Application of machine learning techniques in the diagnostic approach of PTSD using MRI neuroimaging data: A systematic review.

Background: At present, the diagnosis of post-traumatic stress disorder（PTSD） mainly relies on clinical symptoms and psychological scales, and finding objective indicators that are helpful for diagnosis has always been a challenge in clinical practice and academic research. Neuroimaging is a useful and powerful tool for discovering the biomarkers of PTSD,especially functional MRI (fMRI), structural MRI (sMRI) and Diffusion Weighted Imaging（DTI）are the most commonly used technologies, which can provide multiple perspectives on brain function, structure and its connectivity. Machine learning (ML) is an emerging and potentially powerful method, which has aroused people's interest because it is used together with neuroimaging data to define brain structural and functional abnormalities related to diseases, and identify phenotypes, such as helping physicians make early diagnosis. Objectives: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) declaration, a systematic review was conducted to assess its accuracy in distinguishing between PTSD patients, TEHC(Trauma-Exposed Healthy Controls), and HC(healthy controls). Methods: We searched PubMed, Embase, and Web of Science using common words for ML methods and PTSD until June 2023, with no language or time limits. This review includes 13 studies, with sensitivity, specificity, and accuracy taken from each publication or acquired directly from the authors. Results: All ML techniques have an diagnostic accuracy rate above 70%，and support vector machine（SVM） are the most commonly used techniques. This series of studies has revealed significant neurobiological differences in key brain regions among individuals with PTSD, TEHC, and HC. The connectivity patterns of regions such as the Insula and Amygdala hold particular significance in distinguishing these groups. TEHC exhibits more normal connectivity patterns compared to PTSD, providing valuable insights for the application of machine learning in PTSD diagnosis. Conclusion: In contrast to any currently available assessment and clinical diagnosis, ML techniques can be used as an effective and non-invasive support for early identification and detection of patients as well as for early screening of high-risk populations.

[Effect of SLC7A11 gene downregulation on the gefitinib resistance of lung adenocarcinoma PC9/GR cells and its mechanism].

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 µmol/L and 64.01 µmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) µmol/mg vs. (82.18±7.77) µmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.

[Factors affecting BK polyomavirus infection after kidney transplantation in post-school children and a predictive infection model].

Objective: To analyze high-risk factors affecting BK polyomavirus (BKPyV) infection and to construct a prediction model for BKPyV infection in children after renal transplantation. Methods: The clinical data of 332 children who received allogeneic kidney transplantation in the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2022 were retrospectively collected. According to the BKPyV load level, the dynamic change process of lymphocytes at different time points were analyzed. The factors that have potential influence on BKPyV infection were screened by Cox regression analysis, and the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of the predictive model of infection. Results: Among the 332 children, there were 215 males and 117 females; the age of transplantation was (12.2±3.9) years old; 37 cases were preschool (1-5 years old), and 295 cases were post-school age (6-18 years old). BKPyV load in 224 urine samples and 30 blood samples of children were detected. There were 9 cases of BKPyV-associated viruria and 3 cases of BKPyV associated viremia in pre-school children, 76 cases BKPyV associated viruria and 14 cases of BKPyV associated viremia in post-school children. Multivariate Cox regression analysis showed that higher body mass index (BMI) (HR=1.105, 95%CI: 1.020-1.197), antithyroglobulin (ATG) application (HR=2.196, 95%CI: 1.335-3.613), and higher tacrolimus concentration (HR=2.484, 95%CI: 1.298-4.753), higher natural killer (NK) lymphocyte count (HR=1.193, 95%CI: 1.009-1.411), higher CD14++CD16-cell count (HR=1.096, 95%CI: 1.024-1.173) were independent risk factors for BKPyV associated viruria in post-school children. Delayed graft function (DGF) (HR=4.993, 95%CI: 1.555-16.038), Acute rejection (AR) (HR=6.021, 95%CI: 1.930-18.787), higher CD14++CD16-cell count (HR=1.227, 95%CI: 1.081-1.392) were independent risk factors for BKPyV associated viremia in post-school children. The results of ROC curve analysis showed that combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, and CD14++CD16-cell count predicted the occurrence of BKPyV associated viruria in post-school children after kidney transplantation at 0.5, 1, 2, and 5 years with area under curve (AUC) of 0.712 (95%CI: 0.626-0.798), 0.708 (95%CI: 0.612-0.804), 0.754 (95%CI: 0.668-0.840) and 0.767 (95%CI: 0.685-0.849). The sensitivity and specificity of the model were 64.9%, 61.4%, 61.6%, 55.8% and 70.9%, 72.4%, 76.0%, 84.0%, respectively. Combined with DGF, AR, and CD14++CD16-cell counts predicted the occurrence of BKPyV-associated viremia at 0.5, 1, 2, and 5 years after renal transplantation in post-school children with AUC of 0.791 (95%CI: 0.631-0.951), 0.744 (95%CI: 0.547-0.936), 0.786 (95%CI: 0.629-0.946) and 0.812 (95%CI: 0.672-0.948). The sensitivity and specificity of the model were 76.1%, 67.1%, 75.0%, 77.9% and 88.9%, 89.0%, 89.9%, 88.0%, respectively. Conclusions: The postoperative CD14++CD16-cell level can be used as an independent predictor of BKPyV infection in post-school children after renal transplantation. Combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, CD14++CD16-cell count and combined DGF, AR, CD14++CD16-cell count show good fitting effect in predicting the occurrence of BKPyV-associated viruria and viremia after transplantation in post-school children respectively.

