Circumcision and breastfeeding.
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Breast Feeding↗
Biomedical subjects
N Lee
Publications and source records attributed to N Lee.
The mating-type and pathogenicity locus of the fungus Ustilago hordei spans a 500-kb region.
The fungal pathogen Ustilago hordei causes the covered smut disease of barley and oats. Mating and pathogenicity in this fungus are controlled by the MAT locus, which contains two distinct gene complexes, a and b. In this study, we tagged the a and b regions with the recognition sequence for the restriction enzyme I-SceI and determined that the distance between the complexes is 500 kb in a MAT-1 strain and 430 kb in a MAT-2 strain. Characterization of the organization of the known genes within the a and b gene complexes provided evidence for nonhomology and sequence inversion between MAT-1 and MAT-2. Antibiotic-resistance markers also were used to tag the a gene complex in MAT-1 strains (phleomycin) and the b gene complex in MAT-2 strains (hygromycin). Crosses were performed with these strains and progeny resistant to both antibiotics were recovered at a very low frequency, suggesting that recombination is suppressed within the MAT region. Overall, the chromosome homologues carrying the MAT locus of U. hordei share features with primitive sex chromosomes, with the added twist that the MAT locus also controls pathogenicity.
Avena↗
Spectral tuning in the human blue cone pigment.
The first determination of the absolute absorption maximum of the human blue cone visual pigment is presented. After expression in COS cells, reconstitution with 11-cis-retinal, and purification, the blue pigment exhibits an absolute absorption maximum of 414 nm. The pigment reacts rapidly with hydroxylamine in the dark and is capable of activating bovine rod transducin in a light-dependent manner. Products of mutations of proposed spectral tuning residues in the blue pigment do not behave as predicted when using rhodopsin mutants as a model. Mutations of amino acids in the ring portion of the chromophore binding pocket of rhodopsin serve well as a predictive model for mutations in the blue pigment, but mutations near the Schiff base do not.
Animals↗
Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-XL and caspase inhibitors.
Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was approximately 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant. Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-XL was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-XL protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus.
Animals↗
Synthesis and evaluation of 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)- 6-fluoropurine mono- and diesters as potential prodrugs of ganciclovir.
A series of 2-amino-9-(1,3-dihydroxy-2-propoxymethyl)-6-fluoropurine mono- and diesters, 6a-h, were synthesized as potential prodrugs of ganciclovir and evaluated for their oral ganciclovir bioavailability in rats. Treatment of 2-amino-6-chloro-9-(1, 3-dihydroxy-2-propoxymethyl)purine (4) with Me3N in DMF/THF (1/4) followed by the reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)-6-fluoropurine (2) in 83% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) (6 equiv for 6a-d or 1 equiv for 6e-h) in DMF in the presence of a catalytic amount of DMAP produced the diesters 6a-d in 92-98% yields and the monoesters 6e-h in 37-44% yields. Of the prodrugs tested in rats, the monoisobutyrate 6h achieved the highest ganciclovir bioavailability (45%) that is 15-fold higher than that from ganciclovir (3%), followed in order by the diisobutyrate 6d (42%), the diacetate 6a (41%), the monobutyrate 6g (41%), the monopropionate 6f (39%), the dipropionate 6b (35%), the dibutyrate 6c (35%), and the monoacetate 6e (29%). The prodrugs 6e-h were found to be quite stable at pH 6.0 (t1/2 = >29 days), 7.4 (t1/2 = >7 days), and 8.0 (t1/2 = >2 days) but had relatively short half-lives at pH 1.2 (t1/2 = 60-83 min).
Animals↗
A controlled trial of exercise rehabilitation after heart transplantation.
BACKGROUND: In patients who have received a cardiac transplant, the denervated donor heart responds abnormally to exercise and exercise tolerance is reduced. The role of physical exercise in the treatment of patients who have undergone cardiac transplantation has not been determined. We assessed the effects of training on the capacity for exercise early after cardiac transplantation. METHODS: Twenty-seven patients who were discharged within two weeks after receiving a heart transplant were randomly assigned to participate in a six-month structured cardiac-rehabilitation program (exercise group, 14 patients) or to undergo unstructured therapy at home (control group, 13 patients). Each patient in the exercise group underwent an individualized program of muscular-strength and aerobic training under the guidance of a physical therapist, whereas control patients received no formal exercise training. Cardiopulmonary stress testing was performed at base line (within one month after heart transplantation) and six months later. RESULTS: As compared with the control group, the exercise group had significantly greater increases in peak oxygen consumption (mean increase, 4.4 ml per kilogram of body weight per minute [49 percent] vs. 1.9 ml per kilogram per minute [18 percent]; P=0.01) and workload (mean increase, 35 W [59 percent] vs. 12 W [18 percent]; P=0.01) and a greater reduction in the ventilatory equivalent for carbon dioxide (mean decrease, 13 [20 percent] vs. 6 [11 percent]; P=0.02). The mean dose of prednisone, the number of patients taking antihypertensive medications, the average number of episodes of rejection and of infection during the study period, and weight gain did not differ significantly between the groups. CONCLUSIONS: When initiated early after cardiac transplantation, exercise training increases the capacity for physical work.
