BackgroundImplantable brain–computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation.MethodsTwo participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks.ResultsUnsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%–100.00%) (trial mean (median, Q1–Q3)) at a rate of 13.81 (13.44, 10.96–16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%–100.00%) at 20.10 (17.73, 12.27–26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants.ConclusionWe describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.

The CD4 glycoprotein is the major cellular receptor for HIV. CD4 surface expression of monocytes decreases with time in culture while their susceptibility to HIV-1 increases. Our aim was to investigate whether this phenomenon occurs in macrophages that have differentiated in vivo by investigating CD4 expression and HIV-1 infection of human alveolar macrophages (AMs). Using flow cytometry to detect CD4 expression by Leu-3a labeled indirectly with fluorescein isothiocyanate or allophycocyanin, we found that CD4 was expressed at low but detectable levels, despite the high background autofluorescence well described in AMs. This finding was supported by the detection of CD4 mRNA in AMs using RT-PCR. T cell contamination of mRNA extracts of AMs was excluded by amplifying in parallel with primers to the constant region of the T cell receptor. Despite this low level of surface CD4, recombinant soluble CD4 and anti-CD4 antibody completely inhibited HIV-1 infection of AMs. We conclude that CD4, although expressed at low levels on the surface of AMs, appears to be critical to HIV-1 infection of these cells.

Although alveolar macrophages infected in vitro are more permissive for HIV-1 replication than PBM, this difference could not be demonstrated in vivo.

Pulmonary function tests (PFTs) are routinely used to assess lung function, but they do not provide information about regional pulmonary dysfunction. We aimed to assess correlation of quantitative ventilation-perfusion (V/Q) PET/CT with PFT indices. Methods: Thirty patients underwent V/Q PET/CT and PFT. Respirationgated images were acquired after inhalation of 68 Ga-carbon nanoparticles and administration of 68 Ga-macroaggregated albumin. Functional volumes were calculated by dividing the volume of normal ventilated and perfused (%NVQ), unmatched and matched defects by the total lung volume. These functional volumes were correlated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusing capacity for carbon monoxide (DLCO). Results: All functional volumes were significantly different in patients with chronic obstructive pulmonary disease (P , 0.05). FEV1/FVC and %NVQ had the highest correlation (r 5 0.82). FEV1 was also best correlated with %NVQ (r 5 0.64). DLCO was best correlated with the volume of unmatched defects (r 5 −0.55). Considering %NVQ only, a cutoff value of 90% correctly categorized 28 of 30 patients with or without significant pulmonary function impairment. Conclusion: Our study demonstrates strong correlations between V/Q PET/CT functional volumes and PFT parameters. Because V/Q PET/CT is able to assess regional lung function, these data support the feasibility of its use in radiation therapy and preoperative planning and assessing pulmonary dysfunction in a variety of respiratory diseases. Pul monary function tests (PFTs) are simple, noninvasive, and well-established physiologic investigations that provide reliable information about global lung function (1). However, they may be insensitive for detection of early pulmonary dysfunction (2,3) and do not provide spatial information about regional pulmonary dysfunction (4). Although PFTs measure the mechanics of gas exchange properties of the lungs, they provide limited information about pulmonary blood flow, a key component of gas exchange in the lung. Establishing a functional map of the regional ventilation and perfusion in the lungs is highly relevant to understanding the physiologic features of the lungs in many clinical situations, including individualizing and adapting radiation therapy planning (5,6), predicting postoperative lung function after lung resection in lung cancer patients (7), or predicting clinical outcomes after lung volume reduction surgery in patients with emphysema (8).The principle underlying ventilation-perfusion (V/Q) scintigraphy is attractive for lung function assessment because it simultaneously assesses and compares the regional distribution of the 2 major determinants of gas exchange in the lungs. Ventilation is imaged after inhalation of inert gases or radiolabeled aerosols, such as 99m Tc-labeled aerosol (Technegas; Cyclopharm), that reach terminal bronchioles in proportion to regional distribution of ventilation (9). Perfusion is imaged after intravenous administration of 9...