More than just teeth: How oral health can affect the heart.

Epidemiological evidence has revealed a potential relationship between periodontal disease and cardiovascular disease (CVD). Consensus regarding a link between these pathologies remains elusive, however, largely secondary to the considerable overlap between risk factors and comorbidities common to both disease processes. This review article aims to update the evidence for an association by summarizing the evidence for causality between periodontitis and comorbidities linked to CVD, including endocarditis, hypertension (HTN), atrial fibrillation (AF), coronary artery disease (CAD), diabetes mellitus (DM) and hyperlipidemia (HLD). This article additionally discusses the role for periodontal therapy to improved management of the comorbidities, with the larger goal of examining the value of periodontal therapy on reduction of CVD risk. In doing so, we endeavor to further the understanding of the commonality between periodontitis, and CVD.

Neonatal Osteomyelitis.

Osteomyelitis is a serious and potentially life-threatening condition affecting the skeletal system of newborns. The condition is relatively rare in neonates but occurs at higher rates in high-risk pregnancies, in preterm infants, and with the use of invasive devices. As a result of the anatomy and immature immune system of newborns, neonates differ in presentation, diagnosis, and management of osteomyelitis compared to patients of other age groups. An understanding of these differences will assist clinicians in the prompt diagnosis and management of this neonatal infection and lead to improved long-term outcomes.

Oral Health and Cardiovascular Disease.

Several studies have examined a potential relationship between periodontal disease and cardiovascular disease. This article aims to update the evidence for a potential association by summarizing the evidence for causality between periodontitis and comorbidities linked to cardiovascular disease, including hypertension, atrial fibrillation, coronary artery disease, diabetes mellitus, and hyperlipidemia. We additionally discuss the evidence for periodontal therapy as a means to improved management of these comorbidities, with the larger goal of examining the value of periodontal therapy on reduction of cardiovascular disease risk.

Ultrasound-Guided Prospective Screening for Spinal Dysraphism in Offspring of Mothers With Pregestational Diabetes: A Pilot Study.

AIM: Determine the utility of prospective spinal ultrasound in infants of mothers with pregestational diabetes (PGDM) for the diagnosis of closed spinal dysraphism (SDs). METHODS: This prospective observational pilot study was completed at a tertiary care center between May 1, 2020 and December 30, 2022. Infants born to mothers with PGDM and with normal spinal physical examinations were included. A total of 25 mother-infant dyads were enrolled in the study and prospectively screened with spinal ultrasound. The study was registered on ClinicalTrials.gov (Identifier-NCT05033275). RESULTS: Twenty-five spinal ultrasounds were performed over the course of this study with three (8%) resulting in abnormal findings that required further imaging. Follow-up with magnetic resonance imaging found one case of tethered cord syndrome. CONCLUSION: Prospective screening in infants of mothers with PGDM found one case of tethered cord syndrome. This finding suggests that risk stratified screening of mothers with diabetes might be a reasonable approach to care.

Lumbar punctures are safe in patients with ALS and have a risk profile similar to that in the non-ALS population.

INTRODUCTION/AIMS: Analysis of biofluids, especially cerebrospinal fluid (CSF), is critically important for amyotrophic lateral sclerosis (ALS) research. Collection of CSF is typically performed by lumbar puncture (LP). Previous studies have demonstrated the safety of LPs in patients with other neurodegenerative diseases, such as Alzheimer's disease, although there are no published studies of the safety of LPs in patients with ALS. We performed a retrospective analysis of complications resulting from LPs. METHODS: This is a retrospective study of LPs performed between 2015 and 2021 on a total of 233 participants (healthy controls [n = 63], ALS [n = 154], and disease controls [n = 16]) as part of clinical research studies at the Washington University ALS Center. We used bivariate logistical analyses looking for associations between participant characteristics and adverse events (AEs), and likelihood ratio tests were used for significance testing. RESULTS: We found an overall AE rate of 21.03%. AEs included headache, back pain, vasovagal syncope, and severe headache requiring epidural blood patch. Participants with ALS were not more likely to experience post-LP AEs compared to controls (odds ratio [OR] 0.61 [0.32-1.18]). Post-LP headaches were significantly less likely in participants with ALS (OR 0.36 [0.15-0.83]). DISCUSSION: Our findings demonstrate that LP is a safe procedure for participants with ALS, with a similar or lower rate of AEs than in participants without ALS.

