Periosteal fasciitis in a 7-year old girl: a diagnostic dilemma.

Periosteal fasciitis, considered a subtype of nodular fasciitis, is a rare benign soft tissue mass often misdiagnosed as a malignant lesion due to its fast and infiltrative growth pattern and histological features. Nodular fasciitis is usually found in the upper extremities in adults and in the head and neck region in children. Incorrect diagnosis may lead to overtreatment, potentially causing disturbed orofacial development in growing children. A rapidly growing asymptomatic mass, initially suspected to be a malignant bone tumour, was found in the left angle area of the mandible in a healthy 7-year-old girl. Radiographic examination revealed an exophytic, expansile and destructive nodule arising from the periosteal region. A diagnosis of periosteal fasciitis was established based on histological findings in an open biopsy specimen and the lesion was subsequently enucleated. Fluorescence in situ hybridization analysis revealed a USP6 gene rearrangement and confirmed the diagnosis molecularly. Due to the aggressive growth pattern without external trauma and the results of the gene rearrangement test, it is suggested that nodular fasciitis be regarded as a benign neoplasm rather than as a reactive process. The patient remains free of disease at 3 years after surgery.

Acoustic and neurophysiologic observations related to lingual nerve impairment.

The purpose of this study was to determine the acoustic effects of lingual nerve impairment on speech. Neurophysiologic examination and thermal quantitative sensory testing (QST) were carried out to determine if the profile, type or severity of sensory nerve impairment had effects on the degree of speech changes. The study group consisted of 5 women and 5 men with lingual nerve damage following an oral and maxillofacial surgery procedure. Time interval between the examination and the nerve damage ranged from 1 month to 20 years. Formants and fundamental frequency and duration of vowel sounds were analyzed. The patients underwent sensory tests, blink reflex and thermal QST of the lingual nerve area. The lingual nerve impairment had effects on the central acoustic features of vowel sounds. A relationship was observed between warm detection threshold values and the magnitude of second formant changes in men. It is concluded that lingual nerve impairment has gender-specific effects on speech. The variability in the acoustic changes of vowel sounds between different patients indicates individual compensatory manners of speech production following lingual nerve impairment.

Soft tissue attachment on sol-gel-treated titanium implants in vivo.

This study was designed to examine the attachment and reactions of soft tissues to sol-gel-derived TiO2 coatings. In the first experiment, TiO2 coated and uncoated titanium cylinders were placed subcutaneously into the backs of rats for 3, 11 and 90 days. Tissue response and implant surfaces were characterized with routine light microscopy and scanning electron microscopic (SEM) analysis. In the second experiment, TiO2-coated and uncoated discs were implanted subcutaneously into the backs of rats for 14 and 21 days. The discs were pulled out from the implantation sites with a mechanical testing device using a constant speed of 5 mm/min. Rupture force was registered, after which the discs were assigned for SEM and transmission electron microscopic (TEM) analysis. All the coated implants showed immediate contact with the surrounding soft tissues without a clear connective tissue capsule. Significantly better soft tissue response was measured for all the coated compared to the uncoated cylinders (p<0.01). Higher rupture forces were measured for all coated discs, although the differences were not statistically significant. An immediate and tight connection between connective tissue fibroblasts and coatings was noticed in TEM analysis. Our study indicates that TiO2 coatings improve soft tissue attachment on a titanium surface.

Comparison between sol-gel-derived anatase- and rutile-structured TiO2 coatings in soft-tissue environment.

The bioactivity of the surface reactive TiO(2) coatings for medical implants can be locally modified by CO(2) laser processing to match with the properties of surrounding tissues. The TiO(2) coatings heat-treated at 500 degrees C exhibit in vitro bioactivity. With further CO(2) laser treatment they exhibit enhanced in vitro bioactivity. The aim of this in vivo study was to compare the performance of heat-treated anatase-structured TiO(2) coatings with preheat-treated and CO(2) laser-treated rutile-structured coatings in terms of their ability to attach soft connective tissues. The coatings were characterized with TF-XRD and AFM. TiO(2)-coated discs were implanted in rats. The samples were analyzed with routine histology, SEM-EDS, and TEM. In both groups, already at 3 days, soft connective tissues were in immediate contact with the surface. No thick crystalline CaP layer was detected by SEM-EDS, but a thin amorphous CaP layer was detected by XPS. No gap between the cell membrane and the coating could be observed in TEM pictures. No differences were observed between the anatase- and rutile-structured coatings in terms of tissue responses. Further studies are needed to verify if the tissues are adherent to the surface of the implant.

Effects of transitory lingual nerve impairment on speech: an acoustic study of sibilant sound /s/.

By measuring spectral characteristics of the sibilant /s/ this study investigated whether the reduced orosensory feedback caused by lingual nerve impairment affects the acoustics and articulation of sibilants. A further goal was to examine speakers' capability to compensate for the deviant control of the delicate movements required for the proper production of /s/ by experimentally modifying the function of the tongue in a way that reduces the necessary somatosensory information in articulation. Five healthy men with no speech, language or hearing abnormalities were enrolled. They produced the sibilant /s/ in a variety of phonetic contexts in two sessions: first in normal conditions and then with local anaesthesia of the right lingual nerve. From the speech samples, the spectral characteristics of the sibilant sound (i.e. the centre of gravity, standard deviation, skewness and kurtosis) were analysed acoustically. The results showed that the reduced tactile sensation has effects on the tongue function resulting in individual and variable spectral alterations. The variation between different speakers indicates individual ability to compensate for the effects caused by the sensory dysfunction of the tongue. It seems, therefore, that the compensatory mechanisms for speech production are highly speaker-dependent.

The effect of irradiation and hyperbaric oxygenation (HBO) on extracellular matrix of the condylar cartilage after mandibular distraction osteogenesis in the rabbit.

The effects of irradiation and hyperbaric oxygenation (HBO) on the extracellular matrix of condylar cartilage after mandibular distraction were evaluated. Unilateral distraction was performed on 19 rabbits. Five study groups were included: control, low- and high-dose irradiation, and low- and high-dose irradiation groups with HBO. Additionally, four temporomandibular joints (TMJ) were used as control material. The high-dose irradiated animals were given in the TMJ 22.4 Gy/4 fractions irradiation (equivalent to 50 Gy/25 fractions). Low-dose irradiation group received a 2.2 Gy dosage. Two groups were also given preoperatively HBO 18 x 2.5ATA x 90 min. After a two-week distraction period (14 mm lengthening) and four-week consolidation period the TMJs were removed. Proteoglycan (PG) distribution of the extracellular matrix was evaluated using safranin O staining and collagen I and II using immunohistochemistry. The organization of fibrillar network was studied by polarized light microscopy. On the operated side of the control group and on the unoperated side in all, except for high-dose irradiated group, PG distribution and fibrillar network were normal appearing. In the irradiated groups, with or without HBO, the cartilaginous layer was partially or totally devoid of PG and the network structure was severely damaged. In conclusion, irradiation in conjunction with the pressure applied by distraction causes severe damage to extracellular matrix of condylar cartilage.

Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment.

The effects of irradiation and hyperbaric oxygenation (HBO) on osteoblastic activity and angiogenesis in rabbit mandibular distraction (DO) were evaluated. Three groups were studied. The mandible of two groups received a 22.4Gy dose of irradiation. One of the irradiated groups was also given HBO, 18 times at 2.5ATA for 90min per day preoperatively. The third group was given neither radiotherapy nor HBO. Mandibular lengthening was performed unilaterally. Osteoblastic activity was assessed ex vivo by [18F]fluoride digital autoradiography. Neovascularization of distracted bone was evaluated histomorphometrically. Osteoblastic activity was higher in non-irradiated than irradiated animals. In non-irradiated rabbits, the activity was evenly distributed over the distraction area. In the irradiated groups, the activity was greater in the central third of the lengthened bone than the peripheral thirds. HBO changed the osteogenic pattern towards that of non-irradiated bone. In the non-irradiated group the number of blood vessels was 1.7-fold as compared to irradiated rabbits without HBO (P=0.0012), and the fewest number of vessels was found in irradiated rabbits without HBO. Blood vessels were more numerous in the central region than in peripheral regions in non-irradiated animals and irradiated animals with HBO, but not in irradiated rabbits without HBO therapy. It is concluded that radiotherapy disturbs distraction bone formation and neovascularization related to DO. HBO increases osteoblastic activity, but not to the level of non-irradiated bone. Angiogenic response is markedly increased by HBO.

