Biomedical subjects

J R Schultz

Publications and source records attributed to J R Schultz.

At least 19 recordsLinked to original sources

PubMed1998

Hepatic lipase affects both HDL and ApoB-containing lipoprotein levels in the mouse.

Transgenic mice were created overproducing a range of human HL (hHL) activities (4-23-fold increase) to further examine the role of hepatic lipase (HL) in lipoprotein metabolism. A 5-fold increase in heparin releasable HL activity was accompanied by moderate (approx. 20%) decreases in plasma total and high density lipoprotein (HDL) cholesterol and phospholipid (PL) but no significant change in triglyceride (TG). A 23-fold increase in HL activity caused a more significant decrease in plasma total and HDL cholesterol, PL and TG (77%, 64%, 60%, and 24% respectively), and a substantial decrease in lipoprotein lipids amongst IDL, LDL and HDL fractions. High levels of HL activity diminished the plasma concentration of apoA-I, A-II and apoE (76%, 48% and 75%, respectively). In contrast, the levels of apoA-IV-containing lipoproteins appear relatively resistant to increased titers of hHL activity. Increased hHL activity was associated with a progressive decrease in the levels and an increase in the density of LpAI and LpB48 particles. The increased rate of disappearance of 125I-labeled human HDL from the plasma of hHL transgenic mice suggests increased clearance of HDL apoproteins in the transgenic mice. The effect of increased HL activity on apoB100-containing lipoproteins was more complex. HL-deficient mice have substantially decreased apoB100-containing low density lipoproteins (LDL) compared to controls. Increased HL activity is associated with a transformation of the lipoprotein density profile from predominantly buoyant (VLDL/IDL) lipoproteins to more dense (LDL) fractions. Increased HL activity from moderate (4-fold) to higher (5-fold) levels decreased the levels of apoB100-containing particles. Thus, at normal to moderately high levels in the mouse, HL promotes the metabolism of both HDL and apoB-containing lipoproteins and thereby acts as a key determinant of plasma levels of both HDL and LDL.

Animals↗

PubMed1998

Analysis of water from the Space Shuttle and Mir Space Station by ion chromatography and capillary electrophoresis.

Drinking water and condensate samples collected from the US Space Shuttle and the Russian Mir Space Station are analyzed routinely at the NASA-Johnson Space Center as part of an ongoing effort to verify water quality and monitor the environment of the spacecraft. Water quality monitoring is particularly important for the Mir water supply because approximately half of the water consumed is recovered from humidity condensate. Drinking water on Shuttle is derived from the fuel cells. Because there is little equipment on board the spacecraft for monitoring the water quality, samples collected by the crew are transported to Earth on Shuttle or Soyuz vehicles, and analyzed exhaustively. As part of the test battery, anions and cations are measured by ion chromatography, and carboxylates and amines by capillary electrophoresis. Analytical data from Shuttle water samples collected before and after several missions, and Mir condensate and potable recovered water samples representing several recent missions are presented and discussed. Results show that Shuttle water is of distilled quality, and Mir recovered water contains various levels of minerals imparted during the recovery processes as designed. Organic ions are rarely detected in potable water samples, but were present in humidity condensate samples.

Chromatography, Ion Exchange↗

PubMed1998

Yeast Clk-1 homologue (Coq7/Cat5) is a mitochondrial protein in coenzyme Q synthesis.

Mutations in the clk-1 gene result in slower development and increased life span in Caenorhabditis elegans. The Saccharomyces cerevisiae homologue COQ7/CAT5 is essential for several metabolic pathways including ubiquinone biosynthesis, respiration, and gluconeogenic gene activation. We show here that Coq7p/Cat5p is a mitochondrial inner membrane protein directly involved in ubiquinone biosynthesis, and that the defect in gluconeogenic gene activation in coq7/cat5 null mutants is a general consequence of a defect in respiration. These results obtained in the yeast model suggest that the effects on development and life span in C. elegans clk-1 mutants may relate to changes in the amount of ubiquinone, an essential electron transport component and a lipid soluble antioxidant.

