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Oxygen cost of exercise is increased in heart failure after accounting for recovery costs.

STUDY OBJECTIVES: The oxygen cost during exercise has been reported to be decreased in patients with congestive heart failure (CHF), implying an increased efficiency (lower oxygen uptake [VO(2)] per Watt [VO(2)/W]); however, these studies ignored the oxygen debt that is increased in heart failure. SUBJECTS: The primary aim of this research was to evaluate the total oxygen cost (work VO(2)/W) during exercise and recovery in patients with heart failure as compared with healthy adults. DESIGN AND PATIENTS: We performed a retrospective analysis comparing the exercise VO(2)/W, the recovery VO(2)/W, the work VO(2)/W, and the VO(2)/W relationship above and below the ventilatory threshold (VT) in 11 healthy control subjects and 45 patients with CHF. RESULTS: The exercise VO(2)/W was decreased by 29% (p < 0.0001) in patients with CHF; however, the recovery VO(2)/W was increased by 167% (p < 0.0001) and the work VO(2)/W was increased by 14% in patients with CHF (p = 0.014). The VO(2)/W slope increased above the VT (+ 27%, p = 0.0017) in both normal subjects and patients with CHF, suggesting a decrease in efficiency above the VT. There was an inverse correlation (r = 0.646, p < 0.0001) between exercise VO(2)/W and recovery VO(2)/W, implying that subjects with a low exercise VO(2)/W were not efficient but rather accumulated a large oxygen debt that was repaid following completion of exercise. CONCLUSIONS: Heart failure is associated with lower exercise VO(2)/W; however, the patient with heart failure is not efficient, but rather accumulating a large oxygen debt (recovery VO(2)/W) that is repaid following exercise. In addition, the work VO(2)/W (including both exercise and recovery) is increased in patients with heart failure in comparison to control subjects, and correlates inversely with the percentage of predicted VO(2). The large recovery VO(2)/W is likely due to impaired oxygen delivery to exercising muscle during exercise. The increase in the work VO(2)/W is probably due to changes in skeletal muscle fiber type that occur in patients with heart failure (type I to type IIb).

Adult↗

Separation optimization for the recovery of phenyl ethyl alcohol.

Phenyl ethyl alcohol is a compound that occurs naturally in flower petals and in many common beverages, such as beer. Desire for the floral, rose-like notes imparted by phenyl ethyl alcohol has created a unique niche for this chemical in flavor and fragrance industries. Phenyl ethyl alcohol can be produced by Saccharomyces cerevisiae via bioconversion. Often this method of production results in extremely low yields, thus placing a great deal of importance on recovery and purification of the valuable metabolite. To determine the best method for recovering the chemical, a primary recovery step and a secondary recovery step were developed. The primary recovery step consisted of comparing dead-end filtration with crossflow ultrafiltration. Crossflow ultrafiltration was ultimately selected to filter the fermentation broth because of its high flow rates and low affinity for the product. The secondary recovery step consisted of a comparison of liquid- liquid extraction and hydrophobic resin recovery. The hydrophobic resin was selected because of its higher rate of recovery and a higher purity than the liquid-liquid extraction, the current practice of Brown-Forman.

Journal Article↗

The importance of plasma free insulin and counterregulatory hormones for the recovery of blood glucose following hypoglycaemia in type 1 diabetics.

After induction of hypoglycaemia in 31 Type 1 (insulin-dependent) patients, the 10 patients with the slowest recovery of blood glucose from hypoglycaemia were arbitrarily compared with the 10 patients with the fastest recovery of blood glucose. No differences were found between the two groups regarding response of glucagon to hypoglycaemia, whereas the epinephrine (2-fold), norepinephrine (2.4-fold) and cortisol responses were significantly greater in the group with the slow recovery. The plasma free insulin concentrations were higher (2-fold) in the group with slow recovery from 30 min after stop of insulin and throughout the study. This may be explained by a 3-fold greater amount of insulin binding antibodies in this group compared to the group with fast recovery from hypoglycaemia. An inverse significant correlation was demonstrated between the rates of recovery and the amounts of insulin binding antibodies in all the patients (P less than 0.02). This implicates that enhanced counterregulatory hormone responses in the group with the slow recovery from hypoglycaemia could not compensate for the hypoglycaemic effect of a concomitant higher plasma free insulin concentration. Insulin binding antibodies, acting as a depot of circulating insulin, may be a risk factor of prolonged hypoglycaemia in Type 1 diabetics.

