[Correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students].

Objective: To explore the correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students. Methods: 22 628 middle school students in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang were enrolled by multistage cluster sampling method from November 2015 to January 2016. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and Multidimensional Sub-health Questionnaire of Adolescents (MSQA) were applied to acquire basic characteristics, health literacy, mobile phone use dependence and psychopathological symptoms of subjects. Subjects were classified into three groups, low level (P(75)), according to the percentile of the questionnaire score. Multivariate logistic regression model was used to analyze the correlation of health literacy, mobile phone with psychopathological symptoms. Results: The students were (15.4±1.8) years old with 10 990 boys (48.6%). The score of health literacy of students were (104.1±18.7) points. The rate of mobile phone use dependence was 25.4% (5 752/22 628) and the rate of psychopathological symptoms was 29.1% (6 581/22 628). Compared with high health literacy level, medium and low health literacy levels were related to psychopathological symptoms, with OR (95%CI) about 2.30 (2.10-2.52) and 5.40 (4.89-5.97), respectively. Compared with mobile phone use independence, mobile phone use dependence was related to psychopathological symptoms, with OR (95%CI) about 3.60(3.37-3.85). The highest rate of psychopathological symptoms occurred in students with mobile phone use dependence and low health literacy level [68.0% (1 345/1 977)], with OR (95%CI) about 19.59 (17.07-22.48). Conclusion: Health literacy and mobile phone use dependence are related factors of psychopathological symptoms in middle school students.

[Interactive effects between health literacy and mobile phone dependence as well as its relation with unintentional injuries in middle school students].

Objective: To investigate the interaction between health literacy, mobile phone dependence and unintentional injuries in middle school students, and to provide guidance for prevention on unintentional injuries in adolescents. Methods: From November 2015 to January 2016, a questionnaire survey was conducted among 22 628 middle school students in Shenyang of Liaoning province, Bengbu of Anhui province, Xinxiang of Henan province, Ulanqab of Inner Mongolia Autonomous Region, Chongqing and Yangjiang of Guangdong province. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU), and Unintentional Injuries Assessment Scale and demographic variables were used to measure the health literacy, mobile phone dependence and unintentional injuries among the Chinese middle school students. Results: The detection rates of mobile phone dependence and unintentional injuries were 25.4% and 46.7%, respectively. The rates of unintentional injuries of middle school students with mobile phone dependence and with low, medium and high health literacy were 53.6%, 44.4% and 48.8%, 48.1%, 41.7%. Factors as mobile phone dependence, low and middle health literacy were positively related to unintentional injuries (OR=1.452, 1.196, 1.364). However, the multiplicative interaction between mobile phone dependence and health literacy on unintentional injuries was noticed significant (OR=1.217, 95%CI: 1.041-1.422). Conclusions: Our results showed that the prevalence of unintentional injuries was relatively high in middle school students. Health literacy and mobile phone dependence seemed related to unintentional injuries. Interaction between health literacy and mobile phone dependence on unintentional injuries appeared significant.

[Association of the health literacy and the incidence of injuries among Chinese middle school students in five provinces].

Objective: The purpose of this study was to examine the association between health literacy (HL) and the incidence of injuries in middle school students in China. Methods: From November 2013 to February 2014, middle school students in Liaoning, Henan, and Guangdong provinces, Chongqing municipality, Xinjiang Uygur Autonomous Region were selected by using cluster sampling method. A total of 27 044 questionnaires were issued and 25 378 questionnaires were valid. According to the Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), scores were conducted a tripartite group. Multiple logistic regression analyses were conducted to examine the association between HL and injuries. Results: The scores of CAIHLQ were 103.55±23.91 among 25 378 students. The detection rate of self-injuries and unintentional injuries was 27.5% (n=6 971) and 47.8% (n=12 119). Compared with the students with high HL, the OR (95%CI) values of self-injuries among students with low and middle HL were 2.56 (2.35-2.79) and 1.96 (1.81-2.12). Compared with the students with high HL, the OR (95%CI) values of unintentional injuries among students with low and middle HL were 1.63 (1.53-1.73) and 1.47 (1.37-1.58). Conclusion: The risk of self-injuries and unintentional injuries of middle school students is related to HL.

[Investigation of influencing factors associated with neck-shoulder symptoms among middle school students in three cities in China].

