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Cell kinetics in rat small intestine after exposure to 3 Gy of gamma-rays at different times of the day.

Qualitative and quantitative morphological changes in rat jejunum were studied after a whole-body exposure to 3 Gy of gamma rays. Four groups of animals were irradiated at different times of the day, namely midnight, 06.00, 12.00 and 18.00 hours. The number of epithelial cells, labelling and mitotic indices were evaluated in crypt sections and the spatial distribution of S-phase cells was determined. At 12 h after irradiation a marked reduction was observed in all parameters, but the proliferative activity was restored quickly and at 36 h after irradiation the values were significantly higher than the controls. The frequency distribution of labelled cells at different positions in the crypt was reduced at 12 h but a clear expansion of S phase cells to positions near to the crypt villus junction was observed during the recovery phase. The animals irradiated at different times of the day showed a similar general post-irradiation response in the number of cells along the side of the crypt, labelling and mitotic indices and in the distribution of S phase cells along the crypts. It is worth noting that the animals exposed at midnight had a distribution of S phase cells similar to controls at 72 h post-irradiation, i.e. earlier than the other groups.

Animals↗

Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features.

Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.

Animals↗

Movement generated by interactions between the dense material at the ends of microtubles and non-actin-containing microfilaments in Sticholonche zanclea.

Axopods of the planktonic protozoan, Sticholonche, are used as oars to propel the organism through seawater. Within each axopod is an orgainzed array of microtubules which inserts into a dense material that assumes the form of the head of a hip joint. This material, in turn, articulates on the surface of the nucleus. Microfilaments, 20-30 A in diameter, connect the dense material associated with the microtubules to the surface of the nucleus, and they move the axopod by their contractions. The active phase of the movement may take as little as about 0.04 s and the recovery phase may take between 0.2 and 0.4 s. The microfilaments are not actin, as based on: (a) their small diameter, (b) the lack of decoration with heavy meromyosin, and (c) their ability to coil, spiral or fold during contraction. By the use of Thorotrast, we were able to demonstrate that the cell surface is deeply infolded, extending all the way to the hip joint. Here, there is a specialized membrane system that resembles the diad in skeletal muscle. From cytochemical tests and the use of ionophores and chelators, there is some evidence that the motile process may be controlled by calcium. This study demonstrates that, in at least one system, microtubules can be moves by contractile microfilaments attached to the dense material at there tips.

Animals↗

Kinetics of recovery of the dark-adapted salamander rod photoresponse.

The kinetics of the dark-adapted salamander rod photocurrent response to flashes producing from 10 to 10(5) photoisomerizations (Phi) were investigated in normal Ringer's solution, and in a choline solution that clamps calcium near its resting level. For saturating intensities ranging from approximately 10(2) to 10(4) Phi, the recovery phases of the responses in choline were nearly invariant in form. Responses in Ringer's were similarly invariant for saturating intensities from approximately 10(3) to 10(4) Phi. In both solutions, recoveries to flashes in these intensity ranges translated on the time axis a constant amount (tauc) per e-fold increment in flash intensity, and exhibited exponentially decaying "tail phases" with time constant tauc. The difference in recovery half-times for responses in choline and Ringer's to the same saturating flash was 5-7 s. Above approximately 10(4) Phi, recoveries in both solutions were systematically slower, and translation invariance broke down. Theoretical analysis of the translation-invariant responses established that tauc must represent the time constant of inactivation of the disc-associated cascade intermediate (R*, G*, or PDE*) having the longest lifetime, and that the cGMP hydrolysis and cGMP-channel activation reactions are such as to conserve this time constant. Theoretical analysis also demonstrated that the 5-7-s shift in recovery half-times between responses in Ringer's and in choline is largely (4-6 s) accounted for by the calcium-dependent activation of guanylyl cyclase, with the residual (1-2 s) likely caused by an effect of calcium on an intermediate with a nondominant time constant. Analytical expressions for the dim-flash response in calcium clamp and Ringer's are derived, and it is shown that the difference in the responses under the two conditions can be accounted for quantitatively by cyclase activation. Application of these expressions yields an estimate of the calcium buffering capacity of the rod at rest of approximately 20, much lower than previous estimates.

Animals↗

Time course of recovery of spermatogenesis and Leydig cell function after cessation of gonadotropin-releasing hormone antagonist treatment in the adult rat.

