Combination of variable frequency train stimulation and K/sup +/ channel blockade to augment skeletal muscle force

Several innovative approaches are being used to optimize the input-output relationship of muscle, including nonlinear stimulation paradigms and altering muscle membrane ion channel conductances. We tested the hypothesis that the combination of the K+ channel blocker, 3,4-diaminopyridine (DAP), and variable frequency train (VFT) stimulation improves muscle force to a greater extent than either modality alone. Studies were done in vitro on rat diaphragm muscle and contractions were quantified with respect to peak force, mean force, and force area. DAP increased all three force parameters by >50% during conventional 10-20-Hz stimulation, whereas VFT stimulation improved contractile performance for peak force only. When combined, DAP and VFT stimulation augmented peak force to a significantly greater extent than either modality alone. However, this came at a cost of a moderate decline in force area relative to DAP alone, although mean force was preserved. These force increases were generally well-maintained over the course of short-term repetitive stimulation. Thus, VFT stimulation and K+ channel blockade interact in a complex manner to modulate skeletal muscle force. The utility of the combined intervention for functional electrical stimulation may be greatest for mechanical tasks requiring high force levels early during the contraction.     

Differential automatic zero-adjusting amplifier

A method is described for building a low-voltage-drift differential dc amplifier featuring automatic zero adjustment, a high input impedance, and a bandwidth of 10 kHz. This is achieved by an asymmetric two-step process between the input signal and ground. Bandwidth can be extended by the use of a second amplifier during the ground-sampling time. The amplifier can be made with standard electronic components. A major advantage of this method is that an existing amplifier can easily be converted into a low-voltage-drift amplifier by adding the essential elements of the described automatic zero-adjusting amplifier to its input stage. To illustrate the method a practical example is constructed featuring a drift of 0.2 microV/ degrees C.     

Multilead ECG analysis

This paper describes the results of our recent research in computer-assisted ECG/VCG interpretation. It comprises new developments which were initiated by the advent of relatively inexpensive microcomputers. Our previous systems performed an off-line analysis of ECGs. Currently, there is a trend to move computer power near to the patient and to provide on-line analysis of ECGs. Besides the advantage of the direct availability of the ECG interpretation, quality control will reduce the number of uninterpretable ECGs and hence the number of repeated recordings. This paper describes the requirements that were established for a system for on-line ECG analysis. The system is based on our modular approach, just like our off-line system, Modular ECG ANalysis System (MEANS). Changes in the methods and software had to be made mainly because of the simultaneity of all ECG leads and the concurrency of the processing tasks. Other modifications and extensions of the algorithms necessary to meet the requirements of on-line ECG interpretation especially those related to processing speed, are discussed, and evaluation results are presented.     

Genetic Elements Orchestrating Lactobacillus crispatus Glycogen Metabolism in the Vagina

Glycogen in the female lower reproductive tract is a major carbon source for colonization and acidification by common vaginal Lactobacillus species, such as Lactobacillus crispatus. Previously, we identified the amylopullulanase encoding gene pulA of Lactobacillus crispatus to correlate with the ability to autonomously utilize glycogen for growth. Here, we further characterize genetic variation and differential regulation of pulA affecting the presence of its gene product on the outer surface layer. We show that alpha-glucan degrading activity dissipates when Lactobacillus crispatus is grown on glucose, maltose and maltotriose, in agreement with carbon catabolite repression elements flanking the pulA gene. Proteome analysis of the S-layer confirmed that the amylopullulanase protein is highly abundant in an S-layer enriched fraction, but not in a strain with a defective amylopullulanase variant or in an amylopullulanase-sufficient strain grown on glucose. In addition, we provide evidence that Lactobacillus crispatus pulA mutants are relevant in vivo, as they are commonly observed in metagenome datasets of human vaginal microbial communities. Analysis of the largest publicly available dataset of 1507 human vaginal metagenomes indicates that among the 270 samples that contain a Lactobacillus crispatus pulA gene, 62 samples (23%) had a defective variant of this gene. Taken together, these results demonstrate that both environmental, as well as genetic factors explain the variation of Lactobacillus crispatus alpha-glucosidases in the vaginal environment.     

Exciton storage by Mn(2+) in colloidal Mn(2+)-doped CdSe quantum dots

Colloidal Mn (2+)-doped CdSe quantum dots showing long excitonic photoluminescence decay times of up to tau exc = 15 mus at temperatures over 100 K are described. These decay times exceed those of undoped CdSe quantum dots by approximately 10 (3) and are shown to arise from the creation of excitons by back energy transfer from excited Mn (2+) dopant ions. A kinetic model describing thermal equilibrium between Mn (2+ 4)T 1 and CdSe excitonic excited states reproduces the experimental observations and reveals that, for some quantum dots, excitons can emit with near unity probability despite being approximately 100 meV above the Mn (2+ 4)T 1 state. The effect of Mn (2+) doping on CdSe quantum dot luminescence at high temperatures is thus completely opposite from that at low temperatures described previously.     

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.     

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.     

Macro- and Nanoscale Effect of Ethanol on Bovine Serum Albumin Gelation and Naproxen Release

We report extended ethanol-induced gelation procedures of bovine serum albumin (BSA) at 37 °C and investigate the release behavior of a spin-labeled naproxen derivative (SL-NPX) from these hydrogels. The macroscopic mechanical properties of these gels during formation were studied using rheology, while a nanoscopic, more molecular view was obtained by analyzing the secondary structure of the protein during gelation via infrared (ATR-IR) spectroscopy. To evaluate the potential use of BSA hydrogels in controlled drug delivery, SL-NPX-BSA interaction was investigated in detail by continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, which provides information on the interaction of the small drug molecules and the hydrogel. In addition to CW EPR spectroscopy, dynamic light scattering (DLS), which provides insight into the size and nature of released components, was applied to characterize the combined influence of incubation time, ethanol, SL-drug, and BSA concentration on release behavior. It was found that the alteration of initial drug loading percentage, hydrogel incubation time as well as BSA and alcohol concentrations affect and thus tune the release rate of SL-NPX from BSA hydrogels. These results lead to the conclusion that BSA hydrogels as controlled release systems offer a remarkable fine-tuning capability for pharmaceutical applications due to the variety of gelation parameters.     

Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis

Extensive angiogenesis is a characteristic feature in the synovial tissue of rheumatoid arthritis (RA) from a very early stage of the disease onward and constitutes a crucial event for the development of the proliferative synovium. This process is markedly intensified in patients with prolonged disease duration, high disease activity, disease severity, and significant inflammatory cell infiltration. Angiogenesis is therefore an interesting target for the development of new therapeutic approaches as well as disease monitoring strategies in RA. To this end, nuclear imaging modalities represent valuable non-invasive tools that can selectively target molecular markers of angiogenesis and accurately and quantitatively track molecular changes in multiple joints simultaneously. This systematic review summarizes the imaging markers used for single photon emission computed tomography (SPECT) and/or positron emission tomography (PET) approaches, targeting pathways and mediators involved in synovial neo-angiogenesis in RA.