Clinical and laboratory features of cats with feline infectious peritonitis - a retrospective study of 231 confirmed cases (2000-2010)

Objectives The objectives of this study were to review signalment, clinical signs and laboratory features in a large number of naturally occurring cases of feline infectious peritonitis (FIP), and to evaluate potential changes in diagnostic criteria for FIP and compare findings in cats with and without effusion. Methods The medical records of 231 cats with confirmed FIP that presented to the Clinic of Small Animal Medicine of the Ludwig-Maximilian University of Munich, Germany, were reviewed for signalment, history, and clinical and laboratory parameters. Age, sex and breed distribution of the cats were compared with the clinic population. Results Male sex and young age were significantly correlated with FIP. Neutering status was not associated with FIP. No breed predisposition was observed and the majority of cats presented were domestic shorthair and mixed breed. Microcytosis of peripheral erythrocytes was found in 35.1% of cats, of which 42.4% did not have concurrent anaemia. Band neutrophilia was documented in 44.3% (81/183), of which 35.8% did not have mature neutrophilia. Lymphopenia, observed significantly more often with effusion, was documented in only 26.8% of cats without effusion. Hyperbilirubinaemia also occurred significantly more often in cats with vs without effusion. While serum total protein was increased in only 17.5% of cats, hyperglobulinaemia was documented in 89.1%. Nearly 85.0% of cats had an albumin-to-globulin (A:G) ratio <0.8, while 67.8% had an A:G ratio <0.6. Conclusions and relevance Microcytosis was common and can increase suspicion of FIP in the presence of other typical clinical and laboratory abnormalities. The low prevalence of lymphopenia in cats without effusion suggests that this is not a useful parameter in non-effusive FIP. The frequent occurrence of a left shift in the absence of a mature neutrophilia complicates the differentiation of effusive FIP and septic peritonitis. Globulins and A:G ratio were of higher diagnostic value than hyperproteinaemia

Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy

Macaca nemestrina monkeys received unilateral interruption of the spinothalamic tract, producing contralateral hypalgesia and a bilateral decrease in amplitude of the flexion reflex. These effects on operant escape and reflex responses to electrocutaneous stimulation (ES) were monitored for months to evaluate relationships between the extent of each lesion and the presence or absence of recovery from the early postoperative deficits. Before surgery, the animals were trained to perform an operant response that terminated ES to the lateral calf of either leg. The durations of ES tolerated by each monkey were inversely related to stimulus intensities within the pain sensitivity range of human subjects. The vigor of operant escape responses and the frequency of intertrial pulls of the manipulandum were directly related to stimulus intensity. Following anterolateral chordotomy at an upper thoracic level, these measures revealed a contralateral hypalgesia for each animal. Operant responsivity to stimulation contralateral to the lesion recovered to control levels for 7 animals (group R). Sustained contralateral recovery of operant reactivity was not observed for 8 monkeys (group U). Most of the lesions in groups R and U were similar in extent and location, involving the classical distribution of the spinothalamic tract (in the anterolateral and ventral columns). Thus, recovery was not determined solely by lesion configuration. However, when recovery did occur, it was associated with medially extensive lesions. A subgroup of 3 unrecovered animals received superficial lesions that did not substantially involve the gray matter or the ventral columns. For all animals, reflex magnitudes were initially diminished bilaterally and then increased over months of testing. Reflex recovery was greater for the animals that demonstrated recovery of intentional reactions to nociception (group R). An ipsilateral hyperreflexia became apparent for group R. Contralateral recovery to normal levels was observed for group R but not for group U. The time course of recovery for operant and reflex responses clearly differed, indicating that different processes determined changes in these spinal and supraspinal reactions to nociceptive stimulation

The Concordance Cosmic Star Formation Rate: Implications from and for the Supernova Neutrino and Gamma Ray Backgrounds

We constrain the Cosmic Star Formation Rate (CSFR) by requiring that massive stars produce the observed UV, optical, and IR light while at the same time not overproduce the Diffuse Supernova Neutrino Background as bounded by Super-Kamiokande. With the massive star component so constrained we then show that a reasonable choice of stellar Initial Mass Function and other parameters results in SNIa rates and iron yields in good agreement with data. In this way we define a `concordance' CSFR that predicts the optical SNII rate and the SNIa contribution to the MeV Cosmic Gamma-Ray Background. The CSFR constrained to reproduce these and other proxies of intermediate and massive star formation is more clearly delineated than if it were measured by any one technique and has the following testable consequences: (1) SNIa contribute only a small fraction of the MeV Cosmic Gamma-Ray Background, (2) massive star core-collapse is nearly always accompanied by a successful optical SNII, and (3) the Diffuse Supernova Neutrino Background is tantalizingly close to detectability.Comment: Improved discussion. Version accepted for publication in JCA

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study

Adaptive preconditioning in neurological diseases -­ therapeutic insights from proteostatic perturbations

International audienceIn neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson´s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses - and the molecular pathways they recruit - might be exploited for therapeutic gai