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Gestational Diabetes Leading to Cardiovascular Disease
No full textGestational diabetes mellitus (GDM) is an increasingly prevalent complication of preg-nancy leading to adverse maternal outcomes for years postpartum. This primary litera-ture review was conducted to explore what complications of GDM have significant cor-relation with an increased risk for eventual onset of cardiovascular disease (CVD). Overlapping risk factors for GDM and CVD such as obesity, sedentary lifestyle, and poor diet are largely the cause for this correlation. Obesity is a commonly recognized cause of the progression from GDM to CVD. However, there remains the need to iden-tify other factor(s) that elevate CVD risk in women who have had GDM but who are not obese and who lead an active life. The literature review explores the issues that may be secondary to obesity, along with outcomes of GDM that lie outside of obesity entire-ly and remain known exclusively as a by-product of GDM. This allowed for some pos-sible explanations for the increased cardiovascular risk seen in women who had GDM but would typically not be considered high risk for CVD or GDM. GDM results in vari-ous adverse outcomes including hypertension, dyslipidemia, inflammation, endothelial dysfunction, and type 2 diabetes, all of which promote progression to CVD. These may serve as intermediate factors in the onset of CVD up to 25 years postpartum. Seden-tary lifestyle and advanced maternal age are critical factors favoring the progression of GDM to CVD. Further identification of risk factors leading to CVD would allow for pre-vention of onset of CVD following a pregnancy affected by GDM
Expression and Regulation of FGF23 in Osseous and Extra-Skeletal Tissues During Normal and Altered Metabolic States
No full textPhosphorus equilibrium in the body is regulated through uptake and release via the intestine, kidney and bone. These processes are coordinated through the activity and regulation of Fibroblast Growth Factor 23 (FGF23). FGF23 is primarily produced in osseous structures by osteocytes and osteoblasts. Under normal physiological conditions, elevations in serum phosphorus or active 1,25dihydroxyvitamin D stimulate tran-scriptional upregulation of FGF23 and promote the release of the full-length intact FGF23 protein which targets it to downstream tissues. Studies in rare heritable forms of phosphate dysregulation revealed novel pathways of FG23 regulation including iron deficiency and inflammation. Notably, FGF23 expression under these conditions were not confined to the skeletal tissues. Thus, this review will examine the regulation of FGF23 in normal and altered metabolic states as well as how they affect expression within extra-skeletal tissue
Role of adipose triglyceride lipase and CGI-58 in lipid droplet breakdown during Coxiella burnetii infection
No full textCoxiella burnetii is an obligate intracellular bacterium responsible for causing culture negative endocarditis. The manifestation of this condition several years following initial infection exhibits Coxiella’s ability to persist long-term in alveolar macrophages. Our overall goal is to identify the strategies Coxiella employs for successful survival in the host. In our previous studies, examination of Coxiella-infected alveolar macrophages revealed accumulation of host lipid storage organelles called lipid droplets (LDs). Host LD alteration was dependent on Coxiella Type 4 Secretion System (T4SS) which re-leases bacterial proteins in the host cytoplasm and manipulates several host cell processes. Further, manipulating LD metabolism significantly altered Coxiella growth. Specifically blocking the activity of the LD breakdown enzyme adipose triglyceride li-pase (ATGL) completely inhibited Coxiella growth suggesting that ATGL-mediated LD catabolism is important for bacterial intracellular survival. Based on our preliminary studies, we hypothesize that Coxiella manipulates host cell ATGL to promote LD breakdown and support intracellular bacterial growth. To test this, we quantitated ATGL gene expression level in uninfected, wild-type Coxiella-infected and T4SS-mutant Coxi-ella-infected alveolar macrophages. Compared to uninfected cell, Coxiella-infected cells demonstrated increased ATGL gene expression in a T4SS-dependent manner suggesting importance of ATGL during Coxiella infection. Since ATGL activity depends on co-activator CGI-58 binding, we determined CGI-58 gene expression levels in differentially infected cells. However, no differences were observed in CGI-58 suggesting that Coxiella specifically manipulates ATGL via its T4SS and not its co-activator. On-going studies are determining if Coxiella manipulates ATGL protein level and activity. Completion of our studies will identify the mechanism Coxiella employs to manipulate host LD homeostasis to promote its intracellular survival
Passing of the TORCH: A Medical, Historical, and Social Comparison between Rubella and Zika
Get PDFA historical analysis and comparison between rubella and zika reveals that neither virus became prominent until their respective congenital syndromes were classified. Rubella was first described in the 1750s but took until 1941 when Norman McAlister Gregg characterized Congenital Rubella Syndrome to become medically significant. Similarly, zika virus was discovered in 1947 but only made headlines in 2016 when its infection during pregnancy was associated with fetal microcephaly. An investigation into the response levels that each virus received following the discovery of their respective congenital syndromes reveals a fascinating correlation. Despite zika being primarily a disease of the developing world and rubella historically being a worldwide disease, with a previously high prevalence in developed countries such as the United States (US), zika was found to have been studied and controlled at a much faster rate than rubella. This correlation is further highlighted by the fact that there are currently no available therapies or vaccines for zika. Using the US as a benchmark, the rubella vaccine was available in 1969 following the rubella epidemic of 1964-1965. However, it would take until 2004 before the US was declared rubella free. When compared to zika, following the 2015-2016 outbreak in the Americas, the incidence of zika in the US went from 10 cases in 2015 to a staggering 36,512 cases in 2016. Remarkably, by the end of the following year, the incidence had dropped to just 666 cases in the states. In 2018, there were only 148 zika cases in the US. A review of Thomas McKeown’s work on population growth, the McKeown Thesis, provides insight into the US’s successful zika control. The Thesis posits that broad-based social efforts at the population level are more significant at affecting public health than narrow-based medical interventions at the individual level. The swift control of zika despite the lack of specific therapeutics suggests the McKeown Thesis’s applications. This presentation provides an in-depth analysis and comparison between the medical, historical, and social components of rubella and zika to demonstrate their ongoing implications and influences on society. This presentation will reflect on the progress and history of medicine within the past century and demonstrate the need for continued vigilance within the medical community
Participation in an Educational Module for Medical Students in Regards to Complementary and Alternative Medicine (CAM) Therapies
Get PDFBackground and Review of the Literature: In the United States, the use of complementary and alternative medicine (CAM) has increased. The term CAM refers to a variety of alternative therapies and techniques usually not part of standard medical care. According to the National Center for Complementary and Integrative Health (NCCIH), more than thirty percent of adults and twelve percent of children use methods not typically considered conventional, or mainstream practice. Complementary medicine can be utilized with standard medical treatments for a more patient-centered collaborative approach, referred to as integrative medicine (IM). Although gaining popularity and driven by patients, many conventional healthcare providers lack the awareness and familiarity to discuss, recommend, or refer CAM therapies. Purpose: The purpose of this DNP project is to investigate medical students\u27 knowledge, beliefs, attitudes and future collaboration practices related to complementary therapies through the use of an online educational portal Method: This project implemented an educational intervention in order to improve the knowledge of students enrolled in a Doctor or Osteopathic Medicine Program in regards to Complementary and Alternative Medicine. Implementation Procedure: An internet based resource tool was developed as a resource guide, providing information about complimentary licensed practitioners, therapies, best practices, and protocols
CBX5: A Potential Biomarker of Head and Neck Squamous Cell Carcinoma
