Addressing Operational Challenges Faced by COVID-19 Public Health Rapid Response Teams in Non-United States Settings.

The coronavirus disease 2019 (COVID-19) global response underscores the need for a multidisciplinary approach that integrates and coordinates various public health systems-surveillance, laboratory, and health-care systems/networks, among others-as part of a larger emergency response system. Multidisciplinary public health rapid response teams (RRTs) are one mechanism used within a larger COVID-19 outbreak response strategy. As COVID-19 RRTs are deployed, countries are facing operational challenges in optimizing their RRT's impact, while ensuring the safety of their RRT responders. From March to May 2020, United States Centers for Disease Control and Prevention received requests from 12 countries for technical assistance related to COVID-19 RRTs and emergency operations support. Challenges included: (1) an insufficient number of RRT responders available for COVID-19 deployments; (2) limited capacity to monitor RRT responders' health, safety, and resiliency; (3) difficulty converting critical in-person RRT operational processes to remote information technology platforms; and (4) stigmatization of RRT responders hindering COVID-19 interventions. Although geographically and socioeconomically diverse, these 12 countries experienced similar RRT operational challenges, indicating potential applicability to other countries. As the response has highlighted the critical need for immediate and effective implementation measures, addressing these challenges is essential to ensuring an impactful and sustainable COVID-19 response strategy globally.

The role of coping in the relationship between depression and illness severity in chronic fatigue syndrome.

UNLABELLED: The self-regulatory model (SRM) proposes that both cognitive and emotional illness representations influence the coping processes adopted in response to an illness. AIM: This study used the SRM to explore the role of coping in the relationship between depression and self-appraisals of illness severity in a population of patients with chronic fatigue syndrome (CFS). METHODS: The sample comprised 156 participants, 34 men and 121 women, aged between 18 and 78 yrs, who had been medically diagnosed with CFS. Participants were asked to complete three questionnaires: the Cardiac Depression Scale, Ways of Coping Questionnaire, and Severity Subscale of the Illness Perceptions Questionnaire-Revised. RESULTS: Analyses revealed that almost 70% of the participants were moderately or severely depressed. Additionally, two particular subscales, social support seeking and positive reappraisals, emerged as positively contributing to self-appraisals of illness severity (beta = 0.20 [p < 0.05] and beta = 0.21 [p < 0.05], respectively), thereby supporting the SRM. Furthermore, results indicated that a combination of depression and coping was a better predictor of illness severity than depression alone, accounting for 22% of the variance compared with 8%, respectively. CONCLUSIONS: The findings suggest that focusing on depression, and particularly coping styles, during treatment interventions could have important implications for therapeutic interventions. This could lead to better treatment strategies for health professionals who work with patients with CFS.

The matrix protein Fibulin-3 promotes KISS1R induced triple negative breast cancer cell invasion.

Breast cancer is a leading cause of cancer mortality. In particular, triple negative breast cancer (TNBC) comprise a heterogeneous group of basal-like tumors lacking estrogen receptor (ERα), progesterone receptor (PR) and HER2 (ErbB2). TNBC represents 15-20% of all breast cancers and occurs frequently in women under 50 years of age. Unfortunately, these patients lack targeted therapy, are typically high grade and metastatic at time of diagnosis. The mechanisms regulating metastasis remain poorly understood. We have previously shown that the kisspeptin receptor, KISS1R stimulates invasiveness of TNBC cells. In this report, we demonstrate that KISS1R signals via the secreted extracellular matrix protein, fibulin-3, to regulate TNBC invasion. We found that the fibulin-3 gene is amplified in TNBC primary tumors and that plasma fibulin-3 levels are elevated in TNBC patients compared to healthy subjects. In this study, we show that KISS1R activation increases fibulin-3 expression and secretion. We show that fibulin-3 regulates TNBC metastasis in a mouse experimental metastasis xenograft model and signals downstream of KISS1R to stimulate TNBC invasion, by activating matrix metalloproteinase 9 (MMP-9) and the MAPK pathway. These results identify fibulin-3 as a new downstream mediator of KISS1R signaling and as a potential biomarker for TNBC progression and metastasis, thus revealing KISS1R and fibulin-3 as novel drug targets in TNBC.

Implantation failure in female Kiss1-/- mice is independent of their hypogonadic state and can be partially rescued by leukemia inhibitory factor.

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin signaling that underlies the implantation failure. This absence, however, does not prevent the closure of the uterine implantation chamber, proper alignment of the embryo, and the ability of the uterus to undergo decidualization. Instead, the loss of Kiss1 expression specifically disrupts embryo attachment to the uterus. We observed that on the day of implantation, leukemia inhibitory factor (Lif), a cytokine that is absolutely required for implantation in mice, is weakly expressed in Kiss1(-/-) uterine glands and that the administration of exogenous Lif to hormone-primed Kiss1(-/-) female mice is sufficient to partially rescue implantation. Taken together, our study reveals that uterine kisspeptin signaling regulates glandular Lif levels, thereby identifying a novel and critical role for kisspeptin in regulating embryo implantation in the mouse. This study provides compelling reasons to explore this role in other species, particularly livestock and humans.

Use of intravenous proton pump inhibitors in community practice: an explanation for the shortage?

BACKGROUND: Since 2001, one intravenous proton pump inhibitor (pantoprazole) has been available in the United States. A drug shortage bulletin was issued for this agent in 2003. AIM: To evaluate the patterns of use of intravenous proton pump inhibitors (IV PPIs) in routine clinical practice. METHODS: Prospective evaluation of IV PPI use in two community-based teaching hospitals. A computerized pharmacy ordering system was used to identify all patients for whom an IV PPI was ordered. Trained investigators obtained clinical data from patient records and these data were mapped to establish clinical criteria for the use of IV PPIs. RESULTS: Intravenous PPIs were prescribed in 238 patients over a 30-day period and a total of 1,631 doses were prescribed. Primary care providers prescribed 46% of prescriptions. Fifty-six percent of patients who received IV PPIs had no acceptable indication for their use. Of the 126 (81%) patients who were started on PPIs for the first time during their hospital stay, 102 were discharged on a PPI. CONCLUSIONS: Intravenous PPIs are widely used for poor indications, which may contribute to the shortage of these agents.