Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish between ALS phenotypes

Patients with amyotrophic lateral sclerosis (ALS) can present with varying degrees of upper motor neuron (UMN) and lower motor neuron dysfunction. Previous diffusion tensor imaging (DTI) studies, in which ALS patients were not separated by the degree of UMN dysfunction, have resulted in conflicting or inconclusive results. We hypothesized that (1) categorizing ALS patients by their clinical phenotype can reveal differences in DTI abnormalities along the corticospinal tract (CST), and (2) data obtained from routine clinical DTI scans can provide this type of information. Clinical DTI scans were obtained at 1.5T in 87 ALS patients (categorized into four subgroups based on clinical phenotype) and in 12 neurologic controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity values from the CST were compared between ALS subgroups and controls. Significantly reduced FA and elevated MD values were observed in ALS patients compared to controls at the subcortical motor cortex level. Significant differences in AD values were not only seen between control and ALS patients but also between the ALS subgroups, suggesting divergent pathologies in these ALS patients. Classifying ALS patients by phenotype reveals differences in CST abnormalities between subgroups and may provide novel insights into disease mechanisms. The close similarity of our results from routine clinical scans with published research studies suggests wider accessibility to useful DTI metrics.     

Quantitation and characterization of glutathionyl haemoglobin as an oxidative stress marker in chronic renal failure by mass spectrometry

OBJECTIVES: Glutathionyl haemoglobin (GS-Hb) belonging to the class of glutathionylated proteins has been investigated as a possible marker of oxidative stress in different chronic diseases. The purpose of this study was to examine whether glutathionyl haemoglobin can serve as an oxidative stress marker in non-diabetic chronic renal failure patients on different renal replacement therapies (RRT) through its quantitation, and characterization of the specific binding site of glutathione in haemoglobin molecule by mass spectrometric analysis. DESIGN AND METHODS: The study group consisted of non-diabetic chronic renal failure patients on renal replacement therapy (RRT): hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and renal allograft transplant (Txp) patients. Haemoglobin samples of these subjects were analyzed by liquid chromatography electrospray ionization mass spectrometry for GS-Hb quantitation. Characterization of GS-Hb was done by tandem mass spectrometry. Levels of erythrocyte glutathione (GSH) and lipid peroxidation (as thiobarbituric acid reacting substances) were measured spectrophotometrically, while glycated haemoglobin (HbA1c) was measured by HPLC. RESULTS: GS-Hb levels were markedly elevated in the dialysis group and marginally in the transplant group as compared to the controls. GS-Hb levels correlated positively with lipid peroxidation and negatively with the erythrocyte glutathione levels in RRT groups indicating enhanced oxidative stress. De novo sequencing of the chymotryptic fragment of GS-Hb established that glutathione is attached to Cys-93 of the beta globin chain. Mass spectrometric quantitation of total glycated haemoglobin showed good agreement with HbA1c estimation by conventional HPLC method. CONCLUSIONS: Glutathionyl haemoglobin can serve as a clinical marker of oxidative stress in chronic debilitating therapies like RRT. Mass spectrometry provides a reliable analytical tool for quantitation and residue level characterization of different post-translational modifications of haemoglobin.     

A retrospective analysis of complex proximal humerus fractures managed with reverse shoulder arthroplasty in a level 1 trauma center

BackgroundThe treatment of complex 3- and 4-part proximal humerus fractures (PHFs) in the elderly poses significant challenges because of osteoporosis and fracture comminution. The wide range of surgical options available is evidence of the complex nature of the injury. At present, reverse shoulder replacement is gaining popularity among shoulder surgeons for treating these difficult fractures, and the literature has shown equivalent or superior outcomes with reverse shoulder arthroplasty (RSA). We aimed to analyze the long-term results of these complex PHF treated with reverse shoulder replacement.MethodsFor this study, fractures from 39 patients with a mean age of 63.18 years who were treated with RSA for acute complex fractures of the proximal humerus in our institution between 2013 and 2019 were analyzed (n = 31, acute 4-part fractures; n = 4, acute fracture–dislocation; n = 3, fracture with irreparable cuff tear; n = 1, osteoporotic 2-part fracture). All patients had a standard reverse shoulder replacement (cemented humeral stem n = 37 and uncemented stem n = 2) surgery in a level 1 trauma center. The mean follow-up duration was 60 months (24-111 months). The clinical outcomes (Oxford Shoulder Score and Constant Shoulder Score) and the complications at 6 months, 12 months, and 24 months were analyzed.ResultsOur study found a relatively younger population, with 21 patients (53.84%) aged <66 years. Spearman's correlation showed that younger patients had better signs of improvement in Oxford Shoulder Scores at 2 years (P = .008). The average Oxford Shoulder Score was 39.12 ± 4.327, and the average Constant Shoulder Score was 67.67 on the operated side. The mean active forward elevation was 142.56 ± 22.29º, abduction was 136.538 ± 24.31º, external rotation was 27 ± 9.011º, and internal rotation was 33 ± 20.41º. The overall complication rate of 17.94% (periprosthetic infection n = 2, periprosthetic humerus fracture n = 1, and hematoma evacuation n = 4) in our study was similar to those of recent studies in the literature.ConclusionRSA provides a reliable option for PHFs and offers good results in the form of pain relief and good functional outcomes at 2 years even in a younger age group. Thus, it is fast becoming an important option in treating complex PHF, but we must be wary of the steep learning curve and the complications pertinent to this procedure.     

