Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.

The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080.

Functional and immunological mapping of domains of the reticulocyte binding protein, Plasmodium vivax PvRBP2a.

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. We assessed the PvRBP2a epitopes involved in CD98 binding and recognised by antibodies from infected patients using linear epitope mapping. We identified two epitope clusters mediating PvRBP2a-CD98 interaction. One cluster named cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in P. vivax-infected humans. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood stage vaccine against P. vivax.

Prolonged inflammation in patients hospitalized for coronavirus disease 2019 (COVID-19) resolves 2 years after infection.

Long-term complications from coronavirus disease 2019 (COVID-19) are concerning, as survivors can develop subclinical multiorgan dysfunction. It is unknown if such complications are due to prolonged inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination may reduce sequela. We conducted a prospective longitudinal study on hospitalized patients over 24 months. Clinical symptoms were collected by self-reporting during follow-up, along with blood samples for quantification of inflammatory markers and immune cell frequencies. All patients were given one dose of mRNA vaccine at 12-16 months. Their immune profiles at 12 and 24 months were compared. Approximately 37% and 39% of our patients reported post-COVID-19 symptoms at 12 and 24 months, respectively. The proportion of symptomatic patients with more than one symptom decreased from 69% at 12 months to 56% at 24 months. Longitudinal cytokine profiling revealed a cluster of individuals with persistently high inflammatory cytokine levels 12 months after infection. Patients with prolonged inflammation showed elevated terminally differentiated memory T cells in their blood; 54% had symptoms at 12 months. The majority of inflammatory markers and dysregulated immune cells in vaccinated patients recovered to a healthy baseline at 24 months, even though symptoms persisted. Post-COVID-19 symptoms can linger for 2 years after the initial infection and are associated with prolonged inflammation. Prolonged inflammation in hospitalized patients resolves after 2 years. We define a set of analytes associated with persistent inflammation and presence of symptoms, which could be useful biomarkers for identifying and monitoring high-risk survivors.

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

Hinge length contributes to the phagocytic activity of HIV-specific IgG1 and IgG3 antibodies.

Antibody functions such as neutralization require recognition of antigen by the Fab region, while effector functions are additionally mediated by interactions of the Fc region with soluble factors and cellular receptors. The efficacy of individual antibodies varies based on Fab domain characteristics, such as affinity for antigen and epitope-specificity, and on Fc domain characteristics that include isotype, subclass, and glycosylation profile. Here, a series of HIV-specific antibody subclass and hinge variants were constructed and tested to define those properties associated with differential effector function. In the context of the broadly neutralizing CD4 binding site-specific antibody VRC01 and the variable loop (V3) binding antibody 447-52D, hinge truncation and extension had a considerable impact on the magnitude of phagocytic activity of both IgG1 and IgG3 subclasses. The improvement in phagocytic potency of antibodies with extended hinges could not be attributed to changes in either intrinsic antigen or antibody receptor affinity. This effect was specific to phagocytosis and was generalizable to different phagocytes, at different effector cell to target ratios, for target particles of different size and composition, and occurred across a range of antibody concentrations. Antibody dependent cellular cytotoxicity and neutralization were generally independent of hinge length, and complement deposition displayed variable local optima. In vivo stability testing showed that IgG molecules with altered hinges can exhibit similar biodistribution and pharmacokinetic profiles as IgG1. Overall, these results suggest that when high phagocytic activity is desirable, therapeutic antibodies may benefit from being formatted as human IgG3 or engineered IgG1 forms with elongated hinges.

Acute Ultrasonographic Changes in Lower Extremity Muscle Structure after Motor Complete Spinal Cord Injury.

Background: There is a lack of studies examining ultrasonographic muscle changes in patients with acute spinal cord injury (SCI). Methods: We recruited adults with motor complete acute SCI and performed longitudinal ultrasound measurements. The primary outcome measures were rectus femoris and medial gastrocnemius thickness and echo intensity. Results: This study recruited 20 patients, with a mean time to the first ultrasound measurement of 17.2 ± 2.14 days, with the second measurement done 4 weeks after the first measurement. We found that there was a mean decrease in the rectus femoris muscle thickness of 18.7% (P = 0.027), as well as a mean increase in the rectus femoris echo intensity of 13.0 a.u. (P = 0.009), although no significant differences were found for the medial gastrocnemius. Conclusion: This study demonstrates decreased thickness and increased echo intensity in the rectus femoris but not in the medial gastrocnemius in patients with motor complete SCI.

Prevalence and associations of axillary web syndrome in Asian women after breast cancer surgery undergoing a community-based cancer rehabilitation program.

