Care needs of Japanese men for sexual dysfunction associated with prostate cancer treatment.

PURPOSE: Prostate cancer (PC) treatment causes sexual dysfunction (SD) and alters fertility, male identity, and intimate relationships with partners. In Japan, little attention has been paid to the importance of providing care for SD associated with PC treatment. This study is aimed at clarifying the care needs of Japanese men regarding SD associated with PC treatment. METHODS: One-to-one semi-structured interviews were conducted with 44 PC patients to identify their care needs. Data were analyzed using thematic analysis. RESULTS: Four core categories emerged from the analysis. (1) "Need for empathy from medical staff regarding fear of SD": patients had difficulty confiding in others about their sexual problems, and medical staff involvement in their SD issues was lacking. (2) "Need for information that provides an accurate understanding of SD and coping strategies before deciding on treatment": lack of information about SD in daily life and difficulty understanding information from medical institutions, caused men to regret their treatment. (3) "Need for professional care for individuals and couples affected by SD": men faced loss of intimacy because of their partners' unwillingness to understand their SD issues or tolerate non-sexual relationships. (4) "Need for an environment that facilitates interaction among men to resolve SD issues": men felt lonely and wanted to interact with other patients about their SD concerns. CONCLUSION: These findings may help form care strategies tailored to these needs and applicable to other societies with strong traditional gender norms.

Quality control system for mammographic breast positioning using deep learning.

This study proposes a deep convolutional neural network (DCNN) classification for the quality control and validation of breast positioning criteria in mammography. A total of 1631 mediolateral oblique mammographic views were collected from an open database. We designed two main steps for mammographic verification: automated detection of the positioning part and classification of three scales that determine the positioning quality using DCNNs. After acquiring labeled mammograms with three scales visually evaluated based on guidelines, the first step was automatically detecting the region of interest of the subject part by image processing. The next step was classifying mammographic positioning accuracy into three scales using four representative DCNNs. The experimental results showed that the DCNN model achieved the best positioning classification accuracy of 0.7836 using VGG16 in the inframammary fold and a classification accuracy of 0.7278 using Xception in the nipple profile. Furthermore, using the softmax function, the breast positioning criteria could be evaluated quantitatively by presenting the predicted value, which is the probability of determining positioning accuracy. The proposed method can be quantitatively evaluated without the need for an individual qualitative evaluation and has the potential to improve the quality control and validation of breast positioning criteria in mammography.

Sexual dysfunction associated with prostate cancer treatment in Japanese men: a qualitative research.

PURPOSE: We investigated the experiences of Japanese men with sexual dysfunction associated with various prostate cancer treatments. METHODS: We included 38 Japanese men who underwent the following initial treatments for prostate cancer: radical prostatectomy (n = 10), external beam radiotherapy (n = 12), brachytherapy (n = 5), and androgen deprivation therapy (n = 11). Semi-structured interviews were conducted regarding sexual dysfunction associated with prostate cancer treatment. Data were analyzed using a content analysis method. To obtain a unique experience for each treatment, we confirmed and organized the treatment method from which the code that constituted each category was derived. The category reliability was calculated based on Scott's formula for the matching rate of the classification by three qualitative researchers. The criterion for good reliability was set at 70%. RESULTS: Japanese men with sexual dysfunction associated with prostate cancer treatments experienced the following: a desire to maintain sexual function and conflict in decision-making concerning the initial treatment for prostate cancer; a loss of values related to sexual dysfunction; an uncertainty regarding the consequences of sexual dysfunction; a sense of calm with fewer adverse effects of sexual dysfunction at the early treatment stage; an effort to accept sexual dysfunction; and management of their changed body at the later treatment stages. The concordance rates for the categories were 70% and 78%. Additionally, there were glimpses of experiences common to all treatments and trends in treatment-specific experiences. CONCLUSION: It is necessary to provide care based on the experience of Japanese men with sexual dysfunction after prostate cancer treatment.

High Cervical Spinal Cord Compression Associated with Anomaly of Bilateral Vertebral Arteries.