Diagnostic Utility of Spinal Ultrasounds in Neonates.

OBJECTIVE: Ultrasound (US) is a common imaging modality used to evaluate spinal anomalies in newborns. However, many indications for the use of spinal US are associated with low diagnostic yield. The purpose of this study is to evaluate the indications and the diagnostic utility of spinal USs performed in newborns at our institution. We also review patient presentations for caudal regression syndrome (CRS) that was identified from the USs performed. STUDY DESIGN: This study is a retrospective review of spinal USs performed between January 1, 2006, and December 31, 2021, in newborns at a single institution. Indications for each US and any associated abnormalities were noted. Infants with abnormal USs showing CRS are described with their long-term medical outcomes. RESULTS: A total of 592 USs were performed during the specified time period of which 72 (12%) were abnormal. The presence of a sacral dimple was the most common indication for performing a spinal US, although only 14 (4%) were identified as abnormal. Of these 14, 6 (43%) were further evaluated by spinal magnetic resonance imaging (MRI) at the recommendations of a pediatric radiologist and of these, only 2 (14%) had abnormal MRI findings. The two newborns with abnormal MRI findings had mothers with diabetes mellitus in their pregnancies. Of note, one additional newborn had abnormalities on spinal US that was never confirmed on MRI due to being lost to follow-up. Among the other indications, anorectal anomalies (odds ratio [OR], 7.55; 95% confidence interval [CI], 3.01-18.91), spinal mass (OR, 17.99; 95% CI, 7.86-41.2), and meningocele were most associated with abnormal findings. CONCLUSION: Overall, spinal US has a low diagnostic yield. Sacral dimple was the most common indication for performing a spinal US but had a low yield with few long-term sequelae. Anorectal anomalies had a strong association with abnormal US findings. KEY POINTS: · Sacral dimple is a common indication for spinal ultrasound.. · Spinal ultrasound has low diagnostic yield when performed for sacral dimple.. · Caudal regression syndrome is associated with maternal diabetes and numerous long-term comorbidities..

Diabetic Embryopathies.

Diabetic embryopathy is defined as congenital anomalies that are linked to maternal diabetes. The association between diabetes and fetal, neonatal, and long-term complications is well-established. These complications include organ or structural maldevelopment, fetal growth abnormalities, and learning/psychiatric comorbidities. Recent studies have elucidated the pathophysiology behind these conditions and outlined new management approaches. Caudal regression syndrome, also known as sacral agenesis, is a well-known but less described complication of maternal diabetes. The purpose of this review is to summarize existing research on common neonatal morbidities in infants of mothers with diabetes with a focus on caudal regression syndrome and its long-term associations.

First Report Of 50-Day Continuous Fasting in Symptomatic Multivessel Coronary Artery Disease and Heart Failure: Cardioprotection Through Natural Ketosis.

A 64-year-old man with angina and dyspnea due to severe two vessel coronary artery disease (CAD) was recommended for revascularization. The patient had recently learned Siddha fasting and self-inquiry meditative methods at Heartful Living, our eight-week physicianled cardiac wellness group clinic. He declined coronary artery bypass surgery and instead self-initiated a 50-day water-only fast and then switched to a vegan diet. During the fast, the patient experienced severe dehydration and electrolyte abnormalities, requiring IV fluids and electrolyte replacement. However, his hemodynamics remained stable and he had no angina, likely due to natural ketosis mediated cardioprotection. This is the first report of such a prolonged fast targeting cardiac resilience and clinical benefits in severe CAD.

Siddha fasting in obese acute decompensated heart failure may improve hospital outcomes through empowerment and natural ketosis.

BACKGROUND: Morbid obesity (BMI > 35 kg/m2 with comorbid conditions) is present in 25 - 35% of acute decompensated heart failure (AHF) patients. Prevalence of HF increases with duration of morbid obesity from 30% at 15 years to over 90% at 30 years. There is a need to develop pragmatic therapies that address the unique physical and mental challenges faced by obese AHF patients. Siddha is 5,000 year old Tamil Medicine using yoga and mind-body methods towards higher consciousness. Hunger gratitude Experience (HUGE) is intuitive Siddha fasting method which may improve in-hospital AHF outcomes independent of weight reduction. CASE SUMMARY: We present 5 cases of morbidly obese patients with cardiorenal syndrome (CRS) that began intermittent fasting either during their AHF hospitalization or in the outpatient setting for refractory symptoms despite hospitalization. Initiation of fasting correlated with reduction of respiratory distress and edema as well as improvements in psychological wellbeing and functional capacity. DISCUSSION: Siddha fasting mediates hemodynamic and anti-inflammatory effects through natural ketosis and psychological benefits through empowerment in AHF. Potential role of fasting in reducing myocardial workload, coronary steal, angina, volume overload, and CRS needs further study in cardiac patients.

Author Correction: RNA cargos in extracellular vesicles derived from blood serum in pancreas associated conditions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

RNA cargos in extracellular vesicles derived from blood serum in pancreas associated conditions.

Exosomes are extracellular vesicles which are released from healthy and tumor cells into blood circulation. Unique biomolecular cargos such as RNA and protein are loaded in these vesicles. These molecules may have biological functions such as signaling, cell communications and have the potential to be analyzed as biomarkers. In this initial study, we describe the analysis of exosomes in the serum of healthy subjects, intraductal papillary mucosal neoplasms and pancreatic ductal adenocarcinoma including the characterization of their RNA cargos by next generation sequencing (EXO-NGS). Results indicate the presence of a wide variety of RNAs including mRNA, miRNA, lincRNA, tRNA and piRNA in these vesicles. Based on the differential mRNA expression observed upon EXO-NGS analysis, we independently evaluated two protein coding genes, matrix metalloproteinase-8 (MMP-8) and transcription factor T-Box 3 (TBX3) by qRT-PCR for selective expression in the serum samples. Results indicate a variable expression pattern of these genes across serum samples between different study groups. Further, qRT-PCR analysis with the same serum exosomes processed for EXO-NGS, we observed two long non-coding RNAs, malat-1 and CRNDE to be variably expressed. Overall, our observations emphasize the potential value of different exosome components in distinguishing between healthy, premalignant and malignant conditions related to the pancreas.

Molecular targets for tivantinib (ARQ 197) and vasculogenic mimicry in human melanoma cells.

Tivantinib (TivB) was reported previously to target MET and microtubule assembly in different cells resulting in cytotoxicity. However, its other cellular targets remain unknown, especially the proteins involved in focal adhesion and cytoskeletal organization. We studied the effect of TivB on vinculin a focal adhesion protein, and RhoC, a GTPase which promote the reorganization of cytoskeleton. Biomolecules involved in vasculogenic mimicry (VM) previously not reported in melanoma, and their susceptibility to TivB was also evaluated. TivB affects the viability and apoptosis of human melanoma cells depending on the cell type. Vinculin and RhoC were increased in the presence of TivB and affected the integrity of actin filaments and altered the cellular morphology. TivB disrupts the VM exhibited by melanoma cells in 3D matrix. Roundabout Guidance Receptor 4 (Robo4), a receptor protein implicated in axonal guidance and angiogenesis and its ligand Slit2 are expressed in human C8161 and WM793 melanoma cells, but absent in other melanoma cells including normal melanocytes. VM is more prominent in C8161 cells and could be blocked by siRNA mediated silencing of Robo4 mRNA, but TivB does not affect Robo4 in C8161 cells. Immunoblot analysis indicated no changes in Robo4 and Slit2 protein expression, however, both vinculin and RhoC protein increased in TivB treated melanoma cells. These results suggest that TivB affects cell cytoskeleton and morphology by altering proteins such as vinculin and RhoC. Our studies indicate TivB could target molecules other than MET in melanoma cells, which may provide insight into its alternate mechanism of action.

Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone.

The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl)-homoserine lactone (C12-HSL) on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA) cells (DU145 and LNCaP) and prostate small cell neuroendocrine carcinoma (SCNC) PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1) were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.