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Elucidating the impact of Western diet on bone marrow cytokine signatures: understanding poor outcomes in susceptibility to infection and progression of cancer
Get PDFAmong other disease outcomes, obesity is associated with 1) reduction in long-lasting immune protection and 2) acquisition of cancer. Given our interest in hematopoietic stem and progenitor cell (HSPC) dynamics, we questioned if similar mechanisms in the bone marrow microenvironment contribute to obesity-induced HSPC alterations responsible for 1) decreased immune protection and 2) transformation of HSPCs in the pathogenesis of hematologic malignancies. The negative effects of obesity on immune protection are most notably established in influenza models. Influenza infection susceptibility is increased and influenza vaccine-induced immunity wains in obese individuals. Ongoing studies aim to define mechanisms for waning immunity at sites of infection. Little is understood, however, regarding how obesity affects HSPC dynamics in the bone marrow microenvironment upon immunization. We hypothesized that obesity alters the types and quantities of immune cells produced by HSPCs upon immunization. We further hypothesized that this is due to altered availability of cytokines present in the bone marrow. Similarly, we hypothesized that unique cytokine signatures in the bone marrow of obese individuals serve as a mechanism for cancer initiation and progression in those with genetic susceptibility to MDS. To test our hypotheses, we subjected applicable mouse models to low-fat or high-fat diets. In our immunization studies, results indicate that high-fat diet leads to myeloid skewing in flu-immunized mice and that cytokine trends in the bone marrow provide insight into how this occurs. In our cancer studies, MDS-susceptible mice fed a high-fat diet displayed distinct cytokine signatures when compared to those fed a low-fat diet, suggesting that this may be a mechanism by which obesity contributes to hematologic malignancy. Further understanding of the contribution of obesity-induced bone marrow cytokine signatures to poor health outcomes may inform the design of future vaccine formulations or MDS therapeutics for obese patients
Subcutaneous Sarcoid Nodules: A Dermatologic Presentation of Systemic Sarcoidosis for Primary Care Physicians
Get PDFSarcoidosis is a multisystem granulomatous disease primarily characterized by pulmonary manifestations. Extrapulmonary involvement in sarcoidosis is well documented and common, but isolated extrapulmonary involvement is rare at around 10% of cases at the time of diagnosis. Cutaneous presentations vary significantly, with erythema nodosum being the most common. Since extrapulmonary symptoms most likely suggest systemic involvement, any way to identify sarcoidosis early is paramount. We present a case of a 63-year-old Caucasian female with multiple palpable 0.5-3cm nodules under the skin of the bilateral forearms, left hand, and lower extremities. A biopsy of a lesion revealed numerous sarcoidal phenotype granulomas without necrosis surrounded by a mild lymphocytic infiltrate. Imaging confirmed calcified mediastinal, hilar, and sub-carinal lymph nodes, as well as revealed scattered calcified and non-calcified granulomas in the upper lung fields. Treatment is not always required, and this patient’s subcutaneous nodules resolved with a single course of steroids. Therefore, it is vital for primary care providers to maintain a high index of suspicion for sarcoidosis with various dermatological findings, as it may be the presenting symptom for sarcoidosis and allow early recognition, monitoring, and intervention
Prenatal buprenorphine exposure reduces expression of myelin proteins in neonatal longs-Evans rat
Get PDFIn the USA and especially in WV, there has been a surge in the rise of opioid use disorder (OUD), and with it a rise in neonatal abstinence syndrome (NAS). What makes this rise in NAS so unfortunate is that the Medications for OUD (MOUD) do not prevent the development of NAS. Although the relationship between MOUD and NAS is still unclear, it is thought that buprenorphine, one of the main substances used to treat OUD in pregnant women, may feed into the development of NAS, which may affect mental and physiological development and cause other health problems. Via understanding the developmental impact of NAS, we hope to pave the way for future NAS treatments and a brighter future for the children of the USA.
The central hypothesis of this proposal is that developmental issues caused by prenatal buprenorphine exposure are due to reduced expression of white matter development proteins, such as NG2 and MBP, and changes in neuronal proteins such as Kif5A, and that these changes cause deficits in the white matter parts of the brain. To study this hypothesis, we used a rat in utero buprenorphine exposure model to investigate the impact of this opioid on the post-natal time course of protein expression in two white matter tracts, the optic nerve and cerebellum.
Preliminary Western blot analysis indicates that there is a significant interaction between post-natal age and treatment for multiple proteins involved in myelination. Both white matter tracks also showed significant increases of KiF5A late in post-natal development. This data indicates that in utero buprenorphine impacts white matter development promoting a change in the protein expression timelines. If these developmental changes are maintained throughout the life span, they could explain some of the issues associated with the long-term impact of NAS
Magnet Hospitals: An Update on the Impact on Nursing Burnout
Get PDFNurse burnout has been associated with worsened outcomes for nurses, such as increased turnover or quitting and lower job satisfaction. The purpose of this research was to examine Magnet-designation status in U.S. hospitals, specifically shared governance and structural empowerment, and its effects on nurse burnout, nurse turnover, and job satisfaction of nurses. This study utilized a literature review complemented by two semi-structured interviews. The results showed that Magnet hospitals kept lower levels of burnout, better job satisfaction, and less turnover than non-Magnet hospitals, but this was only the case for some studies of Magnet hospitals. Some outcomes could be attributed to Magnet characteristics, such as shared governance, but other factors could have influenced their success
