LDL concentration is correlated with the removal from the plasma of a chylomicron-like emulsion in subjects with coronary artery disease

In animal model studies, the uptake of chylomicron remnants after entering in the space of Disse occurs mainly by low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP). In subjects, the relative importance of each one of these receptors for the clearance of chylomicron remnants is not fully understood. In our study, LDL cholesterol and apolipoprotein (apo) B were correlated to the plasma kinetics of a chylomicron-like emulsion in 77 subjects (11 women, mean age 58 +/- 12 years) with coronary artery disease (CAD). Their total cholesterol was 227 +/- 25 mg/dl, triglyceride 159 +/- 25 mg/dl, LDL cholesterol 148 +/- 27 mg/dl, HDL cholesterol 40 +/- 9 mg/dl, apo A1 1.80 +/- 0.53 g/l and apo B 1.65 +/- 0.48 g/l. The emulsion was double-labeled with 3H-triolein and 14C-cholesteryl oleate and injected intravenously after 12-h fasting. The decay curves of the radioisotopes were determined from blood samples collected at predetermined intervals during 60 min. A negative correlation between FCR of the emulsion cholesterol esters and LDL cholesterol and apo B plasma concentrations was found (r=-0.4, P=0.005 and r=-0.3, P=0.01, respectively) whereas FCR of the emulsion triglycerides did not correlate with any of the plasma lipids or apolipoprotein parameters. Concluding, in patients with CAD, LDL catabolic pathway significantly influences the removal from plasma of chylomicron remnants.     

Hypomagnesemia is a frequent finding in the emergency department in patients with chest pain

STUDY OBJECTIVE--To evaluate the frequency of low blood levels of total and ultrafilterable magnesium (total and ultrafilterable hypomagnesemia) in patients with chest pain in the emergency department, and to determine if hypomagnesemia is associated with other clinically important diagnostic and outcome variables in cardiac care. SETTING--An emergency department of a university teaching hospital. DESIGN--Prospective study of extracellular magnesium homeostasis in patients with chest pain in the emergency department and a cohort of patients without chest pain with a clinical indication for blood sampling. PATIENTS--During a 4-month period, 147 patients presenting to the emergency department were studied: 67 patients (mean +/- SD age, 61.4 +/- 13 years) with a chief complaint of chest pain (study group) and 80 patients (55.6 +/- 19 years) with other diagnoses (control group). RESULTS--Total and ultrafilterable hypomagnesemia occurred more frequently in patients with chest pain (20/67 [30%] and 9/67 [13%]) than in the control group (12/80 [15%] and 3/80 [4%]). Patients with a chief complaint of chest pain who were receiving diuretic medications were hypomagnesemic more frequently (9/16 [56%]) than patients not receiving diuretics (12/51 [23%]). In patients with chest pain admitted to the hospital with a diagnosis of "rule out" myocardial infarction, the frequency of hypokalemia was greater among hypomagnesemic patients (6/14 [43%]) than normomagnesemic patients (3/31 [10%]). A similar frequency of hypomagnesemia was noted in patients with a final diagnosis of myocardial infarction (4/15 [27%]) when compared with other patients admitted with chest pain (10/31 [32%]) in whom myocardial infarction was excluded. No association was noted among hypomagnesemia and length of hospital stay or the occurrence of hypotension or dysrhythmias. CONCLUSIONS--Total and ultrafilterable hypomagnesemia are frequent occurrences in patients with and without chest pain in the emergency department. Diuretic use is associated with hypomagnesemia in patients presenting with chest pain in the emergency department. These results support the concept that hypomagnesemia is common in patients with chest pain in the emergency department and is associated with hypokalemia but is not predictive of whether the patient with chest pain has had an acute myocardial infarction.     

The Non‐Motor Symptoms Scale in Parkinson’s disease: Validation and use

The Non‐Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non‐motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross‐validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health‐related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non‐motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non‐motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non‐motor symptoms in PD.     

Anticipatory synergy adjustments: preparing a quick action in an unknown direction

We studied a mechanism of feed-forward control of a multi-finger action, namely anticipatory synergy adjustments (ASAs), prior to a quick force correction in response to a change in the gain of the visual feedback. Synergies were defined as co-varied across trials adjustments of commands to fingers that stabilized (decreased variance of) the total force. We hypothesized that ASAs would be highly sensitive to prior information about the timing of the action but not to information on its direction, i.e., on whether the gain would go up or down. The subjects produced accurate constant total force by pressing with four fingers on individual force sensors. The feedback signal could change from veridical (the sum of finger forces) to modified, with the middle finger force multiplied by 0.2 or by 1.8. The timing of the gain change and its direction could be known or unknown to the subject in advance. When the timing of the gain change was known, ASA was seen as a drop in the synergy index starting about 250–300 ms prior to the first visible correction of the total force. When the gain change timing was unknown, ASAs started much later, less than 100 ms prior to the total force correction. The magnitude of synergy index changes was significantly larger under the “time known” conditions. Information on the direction of the visual gain change had no effect on the ASA timing, while the ASA magnitude was somewhat larger when this information was not available to the subject. After the total force correction, the synergy index was significantly larger for the force signal computed using the modified gain values as compared to the synergy index value for the actual total force. We conclude that ASAs represent an important feed-forward motor control mechanism that allows preparing for a quick action even when the direction of the action is not known in advance. The results emphasize the subtle control of multi-finger synergies that are specific to the exact contributions of individual fingers to performance variables. The data fit well the central back-coupling hypothesis of synergies and the idea of control with referent body configurations.     

