Elucidating the Histone Deacetylase Gene Expression Signatures in Peripheral Blood Mononuclear Cells That Correlate Essential Cardiac Function and Aid in Classifying Coronary Artery Disease through a Logistic Regression Model.

A proinflammatory role of HDACs has been implicated in the pathogenesis of atherosclerosis as an emerging novel epigenetic diagnostic biomarker. However, its association with the clinical and cardiovascular function in coronary artery disease is largely unknown. The study aimed to profile the gene expression of HDAC1-11 in human peripheral blood mononuclear cells and to evaluate their influence on hematological, biochemical, and two-dimensional echocardiographic indices in CAD. The HDAC gene expression profiles were assessed in 62 angioproven CAD patients and compared with 62 healthy controls. Among the HDACs, upregulated HDACs 1,2, 4, 6, 8, 9, and 11 were upregulated, and HDAC3 was downregulated, which was significantly (p ≤ 0.05) linked with the hematological (basophils, lymphocytes, monocytes, and neutrophils), biochemical (LDL, HDL, and TGL), and echocardiographic parameters (cardiac function: biplane LVEF, GLS, MV E/A, IVRT, and PV S/D) in CAD. Furthermore, our constructed diagnostic model with the crucial HDACs establishes the most crucial HDACs in the classification of CAD from control with an excellent accuracy of 88.6%. Conclusively, our study has provided a novel perspective on the HDAC gene expression underlying cardiac function that is useful in developing molecular methods for CAD diagnosis.

Cellular temperature probing using optically trapped single upconversion luminescence.

BACKGROUND: The thermally coupled energy states that contribute to the upconversion luminescence of rare earth element-doped nanoparticles have been the subject of intense research due to their potential nanoscale temperature probing. However, the inherent low quantum efficiency of these particles often limits their practical applications, and currently, surface passivation and incorporation of plasmonic particles are being explored to improve the inherent quantum efficiency of the particle. However, the role of these surface passivating layers and the attached plasmonic particles in the temperature sensitivity of upconverting nanoparticles while probing the intercellular temperature has not been investigated thus far, particularly at the single nanoparticle level. RESULTS: The analysis of the study on the thermal sensitivity of oleate-free UCNP, UCNP@SiO2, and UCNP@SiO2@Au particles is carried out at a single particle level in a physiologically relevant temperature range (299 K-319 K) by optically trapping the particle. The thermal relative sensitivity of the as-prepared upconversion nanoparticle (UCNP) is found to be greater than that of UCNP@SiO2 and UCNP@SiO2@Au particles in an aqueous medium. An optically trapped single luminescence particle inside the cell is used to monitor the temperature inside the cell by measuring the luminescence from the thermally coupled states. The absolute sensitivity of optically trapped particles inside the biological cell increases with temperature, with a greater impact on the bare UCNP, which exhibits higher values for thermal sensitivity than UCNP@SiO2 and UCNP@SiO2@Au. The thermal sensitivity of the trapped particle inside the biological cell at 317 K indicates the thermal sensitivity of UCNP > UCNP@SiO2@Au > UCNP@SiO2 particles. SIGNIFICANCE AND NOVELTY: Compared to bulk sample-based temperature probing, the present study demonstrates temperature measurement at the single particle level by optically trapping the particle and further explores the role of the passivating silica shell and the incorporation of plasmonic particles on thermal sensitivity. Furthermore, thermal sensitivity measurements inside a biological cell at the single particle level are investigated and illustrated that thermal sensitivity at a single particle is sensitive to the measuring environment.

Optically trapped SiO2@Au particle-dye hybrid-based SERS detection of Hg2+ ions.

The selective ultra-sensitive detection of a very low concentration of analyte in a liquid environment using surface-enhanced Raman spectroscopy (SERS) is a challenging task owing to the poor reproducibility of the Raman signals arising from the nonstationary nature of the substrate. However, plasmonic metal particle-incorporated microparticles can be effectively 3-D arrested in a liquid environment that can serve as a stable SERS substrate by employing an optical trapping force. Herein, we demonstrate a 3-D optically trapped Au-attached SiO2 microparticle as an efficient SERS substrate that can detect 512 pM for Rhodamine6G and 6.8 pM for crystal violet. Further, the substrate allows the simultaneous detection of multiple analytes. By utilizing the Raman signal from Rhodamine 6G as the probe beam, the selective detection of Hg2+ ions as low as 100 pM is demonstrated.

