Biomedical subjects

K Kushida

Publications and source records attributed to K Kushida.

At least 19 recordsLinked to original sources

PubMed2001

Prevalence of vertebral fractures in a population-based sample in Japan.

In order to compare the prevalence of vertebral fractures in caucasian American and Japanese women, we examined the occurrence of vertebral fractures in a population of 1092 female residents of Yamanashi prefecture who participated in a screening program for osteoporosis. The relationship between vertebral fractures and bone mineral density (BMD) of the second metacarpal bone was also studied. Our findings regarding the prevalence of vertebral fractures in Yamanashi agreed strongly with the findings of previous reports in Japan. The prevalence of vertebral fractures was equal or lower among women in Japan compared with caucasians in Minnesota aged from 50 to 60 years. A comparison of the fracture and non-fracture groups revealed significant differences in age, height, and metacarpal BMD. However, after correction for age, no significant difference was found between the two groups.

Aged↗

PubMed2001

Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures.

OBJECTIVE: To examine serum undercarboxylated osteocalcin (OC) with application of an ELISA in normal women and in osteoporotic patients with vertebral fractures or hip fractures, and to investigate the effects of vitamin K and/or D treatment on undercarboxylated OC and intact OC in vertebral fractures. PATIENTS: They were 43 premenopausal (PRE) and 48 postmenopausal healthy females (POST), 89 osteoporotic patients with vertebral fractures (VX) and, 24 patients with hip fracture (HX). MEASUREMENTS: Intact OC was measured by an IRMA and undercarboxylated OC was measured by an ELISA. RESULTS: Intact osteocalcin was significantly higher in POST and VX than in PRE, and was significantly lower in HX than in POST and VX. Undercarboxylated OC tended to be higher in POST, VX and HX than in PRE, but not significantly. The ratio of undercarboxylated OC to intact OC was significantly higher in HX than in POST and in VX. After 4 weeks treatment with K, D, and K + D to 56 VX, undercarboxylated OC decreased significantly in the groups with K and K + D. Intact OC tended to increase slightly in the groups given K, D, K + D, but not significantly so. Vitamin K and vitamin K + D markedly decreased the ratio of undercarboxylated/intact OC to approximately 80%. On the other hand, vitamin D did not decrease that ratio. CONCLUSIONS: There was a disproportion of undercarboxylated osteocalcin to intact osteocalcin between postmenopausal women and osteoporotic patients with vertebral fractures or hip fractures. Vitamin K did decrease undercarboxylated osteocalcin, vitamin D did not change undercarboxylated osteocalcin, and vitamin D did not enhance the effect of vitamin K on undercarboxylated osteocalcin.

Adult↗

PubMed2001

Longitudinal study of age- and menopause-related metacarpal index changes in Japanese adult females.

To establish a comprehensive mode for cortical bone thinning rate, the metacarpal index (MCI) of the index finger of the nondominant hand was measured using computed X-ray microdensitometry. Statistical analysis was used to study the MCI data in relation to age and menopausal status. A total of 383 healthy Japanese women ranging in age from 30 to 79 yr were investigated in 1996 and 1999. The MCI was generally decreased by 1.11% per year. However, accelerative decreases of 1.78 and 2.05% per year were observed within both the age 50-59 yr group and the early postmenopausal period, respectively. In addition, analysis of age-based longitudinal data showed that the age-related loss of MCI in the age 50-59 yr category was significantly higher than that in the other age categories (p < 0.01), indicating that the changes in MCI were more dependent on menopausal status than on aging. Our study suggests that the cortical bone thinning rate is affected by both aging and menopausal status, but the latter may be a predominant factor.

Absorptiometry, Photon↗

PubMed2000

Direct detection of crosslinks of collagen and elastin in the hydrolysates of human yellow ligament using single-column high performance liquid chromatography.

