Ligilactobacillus salivarius V4II-90 eradicates Group B Streptococcus colonisation during pregnancy: a randomised, double-blind, placebo-controlled trial.

Group B Streptococcus (GBS) is the leading cause of bacterial neonatal sepsis. This study aimed to confirm the effect of Ligilactobacillus salivarius V4II-90 on GBS colonisation during pregnancy. A randomised, multicentre, double-blind, placebo-controlled, parallel-group study was conducted in seven hospitals in Madrid, Spain. The sample was broken down into two groups with 20 participants each (n = 40) in order to show reduced GBS colonisation frequency in the probiotic versus the placebo group. Pregnant participants positive for vaginal-rectal colonisation before or during the 13th week of gestation were randomly assigned to either the placebo or the probiotic group. The probiotic, L. salivarius V4II-90 at 1 × 109 cfu/day was administered for 12 weeks, starting at week 21-23 of gestation. The primary outcome was the percentage of participants with vaginal and/or rectal GBS colonisation at the end of the intervention period (35 weeks of gestation). Secondary outcomes were changes in the microbial composition of vaginal and rectal exudates; premature delivery; premature rupture of membranes; intrapartum antibiotics; new-borns with early or late-onset GBS sepsis; adverse events (AEs); and GBS test results performed at the hospital at week 35 of gestation. Of the 481 participants included, 44 were vaginal-rectal colonised with GBS and randomised. 43 completed the study (20 in the probiotic group and 23 in the placebo group). After intervention, GBS was eradicated in six participants (27%) from the placebo group and in twelve participants (63%) from the probiotic group ( P = 0.030). None of the 185 AEs reported were identified as possibly, probably, or definitely related to the investigational product. In conclusion, oral administration of L. salivarius V4II-90 is a safe and successful strategy to significantly decrease the rates of GBS colonisation at the end of pregnancy and, therefore, to reduce the exposure of subjects and their infants to intrapartum antibiotic prophylaxis. Trial registered at ClinicalTrials.gov: number NCT03669094.

Ecological disturbance alters the adaptive benefits of social ties.

Extreme weather events radically alter ecosystems. When ecological damage persists, selective pressures on individuals can change, leading to phenotypic adjustments. For group-living animals, social relationships may be a mechanism enabling adaptation to ecosystem disturbance. Yet whether such events alter selection on sociality and whether group-living animals can, as a result, adaptively change their social relationships remain untested. We leveraged 10 years of data collected on rhesus macaques before and after a category 4 hurricane caused persistent deforestation, exacerbating monkeys' exposure to intense heat. In response, macaques demonstrated persistently increased tolerance and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival after the hurricane, but not before it, revealing a shift in the adaptive function of sociality.

Axion Paradigm with Color-Mediated Neutrino Masses.

We propose a generalized Kim-Shifman-Vainshtein-Zakharov-type axion framework in which colored fermions and scalars act as two-loop Majorana neutrino-mass mediators. The global Peccei-Quinn symmetry under which exotic fermions are charged solves the strong CP problem. Within our general proposal, various setups can be distinguished by probing the axion-to-photon coupling at helioscopes and haloscopes. We also comment on axion dark-matter production in the early Universe.

A Study of PLA Thin Film on SS 316L Coronary Stents Using a Dip Coating Technique.

The dip coating process is one of the recognized techniques used to generate polymeric coatings on stents in an easy and low-cost way. However, there is a lack of information about the influence of the process parameters of this technique on complex geometries such as stents. This paper studies the dip coating process parameters used to provide a uniform coating of PLA with a 4-10 µm thickness. A stainless-steel tube (AISI 316L) was laser-cut, electropolished, and dip-coated in a polylactic acid (PLA) solution whilst changing the process parameters. The samples were characterized to examine the coating's uniformity, thickness, surface roughness, weight, and chemical composition. FTIR and Raman investigations indicated the presence of PLA on the stent's surface, the chemical stability of PLA during the coating process, and the absence of residual chloroform in the coatings. Additionally, the water contact angle was measured to determine the hydrophilicity of the coating. Our results indicate that, when using entry and withdrawal speeds of 500 mm min-1 and a 15 s immersion time, a uniform coating thickness was achieved throughout the tube and in the stent with an average thickness of 7.8 µm.

Natural disaster alters the adaptive benefits of sociality in a primate.