Different mechanisms of syndecan-1 activation through a fibroblast-growth-factor-inducible response element (FiRE) in mucosal and cutaneous wounds.

Syndecan-1 expression is enhanced in cutaneous and mucosal wounds. We have previously demonstrated that wounding-induced syndecan-1 expression in the skin occurs transcriptionally, through a fibroblast-growth-factor-inducible element (FiRE). Here, we show that FiRE is also activated in mucosal wounds. However, both the expression patterns and the activation mechanisms of FiRE are different from those in the skin. In the mucosa in vivo, the activation starts and ends earlier than in cutaneous wounds. FiRE is first detected at around 12 hours in keratinocytes, and the activation declines by the third day after wounding occurs. The activation is seen on the migrating sheet of epithelial mucosa, as in the case of cutaneous wounding. In contrast to the situation in vivo, organ-cultured mucosal wounds exhibit no FiRE activity, while organ-cultured cutaneous wounds show robust activity. Activation in mucosal wounds is enhanced, however, by the application of epidermal growth factor. This suggests that exogenous growth factor activity is required for activation of syndecan-1 in mucosal wounds but not in cutaneous wounds.

Osteodistraction of a previously irradiated mandible with or without adjunctive hyperbaric oxygenation: an experimental study in rabbits.

The purpose of this study was to analyse the effects of irradiation and hyperbaric oxygenation (HBO) on mandibular osteodistraction (OD). Eighteen rabbits were divided into three groups: 1. Irradiation (R), 2. Irradiation+HBO (R-HO), and 3. Control group (C). Animals of groups R and R-HO received in the mandible irradiation 22.4 Gy in four 5.6 Gy fractions (equivalent to 50 Gy/25 fractions). In addition, group R-HO was given HBO at 2.5 ATA for 90 min per day 18 times preoperatively. Unilateral osteotomy was made 1 month after completion of radiotherapy. After a 1 week latency period bone distraction was started at rate of 1 mm per day, continued for 2 weeks, and left to consolidate for 4 weeks. Amount of new bone was measured histomorphometrically from midsagittal sections. Area of new bone was equal in all groups. Bone was more mature and bone spicules better organized in group C than in groups R and R-HO. Cartilaginous cells were found in distracted bone in all groups but larger chondroid islands were evident only in group R. It seems that despite delayed bone formation, OD can be performed after radiotherapy. HBO had a beneficial effect on bone quality of a previously irradiated mandible.

Effect of mandibular distraction osteogenesis on temporomandibular joint after previous irradiation and hyperbaric oxygenation.

The purpose was to evaluate the effect of mandibular distraction osteogenesis (DO) on condylar cartilage after radiotherapy and hyperbaric oxygenation (HBO). Unilateral DO was performed on low- and high-dose irradiated rabbits with or without accompanying HBO, and non-irradiated animals. High-dose irradiated animals were given irradiation in the temporomandibular joint (TMJ) equivalent to 50 Gy in 25 fractions. Low-dose irradiated rabbits received scattered irradiation of 10% of that of high-dose irradiated animals. After radiotherapy, some of the animals were given HBO 18 times at 2.5 ATA for 90 min/day. One month after completion of radiotherapy, distraction osteotomy with distractor placement was performed. After a latency period, distraction was started at the rate of 1 mm/day, continued for 2 weeks, and the regenerate was allowed to consolidate for 1 month. Condyles of non-operated rabbits served as controls. Histological changes were more evident on the distracted than on the non-distracted side. In distracted, non-irradiated animals, condylar cartilage changes were minor and probably clinically insignificant. In irradiated rabbits, condylar cartilage changes on the lengthened side were severe, and often cartilage was either totally or partially sealed off by bone. Condylar heads were morphologically deformed. Even low doses of irradiation resulted in notable changes on the operated side, and HBO did not prevent disadvantageous effects.

Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray.

