Clinical and Demographic Characteristics of Upper Limb Dystonia.

BACKGROUND: Knowledge of characteristics in upper limb dystonia remains limited, derived primarily from small, single-site studies. OBJECTIVE: The objective of this study was to characterize demographic and clinical characteristics of upper limb dystonia from the Dystonia Coalition data set, a large, international, multicenter resource. METHODS: We evaluated clinical and demographic characteristics of 367 participants with upper limb dystonia from onset, comparing across subcategories of focal (with and without dystonia spread) versus nonfocal onset. RESULTS: Focal onset occurred in 80%; 67% remained focal without spread. Task specificity was most frequent in this subgroup, most often writer's cramp and affecting the dominant limb (83%). Focal onset with spread was more frequent in young onset (<21 years). Focal onset occurred equally in women and men; nonfocal onset affected women disproportionately. CONCLUSIONS: Upper limb dystonia distribution, focality, and task specificity relate to onset age and likelihood of regional spread. Observations may inform clinical counseling and design, execution, and interpretation of future studies. © 2020 International Parkinson and Movement Disorder Society.

Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia: A Case Series and Genetic Links.

Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial infarction in young women. An association of fibromuscular dysplasia (FMD) with SCAD has been well established; a significant proportion of SCAD patients may have typical FMD findings in other noncoronary arteries. The current consensus recommends arterial imaging screening from head to pelvis using computed tomography angiography (CTA) or magnetic resonance angiography (MRA) in SCAD. Genetic testing for FMD should be considered in high-risk cases. We present two cases of SCAD associated with FMD and discuss the significance of genetic screening in such patients.

Strategies for Accelerated Drug Development: An Industry Perspective Based on an IQ Consortium Survey of CMC Considerations.

Over the past decade, there has been an increase in accelerated drug development with successful regulatory approval that has provided rapid access of novel medicines to patients world-wide. This has created the opportunity for the pharmaceutical industry to continuously improve the process of quickly bringing new medicines to patients with unmet medical needs. This can be accomplished through sharing the learnings and advancements in drug development, enhancing regulatory interactions, and collaborating with academics on developing the underlying science to reduce drug development timelines. In this paper, the IQ Consortium - Accelerated Drug Development working group members intend to share recommendations for optimizing strategies that build efficiencies in accelerated pathways for regulatory approval. Information was obtained by surveying member pharmaceutical companies with respect to recent expedited submissions within the past 5 years to gain insights as to which development strategies were successful. The learnings from this analysis are provided, which includes shared learnings in formulation development, stability, analytical methods, manufacturing, and importation testing as well as regulatory considerations. Each of these sections provide a summary illustrating the key data collected as well as a discussion that is aimed to guide pharmaceutical companies on strategies to consider streamlining development activities and expedite the drug to market.

Charged gold nanoparticles with essentially zero serum protein adsorption in undiluted fetal bovine serum.

The adsorption of even a single serum protein molecule on a gold nanosphere used in biomedical imaging may increase the size too much for renal clearance. In this work, we designed charged ~5 nm Au nanospheres coated with binary mixed-charge ligand monolayers that do not change in size upon incubation in pure fetal bovine serum (FBS). This lack of protein adsorption was unexpected in view of the fact that the Au surface was moderately charged. The mixed-charge monolayers were composed of anionic citrate ligands modified by place exchange with naturally occurring amino acids: either cationic lysine or zwitterionic cysteine ligands. The zwitterionic tips of either the lysine or cysteine ligands interact weakly with the proteins and furthermore increase the distance between the "buried" charges closer to the Au surface and the interacting sites on the protein surface. The ~5 nm nanospheres were assembled into ~20 nm diameter nanoclusters with strong near-IR absorbance (of interest in biomedical imaging and therapy) with a biodegradable polymer, PLA(1k)-b-PEG(10k)-b-PLA(1k). Upon biodegradation of the polymer in acidic solution, the nanoclusters dissociated into primary ~5 nm Au nanospheres, which also did not adsorb any detectable serum protein in undiluted FBS.

