Emotional Facial Expression Detection in the Peripheral Visual Field

BACKGROUND: In everyday life, signals of danger, such as aversive facial expressions, usually appear in the peripheral visual field. Although facial expression processing in central vision has been extensively studied, this processing in peripheral vision has been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Using behavioral measures, we explored the human ability to detect fear and disgust vs. neutral expressions and compared it to the ability to discriminate between genders at eccentricities up to 40°. Responses were faster for the detection of emotion compared to gender. Emotion was detected from fearful faces up to 40° of eccentricity. CONCLUSIONS: Our results demonstrate the human ability to detect facial expressions presented in the far periphery up to 40° of eccentricity. The increasing advantage of emotion compared to gender processing with increasing eccentricity might reflect a major implication of the magnocellular visual pathway in facial expression processing. This advantage may suggest that emotion detection, relative to gender identification, is less impacted by visual acuity and within-face crowding in the periphery. These results are consistent with specific and automatic processing of danger-related information, which may drive attention to those messages and allow for a fast behavioral reaction

Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses

Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected macaques, whereas natural reservoir hosts exhibit limited disease and pathology. It is, however, unclear how natural hosts can sustain high viral loads, comparable to those observed in the pathogenic model, without developing severe disease. We performed transcriptional profiling on lymph node, blood, and colon samples from African green monkeys (natural host model) and Asian pigtailed macaques (pathogenic model) to directly compare gene expression patterns during acute pathogenic versus non-pathogenic SIV infection. The majority of gene expression changes that were unique to either model were detected in the lymph nodes at the time of peak viral load. Results suggest a shift toward cellular stress pathways and Th1 profiles during pathogenic infection, with strong and sustained type I and II interferon responses. In contrast, a strong type I interferon response was initially induced during non-pathogenic infection but resolved after peak viral load. The natural host also exhibited controlled Th1 profiles and better preservation of overall cell homeostasis. This study identified gene expression patterns that are specific to disease susceptibility, tissue compartmentalization, and infection duration. These patterns provide a unique view of how host responses differ depending upon lentiviral infection outcome

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Secondary Analysis of Short- and Long-Term Variability of Inspiratory Muscle Performance in People Living With SCI

Objectives To explore the expected variability in repeated short-term (ST) and long-term (LT) inspiratory muscle performance (IMP) in individuals with chronic spinal cord injury (SCI). Methods Maximal inspiratory pressure (MIP), sustained MIP (SMIP), and inspiratory duration (ID) were collected from 22 individuals with chronic SCI (C1-T9, American Spinal Injury Association Impairment Scale [AIS] A-C) over 18 months. ST data were collected four times within 2 weeks (n = 19). LT data were collected at two time points at least 7 months apart (n = 20). Results SMIP was the most reliable IMP assessment with an intraclass correlation coefficient (ICC) of 0.959, followed by MIP (ICC 0.874) and ID (ICC 0.689). The ID was the only ST measure to have a significant difference [MIP: F(3, 54) = 2.5, p = .07; SMIP: F(3, 54) = 1.3, p = .29; ID: F(1.4, 25.6) = 4.8, p = .03]. Post hoc analysis showed the mean day 1 ST ID measure was significantly different from both days 3 and 4. The percent change of ID from day 3 to day 6 was 11.6%. No LT measures differed significantly [mean change (SD) [95% CI] for MIP: 5.2 cm H2O (18.8) [−3.6, 13.9], p = .235; SMIP: 60.9 pressure time unit (166.1) [−16.9, 138.6], p = .118; ID: 0.1 s (2.5) [−1.1, 1.3], p = .855]. Conclusion These data provide a foundation for understanding normal variance in ST and LT IMP in the SCI population. Change in MIP function outside 10% is likely a true and meaningful change and may help clinicians recognize individuals with SCI at risk for respiratory compromise. Future studies should explore changes in MIP and SMIP that are associated with meaningful functional changes

A case for inspiratory muscle training in SCI: potential role as a preventative tool in infectious respiratory diseases like COVID-19

Respiratory complications (RC) are a leading cause of death after spinal cord injury (SCI) due to compromised immune function and respiratory muscle weakness. Thus, individuals with SCI are at high risk of developing COVID-19 related RC. Results of a SCI clinical trial showed a supervised respiratory muscle training (RMT) program decreased risk of developing RC. The feasibility of conducting unsupervised RMT is not well documented. Four publications (n = 117) were identified in which unsupervised RMT was performed. Significant improvements in respiratory outcomes were reported in two studies: Maximal Inspiratory and Expiratory Pressure (MIP40% and MEP25%, respectively), Peak Expiratory Flow (PEF9%), seated and supine Forced Vital Capacity (FVC23% and 26%, respectively), and Peak Cough Flow (28%). This review and case report will attempt to show that an inspiratory muscle training (IMT) home exercise program (HEP) is feasible and may prepare the respiratory system for RC associated with COVID-19 in patients with SCI. A 23-year-old with tetraplegia (P1), history of mechanical ventilation, and hospitalization for RC, completed 27 IMT HEP sessions in one month. MIP and sustained MIP (SMIP) increased from baseline by 28% and 26.5%, respectively. Expiratory volumes and rates also improved (FVC, FEV1, and PEF: 11.7%, 8.3%, and 14.2%, respectively). The effects of COVID-19 on patients with SCI remains inconclusive, but recent literature and the results of this case suggest that unsupervised IMT is feasible and may limit the severity of RC in patients with SCI who contract COVID-19