Adolescent↗

Survival and recovery of yeast cells after simultaneous treatment of UV light radiation and heat.

Cell survival, synergistic interaction, liquid-holding recovery (LHR) kinetics and inactivation forms after the simultaneous treatment with UV light (254 nm) and various high temperatures were studied in diploid yeast cells Saccharomyces cerevisiae. The synergistic interaction was observed within a certain temperature range in which there was a temperature that maximizes the synergistic effect. The LHR study revealed that both the extent and the rate of recovery greatly decreased with the increase in exposure temperature. A quantitative approach describing the LHR process as a decrease in the effective radiation dose was used to estimate the probability of recovery per unit time and the irreversible component of damage. Using the experimental data obtained and the mathematical model described, it was shown that the irreversible component, i.e. the fraction of cells incapable of recovery, increased with the exposure temperature, whereas the recovery constant, i.e. the probability of recovery per unit time, was independent of the exposure temperature. The increase in the irreversible component was accompanied by an increase in cell death without postirradiation division. It is concluded based on this that the synergistic interaction of UV light radiation and hyperthermia in yeast cells is not related to the impairment of the recovery process itself and that it may be attributed to an increased yield of the irreversible damage.

Cell Division↗

Tracing recovery from acidification in the western Norwegian Nausta watershed.

A novel method, redundancy analysis (RDA), has been used to examine whether chemical recovery from acidification in the western Norwegian Nausta watershed produces detectable recovery within the community structure of the macro-zoobenthos. The RDA results have been compared with measures of recovery based on the changes detected using highly specialized and regionally defined biological acidity indices. We found that the beginning of biological recovery in the Nausta watershed was recognizable during the period 1989-1998. Recovery occurred in the upper reaches and in the tributaries. The multivariate approach proved to complement the acidity indices approach, and much biological information can be gained by their combined use. The RDA method is conservative, i.e. does not overestimate biological recovery, and it is not geographically constrained as are the acidity indices. We also found that seasonal climatic factors strongly influence the benthic community, and may confound the detection of the biological recovery process.

Acid Rain↗

L-DOPS-Accelerated recovery of locomotor function in rats subjected to sensorimotor cortex ablation injury: pharmacobehavioral studies.

Central norepinephrine (NE) has been shown to play a beneficial role in amphetamine-facilitated recovery of behavior. To give insight into understanding the mechanism, the present studies were conducted to examine (a) the effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) combined with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor) and L-3,4-dihydroxyphenylalanine (L-DOPA), precursors of NE and dopamine (DA), respectively, on the recovery from beam-walking performance deficits in rats subjected to unilateral sensorimotor cortex ablation injury, and (b) the relationships between the behavioral recovery and the frequency of postoperative training and the size of ablation injury. It was found that the combined treatments with L-DOPS and BSZ promoted the recovery of locomotor function as early as 24 hours after injury. L-DOPA alone, however, did not facilitate behavioral recovery. The results of assay for the tissue levels of NE and its major metabolite (3-methoxy-4-hydoxyphenylethylene glycol; MHPG) in the brain using high-pressure liquid chromotography showed MHPG, but not NE, significantly increased in the cerebellum and the hippocampus. The behavioral recovery was also significantly correlated with the frequency of training subsequent to injury, but inversely with the size of cortex ablation. These results suggest that NE is likely to modulate functional recovery in this rodent model.

Animals↗

Na+-dependent recovery of intracellular pH from acid loading in mouse colonic crypt cells.

