Proprioception-related gene mutations in relation to the aetiopathogenesis of idiopathic scoliosis: A scoping review.

Since idiopathic scoliosis is a multifactorial disorder, the proprioceptive defect is considered one of its etiological factors. Genetic studies have separately revealed this relationship, yet it remains indeterminate which specific genes that related to proprioception contributed to the initiation, progression, pathology, and treatment outcomes of the curvature. A systematic search was conducted on four online databases, including PubMed, Web of Science, Embase, and Academic search complete. Studies were included if they involved human or animal subjects with idiopathic scoliosis and evaluated with proprioceptive genes. The search period was the inception of the database to February 21, 2023. Four genes (i.e., Ladybird homeobox 1 [LBX1], Piezo type mechanosensitive ion channel component 2 [PIEZO2], Runx family transcription factor 3 [RUNX3], and neurotrophin 3 [NTF3]) investigated in 19 studies were included. LBX1 has confirmed the correlation with the development of idiopathic scoliosis in 10 ethnicities, whereas PIEZO2 has shown a connection with clinical proprioceptive tests in subjects with idiopathic scoliosis. However, curve severity was less likely to be related to the proprioceptive genes. The potential pathology took place at the proprioceptive neurons. Evidence of proprioception-related gene mutations in association with idiopathic scoliosis was established. Nevertheless, the causation between the initiation, progression, and treatment outcomes with proprioceptive defect requires further investigation.

Quantitative physical performance tests can effectively detect Degenerative Cervical Myelopathy: A systematic review and meta-analysis.

PURPOSE: This review aimed to identify effective physical performance tests (PPT) as clinical outcome indicators for detecting and monitoring degenerative cervical myelopathy (DCM). METHODS: A comprehensive literature search was performed on seven electronic databases on the effectiveness in detection and monitoring of DCM by PPT. All included studies were reviewed and undergone quality assessments on the risk-of-bias by Newcastle-Ottawa Scale and were pooled by random-effect analysis with level of significance at 0.05. Homogeneity among studies was assessed by I2-statistics and effect of PPT was confirmed by Cohen's d effect size and confidence intervals. RESULTS: Totally, 3111 articles were retrieved, and 19 studies were included for review and meta-analysis. There were 13 studies investigating PPT regarding the upper limbs and 12 studies regarding the lower limbs. Performance in 10-second-Grip-and-Release Test (G&R) and 9-Hole-Peg Test (9HPT) was studied in 10 and 3 articles, respectively, while 10-second-Stepping Test (SST), 30-meter-Walking Test (30MWT) and Foot-Tapping Test (FTT) for lower limbs were studied in 5, 4, and 3 articles correspondingly. Only 1 study utilized the Triangle-Stepping Test. High-quality study with fair risk-of-bias was revealed from Newcastle-Ottawa scale. Large effect size facilitated detection and monitoring in DCM was unveiling for G&R, 9HPT, SST, and 30MWT. FTT, while also effective, was hindered by a high-degree heterogeneity in the meta-analysis. CONCLUSION: Effective PPT including G&R, 9HPT, SST, 30MWT, and FTT was identified for disease detection and monitoring in DCM.

Timely Revisit of Proprioceptive Deficits in Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The present review aimed to summarize the evidence regarding differences in proprioception between children with and without adolescent idiopathic scoliosis (AIS). METHODS: Seven electronic databases were searched from their inception to April 10, 2021. Articles were included if they involved: (1) AIS patients aged between 10 and 18 years, (2) measurements of proprioceptive abilities, and (3) comparisons with non-AIS controls. Animal studies, case reports, commentaries, conference proceedings, research protocols, and reviews were excluded. Two reviewers independently conducted literature screening, data extraction, risks of bias assessments, and quality of evidence evaluations. Relevant information was pooled for meta-analyses. RESULTS: From 432 identified citations, 11 case-control studies comprising 1121 participants were included. The meta-analyses showed that AIS participants displayed proprioceptive deficits as compared to non-AIS controls. Moderate evidence supported that AIS participants showed significantly larger repositioning errors than healthy controls (pooled mean difference = 1.27 degrees, P < .01). Low evidence substantiated that AIS participants had significantly greater motion detection threshold (pooled mean difference = 1.60 degrees, P < .01) and abnormal somatosensory evoked potentials (pooled mean difference = .36 milliseconds, P = .01) than non-AIS counterparts. CONCLUSIONS: Consistent findings revealed that proprioceptive deficits occurred in AIS patients. Further investigations on the causal relationship between AIS and proprioception, and the identification of the subgroup of AIS patients with proprioceptive deficit are needed.

Cross-cultural adaptation of Cantonese (Hong Kong) Oswestry Disability Index version 2.1b.

