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Biomedical subjects

P Froom

Publications and source records attributed to P Froom.

At least 37 records · Page 2Linked to original sources

Effect of exposure to lead on postural control in workers.

OBJECTIVES: To examine the effect of lead on postural control of workers who have been exposed to lead. METHODS: 63 Male, lead battery workers mean (SD) age 41.0 (7.4) were compared with 48 age matched male controls after excluding those with acute or chronic diseases. Exposed workers had mean (SD) past blood lead concentrations of 37.5 (9.2) micrograms/dl and 11.2 (5.7) years of employment. Postural control was measured with a computerised postural sway measurement system which measured both sway and total movements. RESULTS: Workers standing straight with eyes open on the bare plates had sway and total movements which were not notably different from controls. On the other hand increased movements were needed in the exposed workers to maintain stability (the general stability quotient 18.2 (5.4) v 15.4 (4.4) in controls, p < 0.01) when standing directly on the foot-plates with closed eyes,, and with the head tilted (15.0 (3.8) v 11.5 (3.0) in controls, p < 0.001). Exposed workers also had a trend for less ability to synchronize anterior posterior and lateral sway in the stress positions (0.0625) than had non-exposed workers. Significant but low correlations were found between the estimate of the chronic internal dose of lead and three of 10 of the postural control measurements, and present lead blood concentrations and only one of the 10 measurements and (r values ranged from 0.21 to 0.31, p < or = 0.03). CONCLUSIONS: These findings suggest that lead affects postural control in asymptomatic workers. Further studies are warranted to find whether workers with decreased postural control are at increased risk of accidents and the relation, if any, of these measurements with subsequent morbidity.

Adult↗

Summer-winter differences in 24 h variability of heart rate.

OBJECTIVE: To examine possible seasonal changes in heart rate variability (HRV). BACKGROUND: Greater than normal mortality from cardiovascular disease (CVD) in the winter has been reported for many countries and might be partly explained by considering seasonal changes in CVD risk factors. Depression of HRV is an independent predictor of arrhythmic complications and of cardiac death, and it is also among the variables that may be affected by the season of the year. METHODS: We compared pairs of 24 h HRV data of 120 healthy men who were examined once in the summer and once in the winter. Multivariate analyses were performed for each dependent variable (HRV indexes) in separate statistical models with age, resting heart rate, serum level of cholesterol, cigarette smoking, body mass index, sports habits, alcohol consumption, systolic blood pressure, physical activity at work, years of education, consumption of energy, and season as the independent variables. RESULTS: Although there were no seasonal differences in mean R-R interval, all indexes of HRV were found to be lower in the summer than they were during winter. Differences and 95% confidence intervals were standard deviation (SD) of coupling intervals between normal beats 12 ms, 6-17 ms; SD of 5 min mean R-R intervals 14 ms, 8-20 ms; mean of all 5 min SD of R-R intervals 2.0 ms, 0.6-2.5 ms; proportion of adjacent R-R intervals differing by > 50 ms 1.5%, 0.6-2.5% and root mean square of the difference between successive normal intervals 3.1 ms, 1.5-4 ms. Multivariate analyses showed that HRV in the winter was less than that in the summer even after adjustment for age, serum level of cholesterol, systolic blood pressure, and body mass index. CONCLUSIONS: HRV indexes of healthy men vary physiologically by season, with lowest values obtained in the winter. Since low HRV is linked to pathologic conditions, the significance of seasonal changes for those suffering from CVD and their possible contribution to the greater mortality rates in winter have to be considered.

Cardiovascular Diseases↗

Stability of common analytes in urine refrigerated for 24 h before automated analysis by test strips.

