Decoding bladder state from pudendal intraneural signals in pigs.

Neuroprosthetic devices used for the treatment of lower urinary tract dysfunction, such as incontinence or urinary retention, apply a pre-set continuous, open-loop stimulation paradigm, which can cause voiding dysfunctions due to neural adaptation. In the literature, conditional, closed-loop stimulation paradigms have been shown to increase bladder capacity and voiding efficacy compared to continuous stimulation. Current limitations to the implementation of the closed-loop stimulation paradigm include the lack of robust and real-time decoding strategies for the bladder fullness state. We recorded intraneural pudendal nerve signals in five anesthetized pigs. Three bladder-filling states, corresponding to empty, full, and micturition, were decoded using the Random Forest classifier. The decoding algorithm showed a mean balanced accuracy above 86.67% among the three classes for all five animals. Our approach could represent an important step toward the implementation of an adaptive real-time closed-loop stimulation protocol for pudendal nerve modulation, paving the way for the design of an assisted-as-needed neuroprosthesis.

Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

The effect of organic matter fractions on micropollutant ozonation in wastewater effluents.

Organic matter (OM) is the most important factor influencing the effectivity and efficiency of micropollutant (MP) ozonation in wastewater effluents. The importance of the quantity of OM is known, because of this, total organic carbon (TOC) is generally used to determine the required ozone dose for any water sample. Still, the effect of OM type on MP ozonation is not well understood. In this study, effluents from five wastewater treatment plants were collected and the organic matter in these effluents was fractionated using membranes (F1-4) and resin (HI, HOA, HON and HOB). Fractions were diluted to the same TOC concentration, spiked with MPs and ozonated at three ozone doses. Our results show that all five effluents had comparable OM compositions and similar MP removal, confirming the suitability of OM quantity (TOC) to compare the ozone requirements for wastewater effluents. From the 19 analysed MPs, three groups were identified that showed similar removal behaviour. The strongest differences between the groups were observed around MP ozone reactivities of 102, 104 and 106 M-1 s-1. This indicates the presence of three OM groups in the samples that interfere with the removal of different MPs. MP removal in the resin fraction HON were higher for MPs with high and medium ozone reactivity, indicating a low interference of OM in this fraction with MP ozonation. OM in the resin fractions HOA and HI showed higher interference with MP ozonation. Therefore, removing the HOA and HI fractions prior to ozonation would result in a lower required ozone dose and a more efficient removal of the MPs. MP removal correlated with the OM characteristics A300, SR and fluorescence component comp 2. These characteristics can be used as inline tools to predict the required ozone dose in water treatment plants.

Heart rhythm characterization during sudden cardiac death in dogs.

INTRODUCTION/OBJECTIVES: Inherited or acquired arrhythmic disorders and cardiac disease have been associated with sudden cardiac death (SCD) in dogs. The electrical mechanism related to death in most of these cases is unknown. This retrospective study aimed to describe arrhythmic events in dogs that experienced SCD during Holter monitoring. ANIMALS, MATERIALS AND METHODS: Nineteen client-owned dogs that experienced SCD during Holter examination were included. Clinical records from a Holter service database were reviewed, and both the rhythm preceding death and the dominant rhythm causing SCD were analysed. Clinical data, Holter diaries and echocardiographic diagnosis were also evaluated. RESULTS: Structural heart disease was identified in 12/19 dogs (dilated cardiomyopathy in five dogs, arrhythmogenic right ventricular cardiomyopathy in four dogs, myxomatous mitral valve disease in two dogs, and suspected myocarditis in one dog), five of which had concurrent congestive heart failure. Sudden cardiac death was related to ventricular premature complexes or monomorphic ventricular tachycardia degenerating into ventricular fibrillation in 42% of dogs, polymorphic ventricular tachycardia, or torsade de pointes-like inducing ventricular fibrillation in 21%, and asystole or presumptive agonal pulseless electrical activity triggered by malignant bradyarrhythmias in 37%. CONCLUSIONS: The most common rhythm associated with SCD in our population of dogs was ventricular tachycardia leading to ventricular fibrillation, although bradyarrhythmia-related SCD, possibly related to inappropriate vagal reflexes, was also a notable cause.

Affective evaluation of food images according to stimulus and subject characteristics.