The membrane transport mechanism for regulating the intracellular pH value (pHi) was investigated in mouse distal colon crypt cells. pHi was measured by microfluorometry in an isolated crypt fragment loaded with the pH-sensitive fluoroprobe, 2',7'-bis-(2-carboxyethyl)-5-(6) carboxyfluorescein. The pHi recovery process after acid loading induced by a 40 mM NH4Cl prepulse was almost totally dependent on Na+ in both the presence and absence of CO2/HCO3- in the perfusion solution. In the CO2/HCO3(-)-free, HEPES-buffered solution, amiloride partially inhibited the pHi recovery rate from acid loading with an ED50 value of 15 microM and maximum inhibition of 83%. In a CO2/HCO3- solution, amiloride inhibited the pHi recovery rate with an ED50 value of 18 microM, which was similar to that in the HEPES-buffered solution, while the rate of pHi recovery remaining in the presence of the maximum effective concentration of amiloride was significantly larger than that in the HEPES-buffered solution. The Na+-dependent pHi recovery from the acid loading was significantly less (by 18%) in the presence of forskolin. These results suggest that the pHi recovery from acid loading was mediated by 1) amiloride-sensitive Na+/H+ exchanger, 2) the amiloride-insensitive Na+/H+ exchanger, and 3) the Na+- and HCO3(-)-dependent acid extruder. The pHi recovery could be inhibited by cAMP.

Amiloride↗

Quantifying population recovery rates for ecological risk assessment.

Ecological effects of modern agrochemicals are typically limited to brief episodes of increased mortality or reduced growth that are qualitatively similar to natural disturbance regimes. The long-term ecological consequences of agrochemical exposures depend on the intensity and frequency of the exposures relative to the rates of recovery of the exposed populations. This paper explores the feasibility of using readily available life history information to quantify recovery rates of aquatic populations. A simple modeling framework based on the logistic population growth model is used to compare population recovery rates for different types of organisms and to evaluate the influence of life history, initial percent reduction, disturbance frequency, and immigration on the time required for populations to recover from simulated agrochemical exposures. Recovery models are developed for aquatic biota ranging in size and longevity from unicellular algae to fish and turtles. Population growth rates and recovery times derived from life history data are consistent with measured recovery times reported in mesocosm and enclosure experiments, thus supporting the use of the models for quantifying population recovery rates for ecological risk assessment.

Agrochemicals↗

An assessment of the role of handling cues in "spontaneous recovery" after extinction.

Three experiments examined the assertion that presession handling cues that accompany training with reinforcement might account for spontaneous recovery when they reoccur following extinction. In Experiment 1, after extensive training on a variable-interval schedule, key pecking in pigeons was extinguished following either normal or distinctively different handling and transportational cues. Those cues resulted in enhanced spontaneous recovery 24 hr later when normal cues were reinstated. In Experiment 2, however, subjects tested following the normal handling cues showed no more spontaneous recovery than did subjects that spent the entire extinction-test interval in the experimental chambers and thus were tested without handling cues altogether. In Experiment 3, a group whose test for recovery began 10 min after being placed in the chambers yielded as much spontaneous recovery as did a group tested normally. Furthermore, a group for which extinction began at mid-session and for which handling therefore could not be a discriminative cue for extinction showed no more spontaneous recovery than did the other two groups. Handling cues thus contributed to spontaneous recovery only after explicit discrimination training, as provided in Experiment 1.

Journal Article↗

Rheumatoid arthritis of the cervical spine. A long-term analysis with predictors of paralysis and recovery.

We analyzed the cases of seventy-three patients who were managed over a twenty-year period for rheumatoid involvement of the cervical spine and were followed for a minimum of two years, with an average follow-up of seven years. A neurological deficit did not develop in thirty-one patients (Ranawat et al. Class I) and paralysis developed in the remaining forty-two patients: Class II in eleven and Class III in thirty-one. Of the forty-two patients in whom paralysis developed, thirty-five had operative stabilization. Seven patients were managed with a soft cervical collar because they refused or were medically unable to have the operation; all of the had an increase in the severity of the paralysis. The posterior atlanto-odontoid interval and the diameter of the subaxial sagittal canal measured on the cervical radiographs demonstrated statistically significant correlations with the presence and severity of paralysis. All of the patients who had a Class-III neurological deficit had a posterior atlanto-odontoid interval or diameter of the subaxial canal that was less than fourteen millimeters. In contrast, the anterior atlanto-odontoid interval, which has traditionally been reported, did not correlate with paralysis. The prognosis for neurological recovery following the operation was not affected by the duration of the paralysis but was influenced by the severity of the paralysis at the time of the operation. The most important predictor of the potential for neurological recovery after the operation was the preoperative posterior atlanto-odontoid interval. In patients who had paralysis due to atlanto-axial subluxation, no recovery occurred if the posterior atlanto-odontoid interval was less than ten millimeters, whereas recovery of at least one neurological class always occurred when the posterior atlanto-odontoid interval was at least ten millimeters. If basilar invagination was superimposed, clinically important neurological recovery occurred only when the posterior atlanto-odontoid interval was at least thirteen millimeters. All patients who had paralysis and a posterior atlanto-odontoid interval or diameter of the subaxial canal of fourteen millimeters had complete motor recovery after the operation. In this series, although only patients who had a neurological deficit were operated on, we observed the range of the posterior atlanto-odontoid interval that was associated with poor or no recovery after the operation, and we identified the safe range on the basis of the patients in whom paralysis did not develop.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Transplantation of preconditioned schwann cells in peripheral nerve grafts after contusion in the adult spinal cord. Improvement of recovery in a rat model.