Blood Pressure↗
Which patients with newly diagnosed prostate cancer need a computed tomography scan of the abdomen and pelvis? An analysis based on 588 patients.
OBJECTIVES: Although a computed tomography (CT) scan of the abdomen and pelvis is often recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. We hypothesized that biopsy Gleason score, serum prostate-specific antigen (PSA) levels, and clinical stage could predict for a positive CT scan and that a low-risk group of patients could be identified in whom CT might be omitted. METHODS: All patients who had both pathologic review of their prostate cancer biopsies and abdominopelvic CT scans at our institution between January 1990 and May 1996 were studied. Gleason score, PSA, and stage were evaluated by univariate (chi-square) and multivariate (logistic regression) analyses for their ability to predict for a positive CT. RESULTS: Of 588 patients, 41 (7%) had a positive CT scan. Multivariate analysis showed Gleason score, PSA, and clinical stage to be significant independent predictors of a positive CT scan, all P <0.001. The odds ratios for a positive CT scan were 6.17 (95% confidence interval [CI] = 1.58 to 24) for Gleason score 8 to 10 versus 2 to 6; 2.25 (CI = 1.24 to 4) for PSA greater than 50 versus 0 to 15 ng/mL; 2.08 (CI = 1.70 to 3.21 ) for Stage T2c-T4 versus T2b or lower. All 244 patients with Gleason score 2 to 7, PSA 1 5 ng/mL or less, and clinical Stage T2b or less had negative CT scans. Of the other 174 patients with a Gleason score of 2 to 7, 8 (5%) had a positive CT scan. Of the 1 26 patients with a Gleason score of 8 to 10, 28 (22%) had a positive CT scan. CONCLUSIONS: Gleason score, PSA, and clinical stage were independent predictors for a positive CT scan of the abdomen and pelvis in patients with newly diagnosed prostate cancer. In this cost-conscious era, we can decrease expenditure by obviating the need for a CT scan in low-risk patients (clinical Stage T2b or less, Gleason score 2 to 7, and PSA 15 ng/mL or less). A CT scan should be considered in all other patients.
Adenocarcinoma↗
Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy.
Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of neurotrophic factors and corresponding receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary neurotrophic factor receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary neurotrophic factor receptor alpha in axotomized sciatic motor neurons. Ciliary neurotrophic factor receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary neurotrophic factor receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary neurotrophic factor receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary neurotrophic factor receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary neurotrophic factor receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary neurotrophic factor receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of ciliary neurotrophic factor receptor alpha protein in response to injury. Moreover, they suggest that the ability of a subpopulation of spinal motor neurons to regulate ciliary neurotrophic factor receptor alpha levels in response to injury may play a role in their survival and axonal regeneration. Consistent with such a role, we also find relatively high, and probably elevated, levels of ciliary neurotrophic factor receptor alpha immunoreactivity in regenerating axons.
Animals↗
Synthesis and evaluation of amino acid esters of 6-deoxypenciclovir as potential prodrugs of penciclovir.
The amino acid ester derivatives of 6-deoxypenciclovir, 11-20, were synthesized as potential prodrugs of penciclovir, and were evaluated for their oral penciclovir bioavailability in mice and rats. Esterification of 6-deoxypenciclovir with N-carbobenzyl-oxyglycine, -L-alanine, -L-valine, -L-leucine, or -L-isoleucine (3.75equiv.) using conventional coupling method (DCC/DMAP) afforded the mono-O-ester derivatives 1-5 in 47-55% yields as a mixture of two diastereomers along with the di-O-ester derivatives 6-10 in 20-29% yields. Reductive cleavage of carbobenzyloxy (Cbz) group (10% Pd/C, 1 atmosphere of H2, room temperature in methanol) followed by subsequent treatment of the resulting free amine with methanolic HCI solution provided the mono-O-ester derivatives 11-15 as di-HCl salt in 51-98% yields and the di-O-ester derivatives 16-20 as tri-HCl salt in 65 98% yields. Of the prodrugs tested in mice and rats, 6-deoxypenciclovir O-L-valinate (13), O-L-isoleucinate (15), and O,O-di-glycinate (16) showed significantly higher urinary recovery of penciclovir compared with that of penciclovir, but those are somewhat lower than that of famciclovir.