BACKGROUND: The food-rich environment in which we live makes the regulation of food choices a very complex phenomenon determined by many factors, as well as their interactions. Much evidence suggests that the sensory perception of food can be considered as a central factor affecting individual food choices. Despite this, the approaches used to study the various food aspects usually do not distinguish between different types of food. METHODS: In the present study, a large and heterogeneous sample of 1149 participants aged 7-90 years was asked to judge food images that were labelled differently (i.e. Raw versus Cooked, Natural versus Transformed and Simple versus Complex) with respect to arousal, valence, typicality and familiarity. RESULTS: We observed that, across food dimensions (i.e., Raw versus Cooked, Natural versus Transformed and Simple versus Complex), arousal, valence and typicality judgments were principally affected by a subjective hunger level and gender (and their interaction) and, to a lesser extent, by age. CONCLUSIONS: As a whole, our findings suggest that the level of transformation (which includes cooking) and the complexity of a foodstuff could at least partially affect food processing, entailing that future research should also address these features.

Pharmacokinetics and pharmacodynamics (PK/PD) of irbesartan in Beagle dogs after oral administration at two dose rates.

Irbesartan (Irb) is an angiotensin II type 1 receptor antagonist widely used in humans to treat hypertension. Age-related diseases such as hypertension are increasingly being diagnosed in dogs and there is the need for new drugs. The PK/PD of Irb was tested in Beagle dogs. Ten healthy Beagles were orally administered two dose rates (2 and 5 mg/kg), according to a cross over study design. Blood collections for PK analysis and systolic blood pressure (SBP), heart and respiratory rate, mucous membranes colour, capillary refill time and temperature evaluations were performed at scheduled intervals. The drug plasma concentration was dose dependent. The dogs administered 5 mg/kg showed a significant reduction in SBP, while in those receiving 2 mg/kg, this parameter was minimally affected. A counter clockwise hysteresis showed no direct correlation between SBP and plasma concentrations. The minimum effective concentration was theorized to be within the range 550-800 ng/mL. Although further studies are necessary, 5 mg/kg seems to be the more appropriate dose to obtain a hypotensive effect in Beagle dogs.

[Intracranial hemorrhage in adults: place of antithrombotic treatment]. / Hémorragies intracrâniennes de l'adulte : implication de plus en plus importante des traitements antithrombotiques ?

BACKGROUND AND PURPOSE: Antithrombotic (anticoagulants and antiplatelets) are responsible for iatrogenic accidents, with a specific impact in neurosurgery. Bleeding complications are the most common and best-known. But the link to antiplatelet or to dual association of antithrombotic treatment with intracranial haemorrhage is not complete yet. We studied the proportion of patients under antithrombotic treatment, when an intracranial hemorrhage occurred, as well as the morbi-mortality of each group of patients (with or without antithrombotic treatment). Finally, we studied the proportion of off-label prescriptions. METHODS: We conducted a monocentric and comprehensive prospective study on a group of patients. All patients that had been admitted for intracranial hemorrhage to our hospital, in a 5-month period were included in the study. RESULTS: One hundred and sixty patients admitted for an intracranial hemorrhage were included during 70days of call. Seventy-four of these patients (46.25%) were under antithrombotic treatment: 40 under antiplatelet treatment (54%), 29 under anticoagulant treatment (39.2%), four under dual antithrombotic treatment (5.4%), and one under Arixtra(®). Half of the patients under antithrombotic treatment had poor prognosis as compared to 40% of patients without antithrombotic treatment. Off-label antithrombotic therapy was estimated at 27.3% of all prescriptions. CONCLUSIONS: The prevalence of antithrombotic therapy in patients is high when intracranial hemorrhage occurs. Some complications could be avoided by decreasing the number of off-label prescriptions and by better controlling their use (using standardized INR). Antiplatelet treatments and new antithrombotic therapies require better drug monitoring which could be part of the establishment of a specific register.

Relationship between bone metabolism and adipogenesis.

Several findings indicate that adipose tissue and bone have a complex reciprocal relationship. The two cells lineages share a common progenitor, and adipocyte endocrine activity may influence bone metabolism. Recent evidence from animal models suggests that bone cells may contribute regulating energy metabolism.

Interpenetrated and Noninterpenetrated Three-Dimensional Networks in the Polymeric Species Ag(tta) and 2 Ag(tta) small middle dotAgNO(3) (tta=tetrazolate): The First Examples of the µ(4)-eta(1):eta(1):eta(1):eta(1) Bonding Mode for Tetrazolate.

A twofold interpenetrated neutral three-dimensional network with rectangular channels (left) and a noninterpenetrated three-dimensional cationic framework (right) are the stuctural motifs observed in the simple salt Ag(tta) and in the double salt 2 Ag(tta) small middle dotAgNO(3), respectively. These compounds exhibit the first examples of the µ(4)-eta(1):eta(1):eta(1):eta(1) bonding mode for tetrazolate (tta).