A large hiatal hernia causing frequent premature ventricular contractions with bigeminy: A case report and review of literature.

Most patients with hiatal hernia (HH) are asymptomatic; however, common symptoms include gastroesophageal reflux disease (GERD) and heart burn. Larger hernia can cause obstruction, ischemia of the bowel, volvulus of the contents of the hernial sac, respiratory distress, and rarely, cardiac abnormalities are also noted. Most reported cardiac abnormalities associated with HH include atrial fibrillation, atrial flutter, supraventricular tachycardia, and bradycardia. We present a rare case of a large HH causing frequent premature ventricular contractions in bigeminy form that resolved with surgical correction of HH and did not recur on subsequent Holter monitoring. We highlight the potential association between HH/GERD and cardiac arrhythmias and reinforce the need to keep HH/GERD as one of the working diagnoses in a patient with cardiac arrhythmia. Learning objective: •Large hiatal hernia can cause several arrhythmias such as atrial fibrillation, atrial flutter, supraventricular tachycardia, bradycardia, and premature ventricular contractions (PVCs).•It is essential to consider hiatal hernia and gastroesophageal reflux disease as one of the differentials in the work up of cardiac arrhythmias including PVCs.

Left ventricular pseudoaneurysm without antecedent myocardial infarction.

A left ventricle pseudoaneurysm (LVPA) occurs when the left ventricle free wall rupture becomes contained by pericardium or adhesions. It is rare and has a poor prognosis. LVPA is strongly associated with myocardial infarction. Surgical management of LVPA carries a high mortality rate but is still recommended for most cases of LVPA as soon as the diagnosis is confirmed. Medical management is generally limited to asymptomatic, incidentally found lesions. We present a case of LVPA without any usual risk factors, which was successfully treated by surgery. Learning objectives: •To identify the left ventricle pseudoaneurysm (LVPA) that can present with chest pain or dyspnea, but at times can be asymptomatic•To keep a high index of suspicion for LVPA even in patients without the common risk factors such as recent myocardial infarction, cardiac surgery, or trauma•To realize that management options are individualized•To understand that despite a high surgical mortality, for large expanding LVPA, surgery is still recommended•Further research needs to be done to establish management guidelines.

Association of triglyceride levels with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction.

Although there is an established association between elevated triglyceride (eTG, ≥175 mg/dl) levels and adverse cardiovascular events, some studies have suggested that eTG levels may be linked to neutral or even improved clinical outcomes, particularly among patients with acute myocardial infarction. However, these studies had certain limitations, including small sample sizes, heterogeneous study populations, and inadequate statistical adjustments. To address these limitations, we conducted an analysis of 5347 patients with ST-segment elevation myocardial infarction (STEMI) between March 2003 and December 2020, using a prospective registry-based cohort from two large, regional STEMI centers. We used a triglyceride level of 175 mg/dl as the cutoff point for eTG levels. Of the study participants, 24.5% (n = 1312) had eTG levels. These patients were more likely to be younger, male, and have a higher number of cardiovascular risk factors compared to those with low TG levels. Despite these unfavorable cardiovascular risk profiles, patients with eTG levels had lower unadjusted risks of 1-year major adverse cardiac events (MACE) -a composite of myocardial infarction, stroke, and death- than those with low TG levels (8.8% vs. 11%, p = 0.034). However, after adjusting for certain clinical factors and lipid profile, eTG levels were not associated with a lower 1-year MACE (aHR: 1.10 (0.71-1.70), p = 0.7). In conclusion, a quarter of STEMI patients had eTG levels and these patients had comparable long-term cardiovascular outcomes compared to those with low TG levels after controlling for clinical factors and lipid profile.

Thermal stability of biodegradable plasmonic nanoclusters in photoacoustic imaging.