Objective: The aim of this study was to describe the distribution of neck-shoulder symptoms among middle school students, and to explore its influence factors. Methods: A cross-sectional survey was conducted on 24 middle schools in Shenyang, Zhengzhou and Shenzhen by purposive sampling method. In each middle school, 3 to 4 classes were selected from each grade all the students in the selected class would be recruited to the survey to investigate the demographic characteristics, neck-shoulder symptoms, physical exercise time, academic stress, screen behavior, sedentary behavior and other information by questionnaire. A total of 10 566 questionnaires were issued and 10 270 valid questionnaires were withdrawn. The prevalence of neck-shoulder symptoms among students were compared by different characteristics. Logistic regression models were applied to examine influencing factors associated with neck-shoulder symptoms. Results: The prevalence of neck-shoulder symptoms among middle school students was 19.2% (1 968/10 270), while it was 22.6% (1 137/5 039) among girls and 15.9% (831/5 231) among boys; the difference showed statistical significance (P<0.001). The prevalence of neck-shoulder symptoms was separately 13.3% (253/1 901) in seventh grade, 16.8% (326/1 942) in eighth grade, 18.5% (299/1 617) in ninth grade, 21.8% (417/1 915) in sophomore, 21.4% (345/1 611) in junior, 25.5% (328/1 284) in senior; the difference showed statistical significance (P<0.001). The multivariate logistic regression analysis showed that in the last 3 months, students who always playing mobile phone ≥40 min continuously (OR=4.66, 95%CI: 3.95-5.49), watching TV ≥40 min continuously (OR=4.01, 95%CI: 3.39-4.73), using computer ≥40 min continuously (OR=3.61, 95%CI: 3.09-4.23), doing homework ≥60 min continuously (OR=3.25, 95%CI: 2.79-3.79), the average daily sitting time ≥10 h (OR=4.95, 95%CI: 4.25-5.77), and always sitting ≥90 min continuously (OR=5.18, 95%CI: 4.42-6.06) were risk factors of neck-shoulder symptoms. Conclusion: The prevalence of neck-shoulder symptoms was high among middle school students in China, especially girls in senior grades. Long time, high frequency video behaviors and sedentary behaviors were related to the occurrence of neck-shoulder symptoms among middle school students.

[Study of association between adverse experiences in childhood, social support, and physical and psychological sub-health status among middle school students in 3 cities in China].

Objective: To explore the relationship between adverse experience in childhood, social support, and physical and psychological sub-health status among middle school students in 3 cities in China. Methods: 15 278 adolescents were selected as subjects from 20 junior and senior middle schools located in 3 cities of China by stratified cluster sampling method. The survey collected the demographic information, ACEs, social support and physical-psychological status. A total of 14 820 valid questionnaires were retained for analysis. We assessed ACE score (count of six categories of childhood adversity), social support (adolescent social support questionnaire), and the prevalence of two outcomes: physiological and psychological sub-health status. Logistic regression was used to analyze the relationship between adverse childhood experiences, social support, and physiological and psychological sub-health status. Results: The prevalence of physiological and psychological sub-health status were 26.4% (3 917/14 820) and 24.1%(3 572/14 820), respectively. A total of 89.4% (13 247/14 820) reported at least 1 adverse childhood experiences. The rates of physiological and psychological sub-health status were higher among girls (28.1%(2 092/7 443), 26.0%(1 932/7 443)) than boys (24.7%(1 825/7 377), 22.2%(1 640/7 377)). Among adolescents without ACEs, the rate of physiological and psychological sub-health status were 15.4%(243/1 573) and 10.4%(163/1 573), for those with 5-6 ACEs, the rate were 40.9%(636/1 556) and 43.6%(678/1 556). Among adolescents with higher social support, the rate of physiological and psychological sub-health status were 19.9%(724/3 635) and 13.0%(474/3 635) for those with lower social support, the rate of physiological and psychological sub-health status were 35.9%(1 403/3 913) and 39.0%(1 528/3 913). The rates of physiological and psychological sub-health status were higher with more ACE exposure or less social support. At each level of ACE exposure, physiological and psychological sub-health status were less in those with greater social support. For example, among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of physiological sub-health status than those in the highest tertile (adjusted prevalence ratio (95%CI)=1.79 (1.23-2.56)); for those reporting no ACEs, the ratio was 3.04 (1.91-4.83). Among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of psychological sub-health status than those in the highest tertile (adjusted prevalence ratio (95%CI)=3.77 (2.57-5.52)); for those reporting no ACEs, the ratio was 3.97(2.33-6.76). Conclusion: The findings suggest that ACEs should be considered as risk factors for physiological and psychological sub-health status among middle school students. Across a range of exposures to ACEs, less social support was associated with more physiological and psychological sub-health status. Identifying those with ACE exposure who also have lower social support could be used to improve the health of adolescents.

