Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration.

Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48-LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN- LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN- LT-HSCs. Emcn-/- and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn-/- LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn-/- or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.

Pd-imidate@SBA-15: a multifunctional heterogeneous catalyst for the aqueous room temperature hydrogenation of CO2 to formic acid.

The incorporation of hydrophilic and basic sites from phosphotriazaadamantane and saccharine in a water-soluble Pd complex and the subsequent confinement into mesoporous silica support increases the activity and stability of the palladium catalytic species for the room-temperature aqueous hydrogenation of either bicarbonate or CO2 into formic acid. The use of low Pd loadings (<0.1mmolPd·g-1) of the well-dispersed complex on SBA-15 mesoporous silica allows performing the reaction under room temperature, and aqueous conditions, exhibiting TON of ca. 40-100, for the CO2 or bicarbonate hydrogenation, respectively, which is one order of magnitude higher than the homogeneous case, allowing the easy isolation and recycling of the solid catalyst.

When to sleep and consume caffeine to boost alertness.

STUDY OBJECTIVES: Sleep loss can cause cognitive impairments that increase the risk of mistakes and accidents. However, existing guidelines to counteract the effects of sleep loss are generic and are not designed to address individual-specific conditions, leading to sub-optimal alertness levels. Here, we developed an optimization algorithm that automatically identifies sleep schedules and caffeine-dosing strategies to minimize alertness impairment due to sleep loss for desired times of the day. METHODS: We combined our previous algorithms that separately optimize sleep or caffeine to simultaneously identify the best sleep schedules and caffeine doses that minimize alertness impairment at desired times. The optimization algorithm uses the predictions of the well-validated Unified Model of Performance to estimate the effectiveness and physiological feasibility of a large number of possible solutions and identify the best one. To assess the optimization algorithm, we used it to identify the best sleep schedules and caffeine-dosing strategies for four studies that exemplify common sleep-loss conditions and compared the predicted alertness-impairment reduction achieved by using the algorithm's recommendations against that achieved by following the U.S. Army caffeine guidelines. RESULTS: Compared to the alertness-impairment levels in the original studies, the algorithm's recommendations reduced alertness impairment on average by 63%, an improvement of 24 percentage points over the U.S. Army caffeine guidelines. CONCLUSIONS: We provide an optimization algorithm that simultaneously identifies effective and safe sleep schedules and caffeine-dosing strategies to minimize alertness impairment at user-specified times.

STEAP2 promotes hepatocellular carcinoma progression via increased copper levels and stress-activated MAP kinase activity.

Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) belongs to a family of metalloreductases, which indirectly aid in uptake of iron and copper ions. Its role in hepatocellular carcinoma (HCC) remains to be characterized. Here, we report that STEAP2 expression was upregulated in HCC tumors compared with paired adjacent non-tumor tissues by RNA sequencing, RT-qPCR, Western blotting, and immunostaining. Public HCC datasets demonstrated upregulated STEAP2 expression in HCC and positive association with tumor grade. Transient and stable knockdown (KD) of STEAP2 in HCC cell lines abrogated their malignant phenotypes in vitro and in vivo, while STEAP2 overexpression showed opposite effects. STEAP2 KD in HCC cells led to significant alteration of genes associated with extracellular matrix organization, cell adhesion/chemotaxis, negative enrichment of an invasiveness signature gene set, and inhibition of cell migration/invasion. STEAP2 KD reduced intracellular copper levels and activation of stress-activated MAP kinases including p38 and JNK. Treatment with copper rescued the reduced HCC cell migration due to STEAP2 KD and activated p38 and JNK. Furthermore, treatment with p38 or JNK inhibitors significantly inhibited copper-mediated cell migration. Thus, STEAP2 plays a malignant-promoting role in HCC cells by driving migration/invasion via increased copper levels and MAP kinase activities. Our study uncovered a novel molecular mechanism contributing to HCC malignancy and a potential therapeutic target for HCC treatment.

Decrease in platelet count in patients with AKI and its association with major adverse kidney events.

INTRODUCTION: A reduction in platelet count in critically ill patients is a marker of severity of the clinical condition. However, whether this association holds true in acute kidney injury (AKI) is unknown. We analyzed the association between platelet reduction in patients with AKI and major adverse kidney events (MAKE). METHODS: In this retrospective cohort, we included AKI patients at the Hospital Civil of Guadalajara, in Jalisco, Mexico. Patients were divided according to whether their platelet count fell >21% during the first 10 days. Our objectives were to analyze the associations between a platelet reduction >21% and MAKE at 10 days (MAKE10) or at 30-90 days (MAKE30-90) and death. RESULTS: From 2017 to 2023, 400 AKI patients were included, 134 of whom had a > 21% reduction in platelet count. The mean age was 54 years, 60% were male, and 44% had sepsis. The mean baseline platelet count was 194 x 103 cells/µL, and 65% of the KDIGO3 patients met these criteria. Those who underwent hemodialysis (HD) had lower platelet counts. After multiple adjustments, a platelet reduction >21% was associated with MAKE10 (OR 4.2, CI 2.1-8.5) but not with MAKE30-90. The mortality risk increased 3-fold (OR 2.9, CI 1.1-7.7, p = 0.02) with a greater decrease in the platelets (<90 x 103 cells/µL). As the platelets decreased, the incidence of MAKE was more likely to increase. These associations lost significance when accounting for starting HD. CONCLUSION: In our retrospective cohort of patients with AKI, a > 21% reduction in platelet count was associated with MAKE. Our results are useful for generating hypotheses and motivating us to continue studying this association with a more robust design.

A reduction in platelet count in critically ill patients has been associated with a worse prognosis, but it is not yet known whether this relationship also exists in patients with acute kidney injury, who are more susceptible to platelet decrease due to the syndrome or due to the onset of hemodialysis. In our study of acute kidney injury patients, we found that those whose platelet count decreased >21% during the first days were more likely to experience a major kidney event. In addition, the greater the decrease in platelet count was, the more likely these events were to occur. The significance of this association was lost in patients who start hemodialysis. Our conclusions could serve to generate hypotheses about this interesting relationship.

Description and Evaluation of Dye and Contrast Media Distribution of Ultrasound-Guided Rectus Sheath Block in Cat Cadavers.

The rectus sheath block is an ultrasound-guided anaesthetic technique which aims to provide analgesia to the abdominal midline. This study aimed to assess the distribution of 0.4 mL kg-1 of a mixture of methylene blue and iopromide injected into each hemiabdomen in the internal rectus sheath in cat cadavers. We hypothesise that this technique would be feasible and would cover the rami ventrales of the last thoracic and the first lumbar spinal nerves. The study was divided into two phases. Phase 1 aimed to study the anatomical structures of the ventral abdominal wall (four cats were dissected). Phase 2 (ten cadavers) consisted of an ultrasound-guided injection of the mixture mentioned above and the assessment of its distribution by computed tomography and anatomical dissection. The results showed the staining of the cranioventral abdominal wall with a craniocaudal spread of four (three to eight) vertebral bodies. Methylene blue stained three (one to four) rami ventrales, affecting T10 (60%), T11 (100%), T12 (90%), T13 (50%) and L1 (5%). Based on these results, it could be stated that this technique could supply anaesthesia to the midline of the abdominal midline cranial to the umbilicus in clinical patients, but it may not be able to provide anaesthesia to the middle and caudal midline abdominal region.

Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells.

ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. In this study, we first evaluated the effect of extracellular ATP depletion with apyrase in SKOV-3, a cell line derived from metastatic ovarian carcinoma. We observed a decrease in cell migration and an increase in transepithelial electrical resistance and cell markers, suggesting a role in maintaining a mesenchymal phenotype. To identify the P2 receptor that mediated the effects of ATP, we compared the transcript levels of some P2 receptors and found that P2RX7 is three-fold higher in SKOV-3 cells than in a healthy cell line, namely HOSE6-3 (from human ovarian surface epithelium). Through bioinformatic analysis, we identified a higher expression of the P2RX7 transcript in metastatic tissues than in primary tumors; thus, P2X7 seems to be a promising effector for the malignant phenotype. Subsequently, we demonstrated the presence and functionality of the P2X7 receptor in SKOV-3 cells and showed through pharmacological approaches that its activity promotes cell migration and contributes to maintaining a mesenchymal phenotype. P2X7 activation using BzATP increased cell migration and abolished E-cadherin expression. On the other hand, a series of P2X7 receptor antagonists (A438079, BBG and OxATP) decreased cell migration. We used a CRISPR-based knock-out system directed to P2RX7. According to the results of our wound-healing assay, SKOV3-P2X7KO cells lacked receptor-mediated calcium mobilization and decreased migration. Altogether, these data let us propose that P2X7 receptor is a regulator for cancer cell migration and thus a potential drug target.