BACKGROUND: Central outpatient laboratories might find processing large numbers of urinary samples that arrive in the late afternoon inconvenient and refrigerate them overnight before testing. Furthermore, in certain settings clinics might have difficulty assuring that the urine arrives at the laboratory during the same day as the collection. Because the stability of urine samples for delayed automated dipstick analysis (Supertron) is unknown, after defining precision, we retested urines refrigerated for 24 h to determine stability. METHODS: Urinalysis was done twice on the same day and repeated after the sample was refrigerated for 24 h. Combur-10S (Roche Diagnostics) dipsticks were read automatically by a Supertron analyzer. Repeat tests on the same day were compared with tests after storage. RESULTS: Leukocyte esterase had high precision, but after storage approximately 25% of the positive samples were less reactive (P: <0.005). Precision of hemoglobin retests was also high but declined significantly after storage for 24 h. Urine protein values increased after storage. The precision and stability were excellent for nitrites, glucose, and ketones. CONCLUSIONS: The stability of the automated dipstick urinalysis varies with the substance tested. After refrigeration for 24 h, there is a risk of false-positive results for protein, false-negative results for leukocytes and erythrocytes, and little effect on glucose, nitrite, and ketone values.

Autoanalysis↗

Serum total cholesterol and cardiovascular mortality in Israeli males: the CORDIS Study. Cardiovascular Occupational Risk Factor Determination in Israeli Industry.

BACKGROUND: The degree to which serum total cholesterol predicts cardiovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all. OBJECTIVE: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males. METHODS: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality. RESULTS: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P = 0.003). CONCLUSIONS: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.

Adult↗

Adverse work and environmental conditions predict occupational injuries. The Israeli Cardiovascular Occupational Risk Factors Determination in Israel (CORDIS) Study.

This study was designed to test whether the total objective adverse work and environmental conditions, expressed as the ergonomic stress level (ESL), would predict occupational injuries over a 2-year period. The study population consisted of 4,096 men from 21 factories in six industrial sectors who were studied as part of the Israeli Cardiovascular Occupational Risk Factors Determination in Israel (CORDIS) Study, 1985-1987. The ESL (assigned four levels, 1-4) was based on an ergonomic assessment which covered 17 risk factors pertaining to safety hazards, overcrowding, cognitive and physical demands, and environmental stressors. The ESL was found to be a highly reliable measure and stable over a period of 2-4 years. The incidence of injuries among workers in low ESL conditions (level 1) was 10.3%. It increased with higher ESL's: 11.7% in level 2 (relative risk (RR) = 1.13, 95% confidence interval (CI) 0.86-1.50); 21.6% in level 3 (RR = 2.09, 95% CI 1.68-2.62); and 23.8% in level 4 (RR = 2.31, 95% CI 1.85-2.88). After adjustment for age, job experience, educational level, managerial status, and occupational status (white/blue collar), injury occurrence was significantly elevated for those at level 3 (adjusted odds ratio (OR) = 1.46, 95% CI 1.12-1.91) and level 4 (adjusted OR = 1.81, 95% CI 1.39-2.37) but not for level 2 (adjusted OR = 0.87, 95% CI 0.65-1.18). The authors conclude that adverse work and environmental conditions, objectively assessed, can predict occurrence of occupational injuries.

Accidents, Occupational↗

Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury.

OBJECTIVE: To determine the ability of apolipoprotein E (APOE) genotypes to predict days of unconsciousness and a suboptimal functional outcome in traumatic brain injury (TBI) survivors. BACKGROUND: TBI is known to be associated with neuropsychological deficits and functional disability. Recent evidence indicates that APOE plays a pivotal role in CNS response to injury. METHODS: In this prospective study the authors determined the APOE genotypes and tested their ability to predict days of unconsciousness and functional outcome after at least 6 months in 69 survivors of TBI. A good functional outcome was defined as no dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive abnormalities; and the ability to live independently. RESULTS: The odds ratio of more than 7 days of unconsciousness was 5.69 in those with the APOE-epsilon4 allele compared with those without the epsilon4 allele (95% CI, 1.69 to 20.0; p = 0.001). Only 1 of 27 subjects (3.7%) with the epsilon4 allele had a good functional outcome compared with 13 of 42 (31.0%) of those without the epsilon4 allele (p = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was 13.93 for those with the epsilon4 allele compared with those without the allele after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; p = 0.02). CONCLUSION: The results demonstrate a strong association between the APOE-epsilon4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.

