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MLKL and RIPK3 are the core signaling proteins of the inflammatory cell death pathway, necroptosis, which is a known mediator and modifier of human disease. Necroptosis has been implicated in the progression of disease in almost every physiological system and recent reports suggest a role for necroptosis in aging. Here, we present the first comprehensive analysis of age-related histopathological and immunological phenotypes in a cohort of Mlkl–/– and Ripk3–/– mice on a congenic C57BL/6 J genetic background. We show that genetic deletion of Mlkl in female mice interrupts immune system aging, specifically delaying the age-related reduction of circulating lymphocytes. -Seventeen-month-old Mlkl–/– female mice were also protected against age-related chronic sterile inflammation in connective tissue and skeletal muscle relative to wild-type littermate controls, exhibiting a reduced number of immune cell infiltrates in these sites and fewer regenerating myocytes. These observations implicate MLKL in age-related sterile inflammation, suggesting a possible application for long-term anti-necroptotic therapy in humans.

Medical personnel play a critical role in caregiver safe infant sleep education. However, training outcomes in the safe infant sleep training literature have been mixed. Promising approaches that warrant further investigation are the use of behavioral skills training and pyramidal training. The current study consisted of two experiments. Experiment 1 extended Carrow et al. (2020) and Vladescu et al. (2020) by teaching medical students safe infant sleep practices using behavioral skills training. Discriminated responding was examined across trained and untrained environmental arrangements using a multiple-baseline design. All participants arranged safe sleep environments following behavioral skills training. In Experiment 2, we used pyramidal behavioral skills training to train medical students to teach others safe sleep practices. Results indicated high procedural integrity scores following training and generalization of skills.

To reduce sleep-related infant deaths, the American Academy of Pediatrics (AAP) has identified safe infant sleep recommendations; however, it is unclear which training strategies to teach safe infant sleep practices are most effective. Since the AAP released updated safe sleep recommendations in 2016, no analysis of the safe infant sleep training literature has been conducted. The purpose of the present review was to evaluate the safe infant sleep training literature of relevant populations such as caregivers and medical personnel, and provide recommendations for future research. The overall efficacy of training strategies was found to be positive or mixed where experiments most commonly implemented an educational session, followed by use of instructional materials, distribution of safe materials, and hospital-wide policy change. Methodological limitations were also identified.

Annually, thousands of infant deaths are classified as sudden unexpected infant deaths (SUIDs). In an effort to reduce the risk of SUIDs, the American Academy of Pediatrics has made a number of recommendations to educate caregivers, childcare providers, and healthcare professionals on safe infant sleep practices. The purpose of the current study was to extend the literature on safe infant sleep practices by teaching caregivers to arrange safe infant sleep environments using a mannequin and common infant items. We partnered with community-based agencies to evaluate the effectiveness of behavioral skills training delivered in a single training session as part of the ongoing pre- or postnatal care these agencies provided. Following training, all participants demonstrated a substantial change in responding and returned favorable social validity ratings. We discuss these outcomes in light of previous studies, limitations, and future directions.

Immune-mediated necrotising myopathy (IMNM) is a recently described entity. We describe a cohort of South Australian IMNM patients in order to define the spectrum of disease, characterise features that distinguish IMNM from other idiopathic inflammatory myopathy (IIM) subtypes and identify factors associated with clinically severe disease. Subjects were identified from the South Australian Myositis Database(SAMD), a histologically defined registry. Consecutive muscle sections from patients with IMNM (n=62), other forms of IIM (n=60) and histologically normal muscle (n=17) were stained using immunohistochemistry and graded. Clinical information was collected from the SAMD and through retrospective chart review. IMNM patients displayed clinical and histological heterogeneity. While most (67%) were profoundly weak at presentation, 24% exhibited mild to moderate weakness and 9% had normal power. Histological myonecros is ranged from minor to florid. The amount of myofibre complement deposition was closely associated with clinical severity. Patients of Aboriginal and Torres Strait Islander heritage and those with anti-SRP auto antibodies present with a severe phenotype. Despite intense immunotherapy,few IMNM patients recovered full power at one year follow up. The identification of clinical, serological and histological features which are associated with severe forms of the disease may have diagnostic and therapeutic utility. Refereed/Peer-reviewed

Objective To externally validate the European League Against Rheumatism/American College of Rheumatism (EULAR/ACR) classification criteria for idiopathic inflammatory myositis (IIM) and determine the optimal cut points for Australian patients. To determine the level of agreement with traditional criteria and assess the effect of including magnetic resonance imaging (MRI) and an extended myositis antibody panel as well as extending histological criteria to include myofiber invasion. Methods Data were collected on adult patients referred for muscle biopsy to two Australian teaching hospitals. Patients were scored for "risk of IIM" according to EULAR/ACR criteria, using clinician diagnosis as the gold standard. Results Overall, 87 of 204 patients had IIM. For patients with muscle biopsy, the optimal cut point of 5.25 (sensitivity 90%, specificity 89%) was lower than the EULAR/ACR cut point of 6.7, which in our cohort showed reduced sensitivity (71% vs 93%) but comparable specificity (89% vs 88%). We found moderate agreement between the EULAR/ACR criteria and Bohan and Peter (κ = 0.45, 95% confidence interval [CI] = 0.28, 0.62, P < 0.001) and Targoff (κ = 0.40, 95% CI = 0.23, 0.57, P < 0.001). Inclusion of MRI (area under curve [AUC] = 0.86, 95% CI = 0.79, 0.93) or non-Jo1 antibodies (AUC = 0.84, 95% CI = 0.77, 0.91) as covariates improved the probability of IIM diagnosis (AUC = 0.80, 95% CI = 0.75, 0.86). Extending histologic criteria to include myofiber invasion slightly improved sensitivity (75% vs 71%) with the same level of specificity (89% vs 89%). Conclusion Application of the EULAR/ACR criteria to an Australian cohort showed comparable specificity but lower sensitivity, and a lower optimal cut point. Inclusion of MRI or non-Jo1 antibodies as covariates may improve the accuracy of determining the probability of IIM diagnoses. Extending the histologic criteria to include myofiber invasion did not reduce specificity.