Pharmacy Students’ Performance and Perceptions in a Flipped Teaching Pilot on Cardiac Arrhythmias

Objective. To implement the flipped teaching method in a 3-class pilot on cardiac arrhythmias and to assess the impact of the intervention on academic performance and student perceptions.Design. An intervention group of 101 first-year pharmacy students, who took the class with the flipped teaching method, were supplied with prerecorded lectures prior to their 3 classes (1 class in each of the following subjects: basic sciences, pharmacology, and therapeutics) on cardiac arrhythmias. Class time was focused on active-learning and case-based exercises. Students then took a final examination that included questions on cardiac arrhythmias. The examination scores of the intervention group were compared to scores of the Spring 2011 control group of 105 first-year students who took the class with traditional teaching methods. An online survey was conducted to assess student feedback from the intervention group.Assessment. The mean examination scores of the intervention group were significantly higher than the mean examination scores of the control group for the cardiac arrhythmia classes in pharmacology (with 89.6 ± 2.0% vs 56.8 ± 2.2%, respectively) and therapeutics (89.2 ± 1.4% vs 73.7 ± 2.1%, respectively). The survey indicated higher student satisfaction for flipped classes with highly rated learning objectives, recordings, and in-class activities.Conclusion. Use of the flipped teaching method in a 3-class pilot on cardiac arrhythmias improved examination scores for 2 of the 3 classes (pharmacology and therapeutics). Student satisfaction was influenced by the quality of the learning objectives, prerecorded lectures, and inclass active-learning activities.     

Circulating T-Cell Subsets,Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

Objective

The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women.

Hemodynamic,Autonomic, and Vascular Effects of Exposure to Coarse Particulate Matter Air Pollution from a Rural Location

Background: Fine particulate matter (PM) air pollution is associated with numerous adverse health effects, including increased blood pressure (BP) and vascular dysfunction. Coarse PM substantially contributes to global air pollution, yet differs in characteristics from fine particles and is currently not regulated. However, the cardiovascular (CV) impacts of coarse PM exposure remain largely unknown.Objectives: Our goal was to elucidate whether coarse PM, like fine PM, is itself capable of eliciting adverse CV responses.Methods: We performed a randomized double-blind crossover study in which 32 healthy adults (25.9 ± 6.6 years of age) were exposed to concentrated ambient coarse particles (CAP; 76.2 ± 51.5 μg/m³) in a rural location and filtered air (FA) for 2 hr. We measured CV outcomes during, immediately after, and 2 hr postexposures.Results: Both systolic (mean difference = 0.32 mmHg; 95% CI: 0.05, 0.58; p = 0.021) and diastolic BP (0.27 mmHg; 95% CI: 0.003, 0.53; p = 0.05) linearly increased per 10 min of exposure during the inhalation of coarse CAP when compared with changes during FA exposure. Heart rate was on average higher (4.1 bpm; 95% CI: 3.06, 5.12; p < 0.0001) and the ratio of low-to-high frequency heart rate variability increased (0.24; 95% CI: 0.07, 0.41; p = 0.007) during coarse particle versus FA exposure. Other outcomes (brachial flow-mediated dilatation, microvascular reactive hyperemia index, aortic hemodynamics, pulse wave velocity) were not differentially altered by the exposures.Conclusions: Inhalation of coarse PM from a rural location is associated with a rapid elevation in BP and heart rate during exposure, likely due to the triggering of autonomic imbalance. These findings add mechanistic evidence supporting the biological plausibility that coarse particles could contribute to the triggering of acute CV events.Citation: Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. 2014. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environ Health Perspect 122:624–630; http://dx.doi.org/10.1289/ehp.1306595     

Electrochemical detection of Cd(ii) ions in complex matrices with nanopipets

Heavy metal contamination and its detrimental health effects are a growing concern globally. Several metal mitigation systems and regulatory approaches have been implemented to minimize the negative impacts on human health. However, none of these function at maximum efficiency, mainly due to the lack of accurate information about metal speciation. Therefore, there is a critical need to develop novel, cheap, efficient, and robust metal detecting sensors. In this study, we describe the application of a nanopipet based electrochemical sensor to detect aqueous Cd(ii) ions. The inner radius of our nanopipets is ∼300 nm, and the fundamental mechanism behind our sensor''s response is ion transfer between two immiscible electrolyte solutions (ITIES). The absence of redox behavior makes ITIES an excellent, attractive electrochemical tool to study various ions in aqueous solutions. In this study, we used 1,10-phenanthroline as our ionophore in the organic phase (dichloroethane) to facilitate the transfer of Cd(ii) ions from the polar aqueous phase to the less polar organic phase. Unlike previous studies, we characterized our nanopipet in complicated matrices, including, but not limited to, tris buffer and artificial seawater. We performed quantitative assessments to determine our sensor''s limit of detection, stability, sensitivity, and selectivity. We further show that our nanosensor can detect free Cd(ii) ions in the presence of strong complexing agents such as ethylenediaminetetraacetic acid, 2,3-dimercaptosuccinic acid, etc. We quantified the concentration of free Cd(ii) ions in a water sample collected from a local lagoon. Thus, we showcased the power of our nanopipets to act as a robust, accurate, and efficient speciation sensor to detect Cd(ii) ions in environmental samples.

A nanopipet electrochemical sensor was successfully utilized to detect free Cd(ll) ions in complicated matrices and real environmental water samples.