Clinical utility of brain-derived neurotrophic factor as a biomarker with left ventricular echocardiographic indices for potential diagnosis of coronary artery disease.

Brain-derived neurotrophic factor (BDNF) plays a central pivotal role in the development of the cardiovascular system. Recent evidence suggests that BDNF has adverse subclinical cardiac remodeling in participants with cardiovascular disease risk factors. Relating serum BDNF levels with two-dimensional echocardiographic indices will provide insights into the BDNF mediated pathophysiology in coronary artery disease (CAD) that may shed light upon potential diagnostic biomarkers. For the study, 221 participants were recruited and classified based on coronary angiogram examination as control (n = 105) and CAD (n = 116). All participants underwent routine blood investigation, two-dimensional echocardiography, and serum BDNF estimation. As a result, total cholesterol, triglyceride, low-density lipid, high-density lipid, HbA1c (glycosylated hemoglobin), serum creatinine, eosinophils, lymphocyte, monocytes, neutrophils, and platelets were significantly elevated in CAD individuals compared to controls. Notably, the serum BDNF was significantly lower in individuals with CAD (30.69 ± 5.45 ng/ml) than controls (46.58 ± 7.95 ng/ml). Multivariate regression analysis showed neutrophils, total cholesterol, left ventricular mass index, mitral inflow E/A ratio, and pulmonary vein AR duration were associated with low BDNF in CAD. Four independent support vector machine (SVM) models performed to ensure the BDNF level in the classification of CAD from healthy controls. Particularly, the model with serum BDNF concentration and blood parameters of CAD achieved significant improvement from 90.95 to 98.19% in detecting CAD from healthy controls. Overall, our analysis provides a significant molecular linkage between the serum BDNF level and cardiovascular function. Our results contribute to the emerging evidence of BDNF as a potential diagnostic value in CAD that might lead to clinical application.

Simultaneous Bilateral Orbital Cellulitis With Meningitis Caused by Methicillin-Resistant Staphylococcus aureus in an Immunocompetent Infant.

The authors report a rare case of fulminant bilateral orbital cellulitis caused by methicillin-resistant Staphylococcus aureus associated with meninigitis in a neonate. The clinical, laboratory, photographic, and radiological records are reviewed. A 17-day-old female infant presented with swelling over both upper eyelids and proptosis in both eyes. Computed tomography showed mutli-loculated abscesses within both orbits. Eyelid swelling and proptosis resolved following transcutaneous aspiration of the purulent material. Cerebrospinal fluid examination yielded Gram-positive cocci, which on culture and polymerase chain reaction testing was identified as methicillin-resistant Staphylococcus aureus. The infant received an extended course of antibiotics. At 12 months of follow-up, the infant was systemically normal with normal milestones, complete ocular movements, and no neurological sequelae. This case highlights the need for cerebrospinal fluid analysis in bilateral orbital cellulitis, even in cases not exhibiting central nervous system involvement. Aggressive medical and surgical treatment is needed in bilateral orbital cellulitis. [J Pediatr Ophthalmol Strabismus. 2020;57:e34-e37.].

A Case of Isolated Unilateral Glossopharyngeal Nerve Palsy.

Isolated palsy of the glossopharyngeal nerve is rare. We report the case of an elderly patient with unilateral right glossopharyngeal nerve palsy secondary to extra cranial ischemia. On examination there was no other deficit other than an absent right gag reflex. She was diagnosed clinically with ischemic stroke of the ninth nerve, and her daily dose of aspirin was increased from 81 mg to 325 mg. Magnetic resonance imaging of the brain showed a normal brainstem and cerebellum with patent intracranial circulation. Total resolution of the paralysis was seen 2 months later. The possible mechanisms suspected were diabetic or hypertensive stenosis of the vasa nervorum or compression of the ninth nerve by an internal carotid artery dissection or aneurysm. This article discusses the various etiologies and mechanisms of this rare condition. It is unique because of the nerve's location and relationship to other structures.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge.

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.

Nontraumatic subperiosteal orbital hemorrhage following upper gastrointestinal endoscopy.