Weather-related disasters can radically alter ecosystems. When disaster-driven ecological damage persists, the selective pressures exerted on individuals can change, eventually leading to phenotypic adjustments. For group-living animals, social relationships are believed to help individuals cope with environmental challenges and may be a critical mechanism enabling adaptation to ecosystems degraded by disasters. Yet, whether natural disasters alter selective pressures on patterns of social interactions and whether group-living animals can, as a result, adaptively change their social relationships remains untested. Here, we leveraged unique data collected on rhesus macaques from 5 years before to 5 years after a category 4 hurricane, leading to persistent deforestation which exacerbated monkeys' exposure to intense heat. In response, macaques increased tolerance for and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival for 5 years after the hurricane, but not before it, revealing a clear shift in the adaptive function of social relationships in this population. We demonstrate that an extreme climatic event altered selection on sociality and triggered substantial and persistent changes in the social structure of a primate species. Our findings unveil the function and adaptive flexibility of social relationships in degraded ecosystems and identify natural disasters as potential evolutionary drivers of sociality. One-Sentence Summary: Testard et al. show that a natural disaster altered selection on sociality in group-living primates triggering persistent changes in their social structure.

Ultra-fast track extubation protocol following cardiovascular surgery: Predictors of failure and outcomes.

OBJECTIVES: Identifying independent predictor factors of failure of ultra-fast track (UFT) extubation and to compare in-hospital outcomes with UFT extubation versus fast track (FT) extubation after cardiovascular surgery in adults. MATERIAL AND METHODS: Retrospective analysis of 1498 consecutive patients aged over 18 years-old undergoing cardiovascular surgery at a single institution. Between December 2014 and December 2016, FT extubation was used (N = 713) while, between December 2016 and December 2018, all patients were preoperatively considered suitable for UFT extubation (N = 785). In this instance, a standardized anaesthetic protocol was applied in all cases. The decision to not extubate in the operating room (OR) was based on intraoperative haemodynamic and ventilation. RESULTS: Extubation in the OR was possible in 699 (89%) patients. Significant independent predictors factors of UFT extubation failure were: preoperative NYHA class III-IV, myocardial infarction within two days prior to surgery, preoperative intra-aortic balloon counterpulsation, urgent/emergent surgery, intraoperative transfusion of platelets and intraoperative inotropic and vasopressor support. UFT extubation was associated with lower rates of cardiovascular complications such as congestive cardiac insufficiency (OR: 1,57; 95% CI: 1,13-2,19; p = 0,008) and new-onset postoperatory atrial fibrillation (OR: 1,40; 95% CI: 1,06-1,86; p = 0,020). Patient extubated in the OR presented lower risk of overall complications, shorter intensive care unit stay and higher short-term survival, although, no statistically significance was found when performing the multivariate adjustment. CONCLUSIONS: A routine immediate extubation in the OR following adult cardiovascular surgery is a feasible and safe practice, associated with low cardiovascular morbidity.

Protocolo de extubación ultra-fast track tras cirugía cardiovascular: predictores de fracaso y resultados / Ultra-fast track extubation protocol following cardiovascular surgery: Predictors of failure and outcomes

Objetivos: Identificar los factores predictores independientes de fracaso de la extubación ultra-fast track (UFT) y comparar los resultados hospitalarios de la extubación UFT frente a la extubación fast track en pacientes adultos sometidos a cirugía cardiovascular. Material y métodos: Análisis retrospectivo de 1.498 pacientes consecutivos mayores de 18 años sometidos a cirugía cardiovascular en un solo centro. Entre diciembre 2014 y diciembre 2016 se utilizó la extubación fast track (n=713), mientras que, entre diciembre 2016 y diciembre 2018 todos los pacientes fueron considerados preoperatoriamente aptos para extubación UFT (n=785). En este caso se empleó el mismo protocolo anestésico estandarizado en todos los pacientes. La decisión de extubar o no en quirófano se basó exclusivamente en parámetros hemodinámicos y ventilatorios. Resultados: La extubación en quirófano fue posible en 699 (89%) pacientes. Los factores predictores independientes de fracaso de la extubación UFT fueron: clase funcional preoperatoria iii-iv de la NYHA, infarto agudo de miocardio dentro de los 2 días previos a la cirugía, balón de contrapulsación intraaórtico preoperatorio, cirugía urgente o emergente, transfusión intraoperatoria de plaquetas y soporte intraoperatorio con fármacos inotrópicos y vasopresores. La extubación UFT se asoció con una menor tasa de complicaciones cardiovasculares, como insuficiencia cardiaca congestiva (OR: 1,57; IC 95%: 1,13-2,19; p=0,008) y fibrilación auricular postoperatoria de novo (OR: 1,40; IC 95%: 1,06-1,86; p=0,020). Los pacientes extubados en quirófanos presentaron un menor riesgo de complicaciones globales, menor estancia en la UCI y mayor supervivencia a corto plazo, aunque no se encontraron diferencias estadísticamente significativas al realizarse el ajuste multivariante. Conclusiones: La extubación inmediata rutinaria en quirófano tras cirugía cardiovascular en adultos es una...(AU)

