Coping in Families with a Retarded Child

The impact of a retarded child on a family has previously been described by individual family members\u27 reports. This study of 40 families, 10 in each of four critical periods during the life of the retarded child, utilized videotaped interviews with whole families, with subsequent clinical observation and analysis based on the Beavers family assessment model. Healthy and problematic adaptations are delineated, with specific attention to systems concepts such as family structure and power, member individuation, feeling expression, and values. The report includes data analysis and a summary of pattern differences in family functioning

Increased Dietary Manganese Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus

Dietary metals can modify the risk to infection. Previously, we demonstrated that heightened dietary manganese (Mn) during systemic Staphylococcus aureus infection increases S. aureus virulence. However, immune cells also operate in these same environments and the effect of dietary Mn on neutrophil function has not been assessed. This study reveals that increased concentrations of Mn impairs mitochondrial respiration and superoxide production in neutrophils responding to S. aureus. As a result, high Mn accelerates primary degranulation, while impairing suicidal neutrophil extracellular trap (NET) formation, which decreases bactericidal activity. , elevated dietary Mn accumulated extracellularly in the heart, indicating that excess Mn may be more bioavailable in the heart. Coinciding with this phenotype, neutrophil function in the heart was most impacted by a high Mn diet, as neutrophils produced lower levels of mitochondrial superoxide and underwent less suicidal NET formation. Consistent with an ineffective neutrophil response when mice are on a high Mn diet, S. aureus burdens were increased in the heart and mice were more susceptible to systemic infection. Therefore, elevated dietary Mn not only affects S. aureus but also renders neutrophils less capable of restricting staphylococcal infection

Mitochondrial Calcium Uniporter Affects Neutrophil Bactericidal Activity during Staphylococcus aureus Infection

Neutrophils simultaneously restrict Staphylococcus aureus dissemination and facilitate bactericidal activity during infection through the formation of neutrophil extracellular traps (NETs). Neutrophils that produce higher levels of mitochondrial superoxide undergo enhanced terminal NET formation (suicidal NETosis) in response to S. aureus; however, mechanisms regulating mitochondrial homeostasis upstream of neutrophil antibacterial processes are not fully resolved. Here, we demonstrate that mitochondrial calcium uptake 1 (MICU1)-deficient (MICU1) neutrophils accumulate higher levels of calcium and iron within the mitochondria in a mitochondrial calcium uniporter (MCU)-dependent manner. Corresponding with increased ion flux through the MCU, mitochondrial superoxide production is elevated, thereby increasing the propensity for MICU1 neutrophils to undergo suicidal NETosis rather than primary degranulation in response to S. aureus. Increased NET formation augments macrophage killing of bacterial pathogens. Similarly, MICU1 neutrophils alone are not more antibacterial toward S. aureus, but rather, enhanced suicidal NETosis by MICU1 neutrophils facilitates increased bactericidal activity in the presence of macrophages. Similarly, mice with a deficiency in MICU1 restricted to cells expressing LysM exhibit lower bacterial burdens in the heart with increased survival during systemic S. aureus infection. Coinciding with the decrease in S. aureus burdens, MICU1 neutrophils in the heart produce higher levels of mitochondrial superoxide and undergo enhanced suicidal NETosis. These results demonstrate that ion flux by the MCU affects the antibacterial function of neutrophils during S. aureus infection