Clinical value and effectiveness profiles of oblique lateral interbody fusion and posterior lumbar interbody fusion in the treatment of lumbar brucellosis spondylitis.

OBJECTIVE: The aim of this study was to assess the clinical efficacy of oblique lateral interbody fusion (OLIF) and posterior lumbar interbody fusion (PLIF) for lumbar brucellosis spondylitis. PATIENTS AND METHODS: Between April 2018 and December 2021, 80 cases of lumbar brucellosis spondylitis admitted to our institution were evaluated for eligibility and randomly assigned to either PLIF (group A, lesion removal by posterior approach + interbody fusion + percutaneous pedicle screw internal fixation) or OLIF (group B, lesion removal by anterior approach + interbody fusion + percutaneous pedicle screw internal fixation). The outcome measures included operative time, intraoperative bleeding, hospital stay, preoperative and postoperative visual analogue scale (VAS) ratings, American Spinal Injury Association (ASIA) classification, Cobb angle, and interbody fusion time. RESULTS: PLIF resulted in shorter operative time and hospital stay and less intraoperative bleeding vs. OLIF (p<0.05). All eligible patients showed significantly lower VAS scores, and smaller ESR values and Cobb angles after treatment (p<0.05), but no significant intergroup differences were observed (p>0.05). The two groups showed similar preoperative ASIA (American Spinal Injury Association) classification and interbody fusion time (p>0.05). PLIF was associated with better ASIA classification at three months postoperatively vs. OLIF (p<0.05). CONCLUSIONS: Both surgical techniques are efficient at removing the lesion, relieving pain, maintaining spinal stability, promoting implant fusion, and facilitating prognostic inflammation control. PLIF features a shorter surgical duration and hospital stay, less intraoperative bleeding, and greater neurological improvement vs. OLIF. Nevertheless, OLIF outperforms PLIF in the excision of peri-vertebral abscesses. PLIF is indicated for posterior spinal column lesions, particularly those with spinal nerve compression in the spinal canal, whereas OLIF is indicated for structural bone deterioration in the anterior column, particularly for those with perivascular abscesses.

[Preventive strategy of economy class syndrome].

Economy class syndrome (ECS) refers to a series of symptoms, such as lower limb swelling, chest pain, dyspnea, and sudden death, that occur during or after a long-distance flight. Its essence is venous thromboembolism. ECS, as a preventable syndrome, is one of the causes of sudden death in long-distance travelers. Medical assistance to the African region is a very important diplomatic matter of China. It often takes medical workers more than 10 hours of long-distance flight to reach the recipient country. Therefore, it is essential to improve the understanding of ECS and corresponding prevention strategies among the long-distance traveling people including medical workers assisting Africa, which could guarantee their health and ensure the smooth implementation of the work of assisting Africa.

[Exploration of construction mode of real-world data system].

Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.

[Real-world data studies of medical products in the context of special healthcare policy: study designs and key considerations].