Subperiosteal hemorrhages are typically the result of blunt orbital or facial trauma. Nontraumatic subperiosteal hemorrhages are uncommon and are usually attributed to increase in central venous pressure and bleeding disorders. Here, we report the case of a 38-year-old female who underwent an upper gastrointestinal (GI) endoscopy and developed bilateral nontraumatic subperiosteal hemorrhages that resolved with conservative treatment. Here, we discuss the source of bleeding and the mechanisms for the occurrence of orbital subperiosteal bleeds. GI surgeons and ophthalmologists should be sensitive to the possibility that orbital hemorrhage that can occur following endoscopy, especially when retching or gagging occurs during the procedure.

Actinomycetes canaliculitis complicating congenital nasolacrimal duct obstruction in an infant.

Actinomyces israelii is a Gram-positive anaerobic organism commonly associated with canaliculitis in adults. Pediatric canaliculitis is relatively rare, especially in infancy. We report the case of an 11-month-old boy who presented with co-existing canaliculitis and congenital nasolacrimal obstruction. The presenting signs included epiphora, discharge, conjunctival congestion, and matting of lashes. On examination, punctual pouting, regurgitation, and yellow canaliculiths were noted. A punctoplasty and canalicular curettage were performed along with nasolacrimal probing. Microbiological tests confirmed the organisms to be A. israelii. We discuss the clinical features and management of Actinomyces-associated canaliculitis and review the available literature on pediatric canaliculitis.

Preparing to take the USMLE Step 1: a survey on medical students' self-reported study habits.

BACKGROUND: The USA Medical Licensing Examination Step 1 is a computerised multiple-choice examination that tests the basic biomedical sciences. It is administered after the second year in a traditional four-year MD programme. Most Step 1 scores fall between 140 and 260, with a mean (SD) of 227 (22). Step 1 scores are an important selection criterion for residency choice. Little is known about which study habits are associated with a higher score. OBJECTIVE: To identify which self-reported study habits correlate with a higher Step 1 score. METHODS: A survey regarding Step 1 study habits was sent to third year medical students at Tulane University School of Medicine every year between 2009 and 2011. The survey was sent approximately 3 months after the examination. RESULTS: 256 out of 475 students (54%) responded. The mean (SD) Step 1 score was 229.5 (22.1). Students who estimated studying more than 8-11 h per day had higher scores (p<0.05), but there was no added benefit with additional study time. Those who reported studying <40 days achieved higher scores (p<0.05). Those who estimated completing >2000 practice questions also obtained higher scores (p<0.01). Students who reported studying in a group, spending the majority of study time on practice questions or taking >40 preparation days did not achieve higher scores. CONCLUSIONS: Certain self-reported study habits may correlate with a higher Step 1 score compared with others. Given the importance of achieving a high Step 1 score on residency choice, it is important to further identify which characteristics may lead to a higher score.

Perceived access to health services and provider information and adverse birth outcomes: findings from LaPRAMS, 2007-2008.

OBJECTIVES: Despite targeted public health efforts, racial disparities and poor birth outcomes are still apparent, particularly in the southern United States. Previous research through qualitative and modest quantitative research demonstrates a possible link between disparities in patient-provider conversations during prenatal visits, perceived access to prenatal care, and poor birth outcomes. METHODS: A secondary analysis was conducted using data from the 2007-2008 Louisiana Pregnancy Risk Assessment Monitoring System to examine perceived access to healthcare services and information received and its impact on birth outcomes. Respondents consisted of 2460 white and black American women who recently experienced a live birth in the state of Louisiana. RESULTS: Racial disparities among Louisiana mothers were evident, with black mothers experiencing significant perceived lack of services or access to resources from a healthcare or insurance provider and poorer birth outcomes. White mothers reported experiencing less access based on the lack of vital prenatal care information from a healthcare provider. Self-perceived access was significantly associated with preterm birth for black women (odds ratio 2.94, 95% confidence interval 1-8; P < 0.05) and infant mortality for white women (odds ratio 340.5, confidence interval 36-999); P < 0.05). CONCLUSIONS: Findings support the need for a better understanding of discriminatory experiences and their impact on women's experiences during prenatal care and poor birth outcomes.

Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status.