BACKGROUND: Recovery after injury to the peripheral nervous system is based on the pro-regenerative relationship between axons and the extracellular matrix, a relationship established by Schwann cells. As mechanical conditioning of Schwann cells has been shown to stimulate their regenerative behavior, we sought to determine whether transplantation of these cells to the central nervous system (i.e., the spinal cord), with its limited regenerative capacity after injury, would improve axonal regeneration and functional recovery. METHODS: A moderate contusion injury of the spinal cord was created with a force-directed impactor in forty-eight adult Sprague-Dawley rats, and, at one week postinjury, the spinal cords were reexposed in all animals. In twenty-four of these animals, peripheral nerve grafts with Schwann cells that had been obtained from the sciatic nerves of donor animals, and had been either untreated or subjected to mechanical conditioning, were transplanted to the contused area of the cords following resection of the glial scar. Another group of animals was treated with glial scar excision only, and a fourth group had the contusion injury but neither glial excision nor transplantation. Scores according to the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale were assigned preoperatively and weekly thereafter. Tract tracing of descending and ascending spinal cord tracts was performed at six weeks postoperatively for quantitative histological evaluation of axonal regeneration. RESULTS: While the recovery following glial scar excision without peripheral nerve transplantation was significantly worse than the recovery in the other groups, both transplantation groups had significantly higher BBB scores than the controls (no transplantation) in the early postoperative period (p < 0.05). Moreover, histological analysis showed markedly increased axonal regeneration at the lesional sites in the animals treated with the mechanically conditioned grafts than in the other groups (p < 0.05). CONCLUSIONS: Functional recovery after spinal cord contusion improved following glial scar excision with transplantation of Schwann cells in peripheral nerve grafts to the contusion areas. Although recovery did not differ significantly between the transplantation groups, only the preconditioned grafts led to axonal regeneration at and past the lesional site. These grafts may further enhance functional recovery as the descending tracts eventually reach their target end-organs.

Animals↗

Single-shot inversion recovery TrueFISP for assessment of myocardial infarction.

OBJECTIVE: The aim of the study was to assess the diagnostic accuracy of imaging the myocardium with a fast multislice inversion recovery 2D single-shot true fast imaging with steady-state precession (trueFISP) sequence during a single breath-hold in comparison with an established segmented inversion recovery turbo fast low-angle shot (turboFLASH) sequence. SUBJECTS AND METHODS: Forty-three patients with myocardial infarction were examined on a 1.5-T MR system 10 min after administration of contrast material (gadodiamide, 0.2 mmol/kg) with a single-shot 2D multislice technique (single-shot inversion recovery trueFISP) that allows one to image the entire short axis during one breath-hold (18 heartbeats) and with a segmented 2D single-slice technique (inversion recovery turboFLASH) that requires one breath-hold per slice (12 heartbeats). Signal intensity was determined in normal myocardium, in infarcted myocardium, and in the left ventricle. The contrast-to-noise ratio (CNR) of normal and infarcted myocardium was determined. The areas of hyperintense infarctions on selected slices and the entire volumes were compared for both sequence techniques. RESULTS: The inversion recovery trueFISP sequence has a lower CNR than the inversion recovery turboFLASH sequence (mean values, 10.0 vs 12.9, respectively; p = 0.005) for differentiation of viable from nonviable myocardium. The CNR of injured myocardium and blood in the left ventricular cavity also has a lower value for the multislice technique compared with the single-slice technique (0.6 vs 1.2, respectively; p = 0.045). Assessment of the area of infarction within one slice (r = 0.97, p < 0.002) and of the volume of the entire infarction (r = 0.96, p < 0.003) is possible with excellent correlation of both techniques. CONCLUSION: Despite having a lower CNR, the inversion recovery 2D single-shot trueFISP sequence allows fast and accurate identification of the area and volume of infarction with high spatial resolution within a single breath-hold.

