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Even when successfully Induced, Immunological tolerance to solid organs remains vulnerable to Inflammatory Insults, which can trigger rejection. In a mouse model of cardiac allograft tolerance in which infection with Listeria monocytogenes (Lm) precipitates rejection of previously accepted grafts, we showed that recipient [CD4.sup.+] TCR75 cells reactive to a donor MHC class I-derived peptide become hypofunctional if the allograft is accepted for more than 3 weeks. Paradoxically, infection-induced transplant rejection was not associated with transcriptional or functional reinvigoration of TCR75 cells. We hypothesized that there is heterogeneity in the level of dysfunction of different allospecific T cells, depending on duration of their cognate antigen expression. Unlike [CD4.sup.+] TCR75 cells, [CD4.sup.+] TEa cells specific for a peptide derived from donor MHC class II, an alloantigen whose expression declines after transplantation but remains inducible in settings of inflammation, retained function in tolerant mice and expanded during Lm-induced rejection. Repeated injections of alloantigens drove hypofunction in TEa cells and rendered grafts resistant to Lm-dependent rejection. Our results uncover a functional heterogeneity in allospecific T cells of distinct specificities after tolerance induction and reveal a strategy to defunctionalize a greater repertoire of allospecific T cells, thereby mitigating a critical vulnerability of tolerance., Introduction Achieving stable donor-specific transplantation tolerance holds the potential for vastly improving the quality of life for transplant recipients by eliminating the lifelong exposure to drug toxicity, higher risk of [...]

Background: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID‐19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years. Methods: We collected the data from multiple surveillance systems, including hospital‐based severe acute respiratory infection surveillance, SHIVERS‐II, ‐III and ‐IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza‐like illness surveillance and SHIVERS‐V sentinel GP‐based ARI surveillance, SHIVERS‐V traveller ARI surveillance and laboratory‐based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions. Results: We observed that border closure to most people, and mandatory government‐managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type‐1. Partial border relaxations through quarantine‐free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022. Conclusion: Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats. [ABSTRACT FROM AUTHOR]

Aim: The fall of a newborn baby to the hospital floor is a devastating experience for the family and staff caring for the mother and baby. The aim of this study was to report our experience in an ethnically diverse and socioeconomically disadvantaged community. Methods: The study was a retrospective case series of all baby falls in the Counties Manukau Health (New Zealand) post‐natal care wards, birthing suites and birthing units from 2015 to 2018. Information from the incident reporting system was used to identify the circumstances surrounding the fall. In addition, medical records of the mother and the baby were examined for the admission during which the fall occurred. Results: There were 32 cases (rate 12.1/10 000 live births). Mothers of babies who fell were more likely to present late for antenatal care, to smoke and be obese. They were more likely to have delivered by caesarean. Falls were more likely to occur at night and around weekends. In most instances (84%) the mother fell asleep with baby on the bed while breastfeeding. There were no major injuries. Conclusions: The rate of baby falls is considerably greater than previous reports. Recommendations are made to reduce this occurrence. These can be incorporated into safe sleep education. [ABSTRACT FROM AUTHOR]

Limiting CD4+ T cell responses is important to prevent solid organ transplant rejection. In a mouse model of costimulation blockade-dependent cardiac allograft tolerance, we previously reported that alloreactive CD4+ conventional T cells (Tconvs) develop dysfunction, losing proliferative capacity. In parallel, induction of transplantation tolerance is dependent on the presence of regulatory T cells (Tregs). Whether susceptibility of CD4+ Tconvs to Treg suppression is modulated during tolerance induction is unknown. We found that alloreactive Tconvs from transplant tolerant mice had augmented sensitivity to Treg suppression when compared with memory T cells from rejector mice and expressed a transcriptional profile distinct from these memory T cells, including down-regulated expression of the transcription factor Special AT-rich sequence-binding protein 1 (Satb1). Mechanistically, Satb1 deficiency in CD4+ T cells limited their expression of CD25 and IL-2, and addition of Tregs, which express higher levels of CD25 than Satb1-deficient Tconvs and successfully competed for IL-2, resulted in greater suppression of Satb1-deficient than wild-type Tconvs in vitro. In vivo, Satb1-deficient Tconvs were more susceptible to Treg suppression, resulting in significantly prolonged skin allograft survival. Overall, our study reveals that transplantation tolerance is associated with Tconvs’ susceptibility to Treg suppression, via modulated expression of Tconv-intrinsic Satb1. Targeting Satb1 in the context of Treg-sparing immunosuppressive therapies might be exploited to improve transplant outcomes. [ABSTRACT FROM AUTHOR]

Objectives. To test prospectively the hypothesis that an infant car seat modification to allow the infant's head to rest in a neutral position on the trunk would prevent narrowing of the upper airway and thus reduce oxygen desaturation in preterm infants who are restrained in car seats. Methods. Seventeen preterm infants who were approved for discharge were evaluated in a car seat for newborns, with and without a foam insert that provided a slot for the back of the infants' head. Respiration timed inspiratory radiographs for assessment of upper airway dimensions were taken during quiet sleep in each position. Infants were monitored in each position for 30 minutes with continuous polygraphic recording of respiratory, cardiac, and nasal airflow activity and pulse oximetry. Results. Placement of the insert in the car seat was associated with a larger upper airway space (mean [+ or -] standard deviation, 5.2 [+ or -] 1.3 vs 3.6 [+ or -] 1.4 mm). This radiologic improvement was associated with a significant reduction in the frequency of episodes of oxygen desaturation to Conclusions. The cause of oxygen desaturation in preterm infants who are restrained in car seats is multi-factorial. The present data strongly support the hypothesis that flexion of the head on the body is a significant contributor to these episodes and that the mechanism is posterocephalic displacement of the mandible, leading to narrowing of the upper airway. Critically, this pilot study demonstrates that the frequency of episodes of desaturation in a standard newborn car seat can be substantially reduced by placement of a simple foam insert that allows the infant to maintain the head in a neutral position on the trunk during sleep. Pediatrics 2003;112:907-913; newborn, premature; apnea of prematurity; infant car seat; infant safety., Premature infants are now widely recognized to be at high risk of oxygen desaturation and secondary central apnea while restrained infant car seats. (1,2) The American Academy of Pediatrics recommends [...]

Discusses the implementation of computers in public schools and ways in which a district-wide media coordinator could help in the process. Highlights include duties of the coordinator, including planning curriculum, training staff, development of a media resource center, and evaluation; effects on the school libraries; and effects on learning. (LRW)