Central Sensitization in the Bladder Pain Syndrome

Introduction: Nociceptive hyper-excitability and Central Sensitization (CS), have been identified as responsible for maintaining pain in several chronic neuropathic pain conditions, among which Bladder pain syndrome (BPS). Aim of the present study was to evaluate in patients with BPS the correlation between CS and the following items pain duration, the number of other CS related diseases, the number of tried treatments for pain and of diagnostic investigations before the proper diagnosis and to identify the cut-off value of the pain delays for predicting the worsening of sensitization. Method: Fifty-eight consecutively BPS outpatients were recruited from 2014 to 2016. They were submitted to Central Sensitization Inventory (CSI), Overactive Bladder Questionnaire (OAB-8v) and visual analogic scale (VAS) for pain. We used a descriptive analysis (mean, standard deviation, range) and Spearman and Kendall test coefficient as correlation index. One-way ANOVA test was used for the comparison between groups. P-value less than 0.05 were required for statistical significance. We used receiver operating characteristic (ROC) curve analysis to retrospectively analyze the association between the years of the disease and pathological values o of CSI. Results: The patients were observed after 13.1 + 11.0 years by the onset of The CSI score was 69.7+15.8. Resulting significantly lower in patients with BPS onset in the last year the correlation between CSI and the disease duration was significant. The number of previous investigations was 3.7 + 2.8while the number of previous treatments for chronic pain was 5.9 + 3.1, resulting significantly related to CSI score. The OAB-8v was 21 + 7.5 (range 2-34). The worsening of the symptoms related to the overactive bladder at OAB-8v was related to a greater CS. After 1,5 years of the onset of the pain the CS show a progressive worsening. The mean number of other diseases (fibromyalgia, irritable bowel syndrome, anxiety or depression, migraine, neck injury, Panic Disorder Attack, chronic fatigue syndrome, temporomandibular joint syndrome, restless leg syndrome, multiple chemical sensitivities) associated to CS was 2.8+1.9. The correlation between the number of diseases associated to CS and the years of disease resulted significant. Conclusion: Patients with long lasting pelvic pain show high levels of CS, and other central sensitivity syndromes (CSS) together to worsening of overactive bladder symptoms, and increasing number of used drugs. The delay of diagnosis is related to a greater sensitization process

Dysphagia in amyotrophic lateral sclerosis: impact on patient behavior, diet adaptation, and riluzole management

This retrospective study aimed to investigate the clinical features associated with deteriorated swallow in amyotrophic lateral sclerosis (ALS) patients with spinal and bulbar onset, describe the modification of diet and liquid intake, and assess the impact of dysphagia on the use of riluzole. One hundred forty-five patients were observed periodically every 3-6 months. They underwent routinely fiberoptic endoscopic evaluation of swallowing (FEES) and spirometry; dysphagia severity was classified according to the Penetration Aspiration Scale and the Pooling score (P-score) integrated with other parameters such as sensation, collaboration, and age (P-SCA score). During a mean follow-up period of about 2 years, the percentage of ALS patients suffering from dysphagia increased to 85 (rising from 35 to 73% in patients with spinal onset and from 95 to 98% in those with bulbar onset). Also, 8% of patients with dysphagia by FEES did not perceive the disorder. The frequency of normal and semi-solid diets decreased over time, while that of pureed diets and percutaneous endoscopic gastrostomy (PEG) prescription increased. Forty-four percent of dysphagic patients refused thickeners or PEG. A significant difference was observed in the mortality rate between patients untreated with riluzole and patients treated with riluzole oral suspension (p < 0.05). Disease duration mainly impacted on the frequency of dysphagia in spinal onset patients, appearing very early in those with bulbar onset. Riluzole oral suspension would allow the safe administration in dysphagic ALS patients to avoid tablet crushing and consequent dispersion in food, common practices that are inconsistent with the safe and effective use of the drug

Clinical and operational value of the extensively drug-resistant tuberculosis definition.

Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

On the (anisotropic) uniform metallic ground states of fermions interacting through arbitrary two-body potentials in d dimensions

We demonstrate that the skeleton of the Fermi surface S_{F;s} pertaining to a uniform metallic ground state (corresponding to fermions with spin index s) is determined by the Hartree-Fock contribution to the dynamic self-energy. The Fermi surface S_{F;s} consists of all points which in addition to satisfying the quasi-particle equation in terms of the Hartree-Fock self-energy, fulfill the equation S_{s}(k) = 0, where S_{s}(k) is defined in the main text; the set of k points which satisfy the Hartree-Fock quasi-particle equation but fail to satisfy S_{s}(k) = 0, constitute the pseudo-gap region of the putative Fermi surface of the interacting system. We consider the behaviour of the ground-state momentum-distribution function n_{s}(k) for k in the vicinity of S_{F;s} and show that whereas for the uniform metallic ground states of the conventional Hubbard Hamiltonian n_{s}(k) is greater/less than 0.5 for k approaching S_{F;s} from inside/outside the Fermi sea, for interactions of non-zero range these inequalities can be violated (without thereby contravening the condition of the non-negativity of the possible jump in n_{s}(k) on k crossing S_{F;s} from directly inside to directly outside the Fermi sea). We discuss, in the light of the findings of the present work, the growing experimental evidence with regard to the `frustration' of the kinetic energy of the charge carriers in the normal states of the copper-oxide-based high-temperature superconducting compounds. [Short abstract]Comment: 30 pages, 3 postscript figures. Brought into conformity with the published versio

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

School-aged children can benefit from audiovisual semantic congruency during memory encoding

Although we live in a multisensory world, children's memory has been usually studied concentrating on only one sensory modality at a time. In this study, we investigated how audiovisual encoding affects recognition memory. Children (n = 114) from three age groups (8, 10 and 12 years) memorized auditory or visual stimuli presented with a semantically congruent, incongruent or non-semantic stimulus in the other modality during encoding. Subsequent recognition memory performance was better for auditory or visual stimuli initially presented together with a semantically congruent stimulus in the other modality than for stimuli accompanied by a non-semantic stimulus in the other modality. This congruency effect was observed for pictures presented with sounds, for sounds presented with pictures, for spoken words presented with pictures and for written words presented with spoken words. The present results show that semantically congruent multisensory experiences during encoding can improve memory performance in school-aged children.Peer reviewe

Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction

Background: In patients with heart failure, chronic kidney disease (CKD) is common and associated with a higher risk of renal events than in patients without CKD. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure and preserved ejection fraction (HFpEF) enrolled in PARAGON-HF. Methods: In this randomized, double-blind, event-driven trial, we assigned 4,822 patients with HFpEF to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein we present the results of the pre-specified renal composite outcome (time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. Results: At randomization, eGFR was 63±19 ml/min/1.73m2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio [HR], 0.50; 95%CI, 0.33 to 0.77; P=0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan compared with valsartan (-1.8 [95%CI, -2.0 to -1.6] vs. -2.4 [95%CI, -2.6 to - 2.2] ml/min/1.73m2/year). Conclusions: In patients with HFpEF, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan

Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi:a modelling study

Background In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. Methods A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. Results Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.</p

Feebly-interacting particles: FIPs 2022 Workshop Report

Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs