Assessing the effects of oxytocin in changes of core body temperature during LPS-induced endotoxemia: A novel approach using Extended Poincaré Plot Analysis.

Oxytocin has shown cardioprotective effects during inflammation and may modify the core body temperature changes in LPS-induced endotoxemia. Notably, the time series analysis of core body temperature fluctuations may indicate thermoregulation alterations. This study aims to assess the effects of oxytocin on changes in the core body temperature by analyzing the fluctuations of the temperature time series of endotoxemic rats. Twelve hours of continuous core body temperature fluctuations time series were obtained from adult male Dark Agouti rats implanted with a telemetric transmitter under the following treatment: lipopolysaccharide (LPS); oxytocin (O); lipopolysaccharide + oxytocin (LPS + O), and vehicle or control (C). The temperature fluctuations time series were analyzed using the Extended Poincaré Plot Analysis (EPPA), a novel approach for measuring nonlinear features, to compute the autocorrelation by Pearson's correlation coefficient r, the standard deviation perpendicular to the line of identity (SD1), and the standard deviation parallel to the line of identity (SD2). The autocorrelation of the temperature fluctuations assessed by Pearson's coefficient was significantly higher in the LPS group compared to control rats (C). Likewise, the co-administration of oxytocin during endotoxemia (LPS + O) significantly reduced the autocorrelation and increased the short-term variability (SD1) of temperature fluctuations compared to those recorded with a single dose of LPS. Thus, we concluded that oxytocin may introduce thermoregulatory changes under LPS-induced endotoxemia. The EPPA is a simple and powerful approach to assess physiological variability that can provide valuable insights into changes in thermoregulation.

Histologic margin status is a predictor of relapse in lentigo maligna melanoma.

BACKGROUND: Most surgical margins for lentigo maligna melanomas reported in the literature are clinical and not histologic. OBJECTIVES: We sought to determine whether histologic margin status is an independent predictor of progression. METHODS: Clinicopathologic information of 268 invasive lentigo maligna melanomas diagnosed from 1990-2019 were analyzed. Statistical analyses were performed using Cox proportional hazards model and Boruta method. RESULTS: A total of 75% of the lesions were located on the head and neck. The range of follow-up for all patients was 0 to 31.8 years (median, 10.2 years). Time to local recurrence ranges from 0 to 20 years (median, 3 years). Progression developed in 54 (20.1%) of 268 patients. Local recurrence was seen only in 36 (13.4%), both local recurrence and subsequent metastasis in 7 (2.6%), and only metastasis in 11 (4.1%) of 268 patients. Histologic margin status (positive and close/<3 mm) and tumor site (head and neck location) significantly correlated with worse progression-free survival. LIMITATIONS: Single institution and retrospective study. CONCLUSIONS: Histologic margin status is the strongest predictor of progression for lentigo maligna melanoma. Patients with positive or close/<3 mm histologic margins should consider a re-excision due to the increased risk of relapse.

Design of Experiments to Compare the Mechanical Properties of Polylactic Acid Using Material Extrusion Three-Dimensional-Printing Thermal Parameters Based on a Cyber-Physical Production System.

The material extrusion 3D printing process known as fused deposition modeling (FDM) has recently gained relevance in the additive manufacturing industry for large-scale part production. However, improving the real-time monitoring of the process in terms of its mechanical properties remains important to extend the lifespan of numerous critical applications. To enhance the monitoring of mechanical properties during printing, it is necessary to understand the relationship between temperature profiles and ultimate tensile strength (UTS). This study uses a cyber-physical production system (CPPS) to analyze the impact of four key thermal parameters on the tensile properties of polylactic acid (PLA). Layer thickness, printing speed, and extrusion temperature are the most influential factors, while bed temperature has less impact. The Taguchi L-9 array and the full factorial design of experiments were implemented along with the deposited line's local fused temperature profile analysis. Furthermore, correlations between temperature profiles with the bonding strength during layer adhesion and part solidification can be stated. The results showed that layer thickness is the most important factor, followed by printing speed and extrusion temperature, with very close influence between each other. The lowest impact is attributed to bed temperature. In the experiments, the UTS values varied from 46.38 MPa to 56.19 MPa. This represents an increase in the UTS of around 17% from the same material and printing design conditions but different temperature profiles. Additionally, it was possible to observe that the influence of the parameter variations was not linear in terms of the UTS value or temperature profiles. For example, the increase in the UTS at the 0.6 mm layer thickness was around four times greater than the increase at 0.4 mm. Finally, even when it was found that an increase in the layer temperature led to an increase in the value of the UTS, for some of the parameters, it could be observed that it was not the main factor that caused the UTS to increase. From the monitoring conditions analyzed, it was concluded that the material requires an optimal thermal transition between deposition, adhesion, and layer solidification in order to result in part components with good mechanical properties. A tracking or monitoring system, such as the one designed, can serve as a potential tool for reducing the anisotropy in part production in 3D printing systems.

