Daily fluctuations in occupation with and worry about COVID-19.

In the first week after the first COVID-19 patient was reported in the Netherlands, we conducted a pre-registered momentary assessment study (7 surveys per day, 50 participants, 7 days) to study the dynamic relationship between individuals' occupation with and worries about COVID-19 in daily life, and the moderating role of neuroticism in this relationship. At the group level, higher scores on occupation and worry co-occurred, and occupation predicted worry 1 h later, but not vice versa. There were substantial individual differences in the magnitudes and directions of the effects. For instance, occupation with COVID-19 was related to increases in worry for some but decreases in worry for others. Neuroticism did not predict any of these individual differences in the links between worry and occupation. This study suggests that it is important to go beyond group-level analyses and to account for individual differences in responses to COVID-19.

THE MODIFIED STAR EXCURSION BALANCE AND Y-BALANCE TEST RESULTS DIFFER WHEN ASSESSING PHYSICALLY ACTIVE HEALTHY ADOLESCENT FEMALES.

BACKGROUND: The modified Star Excursion Balance Test (mSEBT) and Y-Balance Test (YBT) are two common methods for clinical assessment of dynamic balance. Clinicians often use only one of these test methods and one outcome factor when screening for lower extremity injury risk. Dynamic balance scores are known to vary by age, sex and sport. The physically active adolescent female is at high risk for sustaining lower extremity injuries, specifically to the anterior cruciate ligament (ACL). Thus clarity regarding the use of dynamic balance testing results in adolescent females is important. To date, no studies have directly compared the various outcome factors between these two dynamic balance tests for this population. PURPOSE: To determine if there was an association between the mSEBT and YBT scores for measured reach distances, calculated composite score and side-to-side limb asymmetry in the ANT direction in physically active healthy adolescent females. STUDY DESIGN: Cross-sectional study. METHODS: Twenty-five healthy, physically active female adolescents (mean age, 14.0 ± 1.3 years) participated. Reach distances, a composite score and side-to-side limb asymmetry for the mSEBT and YBT, for each limb, were compared and examined for correlation. RESULTS: There were significant differences and moderate to excellent relationships between the measured reach directions between the mSEBT and the YBT. Injury risk classification, based on limb asymmetry in the anterior reach direction, differed between the tests. However, the calculated composite scores from the two tests did not differ. CONCLUSIONS: Performance scores on a particular reach direction should not be used interchangeably between the mSEBT and YBT in physically active adolescent females, and should not be compared to previously reported values for other populations. LEVEL OF EVIDENCE: Level 3.

Accurate determination of rate constants of very slow, tight-binding competitive inhibitors by numerical solution of differential equations, independently of precise knowledge of the enzyme concentration.

This paper is concerned with the determination of rate constants characterizing the binding and release of a slow binding inhibitor to and from an enzyme, here almond beta-glucosidase. We demonstrate the inability of the conventional method to yield reliable rate constants when one or more of these is less than 1 x 10(-4) per second. Instead one must use the much more accurate fitting of rate constants of the set of simultaneous differential equations characterizing the kinetic model. This procedure has the added advantage, when properly used, that the rate constants found pertaining to the inhibitor are largely insensitive to the particular value used for the enzyme concentration; i.e., the same data set may be fitted using a range of enzyme concentrations with no change in the resulting parameters. Hence the method can be used when little is known about the enzyme, except for the value of K(m), which is readily determined. Also, we report the somewhat unexpected finding that the association rate constant for the substrate (4-nitrophenyl-beta-d-glucopyranoside) is about one-third of the value of the corresponding rate constant for the inhibitor. The method is used to determine rate constants at several temperatures for the strong, slow binding inhibitor 2-phenethylglucoimidazole 1, enabling us to compute standard thermodynamic functions. The identity of these functions with those of isofagomine (2) reported earlier leads us to argue that the two compounds share a common binding mechanism, involving the same groups, whereas the different stabilities of the enzyme-inhibitor complexes must reside in those parts of the molecules that are not identical.

Slow inhibition of almond beta-glucosidase by azasugars: determination of activation energies for slow binding.