Collagen and elastin are recognized as two major connective tissue proteins of human yellow ligament. In both collagen and elastin there are many kinds of intra- or intermolecular crosslinks. Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are mature crosslinks which maintain the structure of the collagen fibril. Desmosine (Des) and isodesmosine (Isodes) represent the major crosslinking components of elastin. Pentosidine (Pen), which is a senescent crosslink and one of the advanced glycation end products, accumulates with age in tissue proteins including collagen. We developed a direct and one-injection HPLC method to measure Pyr, Dpyr, Des, Isodes, and Pen in the hydrolysate of human yellow ligament. This method used one column and two detectors. Recovery rates of Pyr, Dpyr, Pen, Des, and Isodes were 86.4-98.3, 83.6-96.8, 78.7-95.6, 83.6-97.9, and 85.6-99.3%, respectively (n = 8). The intraassay coefficients of variation for Pyr, Dpyr, Pen, Des, and Isodes were 3.7, 4.1, 5.4, 4.5, and 4.7%, respectively (n = 8), and the interassay coefficients of variation for Pyr, Dpyr, Pen, Des, and Isodes were 4.4, 5.1, 4.9, 4.6 and 4.1%, respectively. Linear regression analysis showed the linearity (r = 0.99, P = 0.0001) of calibration line for each Pyr, Dpyr, Pen, Des, and Isodes. Using this method, we investigated age-related changes in the crosslinks of collagen and elastin in human yellow ligament. There was a significant correlation between Pen and age, but no correlations with Pyr, Dpyr, Des, and Isodes. We believe that this method is useful for investigating the content of these crosslinks in both collagen and elastin under various conditions.

Chromatography, High Pressure Liquid↗

PubMed2000

The effects of nandrolone decanoate on bone mass and metabolism in ovariectomized rats with osteopenia.

The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism were studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae and the wet weight of the gastrocnemius and soleus skeletal muscles were also examined. Ovariectomy resulted in a significant increase in biochemical markers and a significant decrease in spine BMD (0.221+/-0.016g/cm2 in OVX group vs 0.239+/-0.008g/cm2 in Sham group) and BMC (0.550+/-0.055g in OVX group vs 0.605+/-0.042g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227+/-0.017g/cm2), femoral BMD (0.263+/-0.012g/ cm2), and bone density of femur (1.035+/-0.036g/cm3) in the OVX + ND group were significantly greater than those in the OVX + Vehicle group (0.204+/-0.013g/cm2 for spine BMD, 0.243+/-0.009g/cm2 for femoral BMD, 0.938+/-0.06g/cm3 for bone density of femur) after 24 weeks of treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Histomorphometric findings indicated that ND-treated rats had greater cancellous bone volume, greater trabecular number, greater trabecular thickness, and less trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet weight of the gastrocnemius and soleus muscles than rats treated with ND. The data suggest that the effect of ND on bone mass is not influenced by the condition of the muscles in OVX rats. Our findings indicate that ND blocks further bone loss by inhibition of bone resorption in OVX rats with osteopenia.

Amino Acids↗

PubMed2000

Estimation of the architectural properties of cortical bone using peripheral quantitative computed tomography.

We assessed the volumetric bone mineral density (vBMD) and cross-sectional architecture of cortical bone at the distal radius by peripheral quantitative computed tomography (pQCT). The volumetric bone mineral density [integral bone mineral density (BMDi), trabecular bone mineral density (BMDt) and cortical with subcortical bone mineral density (BMDsc)] and the architectural parameters [cortical bone area (CBA), cortical thickness (C-th), moment of inertia (Im) and polar moment of inertia (Ip)] were measured in 115 healthy premenopausal women, 48 osteoporotic postmenopausal women and 78 age-matched healthy postmenopausal women. Age-matched healthy women had higher values of vBMD and architectural parameters at the distal radius than osteoporotic women. Premenopausal women had higher values of vBMD and architectural parameters at the distal radius than postmenopausal women. The differences in the architectural parameters between age-matched healthy women and osteoporotic women were more pronounced when only the high density area (threshold 0.70 cm(-1)) was included. However, the differences in architectural parameters between premenopausal women and postmenopausal women were significant using even the lowest threshold value of 0.50 cm(-1) in the calculation. Receiver operating characteristic (ROC) curves were constructed and the areas under the curves calculated to evaluate the discriminating power of vBMD and architectural parameters. Comparison of the different ROC curves showed no statistical significance. In conclusion, our results suggest that both the density and mass distribution of the radius were clearly different between the healthy women and osteoporotic women. The differences in architectural parameters were more useful for studying the pathophysiology of osteoporosis than for contributing to the diagnosis. Determination of the cross-sectional mass distribution of bone combined with BMD should offer more information than BMD alone in the study of the pathophysiology of osteoporosis.

Adult↗

PubMed2000

Changes in levels of biochemical markers and ultrasound indices of Os calcis across the menopausal transition.

The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35-59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (% delta IOC, % delta Pyr and % delta Dpyr) and the percentage decreases in the ultrasound indices (% delta SOS, % delta BUA and % delta Stiffness) were calculated. The values of % delta IOC and % delta Dpyr in the perimenopausal subgroup (-4 to -3 years since menopause) and the values of % delta SOS and % delta Stiffness in the perimenopausal subgroup (-2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with % delta SOS (r = -0.467, p < 0.01) and % delta Stiffness (r = -0.330, p < 0.05) and Dpyr was significantly correlated with % delta SOS (r = -0.390, p < 0.05), % delta BUA (r = -0.353, p < 0.05) and % delta Stiffness (r = -0.454, p < 0.05), while % delta IOC was significantly correlated with % delta SOS (r = -0.278, p < 0.05), % delta BUA (r = -0.369, p < 0.01) and % delta Stiffness (r = -0.383, p < 0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient.