Amino Acid Sequence↗

PubMed1998

Classifying complex pediatric feeding disorders.

BACKGROUND: This study defines the multiple characteristics associated with complex pediatric feeding problems and determines the relative frequency of each classification in a population referred to an interdisciplinary feeding team. METHODS: The written reports from team evaluations on 103 children (64 males, 39 females; age range 4 months to 17 years) were reviewed. Prematurity and/or presence of developmental delay was coded. Identified factors related to current feeding problems were coded according to five categories: structural abnormalities, neurological conditions, behavioral issues, cardiorespiratory problems, metabolic dysfunction. RESULTS: Interrater reliability for the classification coding was 88%. Thirty-eight percent of the children had a history of pre- maturity and 74% were reported to have evidence of developmental delay. The following five categories or combinations were coded most frequently: structural-neurological-behavioral (30%), neurological-behavioral (27%), behavioral (12%), structural-behavioral (9%), and structural-neurological (8%). Overall, behavioral issues were coded more often (85%) than neurological conditions (73%), structural abnormalities (57%), cardiorespiratory problems (7%), or metabolic dysfunction (5%). CONCLUSIONS: Data analysis using this classification system revealed that the majority of children in this sample had a behavioral component to their complex feeding problem, regardless of concurrent physical factors. These findings suggest that complex pediatric feeding problems are biobehavioral conditions in which biological and behavioral aspects mutually interact, and both need to be addressed to achieve normal feeding.

Adolescent↗

PubMed1998

Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study.

OBJECT: Cigarette smoking is associated with aneurysmal subarachnoid hemorrhage (SAH) and subsequent vasospasm. The purpose of this study was to quantify this association. METHODS: Nearly 3500 patients with SAH from North America and Europe have been enrolled in five different multicenter, controlled studies coordinated at the Neuroclinical Trials Center of the Virginia Neurological Institute at the University of Virginia. Among the prospective data gathered were whether the patient smoked at the time of their most recent SAH and the evolution of angiographic vasospasm. The rate of smoking in the patients enrolled in the studies was compared with the expected rate by using a chi-square statistic adjusted for age and gender, in the general population in the United States (U.S.) and Europe. In virtually all age and gender subgroups, and for the combined populations in the five clinical trials, patients with SAH reported current smoking rates 2.5 times higher than expected based on U.S. and European national surveys (p < 0.0001). Cigarette smoking was also associated with younger age at onset of SAH (5-10 years, p < 0.0001) and increased incidence of clinically confirmed vasospasm (p < 0.005). CONCLUSIONS: The findings of a significantly increased representation of current cigarette smokers in the study populations and significant association with younger age at the time of SAH and increased incidence of vasospasm concur with recent reports of smoking as a significant risk factor for ruptured aneurysms and subsequent vasospasm.

Adolescent↗

PubMed1997

Sexual behavior of HIV-seropositive young men with congenital coagulopathies. Hemophilia Behavioral Intervention Projects (HBIEP) Study Group.

PURPOSE: To describe the self-reported sexual behaviors of human immunodeficiency virus (HIV)-seropositive youths with congenital coagulopathies in order to guide the development of interventions to prevent secondary transmission. SUBJECTS: A total of 297 HIV-seropositive males, 12-24 years of age, were sampled from 11 hemophilia treatment centers and 28 affiliated subsites. METHODS: Review of clinical records and self-administered survey of HIV-related knowledge, attitudes and behaviors. Subjects were classified and compared by self-reported sexual behavior over the lifetime and the prior 6 months into five mutually exclusive groups (G1-5). RESULTS: A total of 42% of subjects were virgins who never had oral, vaginal, or rectal sex (G1); 10% were nonvirgins who had abstained (G2); 13% were virgins and nonvirgins who had intimate touch only (G3); 21% had intercourse and always used condoms (G4); and 13% had had unsafe intercourse (G5). Among the groups, G5 was the oldest, least likely to forego sex, most angry and anxious when reminded of HIV, and most reluctant to disclose serostatus to friends. CONCLUSIONS: Most subjects (87%) had safer sex or abstained in the last 6 months. A relatively small group of HIV-seropositive youth with bleeding disorders were engaged in unprotected intercourse and in need of intensive help with HIV risk reduction.