Adolescent↗

Chronic burnout, somatic arousal and elevated salivary cortisol levels.

Burnout syndrome, comprised of the symptoms of emotional exhaustion, physical fatigue, and cognitive weariness, is believed to be a result of ineffective coping with enduring stress. This study of 111 nonshift blue-collar workers free of cardiovascular disease (CVD) examined whether chronic burnout is associated with a state of somatic and physiological hyperarousal. Results showed that 37 workers exhibited symptoms of chronic burnout, with symptoms lasting at least 6 months. These workers, compared to those with no burnout symptoms (n = 52) or nonchronic burnout symptoms (n = 22), had higher levels of tension at work, postwork irritability, more sleep disturbances and complaints of waking up exhausted, and higher cortisol levels during the work day. These results suggest that chronic burnout is associated with heightened somatic arousal and elevated salivary cortisol levels. This may be part of the mechanism underlying the emerging association between burnout and risk of CVD.

Adaptation, Psychological↗

Healthy volunteer effect in industrial workers.

Volunteers for epidemiological research, have lower mortality rates than non-volunteers, thereby producing a bias referred to as the "healthy volunteer effect" (HVE). Occupationally active persons have been similarly shown to have a reduced mortality relatively to the general population (the "healthy worker effect"). To determine whether a HVE exists in occupationally active persons, we followed for 8 years a cohort of Israeli male industrial employees, of whom 71.6% agreed to participate in 1985 in screening examinations for cardiovascular disease. We calculated standardized mortality ratios (SMRs) of the entire cohort relative to the general population, and compared the mortality among participants with that of the non-participants. Over 8 years follow up, SMRs were 78% for the entire cohort, 71% for participants and 99% for non-participants. Participants were older than non-participants and worked more commonly in smaller factories. A proportional hazard model indicated that after adjusting for these variables, the all cause mortality hazard ratio among participants and non-participants was 0.69 (95% CI = 0.51-0.94). During the first and last two years of the 8-year follow-up there were 39.6 and 30.0 age-adjusted deaths per 10,000 person-years among participants, and 58.6 and 51.5 respectively among non-participants. We conclude that the HVE occurs in occupationally active persons, and that it may persist for up to 8 years follow-up.

Adult↗

Seasonal changes in calcitropic hormones in Israeli men.

Seasonal changes in calcitropic hormones might be expected, being that dietary calcium intake may differ with fluctuations in climate and temperature, and vitamin D is diet- and sunlight-dependent. While there are studies on elderly subjects, prospective data on younger men is limited. The objective of this study was to clarify possible seasonal changes in homeostatic regulators of calcium in Israeli men aged 25-64 years. The study was a prospective follow-up analysis of data collected during June-August 1995 and 1996 (summer) and January March 1995 and 1996 (winter). Subjects were ninety-five industrial male employees with and without occupational lead exposure. The main outcome measures were summer and winter serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and 1,25-dihydroxyvitamin D (calcitriol). Summer and winter values of PTH were similar (38.2 and 39.8 ng/l, respectively). 25-OH-D levels were significantly higher in summer (32.8 ng/ml) than in winter (25.4 ng/ml) after controlling for possible confounders (p < 0.0001). Calcitriol levels were significantly higher in summer (79.1 pmol/l) than in winter (73.5 pmol/l) in univariate analyses, but not after controlling for possible confounders. We conclude that healthy men show considerable seasonal changes in 25-OH-D levels even in Israel, a relatively sunny country all the year round. Summer values of 25-OH-D, were 35% higher than in winter. These fluctuations should be taken into account during evaluation of pathological conditions and in research. Given an adequate diet and vitamin D status there are no seasonal variations in PTH or in calcitriol levels.