This study examined the time course of recovery of spermatogenesis and its relationship to the temporal changes in circulating levels of gonadotropin and testosterone (T) and intratesticular T levels after cessation of treatment with a potent GnRH antagonist (GnRH-A). Adult male rats were given a daily sc injection of Nal-Glu-GnRH antagonist (1250 micrograms/kg BW) for 4 weeks and killed in groups of five 0, 1, 2, 3, 4, and 6 weeks after discontinuation of treatment. After cessation of treatment, plasma FSH levels returned to control values by 6 weeks, whereas LH levels returned to control values within 1 week. Both circulating as well as intratesticular levels of T returned to normal levels by 3 and 4 weeks, respectively. Interestingly, a rebound in both FSH and intratesticular T, but not in plasma T, beyond control levels occurred early in the recovery phase. The total volume of Leydig cells, which was only 15% of control values, increased 4.3-fold within 1 week and was not significantly different from control values (92% recovery) by 2 weeks posttreatment. Enumeration of earlier phases of germ cells as well as homogenization-resistant advanced (steps 17-19) spermatids revealed a progressive increase in germ cell numbers with time. Complete restoration of the numbers of preleptotene spermatocytes, pachytene spermatocytes, step 7 spermatids, and advanced spermatids occurred 1, 3, 4, and 6 weeks, respectively, after termination of GnRH-A treatment. There was also a complete reversal of GnRH-A-induced changes in testicular weight, tubule diameter, and volume of seminiferous tubules and their lumens by 6 weeks posttreatment, paralleling the recovery of spermatogenesis. These results suggest that 1) complete recovery of spermatogenesis and various other testicular parameters can be achieved in GnRH-A-treated rats after cessation of treatment; 2) the progression of various germ cells during the recovery period follows the normal time schedule of germ cell development; and 3) the recovery of spermatogenesis is preceded by supranormal levels of FSH and intratesticular T. These findings further emphasize the suitability of antagonistic analogs of GnRH for male fertility control.

Animals↗

Increased levels of serum sulfite in patients with acute pneumonia.

Sulfite, a common air pollutant, is toxic for humans, causing hypersensitivity or chronic airway diseases. We previously reported that sulfite is actively produced from neutrophils by stimulation with bacterial endotoxin, lipopolysaccharide (LPS). We also found that the serum sulfite concentration is increased in a rat model of sepsis induced by systemic injection of LPS. However, information on sulfite metabolism in human inflammatory conditions is limited. In the current study, the serum concentration of sulfite was determined in 25 patients with acute pneumonia. Serum sulfite concentration in pneumonia patients was significantly higher than that in control subjects (3.75 +/- 0.88 vs. 1.23 +/- 0.48 microM, respectively, P < 0.05). Among 20 patients, serum sulfite was serially determined before and after antibiotic therapy. The levels of serum sulfite were significantly reduced during the recovery phase compared with those during the acute phase (1.34 +/- 0.56 vs. 3.65 +/- 0.92 microM, respectively, P < 0.05). Moreover, neutrophils obtained from three patients during the acute phase of pneumonia spontaneously produced higher amounts of sulfite in vitro than those obtained after recovery. There was a close positive correlation (r = 0.71, P < 0.05) between serum sulfite and C-reactive protein (CRP) in patients with pneumonia. Taken together, the current findings suggest that serum sulfite increases during systemic inflammation in humans. Activated neutrophils might be responsible, at least in part, for the up-regulation of sulfite. Given various biological effects reported previously, sulfite may act as a mediator in inflammation.

Acute Disease↗

Effects of sympathetic activation on ventricular ectopic beats in subjects with and without evidence of organic heart disease.

In a selected group of 10 apparently healthy subjects and 22 patients with organic heart disease, all with frequent ventricular ectopic beats on Holter monitoring, we assessed the influence of sympathetic activation by comparing the arrhythmogenic effects of a symptom-limited bicycle exercise stress test and 90 degree head up tilt. Tilting reduced ventricular arrhythmias in the normal subjects (-48 +/- 18% from 9 +/- 2 beats min-1, P less than 0.05). Exercise stress testing caused small and insignificant changes in arrhythmias during the early (50-75 W) phases and an almost complete suppression of ventricular ectopic beats in the final stages (-99 +/- 1%, P less than 0.01). In six of the 10 subjects, ventricular arrhythmias reappeared in the early recovery phase. In the 22 patients with organic heart disease, tilting increased ventricular ectopic beats (43 +/- 17% from 9 +/- 3 beats min-1, P less than 0.05); augmented repetitive forms in 12 patients (179 +/- 88% from 1.4 +/- 0.6 per 3 min) and produced repetitive forms in six of the 10 remaining patients who did not show repetitive forms during control conditions. Exercise stress testing caused a marked increase in ectopic activity in the early phase (84 +/- 35%) while the response during the maximal phase of exercise as well as during recovery was related to the effort capabilities. Arrhythmias were increased in 12 patients with limited exercise duration and were reduced in 10 patients with good exercise tolerance. These data indicate that sympathetic activation has different effects on ventricular arrhythmias depending on the clinical setting and that tilting is a useful maneuver to evaluate the arrhythmogenic effects of increased sympathetic activity.