BACKGROUND: Anomalies of the vertebral arteries are rare and usually detected incidentally. However, very rarely, they can manifest with clinical symptoms. We describe such a symptomatic case of high cervical spinal cord compression associated with persistent C2 segmental arteries. CASE DESCRIPTION: A 67-year-old man presented with a 5-year history of worsening left-sided weakness and gait disturbance. Magnetic resonance imaging, 3-dimensional computed tomography, and digital subtraction angiography revealed anomalous courses of the vertebral arteries, which compressed the cervical spinal cord at the C1 level from both sides. Interestingly, the left vertebral artery had fenestration, which supposedly reflected that the intradural paramedian longitudinal axis had developmentally persisted until more distally on the left. Microvascular decompression was performed to transpose the offending vertebral arteries. With vascular tapes made of polyglycolic acid sheets and fascia, the vertebral arteries compressing the cervical spine were anchored to the dura mater of the vertebral arch. This maneuver effectively relieved the neurovascular conflict created by the bilateral anomalous vertebral arteries, and the patient's myelopathy improved after surgery. To our knowledge, this is the first report to clearly demonstrate this combination of vertebral artery anomalies causing clinical symptoms and its successful treatment by microvascular decompression. CONCLUSIONS: Transposition of the vertebral artery by anchoring to the dura mater of the vertebral arch could be an effective and safe option for these disease conditions.

Comprehensive genetic characterization of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection.

A rosette-forming glioneuronal tumor (RGNT) is a rare mixed neuronal-glial tumor characterized by biphasic architecture of glial and neurocytic components. The number of reports of genetic analyses of RGNTs is few. Additionally, the genetic background of the unique biphasic pathological characteristics of such mixed neuronal-glial tumors remains unclear. To clarify the genetic background of RGNTs, we performed separate comprehensive genetic analyses of glial and neurocytic components of five RGNTs, by tissue microdissection. Two missense mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in both components of one case, were detected. In the latter case with PIK3CA mutation, the additional FGFR1 mutation was detected only in the glial component. Moreover, the loss of chromosome 13q in only the neurocytic component was observed in one other case. Their results suggested that RGNTs, which are tumors harboring two divergent differentiations that arose from a single clone, have a diverse genetic background. Although previous studies have suggested that RGNTs and pilocytic astrocytomas (PAs) represent the same tumor entity, their results confirm that the genetic background of RGNTs is not identical to that of PA.

Molecular-genetic and clinicopathological prognostic factors in patients with gliomas showing total 1p19q loss: gain of chromosome 19p and histological grade III negatively correlate with patient's prognosis.

Although 1p19q codeleted gliomas are the most favorable molecular subgroup of lower-grade gliomas, there are cases with early recurrence or short survival. The objective of this study was to elucidate molecular-genetic and clinicopathological prognostic factors in patients with gliomas showing total 1p19q loss. The study included 57 consecutive patients with codeleted gliomas who were operated at Keio University Hospital between 1990 and 2010. These patients were assessed for chromosomal copy number aberrations, promoter methylation status of the O6-methylguanine-DNA methyltransferase gene (MGMT), and demographic and clinicopathological prognostic factors in diffuse gliomas. No significant difference was observed in the overall survival (OS) of the patients with respect to age (≥40 years vs. <40 years), degree of resection, maximum tumor diameter (≥5 cm vs. <5 cm), histological subtype, and MGMT promoter methylation status. Gain of chromosome 19p and grade III histology were associated with shorter OS (P = 0.019, 0.061, respectively). Gain of 19p and histological grade III might be negative prognostic factors for the patients with gliomas showing total 1p19q loss. Further investigation is warranted to confirm these notions.

World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.

Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.

High-Contrast Imaging of Intermediate-Mass Giants with Long-Term Radial Velocity Trends.