Adult↗

Changes in dietary intake account for seasonal changes in cardiovascular disease risk factors.

OBJECTIVES: (1) to compare dietary intake in summer and winter time; (2) to measure the change in body mass index (BMI), blood pressure and serum cholesterol between winter and summer; and (3) to determine the relationships between seasonal differences in dietary intake and BMI, blood pressure and serum cholesterol measurements. SUBJECTS AND METHODS: Ninety-four male industrial employees were screened twice in one year, in their work place, at winter and summer time. Workers were recruited from two factories and response rate was 95%. Health-related variables, including dietary intake, blood pressure and serum cholesterol were evaluated at each season and were compared. Correlation coefficients between seasonal differences in dietary intake and in BMI, blood pressure and serum cholesterol were calculated. RESULTS: From summer to winter the mean values of BMI increase from 26.1 kg/cm2 to 26.6 (P=0.038), systolic blood pressure from 119.6 to 121.6 (P=0.025), diastolic blood pressure from 75.2 to 77.2 mmHg (P=0.001), total cholesterol from 200.8 to 208.6 mg/dL (P=0.001), LDL cholesterol from 125.2 to 134.9 (P=0.001) and HDL cholesterol from 42.7 to 44.3 (P=0.0084). Triglycerides levels decrease from 174 to 145 in the winter (P=0.03). Mean dietary intake of fat increases from 99.1 to 106.0 (P=0.0016), saturated fat from 43.6 to 46.3 (P=0.0137), polyunsaturated fat from 25.1 to 28.3 (P=0.0002), cholesterol from 462.0 to 497.9 (P=0.0313), sodium from 5778.5 to 8208.2 (P=0.0035), zinc from 11.6 to 12.3 (P=0.0001), vitamin B1 from 1.4 to 1.5 (P=0.002), vitamin D from 4.3 to 4.9 (P=0.0323) and vitamin E from 11.2 to 12.7 (P=0.0073). Significant correlation was shown between the seasonal increase in saturated fat and the increase in BMI (r=0.37), total cholesterol (r=0.21) and LDL cholesterol (r=0.29). Seasonal change in dietary cholesterol intake was significantly and positively correlated with serum total cholesterol (r=0.24) and LDL cholesterol (r=0.24). Blood pressure was not associated with nutritional intake variables. CONCLUSIONS: Dietary intake in summer and winter is different as well as blood pressure, BMI and serum cholesterol. The seasonal increase in fat and cholesterol intake at winter time is associated with changes in BMI and serum cholesterol.

Adult↗

Lead exposure in battery-factory workers is not associated with anemia.

Anemia is a manifestation of lead toxicity. However, there are conflicting reports of its prevalence among lead-exposed workers, and it is uncertain whether they should be monitored by periodic hemoglobin (Hb) examinations. To explore the relationship between Hb and lead exposure, we examined the correlation between Hb, blood lead (PbB), and zinc protoporphyrin (ZPP) levels in 961 blood samples obtained from 94 workers in a lead-acid battery plant in Israel between 1980 and 1993. Blood lead levels exceeded 60 micrograms/dL (2.90 mumol/L) in 105 (14%) of the blood samples. The correlation between PbB and logZPP was 0.594. Hb levels did not correlate with PbB or ZPP. We conclude that (a) periodic Hb determinations are not a useful indicator of lead exposure in Israeli industrial workers; (b) the discrepancies between the reported correlation between PbB and Hb levels remain unexplained and in need of further study; and (c) a finding of anemia in a person with PbB levels of up to 80 micrograms/dL should be considered to be due to lead toxicity only after other causes for anemia have been excluded.

Adult↗

Referral to occupational medicine clinics and resumption of employment after myocardial infarction.