[Study on relationship between outdoor activities and self-reported myopia among middle school students].

Objective: To examine the relationship between the prevalence of self-reported myopia and outdoor activities among middle school students and to explore the influence factors of the self-reported myopia. Methods: A total of 12 979 participants were recruited from junior and senior middle school students in in Shenzhen, Nanchang, Zhengzhou and Shenyang by random cluster sampling method between December 2015 and March 2016. All participants completed an anonymous questionnaire to collect the information of demographic characteristics, self-reported myopia, outdoor activities, etc. 12 603 out of 12 979 copies of questionnaire were valid. The prevalence of self-reported myopia was compared among middle school students with different characteristics. Logistic regression models were used to analyze the relationship between myopia and outdoor activities. Results: The prevalence of self-reported myopia among middle school students was 69.6% (8 766/12 603); which was separately 52.1% (1 216/2 335) in seventh grader, 61.6% (1 459/2 369) in eighth grader, 69.0%(1 470/2 129) in ninth grader, 80.0% (1 812/2 265) in freshmen, 79.4% (1 622/2 042) in sophomore, and 81.1%(1 187/1 463) in junior. The prevalence of self-reported myopia showed an increasing trend with the increase of grade (χ(2)=639.67, P<0.001). The prevalence of self-reported myopia was separately 63.5%(4 927/7 756) in non-myopic parents group, 78.0%(2 664/3 415)in either myopic parent group, and 82.1%(1 175/1 432) in both myopic parents group(χ(2)=328.28, P<0.001). Outdoor activities were associated with self-reported myopia. Binary logistic regression analysis showed that the risk of self-reported myopia was significantly increased by always staying at home in extracurricular time among the middle school students (OR=1.58, 95%CI: 1.36-1.82). The risk of self-reported myopia were significantly decreased by always physical exercise and recreational activities after school among middle school students: the ORs were separately 0.67 (95%CI: 0.57-0.78) for physical exercise and 0.77 (95%CI: 0.64-0.92) for recreational activities. After stratified analysis by the parents' myopia status, in non-myopic parents group, exercise and recreational activities after school among middle school students decreased the risk of myopia: the ORs were separately 0.68 (95%CI: 0.55-0.82) for physical exercise and 0.76 (95%CI: 0.61-0.95) for recreational activities; in either myopic parent group, OR(95%CI) were separately 0.65 (0.47-0.90) and 0.68 (0.47-0.98). Conclusion: Outdoor activities was negatively associated with self-reported myopia among middle school students. However, the parents' myopia status may affect the protective effect.

Altered coupling of default-mode, executive-control and salience networks in Internet gaming disorder.

BACKGROUND: Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors. METHODS: DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined. RESULTS: Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving. CONCLUSIONS: These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.

Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.

OBJECTIVE: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. MATERIALS AND METHODS: To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test. RESULTS: The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p < 0.05) but not in the CA1 region (p > 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age. CONCLUSIONS: Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.

Association between aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism and susceptibility to colorectal cancer: a meta-analysis.

Numerous studies have evaluated the association between Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene and colorectal cancer (CRC) risk. However, the specific association remains controversial. To assess the relationship between the ALDH2 Glu504Lys polymorphism and CRC, we conducted a comprehensive meta-analysis of five case-control studies comprising 1664 patients with CRC and 2777 controls. The results of this meta-analysis showed that the ALDH2 Glu504Lys polymorphism was associated with a significantly reduced risk of CRC [Lys/Lys vs Glu/Glu: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.58-1.54; Glu/Lys vs Glu/Glu: OR = 0.85, 95%CI = 0.75-0.97; dominant model: OR = 0.86, 95%CI = 0.76-0.98; recessive model: OR = 1.00, 95%CI = 0.62-1.61]. No significant heterogeneity or publication bias was observed in our meta-analysis. Based on the statistical data, our meta-analysis indicates that the ALDH2 Glu504Lys polymorphism is associated with reduced risk of developing CRC.