Adolescent↗

PubMed1997

Diacylglycerol is the preferred substrate in high density lipoproteins for human hepatic lipase.

The hydrolysis of HDL phospholipids (PL) and glycerides by hepatic lipase (HL) has been investigated in native and reconstituted HDL particles (Lp2A-I). Fasting, normolipidemic HDL exhibit total lipid hydrolytic rates of between 10 and 36 nM FA/h per microM PL. Of the total fatty acids liberated with HDL3 only 1% are from triolein (TG), while 49% are from diolein (DG) and 50% are from PL. A spherical reconstituted particle containing 2 molecules of apoA-I, 120 molecules of PL, and 20 molecules of TG exhibits a total lipid hydrolytic rate of 18 nM FA/h per microM PL and 93% of the fatty acids liberated are from PL. Inclusion of 40 molecules of TG into the Lp2A-I particle doubles the rate of fatty acid hydrolysis by HL through a stimulation of TG hydrolysis. Further addition of 10 molecules of DG to the Lp2A-I complex has no effect on the overall rates of hydrolysis, but changes the substrate specificity, wherein 61% of the fatty acids are from DG and both TG and PL hydrolytic rates are significantly reduced. Increasing the amount of DG in the Lp2A-I particle further stimulates total lipid hydrolysis by raising DG hydrolytic rates at the expense of PL and TG hydrolysis. A particle containing 10 molecules of TG and 40 molecules DG yields the fastest lipid hydrolytic rate of 143 nM FA/h per microM PL, which constitutes 96% DG hydrolysis, 3% TG hydrolysis, and 1% PC hydrolysis. These data indicate that hepatic lipase acts primarily as a surface lipid lipase with HDL particles. DG is the preferred substrate of HL in HDL and the HDL-DG content regulates the hydrolysis of both PL and TG by HL.

Carbon Radioisotopes↗

PubMed1996

Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.

Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.

Antioxidants↗

PubMed1996

Autoxidation of ubiquinol-6 is independent of superoxide dismutase.

Ubiquinone (Q) is an essential, lipid soluble, redox component of the mitochondrial respiratory chain. Much evidence suggests that ubiquinol (QH2) functions as an effective antioxidant in a number of membrane and biological systems by preventing peroxidative damage to lipids. It has been proposed that superoxide dismutase (SOD) may protect QH2 form autoxidation by acting either directly as a superoxide-semiquinone oxidoreductase or indirectly by scavenging superoxide. In this study, such an interaction between QH2 and SOD was tested by monitoring the fluorescence of cis-parinaric acid (cPN) incorporated phosphatidylcholine (PC) liposomes. Q6H2 was found to prevent both fluorescence decay and generation of lipid peroxides (LOOH) when peroxidation was initiated by the lipid-soluble azo initiator DAMP, dimethyl 2,2'-azobis (2-methylpropionate), while Q6 or SOD alone had no inhibitory effect. Addition of either SOD or catalase to Q6H2-containing liposomes had little effect on the rate of peroxidation even when incubated in 100% O2. Hence, the autoxidation of QH2 is a competing reaction that reduces the effectiveness of QH2 as an antioxidant and was not slowed by either SOD or catalase. The in vivo interaction of SOD and QH2 was also tested by employing yeast mutant strains harboring deletions in either CuZnSOD and/or MnSOD. The sod mutant yeast strains contained the same percent Q6H2 per cell as wild-type cells. These results indicate that the autoxidation of QH2 is independent of SOD.

Animals↗

PubMed1996

Neurodevelopmental outcome of infants with viral meningitis in the first three months of life.

We prospectively evaluated the neurodevelopmental outcome of infants with documented viral meningitis to determine (1) whether deficits in physical growth, development, speech and language, hearing, or intelligence occur; and (2) if so, at what age these deficits can be detected. Sixteen infants with documented enteroviral meningitis under the age of 90 days and a control group of 13 patients matched for age, race, sex, and socioeconomic status were followed up prospectively for 3 years with annual evaluations, which included a developmental evaluation by a pediatric developmentalist, articulation and language tests by a speech-language pathologist (Sequenced Inventory of Communication Development, Receptive-Expressive Emergent Language Scale (REEL), Preschool Language Scale (PLS), Revised Peabody Picture Vocabulary Test (PPVT-R), Photo Articulation Test, audiometric screening), and intelligence tests by a psychometrist (Bayley Scales of Infant Development [BSID] and Stanford-Binet). No deficits were demonstrated in growth, development, hearing, BSID, articulation, and expressive language. Subtle but significant (P < 0.05) deficits were documented in the study group compared with the control group in the receptive component of the REEL, all subsections of the PLS, the PPVT-R, and the verbal comprehension/language-processing section (Factor II) of the Stanford-Binet. These differences could be reliably detected by 3 years of age. We conclude that viral meningitis in young infants may cause subtle deficits in language skills, particularly receptive language. We recommend that children who have had enteroviral meningitis during early infancy be monitored carefully for language development and, perhaps, receive increased language stimulation in the home prior to school entry in order to optimize their learning potential.

Analysis of Variance↗

PubMed1995

HIV-infected adolescents with hemophilia: adaptation and coping. The Hemophilia Behavioral Intervention Evaluation Project.

OBJECTIVE: It is estimated that 70% of individuals with factor VIII deficiency hemophilia who received blood products before 1985 are infected with human immunodeficiency virus (HIV). The goal of the current study was to assess how adolescents with hemophilia cope with reminders of their HIV status, because adaptation is likely to have implications for these individuals' quality of life and adherence to safer sex recommendations. METHODS: Participants included 297 HIV-positive adolescents with hemophilia who were recruited from 11 sites across the United States. Adolescents reported on the use and effectiveness of strategies for coping with reminders of their HIV status. RESULTS: A significant degree of distress was reported in response to such reminders, with anger being the most commonly reported emotion. Although a wide variety of coping strategies had been tried, participants reported using resignation (80.9%), self-calming (78.8%), and distraction (76.4%) most frequently in their attempts to cope with reminders of HIV. Self-blame (3.6%), engaging in risky behaviors (22.2%), thinking about sex (25.4%), and drug/alcohol use (29.1%) were used least. These adolescents tended to rate more active cognitive and behavioral coping strategies (eg, cognitive restructuring, seeking social support, physical activity) as most effective, whereas passive strategies (eg, wishful thinking, blaming others) were reported to be least helpful. Those individuals who reported being distressed by reminders of HIV endorsed most of the coping strategies significantly more often than the nondistressed group, although ineffective strategies were commonly chosen. Sexually active adolescents were more likely than their abstinent peers to cope by thinking about sex, engaging in risky behaviors, or using alcohol and drugs. CONCLUSION: In this population of adolescents who have known their serostatus for several years, distress about everyday reminders of HIV appears to be associated with ineffective coping strategies.

Adaptation, Psychological↗

PubMed1994

The properties of HDL in genetically engineered mice.

Genes involved in HDL structure and metabolism have been overexpressed through the introduction of transgenes or inactivated by gene targeting in mice. These new experimental substrates make it possible to address hypotheses relevant to the biology of HDL that were previously inaccessible through human studies. The in-vivo studies performed to date with these engineered mice have provided insight into structural determinants of HDL, uncovered interactions between proteins that act on HDL and clarified the role that HDL-associated proteins play in atherosclerosis. Further use of these animals, coupled with the development of new engineered lines of mice, should help unravel many questions associated with the in-vivo biological properties and metabolism of HDL.

