Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

ABSTRACT: BACKGROUND: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis. METHODS: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups. RESULTS: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-gamma and TNF-alpha production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-gamma production in PPD stimulated cultures, TNF-alpha levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients. CONCLUSION: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-alpha production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.     

18F‐fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: A prospective,randomized, controlled clinical study

The functional imaging technique of ¹⁸F‐fluoride positron emission tomography (¹⁸F‐PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹⁸F‐PET can be used as an early biomarker of treatment efficacy at the hip. Twenty‐seven treatment‐naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. ¹⁸F‐PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of ¹⁸F‐fluoride to bone, K_i, a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K_i was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in K_i in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in K_i were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that ¹⁸F‐PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy.     

Oscillatory activity during maintenance of spatial and temporal information in working memory

Working memory (WM) processes help keep information in an active state so it can be used to guide future behavior. Although numerous studies have investigated brain activity associated with spatial WM in humans and monkeys, little research has focused on the neural mechanisms of WM for temporal order information, and how processing of temporal and spatial information might differ. Available evidence indicates that similar frontoparietal regions are recruited during temporal and spatial WM, although there are data suggesting that they are distinct processes. The mechanisms that allow for differential maintenance of these two types of information are unclear. One possibility is that neural oscillations may differentially contribute to temporal and spatial WM. In the present study, we used scalp electroencephalography (EEG) to compare patterns of oscillatory activity during maintenance of spatial and temporal information in WM. Time-frequency analysis of EEG data revealed enhanced left frontal theta (5–8 Hz), enhanced posterior alpha (9–12 Hz), and enhanced left posterior beta (14–28 Hz) power during the delay period of correct temporal order trials compared to correct spatial trials. In contrast, gamma (30–50 Hz) power at right lateral frontal sites was increased during the delay period of spatial WM trials, as compared to temporal WM trials. The present results are consistent with the idea that neural oscillatory patterns provide distinct mechanisms for the maintenance of temporal and spatial information in WM. Specifically, theta oscillations are most critical for the maintenance of temporal information in WM. Possible roles of higher frequency oscillations in temporal and spatial memory are also discussed.     

Initial Efficacy of Project ImPACT: A Parent-Mediated Social Communication Intervention for Young Children with ASD

Project ImPACT is a parent-mediated social communication intervention for young children with ASD that was developed in community settings to encourage dissemination. A single-subject, multiple-baseline design was conducted across 8 preschoolers with ASD and their mothers to examine the efficacy of the model for improving parent intervention fidelity and child spontaneous language. Multilevel modeling was used to examine the relationship between parent fidelity and child language within session. All parents increased their use of the intervention techniques. Improvements in spontaneous use of language targets were observed for 6 of the 8 children. There was a significant association between parents’ use of the intervention strategies and their child’s spontaneous language use.     

Visual attention in a multiple‐choice task: Influences of image characteristics with and without presentation of a verbal stimulus

Background: Use of multiple‐choice items is common in the assessment of language comprehension. Stimulus‐driven aspects of multiple‐choice images may interfere with valid assessment. Understanding the influences of stimulus‐driven factors is crucial because individuals with neurological disorders have increased susceptibility to them.

Aims: The first goal of this study was to explore the influence of objectively measurable image characteristics in multiple‐choice image sets that are otherwise well controlled in terms of physical stimulus features on individuals' visual attention. The second goal was to explore viewers' visual attention under the influence of a verbal stimulus.

Methods & Procedures: The effects of controlled manipulation of physical image characteristics on visual attention in 40 healthy adults were assessed. Eye movements were recorded while participants viewed 40 image sets with and without a verbal stimulus. Within each set, two images shared the same image characteristics (colour, orientation, size, and luminance) and one image differed in terms of one of those characteristics.

Outcomes & Results: All characteristics had a significant influence on visual attention in verbal and nonverbal conditions. The influence of verbal stimuli on visual attention did not override the tendency for physical stimulus characteristics to distract attention from target images.

Conclusions: Research and clinical relevance is highlighted in terms of the potential for assessment confounds to be greater in individuals with neurological impairments.     

Aphasia LIFT: Exploratory investigation of an intensive comprehensive aphasia programme

Background: Intensive comprehensive aphasia programs (ICAPs) are gaining popularity in the international aphasia rehabilitation community. ICAPs comprise at least three hours of treatment per day over at least two weeks, have definable start and end dates for one cohort and use a variety of formats including individual treatment, group therapy, education and technology to improve language and communication. While intensive treatment approaches have demonstrated equivocal results on impairment-based measures, positive changes on activity/participation measures provide support for ICAPs in rehabilitation of chronic aphasia. Aphasia Language Impairment and Functional Therapy (LIFT) is a research-based ICAP developed for the purpose of evaluating treatment outcomes across the International Classification of Functioning, Disability and Health (ICF) domains.

Aims: The aim of this study was to estimate the magnitude of treatment effects yielded by Aphasia Aphasia LIFT in the domains of language impairment, functional communication and communication-related quality of life (QOL).

Methods & Procedures: Eleven individuals with chronic post-stroke aphasia (mean = 26.9 months) completed Aphasia LIFT. The programme comprised individual impairment-based and functional treatment, group therapy, and computer-based treatment for 40 hours over two weeks (n = 4, LIFT 1) or 100 hours over four weeks (n = 7, LIFT 2). Assessments of confrontation naming, discourse production, functional communication and communication-related quality of life were completed at pre-treatment, immediately post-treatment and six to eight weeks following treatment termination.

Outcomes & Results: Group-level analyses revealed acquisition and maintenance of treatment effects, as evidenced by significant improvement on at least one outcome measure at follow-up in all domains. The most consistent pattern of improvement at an individual level was observed on measures of functional communication and communication-related QOL.

Conclusions: Aphasia LIFT yielded positive outcomes across ICF domains, and in many cases the treatment effect was enduring. These results demonstrate that Aphasia LIFT was successful in meeting the overarching goal of ICAPs, to maximise communication and enhance life participation in individuals with aphasia. Further research into ICAPs is warranted.