Stakeholder pressure and innovation capacity of SMEs in the COVID-19 pandemic: Mediating and multigroup analysis.

During environmental crises, it has always been particularly interesting to investigate how companies, specifically small- and mid-sized enterprises (SMEs), find solutions to survive and learn how to act in adverse situations. We conducted our study during the current coronavirus pandemic to analyse how stakeholder pressure affects both the innovation capabilities of SMEs and their firm performance. On the one hand, we examine whether the market and financial performance are better in the presence of less stakeholder pressure. On the other hand, we analyse whether SMEs implement internal mechanisms that enhance their innovation capacity to solve external problems caused by greater stakeholder pressure, which in turn affects firm performance. Our main findings show that during the pandemic, stakeholder pressure is related to the innovative capacity of SMEs; therefore, the higher the pressure, the more important the innovative response of SMEs. However, with higher pressure, the company's performance would be directly reduced in the short term, as the conditions set would be more unfavourable. Innovation capacity also plays a mediating role in preventing poor business performance because of increased stakeholder pressure. Owing to the importance of the chief executive officer (CEO) in SMEs, we test, through multigroup analysis, the differences based on the CEO's educational level. For example, commitment to innovation in SMEs may be more important for managers with higher education. Finally, our findings show how managers can learn to face new challenges in unfavourable environments.

Vaginal Microbiota Is Stable and Mainly Dominated by Lactobacillus at Third Trimester of Pregnancy and Active Childbirth: A Longitudinal Study of Ten Mexican Women.

In healthy women at reproductive age, the vaginal microbiota is mainly dominated by Lactobacillus bacteria during pregnancy and non-pregnancy stages. However, little is known about longitudinal changes within the vaginal microbiota composition from the third trimester of pregnancy to childbirth in healthy women. Thus, we conducted an exploratory longitudinal study of vaginal microbiota composition of 10 Mexican pregnant women, sampling from the same volunteer at two-time points: third trimester of pregnancy and active childbirth. Vaginal bacterial microbiota was characterized by V3-16S rDNA libraries by high-throughput sequencing and bioinformatics methods. Out of ten, vaginal microbiota from eight women was dominated by the Lactobacillus genus at both time points, whereas the other two women showed vaginal microbiota composition with high abundance of genera Gardnerella, Prevotella, and members of the Atopobiaceae family, without any preterm birth correlation. Importantly, we found no statistically significant differences in relative abundances, absolute reads count, alpha and beta diversity between the third trimester of pregnancy, and active childbirth time points. However, compared to the third trimester of pregnancy, we observed a trend with higher absolute reads counts for Gardnerella, Faecalibaculum, Ileibacterium, and Lactococcus genus at active childbirth and lower absolute reads count of Lactobacillus genus. Our results suggest that the vaginal microbiota composition is stable, and Lactobacillus genus is the dominant taxa in Mexican women's vagina at the third trimester of pregnancy and childbirth.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns in Northeast Mexico.