Mitochondrial disorders are associated with decreased energy production and redox imbalance. Glutathione plays a central role in redox signaling and protecting cells from oxidative damage. In order to understand the consequences of mitochondrial dysfunction on in vivo redox status, and to determine how this varies by mitochondrial disease subtype and clinical severity, we used a sensitive tandem mass spectrometry assay to precisely quantify whole blood reduced (GSH) and oxidized (GSSG) glutathione levels in a large cohort of mitochondrial disorder patients. Glutathione redox potential was calculated using the Nernst equation. Compared to healthy controls (n = 59), mitochondrial disease patients (n = 58) as a group showed significant redox imbalance (redox potential -251 mV ± 9.7, p<0.0001) with an increased level of oxidation by ∼ 9 mV compared to controls (-260 mV ± 6.4). Underlying this abnormality were significantly lower whole blood GSH levels (p = 0.0008) and GSH/GSSG ratio (p = 0.0002), and significantly higher GSSG levels (p<0.0001) in mitochondrial disease patients compared to controls. Redox potential was significantly more oxidized in all mitochondrial disease subgroups including Leigh syndrome (n = 15), electron transport chain abnormalities (n = 10), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (n = 8), mtDNA deletion syndrome (n = 7), mtDNA depletion syndrome (n = 7), and miscellaneous other mitochondrial disorders (n = 11). Patients hospitalized in metabolic crisis (n = 7) showed the greatest degree of redox imbalance at -242 mV ± 7. Peripheral whole blood GSH and GSSG levels are promising biomarkers of mitochondrial dysfunction, and may give insights into the contribution of oxidative stress to the pathophysiology of the various mitochondrial disorders. In particular, evaluation of redox potential may be useful in monitoring of clinical status or response to redox-modulating therapies in clinical trials.

Do home visiting services received during pregnancy improve birth outcomes? Findings from Virginia PRAMS 2007-2008.

OBJECTIVES: Reducing poor birth outcomes are national and state priorities. At the national level participation in home visiting services has gained momentum with the recent appropriation of federal funds for states to implement evidence-based maternal and child health home visiting programs. The effects of having a home visit are unknown at the state level. DESIGN AND SAMPLE: Using cross-sectional data from 2007 to 2008 Virginia Pregnancy Risk Assessment and Monitoring System (PRAMS), maternal and infant outcomes were examined. Women who had a home visit during pregnancy were assigned into the home visiting (HV) participation group and those who did not were assigned to the HV Comparison group and used for the analysis. MEASURES: Bivariate analyses, Rao-Scott chi square tests, and multivariate logistic regression measured and quantified the association between HV participation and outcomes. RESULTS: The HV Participation group were 87.5% less likely to have a low birth weight infant (0.13, 95% CI: 0.020, 0.78), 4.5 times more likely to initiate breastfeeding (aOR: 4.5, 95% CI: 1.05, 19.54), and 39 times more likely to use contraceptives postpartum (aOR: 38.55, 95% CI: 3.14, 473.21). CONCLUSIONS: Receiving home visiting services during pregnancy increased breastfeeding initiation and postpartum contraceptive use while reducing the risk of low birth weight.

Partner support and impact on birth outcomes among teen pregnancies in the United States.

PURPOSE: Despite hypothesized relationships between lack of partner support during a woman's pregnancy and adverse birth outcomes, few studies have examined partner support among teens. We examined a potential proxy measure of partner support and its impact on adverse birth outcomes (low birth weight (LBW), preterm birth (PTB) and pregnancy loss) among women who have had a teenage pregnancy in the United States. METHODS: In a secondary data analysis utilizing cross-sectional data from 5609 women who experienced a teen pregnancy from the 2006-2010 National Survey of Family Growth (NSFG), we examined an alternative measure of partner support and its impact on adverse birth outcomes. Bivariate and multivariable logistic regression were used to assess differences in women who were teens at time of conception who had partner support during their pregnancy and those who did not, and their birth outcomes. RESULTS: Even after controlling for potential confounding factors, women with a supportive partner were 63% less likely to experience LBW [aOR: 0.37, 95% CI: (0.26-0.54)] and nearly 2 times less likely to have pregnancy loss [aOR: 0.48, 95% CI: (0.32-0.72)] compared to those with no partner support. CONCLUSIONS: Having partner support or involvement during a teenager's pregnancy may reduce the likelihood of having a poor birth outcome.