A tracking system for laboratory mice to support medical researchers in behavioral analysis.

The behavioral analysis of laboratory mice plays a key role in several medical and scientific research areas, such as biology, toxicology, pharmacology, and so on. Important information on mice behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. Moreover, behavioral analysis of genetically modified mice allows obtaining important information about particular genes, phenotypes or drug effects. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. Currently, the engineering community is working to explore innovative identification and sensing technologies to develop new tracking systems able to guarantee benefits to animals' behavior analysis. This work presents a tracking solution based on passive Radio Frequency Identification Technology (RFID) in Ultra High Frequency (UHF) band. Much emphasis is given to the software component of the system, based on a Web-oriented solution, able to process the raw tracking data coming from a hardware system, and offer 2D and 3D tracking information as well as reports and dashboards about mice behavior. The system has been widely tested using laboratory mice and compared with an automated video-tracking software (i.e., EthoVision). The obtained results have demonstrated the effectiveness and reliability of the proposed solution, which is able to correctly detect the events occurring in the animals' cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of laboratory mice.

Polioencephalomalacia secondary to hypernatremia in squirrel monkeys (Saimiri sciureus).

Squirrel monkeys (Saimiri spp) are one of the most consistently used New World primates in biomedical research and are increasingly being used in neuroscience research, including models of drug abuse and addiction. Spontaneous neurologic disease in the squirrel monkey is uncommonly reported but includes various infectious diseases as well as cerebral amyloidosis. Hypernatremia is an extremely serious condition of hyperosmolarity that occurs as a result of water loss, adipsia, or excess sodium intake. Neurologic effects of hypernatremia reflect the cellular dehydration produced by the shift of water from the intracellular fluid space into the hypertonic extracellular fluid space. Severe hypernatremia may result in cerebrocortical laminar necrosis (polioencephalomalacia) in human patients as well as in a number of domestic species, including pigs, poultry, and ruminants. We report the clinical, histopathologic, and immunohistochemical findings of polioencephalomalacia in 13 squirrel monkeys. Polioencephalomalacia in these animals was associated with hypernatremia that was confirmed by serum levels of sodium greater than 180 mmol/L (reference range, 134.0-154.0 mmol/L [mEq/L]). All animals had concurrent diseases or experimental manipulation that predisposed to adipsia. Immunohistochemical investigation using antibodies to neuronal nuclei (NeuN), CNPase, Iba-1, and CD31 revealed necrosis of predominantly cerebral cortical layers 3, 4, and 5 characterized by neuronal degeneration and loss, oligodendrocytic loss, microglial proliferation, and vascular reactivity. The squirrel monkey is exquisitely sensitive to hyperosmolar metabolic disruption and it is associated with laminar cortical necrosis.

Mesenchymoproliferative enteropathy associated with dual simian polyomavirus and rhesus cytomegalovirus infection in a simian immunodeficiency virus-infected rhesus macaque (Macaca mulatta).

Opportunistic viral infections are common in simian immunodeficiency virus-infected rhesus macaques and include simian polyomavirus 40 (SV40), which causes interstitial nephritis, pneumonia, meningoencephalitis, and progressive multifocal leukoencephalopathy and rhesus cytomegalovirus (Macacine herpesvirus-3), which is associated with many pathologic manifestations, including the formation of neutrophil-rich gastrointestinal masses. Herein we report the findings of a simian immunodeficiency virus-infected rhesus macaque that presented to necropsy with multiple nodular masses restricted to the proximal jejunum. Histologically, the masses within the lamina propria were composed of abundant, loosely organized, mesenchymal tissue forming broad interlacing whorls and sheets admixed with variable numbers of neutrophils. Cells within the mesenchymoproliferative nodules contained numerous basophilic, intranuclear inclusion bodies with only scattered cytomegalic cells. Immunohistochemistry for rhesus cytomegalovirus and SV40 demonstrated variable numbers of immunopositive cells within the affected nodules. This report is the first description of SV40-associated pathology in the small intestine of a rhesus macaque and highlights the role that opportunistic viral infections can have on gastrointestinal pathology in immunosuppressed rhesus macaques.

Meeting report: Spontaneous lesions and diseases in wild, captive-bred, and zoo-housed nonhuman primates and in nonhuman primate species used in drug safety studies.

The combination of loss of habitat, human population encroachment, and increased demand of select nonhuman primates for biomedical research has significantly affected populations. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from drug-related findings. A workshop and a minisymposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3-4, 2011, in Nashville, Tennessee. The first session had presentations from Drs Lowenstine and Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case reports of rare or newly observed spontaneous lesions in nonhuman primates (see online files for access to digital whole-slide images corresponding to each case report at http://www.scanscope.com/ACVP%20Slide%20Seminars/2011/Primate%20Pathology/view.apml). The minisymposium was composed of 5 nonhuman-primate researchers (Drs Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus and rhesus macaques were emphasized, with some material presented on common marmosets. Congenital, acquired, inflammatory, and neoplastic changes were highlighed with a focus on clinical, macroscopic, and histopathologic findings that could confound the interpretation of drug safety studies.