SGLT2i treatment during AKI and its association with major adverse kidney events.

Background: The association between the administration of sodium-glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known. Methods: This retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30-90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed. Results: From 2021 to 2023, 374 patients were included in the study-316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45-2.56]) or with MAKE30-90 (OR 0.76 [0.42-1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01-0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM (p ≤ 0.05 for all). Conclusion: The use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment.

Influences of a Supplemental Blend of Essential Oils Plus 25-Hydroxy-Vit-D3 and Zilpaterol Hydrochloride (ß2 Agonist) on Growth Performance and Carcass Measures of Feedlot Lambs Finished under Conditions of High Ambient Temperature.

Forty-eight Pelibuey × Katahdin male intact lambs (25.12 ± 3.79 kg LW) were used in a 70-d growing-finishing trial. Dietary treatments consisted of total mixed corn-based diet supplemented with: (1) no feed additives (Control); (2) 150 mg of essential oils blend plus 0.10 mg of 25-hydroxy-Vit-D3/kg diet offered throughout the 70-d experimental period (EOD3); (3) Control diet fed during the first 35 days and zilpaterol hydrochloride (ZH) supplementation at 6 mg/kg diet offered during the final 35 days of the experiment (32 days with ZH with a withdrawal 3-d before harvest), and (4) basal diet supplemented with EOD3 during first 35 days finishing, and EOD3 in combination with ZH (EOD3 + ZH) during the subsequent 32-days with ZH withdrawal 3 days before harvest. The temperature-humidity index during the experiment averaged 80.4 ± 3.2. There were no treatment interactions (p > 0.20) on growth performance and carcass measures. Supplemental EOD3 did not affect (p = 0.43) dry matter intake (DMI), but increased (p < 0.01) carcass adjusted average daily gain (ADG, 9.2%), gain efficiency (GF, 6.7%), and observed vs. expected dietary net energy for maintenance (NEm, 4.8%) and for gain (NEg, 6.4%). Supplemental ZH did not affect dry matter intake (DMI, p = 0.50) but increased (p < 0.01) carcass adjusted ADG (14.5%), GF (13%) and observed vs. expected dietary NEm (9%) and NEg (11.7%). Compared to control lambs, the combination of both additives increased ADG (24.9%), GF (21.2%), and observed vs. expected dietary NEm and NEg (14.2% and 18.9%, respectively). There were no treatment interactions on carcass characteristics, visceral organ mass, or on gene expression of IGF1, IGF2 and mTOR in longissimus muscle (LM). Supplemental EOD3 increased hot carcass weight (HCW; 4.0%, p < 0.01) but did not affect other carcass measures. Supplemental EOD3 decreased (3%, p = 0.03) intestine mass weight (g intestine/kg empty body weight). Supplemental ZH increased HCW (6%, p < 0.01), dressing percentage (1.7%, p = 0.04), and LM area (9.7%, p < 0.01), and decreased kidney-pelvic-fat percentage (16.2%, p < 0.01), fat thickness (14.7%, p = 0.03), and visceral fat. Compared to controls, the combination of EOD3 with ZH increased HCW (10.2%). It is concluded that growth performance responses to supplemental EOD3 and ZH are additive. Both supplements can be fed in combination without detrimental effects on expected benefits when fed separately. In addition, ZH supplementation improves carcass traits.

Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients.

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients. Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCC in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Additionally, serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. The TERT promoter mutation frequency was also remarkably high in the Hispanic cohort. Cell cycles and liver functions were identified as positively- and negatively-enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in the serum samples of HCC patients. Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. The subtype with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. It also had higher levels of immune checkpoint and immune exhaustion markers. Conclusions: Our study revealed some specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management of HCC and provides a unique resource for studying Hispanic HCC.

Evaluation of Cognitive Performance in Patients with Fibromyalgia Syndrome: A Case-Control Study.