Adult↗

Changes in recovery-stress state and performance in elite rowers during preparation for major competitions.

This study investigated changes in the perceived recovery-stress state and performance in 6 highly trained Estonian rowers preparing for major competitions and representing Estonia in double sculls (age: M = 23.0, SD = 1.4 yr.; height: M = 198.0, SD = 0.0 cm; body mass: M = 97.1, SD = 6.4 kg), and quadruple sculls (age: M = 21.5, SD = 2.5 yr.; height: M = 189.5, SD = 5.4 cm; body mass: M = 90.9, SD = 4.8 kg). The subjects were training regularly and had been doing so for the last 10.5 yr. (double scullers, SD = 2.1 yr.) and 7.5 yr. (quadruple scullers, SD = 3.1 yr.), respectively. The Recovery-Stress Questionnaire for Athletes of Kellmann and Kallus was given two days before World Cup competitions. Standardized Stress and Standardized Recovery scores and RESTQ-Index were computed. In addition, resting cortisol in blood was measured at the same time. The performance of both boat classes constantly decreased from World Cup 1 to World Cup 3 as indicated by percent losses for winning boats. Resting cortisol and RESTQ-Index increased and decreased, respectively, at the same time. For double scullers, a decrease in RESTQ-Index mainly reflected the large decrease in the Standardized Recovery score. A decrease in RESTQ-Index was mainly based on a large increase in the Standardized Stress score for rowers performing in a quadruple scull. Present results indicate that the recovery-stress state affects performance of rowers in international competitions. RESTQ-Index could be used as the athletes' resource measure, while the Standardized Stress and Standardized Recovery scores reflect the athletes' extent of stress and recovery separately.

Achievement↗

The role of work in the recovery of persons with psychiatric disabilities.

This study explored the role of work in the recovery of employed and unemployed persons with psychiatric disabilities. Fourteen persons with psychiatric disabilities participated in semi-structured interviews. Content analysis revealed that the experience of recovery was based on six major dimensions: self-definition, empowerment, connections to others, meaning of work, vocational future, and meaning of recovery. Differences in these six dimensions led to the identification of three profiles of recovery: recovery as uncertain, recovery as a self-empowering experience, and recovery as a challenging experience. Each profile described a specific context in which participation in work or avoidance of work can be understood and vocational interventions can be designed.

Adult↗

Immunochemical studies of substance P and cholecystokinin octapeptide recovery in dorsal horn following unilateral lumbosacral ganglionectomy.

Deafferentation of the cat lumbosacral dorsal horn following unilateral ganglionectomy (L2-S3) produced an ipsilateral depletion of substance P (sP) and cholecystokinin octapeptide (CCK) immunoreactivity (IR). The loss of sP IR and CCK IR was most marked at 11 days postlesion, and partial recovery of sP IR and CCK IR was noted in the upper laminae of the dorsal horn ipsilateral to the lesion 14 days after deafferentation. The dorsal horn sP IR and CCK IR distribution and density of staining on the deafferented side were indistinguishable from those on the control side 1 month after ganglionectomy. The pattern and density of methionine-enkephalin (M-ENK) IR was not disrupted by deafferentation, demonstrating that the sP IR and CCK IR depletions were due to the deafferentation and not to nonselective vascular damage. The recovery of sP IR and CCK IR was not affected by midline myelotomy or thoracic cord transections, implying a local origin for the recovered sP IR and CCK IR. Moreover, capsaicin, a primary afferent neurotoxin, depleted sP IR and CCK IR only from the intact side. Thus, these studies indicate that the recovery of two immunochemically identified primary afferent transmitters in the dorsal horn does not involve intraspinal sprouting of primary afferents. Radioimmunoassay (RIA) analysis of the ganglionectomies followed by recovery periods ranging from 7 to 28 days confirmed the depletion and recovery of sP IR, but the RIA indicated a temporal shift in depletion and recovery. Maximal depletion was measured at 21 days and recovery was observed at 28 days after unilateral deafferentation.