Zebrafish response to robotic fish: preference experiments on isolated individuals and small shoals.

Recently developed bioinspired robots imitate their live counterparts in both aspect and functionality. Nevertheless, whether these devices can be integrated within the ecological niche inspiring their design is seldom tested experimentally. An elemental research question concerns the feasibility of modulating spontaneous behaviour of animal systems through bioinspired robotics. The following study explores the possibility of engineering a robotic fish capable of influencing the behaviour of live zebrafish (Danio rerio) in a dichotomous preference test. While we observe that the preference for the robotic fish never exceeds the preference for a conspecific, our data show that the robot is successful in attracting both isolated individuals and small shoals and that such capability is influenced by its bioinspired features. In particular, we find that the robot's undulations enhance its degree of attractiveness, despite the noise inherent in the actuation system. This is the first experimental evidence that live zebrafish behaviour can be influenced by engineered robots. Such robotic platforms may constitute a valuable tool to investigate the bases of social behaviour and uncover the fundamental determinants of animal functions and dysfunctions.

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens.

Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999-1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attention-deficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

First trimester biochemical screening for Down syndrome: free beta hCG versus intact hCG.

To compare free beta hCG versus intact hCG in first trimester Down syndrome screening we analysed 63 cases of Down syndrome and 400 unaffected control pregnancies between 10 and 13 weeks' gestation. The Down syndrome median multiple of the median (MoM) was significantly higher (p=0.001) for free beta hCG (1.89 MoM) than for intact hCG (1.37 MoM). Although distributions for free beta hCG (unaffected, 0.2157; DS, 0.2322) are wider than for intact hCG (unaffected, 0.1697; DS, 0.2158), overall 27% of Down syndrome cases were above the 95th percentile for free beta hCG compared to 19% for intact hCG. Combined with maternal age, free beta hCG detected 45% of Down syndrome pregnancies at a 5% false positive rate. Intact hCG combined with maternal age demonstrated a detection efficiency comparable to maternal age alone (35% versus 32%). In contrast, a recent study (Haddow et al., 1998-NEJM 338: 955-961) indicated that intact hCG yielded a higher first trimester Down syndrome detection efficiency than free beta hCG (29% versus 25% respectively). Re-analysis of distribution parameters in the Haddow et al. study, however, show that free beta hCG was actually the better marker (23% detection for intact hCG versus 29% for free beta hCG).

Intra-operative spinal cord monitoring in orthopaedics.

The surgical correction of spinal deformities carries a small but significant risk of injury to the spinal cord. To detect the onset and possibly reverse the effects of surgical complication, a variety of neurophysiological monitoring procedures can be employed. The purpose of this review is to provide information regarding the various methodologies available for monitoring spinal cord and nerve root function during orthopaedic procedures. Intra-operative monitoring of cortically recorded somatosensory evoked potentials (SEPs) by peripheral nerve stimulation is of value during orthopaedic surgery and is the state-of-the-art in terms of non-invasiveness, versatility, time requirement, lateral discrimination, and ease of electrode placement. Monitoring of motor evoked potentials (MEPs) is useful particularly in combination with SEPs but is still considered investigational. Root function monitoring has limited application and requires more clinical research.

La asociación propinox-clonixinato de lisina en dolor abdominal agudo / The association propinox-lysine clonixinate in acute abdominal pain

