Periodontal tissue engineering by nano beta-tricalcium phosphate scaffold and fibroblast growth factor-2 in one-wall infrabony defects of dogs.

BACKGROUND AND OBJECTIVE: Nanoparticle bioceramics are being investigated for biomedical applications. We fabricated a regenerative scaffold comprising type I collagen and beta-tricalcium phosphate (ß-TCP) nanoparticles. Fibroblast growth factor-2 (FGF-2) is a bioeffective signaling molecule that stimulates cell proliferation and wound healing. This study examined the effects, on bioactivity, of a nano-ß-TCP/collagen scaffold loaded with FGF-2, particularly on periodontal tissue wound healing. MATERIAL AND METHODS: Beta-tricalcium phosphate was pulverized into nanosize particles (84 nm) and was then dispersed. A nano-ß-TCP scaffold was prepared by coating the surface of a collagen scaffold with a nanosize ß-TCP dispersion. Scaffolds were characterized using scanning electron microscopy, compressive testing, cell seeding and rat subcutaneous implant testing. Then, nano-ß-TCP scaffold, nano-ß-TCP scaffold loaded with FGF-2 and noncoated collagen scaffold were implanted into a dog one-wall infrabony defect model. Histological observations were made at 10 d and 4 wk postsurgery. RESULTS: Scanning electron microscopy images show that TCP nanoparticles were attached to collagen fibers. The nano-ß-TCP scaffold showed higher compressive strength and cytocompatibility compared with the noncoated collagen scaffold. Rat subcutaneous implant tests showed that the DNA contents of infiltrating cells in the nano-ß-TCP scaffold and the FGF-2-loaded scaffold were approximately 2.8-fold and 3.7-fold greater, respectively, than in the collagen scaffold. Histological samples from the periodontal defect model showed about five-fold greater periodontal tissue repair following implantation of the nano-ß-TCP scaffold loaded with FGF-2 compared with the collagen scaffold. CONCLUSION: The ß-TCP nanoparticle coating strongly improved the collagen scaffold bioactivity. Nano-ß-TCP scaffolds containing FGF-2 are anticipated for use in periodontal tissue engineering.

Bone augmentation using a highly porous PLGA/ß-TCP scaffold containing fibroblast growth factor-2.

BACKGROUND AND OBJECTIVE: Beta-tricalcium phosphate (ß-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using ß-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/ß-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. MATERIAL AND METHODS: The ß-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/ß-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The ß-TCP scaffold, PLGA-coated scaffold, and ß-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. RESULTS: SEM and TEM observations showed a thin PLGA layer on the ß-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/ß-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/ß-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/ß-TCP scaffold loaded with FGF-2 showed significant bone augmentation. CONCLUSION: The PLGA coating improved the mechanical strength of ß-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/ß-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation.

Impact of the Comprehensive Awareness Modification of Mouth, Chewing and Meal (CAMCAM) Program on the Attitude and Behavior Towards Oral Health and Eating Habits as Well as the Condition of Oral Frailty: A Pilot Study.

OBJECTIVES: Preserving sufficient oral function and maintaining aadequate nutrition are essential for preventing physical frailty and the following long-term care. We recently developed the 6-month Comprehensive Awareness Modification of Mouth, Chewing And Meal (CAMCAM) program, in which participants gather monthly to learn about oral health and nutrition while eating a textured lunch together. This study examined whether the CAMCAM program could improve attitude and behavior towards oral health, mastication, and diet as well as ameliorate oral frailty in community-dwelling older adults. DESIGN: Single-arm pre-post comparison study. SETTING AND PARTICIPANTS: A total of 271 community-dwelling adults (72.3 ± 5.7 years of age; 159 women [58.7%]) in 4 Japanese municipalities were recruited, of which 249 participants (92%) were assessed at the final evaluation. INTERVENTION: Participants gathered once a month at community centers to learn about oral health and nutrition while eating a "munchy" textured lunch containing proper nutrition. MEASUREMENTS: Oral frailty, frailty, and eating behavior were evaluated with the Oral Frailty Index-8 (OFI-8), Kihon checklist (KCL), and CAMCAM checklist, respectively. Participants were divided into Oral frailty (OF) and Robust groups according to OFI-8 scores. The differences in KCL and CAMCAM checklist results between the OF and Robust groups were statistically tested along with changes in scores after the program. RESULTS: KCL and CAMCAM checklist scores were significantly lower in the OF group at the initial assessment. OFI-8 and KCL findings were significantly improved in the OF group after completing the program (all P <0.05). Regarding the CAMCAM checklist, awareness of chewing improved significantly in the Robust group (P=0.009), with a similar tendency in the OF group (P=0.080). CONCLUSION: The findings of this pilot study suggest that the CAMCAM program may improve both oral and systemic frailty in addition to attitudes towards chewing, oral health, and meals, especially in individuals with oral frailty. The CAMCAM program merits expansion as a community-based frailty prevention program.

Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation.

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Hashimoto's encephalopathy after interferon therapy for hepatitis C virus in adult liver transplant recipient accompanied by post-transplant lymphoproliferative disorder related to Epstein-Barr virus infection.

A 55-year-old woman underwent living-donor liver transplantation (LDLT). She had no history of autoimmune diseases. Spleen was preserved. Steroids were withdrawn at 3 months after LDLT. Epstein-Barr virus (EBV) infection occurred at 3.5 years after LDLT. Recurrent hepatitis C virus infection was confirmed at 4.5 years after LDLT, and pegylated interferon was introduced. Diagnosis of EBV-positive post-transplant lymphoproliferative disorder (PTLD) was made at 4.8 years after LDLT, and tacrolimus (Tac) was stopped completely. Then, unconsciousness, convulsion, and cervical stiffness appeared suddenly. Electroencephalography, cerebrospinal fluid analysis, and image studies revealed normal or only nonspecific findings. The patient was in a state of exhaustion; therefore, steroid pulse therapy (SPT) was attempted. Surprisingly, her general condition, including consciousness disturbance, was improved markedly, and Hashimoto's encephalopathy (HE) was suspected, based on this reaction to SPT. Elevations of anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were confirmed. After withdrawal of Tac, and treatment with acyclovir and steroids, EBV-positive PTLD and HE improved, although they recurred at 5.1 years after LDLT. SPT improved only neurological symptoms. Molecular-targeted therapy was given for recurrent PTLD, based on analysis of sampling specimens. This therapy was effective, but tumor lysis syndrome occurred, and the patient died at 5.3 years after LDLT.

Positive Effects of "Textured Lunches" Gatherings and Oral Exercises Combined with Physical Exercises on Oral and Physical Function in Older Individuals: A Cluster Randomized Controlled Trial.

OBJECTIVES: Proper nutrition and physical exercises are essential to prevent frailty in older adults. Proper masticatory performance and oral function may influence on physical activities as well since the mouth is the entrance of nutrition and digestion. Thus, the present study aimed to test the combined program of specially devised lunch gatherings containing textured foods with oral and physical exercises on the improvement of oral and physical function in community-dwelling older adults. DESIGN: A Cluster randomized controlled trial; Setting and Participants: Eighty-six community-dwelling older adults in Daito city, Japan, were randomly assigned into control (n = 43) or intervention (n = 43) groups. INTERVENTION: The control group performed the physical exercise regimen only. The intervention group participated in a 12-week physical and oral exercise program and ate a so-called "munchy lunch" that introduced textured foods with proper nutrients together after performing the physical exercise twice a week following brief dietary instruction at the intervention onset. Physical training and lunch gatherings were held at local public centers. MEASUREMENTS: The differences in measured variables for physical and oral function between baseline and 12 weeks of intervention were statistically tested. RESULTS: Oral function as measured by tongue pressure increased significantly in the intervention group (p=0.031), but not in the control group. Physical properties and activities, including body fat percentage and results of the timed up and go test, decreased more significantly in the intervention group than in controls (p<0.05). CONCLUSIONS: Our findings suggest that a combined program of textured lunch gatherings with oral and physical exercises may improve physical and oral function as a preventative approach for frailty in community-dwelling older adults.

Oxidation-dependent changes in the stability and permeability of lipid bilayers.

Peroxidation-dependent change in the permeability of lipid bilayers was mesaured by using artificial membrane systems, that is, planar lipid bilayers and liposomes. The unsaturated fatty acyl chains of phospholipids in small unilamellar vesicles were peroxidized time-dependently by the hydroxyl radical chemically generated by the reaction of H2O2 and Cu(en)2. In contrast, at the same hydroxyl radical concentration and time ranges, no ionic current through the planar lipid bilayers and no release of K+ from the liposomes were observed. These findings indicate that accumulation of lipid peroxide within lipid bilayers is not responsible for the permeability increase that is often observed in biomembranes exposed to oxidative stresses. Higher concentration of the hydroxyl radical caused break-down of the planar lipid bilayers composed of the mixture (7:3) of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). The bilayer containing 100% PE at least at one leaflet of the bilayer (facing the hydroxyl radical-generating solution) was not broken-down by the application of the hydroxyl radical, suggesting that PE stabilizes the planar lipid bilayer against the attack of the hydroxyl radical.