Objectives: Identifying independent predictor factors of failure of ultra-fast track (UFT) extubation and to compare in-hospital outcomes with UFT extubation versus fast track (FT) extubation after cardiovascular surgery in adults. Material and methods: Retrospective analysis of 1,498 consecutive patients aged over 18 years-old undergoing cardiovascular surgery at a single institution. Between December 2014 and December 2016, FT extubation was used (N=713) while, between December 2016 and December 2018, all patients were preoperatively considered suitable for UFT extubation (N=785). In this instance, a standardized anaesthetic protocol was applied in all cases. The decision to not extubate in the operating room (OR) was based on intraoperative haemodynamic and ventilation. Results: Extubation in the OR was possible in 699 (89%) patients. Significant independent predictors factors of UFT extubation failure were: preoperative NYHA class III-IV, myocardial infarction within two days prior to surgery, preoperative intra-aortic balloon counterpulsation, urgent/emergent surgery, intraoperative transfusion of platelets and intraoperative inotropic and vasopressor support. UFT extubation was associated with lower rates of cardiovascular complications such as congestive cardiac insufficiency (OR: 1,57; 95% CI: 1,13-2,19; P=0,008) and new-onset postoperatory atrial fibrillation (OR: 1,40; 95% CI: 1,06-1,86; P=0,020). Patient extubated in the OR presented lower risk of overall complications, shorter intensive care unit stay and higher short-term survival, although, no statistically significance was found when performing the multivariate adjustment. Conclusions: A routine immediate extubation in the OR following adult cardiovascular surgery is a feasible and safe practice, associated with low cardiovascular morbidity.(AU)

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis, and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation.

Influence of nitric oxide signaling mechanisms in cancer.

Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.

Design, fabrication, characterization and reliability study of CMOS-MEMS Lorentz-force magnetometers.

This article presents several design techniques to fabricate micro-electro-mechanical systems (MEMS) using standard complementary metal-oxide semiconductor (CMOS) processes. They were applied to fabricate high yield CMOS-MEMS shielded Lorentz-force magnetometers (LFM). The multilayered metals and oxides of the back-end-of-line (BEOL), normally used for electronic routing, comprise the structural part of the MEMS. The most important fabrication challenges, modeling approaches and design solutions are discussed. Equations that predict the Q factor, sensitivity, Brownian noise and resonant frequency as a function of temperature, gas pressure and design parameters are presented and validated in characterization tests. A number of the fabricated magnetometers were packaged into Quad Flat No-leads (QFN) packages. We show this process can achieve yields above 95 % when the proper design techniques are adopted. Despite CMOS not being a process for MEMS manufacturing, estimated performance (sensitivity and noise level) is similar or superior to current commercial magnetometers and others built with MEMS processes. Additionally, typical offsets present in Lorentz-force magnetometers were prevented with a shielding electrode, whose efficiency is quantified. Finally, several reliability test results are presented, which demonstrate the robustness against high temperatures, magnetic fields and acceleration shocks.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment. PATIENTS AND METHODS: Patients (n = 124) with advanced biliary tract cancer (ABC) received cisplatin/gemcitabine with cediranib or placebo (ABC-03 trial). Concentrations of pTie2 were measured longitudinally from before treatment until disease progression. Data from patients with ovarian cancer (n = 92, ICON7 trial) and patients with colorectal cancer (CRC) (n = 70, Travastin trial) were also included. RESULTS: Cediranib-treated ABC patients were deconvoluted into distinct groups where in one group pTie2 trajectories resembled those seen in placebo-treated patients and in another pTie2 significantly reduced (t-test P = 2.7 × 10-14). Using the 95% confidence interval for these two groups, we defined a vascular complete response (vCR) as a 24% reduction in pTie2 within 9 weeks; vascular no response (vNR) as a 7% increase in pTie2, and a vascular partial response (between these limits). vCR cediranib-treated patients had significantly improved progression-free survival (8.8 versus 7.5 months, restricted mean ratio 0.73, P = 0.012) and overall survival (18.8 versus 12.1 months, hazard ratio 0.49, P = 0.02). By integrating data across ovarian cancer, CRC and ABC, we show that (i) patients with vNR do not benefit from VEGFi and (ii) Tie2-defined vascular progression occurs sufficiently in advance of radiological progressive disease that changes in treatment could be offered to prevent clinical deterioration. CONCLUSION: pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.

ESMO Congress 2021: highlights from the EORTC gastrointestinal tract cancer group's perspective.

There has been no major change of practice in gastrointestinal oncology at the European Society for Medical Oncology (ESMO) symposium 2021, but confirmation that immunotherapy in combination with chemotherapy has become standard of care in several indications. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Track Cancer Group has selected important phase II and III trials presented during the symposium across all gastrointestinal cancers as well as early reports on new drugs or new combinations that may change practice in the future.