BACKGROUND: Patients who have breast cancer surgery are at risk of axillary web syndrome (AWS), an under-recognized postsurgical complication which can result in shoulder morbidity and functional impairment. Emerging studies have indicated that AWS may persist beyond the first few months after surgery, although few studies have assessed the prevalence and association of AWS beyond a year after diagnosis. Therefore, the aim of this study was to investigate the prevalence and associations for AWS in post-operative breast cancer patients up to 3 years after surgery. METHODS: This cross sectional observational study was conducted at a community-based cancer rehabilitation center. Patients were evaluated for the presence of AWS via physical examination. Disease-related data was obtained from clinical review and medical records. Descriptive statistics were utilized to illustrate patient demographics and clinical characteristics. Logistic regression analyses were used to determine associations of AWS. RESULTS: There were 111 Asian women who were recruited, who had undergone breast surgery and were referred to a national outpatient rehabilitation center. The prevalence of AWS in this population was 28.9%. In the multivariate regression model, significant factors were age < 50 years (OR = 3.51; 95% CI = 1.12-11.0; p = 0.031) and ALND (OR = 6.54; 95% CI = 1.36-31.3; p = 0.019). There was reduced shoulder flexion ROM (p < 0.001) in patients with AWS compared to patients without AWS. CONCLUSIONS: A high prevalence of AWS was reported in breast cancer survivors even at 3 years after breast surgery. Our findings highlight the need to identify breast cancer survivors with AWS even in the survivorship phase, and develop strategies to raise awareness and minimize functional impairment in these patients.

Prevalence and Risk Factors of Adhesive Capsulitis in Asian Breast Cancer Patients Undergoing an Outpatient Community Cancer Rehabilitation Program.

OBJECTIVES: To investigate the prevalence and risk factors for adhesive capsulitis in postoperative breast cancer patients up to 5 years after surgery who were attending an outpatient community cancer rehabilitation program, and to determine whether any significant relationship exists between arm lymphedema and adhesive capsulitis. DESIGN: Cross-sectional observational study. SETTING: National cancer rehabilitation center. PARTICIPANTS: Asian women (N=135) who underwent breast surgery and were referred for an outpatient community cancer rehabilitation program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Presence of adhesive capsulitis, lymphedema. RESULTS: The prevalence of adhesive capsulitis and lymphedema in this population was 22.2% and 33.3%, respectively. A history of mastectomy (odds ratio [OR], 3.93; 95% confidence interval [CI], 1.23-12.63; P=.021), mastectomy with reconstruction (OR, 2.72; 95% CI, 1.27-30.54; P=.024), and lymphedema (OR, 7.92; 95% CI, 2.73-22.95; P<.001) were found to be significantly associated with adhesive capsulitis on multivariate analysis. CONCLUSIONS: Adhesive capsulitis and lymphedema are common in breast cancer survivors. The design of cancer rehabilitation programs for breast cancer survivors should include surveillance and management of adhesive capsulitis, especially in the presence of lymphedema.

Short-Term Effect of Peer Volunteers in Providing Inpatient Rehabilitative Exercises for Patients After Total Knee Arthroplasty.

OBJECTIVE: To investigate the short-term outcomes at discharge of patients who receive additional postoperative rehabilitative exercises by peer volunteers after total knee arthroplasty (TKA). DESIGN: Retrospective cohort study. SETTING: Tertiary teaching hospital. PARTICIPANTS: A total of 476 adult patients who had undergone a primary elective unilateral TKA (N=467). INTERVENTIONS: An intervention group received a standardized postoperative rehabilitative exercise protocol taught and supervised by peer volunteers in additional to standard physiotherapy (n=309) compared with a control group receiving standard physiotherapy alone (n=167). MAIN OUTCOME MEASURES: Discharge outcomes were the pain score using the Numeric Rating Scale pain score, passive knee flexion and extension range of motion (ROM), length of hospitalization, ability to perform an unassisted straight leg raise of the operated leg, ambulation distance, ability in independent walking, walking aids required, discharge destination, and adverse events. RESULTS: On multivariate analysis, patients in the intervention group had an increased discharge passive knee flexion ROM of 7.89 degrees (95% confidence interval, 5.47-10.33; P<.001). There were no significant differences for the other outcome measures between the intervention and control group. CONCLUSIONS: A rehabilitative exercise program by peer volunteers is feasible and safe after TKA in addition to standard physiotherapy and is associated with improved knee flexion ROM on discharge.

Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1.

