genetics, medicinal chemistry and even the cosmetic industry. Studies have shown the similarity between human and zebrafish genomes, encouraging their use as a model to understand the mechanism of action of a tested compound. Interestingly, zebrafish skin shares many similarities with human skin, suggesting that this model organism is suitable for studying melanogenesis inhibitors. Accordingly, several bioactive compounds reported herein for this model are compared in terms of their molecular structure and possible mode of action in zebrafish embryos. In particular, this article described the main metabolites of Trichoderma fungi, in addition to substances from natural and synthetic sources.

Effect of the Association of Fixed Oils from Abelmoschus esculentus (L.) Moench, Euterpe oleracea Martius, Bixa orellana Linné and Chronic SM® on Atherogenic Dyslipidemia in Wistar Rats.

Dyslipidemia presents high levels of serum cholesterol and is characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea oil (OFEO), A. esculentus oil (OFAE), B. orellana oil (OFBO), and Chronic SM® granules (CHR) are rich in bioactive compounds with the potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana, and Chronic SM® on Cocos nucifera L. saturated-fat-induced dyslipidemia. The chromatographic profile showed the majority presence of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol in OFBO and CHR was obtained. Treatments with OFEO, OFAE, OFBO, and CHR were able to significantly reduce glycemia, as well as hypertriglyceridemia, total cholesterol, and LDL-cholesterol, besides increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO, and CHR exhibit antidyslipidemic effects and antiatherogenic activity.

Intramuscular compatibility of an injectable anti-inflammatory nanodispersion from a standardized Bixa orellana oil (Chronic®): a toxicological study in Wistar rats.

Bixa orellana L. is a plant popularly known as "ucurum", "annatto", and "achiote". It is native to South America, and its seeds are an abundant source of geranylgeraniol and tocotrienols. Nanoencapsulation is a valuable technique that can decrease the drug needed to achieve an effect, decreasing potential toxicity, side effects and potentiate the anti-inflammatory effect. This study aimed to evaluate the acute toxicity of an intramuscular application of a nanodispersion containing a standardized extract from the seeds of Bixa orellana (NBO) in Wistar rats. The chemical evaluation showed δ-tocotrienol at 0.725 ± 0.062 mg/mL (72.6 ± 0.9%). The stability study showed the nanoparticles had an average size from 53.15 ± 0.64 to 59.9 ± 3.63 nm, with a polydispersity index ranging from 0.574 ± 0.032 to 0.574 ± 0.32, Zeta potential from 18.26 ± 0.59 to 19.66 ± 1.45 mV. After testing the intramuscular application of NBO with doses from 1 to 5 mg/kg in animals, it was observed that the acute treatment did not elicit any toxic effects within this range. The dose of 10 mg/kg, although not affecting hematological and biochemical parameters (CPK, LDH, myoglobin, AST, ALT, TC, TG, glucose levels, creatinine, and urea), could induce some muscle tissue changes, including leukocyte infiltration, morphological chances, and potentially necrosis. In conclusion, the results showed that the treatments devoided toxicity between 1 and 5 mg/kg.

Cadmium-mediated toxicity in plant cells is associated with the DCD/NRP-mediated cell death response.

Cadmium (Cd2+ ) is highly harmful to plant growth. Although Cd2+ induces programmed cell death (PCD) in plant cells, Cd2+ stress in whole plants during later developmental stages and the mechanism underlying Cd2+ -mediated toxicity are poorly understood. Here, we showed that Cd2+ limits plant growth, causes intense redness in leaf vein, leaf yellowing, and chlorosis during the R1 reproductive stage of soybean (Glycine max). These symptoms were associated with Cd2+ -induced PCD, as Cd2+ -stressed soybean leaves displayed decreased number of nuclei, enhanced cell death, DNA damage, and caspase 1 activity compared to unstressed leaves. Accordingly, Cd2+ -induced NRPs, GmNAC81, GmNAC30 and VPE, the DCD/NRP-mediated cell death signalling components, which execute PCD via caspase 1-like VPE activity. Furthermore, overexpression of the positive regulator of this cell death signalling GmNAC81 enhanced sensitivity to Cd2+ stress and intensified the hallmarks of Cd2+ -mediated PCD. GmNAC81 overexpression enhanced Cd2+ -induced H2 O2 production, cell death, DNA damage, and caspase-1-like VPE expression. Conversely, BiP overexpression negatively regulated the NRPs/GmNACs/VPE signalling module, conferred tolerance to Cd2+ stress and reduced Cd2+ -mediated cell death. Collectively, our data indicate that Cd2+ induces PCD in plants via activation of the NRP/GmNAC/VPE regulatory circuit that links developmentally and stress-induced cell death.

Distance decay 2.0 - A global synthesis of taxonomic and functional turnover in ecological communities.

