Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.

Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment. Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK)-cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH.

Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.

SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity.

Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection.

Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19.

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.

Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.

Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.

Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency.

Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries.

Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes.

Tissue-resident memory CD8 T cells (T) constitute a noncirculating memory T cell subset that provides early protection against reinfection. However, how T arise from antigen-triggered T cells has remained unclear. Exploiting the T-restricted expression of Hobit, we used T reporter/deleter mice to study T differentiation.

Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives.

The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research.

Visual Screen for Dopaminergic Interactions in Discriminates from .

LRRK2 mutations cause Parkinson's, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previous assays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesis in a functional, electroretinogram screen, expressing each with/without in selected dopaminergic neurons.

Comparison of Academic Performance in Traditional and Flipped Classrooms and Students' Attitudes of the Flipped Experience.

Unlabelled: The flipped classroom method allows students to learn formative material before class while acquiring higher-order learning in-class. The purpose of this study was to compare learning outcomes between traditional lecture and the flipped classroom model in a Doctor of Physical Therapy program and to assess student satisfaction with the flipped classroom method.

Methods: Three cohorts of first-year students, Classes 2015, 2016, and 2017 (Class A, B, C respectively) from a 3-year physical therapy education program.

The Use of Yoga by Physical Therapists in the United States.

How physical therapists (PTs) in the United States currently use yoga in their clinical practices is unknown. The purpose of this study was to determine how PTs in the United States view yoga as a physical therapy (PT) tool and how PTs use yoga therapeutically. The authors conducted a 24-item survey via electronic communications of the Geriatric, Orthopedic, Pediatric, and Women's Health Sections of the American Physical Therapy Association.

Comparison of Ai Chi and Impairment-Based Aquatic Therapy for Older Adults With Balance Problems: A Clinical Study.

Background And Purpose: Older adults with balance deficits often fear falling and limit their mobility. Poor balance is multifactorial, influenced by medication interactions, musculoskeletal and sensory system changes, and poor neuromuscular response to changes in body positions. Aquatic physical therapy (APT) is an intervention used to improve balance and decrease falls.

The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts.

We recently reported the association of the PCSK6 gene with handedness through a quantitative genome-wide association study (GWAS; P < 0.5 × 10(-8)) for a relative hand skill measure in individuals with dyslexia. PCSK6 activates Nodal, a morphogen involved in regulating left-right body axis determination.

Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation.

Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks.

Genome-wide analysis identifies a role for common copy number variants in specific language impairment.

An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.

Genome-Wide Studies of Specific Language Impairment.

Specific language impairment (SLI) is a multifactorial neurodevelopmental disorder which occurs unexpectedly and without an obvious cause. Over a decade of research suggests that SLI is highly heritable. Several genes and loci have already been implicated in SLI through linkage and targeted association methods.

Upper extremity neurodynamic tests: range of motion asymmetry may not indicate impairment.

Upper extremity (UE) neurodynamic tests are used to examine neural tissue in patients with neuro-musculoskeletal disorders. Although comparisons between involved and uninvolved limbs are made clinically, minimal data exist reflecting the normal variation between sides. The purpose of this study was to determine if within-subject differences exist between limbs in the UE component of neurodynamic tests of the median, radial, and ulnar nerves.

Reliability of the radial and ulnar nerve biased upper extremity neural tissue provocation tests.

Study Design: Within subjects test-retest design.

Background: Neural tissue provocation tests (NTPTs) are used clinically to examine neural tissue mechanosensitivity in patients with musculoskeletal conditions. Previous studies suggest the median and radial nerve biased tests can be applied reliably using external fixation devices.