No full textHead and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common cancers in the world, and even in developed countries like the United States, the five-year survival is only 65%. This already low survival rate drops precipitously for metastatic disease, but unlike other malignancies, even regional spread significantly decreases 5-year survival. Despite its devastating impact on patient outcomes, conventional modalities to detect local micrometastases in oral cancer are inadequate and often debilitat-ing. Therefore, it is critical to identify more accurate means of predicting metastasis from the primary tumor. Oral cancer is unique in its ability to maintain intratumoral vasculature and several studies have linked increased intratumoral vascularity with in-creased risk of metastasis in oral cancer. However, immunohistochemical analysis of microvessel density alone is insufficient to predict the metastatic propensity of the tumor accurately. As an alternative, it may be possible instead to identify the molecular drivers of this vascularized phenotype and provide a more robust statistical risk assessment. Using an in vivo model of oral cancer metastasis, we have identified Chro-mobox 5 (CBX5) as a putative regulator of intratumoral vascularity and downstream metastasis. CBX5 is an epigenetic regulator that is mainly associated with chromatin remodeling and heterochromatin formation. Loss of CBX5 has been associated with more aggressive tumor types, suggesting that it may epigenetically regulate the tumor microenvironment. Indeed, CBX5 expression is significantly increased in avascular metastatic oral cancer cells compared to those cells that give rise to a vascular tumor phenotype in vivo. We have further hypothesized that overexpressing CBX5 will inhibit the in vitro metastatic phenotype of these cells. We will differentially regulate CBX5 expression in these cells through knockdown and overexpression and subsequently examine their migration, invasion, and motility in vitro. By confirming a mechanistic role for CBX5 in the regulation of a vascularized, metastatic phenotype, we will contribute to the development of a minimally invasive and reliable diagnostic technique that can improve outcomes for oral cancer patients
Sex Is A Strong Variable In The Mineral Metabolism Defects And Endocrine Dysfunction Associated With The Murine Adenine Diet Model Of Chronic Kidney Disease (CKD
No full textIntroduction: The adenine diet is widely used in animal models to produce a tubu-lointerstitial fibrosis and inflammation that mimics human CKD in many aspects. These include the biochemical manifestations hyperphosphatemia and anemia, as well as endocrine dysfunction with elevated FGF23 and hyperparathyroidism. Male rodents are known to be less tolerant of adenine diet regimen than females, however the underlying mechanisms driving the sex differences remain unclear. Additionally, much of the data for adenine studies arises from rats, whereas mice are more commonly used in laboratory settings and are far easier to manipulate genetically. Objective: To this end, as part of a larger study to test the effects of iron-handling in CKD, we assessed the biochemical, molecular, and physical differences between male and female mice receiving an adenine diet to induce CKD. Methods: Flox-Fgf23 mice (8 weeks of age, n=4-6/group; mice were Cre negative, thus phenotypically wild type) were placed on a 0.2% adenine-containing diet (CKD); a matching casein-based diet served as control. After 6 weeks, mice were euthanized, and blood and tissues were collected for analysis. Results: As expected, body weight at baseline was initially higher in males than in females, however males lost significantly more weight. Serum BUN was also elevated in both sexes receiving adenine, although males were higher (1.2 fold; p\u3c0.01). Males also had elevated creatinine and lower total serum iron from baseline whereas females had no significant changes. FGF23 was elevated in all mice, with no significant differ-ences between sexes. Kidney fibrosis and inflammation markers were elevated in the CKD mice, with males having higher expression of Col1a1 and -3a1 versus females (3.5/1.5 fold; p\u3c0.001) and TNFα mRNA (2 fold; p\u3c0.001). Renal expression of the anabolic vitamin D metabolizing enzyme Cyp27b1 (1a-hydroyxlase) and early growth response 1 (Egr1) were increased in CKD mice, with males having higher expression over females. Conversely, CKD males had lower kidney Klotho mRNA expression, and both sexes fed adenine expressed significantly lower NPT2a (sodium- phosphate co-transporter2a) mRNA. Liver expression of ferritin (Fth1) was elevated in male CKD mice compared to diet controls, whereas female mice had no differences. Elevated FGF23 has been linked to ventricular hypertrophy, and CKD males had significantly higher heart weight to femur ratio at completion of the study. Conclusions: Our results support that male mice succumb more rapidly than females to adenine diet mediated CKD phenotypes, potentially enhanced by fibrosis and inflam-mation. It remains to be determined whether the more rapid onset of defects in iron handling parameters accelerate the severe male CKD phenotype
Vitamin C as a Model for a Novel and Approachable Experimental Framework for Investigating Spectrophotometry
No full textEffect of Suboccipital Release on Pain Perception and Autonomic Reflex Responses to Ischemic and Cold Pain
No full textIntroduction: In 2012, approximately 19 million adults in the U.S. used some form of manipulative treatment as part of their overall healthcare. Suboccipital release (SOR) is a commonly used manual medicine technique of the head and neck. SOR and related techniques are also used to treat pain from tension-type and migraine headaches. The clinical effects of SOR are purported to be mediated via the autonomic nervous system, but similar to many manual techniques, the neurophysiological data in this area are sparse. Thus, the effects and mechanisms of SOR are unclear and not well understood. Objective: This study aimed to determine the effects of SOR on the cardiovascular system during cold pain and ischemic pain. Methods: 16 healthy subjects (8 women, 8 men) experienced ischemic (forearm post-exercise muscle ischemia; PEMI) and cold (hand cold pressor test; CPT) pain. Beat-to-beat heart rate (HR; ECG), mean arterial blood pressure (MAP; finger photoplethysmography), baroreflex sensitivity (transfer function analysis), and pain perception were measured. SOR or a sham (modified yaw; 30 cycles/min) was performed in the final minute of pain. To probe potential mechanisms and interactions between manual treatment and a prototypic analgesic, oral aspirin (967 mg) was given 60 min prior to testing to reduce prostaglandin synthesis. Results: PEMI increased MAP by 23±2 and 20±2 mmHg; no differences occurred with the addition of SOR or yaw. PEMI modestly elevated HR during ischemia, followed by a significant reduction from baseline with SOR (-3±2 bpm) and yaw (-4±2 bpm); no differences were observed between treatment and sham. CPT increased MAP (SOR=11±1, yaw=9±2 mmHg) and HR (SOR=10±2, yaw=8±3 bpm) prior to SOR and yaw. Neither treatment nor sham blunted MAP increased (SOR=25±2, yaw=22±2 mmHg) with CPT; both decreased HR (SOR=-3±2, yaw=-2±2 bpm) from baseline. PEMI and CPT caused increased pain without treatment modulation. SOR decreased baroreflex sensitivity in the 0.05-0.15 Hz range and increased it in the 0.15-0.35 Hz range compared to yaw. Aspirin slightly attenuated pain but did not alter cardiovascular changes to PEMI and did not interact with SOR or yaw. These data indicate that “hands-on” interventions during acute pain and SOR post-pain have the capacity to modulate certain pain-induced autonomic effects. Conclusion: The primary findings of this study are that acute hypertensive conditions caused by experimental pain were not modulated by SOR, but HR responses were decreased during both SOR and a “hands-on” sham technique. The changes in BP and blood flow due to pain were not altered by the SOR treatment. However, baroreflex sensitivity was altered in both the low and high frequency ranges during the recovery period after experimentally induced pain, regardless of the type of pain. These data indicate that “hands-on” interventions during acute pain and SOR post-pain have the capacity to modulate certain pain-induced autonomic effects
Should patients with systemic lupus erythematosus (SLE) RECEIVE a heart transplant?
No full textThis was a case study on a patient with SLE who received a heart transplant. Patients with SLE are generally not considered to be ideal candidates for transplantation due to auto-immunity involving many organ systems. Historically, patients with SLE requiring kidney transplantation have had good prognosis, but there is a weaker consensus sur-rounding heart transplantation in patients with SLE-related cardiomyopathy and heart failure. A 24-year-old female patient presented in 2016 with cardiogenic shock with a history of non-ischemic dilated cardiomyopathy with an ejection fraction of 5-10% and SLE com-plicated by nephritis. She required 2-3 hospital visits per year due to heart failure and SLE complications. A chest X-ray revealed cardiomegaly with hypo-inflated lungs. She was placed on inotropic support and followed up with a heart transplant in 2017. During transplantation, her heart was found to have dense adhesions resulting from SLE. In 2018, the patient returned with acute kidney injury and chronic kidney disease (CKD) Stage 3 with metabolic acidosis and a diastolic dysfunction. Her chest X-ray presented with mild cardiomegaly and a kidney ultrasound was negative for hydronephrosis. She was diagnosed with NYHA class III heart failure and was prescribed torsemide and a therapeutic plan to begin her on allopurinol due to her reduced GFR. After immunosup-pressive therapy, her Stage IV lupus nephritis was not active at the time of her dis-charge. Conclusion: This case demonstrates the ongoing challenges that physicians encoun-ter when managing patients with SLE-related cardiac involvement. The literature cites no clear consensus regarding management of patients with cardiac involvement of SLE, especially considering the large range of cardiac involvement. This case supports the growing need for understanding and managing cardiac involvement in patients with SLE