The thermodynamic and activation energies of the slow inhibition of almond beta-glucosidase with a series of azasugars were determined. The inhibitors studied were isofagomine ((3R,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine, 1), isogalactofagomine ((3R,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine, 2), (-)-1-azafagomine ((3R,4R,5R)-4,5-dihydroxy-3-hydroxymethylhexahydropyridazine, 3), 3-amino-3-deoxy-1-azafagomine (4) and 1-deoxynojirimycin (5). It was found that the binding of 1 to the enzyme has an activation enthalpy of 56.1 kJ/mol and an activation entropy of 25.8 J/molK. The dissociation of the enzyme-1 complex had an activation enthalpy of -2.5 kJ/mol and an activation entropy of -297 J/molK. It is suggested that the activation enthalpy of association is due to the breaking of bonds to water, while the large negative activation entropy of dissociation is due at least in part to the resolvation of the enzyme with water molecules. For the association of 1 DeltaH(0) is 58.6 kJ/mol and DeltaS(0) is 323.8 J/molK. Inhibitor 3 has an activation enthalpy of 39.3 kJ/mol and an activation entropy of -17.9 J/molK for binding to the enzyme, and an activation enthalpy of 40.8 kJ/mol and an activation entropy of -141.0 J/molK for dissociation of the enzyme-inhibitor complex. For the association of 3 DeltaH(0) is -1.5 kJ/mol and DeltaS(0) is 123.1 J/molK. Inhibitor 5 is not a slow inhibitor, but its DeltaH(0) and DeltaS(0) of association are -30 kJ/mol and -13.1 J/molK. The large difference in DeltaS(0) of association of the different inhibitors suggests that the anomeric nitrogen atom of inhibitors 1-4 is involved in an interaction that results in a large entropy increase.

Differentiated effects of vasodilators on myogenic reactivity during partial inhibition of myogenic tone in pressurized skeletal muscle small arteries of the rat.

Myogenic tone and reactivity were studied in isolated, cannulated and pressurized small branches of the femoral artery of the rat. Myogenic tone developed spontaneously under control conditions (1.5 mM Ca2+), reducing the diameter at 80 mmHg to 64 +/- 6% of the 'max 80', i.e. the diameter in Ca2+ free solution, which was 221 +/- 23 microns (mean +/- SD, n = 18). The calcium channel blockers verapamil and diltiazem, dose-dependently, decreased this myogenic tone with pIC50 values of 6.9 +/- 0.2 (n = 7) and 6.6 +/- 0.1 (n = 6), respectively. Myogenic reactivity was demonstrated under control conditions as a sustained decrease in diameter, by 5 +/- 3% of max 80 (after an initial, transient distension), in response to a step increase in transmural pressure from 80 to 140 mmHg. This response to the pressure increase was markedly inhibited when myogenic tone had been reduced by 50% with verapamil or diltiazem resulting, in fact, in an increased steady state diameter by 2 +/- 1 and 1 +/- 1% at 140 compared with 80 mmHg. However, if myogenic tone was reduced to the same extent by low extracellular Ca2+ (approximately 0.3 mM) the vessels constricted by 6 +/- 1% in response to the pressure increase, an effect comparable to that in control Ca2+. Moreover, 50% reductions in myogenic tone by ACh (approximately 0.1 microM) or pinacidil (approximately 0.3 microM) were associated with significantly enhanced reactivity; steady state diameter decreased by as much as 11 +/- 4 and 15 +/- 5% of max 80. These results suggest that voltage dependent L-type Ca2+ channels are involved both in myogenic tone and in the myogenic response to a rise in vascular transmural pressure in skeletal muscle arteries. Partial inhibition of myogenic tone by other pharmacological routes do not necessarily interfere with myogenic reactivity since the response was, in fact, enhanced in the presence of ACh or pinacidil.

Membrane stretch evoked by cell swelling increases contractile activity in vascular smooth muscle through dihydropyridine-sensitive pathways.

Effects of the dihydropyridine calcium antagonist felodipine and of calcium reduction were studied on osmotically induced contractile responses in the vascular smooth muscle of the rat isolated portal vein. Previous studies have shown that changes in osmolarity that cause cell swelling are accompanied by increased contractile activity in this smooth muscle (Johansson & Jonsson 1968). A transient enhancement of the contractile activity developed in the portal vein on return to standard Krebs solution after exposure to 60 mM urea. This osmotic response was dependent on extracellular Ca2+ (abolished in Ca2+ free solution +0.1 mM EGTA) and was reduced in proportion to the decrease in spontaneous phasic contractile activity when Ca2+ was lowered from the standard 2.5 mM concentration. Felodipine, 3 nM, reduced the spontaneous activity to approximately 50% but showed an even more pronounced inhibitory effect on the osmotic responses which were reduced to less than 20% of control. Other calcium antagonists such as verapamil, 60 nM and diltiazem, 300 nM, were also more effective in inhibiting the osmotic responses than the spontaneous activity. In contrast, the K+ channel opener, pinacidil, 100-200 nM, reduced the spontaneous activity to 50% but had only minor inhibitory effect on the osmotic responses, about 75% still persisting. It is suggested that stretch of the cell membrane in response to variations in osmolarity induces contractile activity in vascular smooth muscle by mechano-electrical coupling involving dihydropyridine-sensitive pathways.