Afferent Pathways↗

Metabolic syndrome is associated with delayed heart rate recovery after exercise.

Heart rate (HR) recovery after exercise is a function of vagal reactivation, and its impairment is a predictor of overall mortality and adverse cardiovascular events. While metabolic syndrome is associated with sympathetic overactivity, little is known about the relationship between metabolic syndrome and HR recovery. A symptom-limited exercise stress test in healthy subjects (n=1, 434) was used to evaluate HR recovery. Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP-III) criteria. Seventeen percent of subjects had > or =3 criteria for metabolic syndrome. HR recovery was lower in men than women and in smokers than nonsmokers. The subject with metabolic syndrome (vs. without) showed lower HR recovery (10.3+/-11.6 vs. 13.6+/-9.7 per minute) and higher resting HR (64.3+/-10.3 vs. 61.6+/-9.1 per minute). HR recovery correlated inversely to age (r=-0.25, p<0.0001), but not to resting HR or maximal oxygen uptake. Delayed HR recovery was associated with metabolic syndrome after an adjustment for age, sex, resting HR and smoking (p<0.01). Metabolic syn-drome is associated with impaired vagal reactivation. Adverse cardiovascular out-comes associated with metabolic syndrome may be mediated by the failure of vagal reactivation in addition to sympathetic overactivity.

Adult↗

Development of methods for the recovery of Escherichia coil O157:H7 and Salmonella from beef carcass sponge samples and bovine fecal and hide samples.

Culture methods were developed for the concurrent recovery of Escherichia coli O157:H7 and Salmonella from bovine carcass, hide, and fecal samples. Several enrichment conditions were tested for the overall growth of pure cultures; tryptic soy broth for 2 h at 25 degrees C and then for 6 h at 42 degrees C was the protocol selected for use. Immunomagnetic separation (IMS) was incorporated for sensitivity and selectivity, along with a post-IMS enrichment for the recovery of Salmonella as recommended by the manufacturer. Selective agars for plating after IMS were chosen on the basis of ease of target colony identification. Sorbitol MacConkey agar supplemented with cefixime and potassium tellurite and Rainbow agar supplemented with novobiocin and potassium tellurite were chosen for the recovery of E. coli O157:H7. Brilliant green agar with sulfadiazine and Hektoen enteric agar supplemented with novobiocin were selected for the recovery of Salmonella. The resulting methods were evaluated along with standard or previously used methods for the recovery of E. coli O157:H7 and Salmonella from bovine hide and fecal samples and carcass sponge samples. The Meats Research Unit (MRU) methods performed at least as well as the established methods, except that a secondary enrichment in tetrathionate (TT) broth prior to IMS was required for the optimal recovery of Salmonella from feces. Thus, the MRU and MRU-TT methods are effective in the recovery of both E. coli O157:H7 and Salmonella from a single bovine carcass, hide, or fecal sample.

Agar↗

[Study on analysis of viscoelastic property of palatal mucoperiosteum--about the creep recovery].

The purpose of this study was to analyze the creep phenomena of the palatal mucosa under pressure and after pressure release. The measuring device consisted of the control box, which regulated the loading force by air pressure, and the pick-up, which was fixed to the teeth and applied the load onto the mucosa, detected the displacement of the mucosa. The creep was analyzed by the Voigt 4 element model. The ratio of the recovery (S1'/S1, S2'/S2) and the recovery percentage were analyzed on the creep after the pressure release and evaluated from the point of expressing exactly the viscoelastic recovery. The results were as follows: 1. Both the amount of the displacement under pressure and the recovery of the palatal mucosa showed the least value at the center site and at the other sites less at the distal site than the mesial site. 2. The ratio of S1'/S1 was about 0.5 at all sites. On the other hand, the ratio of S2'/S2 showed values higher than 1 except at the center site and was significantly different among the other sites. 3. It was pointed out that the recovery percentage was more suitable than the ratio of the recovery to explain the viscoelastic recovery of the palatal mucosa.

Adult↗