Relevant results from the NA48 experiment

We report relevant results from NA48 experiment at CERN SPS. NA48 was proposed in 1990 \cite{proposal} to study direct CP violation in $K^0\to\pi\pi$ to a level of accuracy sufficient to resolve the inconclusive status left by the previous measurements performed by NA31 \cite{NA31} and E731 \cite{E731}. In 2002 NA48 published the final result \cite{NA48epsoeps}. Small modification to the experimental setup have allowed NA48 to go forward with an extensive investigation of $K^0$ rare decays and hyperon decays. Some results are already available and reported here together with the final CP violation measurement.Comment: 3 pages, 1 eps figure, XXIII Physics in collisio

The influence of light attenuation on the biogeomorphology of a marine karst cave: a case study of Puerto Princesa Underground River, Palawan, the Philippines

Karst caves are unique biogeomorphological systems. Cave walls offer habitat for microorganisms which in-turn have a geomorphological role via their involvement in rock weathering, erosion and mineralisation. The attenuation of light with distance into caves is known to affect ecology, but the implications of this for biogeomorphological processes and forms have seldom been examined. Here we describe a semi-quantitative microscopy study comparing the extent, structure, and thickness of biocover and depth of endolithic penetration for samples of rock from the Puerto Princesa Underground River system in Palawan, the Philippines, which is a natural UNESCO World Heritage Site. Organic growth at the entrance of the cave was abundant (100% occurrence) and complex, dominated by phototrophic organisms (green microalgae, diatoms, cyanobacteria, mosses and lichens). Thickness of this layer was 0.28 ± 0.18 mm with active endolith penetration into the limestone (mean depth = 0.13 ± 0.03 mm). In contrast, phototrophs were rare 50 m into the cave and biofilm cover was significantly thinner (0.01 ± 0.01 mm, p < 0.000) and spatially patchy (33% occurrence). Endolithic penetration here was also shallower (< 0.01 mm, p < 0.000) and non-uniform. Biofilm was found 250 m into the cave, but with a complete absence of phototrophs and no evidence of endolithic bioerosion. We attribute these findings to light-induced stress gradients, showing that the influence of light on phototroph abundance has knock-on consequences for the development of limestone morphological features. In marine caves this includes notches, which were most well-developed at the sheltered cave entrance of our study site, and for which variability in formation rates between locations is currently poorly understood

Fat-free noncontrast whole-heart CMR with fast and power-optimized off-resonant water excitation pulses

Background: Cardiovascular MRI (CMR) faces challenges due to the interference of bright fat signals in visualizing anatomical structures. Effective fat suppression is crucial when using whole-heart CMR. Conventional methods often fall short due to rapid fat signal recovery and water-selective off-resonant pulses come with tradeoffs between scan time and RF energy deposit. A lipid-insensitive binomial off-resonant (LIBOR) RF pulse is introduced, addressing concerns about RF energy and scan time for CMR at 3T. Methods: A short LIBOR pulse was developed and implemented in a free-breathing respiratory self-navigated whole-heart sequence at 3T. A BORR pulse with matched duration, as well as previously used LIBRE pulses, were implemented and optimized for fat suppression in numerical simulations and validated in healthy subjects (n=3). Whole-heart CMR was performed in healthy subjects (n=5) with all four pulses. The SNR of ventricular blood, skeletal muscle, myocardium, and subcutaneous fat, and the coronary vessel sharpness and length were compared. Results: Experiments validated numerical findings and near homogeneous fat suppression was achieved with all pulses. Comparing the short pulses (1ms), LIBOR reduced the RF power two-fold compared with LIBRE, and three-fold compared with BORR, and LIBOR significantly decreased overall fat SNR. The reduction in RF duration shortened the whole-heart acquisition from 8.5min to 7min. No significant differences in coronary arteries detection and sharpness were found when comparing all four pulses. Conclusion: LIBOR enabled whole-heart CMR under 7 minutes at 3T, with large volume fat signal suppression, while reducing RF power compared with LIBRE and BORR. LIBOR is an excellent candidate to address SAR problems encountered in CMR where fat suppression remains challenging and short RF pulses are required.Comment: 25 pages, 7 figures, 2 table

Tautomeric equilibrium in condensed phases

We present an ab initio molecular dynamics (MD) investigation of the tautomeric equilibrium for aqueous solutions of glycine and acetone at realistic experimental conditions. Metadynamics is used to accelerate proton migration among tautomeric centers. Due to the formation of complex water-ion structures involved the proton dynamics in the aqueous environment, standard enhanced sampling approaches may face severe limitations in providing a general description of the phenomenon. Recently, we developed a set of Collective Variables (CVs) designed to study protons transfer reactions in complex condensed systems [Grifoni et al. PNAS, 2019, 116(10), 4054-4057]. In this work we applied this approach to study proton dissociation dynamics leading to tautomeric interconversion of biologically and chemically relevant prototypical systems, namely glycine and acetone in water. Although relatively simple from a chemical point of view, the results show that even for these small systems complex reaction pathways and non-trivial conversion dynamics are observed. The generality of our method allows obtaining these results without providing any prior information on the dissociation dynamics but only the atomic species that can exchange protons in the process. Our results agree with literature estimates and demonstrate the general applicability of this method in the study of tautomeric reactions

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

The role of antioxidants in the interplay between oxidative stress and senescence

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches

The Potential Role of Gut Microbiota in Alzheimer’s Disease: from Diagnosis to Treatment

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease