Autonomic dysfunction and exercise intolerance in post-COVID-19 - An as yet underestimated organ system?

Individuals recovering from COVID-19 often present with persistent symptoms, particularly exercise intolerance and low cardiorespiratory fitness. Put simply, the Wasserman gear system describes the interdependence of heart, lungs, and musculature as determinants of cardiorespiratory fitness. Based on this system, recent findings indicate a contribution of peripheral, cardiovascular, and lung diffusion limitations to persistent symptoms of exercise intolerance and low cardiorespiratory fitness. The autonomic nervous system as an organ system involved in the pathophysiology of exercise intolerance and low cardiorespiratory fitness, has received only little attention as of yet. Hence, our article discusses contribution of the autonomic nervous system through four potential pathways, namely alterations in (1) cerebral hemodynamics, (2) afferent and efferent signaling, (3) central hypersensitivity, and (4) appraisal and engagement in physical activity. These pathways are summarized in a psycho-pathophysiological model. Consequently, this article encourages a shift in perspective by examining the state of the pulmonary and cardiovascular system, the periphery, and auxiliary, the autonomic nervous system as potential underlying mechanisms for exercise intolerance and low cardiorespiratory fitness in patients with post-COVID-19.

Toxicity and physicochemical parameters of composts including distinct residues from agribusiness and slaughterhouse sludge.

Composting is useful for treatment of residues from agribusiness, but the potential toxicity of the final compost should be evaluated before its agricultural destination. The objective of this study was to evaluate the physicochemical characteristics and the toxicity of agribusiness residues using onion seeds as bioindicators. All tested treatments were composed by sludge from a swine slaughterhouse and sawdust. Besides the control, which included no additional materials, the other treatments included aviary bedding, rice husk and residue from tobacco industries as structuring materials. After 120 days of composting, for all treatments, the temperature inside the composting piles approached the environmental temperature, the physicochemical parameters indicated that the composts were stabilized and, except for the treatment including tobacco residues, that could be used for agriculture without impairing plant germination. Although the treatments including tobacco residues and rice husk showed evidence of cytotoxicity and genotoxicity at the beginning of the composting period, that was not observed for the treatment including aviary bedding. Such potential toxicity was not observed at the end of composting for any of the tested treatments.

Development and validation of an HPLC method to be used for simultaneous detection and quantification of different statins after ex vivo skin diffusion studies.

A novel high performance liquid chromatography (HPLC) method was developed and validated to simultaneously analyse all statins currently available globally (atorvastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin). A Venusil XBP C18(2) reverse phase column (150 x 4.6 mm) with a 5 µm particle size was used. The gradient conditions started at 25% acetonitrile, which linearly increased to 90% after 1.0 min, held at 90% until 6.5 min, and lastly, re-equilibrated to starting conditions. The mobile phase consisted of acetonitrile/water and 0.005 M (0.2%) octane sulphonic acid-Na (pH 3.5). The flow rate was set at 1.0 ml/min with a 10 µl injection volume. The HPLC method indicated linearity (R² =0.9999) within the concentration range of 0.2-206.4 µg/ml. The limit of detection (LOD) and limit of quantification (LOQ) values were found to be within the permissible criteria of ≤15% and ≤20%, respectively. Following an appropriate investigation of all the parameters for method validation, it was confirmed that the HPLC method was successfully validated and proven to be accurate to simultaneously quantify statins even in combination with other excipients used during the formulation of nano-emulsions and nano-emulgels.

A novel HPLC method developed and validated for the detection and quantification of atorvastatin, fluvastatin, pitavastatin and pravastatin during transdermal delivery studies.

An HPLC method was developed and validated to quantify and identify several statins (atorvastatin, fluvastatin, pitavastatin and pravastatin) that were used during transdermal drug delivery. The method proved to be most effective with a Restek Ultra C18, 250 x 4.6 mm, 5 µm column, a flow rate of 1.0 ml/min, UV detection at 240 nm and injection volume of 10 µl. The mobile phase used was acetonitrile/Milli-Q® water with 0.1% orthophosphoric acid starting with 30% acetonitrile, which increased linearly to 70% (after 4 min) for up to 10 min and then re-equilibrated to start conditions. This HPLC method indicated linearity (correlation coefficient (R²) of 1) within the concentration range of 0.05-200.00 µg/ml and had an average recovery of 98-103%. Limit of detection (LOD) and limit of quantification (LOQ) showed that statins could still be identified at concentrations of 0.004-0.006 µg/ml with the exception of atorvastatin (quantifiable at 0.013-0.035 µg/ml). Specificity performed during method validation, confirmed that the method was suitable for accurate detection and quantification of the statins when included in the transdermal formulations with other excipients.

Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

[Survey among livestock veterinarians from the Canton of Fribourg investigating the topics of herd-health management, counselling and the use of antimicrobial drugs]. / Umfrage bei Freiburger Nutztierärzten zu den Themen Bestandesmedizin, Beratung und Antibiotikaeinsatz.

INTRODUCTION: The work of veterinarians is continuously undergoing structural changes. A shift from purely curative individual animal care towards herd-health management is observed worldwide in the livestock sector. To illustrate the practical implementation with all its advantages and disadvantages, an online survey was conducted among all practicing livestock veterinarians in the Canton of Fribourg. A link to the survey was sent by email, it was voluntary and possible to complete the questionnaire anonymously. The survey focused on four topics: Demographic data, herd-health management, billing of counselling and use of antimicrobial drugs. Forty veterinarians from at least 79.2% (n = 19) of all veterinary practices located in the canton of Fribourg (n = 24) responded. Of these, 67.5% were practice owners or partner (n = 27) and 32.5% were employed veterinarians (n = 13). In Fribourg, only herd fertility management is included in the herd-health management on a regular basis. The quality and quantity of advanced trainings in herd-health management for veterinarians was assessed as moderate to poor. There are various options for charging herd-health management services. The amount charged was variable. The most frequently used options were hourly rates (100-300 CHF/h), "rate per cow per year excl. visit rate" (22-75 CHF/cow/year) or "rate per cow per year incl. visit rate" (85-98 CHF/ cow/year). Only one veterinarian (2.5%) charges for advisory activities not included in the the herd-health management service, which was asked for separately. However, the time required for counselling (excluding herd-health management) was estimated to be between 5.0-70.0% of the total working time (median 15.0%, interquartile range = 10.0-32.5%). Veterinarians in Fribourg are reHauptluctant to follow the international trend towards a regular, integrated herd-health management. The majority of them do not charge for consultancy outside the herdhealth management service. A nationwide survey should be considered to better assess the situation all over Switzerland.

INTRODUCTION: Les vétérinaires sont soumis à un changement structurel permanent dans leur travail et cette évolution va dans la direction de la médecine de troupeau pour le secteur des animaux de rente. Pour pouvoir décrire les avantages et les inconvénients, une enquête en ligne a été effectuée auprès de tous les vétérinaires praticiens ruraux du canton de Fribourg et des régions limitrophes. Un lien vers l'enquête a été envoyé par courriel. La participation était sur une base volontaire et les données pouvaient être anonymisées, si souhaité. L'enquête portait sur les quatre thématiques principales suivantes: données démographiques, médecine de troupeau, facturation des prestations de conseil et administration d'antibiotiques. Quarante vétérinaires, soit 79.2% (n = 19) de toutes les pratiques vétérinaires rurales fribourgeoises (n = 24), ont répondu. De ceux-ci, 67.5% étaient propriétaires ou associés ( n= 27) et 32.5 % employés (n = 13). Dans le canton de Fribourg, le suivi de fertilité est effectué seulement de manière généralisée et intégré régulièrement dans le suivi de troupeau (100%). L'offre en formation continue aux vétérinaires sur la thématique médecine de troupeau est évaluée de moyenne à médiocre. La facturation des prestations de médecine de troupeau se déroule auprès des participants à l'étude de manière différenciée, avec même de très grandes différences: le plus souvent un barème horaire (100-300 CHF/h), à la seconde place «par vache et année sans le tarif de la visite¼ (22-75 CHF/vache/an) et en troisième position «par vache et année avec le tarif de la visite inclus¼ (85-98 CHF/Vache/an). Seul un vétérinaire (2.5%) a indiqué facturer des prestations de conseil en dehors du suivi de troupeau. Cependant, l'investissement en temps pour le conseil (sans le suivi de troupeau) est estimé de 5.0 à 70% du temps total de travail (moyenne: 15.0%, écart interquartile = 10.0­32.5%). La corporation vétérinaire fribourgeoise suit la tendance internationale à l'introduction d'un suivi de troupeau intégré et régulier, avec un peu de retard. Une enquête au niveau suisse devrait permettre d'évaluer la situation au niveau national.

Physical fitness and nutritional anthropometric status of children from disadvantaged communities in the Nelson Mandela Bay region.

Background: Information about the relationships between physical fitness, body composition and nutrition has increased in recent years; however, little is known about physical fitness and the coexistence of under-/overnutrition among children living in disadvantaged areas. Objectives: To determine the physical fitness status and its association with body composition, growth and selected socio-demographics in primary schoolchildren from disadvantaged communities in the Nelson Mandela Bay region. Methods: Nine hundred and sixty-five children (49% girls, M=9.5 years) participated in this cross-sectional study. Height and weight were measured to establish body mass index, and height-for-age z-scores. Physical fitness was assessed using tests from the Eurofit Physical Fitness test battery (flexibility, upper/lower body muscular strength and cardiorespiratory fitness). Between-group differences and cross-sectional associations were examined with univariate (Chi2-tests, analyses of variance) and multivariate methods (mixed linear/logistic regression). Results: Most children had normal weight (76.7%), while 4.5% were underweight and 18.7% were overweight/obese. Underweight children and children with stunted growth (11.5%) had lower average upper body strength (p<0.001). Overweight/obese children had lower scores in weight-bearing activities (p<0.001). Children with higher socio-economic status were more likely to be overweight and obese (p<0.001). In the multivariate analyses, sex, age, body mass index, and stunting were associated with children's physical fitness. Conclusion: Fitness assessments seem to be a relevant measure of the current health status of children in disadvantaged settings. Compared to international norms, the children in this study had relatively low scores for both upper- and lower body muscular strength. Therefore, effective school-based intervention programmes should be developed to improve children's physical fitness in disadvantaged schools.

Determination of lovastatin, mevastatin, rosuvastatin and simvastatin with HPLC by means of gradient elution.

A novel HPLC method with UV detection was developed and validated in skin penetration (in vitro) studies to identify and quantify lovastatin, mevastatin, rosuvastatin and simvastatin. A Venusil XBP C18 (2), 150 x 4.6 mm, 5 µm column (Agela Technologies, Newark, DE) was used with gradient elution (start at 45 % acetonitrile and increase linearly to 90 % after 1 min; hold at 90 % until 6 min and then re-equilibrate at start conditions) and the mobile phase consisted of (A) Milli-Q ® water and 0.1% orthophosphoric acid, and (B) HPLC grade acetonitrile. The flow rate was set at 1 ml/min, 240 nm UV detection and an injection volume of 10 µl. Linearity was obtained over a range of 0.50-200.00 µg/ml and correlation coefficients ranging from 0.998-1.000 were obtained. Average recovery ranged from 95.9-100.6 %. The LOD and LOQ values obtained from the slope of a calibration curve and the standard deviation of the response ranged from 0.0138-0.0860 µg/ml and 0.0419-0.2615 µg/ml, respectively, where lovastatin and simvastatin could be detected at a concentration similar to the other statins, but could only be quantified at a higher concentration than the remaining statins. The specificity of the method was proved as accurate and quantification of statins was found, even within the incorporation of other compounds.

A Combined EEG-fNIRS Study Investigating Mechanisms Underlying the Association between Aerobic Fitness and Inhibitory Control in Young Adults.

The current evidence suggests that aerobic fitness is associated with inhibitory control of executive functioning in children and older adults. However, the relative contributions of different neurophysiological mechanisms to this relation remain unclear and have not yet been examined in young adults. The present study aimed to compare inhibitory control between high and low-fit young adult men, and to investigate a possible mediation of fitness effects by conflict monitoring (N450 component of event-related potentials) and lateralized oxygenation difference (LOD) in the DLPFC. For the present cross-sectional study, participants with different physical activity levels were recruited and divided into low-fit and high-fit participants based on relative power on the PWC170. A Stroop Color-Word task was administered and combined EEG-fNIRS was simultaneously utilized to assess the N450 and LOD, because these parameters are linked with behavioral performance. The results of the statistical analysis showed that high-fitcompared to low-fit participants showed less Stroop interference and lower negativity of the N450, whereas no difference was found for LOD. Path-analyses further revealed that the relation between aerobic fitness levels and Stroop interference was indirect and mediated by N450. In contrast, LOD was inversely correlated with Stroop interference, but did not explain the relation of aerobic fitness with behavioral performance. The present findings indicate that greater inhibitory control in high- compared to low-fit young men can be explained by more effective conflict monitoring. Moreover, young adults with left-lateralizedDLPFC oxygenation also show higher inhibitory control, but this oxygenation pattern is not influenced by aerobic fitness.

Development and validation of the simultaneous determination of artemisone, clofazimine and decoquinate with HPLC.

The aim of this study was to develop and validate a novel HPLC method for the simultaneous analysis of artemisone, clofazimine and decoquinate. Detection was obtained at two wavelengths; 284 nm (clofazimine) and 210 nm (artemisone and decoquinate). Gradient elution was used with mobile phase A (A) consisting of 0.005 M sodium octanesulphonic-acid (pH 3.5) and mobile phase B (B) of HPLC grade acetonitrile. The flow rate was set to 1.0 ml/min with (A) at 35% and (B) at 65% for 2 min, followed by a gradient shift of 10/90% ((A)/(B)) over a duration of 4 min. After 10 min, the initial gradient conditions were readjusted to 35/65% ((A)/(B)). Distinctive peaks were identified for clofazimine, artemisone and decoquinate, respectively. The proposed HPLC assay method was validated and found to be reliable, reproducible and accurate for simultaneous analysis of the three compounds.

Exploratory data analysis of the dependencies between skin permeability, molecular weight and log P.

Molecular weight and log P remain the most frequently used physicochemical properties in models that predict skin permeability. However, several reports over the past two decades have suggested that predictions made by these models may not be sufficiently accurate. In this study, exploratory data analysis of the probabilistic dependencies between molecular weight, log P and log Kp was performed on a dataset constructed from the combination of several popular datasets. The results suggest that, in general, molecular weight and log P are poorly correlated to log Kp. However, after employing several exploratory data analysis techniques, regions within the dataset of statistically significant dependence were identified. As an example of the applicability of the information extracted from the exploratory data analyses, a multiple linear regression model was constructed, bounded by the ranges of dependence. This model gave reasonable approximations to log Kp values obtained from skin permeability studies of selected non-steroidal ant-inflammatory drugs (NSAIDs) administered from a buffer solution and a lipid-based drug delivery system. A method of testing whether a given drug falls within the regions of statistical dependence was also presented. Knowing the ranges within which molecular weight and log P are statistically related to log Kp can supplement existing methods of screening, risk analysis or early drug development decision making to add confidence to predictions made regarding skin permeability.

A novel RP-HPLC method for the detection and quantification of roxithromycin in topical delivery studies.

A novel HPLC method with UV detection for the identification and quantification of roxithromycin (ROX) during in vitro skin penetration studies has been developed and validated. The method proved to be simple and rapid with isocratic elution (flow rate: 1.0 mL/min) of ROX, using a C18 column and UV detection at 205 nm. The mobile phase consisted of 0.06 M potassium di-hydrogen orthophosphate buffer (pH adjusted to 7.4 with sodium hydroxide) and acetonitrile in a 50:50 (v/v) ratio. This method showed linearity across the concentration range of 5 - 1000 µg/mL with a correlation coefficient of 0.9999. An average recovery of 101.78% was obtained. Limit of detection (LOD) and lower limit of quantification (LLOQ) values proved that ROX can still be detected at a concentration level of 0.3 µg/mL and accurately quantified at a concentration of 0.5 µg/mL. The specificity testing during method validation proved that this method is suitable for the accurate detection and quantification of ROX even when combined with different compounds typically used during the formulation of topical delivery systems.

Natural zeolites in diet or litter of broilers.

This study aims to analyse the influence of adding natural zeolites (clinoptilolite) to the diet or litter of broilers and their effects on growth performance, carcass yield and litter quality. Three consecutive flocks of broilers were raised on the same sawdust litter, from d 1 to d 42 of age, and distributed in three treatments (control with no added zeolites, addition of 5 g/kg zeolite to diet and addition of 100 g/kg zeolites to litter). The addition of zeolites to the diet or litter did not affect growth performance or carcass yield. The addition of zeolites to the diet did not influence moisture content of the litter, ammonia volatilisation was reduced only in the first flock and pH of litter was reduced in the second and third flock. However, the addition of zeolites to the litter reduced moisture content, litter pH and ammonia volatilisation in all flocks analysed. The addition of 5 g/kg zeolite to the diet in three consecutive flocks was not effective in maintaining litter quality, whereas the addition of 100 g/kg natural zeolites to sawdust litter reduced litter moisture and ammonia volatilisation in three consecutive flocks raised on the same litter.

Surfer's myelopathy: a radiologic study of 23 cases.

BACKGROUND AND PURPOSE: Surfing is an uncommon cause of an acute nontraumatic myelopathy. This study describes the MR imaging characteristics and clinical correlates in 23 subjects with surfer's myelopathy. MATERIALS AND METHODS: This was a retrospective review of 23 cases of surfer's myelopathy from 2003-2012. Spinal cord MR imaging characteristics and neurologic examinations with the use of the American Spinal Injury Association scale were reviewed. Logistic regression was used to determine associations between MR imaging characteristics, American Spinal Injury Association scale, and clinical improvement. RESULTS: All subjects (19 male, 4 female; mean age, 26.3 ± 7.4 years) demonstrated "pencil-like," central T2-hyperintense signal abnormalities in the spinal cord extending from the midthoracic region to the conus with associated cord expansion and varying degrees of conus enlargement on spinal cord MR imaging within 24 hours of symptom onset. T1 signal was normal. Faint gadolinium enhancement was present in a minority. Although there was a strong correlation between initial American Spinal Injury Association score and clinical improvement (P = .0032), MR imaging characteristics were not associated with American Spinal Injury Association score or clinical improvement. CONCLUSIONS: Surfer's myelopathy should be considered in the radiographic differential diagnosis of a longitudinally extensive T2-hyperintense spinal cord lesion. MR imaging characteristics do not appear to be associated with severity on examination or clinical improvement.

Contribution of physical education to overall physical activity.

For many children, physical activity (PA) during physical education (PE) lessons provides an important opportunity for being physically active. Although PA during PE has been shown to be low, little is known about the contribution of PA during PE to overall PA. The aim was therefore to assess children's PA during PE and to determine the contribution of PE to overall PA with special focus on overweight children. Accelerometer measurements were done in 676 children (9.3 ± 2.1 years) over 4-7 days in 59 randomly selected classes. Moderate-and-vigorous PA (MVPA; ≥ 2000 counts/min) during PE (MVPAPE), overall MVPA per day (MVPADAY), and a comparison of days with and without PE were calculated by a regression model with gender, grade, and weight status (normal vs overweight) as fixed factors and class as a random factor. Children spent 32.8 ± 15.1% of PE time in MVPA. Weight status was not associated to MVPAPE . MVPAPE accounted for 16.8 ± 8.5% of MVPADAY, and 17.5 ± 8.2% in overweight children. All children were more active on days with PE than on days without PE (differences: 16.1 ± 29.0 min of MVPADAY; P ≤ 0.001; 13.7 ± 28.0 min for overweight children). Although MVPAPE was low, PE played a considerable role in providing PA and was not compensated by reducing extracurricular MVPA.

Physician speciality and pain reduction in patients with depressive symptoms under treatment with venlafaxine.

OBJECTIVES: Excessive pain perception may lead to unnecessary diagnostic testing or invasive procedures resulting in iatrogenic complications and prolonged disability. Naturalistic studies on patients with chronic pain and depressive symptoms investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking. METHODS: In this observational study, we examined whether the magnitude of pain reduction in 444 patients with depressive symptomatology under venlafaxine would relate differently to the medical speciality of the 122 treating physicians, namely psychiatrists (n=110 patients), general practitioners (n=236 patients), and internists (n=98 patients). RESULTS: Independent of age, gender, patient's region of origin, comorbidity, severity and duration of pain, and depressive symptoms at study entry, patients seemed to benefit significantly less in terms of pain reduction (p<0.001) and of reduction in severity of depressive symptomatology by psychiatrists as compared to general practitioners (p<0.019) and internists (p<0.002). CONCLUSIONS: The findings suggest that patients referred to psychiatrists are more difficult to treat than those referred to general practitioners and internists, and might not have been adequately prepared for psychiatric interventions. A supporting cooperation and networking between psychiatrists and primary care physicians may contribute to an integrated treatment concept and therefore, may lead to a better outcome in this challenging patient group.

Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion.

OBJECTIVE: To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc). METHODS: Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion. RESULTS: The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin. CONCLUSIONS: JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.