Adult↗

Serum angiotensin-converting enzyme. Alterations in hyperthyroidism, hypothyroidism, and subacute thyroiditis.

Angiotensin-converting enzyme (ACE) activity was measured in the serum samples of 247 patients with varying thyroid states. In 60 hyperthyroid patients, the mean (+/- SD) ACE level of 29.5 +/- 9.7 units/mL was higher than in all other groups. The serum ACE level was 17.0 +/- 5.1 units/mL in 129 euthyroid subjects and differed from the level of 13.9 +/- 5.1 units/mL observed in 34 hypothyroid patients. Twenty-four patients receiving exogenous thyroid hormone had elevated serum thyroxine values. Their mean serum triiodothyronine level was in the normal range, and the mean ACE level did not differ from the euthyroid mean. The mean serum ACE level fell from 30.8 to 17.4 units/mL in 35 hyperthyroid patients studied before and after therapy. In 12 hypothyroid subjects, the mean serum ACE level rose from 11.6 to 15.8 units/mL after thyroid hormone replacement. In eight of ten patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), their highest ACE levels were observed in the hyperthyroid or transition phase and fell progressively with the lowest values being recorded during the hypothyroid or early recovery phases. Thus, ACE activity may respond to thyroid hormone, and interpretation of serum ACE levels may require knowledge of the patient's thyroid status. Serum ACE may be useful as a probe for exploring peripheral thyroid hormone action.

Adolescent↗

Early mother-infant reciprocity.

By three weeks of age, the human neonate demonstrates behaviours which are quite different with an object and with a human interactant. He also demonstrates an expectancy for interaction with his caregiver which has clearly defined limits, as demonstrated behaviourally. In microanalysis of videotape, we saw regularly a set of interactive behaviours which were demonstrable in optimal face-to-face interaction between infants and their mothers. All parts of the infant's body move in smooth circular patterns as he attends to her. His face-to-face attention to her is rhythmic with approach-withdrawal cycling of extremities. The attention phase and build-up to her cues are followed by turning away and a recovery phase in a rhythm of attention-non-attention which seems to define a cyclical homeostatic curve of attention, averaging several cycles per minute. When she violates his expectancy for rhythmic interaction by presenting a still, unresponsive face to him, he becomes visibly concerned, his movements become jerky, he averts his face, then attempts to draw her into interaction. When repeated attempts fail, he finally withdraws into an attitude of helplessness, face averted, body curled up and motionless. If she returns to her usual interactive responses, he comes alive after an initial puzzled period, and returns to his rhythmic cyclical behaviour which has previously characterized their ongoing face-to-face interaction. This attentional cycling may be diagnostic of optimal mother-infant interactions and seems not to be present in more disturbed interactions.

Attention↗

Sequential studies of pre-S2 antigenemia and anti-pre-S2 antibodies in relation to viral replication in acute hepatitis B followed from the early incubation phase.

To determine the time sequence of expression of pre-S2 peptide (120-150) during the presymptomatic phase of acute hepatitis B, we used a monoclonal antibody radioimmunoassay in five subjects followed from 30 to 70 days before the onset of liver damage. Pre-S2 peptide was present in serum at low levels from the early incubation phase and started to increase immediately after the first detection of HBV-DNA in serum, in parallel with the increase in HBsAg levels. During the symptomatic phase, levels of pre-S2 peptide declined rapidly; it was no longer detectable after recovery. Anti-pre-S2 antibodies were detected, in four patients, only in the recovery phase. These results demonstrate that expression of pre-S2 peptide occurs very early in the incubation phase of acute HBV infection and is cleared in parallel with HBsAg. Anti-pre-S2 antibodies seem to play no role in viral clearance in these patients.

Adolescent↗

Hypothyroid myopathy. A clinical and pathologaical study.