[Laparoscopic reoperation for recurred antireflux surgery of gastroesophageal reflux disease].

OBJECTIVE: To investigate the safety and effectiveness of laparoscopic reoperation for patients with gastroesophageal reflux disease (GERD) recurred form previous anti-reflux surgery. METHODS: Totally 19 patients received laparoscopic reoperation for symptomatic and anatomic recurred GERD in Department of Gastroesophageal Reflux Disease, Rocket Force General Hospital from January 2008 to September 2015 were retrospectively analyzed. There were 12 male and 7 female patients. The average reoperation age was (48±14) years, the average duration of reoperation from original ones was (43±38) months. The patients underwent preoperative barium, endoscopy, manometry and 24-hour pH studies. Laparoscopic hiatal hernia repair plus fundoplication was carried out for reoperation. Gastroesophageal reflux related symptoms (reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation) before and after surgery were compared by a questionnaire. The patients' medication consumption, complications and satisfaction of the reoperation were investigated as well. The repeated measures analysis of variance was used for statistical comparison of data preoperatively and postoperatively. RESULTS: No major complication and death occurred. Six cases (32%) had complications such as diarrhea, increased passing wind, flatulence, dysphagia and abdominal pain. The GERD related symptom score of reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation all significantly decreased (F: 25.0 to 56.7; P: 0.000 to 0.001) after the reoperation, with 68% good outcome of all the patients. After a follow-up of (33±22) months after reoperation, 1 case had partial recurrence at the 3(rd) month after reoperation. For all the patients, 12 cases felt very satisfied or satisfied with the reoperation. CONCLUSION: Laparoscopic reoperation is generally effective with acceptable morbidity rates for patients with esophageal and extraesophageal symptoms recurred form previous hiatal repair and (or) fundoplication.

Evolutionary analysis of the ubiquitin gene of baculovirus and insect hosts.

Baculovirus is the only virus that has been found to encode the ubiquitin protein. In this study, ubiquitin sequences from 16 insects and 49 viruses were collected and compared. The resulting sequences were aligned with virus genomes. Then MAGE 5.0, k-estimated software, as well as other software programs were used for systemic evolutionary, selection pressure, and evolutionary distance analysis. The results of the pairwise ratio of non-synonymous to synonymous substitution values and evolutionary distances showed that ubiquitin from baculovirus and insect hosts have been under purifying selection during evolution and are thus evolutionarily conserved. Moreover, genes from insect hosts were more conserved than those in baculovirus. Analysis of the non-synonymous to synonymous substitution rates at each site and entropy calculations revealed the evolutionary status of every site in the ubiquitin genes of baculovirus and their hosts. Genome locations and phylogenetic trees indicated that granuloviruses and non-photosynthetic vegetation evolved, and granulovirus evolution was more similar to that of insect hosts. Our results suggest that the ubiquitin gene in baculovirus may have been acquired through horizontal transfer from the host.

HLA-B*13:01 and the dapsone hypersensitivity syndrome.

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from drinking water reservoirs in Hong Kong.

AIMS: Freshwater fish has been found to be the reservoir of Laribacter hongkongensis, a recently discovered bacterium associated with community-acquired gastroenteritis. However, little is known about the ecology of this bacterium in the aquatic environment. We carried out a surveillance study to investigate the presence of L. hongkongensis in water and freshwater fish from 10 drinking water reservoirs in Hong Kong. METHODS AND RESULTS: Using membrane filtration, L. hongkongensis was isolated from the waters of six reservoirs, with numbers ranging from 1 to 12 CFU l(-1). Higher recovery rates were observed in summer and during days of higher water and ambient temperatures. Of 27 freshwater fish collected from the reservoirs, L. hongkongensis was recovered from the intestines of two fish, a Goldfish and a Nile tilapia. Overall, 35 different pulsed-field gel electrophoresis patterns are found among the 59 isolates recovered from water and the two isolates from freshwater fish. CONCLUSIONS: The present report represents the first to demonstrate the presence of L. hongkongensis in natural water environments. SIGNIFICANCE AND IMPACT OF THE STUDY: Although it is unlikely that treated, drinking water is an important source of L. hongkongensis-associated gastroenteritis, one should be aware of the possibility of other contaminated water as a source of human infection.

The prevalence of adult female urinary incontinence in Hong Kong Chinese.