Adult↗

PubMed2000

Bone mineral density and bone turnover in patients with knee osteoarthritis compared with generalized osteoarthritis.

The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the lumber spine, femur, and radius, and biochemical markers of bone turnover, pyridinoline (Pyr), deoxypyridinoline (Dpyr), CTx, and osteocalcin were compared among each grade. BMD was also compared with 88 normal controls who were age and weight-matched. In 88 KOA patients, 56 were divided into 28 GOA and 28 non-GOA groups by grading hand radiographs. BMD and biochemical markers were compared between GOA and non-GOA. KOA patients had higher BMD at several skeletal sites compared with age- and weight-matched normals. A significant difference of BMD between each grade was observed between grades 0-1 and 3 (0.774+/-0.143 versus 0.940+/-0.185 g/cm(2), P<0.001), grades 2 and 3 (0.781+/-0.125 versus 0.940+/-0.185 g/cm(2), P<0.01) in the spine, and between grades 0-1 and 3 (0.505+/-0.100 versus 0.564+/-0.127 g/cm(2), P<0.05) in the trochanter. A significant difference of biochemical bone markers was observed between grades 0-1 and 3 (P<0.05) and between grades 2 and 3 (P<0.05) in Pyr and grades 0-1 and 3 (P<0.05) and between grades 1 and 4 (P<0.05) in Dpyr, but not in osteocalcin and CTx. GOA patients had higher BMD of the spine (0.902+/-0.175 versus 0.747+/-0.138 g/cm(2), P<0.01), trochanter (0.535+/-0.107 versus 0.480+/-0.107 g/cm(2), P<0.05), and one-third of the radius (0.526+/-0.068 versus 0.472+/-0. 089 g/cm(2), P<0.05) and had significantly higher biochemical markers in Pyr and Dpyr than non-GOA patients. It is concluded that KOA patients had higher BMD at several skeletal sites. Biochemical bone markers were influenced by some degree of cartilage damage in OA patients. This tendency was stronger in GOA patients than in non-GOA patients.

Aged↗

PubMed2000

Evaluation of isolated fractures of the greater trochanter with magnetic resonance imaging.

The diagnosis of an isolated fracture of the greater trochanter can be done on routine radiographs, but this may not be the whole story. We evaluated fractures of the greater trochanter of the femur by magnetic resonance imaging (MRI). MR images were obtained within 5 days of the time of clinical presentation. Coronal images were performed on T1- and T2-weighted spin-echo images. Eight elderly patients who were diagnosed as having a greater trochanter fracture on standard radiographs underwent MRI. Three were men aged 62-76 (mean 63.4) years, and five were women aged 80-101 (mean 88.6) years. MRI showed that in seven of the eight cases, the fracture line was observed leading from the greater trochanter towards other trochanter regions. In only one case was the fracture limited to the greater trochanter and corresponded to the line observed on the standard radiographs. We suggest that in cases of greater trochanter fracture with somewhat severe symptoms, MRI should be performed in order to discover the appropriate diagnosis and treatment.

Accidental Falls↗

PubMed2000

Age and menopause-related changes in phalangeal bone density of Japanese women, measured by a digital image processing method.

The bone density (BD), phalangeal index (PLI), and metacarpal index (MCI) of the proximal phalangeal and metacarpal bones of the index finger of the nondominant hand were measured, using a digital image processing (DIP) method, in a total of 345 normal Japanese women. In this study, two different locations were measured and the BD, PLI, and MCI decreased significantly after the age of 50 years (P < 0.01 vs values for women in their third decade). The BD, PLI, and MCI of the proximal phalangeal and metacarpal bones showed a significant decrease in postmenopausal groups compared with the pre-menopause group (P < 0.01), which indicated that not only trabecular bone but also cortical bone had an accelerative bone loss in the postmenopausal women. The BD in proximal phalangeal and metacarpal bones decreased by 0.69% and 0.74% / per year, respectively, and there were no significant differences between these annual decreases. The BD of proximal phalangeal bone had a good correlation with that of the metacarpal bone (r = 0.77; P < 0.01), which suggested that the measurement of proximal phalangeal BD was as useful as the measurement of metacarpal BD in screening for osteoporosis (coefficient of variation; CV, 0.64%). The data suggest that DIP has a potential application in screening for osteoporosis.