Ten patients with varying degrees of hypothroid myopathy were studied clinically and by serial percutaneous needle muscle biopsies before and during treatment with L-thyroxine. The biochemical evidence of hypothyroidism was related to the severity of the myopathic and signs before treatment. The severity of myopathic symptoms before and during treatment correlated with the biochemical evidence of hypothyrodism, a type II fibre atrophy and increased central nuclear counts. Likewise, the clinical evidence of a myopathy before and during treatment was correlated with both a type II fibre atrophy and loss and increased central nuclear counts but was not related to the biochemical parameters of hypothyroidism, except the level of thyroid stimulating hormone. In the muscle, before and during treatment, of the two most severely affected patients, intracellular glycogen inclusions were seen in scattered muscle fibres. On light microscopy and on electronmicroscopy, numerous mitochondria were seen responding to L-thyroxine with accumulations of subsarcolemmal honey-combing. Vesicular abnormalities, an electron dense matrix or occasional crystalline deposits were seen in muscle mitochondria from less severely azffected patients. Severely myopathic muscle contained excessive glycogen, membrane bound glycogen and excess lipid in a mainly perinuclear distribution. Occasional myelin and membranous bodies were seen and satellite cells during the recovery phase. A group of patients with hypothyroid myopathy who are likely to have a delayed recovery of full muscle strength on L-thyroxine may be recognised by the presence of severe proximal muscle weakness and characteristic changes on histochemical and electronmicroscopic examination of muscle. The spectrum of histochemical and electronmicroscopic abnormalities of muscle revealed with increasing degree of hypothyrodism, suggests that a generally reversible acquired glycogen storage and mictochondrial disorder is an important feature in the pathogenesis of this condition.

Adult↗

The simulation of human core temperature.

Two fit subjects performed two cycle-ergometer exercise bouts, one of 200 W for 48 min with a following 12-min recovery phase and one of 250 W for 30 min with a subsequent 15-min monitored recovery period. Experiments were performed in ambient conditions of 18 +/- 1 degrees C, 52% relative humidity +/- 5% and 0.5 m.s-1 + 0.5 air velocity (mean +/- range). Experimental values obtained from rectal and tympanic temperature sites were compared with simulation figures produced from a FORTRAN model of human thermoregulation. Data obtained provide qualified experimental support for the concept of a simple feedback model to simulate human core temperature during exercise in ambient temperatures below 20 degrees C.

Body Temperature Regulation↗

The effect of exercise on circulating immunoreactive calcitonin in men.

Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.

Adult↗

Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)-associated coronavirus infection.

To understand the time-course of viraemia and antibody responses to severe acute respiratory syndrome-associated coronavirus (SARS-CoV), RT-PCR and ELISA were used to assay 376 blood samples from 135 SARS patients at various stages of the illness, including samples from patients who were in their early convalescent phase. The results showed that IgM antibodies decreased and became undetectable 11 weeks into the recovery phase. IgG antibodies, however, remained detectable for a period beyond 11 weeks and were found in 100 % of patients in the early convalescent phase. SARS-CoV viraemia mainly appeared 1 week after the onset of illness and then decreased over a period of 1 month, becoming undetectable in the blood samples of the convalescent patients. At the peak of viraemia, viral RNA was detectable in 75 % of blood samples from patients who were clinically diagnosed with SARS 1 or 2 weeks before the test.

Adolescent↗

Protection against heat stress-induced oxidative damage in Arabidopsis involves calcium, abscisic acid, ethylene, and salicylic acid.

Plants, in common with all organisms, have evolved mechanisms to cope with the problems caused by high temperatures. We examined specifically the involvement of calcium, abscisic acid (ABA), ethylene, and salicylic acid (SA) in the protection against heat-induced oxidative damage in Arabidopsis. Heat caused increased thiobarbituric acid reactive substance levels (an indicator of oxidative damage to membranes) and reduced survival. Both effects required light and were reduced in plants that had acquired thermotolerance through a mild heat pretreatment. Calcium channel blockers and calmodulin inhibitors increased these effects of heating and added calcium reversed them, implying that protection against heat-induced oxidative damage in Arabidopsis requires calcium and calmodulin. Similar to calcium, SA, 1-aminocyclopropane-1-carboxylic acid (a precursor to ethylene), and ABA added to plants protected them from heat-induced oxidative damage. In addition, the ethylene-insensitive mutant etr-1, the ABA-insensitive mutant abi-1, and a transgenic line expressing nahG (consequently inhibited in SA production) showed increased susceptibility to heat. These data suggest that protection against heat-induced oxidative damage in Arabidopsis also involves ethylene, ABA, and SA. Real time measurements of cytosolic calcium levels during heating in Arabidopsis detected no increases in response to heat per se, but showed transient elevations in response to recovery from heating. The magnitude of these calcium peaks was greater in thermotolerant plants, implying that these calcium signals might play a role in mediating the effects of acquired thermotolerance. Calcium channel blockers and calmodulin inhibitors added solely during the recovery phase suggest that this role for calcium is in protecting against oxidative damage specifically during/after recovery.

Abscisic Acid↗

Gametic phase estimation over large genomic regions using an adaptive window approach.

