Case study of hypertriglyceridemia from COVID-19 Pfizer-BioNTech vaccination in a patient with familial hypercholesteremia.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is the first novel nucleoside-modified messenger ribonucleic acid (modRNA) vaccine to receive Emergency Use Authorization from the Food and Drug Administration in the United States. It is indicated to be used in patients ≥12 years-of-age as of May 25th, 2021, including populations with high atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the potential impact this vaccine may have on serum lipoprotein levels in patients with familial hypercholesteremia (FH), who are predisposed to high ASCVD burden due to elevated low-density lipoprotein cholesterol (LDL-C). We present an interesting case where a patient with heterozygous FH (HeFH) and elevated triglycerides (TG)-controlled for years on medication and apheresis-experienced significantly elevated TG, one day after receiving his second Pfizer-BioNTech COVID-19 vaccine dose. It is not known whether this adverse event may be seen in other FH patients and may be worth assessing in such patients to determine the possibility of a rare adverse reaction from a COVID-19 vaccine.

Different mother and daughter manifestations due to very high cholesterol-containing lipoproteins.

OBJECTIVE: Familial hypercholesterolemia (FH) is an autosomal codominant genetic disorder associated with defective hepatic uptake of circulating low-density lipoproteins (LDL), which can lead to premature atherosclerotic cardiovascular disease (ASCVD). Evidence suggests elevated lipoprotein(a) (Lp(a)) levels in FH patients may also increase their ASCVD risk. We present a case series of 2 FH patients where a daughter has a higher ASCVD burden than her mother due to the daughter having elevated Lp(a). This underscores the importance of including Lp(a) in cascade lipid screening in FH patients and their first-degree relatives.

A case of abdominal pain with dyslipidemia: difficulties diagnosing cholesterol ester storage disease.

Cholesterol ester storage disease is an exceptionally rare dyslipidemia with less than 150 cases reported in the medical literature. The diagnosis of Cholesterol Ester Storage Disease is often missed by virtue of the fact that the symptoms mimic both inborn metabolic defects and hepatic steatosis. Patients with Cholesterol Ester Storage Disease usually present with atypical complaints including abdominal pain from altered gut motility. Blood analysis typically reveals abnormal liver function tests with coincident dyslipidemia. We present a case of a young woman with Cholesterol Ester Storage Disease who was followed over two decades. We discuss issues common to her initial protracted diagnosis with management options over time.

Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population.

BACKGROUND: As a result of effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It remains unknown whether coinfection with hepatitis C (HCV) changes an HIV person's CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population. METHODS: HIV, HCV, and HIV/HCV patients with clinic visits between 2004 and 2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES), and individually matched on gender, race, and age. We stratified by infection group and conducted separate multivariable linear regression analyses between each infection group and the gender, race, and age matched participants from NHANES. RESULTS: Rochester patients (HIV = 239, HCV = 167, HIV/HCV = 182) were compared 3 : 1 with the NHANES participants. After controlling for weight, marital status, current pharmacotherapies and the matching variables of gender, race, and age, HIV/HCV patients had a 2% higher general FRS compared with the general population (p = 0.03), and vascular age differences that were 4.1 years greater (p = .01). HCV patients had a 2.4% higher general FRS than the general population (p < .001), and vascular age differences that were 4.4 years greater (p < .001). CVD risk was elevated but not significantly different between HIV patients and the general population. CONCLUSION: Cardiovascular disease risk is elevated among HIV/HCV and HCV infected persons compared with the general population.

Greasing the wheels of managing overweight and obesity with omega-3 fatty acids.

The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.

The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin.

Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis.

Nuclear emissions during self-nucleated acoustic cavitation.

A unique, new stand-alone acoustic inertial confinement nuclear fusion test device was successfully tested. Experiments using four different liquid types were conducted in which bubbles were self-nucleated without the use of external neutrons. Four independent detection systems were used (i.e., a neutron track plastic detector to provide unambiguous visible records for fast neutrons, a detector, a NE-113-type liquid scintillation detector, and a NaI gamma ray detector). Statistically significant nuclear emissions were observed for deuterated benzene and acetone mixtures but not for heavy water. The measured neutron energy was

Scattering of 64 eV to 3 keV neutrons from polyethylene and graphite and the coherence length problem.