PURPOSE: Oswestry Disability Index (ODI) was established by Fairbank in 1989 to assess functional disabilities in low back pain (LBP). It was last updated in 2019 as ODI version 2.1b (ODI AU_2.1b). ODI was first translated into Simplified Chinese Oswestry Disability Index (CODI) in 2008 by Lue. The construct validity, internal consistency, level of agreement and the floor and ceiling effects of CODI were found unclear by Yao in 2016. This study will verify how well the adapted Cantonese-Hong Kong Oswestry Disability Index version 2.1b (HKCODI) aligns with ODI AU_2.1b in the Southern Chinese population. METHODS: The translation of ODI AU_2.1b was performed according to guidelines from MAPI Research Trust and American Association of Orthopaedic Surgeons. Psychometric properties of HKCODI were tested statistically by Pearson's correlation, Cronbach's Alpha and Intraclass  Correlation  Coefficient (ICC). RESULTS: A total of 200 subjects (109 males, 91 females) aged from 15 to 85 (mean age = 58.91) with LBP scored from 3/10 to 10/10 in the Visual Analogue Scale (VAS) were recruited in the Occupational Therapy Department of a tertiary referral center. HKCODI demonstrated strong construct validity in comparing with Hong Kong Roland-Morris Disability Questionnaire (HKRMDQ) (r = 0.666, p = 0.000), Short Form Health Survey (SF-36)  Physical Composite Summary (- 0.700, p = 0.000) and VAS (0.487, p = 0.000). Excellent internal consistency and test-retest reliability were confirmed with Cronbach's Alpha of 0.997 and ICC of 0.993 at 95% confidence level. CONCLUSION: Cross-cultural adaptation of ODI AU_2.1b has been translated and validated as   HKCODI and Item-8 (Sex Life) was suggested to skip for patient older than 60. HKCODI is a fully self-administered and highly reliable tool in assessing the functional disability of patients with LBP in the Southern Chinese population.

Tetraspanin CD82 regulates bone marrow homing of acute myeloid leukemia by modulating the molecular organization of N-cadherin.

Communication between acute myeloid leukemia (AML) and the bone marrow microenvironment is known to control disease progression. Therefore, regulation of AML cell trafficking and adhesion to the bone marrow is of significant interest. In this study, we demonstrate that differential expression of the membrane scaffold CD82 modulates the bone marrow homing of AML cells. By combining mutational analysis and super-resolution imaging, we identify membrane protein clustering by CD82 as a regulator of AML cell adhesion and bone marrow homing. Cluster analysis of super-resolution data indicates that N-linked glycosylation and palmitoylation of CD82 are both critical modifications that control the microdomain organization of CD82 as well as the nanoscale clustering of associated adhesion protein, N-cadherin. We demonstrate that the inhibition of CD82 glycosylation increases the molecular packing of N-cadherin and promotes the bone marrow homing of AML cells. In contrast, we find that the inhibition of CD82 palmitoylation disrupts the formation and organization of N-cadherin clusters and significantly diminishes bone marrow trafficking of AML. Taken together, these data establish a mechanism where the membrane organization of CD82, through specific posttranslational modifications, regulates N-cadherin clustering and membrane density, which impacts the in vivo trafficking of AML cells. As such, these observations provide an alternative model for targeting AML where modulation of protein organization within the membrane may be an effective treatment therapy to disrupt the bone marrow homing potential of AML cells.

Optimal blood mononuclear cell isolation procedures for gamma interferon enzyme-linked immunospot testing of healthy Swedish and Tanzanian subjects.

Determination of antigen-specific T-cell responses is an important part of vaccine assessment. High levels of recovery, viability, and functionality of peripheral blood mononuclear cells (PBMCs) are essential for reliable assessment of cell-mediated immune responses. Here, we sought to find the cell preparation technique best suited for two clinical vaccine trial sites: Stockholm, Sweden, and Dar es Salaam, Tanzania. Standard Ficoll-Paque gradient centrifugation, BD Vacutainer cell preparation tube (CPT), and Greiner Bio-One LeucoSep tube techniques were tested. Cell yield and viability were recorded. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) testing was used to assess cell functionality. No differences in mean recovery or mean viability of fresh PBMCs were observed between Ficoll-Paque gradient centrifugation and CPT techniques as used in Stockholm. In Dar es Salaam, recovery of PBMCs isolated by use of the Ficoll-Paque gradient technique was higher than that seen with CPT (1.58 +/- 0.6 versus 1.34 +/- 0.4 million cells/ml of blood [P = 0.0469]), and the viability of PBMCs processed by Ficoll-Paque gradient was higher than that seen with CPT-purified cells (95.8% +/- 2.3% versus 92.6% +/- 4.8% [P = 0.0081]). Furthermore, LeucoSep cell separation gave higher levels of yield (1.10 +/- 0.3 versus 0.92 +/- 0.3 million cells/ml of blood [P = 0.0022]) and viability (95.7% +/- 2.0% versus 93.4% +/- 3.2% [P = 0.0012]) than Ficoll-Paque cell separation. The cells purified by the different techniques at the two sites performed equally well in IFN-gamma ELISPOT assays. Both techniques generated cell preparations with excellent yield, viability, and functionality in Stockholm. In Dar es Salaam, CPT did not perform as well as Ficoll-Paque separation. In a subsequent comparison, LeucoSep performed better than Ficoll-Paque separation. Our findings emphasize the need for on-site assessment of PBMC purification techniques for optimal evaluation of cell-mediated immune responses.

Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen.

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.

Development and evaluation of a flow-cytometric assay of specific cell-mediated immune response in activated whole blood for the detection of cell-mediated immunity against varicella-zoster virus.

A new assay for the detection of specific cell-mediated immune (CMI) responses is described. Whole blood, diluted 1/10 in medium, was cultured in the presence or the absence of specific antigens. Results were assessed by flow cytometric analysis with or without immunophenotyping to detect proliferating lymphoblasts among cultured cells. Interferon-gamma, IL-10, and IL-5 in culture supernatants are measured by ELISAs. The assay was evaluated using samples from 37 VZV-antibody-positive children with a history of chickenpox and samples from 15 seronegative children without a history of chickenpox; it displayed a sensitivity of 95% and a specificity of 100% for the detection of varicella-zoster virus (VZV)-specific CMI. The intraassay and interassay variations of the new test were lower than with the conventional assay for CMI, detecting thymidine incorporation in peripheral blood mononuclear cells (PBMCs). Cytokines were detected in only 70% of cultures from VZV-antibody-positive subjects. The cytokine response was restricted to IFN-gamma in most cases. The Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA) is a precise and accurate yet simple and convenient test that can be readily employed for the examination of single samples as well as for large-scale studies.

Spontaneous production of RANTES and antigen-specific IFN-gamma production in macaques vaccinated with SHIV-4 correlates with protection against SIVsm challenge.

The beta-chemokines, RANTES, MIP-1alpha and MIP-1beta, have been implicated as being some of the protective factors in the immune response against human immunodeficiency virus (HIV) infection. We have presented data previously indicating that these chemokines also play a role in protective immunity against HIV/SIV infection in macaques. The aim of this study was to investigate the production of beta-chemokines in eight cynomolgus macaques vaccinated with non-pathogenic SHIV-4 in relation to protection against pathogenic SIVsm challenge. Four control animals were also included in the study. Two of the vaccinated monkeys were completely protected and one was partially protected against the challenge virus. The monkeys that resisted infectious SIVsm virus challenge showed higher spontaneous beta-chemokine production by peripheral blood mononuclear cells and had higher numbers of antigen-induced IFN-gamma secreting cells compared to the non-protected animals. Our observations support our previous findings that the genetic background of the host and/or environmental factors are involved in the chemokine production and that beta-chemokines contribute to protection against HIV/SIV infection.

Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection.

A human IgA-radioimmunoprecipitation assay (IgA-RIPA) utilizing the galactose-binding lectin jacalin from the jack-fruit Artrocarpus integrifolia was developed. Among the human immunoglobulins, jacalin binds specifically to immunoglobulin A. The IgA-RIPA was used to characterize the serum IgA response to individual rotavirus polypeptides in nine paired sera from children (8-34 months of age) with an acute rotavirus infection. In acute sera the IgA response was mainly directed against the inner capsid proteins VP2 and VP6, with VP2 surprisingly being the most immunogenic protein while in the convalescent sera, the IgA response was directed not only against structural but also against non-structural proteins.

Group specific component and susceptibility to HIV infection and progression to AIDS.

The distribution of phenotypes of the group specific component (Gc) was examined in 85 AIDS patients and in 40 couples, each consisting of one HIV seropositive patient and one seronegative sexual partner. Phenotype and allele frequencies in these groups did not differ significantly from those in a Swedish control population. Our observations did not indicate any involvement of the Gc system in susceptibility to HIV infection or progression to AIDS.

Immunoglobulins in maxillary sinus secretion.

The immunoglobin pattern was studied in maxillary sinus secretion of 17 patients with maxillary sinusitis. By single radial immunodiffusion, measurable amounts of IgM were found in the secretions of 15 patients, and of IgA and IgG in the secretion of all patients. In purulent sinus secretion, IgA levels were significantly lower than in serous secretion. Of the total content of IgA in sinus secretion, 30% (purulent secretion) and 43% (serous secretion) were calculated to be locally produced, on average. For IgG these figures were 15% (purulent secretion) and 18% (serous secretion), whereas IgM could not be estimated by the method used. It was also concluded that the maxillary sinus is a suitable organ for investigation of local immunity in regard to bacterial infections.