OBJECTIVE: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymatic disease worldwide and the prevalence is not well established because of the lack of screening. This study aimed to estimate the prevalence of G6PDd in a Hispanic population from Northeast Mexico. STUDY DESIGN: In this retrospective study, a database was used to analyze the G6PDd in neonates included in the expanded newborn metabolic screening of inherited metabolic disorders during a period of 4 years through the GSP Neonatal G6 kit (PerkinElmer). RESULTS: Among 96,152 (48,462 male) neonates screened for G6PD enzyme activity, a total of 566 (0.58%) cases were deficient for G6PD. Of those 566 patients, 469 (82.8%) attended the second test and the other 97 (17.2%) patients were lost. Of those 469 who did attend, 384 (81.9%) neonates were deficient in the second test and 85 (18.1%) were normal. With the data collected, 384 neonates were confirmed with G6PDd, 348 (88.6%) were male and 36 (11.4%) patients were female. The calculated prevalence for this population was 0.72 cases per 100 male newborns. CONCLUSION: The prevalence of G6PDd in the Northeastern Mexican population is high. Since migration is increasing in the United States, pediatricians should be aware of the need to search for G6PDd in newborns and the wide clinical manifestations they can present. KEY POINTS: · The calculated prevalence of glucose-6-phosphate dehydrogenase deficiency in Northeast Mexico is 3.99 cases per 1,000 newborns.. · Glucose-6-phosphate dehydrogenase deficiency screenings should be included in all newborn metabolic screenings.. · Glucose-6-phosphate dehydrogenase deficiency is a common erythroenzymopathy that must be addressed as a public health concern. To anticipate clinical complications, target population monitoring is required..

Seed and seedling interactions in three tree species from Mediterranean forests as a knowledge base for ecological restoration.

The ecosystems of the Mediterranean regions are severely threatened by human activity, and although we have made progress in physical restoration measures, little is known about the interactions between the plants of these biomes. The objective of this study is to contribute to document interactions between seeds and seedlings of three woody species native to Chile (P. chilensis, Q. saponaria and A. caven), which could be used for restoration actions (e.g., after forest fires). In a first experiment, we evaluated the germination response, the initial elongation and the interactions between the seedlings that germinate exposed to the chemical compounds of the other species. In a second experiment, we compared the survival and growth of seedlings in monospecific versus bispecific mixtures, using a substrate similar to that which is present after a wildfire. Seed extracts of teguments promoted germination of P. chilensis, but cotyledons and whole seed extracts inhibited germination of only one species, Q. saponaria, with very high intensity. The effects of the extracts on initial seedling elongation were more variable, including five inhibitions and one facilitation. Negative effects on germination and elongation included two cases of autotoxicity. The survival of seedlings grown in mixtures showed only two differences between monospecific and bispecific mixtures, both positive, constituting a reciprocal effect between two species. Only in one case was there a significant difference in seedling growth, which was root growth inhibition. Indeed, these results reveal an interaction between species, the type and intensity of which varies according to the condition of the seed or seedling. The negative effect found in seedling root growth reflects an allelopathic interaction that conditions a vital aspect for the establishment of these species, so this information is an opportunity to improve the establishment conditions in future reforestation projects, by avoiding particular species or promoting their proportion in plantation mixtures, either by planting or direct seeding.

Differences in the Asymmetry of Beat-to-Beat Fetal Heart Rate Accelerations and Decelerations at Preterm and Term Active Labor.

The fetal autonomic nervous system responds to uterine contractions during active labor as identified by changes in the accelerations and decelerations of fetal heart rate (FHR). Thus, this exploratory study aimed to characterize the asymmetry differences of beat-to-beat FHR accelerations and decelerations in preterm and term fetuses during active labor. In an observational study, we analyzed 10 min of fetal R-R series collected from women during active preterm labor (32-36 weeks of pregnancy, n = 17) and active term labor (38-40 weeks of pregnancy, n = 27). These data were used to calculate the Deceleration Reserve (DR), which is a novel parameter that quantifies the asymmetry of the average acceleration and deceleration capacity of the heart. In addition, relevant multiscale asymmetric indices of FHR were also computed. Lower values of DR, calculated with the input parameters of T = 50 and s = 10, were associated with labor occurring at the preterm condition (p = 0.0131). Multiscale asymmetry indices also confirmed significant (p < 0.05) differences in the asymmetry of FHR. Fetuses during moderate premature labor may experience more decaying R-R trends and a lower magnitude of decelerations compared to term fetuses. These differences of FHR dynamics might be related to the immaturity of the fetal cardiac autonomic nervous system as identified by this system response to the intense uterine activity at active labor.

A Computerized Bioinspired Methodology for Lightweight and Reliable Neural Telemetry.

