Measuring Gait Parameters from Structural Vibrations.

Measuring gait parameters (e.g. speed, cadence, step duration) accurately is invaluable for evaluation during treatment of older adults who struggle with disability onset, disease progression, balance, and injurious falls. Traditionally stopwatches or timing gates are used to measure gait speed in clinical settings, and these are limited to measuring gait speed. Other wearable and non-wearable technologies offer the ability to measure additional gait parameters though patients are known to walk differently with the devices and even tend to slow down before engaging with a non-wearable such as a floor mat. Floor vibrations are a promising option to measuring gait parameters while not being intrusive and not requiring line-of-sight to the patient for measurements. This paper presents methodology for extracting gait parameters using vibrations with comparisons to APDM Wearable Technologies Mobility Lab sensors and stopwatch measurements. Performance is examined across 97 participants for self-selected speed forward, full speed forward, and backwards walks at three different testing sites for a total of 1039 walks. Gait speed vibrations measurements demonstrated excellent reliability with APDM Mobility Lab (ICC: 0.98; 99% CI: 0.01±0.01 m/s) and stopwatch (ICC: 0.97; 99% CI: -0.01±0.01 m/s) measurements. Similar excellent results are reported for cadence, gait cycle duration, step duration, and stride length parameters.

Footstep localization and force estimation through structural vibrations using the FEEL Algorithm.

Locating individuals within a space has numerous potential uses within a smart environment. Many different technologies have been explored towards this end though privacy-concerns, the need to wear a device, and/or extensive building modifications have presented challenges towards adoption. Structural vibrations caused by footsteps have been shown to overcome these challenges though current methods rely on time-of-flight variations. This paper presents the use of the Force Estimation and Event Localization (FEEL) Algorithm that utilizes lower sampling rates, less sensors, etc than time-of-flight methods towards locating persons. Improvements to FEEL's force estimation and SDFE localization method are additionally presented with demonstrated increases in accuracy. Analysis of 1100 footsteps resulted in 98.6% localization accuracy using the improved FEEL. Ground force reactions (GRF) were estimated by FEEL and used to estimate participant body-weight-ratios (BWR). Estimated BWRs were within ranges reported in previous works for both barefoot and shoe cases.

Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.

BACKGROUND: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. OBJECTIVE: To characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission. DESIGN: Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. SETTING: Tertiary care center. PATIENTS: Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors. MEASUREMENTS: Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. RESULTS: No HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients. LIMITATION: The study involved only 2 patients. CONCLUSION: Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission. PRIMARY FUNDING SOURCE: Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.

Reversible dementia in a patient with central nervous system escape of human immunodeficiency virus.

HIV-associated neurocognitive disorders (HAND) are a group of conditions ranging from asymptomatic neurocognitive impairment to disabling dementia. The clinical spectrum and pathogenesis of these disorders is changing in the era of highly active antiretroviral therapy (HAART). High levels of HIV may exist in the cerebrospinal fluid (CSF) of some patients despite suppression of serum viral loads by HAART. We report a case of a 51-year-old male with profound levels of HIV in the CSF despite low serum levels. Adjusting his HAART regimen based on HIV genotype susceptibility data and a CNS Penetrating Effectiveness (CPE) score resulted in a dramatic improvement in cognitive function. Progressive dementia in this context is a rare but emerging trend and may be reversible.

Ocular syphilis among HIV-infected patients: a systematic analysis of the literature.

BACKGROUND: Ocular syphilis among HIV-infected patients continues to be a problem in the highly active antiretroviral therapy (HAART) era. However, outside of case reports or small case series, little is known about the clinical, laboratory, and treatment outcomes of these patients. Objective To examine the literature on HIV-infected patients and determine the results of treatment. METHODS: Systematic review of cases series and case reports among HIV-infected individuals with ocular syphilis. Reviews, languages other than English and pre-1980 reports were excluded. The effect of CD4 count and virological suppression on clinical manifestations and diagnostic laboratory values was evaluated. RESULTS: A total of 101 HIV-infected individuals in case series and case reports were identified. Ocular syphilis led to the HIV diagnosis in 52% of cases, including patients with CD4 count >200 cells/mm(3). Posterior uveitis was significantly more common in individuals with CD4 count <200 cells/mm(3) (p = 0.002). Three patients with confirmed ocular syphilis had negative non-treponemal tests. Ninety-seven per cent of patients with visual impairment improved following intravenous penicillin or ceftriaxone. CONCLUSIONS: Non-treponemal tests may be negative in HIV-infected patients with ocular syphilis. Ocular syphilis remains an important clinical manifestation that can lead to initial HIV diagnosis.

Ocular syphilis among HIV-infected individuals.

We describe a human immunodeficiency virus (HIV)-infected individual with ocular manifestations of secondary syphilis. Twelve other cases of HIV-associated ocular syphilis are also presented. Six of 12 individuals had normal cerebrospinal fluid study results, and 3 patients required retreatment within 1.5 years. In patients with HIV infection, clinicians should be vigilant for ocular syphilis despite normal cerebrospinal fluid measures and for syphilis reinfection.

Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection.

BACKGROUND: CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-gamma+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were "Controllers" (median 1140 RNA copies/ml plasma, range<50 to 2520), and 20 "progressors" of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to >750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated. CONCLUSIONS/SIGNIFICANCE: These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function.

Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection.

BACKGROUND: Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. METHODS AND FINDINGS: We measured T cell responsiveness by lymphoproliferation and interferon-gamma ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r(2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-gamma response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = -0.94, p = 0.017). CONCLUSIONS: These results indicate that HIV infection impairs the immune response to HCV-including in persons who have cleared HCV infection-and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population.

Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection.

Natural killer (NK) cells are critical in the first-line defense against viral infections. Chronic HIV-1 infection leads to a perturbation in the NK cell compartment, yet the kinetics of this deregulation and the functional consequences are unclear. Here, we characterized changes in the NK cell compartment longitudinally by multiparameter flow cytometry, starting in acute HIV-1 infection. Acute HIV-1 infection was associated with elevated NK cell numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied by reduced functional activity, as measured by CD107a expression and cytokine secretion. Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties.

BK virus-associated hemorrhagic cystitis in a Human Immunodeficiency Virus-infected patient.

BK virus-associated hemorrhagic cystitis is a common clinical problem in bone marrow transplant recipients but is considered rare in other immunosuppressed patient populations. We describe a human immunodeficiency virus-infected patient with non-Hodgkin's lymphoma in whom BK virus-associated hemorrhagic cystitis developed; viruria was quantitated in urine by immunocytochemistry, and the patient showed no response to cidofovir.