The efficacy of prevascularization by basic FGF for hepatocyte transplantation using polymer devices in rats.

This study used polymer devices implanted in rats to investigate the effect of prevascularization by basic fibroblast growth factor (bFGF) on hepatocyte transplantation (HTx). Lewis rats served as both donors and recipients. Polyvinyl alcohol (PVA) sponges with either hydrogel containing bFGF (bFGF group) or distilled water (control group) were implanted between the mesenteric leaves of recipient rats. Hepatotrophic stimulation was induced by a portacaval shunt and a 70% partial hepatectomy. After 1 week of prevascularization, hepatocytes harvested from the donor Lewis rats using a collagenase digestive method were injected into the sponges. Specimens were harvested at 2 weeks, 1 month, and 2 months after HTx. Histologic examination revealed that the control groups contained small numbers of hepatocytes restricted to the peripheral areas of the sponges. However, a large number of hepatocytes, including clusters, was found distributed uniformly in the bFGF group. In the bFGF group at 2 weeks, 1 month, and 2 months, the percentage of the sponge occupied by hepatocytes was 7.21+/-2.64%, 6.98+/-2.59%, and 5.58+/-3.77%, respectively. The corresponding ratios for the control group were 0.40+/-0.39%, 0.40+/-0.40%, and 0.87+/-1.51%. In addition, the mean number of new blood vessels in the bFGF group was significantly greater than that in the control group at 0 days, 2 weeks, and 1 month after HTx. These results suggest that bFGF strongly induced vascularization, which enabled a large number of hepatocytes to survive in the polymer devices.

Growth of the subclavian artery and the anastomosis in Blalock-Taussig shunt: absorbable versus nonabsorbable suture.

BACKGROUND: We evaluated the growth of Blalock-Taussig shunts placed with absorbable suture by cineangiographic findings and long-term results and compared them with those in an earlier group of patients in whom we used nonabsorbable suture. METHODS: Eighty-one patients had postoperative cineangiography 1 year or more after a Blalock-Taussig shunt procedure. From September 1985 to December 1994, 40 patients (group I) underwent a Blalock-Taussig shunt procedure with the use of absorbable polydioxanone suture, and from January 1980 to August 1989, 41 (group II) underwent the same operation with nonabsorbable polypropylene suture. Cineangiograms were reviewed to assess shunt patency and growth of the subclavian arteries and the subclavian artery-pulmonary artery anastomoses. RESULTS: At the Blalock-Taussig shunt operation, mean outer diameters of the subclavian artery and the anastomosis in group I were 3.8 +/- 0.1 mm and 4.1 +/- 0.1 mm, respectively and 3.9 +/- 0.1 mm and 4.0 +/- 0.1 mm in group II. The mean inner diameters of the subclavian artery and the anastomosis measured in postoperative cineangiograms were 7.9 +/- 0.5 mm and 4.6 +/- 0.2 mm, respectively in group I and 6.6 +/- 0.4 mm and 3.1 +/- 0.2 mm in group II. The diameters of both the subclavian artery (p < 0.05) and the anastomosis (p < 0.001) were significantly greater in group I than in group II. Five years after operation, 71.1% +/- 7.4% of patients in group I and 54.8% +/- 8.0% in group II had good palliation. CONCLUSIONS: The use of absorbable polydioxanone suture has an advantage in terms of growth of the diameters of the subclavian artery and the anastomosis in a Blalock-Taussig shunt and may improve the long-term results after this shunt operation in infancy.

The ultrastructure and hardness of the transparent layer of human carious dentin.

The ultrastructure of the transparent layer of carious dentin was investigated in relation to hardness. This layer was the deeper part of the intermediately-softened inner carious dentin. Intratubular deposition of fine crystals was initially observed at the uppermost layer of normal dentin, increased in the subtransparent layer, and gradually shifted to deposition of rhomboid-shaped crystals in the transparent layer. Crystals were not seen in the tubules in the overlying discolored layer. Softening, due to demineralization of the intertubular and peritubular dentin, started at the bottom of the subtransparent layer and increased in the outward direction.

Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy.

Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy were investigated. Acrylic and stainless steel cylindrical cones of 6, 7, and 8 cm in diameter and electron beams of energies 6, 9, 12, 15, 18, and 21 MeV were used for the measurements. Both acrylic and stainless steel cones showed high dose areas along the rim. The dose along the rim grew with increasing electron beam energy. The highest dose along the rim was 115% of the maximum dose on a central axis when a 6-cm-diameter acrylic cone and 21-MeV electrons were combined.

Thermal membrane potential across charged membranes in 2-1 and 1-2 electrolyte solutions.

Measurements of thermal membrane potential across cation exchange membranes in MgCl2, CaCl2 and BaCl2 solutions and across anion exchange membranes in K2SO4, Na2SO4 and K2CO3 solutions were carried out. The magnitude of the thermal membrane potential for divalent counterions is lower than that for monovalent counterions. If the transport number of counterions in the membrane phase is unity, the slopes of the temperature coefficient of thermal membrane potential against logarithmic activities of counterion in the external solution are predicted to be--R/2F for 2-1 electrolytes with cation exchange membranes and R/2F for 1-2 electrolytes with anion exchange membranes, respectively.

G-proteins coupled to phosphoinositide hydrolysis in the cochlear and vestibular sensory epithelia of the rat are insensitive to cholera and pertussis toxins.

In the cochlear (CSE) and vestibular sensory epithelia (VSE), phosphoinositides are hydrolyzed in response to stimulation of phospholipase C (PLC) by cholinergic muscarinic and purinergic P2y agonists. Such receptor-mediated activation of PLC is expected to be coupled through guanine nucleotide-binding proteins (G-proteins). Although several classes of G-proteins have been identified in the inner ear, nothing is known about the type of G-proteins associated with the phosphoinositide second messenger system in CSE and VSE. Phosphoinositide hydrolysis was determined by the release of radiolabeled inositol phosphates (InsPs). Ten mM NaF plus 10 microM AlCl3 increased basal InsPs accumulation 2-fold in both CSE and VSE of the rat. Release of InsPs was also enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) in saponin-permeabilized tissues. Furthermore, release of InsPs stimulated by both carbamylcholine (CCh) and adenosine 5'-O-[3-thiotriphosphate] (ATP-gamma-S) was significantly inhibited by 100 microM guanosine 5'-O-[2-thiodiphosphate] (GDP-beta-S). These results strongly suggest the involvement of G-proteins in the receptor-PLC coupling in CSE and VSE. ADP-ribosylation in membrane fractions of CSE and VSE in the presence of cholera toxin (CTX) or pertussis toxin (PTX) indicated the existence of Gs- and G(i)-type G-proteins. However, neither CTX nor PTX affected basal or agonist-stimulated release of InsPs. These observations suggest that muscarinic and P2y purinergic receptors are coupled to PLC via CTX- and PTX-insensitive G-proteins in CSE and VSE.

High-pressure magnetic resonance imaging up to 40 MPa.

A high-pressure vessel designed for use with commercial magnetic resonance imaging equipment at up to 40 MPa of pressure was used and tested. Special features of the vessel are the following: 1) 12.6 mm sample chamber i.d.; 2) only non-magnetic parts; 3) visible sample from the outside; 4) resistant to corrosive chemicals, and; 5) sample could be manually translated and rotated in situ. This apparatus was demonstrated through observation of CO(2) clathrate-hydrate growth in a water droplet injected into liquid CO(2) at 20 MPa.

Quantitative comparison of two types of planar lipid bilayers--folded and painted--with respect to fusion with vesicles.

Two major types of planar lipid bilayers, painted and folded, were compared with respect to vesicle fusion using one chamber for the preparation of both bilayers. Liposomes containing ion channels composed of nystatin and ergosterol were used as the vesicle sample. Fusion of the liposome to either bilayer elicited a spike-like current change, which corresponds to a fusion event. The lag time between the first fusion event and the addition of the vesicles is an index of the ease with which the vesicles fuse with the bilayers. The lag time in the painted bilayer at a KCl concentration (cis) of 450 mM was 1.58+/-1.18 min, similar to that in the folded bilayer (1.65+/-0.64 min). The lag time decreased with increase of the osmotic difference across the painted bilayer, whereas this change was small in the folded bilayer. The fusion of the liposomes to the painted bilayer was markedly reduced by stopping the stirring in the cis compartment, whereas the fusion to the folded bilayer was not affected significantly. These results imply that no practical difference exists in the ability of vesicles to fuse with the painted and folded bilayers. For the study of single channel behavior, the painted bilayer could have an advantage because simply stopping the stirring prevents excess fusion.

Surgical treatment of ventricular septal perforation with right ventricular infarction.

A 71-year-old woman underwent an emergency surgery for ventricular septal perforation together with right ventricular infarction. The perforation of the anterior septum was closed using. Dacron patch combined with a little larger bovine pericardium, the surplus of which was stitched in the surrounding viable muscle. This procedure was performed only through the infarct of the right ventricle. She has been doing well with no residual shunt and lives a normal life now.

[A comparative study of UFT enteric-coated granules with UFT capsules on the occurrence of side effects in patients with head and neck cancers--a special attention to the upper gastrointestinal tract disorders].

A comparative study on the occurrence of gastrointestinal side effects between UFT enteric-coated granules (UE) and UFT capsules (UC) was made by crossover method in 50 patients with head and neck cancer who were treated by these drugs as a surgical and/or radiation adjuvant chemotherapy. UE was significantly low in the occurrence of upper gastrointestinal side effects; remarkably low in such side effects as nausea and vomiting, in particular. On the other hand, there was little difference between UE and UC in the occurrence of such side effects as diarrhea, stomatitis, dry mouth and hematotoxic signs. The present result suggests that UE is clinically useful for treating the patients with cancer, with less occurrence of gastrointestinal side effects.

[Biliary endoprosthesis using metallic stents in management of malignant biliary strictures].

Metallic stents were placed percutaneous-transhepaticaly in 65 patients for palliation of malignant biliary obstruction. Fifty-five patients were managed without jaundice 1-12 months (median, 6.8 months) after stent placement. Ten patients had recurrent jaundice due to ingrowth of tumor through the stents. No stent-related complications were seen in all patients. The small transhepatic track required makes insertion easier, less painful, and probably safer when compared with plastic stents, and the large internal lumen reduces the rate of occlusion by encrusted bile. The metallic biliary stent is suggested as an effective treatment for malignant biliary obstruction.

Pre-clinical evaluation of a new dental panoramic radiographic system based on tomosynthesis method.

OBJECTIVES: The purpose of the study was to compare the image generated by a classic panoramic machine equipped with a cadmium telluride sensor capable of digital tomosynthesis and special software with images produced by other popular panoramic X-ray machines using a charge-coupled device and native software for image capture. METHODS: Panoramic images were made using a phantom of a human skull on Planmeca ProMax, Planmeca EC Proline, Kodak 8000 and PC-1000. With the last machine we used the PanoACT® software to adjust the entire arch and to adjust the image in selected regions of interest (ROIs). Ten viewers evaluated the images and provided the viewer data. ANOVA for repeated measures was used to compare the means by pairwise comparisons of means. RESULTS: The image of the entire arch adjusted by the PanoACT® software was statistically superior to the images produced by other machines. The images generated and individually adjusted by PanoACT® were statistically superior to all other images. CONCLUSIONS: The image generated by the cadmium telluride sensor has great potential and can be processed to create superior images to those taken with other machines. Furthermore, the ROI individual images enhanced by the PanoACT® were superior to the entire arch adjusted by the same software.

Development of a new dental panoramic radiographic system based on a tomosynthesis method.

The objective of this study was to develop a new practical method to reconstruct a high-quality panoramic image in which radiographers would be free from the onerous task of correctly locating the patient's jaws within the image layer of the panoramic unit. In addition, dentists would be able to freely select any panoramic plane to be reconstructed after the acquisition of the raw scan data. A high-speed data acquisition device was used with a CdTe (cadmium telluride) semiconductor detector and a sophisticated digital signal-processing technique based on tomosynthesis was developed. The system processes many vertical strip images acquired with the detector and generates a high-resolution and high-contrast image. To apply the tomosynthesis technique to the acquired strip images correctly, the actual movement of the panoramic unit was measured, including the X-ray tube and detector, in a scan using a calibration phantom and the authors generated a shift amount table needed for the shift-and-add tomosynthesis operation. The results of the experiments with a PanoACT-1000 panoramic unit, which was a PC-1000 panoramic unit fitted with a high frame rate semiconductor detector SCAN-300FPC, demonstrated the capability of a tomosynthesis technique which, when applied to the strip images of a dry skull phantom, could change the location and inclination of an imaging plane. This system allowed the extraction of an optimum-quality panoramic image regardless of irregularities in patient positioning. Moreover, the authors could freely reconstruct a fine image of an arbitrary plane with different parameters from those used in the original data acquisition to study fine anatomical details in specific locations.