ALLERGIC ENCEPHALOMYELITIS IN MONKEYS IN RESPONSE TO INJECTION OF NORMAL MONKEY NERVOUS TISSUE

By subcutaneous injection of central nervous tissue emulsified with adjuvants according to Freund''s technique it has been possible to induce in the majority of monkeys an acute disseminated encephalomyelitis which is interpreted as an isoimmunization to CNS tissue. Positive reactions occurred only in response to CNS tissue containing white matter; i.e., cerebral white matter, spinal cord (whether normal or poliomyelitis-infected), and cortical "gray" matter (with an estimated 10 per cent contamination with white matter). No reaction occurred when peripheral nerve or kidney suspension or saline alone was injected with adjuvants. The perivascular and extravascular infiltration induced was confined to the CNS.     

Relation between induction of the mar operon and cyclohexane tolerance and reduction in fluoroquinolone susceptibility in Salmonella spp.

The relationship between cyclohexane tolerance and induction of the mar operon and a decrease in susceptibility to ciprofloxacin and moxifloxacin in isolates of Salmonella spp. from food and clinical isolates of Salmonella spp. was studied. We studied the influence of the mar operon using an inductor (acetylsalicylic acid) and we also studied the cyclohexane resistance. Induction was seen to produce an increase in the minimum inhibitory concentration (MIC) of these quinolones, which suggested that there was overexpression of the AcrAB type active efflux systems due to induction of the mar operon. Cyclohexane susceptibility was not shown to be a very sensitive method for studying this process, as only 3% (5/176) of the clinical isolates studied were cyclohexane-resistant; most of these belonged to the Hadar serotype. This study confirmed the participation of active efflux systems in the decrease in fluoroquinolone susceptibility in Salmonella spp. Furthermore, the study has indicated that these mechanisms (i.e., active efflux systems) are present in strains that are susceptible to the fluoroquinolone compounds, so their stimulation may be one of the mechanisms involved in the reduction in fluoroquinolone susceptibility. This suggests that the exposure of Salmonella spp. to antibiotics should be limited in order to prevent these active efflux systems from being activated. Consequently, the use of fluoroquinolones, both in the treatment of humans and in veterinary practice, should be controlled and rationalized in an attempt to curb the increase in the number of strains that are resistant to these compounds.     

What Are You Looking at? Joint Attention and Visual Perspective Taking in Young Children With Autism Spectrum Disorder

This study investigated joint attention and visual perspective taking abilities in young children. Twenty children with autism spectrum disorder in the age range of 3–7 years, and 20 age-matched control children participated in the study. Joint attention was assessed by a spontaneous gaze monitoring task, and two tasks measuring eye contact in ambiguous situations. Visual perspective taking was measured using a Level 1 task [(Flavell, J. H., 1978). Nebraska symposium on motivation, Vol. 25, University of Nebraska Press, Lincoln]. The children with autism spectrum disorder were not only found to be impaired in their joint attention abilities, but they also showed problems on the visual perspective taking task. These results suggest that the basic dyadic person-object processes may develop in a slower and perhaps qualitatively different way in children with autism spectrum disorder.     

Preclinical and Translational Studies in Small Ruminants (Sheep and Goat) as Models for Osteoporosis Research

Purpose of the Review

This review summarizes research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies.

Recent Findings

The most frequent osteoporotic sheep model used is the ovariectomized sheep with 12 months post-operatively or more and the combined treatment of ovariectomized sheep associated to calcium/vitamin D-deficient diet and glucocorticoid applications for 6 months, but other methods are also described, like pinealectomy or hypothalamic-pituitary disconnection in ovariectomized sheep. The goat model for osteoporosis research has been used in a very limited number of studies in osteoporosis research relative to sheep. These osteoporotic small ruminant models are applied for biomaterial research, bone augmentation, efficacy of implant fixation, fragility fracture-healing process improvement, or bone-defect repair studies in the osteopenic or osteoporotic bone.

Summary

Sheep are a recognized large animal model for preclinical and translational studies in osteoporosis research and the goat to a lesser extent. Recently, the pathophysiological mechanism underlying induction of osteoporosis in glucocorticoid-treated ovariectomized aged sheep was clarified, being similar to what occurs in postmenopausal women with glucocorticoid-induced osteoporosis. It was also concluded that the receptor activator of NF-κB ligand was stimulated in the late progressive phase of the osteoporosis induced by steroids in sheep. The knowledge of the pathophysiological mechanisms at the cellular and molecular levels of the induction of osteoporosis in small ruminants, if identical to humans, will allow in the future, the use of these animal models with greater confidence in the preclinical and translational studies for osteoporosis research.

     

Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study

OBJECTIVE: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives. METHOD: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months. RESULTS: Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant). CONCLUSION: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.     

Rethinking cultural safety while waiting to do fieldwork: methodological implications for nursing research

The concept of culture has been widely applied as an explanatory concept within health care, often within a framework representing culture as a fixed, reified entity, with cultural groups existing in a binary sense vis-;-vis mainstream culture. However, if our scholarship is to generate knowledge that addresses longstanding patterns of inclusion and exclusion along lines such as race, ethnicity, class, and gender, interpretive frames are needed that account for culture as embedded in fields of power relations; as mediated by social forces such as economics, politics, and historical patterns of oppression and colonization; and as being constantly renegotiated. In this article we trace a series of theoretical explorations, centered on the concept of cultural safety, with corresponding methodological implications, engaged in during preparation for an intensive period of fieldwork to study the hospitalization and help-seeking experiences of diverse ethnocultural populations.     

Some patients (and some of us) respond better to some biological therapies: the as yet unsolved conundrum

Very often, treatment for many common musculoskeletal conditions is only palliative, or involves surgery with major shortcomings. Biological interventions—in particular, platelet-rich plasma (PRP) therapies—may well provide more effective treatments, but their actual efficacy is under scrutiny. PRP is biologically unique to each individual depending on endogenous and exogenous factors, including, but not limited to, demographic factors (i.e. age), immune status (i.e. microbiota), metabolic diseases and concomitant medications. All these potential modifiers of the ultimate effects of PRP have been poorly explored, and their relationship with efficacy has not been established.     

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

The colony‐stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1‐mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil‐derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.