Shortened total spine MRI protocol in the detection of spinal cord compression and pathology for emergent settings: a noninferiority study.

BACKGROUND AND PURPOSE: Spinal cord compression (SCC) requires rapid diagnosis in the emergent setting; however, current MRI protocols may be cumbersome for patients and clinicians. We sought to validate an abbreviated total spine MRI (TS-MRI) protocol using standard non-contrast sequences in the detection of SCC and other clinically significant findings (OCSF). METHODS: Two hundred six TS-MRI scans obtained over a 30-month period for SCC were included. Sagittal T2 (T2sag), sagittal T1 (T1sag), and sagittal STIR (IRsag), as well as axial T2 (T2ax) images, were individually assessed independently by 2 reviewers for SCC, cauda equina compression (CEC), and OCSF. A protocol consisting of all the sequences was considered the gold standard. Sensitivity and specificity of single and combined MRI sequences for SCC/CEC and OCSF were determined and were tested for noninferiority relative to standard non-contrast sequences using a 5% noninferiority margin. RESULTS: An abbreviated protocol of IRsag + T2ax provided the best performance with sensitivity and specificity of 100% (95%CI, 96.0-100.0) and 98.6% (95%CI, 95.6-99.7) for SCC/CEC and 100.0% (95%CI, 96.7-100.0), and 99.3% (95%CI, 96.6-99.9) for OCSF. The mean difference of sensitivity and specificity between IRsag + T2ax and standard protocol was 0.0% (95%CI, 0.0-4.0) and - 2.1% (95%CI, - 5.4 to - 0.6) for SCC/CEC and 0.0% (95%CI, 0.0-3.3) and - 1.5% (95%CI, - 4.8 to - 0.3) for OCSF, all within the noninferiority margin of 5%. CONCLUSIONS: An abbreviated TS-MRI protocol of IRsag + T2ax is noninferior to the standard non-contrast protocol, potentially allowing for faster emergent imaging diagnosis and triage.

An acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans.

BACKGROUND: A sustained elevation in respiratory drive following removal of the inducing stimulus is known as respiratory long-term facilitation (rLTF). We investigated whether an acute exposure to intermittent negative airway pressure (INAP) elicits rLTF in humans. METHOD: 13 healthy males (20.9 ±â€¯2.8 years) undertook two trials (INAP and Control). In the INAP trial participants were exposed to one hour of 30-second episodes of breathing against negative pressure (-10 cmH2O) interspersed by 60-second intervals of breathing at atmospheric pressure. In the Control trial participants breathed at atmospheric pressure for one hour. Ventilation following INAP (recovery phase) was compared to that during baseline. RESULTS: Ventilation increased from baseline to recovery in the INAP trial (14.9 ±â€¯0.9 vs 19.1 ±â€¯0.7 L/min, P = 0.002). This increase was significantly greater than the equivalent during the Control trial (P = 0.019). Data shown as mean ± SEM. CONCLUSION: In this study INAP elicited rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms.

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson's Disease.

BACKGROUND: Paradoxical kinesis has been observed in bradykinetic people with Parkinson's disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson's disease tested on medication and in age-matched controls. METHODS: Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant's performance on previous trials using a staircase tracking procedure. RESULTS: On trials with threat of shock, both patients with Parkinson's disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. CONCLUSIONS: When motivated to avoid mild electric shock, patients with Parkinson's disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson's disease.

Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection.

While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control. These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.

Long-term facilitation of ventilation following acute continuous hypoxia in awake humans during sustained hypercapnia.

In awake humans, long-term facilitation of ventilation (vLTF) following acute intermittent hypoxia (AIH) is only expressed if CO2 is maintained above normocapnic levels. vLTF has not been reported following acute continuous hypoxia (ACH) and it is not known whether this might be unmasked by elevated CO2. Twelve healthy participants completed three trials. In all trials end-tidal pressure of CO2 was elevated 4-5 mmHg above normocapnic levels. During Trial 1 (AIH) participants were exposed to eight 4 min episodes of hypoxia. During Trial 2 (ACH) participants were exposed to continuous hypoxia for 32 min. In Trial 3 (Control) participants were exposed to euoxia throughout. To assess the contribution of the carotid body (CB) in observed ventilatory responses, CB afferent discharge before and after each trial was transiently inhibited with hyperoxia. Minute ventilation ( ˙V E) increased following all trials, but was significantly greater in Trials 1 and 2 when compared with Trial 3 (Trial 1: 4.96 ± 0.87, Trial 2: 5.07 ± 0.7, Trial 3: 2.55 ± 0.98 l min-1, P < 0.05). Hyperoxia attenuated VE to a similar extent in baseline and recovery in all trials (Trial 1: 3.0 ± 0.57 vs. 3.27 ± 0.68, Trial 2: 1.97 ± 0.62 vs. 2.56 ± 0.62, Trial 3: 2.23 ± 0.49 vs. 2.15 ± 0.55 l min-1, P > 0.05). Data are means ± SEM. In awake humans with elevated CO2, ACH evokes a sustained increase in ventilation that is comparable to that evoked by AIH. However, a gradual positive drift in ventilation in response to elevated CO2 accounts for approximately half of this apparent vLTF. Additionally, our data support the view that the CB is not directly involved in maintaining vLTF.