Se estudiaron 1625 pacientes portadores de dolor cólico abdominal agudo (cólico intestinal y renal, discinesia biliar con o sin litiasis, dispepsia no ulcerosa, dismenorrea, movilización del DIU y criocirugía del cuello uterino) que presentaron al momento de la incorporación dolor de intensidad moderada o severa. Fueron asignados al azar y doble ciego en 2 grupos expermientales con Clonixinato de lisina 125 mg asociado a Propinox 10 mg (CLP) (N=818) o N-butilbromuro de hioscina 10 mg asociado a Paracetamol 500 mg (PB) (N=807). El tratamiento consistió en un comprimido, de igual aspecto en ambas drogas, como dosis única. El efecto analgésico-antiespasmódico fue evaluado horariamente durante un lapso de 4 hs. En cada control se estabaleció la evolución del dolor, como así también de otros síntomas acompañantes, mediante escala visual análoga (EVA) de 10 cm y escala de categorización verbal de 4 niveles. Asimismo, en cada oportunidad se indagaron la frecuencia de eventos adversos. En el control final de las 4 horas el paciente y el médico efectuaron una evaluación global sobre la eficacia y tolerancia al tratamiento. Ambos grupos fueron equivalentes entre sí en lo referente a condiciones basales (características demográficas, etiológicas y dolor espontáneo), por lo que se asume que se trata de muestras homogéneas y comparables entre sí. Con ambos métodos de registro se demostró una reducción progresiva de la intensidad del dolor, que se hizo significativa a partir del control de la 1a. hora, con una reducción para los 2 tratamientos en alrededor de un 43 por ciento respecto del valor inicial.La actividad analgésica sostenida queda demostrada para ambos tratamientos en razón que en el control final de las 4 hs los valores de EVA fueron menores de 1. La salida del ensayo por ineficacia en el control de la 1a. hora fue similar: 14 por ciento por el CLLP y 12 por ciento para PB. No se demostraron diferencias estadísticas en las intensidades de dolor en cada tiempo entre los 2 tratamientos. Los signos y síntomas asociados a la patología de inclusión (cefaleas, náuseas y diarrea) se redujeron significativamente entre la 1a. y 2da. hora de control. Se observó un ligero incremento (no significtivo) en la incidencia de boca seca y visión borrosa. La evaluación global de eficacia analgésica fue considerada buena en el 81 por ciento (CLP) y 80 por ciento (PB) de las opiniones de médico y en un 78 por ciento y 79 por ciento respectivamente cuando lo hizo el paciente

La asociación propinox-clonixinato de lisina en dolor abdominal agudo / The association propinox-lysine clonixinate in acute abdominal pain

Se estudiaron 1625 pacientes portadores de dolor cólico abdominal agudo (cólico intestinal y renal, discinesia biliar con o sin litiasis, dispepsia no ulcerosa, dismenorrea, movilización del DIU y criocirugía del cuello uterino) que presentaron al momento de la incorporación dolor de intensidad moderada o severa. Fueron asignados al azar y doble ciego en 2 grupos expermientales con Clonixinato de lisina 125 mg asociado a Propinox 10 mg (CLP) (N=818) o N-butilbromuro de hioscina 10 mg asociado a Paracetamol 500 mg (PB) (N=807). El tratamiento consistió en un comprimido, de igual aspecto en ambas drogas, como dosis única. El efecto analgésico-antiespasmódico fue evaluado horariamente durante un lapso de 4 hs. En cada control se estabaleció la evolución del dolor, como así también de otros síntomas acompañantes, mediante escala visual análoga (EVA) de 10 cm y escala de categorización verbal de 4 niveles. Asimismo, en cada oportunidad se indagaron la frecuencia de eventos adversos. En el control final de las 4 horas el paciente y el médico efectuaron una evaluación global sobre la eficacia y tolerancia al tratamiento. Ambos grupos fueron equivalentes entre sí en lo referente a condiciones basales (características demográficas, etiológicas y dolor espontáneo), por lo que se asume que se trata de muestras homogéneas y comparables entre sí. Con ambos métodos de registro se demostró una reducción progresiva de la intensidad del dolor, que se hizo significativa a partir del control de la 1a. hora, con una reducción para los 2 tratamientos en alrededor de un 43 por ciento respecto del valor inicial.La actividad analgésica sostenida queda demostrada para ambos tratamientos en razón que en el control final de las 4 hs los valores de EVA fueron menores de 1. La salida del ensayo por ineficacia en el control de la 1a. hora fue similar: 14 por ciento por el CLLP y 12 por ciento para PB. No se demostraron diferencias estadísticas en las intensidades de dolor en cada tiempo entre los 2 tratamientos. Los signos y síntomas asociados a la patología de inclusión (cefaleas, náuseas y diarrea) se redujeron significativamente entre la 1a. y 2da. hora de control. Se observó un ligero incremento (no significtivo) en la incidencia de boca seca y visión borrosa. La evaluación global de eficacia analgésica fue considerada buena en el 81 por ciento (CLP) y 80 por ciento (PB) de las opiniones de médico y en un 78 por ciento y 79 por ciento respectivamente cuando lo hizo el paciente

Postural stability in Parkinson's disease: the effects of disease severity and acute levodopa dosing.

We systematically assessed the potential effects of disease severity and acute levodopa dosing on body balance by a stable force measuring platform in 56 patients with Parkinson's disease, and compared them to 34 healthy volunteers. Postural sway variables were significantly higher in both patient groups without (Hoehn and Yahr 1-2) and with (Hoehn and Yahr 3-4) a clinically evident deficit of postural stability compared to controls. Levodopa dosing significantly increased postural sway 1 and 2 hours post-dose. The standardization of static posturography with respect to the clinical characteristics and drug schedule of patients may improve the sensitivity of the test, disclosing abnormalities of postural stance even at the early stages of the disease and revealing possible acute drug effects.