Personalized health monitoring of neural signals usually results in a very large dataset, the processing and transmission of which require considerable energy, storage, and processing time. We present bioinspired electroceptive compressive sensing (BeCoS) as an approach for minimizing these penalties. It is a lightweight and reliable approach for the compression and transmission of neural signals inspired by active electroceptive sensing used by weakly electric fish. It uses a signature signal and a sensed pseudo-sparse differential signal to transmit and reconstruct the signals remotely. We have used EEG datasets to compare BeCoS with the block sparse Bayesian learning-bound optimization (BSBL-BO) technique-A popular compressive sensing technique used for low-energy wireless telemonitoring of EEG signals. We achieved average coherence, latency, compression ratio, and estimated per-epoch power values that were 35.38%, 62.85%, 53.26%, and 13 mW better than BSBL-BO, respectively, while structural similarity was only 6.295% worse. However, the original and reconstructed signals remain visually similar. BeCoS senses the signals as a derivative of a predefined signature signal resulting in a pseudo-sparse signal that significantly improves the efficiency of the monitoring process. The results show that BeCoS is a promising approach for the health monitoring of neural signals.

Phase Entropy Analysis of Electrohysterographic Data at the Third Trimester of Human Pregnancy and Active Parturition.

Phase Entropy (PhEn) was recently introduced for evaluating the nonlinear features of physiological time series. PhEn has been demonstrated to be a robust approach in comparison to other entropy-based methods to achieve this goal. In this context, the present study aimed to analyze the nonlinear features of raw electrohysterogram (EHG) time series collected from women at the third trimester of pregnancy (TT) and later during term active parturition (P) by PhEn. We collected 10-min longitudinal transabdominal recordings of 24 low-risk pregnant women at TT (from 35 to 38 weeks of pregnancy) and P (>39 weeks of pregnancy). We computed the second-order difference plots (SODPs) for the TT and P stages, and we evaluated the PhEn by modifying the k value, a coarse-graining parameter. Our results pointed out that PhEn in TT is characterized by a higher likelihood of manifesting nonlinear dynamics compared to the P condition. However, both conditions maintain percentages of nonlinear series higher than 66%. We conclude that the nonlinear features appear to be retained for both stages of pregnancy despite the uterine and cervical reorganization process that occurs in the transition from the third trimester to parturition.

Genetics of vascular malformation and therapeutic implications.

PURPOSE OF REVIEW: Vascular malformations (VaMs) are a consequence of disrupted morphogenesis that may involve arterial, capillary, venous, or lymphatic endothelium alone or in a combination. VaMs can have serious health impacts, leading to life-threatening conditions sometimes. Genetic mutations affecting proliferation, migration, adhesion, differentiation, and survival of endothelial cells, as well as integrity of extracellular matrix are believed to be the pathogenesis of these disorders. Here, we present an updated review of genetic mutations and potential therapeutic targets for VaMs. RECENT FINDINGS: Increased number of genetic mutations have been discovered in vascular anomalies via targeted deep sequencing. When a genetic defect is identified, it often presents in only a small percentage of cells within the malformation. In addition, mutations within the same gene may result in different clinical phenotypes. Management of VaMs can be challenging depending on the severity and functional impairment associated. There are no standard treatment algorithms available to date for VaMs, therefore the disorder has significant unmet clinical needs. Currently, the focus of therapeutic development is to target constitutively activated intracellular signaling pathways resulted from genetic mutations. SUMMARY: Knowledge about the genetic mutations and altered signaling pathways related to VaMs have improved our understanding about the pathogenesis of vascular anomalies and provided insights to the development of new targeted therapies.

Increased PON lactonase activity in morbidly obese patients is associated with impaired lipid profile.