Acyclovir↗
Synthesis and evaluation of 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine mono- and diesters as potential prodrugs of penciclovir.
2-Amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7), and its mono- and diesters 8-15 were prepared and evaluated for their potential as prodrugs of penciclovir. Treatment of 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (5) with trimethylamine in THF followed by a reaction of the resulting trimethylammonium chloride salt 6 with KF in DMF afforded 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7) in 80% yield. Esterification of 7 with an appropriate acid anhydride [Ac2O, (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O] in DMF in the presence of a catalytic amount of DMAP produced the mono-esters 8-11 in 42-45% yields and diesters 12-15 in 87-99% yields. Of the prodrugs tested in rats, the monoisobutyrate 11 was the most efficiently absorbed and metabolized to 7, showing the mean maximum total concentration of penciclovir (5.5 microg/mL) and 7 (10.8 microg/mL) in the blood was much higher than the mean maximum concentration of penciclovir (11.5 microg/mL) from famciclovir. However, the mean concentrations of penciclovir from 11 were lower than those from famciclovir because of the limited conversion of a major metabolite 7 to penciclovir by adenosine deaminase.
Acyclovir↗
Synthesis and evaluation of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines and 2-amino-9-(3-alkoxycarbonyloxymethyl-4-alkoxycarbonyloxybut-1- yl)purines as potential prodrugs of penciclovir.
A series of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purin es (1-8) and 2-amino-9-(3-alkoxycarbonyl-oxymethyl-4-alkoxycarbonyloxybut -1-yl)purines (9-12) were synthesized as potential prodrugs of penciclovir. Treatment of 6-deoxypenciclovir with trimethyl orthoacetate or triethyl orthopropionate (1.2 equiv) in DMF in the presence of p-TsOH.H2O (0.1 equiv) followed by quenching with excess H2O gave the corresponding mono-O-acetyl or mono-O-propionyl compound, 17 or 18, in excellent yields of 95 and 92%, respectively. Reactions of 17 or 18 with an appropriate alkyl (Me, Et, n-Pr, and i-Pr) 4-nitrophenyl carbonate (1.2 equiv) in pyridine in the presence of a catalytic amount of DMAP (0.1 equiv) at 80 degrees C afforded the monoacyl, monocarbonate derivatives of 6-deoxypenciclovir, 1-8, in 86 94% yields. Similar reactions of 6-deoxypenciclovir with 2.1 equiv of alkyl 4-nitrophenyl carbonate produced the dicarbonate derivatives 9 12 in 81-83% yields. Of the prodrugs tested in rats, 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (4) achieved the highest mean urinary recovery of penciclovir (36%), followed in order by compounds 2 (35%), 6 (35%), 7 (34%), 10 (34%), 8 (32%), 3 (32%), and famciclovir (31%). The mean urinary recovery of penciclovir and concentrations of penciclovir in the blood from 4 in mice were also slightly higher than those from famciclovir. The in vivo antiviral efficacy of 4 in HSV-1-infected normal BALB/c mice was higher than those of famciclovir and valaciclovir in terms of mortality (100, 80, and 40%) and mean survival time ( > 21, 13+/-5.0 (SEM), and 13+/-1.6 days). Compound 4 demonstrated an effective anti-hepadnaviral response with intrahepatic viral load being reduced by 90%, the viral supercoiled DNA levels reduced by 70% and Pre-S expression inhibited by 30% against duck hepatitis B virus (DHBV) in vivo, and did not cause any significant hepatotoxicity after 4 weeks of treatment.
Acyclovir↗
Portal vein embolization with use of a new liquid embolic material: an experimental study.
PURPOSE: To evaluate the efficacy and safety of a new liquid embolic material in portal vein embolization (PVE). MATERIALS AND METHODS: A new embolic material (Embol) was percutaneously injected into the left portal vein of 13 swine, using a balloon catheter to prevent reflux. The swine were killed immediately (n = 6), 2 weeks (n = 4), and 4 weeks (n = 3) after the PVE, and the volumes of the right and left lobes were measured. The changes in body temperature, aspartate aminotransferase (AST) (formerly SGOT), alanine aminotrasferase (ALT) (formerly SGPT), and bilirubin levels after the PVE were studied, and the histopathologic changes in the embolized and nonembolized lobes were examined with light microscopy. RESULTS: The average volume ratio of the right:left lobe immediately after the PVE was 55(+/-2):45(+/-1), and changed to 71(+/-3):29(+/-3) at 2 weeks and 82(+/-3):18(+/-3) at 4 weeks after embolization. There were only mild changes in AST, ALT, and bilirubin levels, and only one pig showed a significant elevation in body temperature after PVE. Microscopically, the embolized lobe showed contraction of hepatocyte without any sign of necrosis and the nonembolized lobe expansion of hepatocyte. CONCLUSIONS: The new embolic material seems effective and safe for PVE.
