Prolactin Mediates Long-Term, Seasonal Rheostatic Regulation of Body Mass in Female Mammals.

A series of well-described anabolic and catabolic neuropeptides are known to provide short-term, homeostatic control of energy balance. The mechanisms that govern long-term, rheostatic control of regulated changes in energy balance are less well characterized. Using the robust and repeatable seasonal changes in body mass observed in Siberian hamsters, this report examined the role of prolactin in providing long-term rheostatic control of body mass and photoinduced changes in organ mass (ie, kidney, brown adipose tissue, uterine, and spleen). Endogenous circannual interval timing was observed after 4 months in a short photoperiod, indicated by a significant increase in body mass and prolactin mRNA expression in the pituitary gland. There was an inverse relationship between body mass and the expression of somatostatin (Sst) and cocaine- and amphetamine-regulated transcript (Cart). Pharmacological inhibition of prolactin release (via bromocriptine injection), reduced body mass of animals maintained in long photoperiods to winter-short photoperiod levels and was associated with a significant increase in hypothalamic Cart expression. Administration of ovine prolactin significantly increased body mass 24 hours after a single injection and the effect persisted after 3 consecutive daily injections. The data indicate that prolactin has pleiotropic effects on homeostatic sensors of energy balance (ie, Cart) and physiological effectors (ie, kidney, BAT). We propose that prolactin release from the pituitary gland acts as an output signal of the hypothalamic rheostat controller to regulate adaptive changes in body mass.

Management of Sternal Wounds, Infections, and Sternal Non-Union with Plate Fixation: Result from a Single Site Experience.

Background: Patients with sternal wounds, infection, or non-union after cardiac surgery continue to have increased morbidity and mortality rates compared with those without sternal complications. Reconstructive methods have largely centered on soft tissue approaches, including muscle or omental flaps, which result in functional loss. Some data show early positive advantages using sternal rigid plate fixation (SRPF), however, it is debated in the setting of active infection. The goal of this study is to examine the outcomes of SRPF in patients with and without infections. Patients and Methods: This is a retrospective study of consecutive patients who underwent SRPF by a single plastic surgeon from April 2013 to August 2021. Patients treated without SRPF, lacking at least six months of follow-up, or those plated more than once were excluded. Ninety-seven patients were included. Demographic and peri-operative factors associated with sternal infection after SRPF were evaluated. Results: Sixty-eight patients were clinically infected/culture positive or open (INFECTED), and 29 were clean/primary plating (CLEAN). Sixteen percent of the INFECTED cases (11/68) returned with infection. Fourteen percent of the CLEAN cases (4/29) had subsequent infections. Additionally, we did note a decrease in rates of infections overall (p < 0.0001) as experience and frequency of plate fixation increased (p < 0.0001). Regardless of infection status, all but one patient had a healed and stable sternum at the end of data collection. Conclusions: There is no statistically significant difference between wound class prior to SRPF and development of infection after SRPF. Even in infected settings, patients can be treated successfully with SRPF. Further study is needed.

Delivery of 
Clinical Services: Mobilizing Advanced Practice Providers to Enhance Patient Care.

Advanced practice providers (APPs) are increasingly being used in a variety of healthcare settings to provide care, treatment, and services to patients with cancer. They are also being deployed to acute oncologic settings to enhance patient care delivery and address the ever-evolving needs of patients in academic medicine. In response, the University of Texas MD Anderson Cancer Center developed a series of innovative clinical programs staffed by acute care APPs. These provide an opportunity to rapidly adapt to the acute care needs of patients with cancer while fostering the professional development of APPs within the full scope of their oncologic clinical practice.
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G protein-coupled KISS1 receptor is overexpressed in triple negative breast cancer and promotes drug resistance.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this signaling pathway plays anti-metastatic roles. However, in TNBC, KISS1R promotes tumor invasion. We show that KISS1 and KISS1R mRNA and KISS1R protein are upregulated in TNBC tumors, compared to normal breast tissue. KISS1R signaling promotes drug resistance by increasing the expression of efflux drug transporter, breast cancer resistance protein (BCRP) and by inducing the activity and transcription of the receptor tyrosine kinase, AXL. BCRP and AXL transcripts are elevated in TNBC tumors, compared to normal breast, and TNBC tumors expressing KISS1R also express AXL and BCRP. Thus, KISS1R represents a potentially novel therapeutic target to restore drug sensitivity in TNBC patients.

The differential effects of low birth weight and Western diet consumption upon early life hepatic fibrosis development in guinea pig.

Postnatal intake of an energy dense diet, the Western diet (WD), is a strong risk factor for liver fibrosis. Recently, adverse in utero conditions resulting in low birth weight (LBW) have also been associated with postnatal fibrosis development. We assessed the independent and possible synergistic effects of placental insufficiency-induced LBW and postnatal WD consumption on liver fibrosis in early adulthood, with a specific focus on changes in inflammation and apoptosis pathways in association with fibrogenesis. Male LBW (uterine artery ablation) and normal birth weight (NBW) guinea pig pups were fed either a control diet (CD) or WD from weaning to 150 days. Significant steatosis, mild lobular inflammation, apoptosis and mild stage 1 fibrosis (perisinusoidal or portal) were evident in WD-fed offspring (NBW/WD and LBW/WD). In LBW/CD versus NBW/CD offspring, increased transforming growth factor-beta 1 and matrix metallopeptidase mRNA and sma- and Mad-related protein 4 (SMAD4) were present in conjunction with minimal stage 1 portal fibrosis. Further, connective tissue growth factor mRNA was increased and miR-146a expression decreased in LBW offspring, irrespective of diet. Independent of birth weight, WD-fed offspring exhibited increased expression of fibrotic genes as well as elevated inflammatory and apoptotic markers. Moreover, the augmented expression of collagen, type III, alpha 1 and tumor necrosis factor-alpha was associated with increased recruitment of RNA polymerase II and enhanced histone acetylation (K9) to their respective promoters. These data support a role for both LBW and postnatal WD as factors contributing to hepatic fibrosis development in offspring through distinct pathways.