Non-invasive mouse models of post-traumatic osteoarthritis.

Animal models of osteoarthritis (OA) are essential tools for investigating the development of the disease on a more rapid timeline than human OA. Mice are particularly useful due to the plethora of genetically modified or inbred mouse strains available. The majority of available mouse models of OA use a joint injury or other acute insult to initiate joint degeneration, representing post-traumatic osteoarthritis (PTOA). However, no consensus exists on which injury methods are most translatable to human OA. Currently, surgical injury methods are most commonly used for studies of OA in mice; however, these methods may have confounding effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury. Non-invasive injury methods avoid this complication by mechanically inducing a joint injury externally, without breaking the skin or disrupting the joint. In this regard, non-invasive injury models may be crucial for investigating early adaptive processes initiated at the time of injury, and may be more representative of human OA in which injury is induced mechanically. A small number of non-invasive mouse models of PTOA have been described within the last few years, including intra-articular fracture of tibial subchondral bone, cyclic tibial compression loading of articular cartilage, and anterior cruciate ligament (ACL) rupture via tibial compression overload. This review describes the methods used to induce joint injury in each of these non-invasive models, and presents the findings of studies utilizing these models. Altogether, these non-invasive mouse models represent a unique and important spectrum of animal models for studying different aspects of PTOA.

Differentiation of attention-deficit/hyperactivity disorder subtypes: application of a neuropsychological model of attention.

This study represents a neuropsychological attempt to differentiate subtypes of Attention Deficit/Hyperactivity Disorder (ADHD). Participants (N = 80) were grouped by gender and ADHD subtype-Predominantly Inattentive (ADHD-I) versus Combined (ADHD-C)-resulting in four age-matched groups. Statistical analysis revealed significant differences in performance on selective attention tasks for those with ADHD-I and those with ADHD-C. Relative to their counterparts without hyperactivity, participants with ADHD-C earned disproportionately lower scores on tasks associated with executive control. Both subgroups with ADHD-I and ADHD-C demonstrated significant difficulty on some tasks assessing complex mental operations relative to age-standardized normative data. Discriminant analysis revealed that a combination of five neuropsychological measures discriminated between the ADHD-I and ADHD-C subgroups with 80% accuracy. Results provide support for the notion of the Predominantly Inattentive and Combined subtype classifications as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (American Psychiatric Association, 1994). Further, findings from this study lend preliminary support for the utility of a neurophysiologically sensitive model of attention in the differentiation of these subtypes.

Subtypes of cognitive impairment in depressed older adults.

The authors examined the cognitive profiles of 104 older adults with major depression and empirically identified three subgroups with distinct patterns of cognitive impairment. The entire sample demonstrated memory impairment relative to age-standardized scores, distributed equally across the three cognitive subgroups. One-third of subjects displayed either executive impairment or attentional deficits. The subgroup with executive dysfunction had greater behavioral disability. Identification of executive impairment in depressed older adults may facilitate intervention for disturbances in planning, sequencing, organizing, and abstracting. Demonstrating the presence of subtypes of cognitive impairments in older adults may provide the basis for further investigation of mechanisms of late-life depression and the pathophysiology of antidepressant response. The association of behavioral disability with executive dysfunction can initiate an inquiry into the biology of functional impairment ultimately linking biological research to studies of treatment effectiveness.