Mild-to-moderate COVID-19 impact on the cardiorespiratory fitness in young and middle-aged populations.

The goal of the present study was to compare pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) performance in COVID-19 survivors with a control group (CG). This was a cross-sectional study. Patients diagnosed with COVID-19, without severe signs and symptoms, were evaluated one month after the infection. Healthy volunteers matched for sex and age constituted the control group. All volunteers underwent the following assessments: i) clinical evaluation, ii) PTF; and iii) CPET on a cycle ergometer. Metabolic variables were measured by the CareFusion Oxycon Mobile device. In addition, heart rate responses, peak systolic and diastolic blood pressure, and perceived exertion were recorded. Twenty-nine patients with COVID-19 and 18 healthy control subjects were evaluated. Surviving patients of COVID-19 had a mean age of 40 years and had higher body mass index and persistent symptoms compared to the CG (P<0.05), but patients with COVID-19 had more comorbidities, number of medications, and greater impairment of lung function (P<0.05). Regarding CPET, patients surviving COVID-19 had reduced peak workload, oxygen uptake (V̇O2), carbon dioxide output (V̇CO2), circulatory power (CP), and end-tidal pressure for carbon dioxide (PETCO2) (P<0.05). Additionally, survivors had depressed chronotropic and ventilatory responses, low peak oxygen saturation, and greater muscle fatigue (P<0.05) compared to CG. Despite not showing signs and symptoms of severe disease during infection, adult survivors had losses of lung function and cardiorespiratory capacity one month after recovery from COVID-19. In addition, cardiovascular, ventilatory, and lower limb fatigue responses were the main exercise limitations.

Mild-to-moderate COVID-19 impact on the cardiorespiratory fitness in young and middle-aged populations

The goal of the present study was to compare pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) performance in COVID-19 survivors with a control group (CG). This was a cross-sectional study. Patients diagnosed with COVID-19, without severe signs and symptoms, were evaluated one month after the infection. Healthy volunteers matched for sex and age constituted the control group. All volunteers underwent the following assessments: i) clinical evaluation, ii) PTF; and iii) CPET on a cycle ergometer. Metabolic variables were measured by the CareFusion Oxycon Mobile device. In addition, heart rate responses, peak systolic and diastolic blood pressure, and perceived exertion were recorded. Twenty-nine patients with COVID-19 and 18 healthy control subjects were evaluated. Surviving patients of COVID-19 had a mean age of 40 years and had higher body mass index and persistent symptoms compared to the CG (P<0.05), but patients with COVID-19 had more comorbidities, number of medications, and greater impairment of lung function (P<0.05). Regarding CPET, patients surviving COVID-19 had reduced peak workload, oxygen uptake (V̇O2), carbon dioxide output (V̇CO2), circulatory power (CP), and end-tidal pressure for carbon dioxide (PETCO2) (P<0.05). Additionally, survivors had depressed chronotropic and ventilatory responses, low peak oxygen saturation, and greater muscle fatigue (P<0.05) compared to CG. Despite not showing signs and symptoms of severe disease during infection, adult survivors had losses of lung function and cardiorespiratory capacity one month after recovery from COVID-19. In addition, cardiovascular, ventilatory, and lower limb fatigue responses were the main exercise limitations.

A combination of electrochemistry and mass spectrometry to monitor the interaction of reactive species with supported lipid bilayers.

Reactive oxygen and nitrogen species (RONS), e.g. generated by cold physical plasma (CPP) or photodynamic therapy, interfere with redox signaling pathways of mammalian cells, inducing downstream consequences spanning from migratory impairment to apoptotic cell death. However, the more austere impact of RONS on cancer cells remains yet to be clarified. In the present study, a combination of electrochemistry and high-resolution mass spectrometry was developed to investigate the resilience of solid-supported lipid bilayers towards plasma-derived reactive species in dependence of their composition. A 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer was undisturbed by 200 µM H2O2 (control) but showed full permeability after CPP treatment and space-occupying oxidation products such as PoxnoPC, PAzePC, and POPC hydroperoxide were found. Electron paramagnetic resonance spectroscopy demonstrated the presence of hydroxyl radicals and superoxide anion/hydroperoxyl radicals during the treatment. In contrast, small amounts of the intramembrane antioxidant coenzyme Q10 protected the bilayer to 50% and LysoPC was the only POPC derivative found, confirming the membrane protective effect of Q10. Such, the lipid membrane composition including the presence of antioxidants determines the impact of pro-oxidant signals. Given the differences in membrane composition of cancer and healthy cells, this supports the application of cold physical plasma for cancer treatment. In addition, the developed model using the combination of electrochemistry and mass spectrometry could be a promising method to study the effect of reactive species or mixes thereof generated by chemical or physical sources.

Chemical fingerprints of cold physical plasmas - an experimental and computational study using cysteine as tracer compound.

Reactive oxygen and nitrogen species released by cold physical plasma are being proposed as effectors in various clinical conditions connected to inflammatory processes. As these plasmas can be tailored in a wide range, models to compare and control their biochemical footprint are desired to infer on the molecular mechanisms underlying the observed effects and to enable the discrimination between different plasma sources. Here, an improved model to trace short-lived reactive species is presented. Using FTIR, high-resolution mass spectrometry, and molecular dynamics computational simulation, covalent modifications of cysteine treated with different plasmas were deciphered and the respective product pattern used to generate a fingerprint of each plasma source. Such, our experimental model allows a fast and reliable grading of the chemical potential of plasmas used for medical purposes. Major reaction products were identified to be cysteine sulfonic acid, cystine, and cysteine fragments. Less-abundant products, such as oxidized cystine derivatives or S-nitrosylated cysteines, were unique to different plasma sources or operating conditions. The data collected point at hydroxyl radicals, atomic O, and singlet oxygen as major contributing species that enable an impact on cellular thiol groups when applying cold plasma in vitro or in vivo.

Effect of head group and lipid tail oxidation in the cell membrane revealed through integrated simulations and experiments.

We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane. Our simulations are validated by experiments using a cold atmospheric plasma as external ROS source. We found that plasma treatment leads to a slight initial rise in membrane rigidity, followed by a strong and persistent increase in fluidity, indicating a drop in lipid order. The latter is also revealed by our simulations. This study is important for cancer treatment by therapies producing (extracellular) ROS, such as plasma treatment. These ROS will interact with the cell membrane, first oxidizing the head groups, followed by the lipid tails. A drop in lipid order might allow them to penetrate into the cell interior (e.g., through pores created due to oxidation of the lipid tails) and cause intracellular oxidative damage, eventually leading to cell death. This work in general elucidates the underlying mechanisms of ROS interaction with the cell membrane at the atomic level.

Elasticity and tumorigenic characteristics of cells in a monolayer after nanosecond pulsed electric field exposure.

Nanosecond pulsed electric fields (nsPEFs) applied to cells can induce different biological effects depending on pulse duration and field strength. One known process is the induction of apoptosis whereby nsPEFs are currently investigated as a novel cancer therapy. Another and probably related change is the breakdown of the cytoskeleton. We investigated the elasticity of rat liver epithelial cells WB-F344 in a monolayer using atomic force microscopy (AFM) with respect to the potential of cells to undergo malignant transformation or to develop a potential to metastasize. We found that the elastic modulus of the cells decreased significantly within the first 8 min after treatment with 20 pulses of 100 ns and with a field strength of 20 kV/cm but was still higher than the elasticity of their tumorigenic counterpart WB-ras. AFM measurements and immunofluorescent staining showed that the cellular actin cytoskeleton became reorganized within 5 min. However, both a colony formation assay and a cell migration assay revealed no significant changes after nsPEF treatment, implying that cells seem not to adopt malignant characteristics associated with metastasis formation despite the induced transient changes to elasticity and cytoskeleton that can be observed for up to 1 h.

Risk assessment of a cold argon plasma jet in respect to its mutagenicity.

Cold atmospheric pressure plasmas represent a favorable option for the treatment of heat sensitive materials and human or animal tissue. Beneficial effects have been documented in a variety of medical conditions, e.g., in the treatment of chronic wounds. It is assumed that the main mechanism of the plasma's efficacy is mediated by a stimulating dissipation of energy via radiation and/or chemical energy. Although no evidence on undesired side effects of a plasma treatment has yet been presented, skepticism toward the safety of the exposure to plasma is present. However, only little data regarding the mutagenic potential of this new treatment option is available. Accordingly, we investigated the mutagenic potential of an argon plasma jet (kinpen) using different testing systems in accordance with ISO norms and multiple cell lines: a HPRT1 mutation assay, a micronucleus formation assay, and a colony formation assay. Moderate plasma treatment up to 180 s did not increase genotoxicity in any assay or cell type investigated. We conclude that treatment with the argon plasma jet kinpen did not display a mutagenic potential under the test conditions applied and may from this perspective be regarded as safe for the use in biomedical applications.

Aphyllin, the first isoferulic acid glycoside and other phenolics from Tamarix aphylla flowers.

The first glycosylated isoferulic acid, isoferulic acid 3-O-beta-glucopyranoside, together with the new phenolics, tamarixetin 3,3'-di-sodium sulphate and dehydrodigallic acid dimetyl ester have been characterized from a flower extract of Tamarix aphylla. The structures were established on the basis of spectral data. The extract exhibited a distinct radical scavenging effect and to improve the viability of human keratinocytes (HaCaT cells). Also, the known isoferulic acid and ferulic acid which have been determined to be the major components of the investigated extract by HPLC/ESI mass spectrometric screening have been separated, characterized and evaluated as active antioxidants and as cell activity stimulating agents as well.