The molecular and genetic characteristics of ameloblastoma are still poorly understood. We analyzed gene expression in fresh-frozen ameloblastomas and human fetal tooth germs, using a cDNA microarray. Thirty-four genes exhibited significant changes in expression levels in the ameloblastoma. Eleven genes were overexpressed more than three-fold, and 23 genes were underexpressed to below 0.4 of the control level. The oncogene FOS was the most overexpressed gene (from eight- to 14-fold), followed by tumor-necrosis-factor-receptor 1 (TNFRSF1A). Genes for sonic hedgehog (SHH), TNF-receptor-associated-factor 3 (TRAF3), rhoGTP-ase-activating protein 4 (ARHGAP4), deleted in colorectal carcinoma (DCC), cadherins 12 and 13 (CDH12 and 13), teratocarcinoma-derived growth-factor-1 (TDGF1), and transforming growth-factor-beta1 (TGFB1) were underexpressed in all tumors. In selected genes, a comparison between cDNA microarray and real-time RT-PCR confirmed similar relative gene expression changes. The gene expression profile identifies candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development.

Osteoblast differentiation of bone marrow stromal cells cultured on silica gel and sol-gel-derived titania.

Primary cultures of osteogenic precursor cells derived from rat bone marrow stroma were performed on commercially available pure titanium discs (Ti c.p.) and surface modified Ti c.p.using a sol-gel technique (Ti sol). In separate repeated experimental runs, cell behavior and in vitro mineralization were compared with cultures on silica gel bioactive glass discs (S53P4). All substrates were incubated in simulated body fluid prior to the experiment. Overall, variable effects between experimental runs were seen. Apparently, this was due to the heterogeneous nature of the used cell population. Therefore, only careful conclusions can be made. Initial cell adhesion and growth rates between 3 and 5 days of culture--analyzed by cell numbers--were in general comparable for the two titanium substrates, while initial growth up to day 3 is suggested to be higher in Ti c.p. compared to Ti sol. Although initial cell adhesion on the S53P4 glass discs was lower than the titanium substrates, cell growth rates appeared to be higher on the silica gel compared to the two titanium substrates. Further, there were some indications that the early and late osteoblast differentiation markers, alkaline phosphatase and osteocalcin, monitored up to day 24, were elevated in Ti c.p cultures compared to Ti sol cultures. There were no differences observed in in vitro mineralization between the titanium groups. S53P4 seemed to display a substantially higher differentiating capacity for both osteogenic cell markers as well as in vitro mineralization compared to the two titanium substrates.

Craniofacial morphology in preschool children with sleep-related breathing disorder and hypertrophy of tonsils.

UNLABELLED: The purpose of this study was to examine craniofacial morphology, pharyngeal airway space and hyoid bone position in preschool children with sleep-related breathing disorder associated with hypertrophy of tonsils (SBDT). Thirty-eight preschool children, mean age 4.7 y, with SBDT and with an apnoea index (AI) of 0 < AI < 5, were divided into two groups. One consisted of 15 children with sleep-related breathing disorder (SBD) and more than 75% of the tonsils visible (GIII) and the other of 23 children with SBD and 25-75% of the tonsils visible (GII). The control group consisted of 31 children without ear, nose and throat disease and with GI (barely visible) tonsils. Compared with the controls, GIII children had a retrognathic mandible, a large posterior facial height, a large interincisal angle with retroclined lower incisors, a narrow pharyngeal airway space, an anterior tongue base position and a long soft palate. Compared with the controls, GII children had a large anterior lower facial height and a short nasal floor. However, like the controls, GII children did not have a retrognathic mandible. CONCLUSION: The findings show that children with SBDT display a characteristic facial appearance at an early age. Since the condition has an effect on growth, it needs to be prevented by controlling morphology and function at the preschool age.

Reduction of syndecan-1 expression is associated with dysplastic oral epithelium.

Syndecans are a family of integral membrane proteoglycans that participate in cell-matrix interactions and growth factor binding. Syndecan-1 expression is induced during keratinocyte differentiation and reduced in squamous cell carcinomas. The purpose of this study was to examine the alteration in syndecan-1 expression in dysplastic oral epithelium. Sixty-six oral biopsy specimens (43 epithelial dysplasias, 3 carcinoma in situ and 20 squamous cell carcinomas) were studied using immunohistochemical methods. The normal epithelium specimens were highly positive for syndecan-1. Fifteen of 46 dysplasias or carcinoma in situ specimens showed negative or weak staining for syndecan-1, two of which were totally negative. Intermediate and strong staining were observed in 17 and 14 dysplasias or carcinoma in situ specimens, respectively. Thirteen (65%) squamous cell carcinomas showed negative or weak staining for syndecan-1, seven of which were totally negative. Only three carcinomas had a strong syndecan-1 expression. Four of the 34 patients with dysplasia who were followed up developed squamous cell carcinoma. All these dysplasias had weak or totally negative syndecan-1 expression. The results suggest that the loss of syndecan-1 is associated with dysplastic changes in oral epithelium.