This was a community-based study to evaluate the prevalence and characteristics of female urinary incontinence in women aged 18 and above in the Shatin District of Hong Kong. Of a total of 1018 female households contacted, 362 individuals were successfully interviewed and 123 women (34%) reported they had experienced at least one episode of urinary incontinence as adults. Of these, 18.5% reported persistent incontinence and 15.5% reported absence of incontinence after a single episode of urine loss. The risk factors for incontinence revealed by this study were body mass index and parity. Women who had never been incontinent had a lower body mass index and were usually nulliparous. Most of the respondents (43.9%) who had urinary incontinence considered the condition to be a minor problem and did not seek professional advice. This investigation indicates that a territory-wide study should be carried out to determine the incidence of urinary incontinence throughout Hong Kong.

Effect of macular edema on surgical visual outcome in eyes with idiopathic epiretinal membrane.

OBJECTIVE: To determine whether macular edema affects the surgical outcome in eyes with idiopathic epiretinal membrane. DESIGN: Case series. SETTING: University-based referral practice in Vancouver. PATIENTS: Sixty-one patients (63 eyes) (37 women and 24 men ranging in age from 47 to 96 [mean 70] years) who underwent pars plana vitrectomy with membrane peeling for idiopathic epiretinal membrane. OUTCOME MEASURES: Degree of macular edema on preoperative fluorescein angiograms (none, mild or severe), as rated independently by two masked observers, and preoperative and postoperative Snellen visual acuity. RESULTS: Of the 63 eyes 32 had no macular edema, 21 had mild edema, and 10 had severe edema. Fifty-two eyes (83%) had an improvement in visual acuity. The mean number of lines of improvement in visual acuity for the three groups was 2.2, 3.7 and 2.6 respectively. Multiple regression analysis showed that the factor with the greatest adverse effect on visual outcome was intraoperative macular hole formation. The presence of macular edema preoperatively did not significantly affect visual outcome. CONCLUSIONS: Our results suggest that even eyes with significant macular edema secondary to idiopathic epiretinal membranes may benefit from vitrectomy with membrane peeling.

Reconstruction of the bone--bone marrow organ by osteogenin, a bone morphogenetic protein, and demineralized bone matrix in calvarial defects of adult primates.

Information concerning the efficacy of osteogenin, a bone morphogenetic protein, and demineralized bone matrix in orthotopic sites in nonhuman primates is a prerequisite for potential clinical application in humans. After exposure of the calvaria, 84 cranial defects, 25 mm in diameter, were prepared in 26 adult male baboons (Papio ursinus). Defects were implanted with insoluble collagenous bone matrix (ICBM, the inactive collagenous residue after dissociative extraction of bone matrix with 4 M guanidine hydrochloride) reconstituted with osteogenin fractions isolated from baboon bone matrix by chromatography on heparin-Sepharose and hydroxyapatite-Ultrogel (Og Hep-HA) or osteogenin further purified using Sephacryl S-200 gel filtration chromatography (Og S-200). Baboon osteogenin with the highest biologic activity in a rodent bioassay, as determined by alkaline phosphatase activity, calcium content, and histologic analysis, was used for orthotopic implantation in baboons. Additional defects were implanted with baboon demineralized bone matrix (DBM) or ICBM without osteogenin as control. Defects also were grafted with corticocancellous bone harvested from the iliac crest or left ungrafted to monitor the spontaneous regeneration potential of the adult baboon calvaria. Undecalcified bone sections at 7 microns were prepared from the harvested specimens 30 and 90 days after surgery. Histomorphometry demonstrated that Og S-200 induced copious amounts of bone and osteoid as early as day 30 (P < 0.01 versus ICBM, autogenous grafts and untreated defects). At day 90, in implants of Og S-200, Og Hep-HA, and DBM, bone and marrow formation was extensive, culminating in complete regeneration of the craniotomies. In implants of DBM, bone formed with an intervening phase of cartilage development. This provides the phenotypic evidence of endochondral bone differentiation by induction in defects of membranous calvarial bone in adult primates. These results establish the potential therapeutic application of osteogenin and demineralized bone matrix for the architectural reconstruction of the bone-bone marrow organ in humans.

Osteogenin, a bone morphogenetic protein, adsorbed on porous hydroxyapatite substrata, induces rapid bone differentiation in calvarial defects of adult primates.