Aim: Understanding the variation in community composition and species abundances (i.e., ß-diversity) is at the heart of community ecology. A common approach to examine ß-diversity is to evaluate directional variation in community composition by measuring the decay in the similarity among pairs of communities along spatial or environmental distance. We provide the first global synthesis of taxonomic and functional distance decay along spatial and environmental distance by analysing 148 datasets comprising different types of organisms and environments. Location: Global. Time period: 1990 to present. Major taxa studied: From diatoms to mammals. Method: We measured the strength of the decay using ranked Mantel tests (Mantel r) and the rate of distance decay as the slope of an exponential fit using generalized linear models. We used null models to test whether functional similarity decays faster or slower than expected given the taxonomic decay along the spatial and environmental distance. We also unveiled the factors driving the rate of decay across the datasets, including latitude, spatial extent, realm and organismal features. Results: Taxonomic distance decay was stronger than functional distance decay along both spatial and environmental distance. Functional distance decay was random given the taxonomic distance decay. The rate of taxonomic and functional spatial distance decay was fastest in the datasets from mid-latitudes. Overall, datasets covering larger spatial extents showed a lower rate of decay along spatial distance but a higher rate of decay along environmental distance. Marine ecosystems had the slowest rate of decay along environmental distances. Main conclusions: In general, taxonomic distance decay is a useful tool for biogeographical research because it reflects dispersal-related factors in addition to species responses to climatic and environmental variables. Moreover, functional distance decay might be a cost-effective option for investigating community changes in heterogeneous environments.

Probing the electronic structure and hydride occupancy in barium titanium oxyhydride through DFT-assisted solid-state NMR.

Perovskite-type oxhydrides such as BaTiO3-xHy exhibit mixed hydride ion and electron conduction and are an attractive class of materials for developing energy storage devices. However, the underlying mechanism of electric conductivity and its relation to the composition of the material remains unclear. Here we report detailed insights into the hydride local environment, the electronic structure and hydride conduction dynamics of barium titanium oxyhydride. We demonstrate that DFT-assisted solid-state NMR is an excellent tool for differentiating between the different feasible electronic structures in these solids. Our results indicate that upon reduction of BaTiO3 the introduced electrons are delocalized among all Ti atoms forming a bandstate. Furthermore, each vacated anion site is reoccupied by at most a single hydride, or else remains vacant. This single occupied bandstate structure persists at different hydrogen concentrations (y = 0.13-0.31) and a wide range of temperatures (∼100-300 K).

Oxytocin at Elective Cesarean Delivery: A Dose-Finding Study in Pregnant People With Twin Pregnancy.

BACKGROUND: Multiple pregnancy is associated with higher risk of uterine atony, postpartum hemorrhage (PPH), blood transfusion, hysterectomy, and death. The optimal dose of oxytocin at cesarean delivery in people with twin pregnancy is unknown. We sought to determine the effective bolus dose of oxytocin required to initiate adequate uterine tone in 90% of people (ED90) with twin pregnancy undergoing elective cesarean delivery. Our hypothesis was that the dose of oxytocin would be higher than 0.5 international units (IU) but lower than 5 IU. METHODS: A double-blind dose-finding study using the biased coin up-down method was undertaken in people with twin pregnancy ≥36 weeks gestational age undergoing elective cesarean delivery under neuraxial anesthesia. Those with additional risk factors for PPH, apart from twin pregnancy, were excluded. Oxytocin was administered as an intravenous bolus over 1 minute on delivery of the second fetus. The first patient received 0.5 IU, and subsequent oxytocin doses were administered according to a sequential allocation scheme. The actual doses administered were 0.5, 1, 2, 3, 4, and 5 IU of oxytocin. The primary outcome was the response defined as the satisfactory uterine tone at 2 minutes after completion of administration of the oxytocin bolus, as assessed by the operating obstetrician. Secondary outcomes included need for rescue uterotonic drugs, adverse effects, and estimated blood loss. The ED90 was estimated using the Dixon-Mood and the isotonic regression methods. RESULTS: Thirty patients were included in study. The estimated ED90 of oxytocin was 4.38 IU (95% confidence interval [CI], 3.68-4.86 IU) and 3.41 IU (95% CI, 2.83-3.98 IU) by the isotonic regression and Dixon-Mood methods, respectively. Seven patients had inadequate tone at the 2-minute evaluation point and required rescue uterotonic drugs. The median (interquartile range [IQR]) estimated blood loss was 1031 mL (732-1462 mL) calculated by the change in 24-hour hematocrit. Incidence of hypotension after oxytocin administration was 27%, nausea 30%, and vomiting 17%. CONCLUSIONS: Our results demonstrated that people with twin pregnancy require a much higher dose of oxytocin than those with singleton pregnancies. We recommended people with twin pregnancies should receive an initial 5 IU bolus over at least 1 minute when undergoing elective cesarean delivery under neuraxial anesthesia.

Hepatitis B virus genotypes and subgenotypes and the natural history and epidemiology of hepatitis B.

INTRODUCTION AND OBJECTIVES: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital. MATERIALS AND METHODS: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+)  and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. RESULTS: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. CONCLUSIONS: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively.

