Sucking behaviors of normal 3-day-old female neonates during a 24-hr period

Feeding behaviors were measured during six feeding sessions distributed throughout a 24-hr period in 10 normal 3-day-old female infants. Infants were individually videotaped during feeding sessions at 13:00, 17:00, 21:00, 01:00, 05:00, and 09:00 hours. Total mealtime, nutritive sucking time, pause time, number of nutritive sucks, and amounnt of nutrient consumed were measured. None of these feeding variables were affected by the time of day an infant was fed. Maternal interactions with their infants such as auditory stimulation, caretaking touches or tender touches were unaffected by the time of a feed. These maternal behaviors did not correlate with any of the feeding variables. These findings suggest that 3-day-old infants experiencing routine nursery care do not express specific day-night feeding differences and that certain maternal behaviors do not influence the infants' feeding pattern.     

The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases

Coffin-Siris syndrome (CSS) is a rare, clinically heterogeneous disorder often considered in the setting of cognitive/developmental delay and 5th finger/nail hypoplasia. Due to the clinical variability of facial and other features, this diagnosis is often difficult to confirm clinically and the existence of this disorder as a specific diagnosis has been at times an issue of debate. In an effort to further delineate the spectrum and key phenotypic features, we reviewed 80 previously reported cases to define features in patients that most closely correlated with a convincing diagnosis. There appear to be two subtypes of CSS, one which displays the "classic" coarse facial features previously described; another displays "variant" facial features which are less striking. Using these features, we defined an algorithm to rank the confidence of diagnosis and applied it to 15 additional patients who had been previously characterized by chromosome microarray. This approach will also facilitate uniform categorization for whole-exome analysis.     

A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability

Glutamine (Q) expansion diseases are a family of degenerative disorders caused by the lengthening of CAG triplet repeats present in the coding sequences of seemingly unrelated genes whose mutant proteins drive pathogenesis. Despite all the molecular evidence for the genetic basis of these diseases, how mutant poly-Q proteins promote cell death and drive pathogenesis remains controversial. In this report, we show a specific interaction between the mutant androgen receptor (AR), a protein associated with spinal and bulbar muscular atrophy (SBMA), and the nuclear protein PTIP (Pax Transactivation-domain Interacting Protein), a protein with an unusually long Q-rich domain that functions in DNA repair. Upon exposure to ionizing radiation, PTIP localizes to nuclear foci that are sites of DNA damage and repair. However, the expression of poly-Q AR sequesters PTIP away from radiation-induced nuclear foci. This results in sensitivity to DNA-damaging agents and chromosomal instabilities. In a mouse model of SBMA, evidence for DNA damage is detected in muscle cell nuclei and muscular atrophy is accelerated when one copy of the gene encoding PTIP is removed. These data provide a new paradigm for understanding the mechanisms of cellular degeneration observed in poly-Q expansion diseases.     

Mode of death and hospitalization from the Second Follow-up Serial Infusions of Nesiritide (FUSION II) trial and comparison of clinical events committee adjudicated versus investigator reported outcomes

The aim of this study was to evaluate the mode of death and hospitalizations in advanced heart failure (HF) patients with renal dysfunction and to examine the rate of concordance between events reported by the clinical events committee and site investigators (using case report forms) in the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of death and hospitalization in patients with advanced HF. FUSION II was a randomized, double-blind, placebo-controlled trial evaluating outpatient nesiritide infusions versus placebo, with 911 patients with advanced HF (New York Heart Association class III or IV) and renal dysfunction enrolled. There were 151 deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or unknown. Kappa statistics and McNemar tests were used to assess agreement (overall and by individual modes of death and hospitalization indications). In conclusion, the most common cause of death or hospitalization was cardiac related, with 70% of deaths and 60% of hospitalizations due to cardiac causes. There was 74% agreement (26% disagreement) on cardiac cause of death (κ = 0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the investigators and the clinical events committee on cardiac classification for hospitalization (κ = 0.49, McNemar p <0.0001).     

Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity

Females are more susceptible than males to many autoimmune diseases. The processes causing this phenomenon are incompletely understood. Here, we demonstrate that aged female mice acquire a previously uncharacterized population of B cells that we call age-associated B cells (ABCs) and that these cells express integrin α(X) chain (CD11c). This unexpected population also appears in young lupus-prone mice. On stimulation, CD11c(+) B cells, both from autoimmune-prone and healthy strains of mice, secrete autoantibodies, and depletion of these cells in vivo leads to reduction of autoreactive antibodies, suggesting that the cells might have a direct role in the development of autoimmunity. We have explored factors that contribute to appearance of ABCs and demonstrated that signaling through Toll-like receptor 7 is crucial for development of this B cell population. We were able to detect a similar population of B cells in the peripheral blood of some elderly women with autoimmune disease, suggesting that there may be parallels between the creation of ABC-like cells between mice and humans.