AIMS: The paraoxonase-1 (PON1) enzyme could play an important role in the anti-oxidant capacity of high-density lipoprotein. However, there are no studies which analyse the evolution of the three activities of PON1 (PON arylesterase, PON paraoxonase and PON lactonase) after Roux-en-Y Gastric Bypass (RYGB) in morbidly obese subjects. We analysed the association of PON concentration and activities with the evolution of morbidly obese subjects who underwent RYGB, and its relationship with biochemical variables and different atherogenic indices. METHODS: Twenty-seven non-obese and 82 morbidly obese subjects were studied before and 6 months after RYGB. RESULTS: Before RYGB, morbidly obese subjects had a lower PON1 concentration (P < 0.05) and higher PON lactonase activity (P < 0.001) than non-obese subjects, with no differences in PON arylesterase and PON paraoxonase activities. After RYGB, PON1 concentration (P < 0.05) and PON lactonase activity (P < 0.001) decreased with regard to the presurgery state. PON lactonase activity correlated with the atherogenic index of plasma before (r = 0.19, P = 0.047) and after RYGB (r = 0.27, P = 0.035). In different multiple lineal regression analysis models, presurgery PON lactonase activity was associated with total cholesterol (ß = 0.909, P < 0.001), LDL (ß = 0.632, P = 0.006) and DBP (ß = 0.230, P = 0.030) (R2  = 0.295), postsurgery PON lactonase activity was associated with esterified cholesterol (ß = 0.362, P = 0.011) (R2  = 0.131), and the change (Δ) in PON lactonase activity after RYGB was associated with Δesterified cholesterol (ß = 0.304, P = 0.030) (R2  = 0.093). CONCLUSIONS: PON lactonase activity is associated with the presence of morbid obesity and with an impaired lipid profile. All associations found could indicate the relationship between PON lactonase activity and the development of atherosclerosis.

High density of M2-macrophages in acral lentiginous melanoma compared to superficial spreading melanoma.

AIMS: Acral lentiginous melanoma (ALM) is the most common type of melanoma in people with darker skin phototypes. There is some evidence that the aetiology, pathogenesis, risk factors and natural history of ALM differ from those of superficial spreading melanoma (SSM). ALM behaves more aggressively than SSM, but the biological explanation for these differences remains unknown. The presence of one subtype of macrophages, termed M2-macrophage (M2-M), has been found to be related to local progression, metastasis and poor prognosis in several neoplasms. The aim of this study was to compare the density of M2-Ms in ALMs versus SSMs, and to examine whether or not the density of M2-Ms is associated with histopathological features predictive of adverse prognosis in cutaneous melanoma (CM), as well as development of metastasis. METHODS AND RESULTS: Sixty-seven ALMs and 67 SSMs cases were analysed. The tumours were classified according to thickness, ulceration, mitosis and metastasis. M2-M quantity was evaluated using immunohistochemistry with anti-CD163 and anti-CD206 antibodies. M2-Ms were increased in ALM compared with SSM, and were related to the histopathological features predictive of adverse prognosis in CM, such as thickness > 1.0 mm, ulceration and mitotic activity, and the development of metastasis. CONCLUSIONS: Our study is the first, to our knowledge, to demonstrate the increased presence of M2-Ms in ALM compared with SSM. Our findings suggest that the increased M2-Ms in ALM are associated with the main histopathological features predictive of adverse prognosis in CM, as well as the presence of metastasis, and that these cells can be related to the aggressive behaviour seen in ALMs.

Near-infrared spectroscopic models for analysis of winter pea (Pisum sativum L.) quality constituents.

BACKGROUND: Winter pea (Pisum sativum L.) grows well in a wide geographic region, both as a forage and cover crop. Understanding the quality constituents of this crop is important for both end uses; however, analysis of quality constituents by conventional wet chemistry methods is laborious, slow and costly. Near infrared reflectance spectroscopy (NIRS) is a precise, accurate, rapid and cheap alternative to using wet chemistry for estimating quality constituents. We developed and validated NIRS calibration models for constituent analysis of this crop. RESULTS: Of the 11 constituent models developed, nine constituents including moisture, dry-matter, total-nitrogen, crude protein, acid detergent fiber, neutral detergent fiber, AD-lignin, cellulose and non-fibrous carbohydrate had low standard errors and a high coefficient of determination (R2 = 0.88-0.98; 1 - VR, which is the coefficient of determination during cross-validation = 0.77-0.92) for both calibration and cross-validation, indicating their potential for quantitative predictability. The calibration models for ash (R2 = 0.65; 1 - VR = 0.46) and hemicellulose (R2 = 0.75; 1 - VR = 0.50) also appeared to be adequate for qualitative screening. Predictions of an independent validation set yielded reliable agreement between the NIRS predicted values and the reference values with low standard error of prediction (SEP), low bias, high coefficient of determination (r2 = 0.82-0.95), high ratios of performance to deviation (RPD = SD/SEP; 2.30-3.85) and high ratios of performance to interquartile distance (RPIQ = IQ/SEP; 2.57-7.59) for all 11 constituents. CONCLUSION: Precise, accurate and rapid analysis of winter pea for major forage and cover crop quality constituents can be performed at a low cost using the NIRS calibration models developed. © 2018 Society of Chemical Industry.

Women Serum Concentrations of the IL-10 Family of Cytokines and IFN-γ Decrease from the Third Trimester of Pregnancy to Active Labor.

Labor is regarded as increased myometrial activity with a regular contractility pattern. At this final stage of pregnancy, myometrial quiescence is lost, accompanied by altered immune homeostasis. It is well known that the interleukin (IL)-10 family of cytokines modulates immunological responses mainly in epithelial cells, including the endometrium. To investigate their inflammatory profile during labor, we performed a longitudinal study in a group of healthy pregnant women (n = 20) with uncomplicated pregnancies in the third trimester of pregnancy and during active labor. Blood was sampled from pregnant women in the third trimester (gestational age 32-38 weeks, mean 36 ± 2 weeks) and during active labor (39-41 weeks of gestation, mean 40 ± 1 weeks). Serum levels of several cytokines were measured using multiplex immunoassays for both stages, indicating that the concentrations of IL-10, IL-20, IL-22, IL-28A, and interferon (IFN)-γ were significantly decreased during active labor in comparison with third-trimester levels (p < 0.05). Our analysis did not find significant correlations between IL-10, IL-20, IL-22, IL-28A, and IFN-γ levels and gestational age. However, our data suggest that the systemic downregulation of several members of the IL-10 family of cytokines plays an important role in the activation of myometrial smooth cells associated with uterine contractions during active labor. Downregulation of this IL-10 family of cytokines seems to coincide with the well-reported functional progesterone withdrawal during labor. Likewise, lower plasma IFN-γ concentrations may indicate a role for IFN-γ in active labor.

The pro-/anti-inflammatory effects of different fatty acids on visceral adipocytes are partially mediated by GPR120.

PURPOSE: This study examines whether G-protein coupled receptor 120 (GPR120) is involved in the pro-/anti-inflammatory effects of different types of fatty acids (FAs) in human visceral adipocytes, and whether these effects may be altered in obesity, a state with a chronic inflammation. METHODS: Pro-/anti-inflammatory effects of palmitic, oleic, linoleic and docosahexaenoic acids on human visceral adipocytes were tested in mature adipocytes from non-obese and morbidly obese (MO) subjects. Also, the effects of these FAs were tested when the GPR120 gene was silenced. RESULTS: In adipocytes from non-obese subjects, palmitic and linoleic acids increased TNF-α and IL-6 mRNA expression (p < 0.05), and decreased IL-10 and adiponectin expression (p < 0.05). However, oleic and docosahexaenoic acids (DHA) produced the opposite effect (p < 0.05). In adipocytes from MO subjects, all FAs used increased TNF-α and IL-6 expression (p < 0.05). Palmitic and linoleic acids decreased IL-10 and adiponectin expression (p < 0.05), but oleic acid and DHA did not have significant effects. Only oleic acid increased adiponectin expression (p < 0.05). The effects of FAs on TNF-α, IL-6, IL-10 and adiponectin expression in non-obese and MO subjects were significantly annulled when the GPR120 gene was silenced in visceral adipocytes differentiated from human mesenchymal stem cells. CONCLUSIONS: FAs are capable of directly acting on visceral adipocytes to modulate differently TNF-α, IL-6, IL-10 and adiponectin expression, with a different and greater effect in MO subjects. These effects are largely annulled when GPR120 expression was silenced, which suggests that they could be mediated by GPR120.

Secretion of biologically active human interleukin 22 (IL-22) by Lactococcus lactis.

Interleukin-22 (IL-22) participates in the modulation of innate immunity and inflammation. This cytokine has important therapeutic potential, such as with ulcerative colitis, liver and lung injury, and infection, in different animal models. We generated a Lactococcus lactis strain that secretes human IL-22 under the regulation of the nisin-inducible promoter. Identification and secretion of this cytokine was demonstrated using western blots of culture supernatants from IL-22-expressing bacteria. The recombinant IL-22 protein produced by L. lactis was biologically active as determined by its ability to induce IL-10 secretion when co-cultured with a colon epithelial cell line in vitro. We consider this novel strain a promising live vaccine for various therapeutic applications.