We measured the neutron scattering intensity ratios from polyethylene (CH2) relative to graphite (C) at several discrete final energies, of narrow widths (approximately 3 eV) between 64 eV and 3 keV. The final energies were selected using a 238U filter. This experiment was carried out to search for any anomaly in the n-p scattered intensities from CH2 caused by the neutron coherence length. The scattered intensity ratios were found to conform to conventional expectations and no anomaly was observed.

Neodymium neutron cross section measurements.

Neutron capture and transmission measurements were performed by the time-of-flight technique at the Rensselaer Polytechnic Institute LINAC using metallic neodymium samples. The capture measurements were made at the 25-m-long flight station with a 16-segment NaI(Tl) multiplicity detector, and the transmission measurements were performed at 15 and 25 m flight stations with a 6Li glass scintillation detector. After the data were collected and reduced, resonance parameters were determined by simultaneously fitting the transmission and capture data with the multilevel R-matrix Bayesian code SAMMY. The resonance parameters for all naturally occurring neodymium isotopes lie within the energy range of 1.0-500 eV. The resulting resonance parameters were used to calculate the capture resonance integral with this energy region and were compared to calculations obtained when using the resonance parameters from ENDF-B/VI. The RPI parameters gave a resonance integral value of 32 +/- 0.5 b that is approximately 7% lower than that obtained with the ENDF-B/VI parameters. The current measurements significantly reduce the statistical uncertainties on the resonance parameters when compared with previously published parameters.

Search for anomalous scattering of keV neutrons from H2O-D2O mixtures.

We measured the neutron scattering intensities from pure liquid H2O relative to that of pure D2O and also relative to H2O-D2O mixtures, at room temperature. This study is relevant to the problem of quantum entanglement. The neutrons were generated from an electron Linac and the final energy of the scattered neutrons was fixed at 24.3 keV using a 20 cm thick pure iron filter. The scattering intensity ratios were found to agree with expected values deduced from the tabulated total cross sections within an accuracy of 3%. Thus no anomaly was observed.

Additional evidence of nuclear emissions during acoustic cavitation.

Time spectra of neutron and sonoluminescence emissions were measured in cavitation experiments with chilled deuterated acetone. Statistically significant neutron and gamma ray emissions were measured with a calibrated liquid-scintillation detector, and sonoluminescence emissions were measured with a photomultiplier tube. The neutron and sonoluminescence emissions were found to be time correlated over the time of significant bubble cluster dynamics. The neutron emission energy was less than 2.5 MeV and the neutron emission rate was up to approximately 4 x 10(5) n/s. Measurements of tritium production were also performed and these data implied a neutron emission rate due to D-D fusion which agreed with what was measured. In contrast, control experiments using normal acetone did not result in statistically significant tritium activity, or neutron or gamma ray emissions.

Evidence for nuclear emissions during acoustic cavitation.

In cavitation experiments with deuterated acetone, tritium decay activity above background levels was detected. In addition, evidence for neutron emission near 2.5 million electron volts was also observed, as would be expected for deuterium-deuterium fusion. Control experiments with normal acetone did not result in tritium activity or neutron emissions. Hydrodynamic shock code simulations supported the observed data and indicated highly compressed, hot (10(6) to 10(7) kelvin) bubble implosion conditions, as required for nuclear fusion reactions.

Modulation of nicotine-induced analgesia by calcium agonist and antagonist in adult rats.

The involvement of calcium in nicotine-induced analgesia in male rats was explored using the tail-flick test. A single dose of nicotine (1 mg/kg SC) produced a maximal effect on tail-flick latency (15 s) within 8-10 min, which lasted for 4 min. Pretreatment with the calcium chelator, EDTA (250 microM/kg SC four injections at 15 min intervals), before the single dose of nicotine accelerated the onset and prolonged the duration of the nicotine-induced analgesia. The maximal effect on tail-flick latency occurred within 2 min and lasted for 10-20 min. Conversely, pretreatment with calcium chloride (1.5 mM/kg IP) attenuated nicotine-induced analgesia. It is suggested that nicotine may exert its antinociceptive effects via modulation of calcium fluxes across the neural membrane.

Nicotine-induced analgesia in rats: the role of calcium and the diversity of responders and nonresponders.

Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant antinociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 microM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotine alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl2 (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.)--induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl2 completely abolishes, nicotine-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect.