Pilot Study Protocol of a Mhealth Self‐Management Intervention for Family Members of Pediatric Transplant Recipients

Solid‐organ transplantation is the treatment of choice for end‐stage organ failure. Parents of pediatric transplant recipients who reported a lack of readiness for discharge had more difficulty coping and managing their child\u27s medically complex care at home. In this paper, we describe the protocol for the pilot study of a mHealth intervention (myFAMI). The myFAMI intervention is based on the Individual and Family Self‐Management Theory and focuses on family self‐management of pediatric transplant recipients at home. The purpose of the pilot study is to test the feasibility of the myFAMI intervention with family members of pediatric transplant recipients and to test the preliminary efficacy on postdischarge coping through a randomized controlled trial. The sample will include 40 family units, 20 in each arm of the study, from three pediatric transplant centers in the United States. Results from this study may advance nursing science by providing insight for the use of mHealth to facilitate patient/family–nurse communication and family self‐management behaviors for family members of pediatric transplant recipients

Targeting the CBM complex causes Treg cells to prime tumours for immune checkpoint therapy.

Solid tumours are infiltrated by effector T cells with the potential to control or reject them, as well as by regulatory T (Treg) cells that restrict the function of effector T cells and thereby promote tumour growth1. The anti-tumour activity of effector T cells can be therapeutically unleashed, and is now being exploited for the treatment of some forms of human cancer. However, weak tumour-associated inflammatory responses and the immune-suppressive function of Treg cells remain major hurdles to broader effectiveness of tumour immunotherapy2. Here we show that, after disruption of the CARMA1-BCL10-MALT1 (CBM) signalosome complex, most tumour-infiltrating Treg cells produce IFNγ, resulting in stunted tumour growth. Notably, genetic deletion of both or even just one allele of CARMA1 (also known as Card11) in only a fraction of Treg cells-which avoided systemic autoimmunity-was sufficient to produce this anti-tumour effect, showing that it is not the mere loss of suppressive function but the gain of effector activity by Treg cells that initiates tumour control. The production of IFNγ by Treg cells was accompanied by activation of macrophages and upregulation of class I molecules of the major histocompatibility complex on tumour cells. However, tumour cells also upregulated the expression of PD-L1, which indicates activation of adaptive immune resistance3. Consequently, blockade of PD-1 together with CARMA1 deletion caused rejection of tumours that otherwise do not respond to anti-PD-1 monotherapy. This effect was reproduced by pharmacological inhibition of the CBM protein MALT1. Our results demonstrate that partial disruption of the CBM complex and induction of IFNγ secretion in the preferentially self-reactive Treg cell pool does not cause systemic autoimmunity but is sufficient to prime the tumour environment for successful immune checkpoint therapy

Respiratory treatment history predicts suck pattern stability in preterm infants

Sensory deprivation and motor restriction associated with extensive oxygen therapy may lead to poor oromotor control in preterm infants. Non-nutritive suck is one of the first complex oromotor behaviors infants perform. This study determined the spatiotemporal variability of non-nutritive suck (NNS) pressure trajectories in three preterm groups with differing oxygen histories—one control group with minimal or no O2 therapy, and two Respiratory Distress Syndrome (RDS) groups with either a mild/moderate (RDS1) or moderate/severe (RDS2) O2 history. The Non-nutritive Suck Spatiotemporal Index (NNS STI) quantifies spatial and temporal variability across kinematic trajectories, and was calculated from digital representations of infants’ suck pressure signals. An ANCOVA revealed a significant effect for group (p \u3c .001) on the NNS STI measure, with RDS2 infants showing highly variable NNS patterning, and thus relatively underdeveloped suck. Extensive oxygen therapy, which alters the oral sensory environment and reduces motor experiences, disrupts the development of coordinated NNS in preterm infants

Dedifferentiation of committed epithelial cells into stem cells in vivo

Summary Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes, and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. We now present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. Following the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts to repair epithelial injury. Indeed, single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. In contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate was inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may play a more general role in the regeneration of many tissues and in multiple disease states, notably cancer

Effective suckling in relation to naked maternal-infant body contact in the first hour of life: an observation study

Background Best practice guidelines to promote breastfeeding suggest that (i) mothers hold their babies in naked body contact immediately after birth, (ii) babies remain undisturbed for at least one hour and (iii) breastfeeding assistance be offered during this period. Few studies have closely observed the implementation of these guidelines in practice. We sought to evaluate these practices on suckling achievement within the first hour after birth. Methods Observations of seventy-eight mother-baby dyads recorded newborn feeding behaviours, the help received by mothers and birthing room practices each minute, for sixty minutes. Results Duration of naked body contact between mothers and their newborn babies varied widely from 1 to 60 minutes, as did commencement of suckling (range = 10 to 60 minutes). Naked maternal-infant body contact immediately after birth, uninterrupted for at least thirty minutes did not predict effective suckling within the first hour of birth. Newborns were four times more likely to sustain deep rhythmical suckling when their chin made contact with their mother’s breast as they approached the nipple (OR 3.8; CI 1.03 - 14) and if their mothers had given birth previously (OR 6.7; CI 1.35 - 33). Infants who had any naso-oropharyngeal suctioning administered at birth were six times less likely to suckle effectively (OR .176; CI .04 - .9). Conclusion Effective suckling within the first hour of life was associated with a collection of practices including infants positioned so their chin can instinctively nudge the underside of their mother’s breast as they approach to grasp the nipple and attach to suckle. The best type of assistance provided in the birthing room that enables newborns to sustain an effective latch was paying attention to newborn feeding behaviours and not administering naso-oropharyngeal suction routinely