Psychometric Testing and Clinical Utility of a Modified Version of the Function in Sitting Test for Individuals With Chronic Spinal Cord Injury

Seated balance (SB) is substantially compromised and greatly impacts the function of individuals living with a spinal cord injury (SCI). A clinically applicable criterion standard measure for SB does not exist for this population. Initial validation and reliability analysis of the Function in Sitting Test (FIST) in SCI has been published, but the authors of this study report that modifications to the tool may be necessary. This study aimed to explore the psychometrics and clinical utility of a modified version of the FIST to better measure SCI-specific functional tasks in sitting. The FIST was modified (FIST-SCI) by an expert panel and used by 2 graders to evaluate the SB of individuals with chronic SCI (cSCI) on 2 separate days. The Motor Assessment Scale item 3 (MAS-SCI) was included as a comparison measure. Research facility. Individuals with cSCI longer than 1 year (N=38) participated in the study. Injury levels of individuals participating in this study spanned C1 to T10 (American Spinal Injury Association Impairment Scale A, 17 subjects; B, 12 subjects; and C, 9 subjects). Thirteen individuals required assistance to transfer. Not applicable. Validity, reliability, internal consistency, sensitivity, specificity, and responsiveness. Validity testing found a moderate relationship between the MAS-SCI and the FIST-SCI (ρ, .522; P<.05). FIST-SCI scores distinguished individuals requiring assistance to transfer from those who were independent (t=4.51; P<.05). Inter- and intra-rater reliability were excellent (intraclass correlation coefficient (2,k)=.985 and .983, respectively) and internal consistency was excellent (α=.94). A FIST-SCI cutoff score of 45 or greater was 92% sensitive and specific in characterizing transfer ability. Standard error of the measure (1.3) and minimal detectable change (3.5) were similar to previous work. Initial validity of the FIST-SCI is reported, but further assessment is required. Reliability is excellent in the cSCI population. FIST-SCI scores provide clinical insight into the seated functional ability of individuals with cSCI

Clinician-Focused Overview of Bionic Exoskeleton Use After Spinal Cord Injury

Spinal cord injury (SCI) resulting in paralysis of lower limbs and trunk restricts daily upright activity, work capacity, and ambulation ability, putting persons with an injury at greater risk of developing a myriad of secondary medical issues. Time spent in the upright posture has been shown to decrease the risk of these complications in SCI. Unfortunately, the majority of ambulation assistive technologies are limited by inefficiencies such as high energy demand, lengthy donning and doffing time, and poor gait pattern precluding widespread use. These limitations spurred the development of bionic exoskeletons. These devices are currently being used in rehabilitation settings for gait retraining, and some have been approved for home use. This overview will address the current state of available devices and their utility

Adherence to and impact of home-based high-intensity IMT in people with spinal cord injury: a pilot study

Study design The pilot study was completed in 5 phases (Control and 4 phases of IMT) incorporating assessments at Baseline 1 (BL1), BL2, Follow-up 1 (F1), F2, F3, and F4. Objective To assess the adherence and impact of a daily high-intensity (80% of max) inspiratory muscle training (IMT) home program with once weekly supervision for people with spinal cord injury (SCI). Setting Assessments: research institution or zoom. IMT: participant's home. Methods Participants completed daily IMT in IMT Phase 1 and 2, once weekly in IMT Phase 3, self-selected frequency in IMT Phase 4. All phases had one weekly supervised session except IMT Phase 4. Primary outcomes included adherence and a difficulty score [DS (0- not difficult to 10- the most difficult)]. Secondary outcomes included respiratory function and seated balance. Results Data from 10 people with chronic SCI (>1 year) (Cervical level of injury: 6, AIS: A-B, injury duration: 10.9 years 95% CI [3.9, 18.1]) were used in the analysis. Participants completed 69% of their training days in IMT Phase 1 and 65% overall reporting an average DS of 7.4 +/- 1.4. Only one participant completed training during IMT Phase 4. One participant's training load was reduced due to suspected overtraining. Maximal inspiratory pressure (MIP), sustained MIP (SMIP), and total power (TP), improved significantly (p < 0.05) from BL2 to F1. Conclusion Our data suggest that people with SCI can perform high-intensity IMT at home to improve inspiratory performance. It is strongly recommended that participants be intermittently monitored for adherence and safety. ClinicalTrials.gov Registration number: NCT04210063