Animals↗
Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism.
OBJECTIVES: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. DESIGN: Eighteen healthy women participated in a three-way cross-over study for five week periods separated by seven week washout periods, diets were assigned in random order. SUBJECTS: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3/3, 3/2, 4/3, and 4/2). INTERVENTION: During the first week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10en% polyunsaturated fat and 14en% monounsaturated fat. Followed by test diets with 19en% saturated fat (including 14en% test saturated fatty acid), 3en% polyunsaturated fat, and 14en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. RESULTS: Mean concentrations of serum total, esterified and LDL cholesterol were significantly lower after 18:0 than after 16:0 (n = 16-18, P < 0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect. Receptor-mediated degradation of 125I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n = 16-18, P=0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. CONCLUSIONS: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride, was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype influenced the cholesterolemic response particularly when diets high in 16:0 were eaten.
Adult↗
Nosocomial infections with ceftazidime-resistant Pseudomonas aeruginosa: risk factors and outcome.
Prospective studies were conducted for nosocomial Pseudomonas aeruginosa infections from February 1, 1994, to October 30, 1995. Of 97 P. aeruginosa isolates from 97 patients, 35 were resistant to ceftazidime. Logistic regression revealed previous cephalosporin or piperacillin use as independent risk factors for nosocomial ceftazidime-resistant P. aeruginosa infection. Pulsed-field gel electrophoresis revealed that four nosocomial ceftazidime-resistant P. aeruginosa infections were caused by cross-infection, probably through medical personnel.
Ceftazidime↗
Lupus profundus (panniculitis) in a chronic haemodialysis patient.
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Adolescent↗
Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy.
PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60-80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE. METHODS: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA). RESULTS: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies. CONCLUSIONS: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.
Adolescent↗
Combination of fluorescent in situ hybridization and microautoradiography-a new tool for structure-function analyses in microbial ecology.
A new microscopic method for simultaneously determining in situ the identities, activities, and specific substrate uptake profiles of individual bacterial cells within complex microbial communities was developed by combining fluorescent in situ hybridization (FISH) performed with rRNA-targeted oligonucleotide probes and microautoradiography. This method was evaluated by using defined artificial mixtures of Escherichia coli and Herpetosiphon aurantiacus under aerobic incubation conditions with added [3H]glucose. Subsequently, we were able to demonstrate the potential of this method by visualizing the uptake of organic and inorganic radiolabeled substrates ([14C]acetate, [14C]butyrate, [14C]bicarbonate, and 33Pi) in probe-defined populations from complex activated sludge microbial communities by using aerobic incubation conditions and anaerobic incubation conditions (with and without nitrate). For both defined cell mixtures and activated sludge, the method proved to be useful for simultaneous identification and analysis of the uptake of labeled substrates under the different experimental conditions used. Optimal results were obtained when fluorescently labeled oligonucleotides were applied prior to the microautoradiographic developing procedure. For single-cell resolution of FISH and microautoradiographic signals within activated sludge flocs, cryosectioned sample material was examined with a confocal laser scanning microscope. The combination of in situ rRNA hybridization techniques, cryosectioning, microautoradiography, and confocal laser scanning microscopy provides a unique opportunity for obtaining cultivation-independent insights into the structure and function of bacterial communities.
Aerobiosis↗
Evaluation of exposure to ethylene glycol monoethyl ether acetates and their possible haematological effects on shipyard painters.
OBJECTIVES: To evaluate exposure to mixed solvents containing ethylene glycol monoethyl ether acetate (EGEEA) in shipyard painters, to determine if EGEEA is toxic to the bone marrow. METHODS: An industrial hygiene survey was performed to identify exposure to EGEEA of two groups of shipyard painters, a low exposure group (n = 30) and a high exposure group (n = 27). Urinary ethoxyacetic acid and methyl hippuric acid as well as haemoglobin, packed cell volume, red cell indices, total and differential white blood cell counts (WBCs), and platelet count for the shipyard painters and the control subjects were measured. RESULTS: The mean (range) exposure concentration (ppm) to EGEEA in the high and low exposure groups were 3.03 (not detectable to 18.27), 1.76 (not detectable to 8.12), respectively. The concentrations of methyl hippuric acid and ethoxyacetic acid in the high exposure group were significantly higher than those in the control group. The mean WBCs in the high exposure group were significantly lower than in the control group, and a significant proportion, six (11%) of the 57 painters, were leucopenic; none of the controls were affected. CONCLUSION: The high rate of possible haematological effects among shipyard painters and a hygienic evaluation of their working environment in the present study suggests that EGEEA might be toxic to bone marrow.
Adult↗