The photothermal stability of plasmonic nanoparticles is critically important to perform reliable photoacoustic imaging and photothermal therapy. Recently, biodegradable nanoclusters composed of sub-5 nm primary gold particles and a biodegradable polymer have been reported as clinically-translatable contrast agents for photoacoustic imaging. After cellular internalization, the nanoclusters degrade into 5 nm primary particles for efficient excretion from the body. In this paper, three different sizes of biodegradable nanoclusters were synthesized and the optical properties and photothermal stability of the nanoclusters were investigated and compared to that of gold nanorods. The results of our study indicate that 40 nm and 80 nm biodegradable nanoclusters demonstrate higher photothermal stability compared to gold nanorods. Furthermore, 40 nm nanoclusters produce higher photoacoustic signal than gold nanorods at a given concentration of gold. Therefore, the biodegradable plasmonic nanoclusters can be effectively used for photoacoustic imaging and photothermal therapy.

Quadricuspid Aortic Valve: An Introduction for Clinicians.

Quadricuspid aortic valve (QAV) is a congenital heart anomaly in which the aortic valve has four cusps of various size possibilities, as opposed to the three symmetrical cusps generally observed. This cardiac valvular abnormality is rarely identified, with an estimated incidence rate of 0.013% to 0.043%, although recent technological advancements in diagnostics have contributed to an increase in detection. Historically, it had been typically encountered during open heart surgery or postmortem; however, it is presently diagnosed primarily via ultrasound echocardiography, and could go undetected unless specifically considered. It was first reported by Babington in 1847, and since then approximately 300 cases have been published. This condition is sporadically associated with additional congenital cardiovascular defects, with coronary artery irregularities being the most common. In more than half of published QAV incidences it has led to the progressive development of aortic regurgitation (AR) usually sans aortic stenosis, particularly amongst elderly patients, often requiring surgical intervention after 50 years of age. A fifth of total instances, but two-thirds of instances with AR, warrant surgery seldom amidst complications, with reconstructive tricuspidization preferred over valve replacement.

Cardiac MRI in myocardial infarction without obstructive coronary artery disease (MINOCA) helps arrive at correct diagnosis - A case report and discussion.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is a common condition with estimated prevalence of 5 to 15 %. It is not a benign condition and diagnosing the exact underlying etiology can be challenging, but it is important to ensure appropriate management of MINOCA patients. Cardiac magnetic resonance imaging (CMRI) can be a valuable and non-invasive test to identify the underlying etiology, as well as to risk-stratify such patients. Both the European Society of Cardiology and the American Heart Association recommend CMRI in diagnostic work up of MINOCA patients. We report a case of an 83-year-old man who presented to the emergency department with atypical chest pain but had significantly elevated cardiac troponin levels, with non-obstructive coronary artery disease on left heart catheterization. Subsequent CMRI led to the diagnosis of acute myocarditis. He was medically managed with good clinical outcomes. We discuss this case in detail and highlight the role of CMRI in MINOCA patients. As our understanding of troponin elevation and its various mechanisms continues to evolve, cardiac MRI has a significant role in diagnosis and management, as demonstrated in our case. Learning objectives: 1.Illustrate the clinical relevance and diagnosis of myocardial infarction without obstructive coronary artery disease (MINOCA).2.Explain the role of cardiac magnetic resonance imaging in diagnosis and management of MINOCA.

Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging.

Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced. In this Letter, we demonstrate the feasibility of biodegradable nanoclusters as a photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging of a tissue-mimicking phantom with inclusions containing nanoclusters at various concentrations. The results indicate that the biodegradable gold nanoclusters can be used as effective contrast agents in photoacoustic imaging.

Kinetic assembly of near-IR-active gold nanoclusters using weakly adsorbing polymers to control the size.

Clusters of metal nanoparticles with an overall size of less than 100 nm and high metal loadings for strong optical functionality are of interest in various fields including microelectronics, sensors, optoelectronics, and biomedical imaging and therapeutics. Herein we assemble approximately 5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, that contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces. The cluster size and optical properties are tuned as a function of particle volume fractions and polymer/gold ratios to modulate the interparticle interactions. The close spacing between the constituent gold nanoparticles and high gold loadings (80-85 w/w gold) produce a strong absorbance cross section of approximately 9 x 10(-15) m(2) in the NIR at 700 nm. This morphology results from VDW and depletion attractive interactions that exclude the weakly adsorbed polymeric stabilizer from the cluster interior. The generality of this kinetic assembly platform is demonstrated for gold nanoparticles with a range of surface charges from highly negative to neutral with the two different polymers.

Extraction of winding parameters for 33/11 kV, 30 MVA transformer based on finite element method for frequency response modelling.

This paper proposes an alternative approach to extract transformer's winding parameters of resistance (R), inductance (L), capacitance (C) and conductance (G) based on Finite Element Method (FEM). The capacitance and conductance were computed based on Fast Multiple Method (FMM) and Method of Moment (MoM) through quasi-electrostatics approach. The AC resistances and inductances were computed based on MoM through quasi-magnetostatics approach. Maxwell's equations were used to compute the DC resistances and inductances. Based on the FEM computed parameters, the frequency response of the winding was obtained through the Bode plot function. The simulated frequency response by FEM model was compared with the simulated frequency response based on the Multi-conductor Transmission Line (MTL) model and the measured frequency response of a 33/11 kV, 30 MVA transformer. The statistical indices such as Root Mean Square Error (RMSE) and Absolute Sum of Logarithmic Error (ASLE) were used to analyze the performance of the proposed FEM model. It is found that the simulated frequency response by FEM model is quite close to measured frequency response at low and mid frequency regions as compared to simulated frequency response by MTL model based on RMSE and ASLE analysis.

Effect of shield placement for transient voltage mitigation due to switching surges in a 33/11 kV transformer windings.

This study presents an investigation on the effect of shield placement for mitigation of transient voltage in a 33/11 kV, 30 MVA transformer due to Standard Switching Impulse (SSI) and Oscillating Switching Impulse (OSI) surges. Generally, the winding and insulation in transformers could experience severe voltage stress due to the external impulses i.e. switching events. Hence, it is important to examine the voltage stress and identify the mitigation action i.e. shield placements in order to reduce the adverse effect to the transformer windings. First, the resistances, inductances, and capacitances (RLC) were calculated for disc type transformer in order to develop the winding RLC equivalent circuit. The SSI and OSI transient voltage waveforms were applied to the High Voltage (HV) winding whereby the transient voltages were simulated for each disc. The resulting voltage stresses were mitigated through different configurations of electrostatic shield placements. The resonant oscillations generated due to switching surges were analysed through initial voltage distribution. The analyses on the transient voltages of the transformer winding and standard error of the slope (SEb) reveal that the location of shield placement has a significant effect on the resonant switching voltages. The increment of the shield number in the windings does not guarantee optimize mitigation of the resonant switching transient voltages. It is found that the voltage stress along the windings is linear once a floating shield is placed between the HV and Low Voltage (LV) windings of the disc-type transformer under the SSI and OSI waveforms. These findings could assist the manufacturers with appropriate technical basis for mitigation of the transformer winding against the external transient switching overvoltage surges.

Cardiac Lipoma: An Uncharacteristically Large Intra-Atrial Mass Causing Symptoms.