Rhythmic contractions of isolated, pressurized small arteries from rat.

The present study was undertaken to examine the influence of transmural pressure on vasomotion and to determine if any such influence was endothelium-dependent. Responses to changes in intravascular pressure of cannulated mesenteric small arteries were investigated under no-flow conditions. Both intact and endothelium-denuded arteries dilated passively when intravascular pressure was increased stepwise from 20 to 140 mmHg. When tone was induced by noradrenaline, pressure increase resulted only in dilatation, independent of endothelium. The sensitivity to noradrenaline was significantly increased in vessels without endothelium, indicating a relaxing influence of the endothelium. Rhythmic contractions in response to noradrenaline occurred in all intact arteries, but were absent when the endothelium was removed. The amplitude of the rhythmic contractions decreased significantly when transmural pressure was elevated. The frequency increased when pressure was elevated from 20 to 80 mmHg and then remained rather constant during further pressure increases. As shown previously in non-pressurized arteries, exogenous cyclic GMP induced oscillations in endothelium-denuded arteries. Pressure-related effects on vasomotion were not dependent on an intact endothelium. Ryanodine, ouabain or verapamil inhibited the rhythmic activity, confirming previous results in non-pressurized arteries. Thus, changes in transmural pressure can modulate vasomotion, but this effect does not appear to be mediated by the endothelium. Generation of vasomotion may depend on release of Ca2+ from intracellular stores, the activity of the Na+, K(+)-pump and transmembrane Ca2+ inflow in a pressurized artery as shown previously in these arteries under isometric conditions.

Effect of felodipine on the myogenic response to dynamic stretch in vascular smooth muscle.

In the present experiments we examined the effect of felodipine, a vasoselective dihydropyridine calcium antagonist, on contractile responses to dynamic and static stretch of the isolated portal vein of the rat. Dynamic stretch was applied to the vascular smooth muscle at graded rates (from 0.5-1.5% muscle length s-1). Earlier observations (Johansson & Mellander 1975) of a rate-dependent excitation of the vascular smooth muscle by dynamic stretch were confirmed. Addition of felodipine, 3 nM, reduced the spontaneous activity at static lengths to about 50% but resulted in much stronger inhibition of the dynamic stretch responses. Particularly the rate-dependent increase in active force was no longer evident since the response at high rates of passive lengthening was most clearly reduced by felodipine. By contrast, lowering of the extracellular Ca2+ concentration resulted in a comparable attenuation of the spontaneous contractile activity and of the dynamic stretch responses which still showed the typical rate dependence. Therefore, the pronounced inhibition by felodipine of the dynamic myogenic reactivity of the rat portal vein appeared to be a specific effect and not simply related to the overall reduction in contractile activity. We suggest that felodipine, in addition to its inhibition of action potentials and excitation-contraction coupling may exert a special negative influence on the mechano-electrical coupling, i.e. the process that couples dynamic stretch of the vascular smooth muscle to membrane excitation.

[Anesthesia of horses in the standing position]. / Untersuchungen zur Standnarkose des Pferdes.

Painful interventions can be performed on horse in standing position by means of sedative analgesia, also called standing-position anaesthesia. Combinations of anaesthetics are quite often used, in that context, for the purpose of producing analgetic effects stronger and more reliable than those that would be obtainable from one anaesthetic alone. The following combinations were comparatively tested for their analgetic and sedative effects and their effects upon the organism: Chloralhydrate with Ursonarkon (oxazolidone), Chloralhydrate with Rompun (xylazine), Chloralhydrate with morphine hydrochloride, Chloralhydrate with morphine hydrochloride and Ursonarkon, local anaesthesia in conjunction with sedation by Ursonarkon. 50 experiments were conducted on an experimental group of 10 horses under standardised conditions together with complementary tests on 71 horses under field conditions. The experimental methodology used for assessment of analgetic effects was based on defined electrical and thermic stimuli to enable determination of reactive thresholds. An objective comparison was thus possible between the above variants. Local anaesthesia in combination with complementary sedation proved to meet all demands on standing-position anaesthesia, as it was found to eliminate pain and tactile reflexes. Defence movements have to be expected, whenever preparations are used that attack the central nervous system, since while sensations of pain are suppressed, tactile stimuli may be met with reflex responses via the spinal cord and its intrinsic function.