A radial velocity (RV) survey for intermediate-mass giants has been operated for over a decade at Okayama Astrophysical Observatory (OAO). The OAO survey has revealed that some giants show long-term linear RV accelerations (RV trends), indicating the presence of outer companions. Direct imaging observations can help clarify what objects generate these RV trends. We present the results of high-contrast imaging observations of six intermediate-mass giants with long-term RV trends using the Subaru Telescope and HiCIAO camera. We detected co-moving companions to γ Hya B ( 0.61 - 0.14 + 0.12 M ⊙ ) , HD 5608 B (0.10 ± 0.01M ⊙), and HD 109272 B (0.28 ± 0.06M ⊙). For the remaining targets(ι Dra, 18 Del, and HD 14067) we exclude companions more massive than 30-60 M Jup at projected separations of 1''-7''. We examine whether these directly imaged companions or unidentified long-period companions can account for the RV trends observed around the six giants. We find that the Kozai mechanism can explain the high eccentricity of the inner planets ι Dra b, HD 5608 b, and HD 14067 b.

Near-infrared imaging polarimetry of LkCa 15: A possible warped inner disk.

We present high-contrast H-band polarized intensity images of the transitional disk around the young solar-like star LkCa 15. By utilizing Subaru/HiCIAO for polarimetric differential imaging, the angular resolution and the inner working angle reach 0.07 and r = 0″.1, respectively. We obtained a clearly resolved gap (width ≲ 27 au) at ~48 au from the central star. This gap is consistent with images reported in previous studies. We also confirmed the existence of a bright inner disk with a misaligned position angle of 13° ±4° with respect to that of the outer disk, i.e., the inner disk is possibly warped. The large gap and the warped inner disk both point to the existence of a multiple planetary system with a mass of ≲ 1 M Jup.

PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas.

Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

Spatial Relationship between Hypoglossal Schwannoma and the Vertebral Artery Using the Far-Lateral Approach.

In hypoglossal schwannoma removal via the far-lateral approach needs care as the vertebral arteries are usually adjacent to the tumors. Thus, it is important to understand their location respective to schwannoma to conduct a safe surgery. We reviewed the data of eight patients with hypoglossal schwannoma who underwent surgery in Keio University Hospital in 2005-2013. There were five males and three females (mean age at initial presentation was 48.6 years, range 38-72 years). We especially focused on the spatial relationship between the vertebral artery and the tumor, and evaluated their spatial relationship from intraoperative findings. All eight hypoglossal schwannomas included in the current study were type B according to Kaye's classification. As for spatial relationship between the tumor and the vertebral artery, in six out of eight cases, the vertebral artery was located inside or beneath the tumor; in contrast, in the other two cases, it was pushed out by the tumor and identified just after dural opening. Through the far-lateral approach, we found that the vertebral artery was located inside or beneath in most hypoglossal schwannoma; however, the vertebral artery was occasionally located on the tumor surface. From an anatomical perspective, we speculate this unique location of the vertebral artery in these cases is due to the unusual course of the hypoglossal nerve of tumor origin.

Molecular-genetic and clinical characteristics of gliomas with astrocytic appearance and total 1p19q loss in a single institutional consecutive cohort.

The prognostic significance of 1p19q loss in astrocytic gliomas has been inconclusive.We collected 57 gliomas with total 1p19q loss from among 218 cases of WHO grade-II/III gliomas operated at Keio University Hospital between 1990 and 2010. These tumors were classified as oligodendroglial or "astrocytic" by a WHO-criteria-based institutional diagnosis. Chromosomal copy number aberrations (CNAs), IDH 1/2 mutations, MGMT promoter methylation, and expression of p53 and ATRX were assessed. Survival outcome was compared between the two histological groups.Of the 57 codeleted gliomas, 37, 16, and four were classified as oligodendroglial, "astrocytic", and unclassified, respectively. Comparative genomic hybridization revealed that although chromosome 7q/7 gain was more frequent in "astrocytic" gliomas, other CNAs occurred at a similar frequency in both groups. None of the "astrocytic" gliomas showed p53 accumulation, and ATRX loss was found in three of the 15 "astrocytic" gliomas. The estimated overall survival (OS) curves in the patients with codeleted oligodendroglial and "astrocytic" gliomas overlapped, and the median OS was 187 and 184 months, respectively. Histopathological re-assessment by a single pathologist showed consistent results.Gliomas with total 1p19q loss with "astrocytic" features have molecular and biological characteristics comparable to those of oligodendroglial tumors.

Dumbbell-shaped abducens schwannoma: case report.