Patients with fibromyalgia syndrome tend to report deficits in cognitive functions; however, there is no clear consensus on which cognitive domains are impaired. The aim of this study was to compare the differences in cognitive performance between a group of patients with fibromyalgia syndrome and a group of pain-free subjects controlling for the covariables anxiety, depression, and sleep quality. In total, 130 patients with fibromyalgia syndrome and 111 pain-free subjects with an average age of 54.96 years completed the evaluation protocol consisting of sociodemographic data, psychological data, and neurocognitive tests. All data were collected from May 2022 to May 2023. Multivariate analyses of covariance (MANCOVAs) were conducted to assess intergroup differences in all neurocognitive tests. MANCOVA analyses showed that the group of patients with fibromyalgia showed a worse cognitive performance than the group of pain-free subjects after controlling for anxiety, depression, and sleep quality. This study found that fibromyalgia patients exhibited worse cognitive performance and executive function than pain-free subjects. Thus, cognitive performance seems to not be related with anxiety, depression, or sleep quality in our sample of women with FMS.

Has the balloon really burst? Analysis of "the UK-REBOA randomized clinical trial".

BACKGROUND: Uncontrolled hemorrhagic shock is a leading cause of early death after injury. Resuscitative endovascular balloon occlusion of the aorta (REBOA) represents a paradigm shift in achieving hemodynamic stability and its implementation still remain controversial in different settings. The recently published UK-REBOA Randomized Clinical Trial aimed to determine the effectiveness of REBOA in patients with hemorrhagic shock, concluding its increased mortality compared with standard care alone. METHODS: An adjustment of the statistical analysis was performed and a comprehensive analysis was proposed to address the study's limitations and demonstrate that these conclusions cannot be considered as benchmarks. RESULTS: Primary and secondary outcomes were analyzed using Bayesian logistic regression and generalized linear models suitable for the outcome distribution. No statistically significant differences were observed between the two groups for the primary outcome (p-value 0.3341) nor in most of the secondary outcomes. The results of the principal stratum analyses (to account for intercurrent events) also did not show significant differences after the statistical analysis tests. CONCLUSION: It cannot be stated that REBOA increases mortality compared with standard care alone in trauma patients with exsanguinating hemorrhage. Further studies and adequate simulation training programs in REBOA are critical to its successful implementation within a trauma system and to identify the optimum settings and patients.

Assessing the negative impact of chlorantraniliprole, isoxaflutole, and simazine pesticides on phospholipid membrane models and tilapia gill tissues.

The indiscriminate and, very often, incorrect use of pesticides in Brazil, as well as in other countries, results in severe levels of environmental pollution and intoxication of human life. Herein, we studied plasma membrane models (monolayer and bilayer) of the phospholipid Dioleoyl-sn-glycerol-3-phosphocholine (DOPC) using Langmuir films, and large (LUVs) and giant (GUVs) unilamellar vesicles, to determine the effect of the pesticides chlorantraniliprole (CLTP), isoxaflutole (ISF), and simazine (SMZ), used in sugarcane. CLTP affects the lipid organization of the bioinspired models of DOPC π-A isotherms, while ISF and SMZ pesticides significantly affect the LUVs and GUVs. Furthermore, the in vivo study of the gill tissue in fish in the presence of pesticides (2.0 × 10-10 mol/L for CLTP, 8.3 × 10-9 mol/L for ISF, and SMZ at 9.9 × 10-9 mol/L) was performed using optical and fluorescence images. This investigation was motivated by the gill lipid membranes, which are vital for regulating transporter activity through transmembrane proteins, crucial for maintaining ionic balance in fish gills. In this way, the presence of phospholipids in gills offers a model for understanding their effects on fish health. Histological results show that exposure to CLTP, ISF, and SMZ may interfere with vital gill functions, leading to respiratory disorders and osmoregulation dysfunction. The results indicate that exposure to pesticides caused severe morphological alterations in fish, which could be correlated with their impact on the bioinspired membrane models. Moreover, the effect does not depend on the exposure period (24h and 96h), showing that animals exposed to pesticides for a short period suffer irreparable damage to gill tissue. In summary, we can conclude that the harm caused by pesticides, both in membrane models and in fish gills, occurs due to contamination of the aquatic system with pesticides. Therefore, water quality is vital for the preservation of ecosystems.

Coexistent HCN4 and GATA5 Rare Variants and Atrial Fibrillation in a Large Spanish Family.