Pupil reflex as a marker of activity and prognosis in heart failure: a longitudinal and prospective study.

AIMS: Compensatory mechanisms in heart failure (HF) are triggered to maintain adequate cardiac output. Among them, hyperactivation of the sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS, and we can evaluate it through pupillometry. The aim of the study was to compare the differences in pupillary reflex between patients with acute HF and controls and to analyse whether these differences in pupillary reflex may offer a new and easy prognostic factor in such patients. METHODS AND RESULTS: We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 h after admission and prior to discharge. The results were compared with those of a group of 100 healthy volunteers who also underwent pupillometry. The maximum baseline pupil size (MBPS) and the minimum pupil diameter (MPD) were measured. Patients with decompensated HF have a higher MBPS (3.64 ± 0.81) and higher MPD (2.60 ± 0.58) than HF patients at discharge and in the control group (P-value = 0.01 and 0.01, respectively). Also, HF patients presented an improvement in pupillometric values at discharge [MBPS (3.47 ± 0.79) and MPD (2.51 ± 0.58)] and showed no differences compared with the control group [MBPS (3.34 ± 0.82) and MPD (2.40 ± 0.53)] (P-value = 0.19 and 0.14, respectively). In addition, MBPS provides a good independent predictor of in-hospital and 1 month mortality in patients admitted with HF. Six patients (5.61%) died during hospital admission, and 11 patients (10.2%) died in the first month after discharge. Also, four patients (3.74%) were readmitted within 1 month of discharge. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality through MBPS was 0.823. No patient with an MBPS < 3.7 mm died. The ROC curve for predicting combined mortality or readmission within the first month for MBPS was 0.698. CONCLUSIONS: Pupillometry may be a new, non-invasive, and simple tool to determine the status of SNS, help in the prognostic stratification of acute HF patients, and improve therapeutic management.

Well-defined Cu(I) complexes based on [N,P]-pyrrole ligands catalyzed a highly endoselective 1,3-dipolar cycloaddition.

We herein report the synthesis and catalytic application of a new family of dinuclear Cu(I) complexes based on [N,P]-pyrrole ligands. The Cu(I) complexes (4a-d) were obtained in good yields and their catalytic properties were evaluated in the1,3-dipolar cycloaddition of azomethine ylides and electron-deficient alkenes. The air-stable complexes 4a-d exhibited high endo-diasteroselectivity to obtain substituted pyrrolidines, and the catalytic system showed excellent reactivity and wide substitution tolerance.

Analysis of fetal heart rate fluctuations in women diagnosed with preeclampsia during the latent phase of labor.

Introduction: Fetal heart rate variability (fHRV) is a tool used to investigate the functioning of the fetal autonomic nervous system. Despite the significance of preeclampsia, fHRV during the latent phase of labor has not been extensively studied. This study aimed to evaluate fetal cardiac autonomic activity by using linear and nonlinear indices of fHRV analysis in women diagnosed with preeclampsia without hypertensive treatment during gestation, compared to normotensive women during the latent phase of labor. Methods: A cross-sectional and exploratory study was conducted among pregnant women in the latent phase of labor, forming three study groups: normotensive or control (C, 38.8 ± 1.3 weeks of pregnancy, n = 22), preeclampsia with moderate features (P, 37.6 ± 1.4 weeks of pregnancy n = 10), and preeclampsia with severe features (SP, 36.9 ± 1.2 weeks of pregnancy, n = 12). None of the participants received anti-hypertensive treatment during their pregnancy. Linear and nonlinear features of beat-to-beat fHRV, including temporal, frequency, symbolic dynamics, and entropy measures, were analyzed to compare normotensive and preeclamptic groups. Results: Significantly lower values of multiscale entropy (MSE) and short-term complexity index (Ci) were observed in the preeclamptic groups compared to the C group (p < 0.05). Additionally, higher values of SDNN (standard deviation of R-R intervals) and higher values of low-frequency power (LF) were found in the P group compared to the C group. Conclusion: Our findings indicate that changes in the complexity of fetal heart rate fluctuations may indicate possible disruptions in the autonomic nervous system of fetuses in groups affected by undiagnosed preeclampsia during pregnancy. Reduced complexity and shifts in fetal autonomic cardiac activity could be associated with preeclampsia's pathophysiological mechanisms during the latent phase of labor.