High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism.

Delayed HIV-1 disease progression is associated with a single nucleotide polymorphism upstream of the HLA-C gene that correlates with differential expression of the HLA-C Ag. This polymorphism was recently shown to be a marker for a protective variant in the 3'UTR of HLA-C that disrupts a microRNA binding site, resulting in enhanced HLA-C expression at the cell surface. Whether individuals with "high" HLA-C expression show a stronger HLA-C-restricted immune response exerting better viral control than that of their counterparts has not been established. We hypothesized that the magnitude of the HLA-C-restricted immune pressure on HIV would be greater in subjects with highly expressed HLA-C alleles. Using a cohort derived from a unique narrow source epidemic in China, we identified mutations in HIV proviral DNA exclusively associated with HLA-C, which were used as markers for the intensity of the immune pressure exerted on the virus. We found an increased frequency of mutations in individuals with highly expressed HLA-C alleles, which also correlated with IFN-γ production by HLA-C-restricted CD8(+) T cells. These findings show that immune pressure on HIV is stronger in subjects with the protective genotype and highlight the potential role of HLA-C-restricted responses in HIV control. This is, to our knowledge, the first in vivo evidence supporting the protective role of HLA-C-restricted responses in nonwhites during HIV infection.

Judging political affiliation from faces of UK MPs.

Subjects were shown photographs of UK MPs' faces and asked to judge their political affiliations. Participants were unable to correctly distinguish between Conservative and Labour politicians. However, their responses were used to create computer-generated idealised faces representative of each party, which independent evaluators could correctly identify. These faces give an indication of the mental images we might reference when imagining MPs from the two main UK political parties.

Relative faces: encoding of family resemblance relative to gender means in face space.

Neurophysiological (W. A. Freiwald, D. Y. Tsao, & M. S. Livingstone, 2009; D. A. Leopold, I. V. Bondar, & M. A. Giese, 2006) and psychophysical (D. A. Leopold, A. J. O'Toole, T. Vetter, & V. Blanz, 2001; G. Rhodes & L. Jeffery, 2006; R. Robbins, E. McKone, & M. Edwards, 2007) evidence suggests that faces are encoded as differences from a mean or prototypical face, consistent with the conceptual framework of a mean-centered face space (T. Valentine, 1991). However, it remains unclear how we encode facial similarity across classes such as gender, age, or race. We synthesized Caucasian male and female cross-gender "siblings" and "anti-siblings" by projecting vectors representing deviations of faces from one gender mean into another gender. Subjects perceived male and female pairings with similar vector deviations from their gender means as more similar, and those with opposite vector deviations as less similar, than randomly selected cross-gender pairings. Agreement in relative direction in a space describing how facial images differ from a mean can therefore provide a basis for perceived facial similarity. We further demonstrate that relative coding for male and female faces is based on the activation of a shared neural population by the transfer of an identity aftereffect between a face and its cross-gender sibling. These results imply whereas structural similarity may be reflected in the Euclidean distance between points in face space configural similarity may be coded by direction in face space.

Metabolically exaggerated cardiac reactions to acute psychological stress: the effects of resting blood pressure status and possible underlying mechanisms.

The study aimed to: confirm that acute stress elicits metabolically exaggerated increases in cardiac activity; test whether individuals with elevated resting blood pressure show more exaggerated cardiac reactions to stress than those who are clearly normotensive; and explore the underlying mechanisms. Cardiovascular activity and oxygen consumption were measured pre-, during, and post-mental stress, and during graded sub-maximal cycling exercise in 11 young men with moderately elevated resting blood pressure and 11 normotensives. Stress provoked increases in cardiac output that were much greater than would be expected from contemporary levels of oxygen consumption. Exaggerated cardiac reactions were larger in the relatively elevated blood pressure group. They also had greater reductions in total peripheral resistance, but not heart rate variability, implying that their more exaggerated cardiac reactions reflected greater beta-adrenergic activation.

Quality of life in Parkinson's disease: the relative importance of the symptoms.

A body of literature now exists, which demonstrates that idiopathic Parkinson's disease (PD) has a major negative impact on quality of life (QoL), and that depression and cognitive impairment are among the main predictors of poor QoL in this disorder. Relatively little work has been done to assess the differential contribution of the specific symptoms of PD to QoL, which was the aim of this study. One hundred thirty patients with PD completed a booklet of questionnaires, which included the PDQ39 as a disease-specific measure of QoL, a symptom checklist, a mobility checklist, as well as patient ratings of disease stage and disability. The results indicated that the contribution of physical, medication-related, and cognitive/psychiatric symptoms to QoL can be significant. Sudden unpredictable on/off states, difficulty in dressing, difficulty in walking, falls, depression, and confusion were PD symptoms, which significantly influenced QoL scores. Among the mobility problems associated with PD, start hesitation, shuffling gait, freezing, festination, propulsion, and difficulty in turning had a significant effect on QoL scores. In addition to depression and anxiety, the major predictors of QoL were shuffling, difficulty turning, falls, difficulty in dressing, fatigue, confusion, autonomic disturbance particularly urinary incontinence, unpredictable on/off fluctuations, and sensory symptoms such as pain. The implications of these results for the medical management of PD are discussed.