BACKGROUND: Familial association of atrial fibrillation (AF) can involve single gene variants related to known arrhythmogenic mechanisms; however, genome-wide association studies often disclose complex genetic variants in familial and nonfamilial AF, making it difficult to relate to known pathogenetic mechanisms. METHODS: The finding of 4 siblings with AF led to studying 47 members of a family. Long-term Holter monitoring (average 298 hours) ruled out silent AF. Whole-exome sequencing was performed, and variants shared by the index cases were filtered and prioritised according to current recommendations. HCN4 currents (IHCN4) were recorded in Chinese hamster ovary cells expressing human p.P1163H or native HCN4 channels with the use of the patch-clamp technique, and topologically associating domain analyses of GATA5 variant were performed. RESULTS: The clinical study diagnosed 2 more AF cases. Five family members carried the heterozygous p.P1163H HCN4 variant, 14 carried the intronic 20,61040536,G,A GATA5 rare variant, and 9 carried both variants (HCN4+GATA5). Five of the 6 AF cases (onset age ranging from 33 to 70 years) carried both variants and 1 carried the GATA5 variant alone. Multivariate analysis showed that the presence of HCN4+GATA5 variants significantly increased AF risk (odds ratio 32.7, 95% confidence interval 1.8-591.4) independently from age, hypertension, and overweight. Functional testing showed that IHCN4 generated by heterozygous p.P1163H were normal. Topologically associating domain analysis suggested that GATA5 could affect the expression of many genes, including those encoding microRNA-1. CONCLUSION: The coincidence of 2 rare gene variants was independently associated with AF, but functional studies do not allow the postulation of the arrhythmogenic mechanisms involved.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Effect of heat stress during the dry period on milk yield and reproductive performance of Holstein cows.

This study aimed to determine the influence of heat stress during the dry period on milk yield and reproductive performance of Holstein cows in a hot environment. Breeding and milk production records of cows, as well as meteorological data between 2017 and 2020 from a commercial dairy herd (n = 12,102 lactations), were used to determine the relationship between climatic conditions during the dry period (average of the temperature-humidity index (THI) at the beginning, middle, and end of the dry period) and reproductive efficiency and milk yield traits. THI was divided into < 70 (no heat stress), 70-80 (moderate heat stress), and > 80 (severe heat stress). First-service pregnancy rate of cows decreased (P < 0.01) with increasing hyperthermia during the dry period (9.5, 7.3, and 3.4% for THI < 70, 70-80, and > 80, respectively). All-service pregnancy rate was highest (P < 0.01) for cows not undergoing heat stress during the dry period (60.2%) and lowest (42.6%) for cows with severe heat stress during the dry period. Cows not experiencing heat stress during the dry period required a mean ± SD of 5.6 ± 3.8 services per pregnancy compared with 6.5 ± 3.6 (P < 0.01) for cows subjected to THI > 80 during the dry period. Cows not suffering heat stress during the dry period produced more (P < 0.01) 305-day milk (10,926 ± 1206 kg) than cows subjected to moderate (10,799 ± 1254 kg) or severe (10,691 ± 1297 kg) heat stress during the dry period. Total milk yield did not differ (P > 0.10) between cows not undergoing heat stress (13,337 ± 3346 kg) and cows subjected to severe heat stress during the dry period (13,911 ± 4018 kg). It was concluded that environmental management of dry cows during hot months is warranted to maximize reproductive performance and milk yield in the following lactation.

Cytotoxicity Activity of Some meso-Dihydroguaiaretic Acid Derivatives and Mode of Action of the Most Active Compound.

The aim of this study was to screen sixteen meso-1 semi-synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF-7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 µM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 µM, the aminoether derivative meso-11 and the esther derivative meso-20 against A549 (44.15±0.78 %) and MCF-7 (41.60±0.92 %), respectively. Then, it was determined the IC50 value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso-11 showed potent cytotoxicity against A549 (IC50 =17.11±2.11 µM), whereas it resulted more cytotoxic against the LL-47 lung normal cell line (IC50 =9.49±1.19 µM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso-20 exhibited potent activity against MCF-7 (IC50 =18.20±1.98 µM), whereas it displayed moderate cytotoxicity against the MCF-10 breast normal cell line (IC50 =41.22±2.17 µM) with a SI of 2.2. Finally, studies on the mechanism of action of meso-20 indicated disruption of MCF-7 plasma membrane in vitro and the AMPK activation in silico.

Can we rely on wearable sleep-tracker devices for fatigue management?