Programmed intermittent epidural bolus for labour analgesia: a randomized controlled trial comparing bolus delivery speeds of 125 mL·hr-1 versus 250 mL·hr-1.

PURPOSE: Programmed intermittent epidural bolus (PIEB) provides better analgesia for labour pain than continuous epidural infusion does. Nevertheless, commonly used PIEB regimens are associated with high sensory block. We hypothesized that a PIEB technique with slower bolus delivery speed would produce lower sensory levels. METHODS: We recruited term nulliparous women with singleton pregnancies during the first stage of labour. All participants had an American Society of Anesthesiologists Physical Status score of II-III, had epidural catheters placed at L3/4, and had epidural analgesia maintained with PIEB 10 mL every 40 min using 0.0625% bupivacaine with fentanyl 2 µg·mL-1. Women were randomized to receive PIEB delivered at 250 mL·hr-1 (G250) or 125 mL·hr-1 (G125). The study was completed six hours after the loading dose or at full cervical dilatation, whichever occurred first. The primary outcome was the presence of sensory block to ice ≥ T6 in at least one assessment during the study period (maximum six hours). RESULTS: We analyzed data from 90 women. The proportion of women presenting sensory block ≥ T6 at any time was not different between G125 and G250 groups (60.0% vs 64.4%; difference, -4.4%; 95% confidence interval [CI], -24.5 to 15.6; P = 0.66). The median [interquartile range] highest sensory block level was also not different between G125 and G250 groups (T6 [T7-T5] vs T5 [T7-T5], P = 0.39). Women in the G125 group had a lower incidence of hypotension than women in the G250 group did (11.1% vs 33.3%; difference, -22.2%; 95% CI, -38.8 to -5.67; P = 0.01). Quality of analgesia and patient satisfaction were not different between groups. CONCLUSION: The maintenance of epidural analgesia with a PIEB delivery speed of 125 mL·hr-1 did not produce lower sensory block levels when compared with 250 mL·hr-1. The slower injection speed regimen was associated with lower incidence of hypotension, but this secondary finding warrants confirmation in a future trial. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03236298); registered 1 August 2017.

RéSUMé: OBJECTIF: L'administration programmée intermittente de bolus périduraux (PIEB, pour programmed intermittent epidural bolus) fournit une meilleure analgésie pour la douleur du travail que l'analgésie péridurale par perfusion continue. Néanmoins, les régimes de PIEB couramment utilisés sont associés à un bloc sensoriel élevé. Nous avons émis l'hypothèse qu'une technique de PIEB avec une vitesse d'administration plus lente du bolus produirait des niveaux sensoriels inférieurs. MéTHODE: Nous avons recruté des femmes nullipares à terme ayant des grossesses uniques au cours de la première étape du travail obstétrical. Toutes les participantes avaient un score de statut physique II-III de l'American Society of Anesthesiologists, des cathéters périduraux placés au niveau L3/4 et une analgésie péridurale maintenue avec des PIEB de 10 mL de bupivacaïne 0,0625 % et de 2 µg·mL-1 de fentanyl, administrés toutes les 40 minutes. Les femmes ont été randomisées à recevoir des PIEB administrés à une vitesse de 250 mL·h-1 (G250) ou 125 mL·h-1 (G125). L'étude se terminait six heures après la dose de charge ou lors de la dilatation cervicale complète, selon la première éventualité. Le critère d'évaluation principal était la présence d'un bloc sensoriel à la glace ≥ T6 lors d'au moins une évaluation au cours de la période à l'étude (pour un maximum de six heures). RéSULTATS: Nous avons analysé les données de 90 femmes. La proportion de femmes présentant un bloc sensoriel ≥ T6 à tout moment n'était pas différente entre les groupes G125 et G250 (60,0 % vs 64,4 %; différence, -4,4 %; intervalle de confiance [IC] à 95 %, -24,5 à 15,6; P = 0,66). Le niveau médian [écart interquartile] le plus élevé de bloc sensoriel n'était pas non plus différent entre les groupes G125 et G250 (T6 [T7-T5] vs T5 [T7-T5], P = 0,39). Les femmes du groupe G125 avaient une incidence d'hypotension plus faible que les femmes du groupe G250 (11,1 % vs 33,3 %; différence, -22,2 %; IC 95 %, -38,8 à -5,67; P = 0,01). La qualité de l'analgésie et la satisfaction des patientes n'étaient pas différentes d'un groupe à l'autre. CONCLUSION: Le maintien de l'analgésie péridurale avec une vitesse d'administration des PIEB de 125 mL·h-1 n'a pas entraîné de taux de blocs sensoriels inférieurs par rapport à une vitesse de 250 mL·h-1. Le régime de vitesse d'injection plus lente a été associé à une incidence plus faible d'hypotension, mais cette constatation secondaire mérite d'être confirmée dans une étude future. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03236298); enregistrée le 1er août 2017.