Placental mTOR complex 1 regulates fetal programming of obesity and insulin resistance in mice.

Fetal growth restriction, or low birth weight, is a strong determinant for eventual obesity and type 2 diabetes. Clinical studies suggest placental mechanistic target of rapamycin (mTOR) signaling regulates fetal birth weight and the metabolic health trajectory of the offspring. In the current study, we used a genetic model with loss of placental mTOR function (mTOR-KOPlacenta) to test the direct role of mTOR signaling on birth weight and metabolic health in the adult offspring. mTOR-KOPlacenta animals displayed reduced placental area and total weight, as well as fetal body weight at embryonic day (E) 17.5. Birth weight and serum insulin levels were reduced; however, ß cell mass was normal in mTOR-KOPlacenta newborns. Adult mTOR-KOPlacenta offspring, under a metabolic high-fat challenge, displayed exacerbated obesity and metabolic dysfunction compared with littermate controls. Subsequently, we tested whether enhancing placental mTOR complex 1 (mTORC1) signaling, via genetic ablation of TSC2, in utero would improve glucose homeostasis in the offspring. Indeed, increased placental mTORC1 conferred protection from diet-induced obesity in the offspring. In conclusion, placental mTORC1 serves as a mechanistic link between placental function and programming of obesity and insulin resistance in the adult offspring.

Technology-Assisted Self-Monitoring of Lifestyle Behaviors and Health Indicators in Diabetes: Qualitative Study.

BACKGROUND: Self-monitoring is key to successful behavior change in diabetes and obesity, and the use of traditional paper-based methods of self-monitoring may be time-consuming and burdensome. OBJECTIVE: This study aimed to explore participant experiences while using technology-assisted self-monitoring of lifestyle behaviors and health indicators among overweight or obese adults with type 2 diabetes. METHODS: Qualitative data collected from the intervention group of a 6-month, three-arm (control, paper diary, and technology-assisted self-monitoring groups) randomized clinical trial were analyzed. Study participants in the intervention group monitored their diet, exercise, and weight using the LoseIt! app, and their blood glucose levels using a glucometer and the Diabetes Connect app. Semistructured group discussions were conducted at 6 weeks (n=10) from the initiation of the behavioral lifestyle intervention and again at 6 months (n=9). All group interviews were audiotaped and transcribed verbatim. Using a combination of thematic and comparative analysis approaches, two trained professionals coded the transcriptions independently and then discussed and concluded common themes for the 6-week and 6-month discussions separately. RESULTS: The sample (n=10), which primarily involved African American participants (n=7) and female participants (n=8), had a mean age of 59.4 years. The following eight themes emerged: (1) perceived benefits of technology-assisted self-monitoring; (2) perceived ease of use (eg, barriers: technical difficulties and lack of self-discipline; facilitators: help from family, friends, and the program); (3) use of technology-assisted self-monitoring; (4) facilitators of engaging in healthy lifestyle behaviors (eg, visualization and awareness of calorie input/expenditure); (5) positive lifestyle change; (6) barriers of engaging in healthy lifestyle behaviors (eg, event influence); (7) learning curve; and (8) monitored data sharing. The first six of these themes were shared between the 6-week and 6-month timepoints, but the codes within these themes were not all the same and differed slightly between the two timepoints. These differences provide insights into the evolution of participant thoughts and perceptions on using technology for self-monitoring and subsequent behavioral lifestyle changes while participating in lifestyle interventions. The findings from the 6-week and 6-month data helped to paint a picture of participant comfort and the integration of technology and knowledge overtime, and clarified participant attitudes, difficulties, behavioral processes, and modifications, as well as health indicators that were experienced throughout the study. CONCLUSIONS: Although there were some barriers, participants were able to identify various individual and external facilitators to adjust to and engage in technology-assisted self-monitoring, and it was concluded that the technology-assisted self-monitoring approach was beneficial, safe, and feasible to use for positive lifestyle change. These patient perspectives need to be considered in future research studies when investigating the effectiveness of using technology-assisted self-monitoring, as well as in clinical practice when recommending technology-assisted self-monitoring of lifestyle behaviors and health indicators to improve health outcomes.

A synthetic peptide analog of in silico-predicted immunogenic epitope unique to dengue virus serotype 2 NS1 antigen specifically binds immunoglobulin G antibodies raised in rabbits.

Development of a serotyping-capable dengue detection test is hampered by the absence of an identified unique marker that can detect specific dengue virus (DENV) serotype. In the current commercially available antibody-capture diagnostic methods, immobilized nonstructural 1 (NS1) antigen indiscriminately binds and detects immunoglobulin M or immunoglobulin G against any serotype, thus limiting its capability to distinguish existing serotypes of dengue. Identification of dengue serotype is important because certain serotypes are associated with severe forms of dengue as well as dengue hemorrhagic fever. In this study, we aimed to identify an immunogenic epitope unique to DENV2 NS1 antigen and determine the binding specificity of its synthetic peptide mimotope to antibodies raised in animal models. Selection of a putative B-cell epitope from the reported DENV2 NS1 antigen was done using Kolaskar and Tongaonkar Antigenicity prediction, Emini surface accessibility prediction, and Parker hydrophilicity prediction available at the immune epitope database and analysis resource. Uniqueness of the B-cell epitope to DENV2 was analyzed by BLASTp. Immunogenicity of the synthetic peptide analog of the predicted immunogenic epitope was tested in rabbits. The binding specificity of the antibodies raised in animals and the synthetic peptide mimotope was tested by indirect ELISA. A synthetic peptide analog comprising the unique epitope of DENV2 located at the 170th-183rd position of DENV2 NS1 was found to be immunogenic in animal models. The antipeptide antibody produced in rabbits showed specific binding to the synthetic peptide mimotope of the predicted unique DENV2 NS1 immunogenic epitope.

Caring for Pregnant Women with Opioid Use Disorder in the USA: Expanding and Improving Treatment.

PURPOSE OF THE REVIEW: Opioid use disorder in the USA is rising at an alarming rate, particularly among women of childbearing age. Pregnant women with opioid use disorder face numerous barriers to care, including limited access to treatment, stigma, and fear of legal consequences. This review of opioid use disorder in pregnancy is designed to assist health care providers caring for pregnant and postpartum women with the goal of expanding evidence-based treatment practices for this vulnerable population. RECENT FINDINGS: We review current literature on opioid use disorder among US women, existing legislation surrounding substance use in pregnancy, and available treatment options for pregnant women with opioid use disorder. Opioid agonist treatment (OAT) remains the standard of care for treating opioid use disorder in pregnancy. Medically assisted opioid withdrawal ("detoxification") is not recommended in pregnancy and is associated with high maternal relapse rates. Extended release naltrexone may confer benefit for carefully selected patients. Histories of trauma and mental health disorders are prevalent in this population; and best practice recommendations incorporate gender-specific, trauma-informed, mental health services. Breastfeeding with OAT is safe and beneficial for the mother-infant dyad. SUMMARY: Further research investigating options of OAT and the efficacy of opioid antagonists in pregnancy is needed. The US health care system can adapt to provide quality care for these mother-infant dyads by expanding comprehensive treatment services and improving access to care.

Intervention rates for placental removal following induction abortion with misoprostol.

BACKGROUND: Second-trimester terminations can be performed via surgical or medical methods. It is essential to have the ability to safely and effectively perform induction terminations to offer a full range of services. Many studies of induction abortions report routine operative removal of the placenta after a set time period resulting in high rates of operative procedures. STUDY DESIGN: A retrospective chart review was performed for 233 women who underwent second-trimester induction abortions between November 2003 and November 2006. All women received intraamniotic injection of digoxin for feticide 1 day prior to induction. All inductions were performed using a schedule of 400 mcg of misoprostol initially followed by 200 mcg every 6 h for a maximum of 48 h. There were three methods of administering misoprostol: (1) vaginal administration for all doses, (2) vaginal and buccal used in combination and (3) buccal for all doses. Spontaneous expulsion of the placenta was expected. Operative intervention was performed for excessive bleeding or to expedite hospital discharge after a minimum of 4 h. No manual removal of placenta was done. RESULTS: The rate of operative intervention for retained placentas was 6% (14/233). Most (11/14) of the patients who underwent operative extraction for retained placentas did so to expedite discharge from the hospital. Overall, expectant management to allow spontaneous expulsion of the placenta for at least 4 h was not associated with serious morbidity. CONCLUSIONS: Our regimen of digoxin and misoprostol with a policy of expectant management of placental passage is associated with a very low rate of instrumented removal of the placenta. In the absence of bleeding, patients may be afforded intervals to at least 4 h for spontaneous expulsion of the placenta after fetal expulsion.