The effect of PUVA on langerhans cells in rat oral epithelium photosensitized with systemic methoxsalen or topical trioxsalen.

BACKGROUND/PURPOSE: Ultraviolet-A radiation (UVA) of the oral mucosa after photosensitization with either systemic methoxsalen (8-MOP) or topical trioxsalen (TMP), i.e. mouth-PUVA, has been reported to be successful in the treatment of oral lichenoid lesions. In the case of PUVA treatment of skin disorders, local immune suppressive effects have been demonstrated, and the antigen presenting epithelial Langerhans cells (LCs) have been shown to be especially sensitive to ultraviolet treatments. Our aim was to compare the photobiological effects of PUVA in oral mucous membrane (OMM) using topical TMP or systemic 8-MOP photosensitization. METHODS: Rat OMM photosensitized with topical TMP or systemic 8-MOP was treated with PUVA using UVA doses of 1-8 J/cm2. The LCs were demonstrated in epithelial sheets of the treated OMM with ATPase staining. RESULTS: Both treatments caused a sim ilar, dose-dependent depletion of ATPase-positive LCs, with a maximal depletion of 80% or 73% with 8 J/cm2 at 2 days after irradiation as photosensitized with TMP or 8-MOP, respectively. This contrasts with earlier published findings in human skin, where topical TMP is an order of magnitude greater a sensitizer than 8-MOP, and PUVA-induced depletion of LCs occurs maximally 5 days after irradiation. CONCLUSION: The depletion of LCs of rat OMM after PUVA treatment is greater using topical TMP compared to systemic 8-MOP, but the difference is significantly smaller than reported earlier in human skin.

Intraocular lens bioactivity tested using rabbit corneal tissue cultures.

PURPOSE: To evaluate the effects of different intraocular lens (IOL) materials on epithelial cell growth to test the sandwich theory; i.e., a bioactivity-based explanation of posterior capsule opacification (PCO) after cataract surgery. SETTING: Central Hospital, Vaasa, and Institute of Dentistry and Turku Center for Biomaterials, University of Turku, Finland. METHODS: Rabbit corneal tissue cultures were set up on poly(methyl methacrylate) (PMMA), heparin-surface-modified (HSM) PMMA, silicone, acrylate, and hydrogel IOLs for 1 week. The tissue consisted of intact epithelium and half the thickness of the corneal stroma, which was placed against the IOL. The growth of the epithelium was examined by light microscopy to evaluate the attachment of the corneal explant to the IOL surface. RESULTS: All tissue samples grew well under the culture conditions. When grown on PMMA, HSM PMMA, silicone, and hydrogel, the tissue did not attach to the IOL or the epithelium grew around the explant, suggesting that the attachment of the stroma to the IOL was poor or nonexistent. Some explants on acrylate IOLs attached directly to the IOL surface with no epithelial ingrowth between the stroma and the IOL. CONCLUSIONS: This tissue culture method can be used to examine the behavior of corneal tissue in contact with different IOL materials. The results suggest that the acrylate IOL may have bioactive properties. This, with the lens optic's square edge, may hinder lens epithelial cell proliferation and thus prevent PCO.

Osteopontin (OPN) distribution in premalignant and malignant lesions of oral epithelium and expression in cell lines derived from squamous cell carcinoma of the oral cavity.