Animals↗

PubMed1993

Protein composition determines the anti-atherogenic properties of HDL in transgenic mice.

High-density lipoprotein (HDL) contains two major proteins, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), comprising about 70% and 20% of the total HDL protein mass, respectively. HDL exists in human plasma in two main forms, one containing apoA-I with apoA-II (AI/AII-HDL) and another containing apoA-I without apoA-II (AI-HDL). A strong inverse relationship exists between total plasma HDL concentration and atherosclerosis, but the results of studies examining the relationship between AI-HDL and AI/AII-HDL and atherosclerosis have been conflicting. To determine whether these two HDL populations have different effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis-susceptible strain. Following an atherogenic diet, despite similar total cholesterol and HDL cholesterol concentrations, the area of atherogenic lesions in the AI/AII mice was 15-fold greater than in the AI animals. These studies show that the protein composition of HDL significantly affects its role in atherogenesis and that AI-HDL is more antiatherogenic than AI/AII-HDL.

Animals↗

PubMed1993

Hypokalemia and anesthetic implications.

Reductions in serum potassium influence myocardial cell excitability by increasing membrane potential, diastolic depolarization, duration of refractory period and action potential, and decreasing conduction velocity. Disturbances in electrolyte balance typically involve alterations in two or more cations whose effects can be additive or antagonist. Serum magnesium and calcium have been demonstrated to influence the electrophysiologic effects of potassium imbalances. The arrhythmogenic potential of hypokalemia is thought to result from electrical inhomogeneity, alterations in conduction, changes in automaticity and disturbances in sodium pump kinetics. Potassium balance is maintained by two separate, yet interrelated, systems: distribution and the balance between intake and excretion. Cell wall integrity, osmolality, hormones and acid-base balance influence the relative concentrations of potassium between the intracellular and extracellular compartments. Renal excretion is the major route of elimination and is affected by acid-base balance, potassium and sodium intake, urinary flow rates and mineralocorticoid states. Serum potassium is not an accurate reflection of total body potassium stores. Acute hypokalemia differs from chronic, for the former results in a change in only the serum potassium concentration, whereas the latter is accompanied by a reduction in both the total body stores and serum levels. The importance of intracellular and extracellular concentrations lies in their determination of the resting membrane potential and, therefore, membrane excitability. Although experimental studies have demonstrated an association between ventricular ectopy and hypokalemia, the clinical studies to date have reported conflicting results. The arrhythmogenic role of hypokalemia has been examined in ambulatory hypertensive patients with acute myocardial infarctions and those with magnesium deficiencies, the results of which have been difficult to interpret because of differences in study design, durations, and characteristics of study population. During general anesthesia, both experimental and clinical studies have failed to demonstrate an increase in the incidence of ventricular ectopy in hypokalemic patients. The common practice of acute repletion therapy or cancellation is not warranted based on the studies to date. Repletion therapy is neither inexpensive nor benign. In one study of 4921 hospitalized patients, the frequency of dangerous complications of oral and/or intravenous potassium therapy was approximately 1 in 175. Certain patients are susceptible to hyperkalemia, so commonly prescribed medication can promote elevations in serum potassium including indomethacin, amiloride, beta-adrenergic blocking agents, and angiotensin-converting enzyme inhibitors. Evaluation of hypokalemia should include identification of the etiology precipitating the electrolyte imbalance. Examinations should include the duration and severity of the depletion, history of past and present illness, current medications, and the presence of concurrent electrolyte disturbances.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmias, Cardiac↗

PubMed1992

Expression of human apolipoprotein A-II and its effect on high density lipoproteins in transgenic mice.

Apolipoproteins A-I and A-II comprise approximately 70 and 20%, respectively, of the total protein content of HDL. Evidence suggests that apoA-I plays a central role in determining the structure and plasma concentration of HDL, while the role of apoA-II is uncertain. To help define the function of apoA-II and determine what effect increasing its plasma concentration has on HDL, transgenic mice expressing human apoA-II and both human apoA-I and human apoA-II were produced. Human apoA-II mRNA is expressed exclusively in the livers of transgenic animals, and the protein exists as a dimer as it does in humans. High level expression of human apoA-II did not increase HDL concentrations or decrease plasma concentrations of murine apoA-I and apoA-II in contrast to what was observed in mice overexpressing human apoA-I. The primary effect of overexpressing human apoA-II was the appearance of small HDL particles composed exclusively of human apoA-II. HDL from mice transgenic for both human apoA-I and human apoA-II displayed a unique size distribution when compared with either apoA-I or apoA-II transgenic mice and contain particles with both these human apolipoproteins. These results in mice, indicating that human apoA-II participates in determining HDL size, parallel results from human studies.

Animals↗

PubMed1991

Small differences in Drosophila tropomyosin expression have significant effects on muscle function.

The effects of promoter deletions on Drosophila tropomyosin I (TmI) gene expression have been determined by measuring TmI RNA levels in transformed flies. Decreases in RNA levels have been correlated with rescue of flightless and jumpless mutant phenotypes in Ifm(3)3 mutant transformed flies and changes in muscle ultrastructure. The results of this analysis have allowed us to identify a region responsible for 20% of maximal TmI expression, estimate threshold levels of TmI RNA required for indirect flight and jump muscle function, and obtain evidence suggesting that sarcomere length may be an important determinant of flight muscle function.

Animals↗

PubMed1991

A muscle-specific intron enhancer required for rescue of indirect flight muscle and jump muscle function regulates Drosophila tropomyosin I gene expression.

The control of expression of the Drosophila melanogaster tropomyosin I (TmI) gene has been investigated by P-element transformation and rescue of the flightless and jumpless TmI mutant strain, Ifm(3)3. To localize cis-acting DNA sequences that control TmI gene expression, Ifm(3)3 flies were transformed with P-element plasmids containing various deletions and rearrangements of the TmI gene. The effects of these mutations on TmI gene expression were studied by analyzing both the extent of rescue of the Ifm(3)3 mutant phenotypes and determining TmI RNA levels in the transformed flies by primer extension analysis. The results of our analysis indicate that a region located within intron 1 of the gene is necessary and sufficient for directing muscle-specific TmI expression in the adult fly. This intron region has characteristics of a muscle regulatory enhancer element that can function in conjunction with the heterologous nonmuscle hsp70 promoter to promote rescue of the mutant phenotypes and to direct expression of an hsp70-Escherichia coli lacZ reporter gene in adult muscle. The enhancer can be subdivided further into two domains of activity based on primer extension analysis of TmI mRNA levels and on the rescue of mutant phenotypes. One of the intron domains is required for expression in the indirect flight muscle of the adult. The function of the second domain is unknown, but it could regulate the level of expression or be required for expression in other muscle.

Animals↗

PubMed1983

Timing of elective hypospadias repair in children.

Psychological concerns for the timing of medical procedures on children result from the longstanding realization that events and behavioral patterns of childhood have wide-ranging effects on the later behavior of the adult. A review of the literature regarding the effects of surgery on psychological development is presented. Particular reference is made to the impact of genitourinary surgery with specific emphasis on the repair of hypospadias, a congenital anomaly affecting 1:250 to 1:400 live male births. Studies of adults who underwent hypospadias repair as children suggest that they are psychologically different from their peers who did not have this surgery. Specifically, as adults they frequently have sexual difficulty despite erectile competence and they generally occupy less responsible, less competitive, and less independent professions than similarly intelligent cohorts. These findings imply that the experience of hypospadias or its surgical repair may in some way affect psychological development. By examining these experiences in light of emotional and cognitive development and the emergence of body image and sexual identity, predictions for psychologically optimal timing of surgery are made. Importance of the role of the family in the psychological outcome and a discussion of surgical considerations are also provided.

Age Factors↗