The authors present ELB, an easy to programme and computationally fast algorithm for inferring gametic phase in population samples of multilocus genotypes. Phase updates are made on the basis of a window of neighbouring loci, and the window size varies according to the local level of linkage disequilibrium. Thus, ELB is particularly well suited to problems involving many loci and/or relatively large genomic regions, including those with variable recombination rate. The authors have simulated population samples of single nucleotide polymorphism genotypes with varying levels of recombination and marker density, and find that ELB provides better local estimation of gametic phase than the PHASE or HTYPER programs, while its global accuracy is broadly similar. The relative improvement in local accuracy increases both with increasing recombination and with increasing marker density. Short tandem repeat (STR, or microsatellite) simulation studies demonstrate ELB's superiority over PHASE both globally and locally. Missing data are handled by ELB; simulations show that phase recovery is virtually unaffected by up to 2 per cent of missing data, but that phase estimation is noticeably impaired beyond this amount. The authors also applied ELB to datasets obtained from random pairings of 42 human X chromosomes typed at 97 diallelic markers in a 200 kb low-recombination region. Once again, they found ELB to have consistently better local accuracy than PHASE or HTYPER, while its global accuracy was close to the best.

Algorithms↗

Mechanics, power output and efficiency of the swimming muskrat (Ondatra zibethicus).

The surface swimming of muskrats (Ondatra zibethicus Linnaeus) was studied by forcing individual animals to swim against a constant water current, of velocity ranging from 0.2 to 0.75 m s-1, in a recirculating water channel. Lateral and ventral views of the swimming muskrats were filmed simultaneously for analysis of thrust by the propulsive appendages. Drag measurements and flow visualization on dead muskrats demonstrated that these animals experience large resistive forces due to the formation of waves and a turbulent wake, because of the pressure and gravitational components which dominate the drag force. Biomechanical analysis demonstrated that thrust is mainly generated by alternating strokes of the hindfeet in the paddling mode. A general lengthening of the hindfeet and presence of lateral fringe hairs on each digit increase the surface area of the foot to produce thrust more effectively during the power phase of the stroke cycle. Increased energy loss from drag on the foot during the recovery phase is minimized by configural and temporal changes of the hindfoot. Employing the models developed by Blake (1979, 1980a,b) for paddle propulsion, it was found that as the arc through which the hindfeet were swept increased with increasing velocity the computed thrust power increased correspondingly. However, the frequency of the stroke cycle remained relatively constant across all velocities at a level of 2.5 Hz. Both mechanical and aerobic efficiencies rose to a maximum with increasing swimming velocity. The aerobic efficiency, which examined the transformation of metabolic power input to thrust power output reached a value of 0.046 at 0.75 m s-1. The mechanical efficiency expressing the relationship of the thrust power generated by the paddling hindfeet and laterally compressed tail (Fish, 1982a,b) to the total mechanical power developed by the propulsive appendages increased to a maximum of 0.33 at 0.75 m s-1. I conclude that the paddling mode of swimming in the muskrat is relatively inefficient when compared to swimming modes which maintain a nearly continuous thrust force over the entire propulsive cycle. However, the paddling mode permits the muskrat to generate propulsive forces effectively while swimming at the surface. The evolution of this mode for semi-aquatic mammals represents only a slight modification from a terrestrial type of locomotion.

Animals↗

Ciliary beat of cultured human respiratory cells studied with differential interference microscope and high speed video system.

The ciliary beating of upper respiratory tract cells cultured on cover glasses was studied by using differential interference microscope equipped with high speed video. By culturing the cells on collagen coated cover glasses, objectives with higher magnifications could be used. With this system we could evaluate not only ciliary beat frequency, but also amplitude, wave form, orientation and synchrony of ciliary beating. Also some structural anomalies such as compound cilia and tide cilia bundles could be recognized. Ciliary beat frequency measured from 1,026 ciliated cells was 20.6 +/- 4.7 Hz (mean +/- SD). The orientation of ciliary beat directions was random and the mean standard deviation for measured angles was 73.0 degrees +/- 28.9 degrees (mean SD +/- SD). When the ciliary beat frequency was 20 Hz, the time used for effective phase was 0.022 +/- 0.002 s (mean +/- SD), and 0.028 +/- 0.004 s (mean +/- SD) for the recovery phase of beat. This system is advantageous for studying ciliary function because all parts can be studied simultaneously with higher magnification, and the effects of chemical physical mediators can be studied without disturbing effects of the autonomic nervous system or secretory cells. Also, the same cells could be observed before and after challenge with test medication and thus evaluated more accurately.

Cilia↗