The objectives of this study were to assess the immunolocalization of human osteopontin (OPN) in oral lesions and to identify human cell lines of oral squamous cell carcinoma (OSCC) origin that express OPN mRNA. OPN was localized using immunohistochemistry in the following oral specimens: normal epithelium (n=6), epithelial hyperplasia (n=4), epithelial dysplasia (n=28), carcinoma in situ (n=11) and squamous cell carcinoma (n=43). Cell lines UMSCC-1, MDA TU 138, MDA 686LN, SCC4, SCC9, SCC25, CAL 27 and MDA 1483 were characterized for OPN mRNA expression using Northern blotting. OPN was not detected in normal oral epithelium. Intracellular and intercellular immunoreactivity was seen in 75% of hyperplasias, 57% of dysplasias, 54% of carcinoma in situ and 67% of squamous cell carcinomas. UMSCC-1 expressed high levels of OPN mRNA. We conclude that OPN protein is detectable in premalignant and malignant lesions arising from oral epithelium. UMSCC-1 may be a useful cell line in which to conduct in vitro studies designed to clarify the role of OPN in OSCC.

Immunocompetent cells in amalgam-associated oral lichenoid contact lesions.

Inflammatory cells in amalgam-associated, oral lichenoid contact lesions (OLL) were studied in 19 patients by immunocytochemistry using monoclonal antibodies. Ten of the patients displayed allergic patch test (PT) reactions to several mercury compounds and nine were negative. The immunocytochemical quantification showed a uniform composition of the inflammatory mononuclear cells in the two study groups. The number of HLA-D/DR-positive dendritic cells (P<0.001) and CD1a-positive Langerhans cells (P=0.035) was significantly lower in the PT-negative than PT-positive patients. HLA-D/DR expression on keratinocytes varied from negative to full thickness staining of the epithelium. HLA-D/DR expression in the full thickness of epithelium (3) or through the basal and spinous cell layers (2) was seen in 5 of 8 PT-positive patients, whereas none of the PT-negative patients had this staining pattern (P=0.045). These patients also showed a good clinical response after amalgam removal. Consequently, OLL may represent a true delayed hypersensitivity reaction with a trans-epithelial route of entrance of the metal haptens released from dental restorative materials.

Obliteration of the frontal sinus cavity with bioactive glass.

BACKGROUND: Bioactive glass (BG) is a glass ceramic material. It has been used as surgical bone replacement material in ear and oral surgery, orthopedics, and dentistry. METHODS: Bioactive glass was used as obliteration material in a series of osteoplastic frontal sinus operations on 10 patients suffering from chronic frontal sinusitis, which other, more-conservative treatment modalities had failed to cure. RESULTS: Bioactive glass is easy to handle, and complete obliteration of all sinusal recesses and excavations is easily achieved. No adverse effects of the implant material have been seen over a mean follow-up period of 5.0 years. One patient with a local recurrent infection in the outer table of the sinus was reoperated on 5 months after primary surgery. Repeated postoperative computed tomographic scans analyzed by digital region-of-interest (ROI) selection showed no remarkable changes in the frontal sinus cavities but a slight, yearly decrease in the density of the occlusion material. Laboratory monitoring of patients and histopathologic examination of two postoperative biopsy specimens indicated that the material is well tolerated and stable. CONCLUSIONS: Bioactive glass is a promising and well-tolerated bone graft suitable for osteoplastic frontal sinus operations. Total accurate obliteration of the sinus is achieved with different sizes of granules and blocks. The results of the obliteration are maintained owing to the stability of the material.

An open clinical trial of a new mouth-PUVA variant in the treatment of oral lichenoid lesions.

OBJECTIVE: To investigate the feasibility of topical psoralen PUVA (sensitization in photosensitizing psoralen drug + UVA radiation) treatment of oral lichenoid lesions (OLL). STUDY DESIGN: A total of 16 patients with OLL were treated using a 0.01% trioxsalen ointment and UVA doses in the 0.09 to 1.80 J/cm2 range. The average number of sessions was 8.7 and a mean cumulative irradiation dose was 4.25 J/cm2. RESULTS: A marked-to-complete healing occurred in 3 to 16 (19%) patients immediately after therapy, in 4 of 14 (29%) after 3 months, and in 5 of 14 (38%) after 14 months, respectively. Of the 16 subjects with OLL, five were diagnosed as oral lichen planus (OLP) and 11 were classified as oral lichenoid reaction (OLR). Post-PUVA amelioration rate in patients with genuine OLP (4 of 5, 80%) was superior to that in patients with OLR (1 of 9, 11%). CONCLUSION: Topical trioxsalen photosensitization can be used in mouth-PUVA treatment, and lichen planus is a main indication for this therapy.