Bone mineralization enhancing activity of a methoxyellagic acid glucoside from a Feijoa sellowiana leaf extract.

The capability of an aqueous methanol extract obtained from the leaves of Feijoa sellowiana Berg. on possible prevention and treatment of osteoporosis has been examined by evaluating its stimulating effect on the two human osteoblastic cell lines HOS58 and SaOS-2. The extract was found to increase significantly the mineralization of cultivated human bone cell, whereby a clear increment (15.3 +/- 2.7%) in von Kossa positive area was determined when administering 25 microg/ml leaf extract. A phytochemical investigation of the extract has demonstrated the high phenolic content and led to the isolation and identification of twenty three of them, among which the new 3-methoxyellagic acid 4-O-beta-glucopyranoside was fully identified. All structures were elucidated on the basis of conventional analytical methods and confirmed by FTMS, 1D- and 2D-NMR data. The new compound was found to cause a significant increase of mineralized area at 20 microg/mL, while at lower concentrations the effect was not significant. However, an increase of the number of mineralized spots (nodules) at all tested concentrations of the compound was observed.

Red clover extracts stimulate differentiation of human osteoblastic osteosarcoma HOS58 cells.

Different extracts from red clover (Trifolium pratense L.) were tested for their ability to stimulate the activity of osteoblastic osteosarcoma cells (HOS58). As a key marker of osteoblasticity we chose the activity of alkaline phosphatase (ALP). Whereas butanol and methanol extracts had no influence on either ALP or cellular protein production, enzyme activity was increased significantly on incubation with chloroform extracts. All extracts were analysed for isoflavone content. The data clearly suggest a role for red clover isoflavonoids in the stimulation of osteoblastic cell activity.

[Feedback control of muscle relaxation with a varying on-off controller using cisatracurium]. / Regelkreisgesteuerte Muskelrelaxation mit einem modifizierten Zweipunktregler mit Cisatracurium.

BACKGROUND: Under clinical conditions constant neuromuscular blockade can also be maintained by a simple closed-loop system. However, delayed onset time, non-linearity of the dose-response curve and different sensitivity to muscle relaxants for each patient are limiting factors. METHODS: In 20 patients who underwent elective surgical procedures under continuous propofol/alfentanil anaesthesia and relaxation with cisatracurium, the maintenance of an electromyographically controlled cisatracurium block of 90% was achieved by a varying on-off control system. Using an own computer-aided measuring device, the course of the neuromuscular blockade and deviations from the desired neuromuscular block were registered. RESULTS: Over a period of 64.2+/-14.0 min, neuromuscular block could be controlled on average at a T(1)-level of 10% (90% block). The mean error of the deviation of the obtained neuromuscular blockade from the set-point was -1.6+/-0.9% on average. To maintain this neuromuscular blockade, a dose rate of 1.4+/-0.9 micro g x kg(-1) x min(-1) cisatracurium was necessary. CONCLUSIONS: It can be concluded that a simple closed-loop system allows the safe use of the intermediate term muscle relaxant cisatracurium for the performance of surgical procedures.

Actaeaepoxide 3-O-beta-D-xylopyranoside, a new cycloartane glycoside from the rhizomes of Actaea racemosa (Cimicifuga racemosa).

A new cycloartane glycoside (1) was obtained from a minor triterpene fraction of the rhizome extract of Actaea racemosa (synonym: Cimicifuga racemosa) along with a known compound, cimigenol 3-O-beta-D-xylopyranoside. The structure of 1 was elucidated as 20(S),22(R),23(R),24(S)-12beta-acetoxy-16beta:23,23alpha:24-diepoxy-3beta,22beta,25-trihydroxy-9,19-cyclolanost-7-ene 3-O-beta-D-xylopyranoside (actaeaepoxide 3-O-beta-D-xylopyranoside) on the basis of spectral and chemical evidence.

Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group.

Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon beta-1a (IFNbeta-1a, 30 microg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNbeta-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNbeta-1a group. These results support and extend previous observations of significant beneficial effects of IFNbeta-1a for relapsing MS.

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Are quantitative functional measures more sensitive to worsening MS than traditional measures?

The authors used data collected prospectively during a multicenter trial in 133 patients with secondary progressive MS to assess the relative sensitivity of quantitative functional tests and traditional measures, including the Expanded Disability Status Scale (EDSS) and Ambulation Index. Quantitative functional measures worsened in 69% of patients during an average of 6 months of observation, whereas the Clinical Global Impression of Change worsened in 33% and the EDSS worsened in 25% of patients. These changes should be interpreted in the context of the test-retest reliability for each measure.

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.

The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.