STUDY OBJECTIVES: Wearable sleep-tracker devices are ubiquitously used to measure sleep; however, the estimated sleep parameters often differ from the gold-standard polysomnography (PSG). It is unclear to what extent we can tolerate these errors within the context of a particular clinical or operational application. Here, we sought to develop a method to quantitatively determine whether a sleep tracker yields acceptable sleep-parameter estimates for assessing alertness impairment. METHODS: Using literature data, we characterized sleep-measurement errors of 18 unique sleep-tracker devices with respect to PSG. Then, using predictions based on the unified model of performance, we compared the temporal variation of alertness in terms of the psychomotor vigilance test mean response time for simulations with and without added PSG-device sleep-measurement errors, for nominal schedules of 5, 8, or 9 hours of sleep/night or an irregular sleep schedule each night for 30 consecutive days. Finally, we deemed a device error acceptable when the predicted differences were smaller than the within-subject variability of 30 milliseconds. We also established the capability to estimate the extent to which a specific sleep-tracker device meets this acceptance criterion. RESULTS: On average, the 18 sleep-tracker devices overestimated sleep duration by 19 (standard deviation = 44) minutes. Using these errors for 30 consecutive days, we found that, regardless of sleep schedule, in nearly 80% of the time the resulting predicted alertness differences were smaller than 30 milliseconds. CONCLUSIONS: We provide a method to quantitatively determine whether a sleep-tracker device produces sleep measurements that are operationally acceptable for fatigue management.

Brazilian airway surgery survey indicates low overall numbers and need for improved teaching skills.

OBJECTIVES: The Brazilian Society of Thoracic Surgeons conducted an online survey to determine the number of surgeons that perform adult and paediatric airway surgery and to understand the practice patterns along the country. METHODS: Active members were electronically invited to complete the questionnaire through the REDCapR platform. Invitations were sent from January to April 2020. The survey encompassed 40 questions that explored 4 different topics in the assessment of tracheal diseases: (i) surgeon's demography; (ii) institutional profile, (iii) education and training in laryngo-tracheal surgery and (iv) preoperative and postoperative evaluation. RESULTS: Eighty-nine percentage of the responders declared to perform tracheal surgery with a median of 5 tracheal resection procedures per year [interquartile range (IQR) 3-12]. Interaction with other specialties occurs in 37.3% of cases. Access to technology and devices is highly variable across the country. Resident training in airway surgery consists in traditional lectures in 97% of the cases. Training in animals (15.2%), cadavers (12.1%) and simulators (6.1%) are rare. Preoperatory evaluation encompasses flexible bronchoscopy (97.8%) and/or computed tomography (CT) scan of the airways (90.6%). Swallowing (20.1%) and voice (14.4%) disorders are rarely evaluated. Eighty-nine percentage of the surgeons consider bronchoscopy to be the preoperatory gold-standard exam, followed by CT scan (38.8%) and CT-3D reconstruction (37.4%). CONCLUSIONS: Brazilian surgeons refer that airway resection and reconstruction are part of their current practice, but the total number of procedures per surgeon per year is low. Access to high-end technology and equipment is heterogenous. Training offered to residents in most academic institutions relies on traditional lectures.

Modified Ultrasound-Guided Dorsal Quadratus Lumborum Block in Cat Cadavers.

The quadratus lumborum (QL) block is an ultrasound-guided locoregional anesthesia technique which aims to provide analgesia to the abdomen. The main objective of this study was to assess a modified ultrasound-guided dorsal QL block in cat cadavers. For this purpose, a volume of 0.4 mL kg-1 of a mixture of iopromide and methylene blue was administered between the psoas minor muscle and the vertebral body (VB) of the first lumbar vertebra, and its distribution was assessed in thirteen cat cadavers. We hypothesized that this injection point would be feasible, offering a more cranial distribution of the injectate and a more consistent staining of the truncus sympathicus. The study was divided into two phases. Phase 1 consisted of an anatomical study (three cadavers were dissected). Phase 2 consisted of the ultrasound-guided administration of the injectate and the assessment of its distribution by computed tomography and anatomical dissection. The results showed a consistent distribution of contrast media within five (4-8) VBs from T10 to L5. Methylene blue stained three (2-6) rami ventrales, affecting T11 (10%), T12 (20%), T13 (60%), L1 (85%), L2 (95%) and L3 (65%). The truncus sympathicus was dyed in all cadavers with a spread of five (3-7) VBs. Finally, the splanchnicus major nerve was stained in all cadavers (100%). These results suggest that this technique could provide analgesia to the abdominal viscera and the abdominal wall, probably with the exception of the cranial aspects of the abdominal wall.