Adult↗

PubMed2000

Comparison of the analytical and clinical performance characteristics of an N-MID versus an intact osteocalcin immunoradiometric assay.

Osteocalcin is the most abundant non-collagenous protein in bone, reflecting its formation. It was reported that the instability of intact osteocalcin results from the cleavage of the C-terminal sequence of osteocalcin to produce a large N-terminal osteocalcin fragment. A two-site immunoassay for detecting both the N-terminal osteocalcin fragment and the intact osteocalcin was developed that were both independent of an unstable C-terminal sequence. The aim of this study is to investigate the performance of an N-MID osteocalcin immunoradiometric assay and to compare it with an intact osteocalcin assay. Ten serum samples were repeatedly frozen and thawed up to seven times. The variability of the values of N-MID osteocalcin was less than that of the intact osteocalcin. For stability of osteocalcin in serum after storage, the mean value of N-MID was 94. 3% of the initial value after 7 days at 4 degrees C, whereas the intact was 73.4%. The reduction of intact values were significantly larger than that of N-MID after 2, 5 and 7 days. At -30 degrees C, the values of N-MID did not change for up to 10 weeks. The concentrations of osteocalcin measured by an N-MID osteocalcin and an intact osteocalcin were investigated in 27 premenopausal subjects, 27 postmenopausal subjects, and 68 osteoporotic patients (23 with vertebral fractures and 45 with hip fractures). The percent mean increase of osteocalcin in postmenopausal subjects over premenopausal subjects was 98% in N-MID versus 42% in the intact assay. The z-scores of N-MID and intact showed similar results in all groups. N-MID osteocalcin significantly correlated with intact osteocalcin (r=0.755), and other biochemical markers for bone formation, such as bone specific alkaline phosphatase (r=0.606) and C-terminal propeptide of type I procollagen (PICP) (r=0.568). An N-MID IRMA had better stability during storage than intact and had the discriminative ability which is similar to the intact assay in postmenopause and osteoporosis. Therefore, an N-MID osteocalcin IRMA could improve the clinical utility and evaluation of osteocalcin.

Adult↗

PubMed2000

The efficacy of biochemical markers in patients with ossification of posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum levels of carboxyterminal propeptide of type I collagen (PICP), osteocalcin (OC), carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in patients with ossification of posterior longitudinal ligament of the spine (OPLL) and age-matched control subjects. OBJECTIVES: To evaluate the efficacy of these biochemical markers of the patients with OPLL. SETTING: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. METHODS: Spot urine and blood samples were obtained from 20 healthy males aged 45 - 78 (mean+/-SD; 63. 0+/-11.5) and 22 male patients with OPLL aged 46 - 77 (mean+/-SD; 59. 9+/-8.8), and serum levels of PICP, OC, ICTP and urinary levels of Pyr and Dpyr were measured. RESULTS: There were no significant difference in age, serum PICP, OC, ICTP, urinary Pyr and Dpyr levels between OPLL and control group. CONCLUSION: Neither bone formation nor bone resorption was accelerated in the patients with OPLL.

Aged↗

PubMed2000

Scapholunate dissociation caused by gouty arthritis of the wrist. Case report.

Gouty arthritis of the wrist is rare, and may be associated with scapholunate dissociation. To our knowledge, only two cases have been reported so far. In this report, we describe a 40-year-old patient with scapholunate dissociation caused by acute gouty arthritis of the wrist. His clinical findings and radiographs mimicked infectious arthritis or osteomyelitis of the carpal bones.

Adult↗

PubMed2000

The effect of prostaglandin E1 on human bone metabolism: evaluation by biochemical markers for bone turnover.

Prostaglandins (PGs) have complex and multiple effects on bone metabolism. Although the osteogenic effect of PGE in humans was initially found in an infant with a congenital heart disease, there have been few reports on the effect of PGE in human in vivo. The aim of this study was to investigate the effect of PGE1 on human bone metabolism, using biochemical bone markers. A total of 18 subjects were treated with PGE1 in lipid microspheres. Six subjects were given 10 microg of lipo-PGE, intravenously daily for 14 days, and twelve subjects were given the same dose twice a week for 7 weeks. Before and after the administration of PGE1, blood and a spot urine was obtained in the morning. Bone formation markers (alkaline phosphatase, osteocalcin, procollagen I carboxy-terminal peptide) did not change. In the subjects with daily administration for 2 weeks, type I collagen pyridinolines crosslinked C-telopeptide (ICTP) increased significantly. In the subjects treated twice a week, free deoxypyridinoline (Dpd) increased significantly. When all subjects were analyzed, bone resorption markers (ICTP and Dpd) increased, but not significantly (p=0.055 for ICTP, p=0.055 for Dpd). Therefore, PGE1 at the dosage used in this study did not increase bone formation but increased bone resorption in humans.