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE ε4 carriers: a preliminary study.

The APOE ε4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 ε4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the ε4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the ε4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the ε4 carriers. In ε4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process.

Abnormal of inter-hemispheric functional connectivity in elderly subjects with overweight/obesity.

BACKGROUND: There is a growing literature documenting a variety of brain abnormalities associated with obesity. However, little is known about the effects of obesity on inter-hemispheric connectivity in aging people. METHODS: Participants included 61 cognitively intact elderly (including people with obesity, overweight, and lean controls) who underwent structural MRI, resting-state functional magnetic resonance imaging (rsfMRI) and standard neuropsychological batteries. Techniques including FreeSurfer and Voxel-mirrored Homotopic Connectivity (VMHC) were employed to evaluate inter-hemispheric structural and functional connectivity respectively. RESULTS: There were no differences of cognitive abilities and vascular risks among groups. When compared to lean controls, obese group had greater VMHC in fusiform gyrus (FG); while overweight group had greater VMHC in FG, calcarine gyrus, inferior temporal gyrus (ITG), and postcentral gyrus (PCG). Moreover, the obesity group had lower VMHC in calcarine gyrus and PCG than overweight group (p<0.05, corrected). CONCLUSIONS: The present study suggested, increased inter-hemispheric information transmission in networks supporting visual and sensorimotor function may lead to gain in weight, by possibly mediating diet behaviours of individuals.

Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid precursor protein transgenic mice.

Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We previously demonstrated DSCAM overexpression in the cortex of amyloid precursor protein (APP) transgenic mice, suggesting possible regulatory interactions between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent learning and memory. In this preliminary study, we examined age-related changes in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and 12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and age-matched wild type littermates (WTs) using the Morris water maze (MWM). The cellular distribution of hippocampal DSCAM and total expression at both mRNA and protein levels were measured by immunohistochemistry, qRT-PCR, and western blotting, respectively. APP mice exhibited spatial memory deficits in the MWM. Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and protein expression levels were substantially higher in APP mice than WTs at 1 and 3 months of age. Expression decreased with age in both groups but remained higher in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months of life in APP mice, but especially during maturation to adulthood. In conclusion, these results suggest an association between DSCAM and APP mice, which is characterized by neuropathology and behavioral deficits. These results provide some clues for future studies on the role of DSCAM overexpression in the precocious cognitive decline observed in APP transgenic mice.

[High glucose reduced the repair function of kidney stem cells conditional medium to the hypoxia-injured renal tubular epithelium cells].

OBJECTIVE: To evaluate the impacts of high glucose on the repair function of kidney stem cells (KSC) conditional medium to the hypoxia-injured renal tubular epithelium cells (RTEC). METHODS: KSC were isolated from the renal papilla in 4-week-Sprague-Dawley rats. The KSC were pretreated in media with high glucose (30 mmol/L) or with normal glucose (5.6 mmol/L), respectively. The supernatants of the pre-treated KSC were collected as the conditional media. The hypoxia/reoxygenation (H/R) model of rat RTEC was established using the NRK-52E cell line. The effects of KSC conditional media on the H/R RTEC were investigated. RESULTS: (1) The best H/R model of RTEC was established using hypoxia for 4 h and reoxygenation 2 h. (2) After hypoxia, the early and late cell apoptosis rates of the H/R RTEC were increased. The H/R RTEC were co-cultured with KSC conditional media for 12 h and 24 h, respectively. The H/R RTEC were co-cultured with DMEM/F12 as a control group. The cell apoptosis rate of H/R RTEC was lower after co-cultured with KSC conditional media (P<0.01), and the cell apoptosis rate of H/R RTEC in high glucose group was much higher than that in normal glucose group after co-cultured 24 h (P=0.02). (3) After hypoxia, the lactic dehydrogenase (LDH) and malondialdehyde (MDA) levels of the H/R RTEC supernatant were increased, and the superoxide dismutase (SOD) level decreased. The LDH and MDA levels were lower and the SOD level was higher after co-cultured with KSC conditional media for 12 h and 24 h, respectively (P<0.01). The LDH and MDA levels of H/R RTEC supernatant were much higher in the high glucose group than in the normal glucose group (P<0.05), and the SOD level of H/R RTEC supernatant was much lower in the high glucose group than in the normal glucose group (P<0.01). CONCLUSION: KSC conditional media could repair the H/R injury of RTEC. The effects were mainly by inhibiting cell apoptosis, and reducing oxidative stress; the anti-cell apoptosis ability and the anti-oxidative stress capacity of the conditional medium were reduced after KSC were pre-treated with high glucose.