The present study used behavior skills training (BST) to teach three adult participants to implement a video modeling intervention aimed at teaching social skills to adults with autism spectrum disorder (ASD). During baseline trials, participants were given access to written instructions before role-play with two actors (who simulated a quiet conversation) and one confederate (who played the role of an adult with ASD). During treatment, participants were given a video model with voiceover instruction depicting how to implement the video modeling intervention to teach social skills, repeated roleplay trials, and feedback following their performance. All participant scores (percentage of steps correctly implemented in each session) increased from baseline to treatment, and generalization was demonstrated with an actual consumer diagnosed with ASD. Additionally, after training participants to use a video model to teach one social skill, there was generalization to teaching as many as three additional novel social skills. Participants showed maintenance of skills during a treatment study that involved training adult clients with ASD to engage in the social skills.

To determine the presence and genotypic macrolide susceptibility of Mycoplasma amphoriforme, and the presence of Ureaplasma spp. and Mycoplasma fermentans among clinical samples from England previously investigated for Mycoplasma pneumoniae.Quantitative and conventional PCR methods were used to retrospectively screen a collection of 160 clinical samples previously submitted to Public Health England (PHE) for the detection of M. pneumoniae between October 2016 and December 2017. Samples which were positive for M. amphoriforme DNA were further investigated for mutations associated with genotypic macrolide resistance by sequencing domain V of the 23s rRNA.M. amphoriforme was detected in 10/160 samples (6.3%), Ureaplasma parvum was detected in 4/160 samples (2.5%), and M. fermentans was not detected in any samples (0/160). Of the nine individuals (two samples were from the same patient) in which M. amphoriforme was detected, eight were male (age range 10-60 years) and one was female (age range 30-40 years). One individual with cystic fibrosis was positive for both M. amphoriforme and U. parvum. All M. amphoriforme DNA was genotypically susceptible to macrolides.Mycoplasma amphoriforme was found in clinical samples, including lower respiratory tract samples of patients with pneumonia. In the absence of other respiratory pathogens, these data suggest a potential role for this organism in human disease, with no evidence of acquired macrolide resistance. Ureaplasma parvum was detected in cerebrospinal fluid and respiratory tract samples. These data suggest that there is a need to consider these atypical respiratory pathogens in future diagnostic investigations.

Antiphospholipid syndrome is an autoimmune condition, characterised by the persistent presence of antiphospholipid antibodies and either thrombosis or obstetric morbidity. The cornerstone of therapy is long-term anticoagulation to reduce morbidity and mortality; however, better understanding of the immunological pathways may direct us to develop future therapeutic strategies. We provide an overview of the current understanding of the immunopathogenesis of this perplexing condition and its associated morbidities and current evidence for some of the immunotherapeutic strategies.

Preschool classrooms with varying levels of structural quality requirements across the state of West Virginia were investigated for differences in measured structural and process quality. Quality was measured using group size, child-to-teacher/staff ratio, teacher education, and the Early Childhood Environmental Rating Scale-Revised (ECERS-R; Harms, T., Clifford, R. M., & Cryer, D. (2005). The early childhood environment rating scale-revised. New York, NY: Teachers College Press). Thirty-six classrooms with less structural quality requirements and 136 with more structural quality requirements were measured. There were significant differences between classroom type, with classrooms with more structural quality requirements having significantly higher teacher education levels and higher environmental rating scores on the ECERS-R subscales of Space and Furnishings, Activities, and Program Structure. Results support previous research that stricter structural state regulations are correlated with higher measured structural and process quality in preschool classrooms. Implications for preschool state quality standards are discussed.

This study is a replication and extension of Reeve, Reeve, Townsend, and Poulson (2007) evaluating the effects of a treatment package that included multiple-exemplar training, video modeling, prompting, and reinforcement on helping of 3 adolescents with autism. Results demonstrated that all participants acquired the helping responses. Probes before and after intervention also demonstrated generalization of helping across settings and categories of helping behavior.

To the Editor: Legionella species are significant pathogens with most infections being caused by Legionella pneumoniae and presenting as Legionnaire disease or Pontiac fever1. Extrapulmonary legionellosis is uncommon and is often thought to arise from hematogenous spread after primary pulmonary infection2. To date, the extrapulmonary sites of infections that have been reported in the literature include spleen, kidneys, liver3, infective endocarditis4, myositis5, cellulitis, and cutaneous abscesses5. The majority of extrapulmonary Legionella infections have been described in immunocompromised patients. A 69-year-old female florist presented to hospital with 1 week of worsening pain and swelling of the right hand, having been treated in the community for presumed seronegative arthritis for the preceding 6 months. Her presentation 6 months earlier was with pain and swelling in her right hand and mild, transient symptoms in the left hand. Clinical examination at that time found synovitis in multiple proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints and palmar tenosynovitis in the right hand. Otherwise, joint examination was normal. The tenosynovitis was confirmed on ultrasound (US). She was treated with ceftriaxone, but failed to improve. … Address correspondence to Dr. L. Chou, Department of Rheumatology, Royal Melbourne Hospital, 300 Grattan St., Parkville, Melbourne, Australia 3050. E-mail: louisa.chou{at}monash.edu