Aged↗

PubMed2000

Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fractures. Contact Ultrasound Bone Analyzer.

The purpose of this study was to assess the ultrasound (US) parameters measured by Contact Ultrasound Bone Analyser (CUBA) clinical system for discriminating the subjects with vertebral fractures from those without vertebral fractures. The subjects consisted of 114 postmenopausal women over age 50 (mean +/- SD: 72.2 +/- 8.7). Seventy-three had vertebral fractures (fracture group) and 41 had no vertebral fractures (control group). Values of all US parameters and bone mineral density (BMD) in the fracture group were significantly lower than those in the control group, even after adjusting for age. Areas under the receiver operating characteristic (ROC) curve was 0.768 +/- 0.056 (mean +/- SE) for broadband ultrasound attenuation (BUA) 0.828 +/- 0.045 for velocity of sound (VOS), 0.707 +/- 0.058 for lumbar spine, 0.872 +/- 0.050 for femur neck, 0.790 +/- 0.050 for trochanter, and 0.695 +/- 0.060 for Ward's triangle. There were no significant differences among the areas under the ROC curves in BUA, VOS, lumbar spine, femur neck, trochanter, and Ward's triangle. US parameters (BUA and VOS) had the same discriminatory power as spine and hip BMD for evaluating the vertebral fracture risk. As far as disadvantages of the use of BMD measurement against US measurement, US measurement is potentially useful for screening of vertebral fractures. However, the bias concerning the propotion of the number of patients with or without vertebral fractures could not be neglected in this study.

Aged↗

PubMed2000

Biochemical markers and bone mineral density in patients with hip fractures in men.

The purpose of this study was to determine whether males with hip fractures have associated decreased gonadal function. Second void urine and serum samples were obtained from 25 male hip fracture patients (mean age+/-SD, 78.5+/-5.9 years) and 19 age- and gender-matched controls (77.6+/-6.2 years). Serum levels of luteinizing hormone (LH), total testosterone (Te), total estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), 1,25(OH)2D3, N-mid osteocalcin (OC(N-mid)), type I collagen degradation products (S-CTx) and urinary levels of pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen degradation products (U-CTx) were measured. Bone mineral density (BMD) of the L2-4 spine, femoral neck, trochanter, Ward's triangle, distal one third portion of the radius and ultradistal radius were also measured in the fracture group. Serum levels of LH, E2, Te, DHEAS, 1,25(OH)2D3 and OCN-mid in the fracture group were not statistically different from those in the control group. Levels of urinary Pyr, CTx and S-CTx in the fracture group increased significantly compared with those in the control group. In the fracture group, serum levels of Te correlated positively with distal one third portion of the radius BMD and ultradistal radius BMD. U-CTx and S-CTx correlated negatively with all the BMD measurement sites in the hip region and with the radius BMD. An imbalance between bone resorption and bone formation was evident in male hip fracture patients. However, male patients with hip fractures did not show associated decreased gonadal function in this study.

Aged↗

PubMed2000

[Shift to home treatment and the function of pharmacies].

A crisis point has been reached in the medical health system in Japan, where there has been a rapid aging of the population. The method of providing health system benefits is being reconsidered. As a result, medical treatment has been classified into inpatient, outpatient, and home care systems according to treatment functions. In concrete terms, the insurance system now classifies medical treatment and care separately, payment for medical fees has changed from payment at piece rates to a fixed amount system, and the number of days patients stay in hospital has been reduced. It is predicted that hospital treatment will increasingly rely on early discharge, and patients highly reliant on medical treatment will be shifted to home treatment. For this shift to home treatment, therefore, supplies of injectable agents such as used in total parenteral nutrition, and equipment by specialist pharmacies have become necessary. However, to dispense injectable agents, "standards of compounded sterile pharmaceuticals by licensed pharmacies" is applied, meaning there are very few pharmacies that can meet these standards. In the present survey, we found that 40 pharmacies have been recognized as meeting these standards.

Home Care Services, Hospital-Based↗

PubMed2000

[Role of the pharmacy for home cancer patients].

Otsukadai Pharmacy compounded morphine chloride for injection in 32 cancer patients. In 22 cases we compounded morphine into a TPN bag. However we recommend using an infusion pump to control the patient's pain at home. We think that we need a system with a pharmacy for cancer patients before they leave the hospital for home care.

Female↗