The humoral response to invading mucosal pathogens comprises multiple antibody isotypes derived from systemic and mucosal compartments. To understand the contribution of each antibody isotype/source to the mucosal humoral response, parallel investigation of the specificities and functions of antibodies within and across isotypes and compartments is required. The role of IgA against HIV-1 is complex, with studies supporting a protective role as well as a role for serum IgA in blocking effector functions. Thus, we explored the fine specificity and function of IgA in both plasma and mucosal secretions important to infant HIV-1 infection, i.e., breast milk. IgA and IgG were isolated from milk and plasma from 20 HIV-1-infected lactating Malawian women. HIV-1 binding specificities, neutralization potency, inhibition of virus-epithelial cell binding, and antibody-mediated phagocytosis were measured. Fine-specificity mapping showed IgA and IgG responses to multiple HIV-1 Env epitopes, including conformational V1/V2 and linear V2, V3, and constant region 5 (C5). Env IgA was heterogeneous between the milk and systemic compartments (Env IgA, τ = 0.00 to 0.63, P = 0.0046 to 1.00). Furthermore, IgA and IgG appeared compartmentalized as there was a lack of correlation between the specificities of Env-specific IgA and IgG (in milk, τ = -0.07 to 0.26, P = 0.35 to 0.83). IgA and IgG also differed in functions: while neutralization and phagocytosis were consistently mediated by milk and plasma IgG, they were rarely detected in IgA from both milk and plasma. Understanding the ontogeny of the divergent IgG and IgA antigen specificity repertoires and their effects on antibody function will inform vaccination approaches targeted toward mucosal pathogens.IMPORTANCE Antibodies within the mucosa are part of the first line of defense against mucosal pathogens. Evaluating mucosal antibody isotypes, specificities, and antiviral functions in relationship to the systemic antibody profile can provide insights into whether the antibody response is coordinated in response to mucosal pathogens. In a natural immunity cohort of HIV-infected lactating women, we mapped the fine specificity and function of IgA in breast milk and plasma and compared these with the autologous IgG responses. Antigen specificities and functions differed between IgG and IgA, with antiviral functions (neutralization and phagocytosis) predominantly mediated by the IgG fraction in both milk and plasma. Furthermore, the specificity of milk IgA differed from that of systemic IgA. Our data suggest that milk IgA and systemic IgA should be separately examined as potential correlates of risk. Preventive vaccines may need to employ different strategies to elicit functional antiviral immunity by both antibody isotypes in the mucosa.

Caregiver burden in familial caregivers and foreign domestic workers of patients with traumatic brain injury in a multi-ethnic Asian population.

OBJECTIVE: The purpose of this study was to investigate the prevalence and risk factors associated with caregiver burden in familial caregivers and foreign domestic workers of patients with severe traumatic brain injury. METHODS: A total of 77 caregivers were consecutively recruited, who were either familial caregivers or foreign domestic workers. All caregivers were evaluated with the Zarit Burden Index (ZBI), Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder 7-item (GAD-7) scale. Logistic regression analysis was conducted to determine factors associated with caregiver burden. RESULTS: The majority of participants were familial caregivers (N = 60), of which 70% experienced significant caregiver burden. In this group, 10.0% caregivers had clinically significant depression and 16.7% caregivers who had clinically significant anxiety. On multivariate analysis, factors found to be associated with caregiver burden were Glasgow Outcome Scale Extended (GOSE) of <7, presence of neuropsychiatric complications, and presence of anxiety. There was also a high prevalence of caregiver burden in foreign domestic workers (29.4%). CONCLUSION: There is a high rate of caregiver burden in both familial caregivers and foreign domestic workers who care for patients with severe traumatic brain injury. Caregivers experiencing stress should also be monitored for the presence of anxiety or depression.

HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.

Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments.IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the functional properties of HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1-specific IgA, specifically for vaccine-elicited IgA. Characterization of the functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human vaccine clinical trials are critical toward understanding the capacity of the host immune response to block HIV-1 acquisition.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.

Relationship of serial muscle ultrasound of rectus femoris and ambulatory recovery in patients with acute incomplete spinal cord injury: A prospective observational study.

CONTEXT/OBJECTIVE: To investigate the change in serial muscle ultrasound of rectus femoris of patients with incomplete spinal cord injury (SCI) performed within 2 months after SCI during acute rehabilitation, and the relationship with functional outcomes at 1 year post-injury. DESIGN: Prospective observational study. SETTING: Inpatient multi-speciality tertiary rehabilitation center in Singapore. PARTICIPANTS: Fifty-four patients with incomplete SCI, defined as American Spinal Injury Association Impairment Scale B-D, with SCI above L2, were recruited from March 2020 to June 2021. Serial muscle ultrasound of the rectus femoris thickness and echo intensity were obtained at 1 week post-injury and after 2 months via standardized protocols. OUTCOME MEASURES: Functional Independence Measure (FIM) motor score, Lower Extremity Motor Score (LEMS), Spinal Cord Independence Measure III (SCIM III) indoor mobility component and Walking Index for Spinal Cord Injury II (WISCI II) were assessed in the first week post-admission and at 1 year. RESULTS: There was a significant positive correlation between change in rectus femoris muscle thickness over 2 months and FIM motor score (P < 0.001), LEMS (P < 0.001), SCIM III indoor mobility component (P < 0.001) and WISCI II (P < 0.001) at 1 year. For the change in echo intensity over 2 months, there was a significantly negative correlation with FIM motor score (P = 0.002), LEMS (P = 0.002), SCIM III indoor mobility component (P = 0.001) and WISCI II (P = 0.001) at 1 year. CONCLUSION: The findings suggest that ultrasonographic serial assessment of rectus femoris muscle thickness and echo intensity during rehabilitation may be useful for determining the long-term functional outcomes in patients with incomplete SCI.

Return to Work in Breast Cancer Patients following an Interdisciplinary Rehabilitation Program in a Community-Based Cancer Rehabilitation Center: A Pilot Study.

Despite curative treatment and discharge from acute hospital settings, breast cancer patients often have cancer- and treatment-related morbidity which impairs them from returning to work. Hence, the role of community-based return to work rehabilitation programs is important to help these patients transition back to work. This was a retrospective cohort study involving patients with breast cancer conducted at a community-based cancer rehabilitation center. Patients were involved in an interdisciplinary vocational rehabilitation program involving physiatrists, occupational therapists, physiotherapists and social workers. We recruited 63 patients for this study cohort, with 46 (73.0%) patients ≤ 60 years old. After undergoing the rehabilitation program, there were 37 (58.7%) participants who successfully returned to work. These participants returned to work at either within 6 months (27.0%), 12 months (29.7%) or 24 months (43.2%) after enrollment into the program, with a majority enrolling in white collar jobs. Multivariate regression analysis revealed that significant negative factors for return to work were advanced stage of cancer (p = 0.004), along with clinically significant fatigue, measured on the Brief Fatigue Inventory (p < 0.001). However, perceived work ability (p = 0.020) was found to be a positive factor.

Unraveling stroke gait deviations with movement analytics, more than meets the eye: a case control study.

Background: This study aimed to identify and quantify the kinematic and kinetic gait deviations in post-stroke hemiplegic patients with matched healthy controls using Statistical Parametric Mapping (SPM). Methods: Fifteen chronic stroke patients [4 females, 11 males; age 53.7 (standard deviation 12.2) years; body mass 65.4 (10.4) kg; standing height 168.5 (9.6) cm] and 15 matched healthy controls [4 females, 11 males; age 52.9 (11.7) years; body weight 66.5 (10.7) years; standing height 168.3 (8.8) cm] were recruited. In a 10-m walking task, joint angles, ground reaction forces (GRF), and joint moments were collected, analyzed, and compared using SPM for an entire gait cycle. Results: Generally, when comparing the stroke patients' affected (hemiplegic) and less-affected (contralateral) limbs with the control group, SPM identified significant differences in the late stance phase and early swing phase in the joint angles and moments in bilateral limbs (all p < 0.005). In addition, the vertical and anteroposterior components of GRF were significantly different in various periods of the stance phase (all p < 0.005), while the mediolateral component showed no differences between the two groups. Conclusion: SPM was able to detect abnormal gait patterns in both the affected and less-affected limbs of stroke patients with significant differences when compared with matched controls. The findings draw attention to significant quantifiable gait deviations in the less-affected post-stroke limb with the potential impact to inform gait retraining strategies for clinicians and physiotherapists.

Imprinting of IgA responses in previously infected individuals receiving bivalent mRNA vaccines (WT and BA.4/BA.5 or WT and BA.1).

OBJECTIVES: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants. METHODS: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster. RESULTS: We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees. CONCLUSION: The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection.

B-cell ELISpot assay to analyze human memory B cell and plasmablast responses specific to SARS-CoV-2 receptor-binding domain.

B-cell ELISpot is an extremely sensitive assay based on the secretion of antibodies by B cells that requires the differentiation of B cells into antibody-secreting cells. Here, we describe the procedure to analyze both plasmablast (PB) and memory B cell (MBC) responses specific to SARS-CoV-2 receptor-binding domain (RBD) in the context of acute SARS-CoV-2 infection and vaccination. We detail steps for MBC stimulation, MBC and PB plating, detection, and counting of total IgG and RBD-specific spots. For complete details on the use and execution of this protocol, please refer to Tay et al. (2022).1.