Schwannomas of the abducens nerve are uncommon. Nineteen cases have been reported in the literature and are classified into two types: Type 1, in the cavernous sinus, and Type 2, in the prepontine area. However, a dumbbell-shaped type has not yet been reported. Here we report the first case of a dumbbell-shaped abducens schwannoma and classify this type into a new category (Type 3). A 36-year-old woman presented with left hearing disturbance for 4 years, dizziness for 2 years, and dysphagia for 6 months. Neurological examination showed left sensorineural hearing impairment, hypesthesia in the distribution of the left first and second branches of the trigeminal nerve, left curtain sign, and gait disturbance. Computed tomography and magnetic resonance imaging revealed a dumbbell-shaped tumor located in the cavernous sinus that extended to the right cerebellopontine angle. She underwent a two-staged operation; the first operation was via ananterior transpetrosal approach for the lesion in the middle fossa and the upper part in the posterior fossa, and the second surgery was via alateral suboccipital approach for the lower part in the posterior fossa. In the first operation, the abducens nerve was sacrificed. Histological examination confirmed schwannoma. Postoperatively, hearing disturbance and ataxia were improved and complete abducens nerve paresis appeared. The dumbbell-shaped abducens schwannoma has novel clinical features, difficulty of sixth nerve preservation, and unique surgical approach.

Genotypic characterization of Staphylococcus aureus isolates from cases of keratitis and healthy conjunctival sacs.

PURPOSE: Staphylococcus aureus is the predominant pathogen that causes keratitis, and the rate of occurrence of drug-resistant S. aureus is increasing. However, little is known about its clinical epidemiology in Japan. This study was designed to characterize the genotypes of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates from keratitis and healthy conjunctival sacs. METHODS: Thirty keratitis isolates (19 MSSA and 11 MRSA) and 18 healthy conjunctival sac isolates (16 MSSA and 2 MRSA) obtained before cataract surgery were used. They were characterized by multilocus sequence typing. The prevalence of Panton-Valentine leukocidin was determined. RESULTS: In multilocus sequence typing analysis, ST5 and ST764 (ST5 variant) were the most frequently identified sequence types in MRSA strains from both keratitis and healthy conjunctival sacs. ST188 was the most frequently identified sequence type in the 19 MSSA isolates from keratitis (4 isolates, 21.1%), but was only identified in 1 of the 16 commensal MSSA strains. ST8 was found to be predominant among the 16 commensal MSSA strains (5 isolates, 31.3%). None of the isolates had Panton-Valentine leukocidin genes. CONCLUSIONS: MRSA isolates from keratitis and healthy conjunctival sacs may have similar genotypic characteristics, but certain clones occur more often among MSSA isolates from keratitis than among commensal MSSA strains. These results suggest that specific MSSA lineages that possess genotypic characteristics can more effectively cause keratitis.

Immunohistochemical and molecular genetics study of a granular cell astrocytoma: a case report of malignant transformation to a glioblastoma.

We treated a 56-year-old woman who had a right temporal lobe tumor found by chance after a traffic accident. MRI confirmed a heterogeneously enhanced tumor in the temporal lobe with large peritumoral edema extending to the superior parietal lobe. The patient underwent tumor resection. The tumor consisted largely of distinct cells with discrete borders and granular cytoplasm. In granular cells, the accumulation of PAS-positive granules was observed. Immunohistochemical analysis demonstrated positive staining for GFAP, S-100, and oligodendrocyte transcription factor 2 and negative staining for synaptophysin. CD68 was negative in granular cells, but positive in stromal cells. Ki-67 labeling index was quite low. The tumor was diagnosed as a granular cell astrocytoma (GCA). Postoperative radiotherapy combined with temozolomide was administered. One month after chemoradiotherapy, the tumor occurred in the parietal lobe, and a tumorectomy was performed. The tumor was composed of poorly differentiated astrocytic tumor cells with prominent microvascular proliferation and necrosis. A small number of granular cells were locally observed and the tumor was diagnosed as a glioblastoma. O6-methylguanine-DNA methyltransferase promoter methylation was detected in the GCA but not in the glioblastoma. Isocitrate dehydrogenase mutations were not detected in either tumor. Comparative genomic hybridization analysis demonstrated that no chromosomal abnormality was found in the GCA; however, a gain of chromosomes 7 and 19 and a loss of chromosomes 10 and 9p21 (CDKN2A) were found in the glioblastoma. p53 was strongly expressed in both the GCA and glioblastoma. The tumor progressed despite extensive chemotherapy, and the patient died 1 year after the initial treatment. Our immunohistochemical, genetic and chromosomal analyses indicate that the glioblastoma was transformed from the GCA.

PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

RATIONALE: Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected. OBJECTIVE: We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity. METHODS AND RESULTS: Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage. CONCLUSIONS: Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

Changing modified regions in the genome in hematopoietic stem cell differentiation.

In the process of hematopoietic stem cell (CD133+ cell) differentiation, a drastic change in gene expression occurs which must be regulated by epigenetic mechanisms. One strategy for CD133+ cell differentiation analysis is to identify genomic DNA regions that have been modified in the process of differentiation. However, it is difficult to obtain large amounts of genomic DNA from uniform CD133+ cells. Based on this situation, we screened genomic DNA regions where modifications change during the process of differentiation in human CD133+ cells using differential methylation site scanning (DMSS), which is a method of identifying differentially methylated regions of the genome from a small number of cells. As a result, we cloned three DNA fragments which corresponded to centrosomal protein 68kDA (Cep68), TRIO and F-actin binding protein (TRIOBP), and AMP-activated protein kinase beta (AMPKb).

Synchrotron radiation coronary microangiography for morphometric and physiological evaluation of myocardial neovascularization induced by endothelial progenitor cell transplantation.

BACKGROUND: Therapeutic effect of stem cell transplantation (SCTx) for myocardial neovascularization has been evaluated by histological capillary density in small animals. However, it has been technically difficult to obtain imaging evidence of collateral formation by conventional angiography. METHODS AND RESULTS: Peripheral blood CD34+ and CD34- cells were isolated from patients with critical limb ischemia. PBS, CD34- cells, or CD34+ cells were intramyocardially transplanted after ligating LAD of nude rats. Coronary angiography of ex vivo beating hearts 5 and 28 days after the treatment was performed using the third generation synchrotron radiation microangiography (SRM), which has potential to visualize vessels as small as 20 microm in diameter. The SRM was performed pre and post sodium nitroprusside (SNP) to examine vascular physiology at each time point. Diameter of most collateral vessels was 20 to 120 microm, apparently invisible size in conventional angiography. Rentrop scores at day 28 pre and post SNP were significantly greater in CD34+ cell group than other groups (P<0.01). To quantify the extent of collateral formation, angiographic microvessel density (AMVD) in the occluded LAD area was analyzed. AMVD on day 28 post SNP, not pre SNP, was significantly augmented in CD34+ cell group than other groups (P<0.05). AMVD post SNP closely correlated with histological capillary density (R=0.82, P<0.0001). CONCLUSIONS: The SRM, capable of visualizing microvessels, may be useful for morphometric and physiological evaluation of coronary collateral formation by SCTx. The novel imaging system may be an essential tool in future preclinical/translational research of stem cell biology.

Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing.

Failures in fracture healing are mainly caused by a lack of vascularization. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to differentiate into osteoblasts in vitro; however, the therapeutic potential of CD34+ cells for fracture healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that functional fracture healing is supported by vasculogenesis and osteogenesis via regenerative plasticity of CD34+ cells. Peripheral blood CD34+ cells, isolated from total mononuclear cells of adult human volunteers, showed gene expression of osteocalcin in 4 of 20 freshly isolated cells by single cell reverse transcriptase-polymerase chain reaction analysis. Phosphate-buffered saline, mononuclear cells, or CD34+ cells were intravenously transplanted after producing nonhealing femoral fractures in nude rats. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining at the peri-fracture site demonstrated molecular and histological expression of human-specific markers for endothelial cells and osteoblasts at week 2. Functional bone healing assessed by biomechanical as well as radiological and histological examinations was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data suggest circulating human CD34+ cells have therapeutic potential to promote an environment conducive to neovascularization and osteogenesis in damaged skeletal tissue, allowing the complete healing of fractures.