Rehabilitation after acute myocardial infarction (AMI) consists of education, exercise, and an encouragement to return to work (RTW). This study attempts to (1) determine whether the time interval between AMI and the visit at occupational medicine (OM) clinics predicts resumption of full employment, and (2) estimate the incidence of work-related recurrent AMI after RTW. We followed 216 consecutive AMI patients at a single OM clinic. The independent variables were clinical and personal data, physical workload and time between AMI, and first visit to the OM clinic. The outcome variables were full employment 24 months after the acute event and recurrent AMI during this period. Of all patients, 168 attempted RTW. Of these, 18 stopped working subsequently. Of the remaining 150 patients, 54 returned to part-time work and 96 were employed full-time after 2 years. Logistic regression indicated that a failure to resume full employment was independently associated with diabetes, older age, Q wave AMI, angina before AMI, heavy work, and a late visit to the OM clinic. For each month's delay in referral to the OM clinic, there was a 30% decrease in the chance for full employment 24 months after AMI. Six (4%) of the 150 patients who resumed employment sustained a recurrent AMI, two of them while at work. A delayed referral to the OM clinic was associated with work disability after AMI. Late referrals to OM clinics should receive a more intensive and sustained rehabilitation than early referrals. Whether an earlier referral to OM clinics will result in increased RTW rates is unknown. Patients who attempted to resume employment had a 1.2% risk of a recurrent ischemic event at their workplace.

Adult↗

Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos.

OBJECTIVES: Epidermal growth factor receptor (EGFR) and oncogene Neu belong to a family of growth factor receptors which may play a part in carcinogenesis. Although increased serum concentrations of Neu and EGFR have been shown in several patients with asbestosis who later developed cancer, serum concentrations have not been studied in workers exposed in the past to asbestos but without asbestos related diseases. METHODS: Serum concentrations of secreted growth factor receptors were studied in 300 workers exposed in the past to asbestos and the results were compared with those of 70 controls. RESULTS: In the controls 4.3% (3/70) had EGFR values > 912 units/ml, compared with 39% (117/299) of the exposed group (p < 0.001). The difference in high values was even more pronounced for Neu with 4.3% of controls having Neu values > 2580 fmol/ml compared with 72% (216/299) of the exposed workers (p < 0.001). Pleural plaques predicted lower serum concentrations of EGFR but not lower Neu concentrations, and this finding remained significant after adjustment for age, exposure time, smoking, and time from initial exposure. CONCLUSIONS: Enhanced secretion of EGFR and Neu was found in a large cohort of retired asbestos workers with a wide range of exposure and latency periods. They did not have asbestosis or cancer and their EGFR values were higher in those without plaques. Further studies are needed to confirm our results, to determine the source of the secreted growth factor receptors, and to study their possible value as risk factors in the development of cancer.

Adult↗

Smoking cessation and body mass index of occupationally active men: the Israeli CORDIS Study.

OBJECTIVES: This study estimated weight gain after smoking cessation and identified factors attenuating this gain. METHODS: We conducted a prospective follow-up of 1209 male factory workers for 2 to 4 years. The independent variables were smoking habits. age, sports activity, education, alcohol consumption, ethnicity, duration of follow-up, and body mass index (BMI, kg/m2) at entry. The dependent variable was increase in BMI during follow-up. RESULTS: The mean age-adjusted BMI at entry into the study was 26.6 kg/m2 among past smokers and 25.4 kg/m2 among current smokers. There were no differences in BMI between those who quit less than 3 years before entry and those who quit more than 6 years before entry. During follow-up, the average increase in BMI was 0.07 kg/m2 among never smokers, 0.19 kg/m2 among smokers who had stopped smoking before entry, 0.24 kg/m2 among current smokers, and 0.99 kg/m2 among those who stopped smoking after entry. Cessation of smoking after entry predicted an increased gain in BMI; older age, a higher BMI at entry, sports activity, and alcohol consumption attenuated this gain. CONCLUSIONS: The increased rate of weight gain after smoking cessation is transient. However, the weight gained is retained for at least 6 years.

Adult↗

The association between occupational lead exposure and serum cholesterol and lipoprotein levels.