[Age-related differences in the clinical symptoms and triggering factors among Chinese patients with acute myocardial infarction].

OBJECTIVE: To analyze the age-related differences in the clinical symptoms and triggering factors among Chinese patients with acute myocardial infarction. METHODS: Acute myocardial infarction Patients (n=14 854) registered in the China Acute Myocardial Infarction Registry from January 2013 to March 2014 were included in this study. Patients were divided into 4 groups: <55 years old group (3 950 patients), 55-64 years old group (4 361 patients), 65-74 years old group ( 3 759 patients), and ≥75 years old group (2 784 patients). Demographic features, medical history, clinical presentation and triggering factors were obtained via electronic data capture system. RESULTS: (1)Persistent chest pain and sweat were the major typical symptoms 66.4%(9 863/14 854) and 63.8%(9 471/14 854)) in the whole cohort. Prevalence of persistent chest pain among four groups were 73.8%(2 915/3 950), 69.2%(3 016/4 361), 63.6%(2 394/3 759) and 55.2%(1 538/2 784), and radiating pain among four groups were 36.2%(1 428/3 950), 34.1%(1 487/4 361), 30.9%(1 160/3 759)and 25.9%(722/2 784), and sweat among four groups were 70.0%(2 765/3 950), 66.5%(2 898/4 361), 61.8%%(2 323/3 759)and 53.3%(1 485/2 784), and there were statistical significance for all above symptoms among groups (all P<0.001). (2)triggering factors before acute myocardial infarction could be found in 19.4%(2 879/14 854) of the patients. Prevalence of existed triggering factors among four groups were 23.8%(941/3 950), 21.0%(914/4 361), 16.6%(625/3 759) and 14.3%(399/2 784, P<0.001). Recent excessive unhealthy lifestyles among four groups were 20.8%(196/3 950), 11.9%(109/4 361), 10.1%(63/3 759) and 9.0%(36/2 784) among the 4 groups (P<0.001). CONCLUSIONS: Persistent chest pain and sweat are absent in nearly half of Chinese patients in ≥75 years old group. Triggering factors prior to acute myocardial infarction could be evidenced in about twenty percent patients, and which are more often in young patients. Clinical Trail Registry: National Institutes of Health，NCT018746.

Characterization of novel nitrate reductase-deficient mutants for transgenic Dunaliella salina systems.

The aim of the present study was to isolate and characterize novel nitrate reductase (NR)-deficient mutants, which may be useful for the transgenic manipulation of Dunaliella salina. Three NR-deficient mutants of D. salina, J-1, J-2, and J-3, were successfully isolated by screening for chlorate resistance after chemical mutagenesis with ethylnitrosourea. NR activity was not detected in the mutants and the expression of NR mRNA was significantly decreased. Growth analysis of D. salina strains grown in media containing different nitrogen sources revealed that these mutants were capable of utilizing nitrite and urea, but not nitrate as a nitrogen source, indicating that these mutants are indeed NR-deficient. Mutation analysis of NR cDNA sequences revealed that there were 11 point mutations shared by the J-1, J-2, and J-3 mutants. Furthermore, the results of the functional complementation experiment showed that NR activity of transformant T-1 derived from J-1 was recovered to 48.1 % of that of the wild-type D. salina. The findings of the present study indicate that nitrate may be used as a selective agent rather than antibiotics or herbicides for the isolated NR-deficient mutants in future transgenic D. salina systems.

Natural variation of rice blast resistance gene Pi-d2.