Rho guanine nucleotide exchange factor is an NFL mRNA destabilizing factor that forms cytoplasmic inclusions in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive disorder of unknown etiology characterized by the selective degeneration of motor neurons. Recent evidence supports the hypothesis that alterations in RNA metabolism in motor neurons can explain the development of protein inclusions, including neurofilamentous aggregates, observed in this pathology. In mice, p190RhoGEF, a guanine nucleotide exchange factor, is involved in neurofilament protein aggregation in an RNA-triggered transgenic model of motor neuron disease. Here, we observed that rho guanine nucleotide exchange factor (RGNEF), the human homologue of p190RhoGEF, binds low molecular weight neurofilament mRNA and affects its stability via 3′ untranslated region destabilization. We observed that the overexpression of RGNEF in a stable cell line significantly decreased the level of low molecular weight neurofilament protein. Furthermore, we observed RGNEF cytoplasmic inclusions in ALS spinal motor neurons that colocalized with ubiquitin, p62/sequestosome-1, and TAR (trans-active regulatory) DNA-binding protein 43 (TDP-43). Our results provide further evidence that RNA metabolism pathways are integral to ALS pathology. This is also the first described link between ALS and an RNA binding protein with aggregate formation that is also a central cell signaling pathway molecule.     

Chronic relapsing inflammatory optic neuropathy in a patient with triple antiphospholipid antibody positivity

Neurological Sciences -     

Sex-specific impact of severe obesity in the outcomes of hospitalized patients with COVID-19: a large retrospective study from the Bronx,New York

It has been demonstrated that obesity is an independent risk factor for worse outcomes in patients with COVID-19. Our objectives were to investigate which classes of obesity are associated with higher in-hospital mortality and to assess the association between obesity and systemic inflammation. This was a retrospective study which included consecutive hospitalized patients with COVID-19 in a tertiary center. Three thousand five hundred thirty patients were included in this analysis (female sex: 1579, median age: 65 years). The median body mass index (BMI) was 28.8 kg/m². In the overall cohort, a J-shaped association between BMI and in-hospital mortality was depicted. In the subgroup of men, BMI 35–39.9 kg/m² and BMI ≥40 kg/m² were found to have significant association with higher in-hospital mortality, while only BMI ≥40 kg/m² was found significant in the subgroup of women. No significant association between BMI and IL-6 was noted. Obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.

     

The influence of individual characteristics and non‐respiratory diseases on blood eosinophil count

BackgroundBlood eosinophil (B‐Eos) count is an emerging biomarker in the management of respiratory disease but determinants of B‐Eos count besides respiratory disease are poorly described. Therefore, we aimed to evaluate the influence of non‐respiratory diseases on B‐Eos count, in comparison to the effect on two other biomarkers: fraction of exhaled nitric oxide (FeNO) and C‐reactive protein (CRP), and to identify individual characteristics associated with B‐Eos count in healthy controls.MethodsChildren/adolescents (<18 years) and adults with complete B‐Eos data from the US National Health and Nutritional Examination Surveys 2005–2016 were included, and they were divided into having respiratory diseases (n = 3333 and n = 7,894, respectively) or not having respiratory disease (n = 8944 and n = 15,010, respectively). After excluding any respiratory disease, the association between B‐Eos count, FeNO or CRP, and non‐respiratory diseases was analyzed in multivariate models and multicollinearity was tested. After excluding also non‐respiratory diseases independently associated with B‐Eos count (giving healthy controls; 8944 children/adolescents and 5667 adults), the independent association between individual characteristics and B‐Eos count was analyzed.ResultsIn adults, metabolic syndrome, heart disease or stroke was independently associated with higher B‐Eos count (12%, 13%, and 15%, respectively), whereas no associations were found with FeNO or CRP. In healthy controls, male sex or being obese was associated with higher B‐Eos counts, both in children/adolescents (15% and 3% higher, respectively) and adults (14% and 19% higher, respectively) (p < 0.01 all). A significant influence of race/ethnicity was also noted, and current smokers had 17% higher B‐Eos count than never smokers (p < 0.001).ConclusionsNon‐respiratory diseases influence B‐Eos count but not FeNO or CRP. Male sex, obesity, certain races/ethnicities, and current smoking are individual characteristics or exposures that are associated with higher B‐Eos counts. All these factors should be considered when using B‐Eos count in the management of respiratory disease.