OBJECTIVES: This study sought to clarify the possible associations between blood lead level and serum cholesterol and lipoprotein levels in subjects occupationally exposed to lead. METHODS: Levels of blood lead, serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides in 56 male industrial employees who were exposed to lead were compared with those in 87 unexposed employees. RESULTS: Mean blood lead levels were 42.3 (+/- 14.9) micrograms/dL in the exposed group and 2.7 (+/- 3.6) micrograms/dL in the nonexposed group. The exposed subjects had higher mean levels of total cholesterol and HDL cholesterol. CONCLUSIONS: Blood lead levels are positively associated with total and HDL cholesterol.

Adult↗

Significance of low hematocrit levels in asymptomatic young adults: results of 15 years follow-up.

HYPOTHESIS: Periodic complete blood counts are not recommended for disease prevention in low-risk, non-pregnant adults. Consequently, there are few follow-up studies of the prevalence of incidentally detected anemia in asymptomatic subjects and its significance for their well-being. The objective of this survey is to determine the frequency of anemia and its predictive value for disease over a 15-yr annual follow-up of a cohort of asymptomatic young males, selected for physical fitness and intelligence. METHODS: One thousand Israeli airmen aged 18-30 yr at entry into this historical-prospective study in 1968 were used as subjects. Hematocrit (Hct) levels were examined annually. On the average each subject had 13.2 tests in the course of the 15 yr follow-up. We arbitrarily defined anemia as a Hct of 40% or less on two or more tests, and compared the prevalence of diagnosed disorders in subjects with and without anemia. RESULTS: During follow-up, anemia was found in 125 (12.5%) of the subjects. On successive annual examinations of the same individual Hct levels varied by 3% or more in 3.5% of those without anemia, and in 10.5% of those with anemia. The frequency of diagnosed disorders, excluding inter-current infections and trauma, was 25.6%, and 10.9% among those with and without anemia, respectively (OR = 2.8, 95% CI 1.8-4.6). Anemia was associated with inflammatory bowel disease (OR = 12.1, 95% CI 2.3 78.6) and malignancy (OR = 3.6, 95% CI 1.1-10.7). It preceded diagnosis only in one case with Waldenstr 246 m's macroglobulinemia, in one case of inflammatory bowel disease and two cases of myocardial infarction. CONCLUSIONS: A finding of anemia doubled the likelihood of chronic disease. However, it had a limited predictive value for subsequent morbidity and did not lead to detection of treatable disorders or to disorders that might otherwise have endangered flight safety. Fluctuations of up to 3% in Hct over time may be viewed as normal in young males.

Adolescent↗

Calcitropic hormones and occupational lead exposure.

The authors sought to clarify in a cross-sectional study the possible associations between homeostatic regulators of calcium and occupational exposure to lead. Subjects were 146 industrial male employees, 56 with and 90 without occupational lead exposure. The main outcome measures were serum concentration of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median values of blood lead were 40.5 microg/dl in the exposed group and 4.0 microg/dl in the controls. There were no differences between groups in dietary history and serum calcium levels. PTH and calcitriol levels were significantly higher in the exposed than in the nonexposed subjects (42.0+/-24.2 vs. 33.6+/-14.9 pg/ml, p <0.05; and 83.8+/-27.0 vs. 67.9+/-17.6 pmol/liter, p <0.001, respectively). Multivariate analyses showed that after controlling for possible confounders, occupational lead exposure (no/yes) was independently associated with PTH level (pg/ml) (beta = 7.81, 95% confidence interval (CI) 3.7-11.5) and with calcitriol (pmol/liter) (beta = 12.3, 95% CI 3.84-20.8). It is concluded that subjects occupationally exposed to lead show a substantial compensatory increase in PTH and calcitriol activities which keep serum calcium levels within normal range. This may be of clinical significance since a sustained increase in calcitropic hormones in susceptible subjects may eventually increase the risk of bone disorders.

Adult↗