Primary tumours of the heart are often encountered in clinical practice. Different autopsy series estimate the incidence to be anywhere from 0.001% to 0.19%. Cardiac lipoma is a rare type of tumour of the heart and pericardium. It comprises approximately 10-19% of all cardiac tumours. We present a case of a large cardiac lipoma in a fifty-year-old female. She presented with sharp chest pains, palpitations, and dizziness. Acute coronary syndrome was ruled out. A transthoracic echocardiogram showed an abnormal, large, fixed right atrial mass. The mass was noted to be occupying most of the right atrium. It was excised due to its large size and persistent symptoms. On pathophysiology, the mass was definitively diagnosed to be an 80 mm × 70 mm cardiac lipoma. Postoperatively, the patient did well with resolution of her symptoms. This case provides evidence that even large, invasive, symptomatic cardiac lipomas can be successfully resected with good outcomes.

Hypothermia as a forgotten sign of prolonged severe hypoglycaemia.

Hypothermia is often a sign of serious illness. Commonly reported aetiologies include but are not limited to sepsis, exposure to cold and endocrine disorders. Hypoglycaemia, a common occurrence, is rarely associated with hypothermia. We present a case of prolonged, severe hypothermia due to hypoglycaemia. A 58-year-old man with diabetes who presented with chest pain and was diagnosed with Non-ST elevation myocardial infarction. He was given nothing per mouth in preparation for a left heart catheterisation but received his reported insulin glargine dosage at bedtime. A few hours later, he was noted to have diaphoresis and hypoglycaemia, and his temperature steadily started dropping which was unresponsive to local warming. Once his hypoglycaemia was successfully treated with dextrose infusion, his temperature improved. An extensive workup revealed no infective or endocrine disorder.

Left ventricle pseudoaneurysm: Diagnosis by a new murmur.

Incomplete rupture of the ventricle free wall can occur after myocardial infarction. This occurs when an organized thrombus and the pericardium seal the ventricular perforation. This can progress to the formation of a left ventricle pseudoaneurysm (LVPA). A 70-year-old male with an antero-septal ST-elevation myocardial infarction (STEMI) underwent an emergent left heart catheterization which revealed severe three-vessel disease with occluded grafts, non-amenable to re-vascularization, and an apical thrombus. As he was high-risk for repeat coronary artery bypass graft, he was medically managed. Transthoracic echocardiogram (TTE) showed a normal left ventricle ejection fraction (LVEF), apical anterior and inferior wall akinesis, moderate sized apical thrombus, and pericardial thickening. On hospital day 7, examination revealed a new 3/6 to-and-fro murmur that was loudest at the apex. The patient was asymptomatic with normal vital signs. A repeat TTE revealed an apical wall rupture with flow into the pericardial cavity and absence of the apical thrombus. A LVPA was diagnosed and the patient was immediately referred for surgical repair. This case illustrates the potential for developing LVPA in STEMI patients and the importance of physical examination. If identified early a potential emergent situation in a previously asymptomatic patient can be averted, thereby preventing fatal consequences. .

Epinephrine use results in 'stress' cardiomyopathy.

Epinephrine is a frequently used catecholamine, particularly in emergencies and during resuscitation attempts. It is not without side effects. We report a rare case of epinephrine-induced cardiomyopathy. Epinephrine was administered for bradycardia in our patient. He was treated conservatively and responded well to the treatment. Through our work we wish to highlight this adverse cardiac effect of epinephrine. We hope to increase awareness among residents and practicing physicians while using epinephrine. .

Is HPS2-THRIVE the death knell for niacin?

Niacin is a lipid-modifying therapy with proven efficacy for reducing cardiovascular events as monotherapy and when used in combination with other lipid-modifying medications impacts rates of atherosclerotic disease progression. Large outcome trials using niacin against a background of statin therapy with optimal control of atherogenic lipoprotein burden in serum were unable to demonstrate incremental benefit of niacin beyond statin therapy. We address 2 key questions: (1) Can the results from randomized clinical trials performed in stable ischemic heart disease populations (AIM-HIGH and HPS2-THRIVE) be applied to patients who sustain an acute coronary syndrome or myocardial infarction? (2) Are patients with very low baseline levels of high-density lipoprotein cholesterol (<30 mg/dL) at particularly high risk for subsequent cardiac events?