Osteogenin, a bone morphogenetic protein, in conjunction with insoluble collagenous bone matrix initiates local endochondral bone differentiation by induction in vivo. This study, by exploiting the affinity of native osteogenin for hydroxyapatite, was designed to construct a delivery system for the expression of the biologic activity of osteogenin in nonhealing calvarial defects of adult primates. After exposure of the calvaria, 64 cranial defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). Defects were implanted with disks of porous nonresorbable and resorbable hydroxyapatite substrata obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. In each animal, one disk of each hydroxyapatite preparation was treated with osteogenin isolated and purified from baboon bone matrix after sequential chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200 gel filtration columns. The remaining two defects were implanted with one disk of each hydroxyapatite preparation without osteogenin as control. Histomorphometry on decalcified sections prepared on days 30 and 90 showed superior osteogenesis in osteogenin-treated nonresorbable hydroxyapatite specimens as compared with controls. On day 90, substantial bone formation also had occurred in control nonresorbable hydroxyapatite specimens. On day 90, but not on day 30, significantly greater amounts of bone had formed in osteogenin-treated resorbable specimens as compared with resorbable controls. Overall, resorbable substrata performed poorly when compared with nonresorbable substrata, perhaps due to a premature dissolution of the implants. These results provide evidence that the biologic activity of osteogenin can be restored and delivered by a substratum other than the organic collagenous matrix, inducing rapid bone differentiation in calvarial defects of adult nonhuman primates. The adsorption strategy of osteogenin on porous inorganic nonimmunogenic substrata may help to design appropriate osteogenic delivery systems for craniofacial and orthopedic applications in humans.

Induction of bone in composites of osteogenin and porous hydroxyapatite in baboons.

A major goal of the combined effort of basic scientists and plastic and reconstructive surgeons is the development of novel bone substitutes based on osteogenic growth and differentiation factors with optimal delivery systems for skeletal repair. Osteogenin is a protein initiator of bone differentiation. The present study examined the osteogenic potential of osteogenin in combination with porous hydroxyapatite replicas obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. Bovine osteogenin, with an apparent molecular weight of 28 to 42 kDa, purified by hydroxyapatite-Ultrogel adsorption chromatography, heparin-Sepharose affinity chromatography, and HR Sephacryl S-200 molecular sieve chromatography, was delivered into rods of nonresorbable and resorbable hydroxyapatite replicas with an average porosity of 600 microns. A total of 48 rods were bioassayed for osteogenic activity by intramuscular implantation into eight adult baboons (Papio ursinus) as a prerequisite for clinical trials in humans. Bovine osteogenin fractions reconstituted with baboon insoluble collagenous bone matrix were implanted in an additional four adult baboons. Specimens were harvested at 30 and 90 days after implantation and subjected to histomorphometry and alkaline phosphatase activity determination. Differentiation of bone occurred in nonresorbable hydroxyapatite rods, both osteogenin-treated and controls. However, no bone formation was observed in resorbable rods, even in the presence of osteogenin. These results demonstrate that the surface and chemical characteristics of the substratum, independent of the osteogenic stimulus, have a profound influence on the morphogenesis of bone. The demonstration of bone induction in nonhuman primates with porous nonresorbable hydroxyapatite replicas and baboon insoluble collagenous bone matrix reconstituted with bovine osteogenin establishes the therapeutic potential of the principle of bone induction in craniofacial, periodontal, and orthopedic reconstructive surgery.

Induction and maintenance of new bone formation by growth and differentiation factors.

The cell biology of bone formation can be better understood by dissecting the complex multistep process into individual steps. It is well known that demineralized matrix has the potential to initiate new bone formation locally at a heterotopic site of implantation. The sequential development of bone in response to bone matrix is reminiscent of the cellular lineages in the epiphyseal growth plate. The developmental cascade has permitted the operational distinction of the major phases of new bone formation such as: migration of progenitor cells; mitosis of mesenchymal stem cells; differentiation to cartilage and bone; mineralization and remodelling; and finally hematopoietic marrow differentiation. Thus the initiation of bone formation can be investigated as opposed to maintenance of already formed bone as in the orthotopic sites. Recent work has resulted in the identification and isolation of osteogenin, a bone-inductive protein. The newly formed bone is then maintained by a variety of polypeptide growth factors which have a regulatory role. The local action of initiation and maintenance factors is further modulated in a collaborative manner by systemic factors such as hormones and nutrition and the extracellular matrix.