Studying natural variation in rice resistance genes of cultivated and wild rice relatives can predict resistance stability to rice blast fungus. In the present study, the protein coding regions of the rice R gene Pi-d2 in 35 rice accessions, including Oryza sativa L. subsp. indica Kato (Aus), indica (IND), temperate japonica (TEJ), tropical japonica (TRJ), aromatic (ARO); subgroups of Oryza sativa; 6 accessions of wild rice varieties; O. nivara; and O. rufipogon were analyzed. A total of 13 nucleotide differences were found in the open reading frames (ORFs) of Pi-d2. Translation of these ORFs revealed 9 variants; 3 were novel Pi-d2 variants. Variants H2 and H5 were identified in accessions of cultivated rice and O. nivara, H1, H3, H4, H6, and H8 were only identified in cultivated rice. H2 and H5 were the common types of IND and O. nivara, H8 was the common type of TRJ and AUS, H6 was the specific type of AUS, and H3 was the specific type of ARO. H7 and H9 were specific haplotypes of O. nivara and O. rufipogon, respectively. These findings demonstrate that Pi-d2 variants are useful indicators for each subgroup, and Pi-d2 is an ancient gene that predates speciation of rice subgroups.

Anterior maxillary segmental distraction for correction of maxillary hypoplasia and dental crowding in cleft palate patients: a preliminary report.

To evaluate the feasibility of anterior maxillary segmental distraction (AMSD) to correct maxillary hypoplasia and severe dental crowding in cleft lip and palate (CLP) patients, 7 patients (average age 16.4 years) with maxillary hypoplasia, shortened maxillary dental arch length and severe anterior dental crowding secondary to CLP were selected for this study. After anterior maxillary segmental osteotomy, 3 patients were treated using bilateral internal distraction devices, and 4 patients were treated using rigid external distraction devices. Photographs and radiographs were taken to review the improvement in facial profile and occlusion after distraction. An average 10.25 mm anterior maxillary advancement was obtained in all patients after 10-23 days of distraction and 9-16 weeks of consolidation. The sella-nasion-point A (SNA) angle increased from 69.5 degrees to 79.6 degrees. Midface convexity was greatly improved and velopharyngeal competence was preserved. The maxillary dental arch length was greatly increased by 10.1 mm (P<0.01). Dental crowding and malocclusion were corrected by orthodontic treatment. These results show that AMSD can effectively correct the hypoplastic maxilla and severe dental crowding associated with CLP by increasing the midface convexity and dental arch length while preserving velopharyngeal function, and dental crowding can be corrected without requiring tooth extraction.

Long-term outcome of secondary alveolar bone grafting in patients with various types of cleft.

OBJECTIVE: To evaluate the results of secondary alveolar bone grafting in patients with various types of cleft. DESIGN: One hundred and seventy patients were classified as cleft lip and alveolar process alone (CLAP), complete unilateral cleft lip and palate (UCLP), and complete bilateral cleft lip and palate (BCLP). The Bergland criteria were used to assess the long-term outcome of alveolar bone grafting. RESULTS: In the UCLP and BCLP groups, the success rate was significantly better (P<0.05) when the cleft was grafted before the eruption of canines. When the operation was done after the eruption of canines, there was a significant difference in the success rate between CLAP and BCLP (P<0.05). CONCLUSION: The timing of the operation was the critical variable that affected the outcome in patients with complete cleft lip and palate. The severity of the deformity influenced the success rate when alveolar bone grafting was done after the eruption of canines.

Bilateral alveolar bone grafting: a report of 55 consecutively-treated patients.

A retrospective study was undertaken to evaluate the long-term results of bilateral alveolar bone grafting carried out at Great Ormond Street Hospital from 1983 to 1993. Fifty-five consecutive complete bilateral cleft lip and palate patients (36 males and 19 females) who had the operation were included in this study. The total number of cleft sites was 110. At the time of alveolar bone grafting, the mean age of the patients was 12.3 years with a range of 8.4-19.9 years. Cancellous bone from the iliac crest was grafted into the alveolar cleft areas. The cleft sites were studied in two groups according to whether the cleft canine had erupted prior to bone grafting or not. The erupted canine group was composed of 43 cleft sites and the unerupted canine group of 67 sites. At the time of this study, the cleft canine had subsequently erupted at 101 sites. Anterior occlusal radiographs were taken before and after bone grafting. The minimum period of observation after alveolar bone grafting was one year. Criteria described previously were utilized to assess the height of the interdental septum. The results show that bone grafting before canine eruption has a higher clinical success rate compared with that carried out after canine eruption. The critical variable affecting the quality of bilateral alveolar bone grafting is the timing of the surgery.

Measurement of elastic properties of Xenopus oocytes.

Elastic properties of Xenopus oocytes were examined by measuring intracellular pressure (Pic) and cell volume (Vc) in cells undergoing osmotic swelling. Pic was measured by micropuncture, using the servo-null technique. Vc was obtained by analyzing images acquired from a microscope having a video camera attachment. During osmotic swelling, Pic increased from 61 +/- 17 to 500 +/- 59 Pa (mean +/- SE), but the relationship with volume was not linear. In cells that underwent sequential swelling and shrinking, Pic was always lower on shrinking and the cells showed hysteresis. Cells with vitelline envelope (VE) removed had Pic-Vc curves similar in shape to those of intact cells; however, Pic values were significantly lower. Specific elastance[delta Pic/(delta Vc/Vc)] was reduced by removal of the VE. The data indicate that oocytes are weakly elastic and that a large part of their resistance to expansion resides in the VE.

Effects of cAMP on serotonin evoked calcium transients in cultured rat airway smooth muscle cells.

Agents increasing intracellular adenosine 3',5'-cyclic monophosphate (cAMP) cause relaxation of airway smooth muscle. However, the mechanisms of their action are not fully understood. We investigated the role of cAMP in the modulation of intracellular Ca2+ concentration ([Ca2+]i) transients evoked by serotonin (5-HT) in cultured rat tracheal smooth muscle (TSM) cells. Forskolin (10(-7) M) caused a significant elevation of intracellular cAMP and a 60% relaxation of tracheal rings contracted with 5-HT but did not affect [Ca2+]i in TSM cells. Forskolin (10(-5) M) completely relaxed tracheal rings and significantly decreased [Ca2+]i during the sustained phase of the 5-HT response. Forskolin-induced relaxation was attenuated by the cAMP-dependent protein kinase A (PKA) inhibitor Rp diastereomer of cAMP (Rp-cAMPS; 10(-4) M) and by the guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor [Rp isomer of 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, 10(-4) M]. The effects of forskolin on [Ca2+]i were not altered by the PKA inhibitor but were abolished by the PKG inhibitor and thapsigargin. These results indicate that, in rat TSM, the relaxant effects of high concentrations of cAMP may be mediated, at least in part, by facilitating the sequestration of Ca2+ into intracellular stores by a mechanism involving PKG.

Mechanisms mediating the vasodilatory effects of N-hydroxy-L-arginine in coronary arteries.

We assessed the mechanisms of action of NG-hydroxy-L-arginine in isolated porcine large coronary arterial rings. Increasing (1, 10 and 100 microM) concentrations of NG-hydroxy-L-arginine evoked endothelium-dependent dilation which was eliminated by 100 microM of NG-nitro-L-arginine methyl ester, but not affected by a cytochrome P450 inhibitors (miconazole or 7-ethoxyresorufin). At a given concentration, the dilatory response to NG-hydroxy-L-arginine was stronger than that elicited by L-arginine. NG-Hydroxy-L-arginine (100 microM), but not NG-hydroxy-D-arginine, potentiated the endothelium-dependent dilation of calcium ionophore A23187 but had no effect on endothelium-independent dilation evoked by an NO donor. NO release by endothelium-intact porcine coronary arterial rings was measured with a chemiluminescence analyser. A23187 (10 microM), NG-Hydroxy-L-arginine (100 microM), and to a lesser extent NG-hydroxy-D-arginine (100 microM), significantly increased NO concentration over 15 min observation period. When A23187 and NG-hydroxy-L-arginine were combined, NO concentration increased in an additive fashion. Enhanced NO release by either A23187, NG-hydroxy-L-arginine or NG-hydroxy-D-arginine was attenuated by NG-nitro-L-arginine methyl ester. We conclude that NG-hydroxy-L-arginine exerts its effects on the contractility of coronary arteries by acting as a substrate for the endothelial nitric oxide synthase leading to enhanced NO production. Cytochrome P450 were not involved the dilatory response to NG-hydroxy-L-arginine. In this respect, porcine coronary arteries differ significantly from cultured smooth muscle cells in metabolising NG-hydroxy-L-arginine.