Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (Allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety, and depression as a result. We theorized that a stress management adapted for Allo-HSCT caregivers would reduce distress compared to treatment as usual (TAU). From 267 consecutive caregivers of Allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (n=74) or TAU (n=74). Eight 1-on-1 stress management sessions delivered across the 100 day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration, and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post-transplant (Mean=20.0, CI95=17.9-22.0) compared to TAU (Mean=23.0, CI95=21.0-25.0) with an effect size (ES) of 0.39 (p=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66 respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in Allo-HSCT caregivers.

Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut–draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1–fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation.

Fetal cortisol exposure was determined using this approach for processing small amounts of hair. Preterm neonates have significantly lower HCC than term neonates and fetal HCC is associated with GA at delivery and birth weight. Fetal HCC is significantly higher than maternal HCC cut on the same day. These data provide novel information on the intrauterine fetal cortisol environment.

SOCS1−/− mice, which are lymphopenic, die less than 3 weeks after birth of a T cell mediated autoimmune inflammatory disease characterized by leukocyte infiltration and destruction of vital organs. Notably, Foxp3+ regulatory T cells (Tregs) have been shown to be particularly potent in inhibiting inflammation associated autoimmune diseases. We observed that SOCS1−/− mice were deficient in peripheral Tregs despite enhanced thymic development. The adoptive transfer of SOCS1 sufficient Tregs; CD4+ T lymphocytes; or administration of SOCS1-KIR, a peptide that partially restores SOCS1 function, mediated a statistically significant, but short-term survival of SOCS1−/− mice. However, the adoptive transfer of SOCS1 sufficient CD4+ T lymphocytes, combined with the administration of SOCS1-KIR, resulted in a significant increase in the survival of SOCS1−/− mice both short term and long term, where 100 percent death occurred by day 18 in the absence of treatment. Moreover, the CD4+/SOCS1-KIR combined therapy resulted in decreased leukocytic organ infiltration, reduction of serum IFNγ, and enhanced peripheral accumulation of Foxp3+ Tregs in treated mice. These data show that CD4+/SOCS1-KIR combined treatment can synergistically promote the long-term survival of peri-natal lethal SOCS1−/− mice. In addition, these results strongly suggest that SOCS1 contributes to the stability of the Foxp3+ Treg peripheral population under conditions of strong pro-inflammatory environments.