We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD. 相似文献
Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women. 相似文献
The purpose of this study was to identify the performance differences between two groups of Austrian dental students (one with a prior medical degree and one without a medical degree) during their dental school training and final dental licensure examination. A specific aim was to determine if having a medical degree is a predictive factor for dental students' scores on the Austrian Dental Admission Test (Austrian DAT), performance in the dental clinic, and scores on final exam. The study consisted of a retrospective analysis of 122 students (thirty-nine with a medical degree and eighty-three without a medical degree) who were enrolled in the Dental Clinic at Innsbruck Medical University, Innsbruck, Austria, between 2001 and 2006. Three performance categories were considered: Austrian DAT results, clinical performance after the first clinical year in dental school, and performance on the final dental licensure examination. Information on students' age, gender, and previous medical degree was collected from official records. Analyses with student's t-test and Pearson's chi-square test revealed that the students with a medical degree had significantly higher Austrian DAT total test scores, grade point averages after the first clinical year, and scores on the final exam. Additionally, those students had significantly better performance on the final exam in prosthodontics and oral and maxillofacial surgery. The linear regression analysis showed that a medical degree had an independent effect on average scores on the final exam, age, and Austrian DAT test scores, while gender showed no statistically significant effect. Overall, the study found that dental students with a prior medical degree had significantly higher Austrian DAT total test scores and performed significantly better in the first clinical year and on the final exam than those without a prior medical degree. 相似文献
Early childhood caries (ECC) is recognized as an infectious disease. The first step in its development is primary infection by the bacterium S. mutans which has been identified as the primary etiologic factors in dental caries. Lactobacilli were also found to play a role in the progression of disease. However the underlying mechanism of immune response to caries is unclear. The association between secretory IgA (s.IgA) and cariogenic microorganisms is still controversial. The purpose of this study was to assess the level of salivary IgA in caries free children, and children with SECC and their corresponding mothers. The study also aims at correlating the children's levels to their mothers'. Sixty children and their mothers attending the dental clinic in King Abdulaziz University participated in our study. Their age ranged from 3 - 5 years. The study groups consisted of thirty children with SECC and a control group consisting of thirty caries free children. Children together with their mothers were examined and their caries level was recorded. Stimulated saliva was collected from each participant for immunological assessment. The secretory IgA (s. IgA) level was assessed by ELISA test. Our study has shown that children with SECC and their mothers had higher levels of s. IgA than the caries free children and their mothers. A positive high correlation was found between secretory IgA of mothers and children in both groups. 相似文献
Intraforaminal ligaments (IFL) are of great interest to anatomists and clinicians to fully understand the detailed anatomy of the neuroforamina and to diagnose unclear radicular symptoms. Studies published until now have described radiological imaging of the IFLs using magnetic resonance imaging (MRI) on donor bodies. In the present study, we investigated the detectability of lumbar IFLs in vivo in adults using the high spatial resolution of the constructive interference in steady state (CISS) sequence.
Methods
A total of 14 patients were studied using a 1.5 T MRI scanner. The lumbar spine was imaged using the parasagittal CISS sequence, and the detectability of the IFLs was assessed for each lumbar level. All image datasets were analyzed by a radiologist, an orthopedic surgeon, and an anatomist. Interrater reliability was expressed as Fleiss’ Kappa. Using a single data set, a three-dimensional (3D) model was created to map the location of the IFLs within the intervertebral foramen (IF) and the immediate surrounding vessels.
Results
Overall, the radiologist was able to detect IFLs in 60% of all imaged IFs, the orthopedic surgeon in 62%, and the anatomist in 66%. Fleiss’ Kappa for the various segments varies from 0.71 for L4/5 up to 0.90 for L3/4.
Conclusion
Lumbar IFLs were successfully detected in vivo in every patient. The detection frequency varied from 42–86% per IF. We demonstrated reproducible imaging of the IFLs on MRI, with good interrater reliability. The present study was a launching point for further clinical studies investigating the potential impact of altered IFLs on radicular pain.
INTRODUCTION: EnSite NavX (NavX) is a novel mapping and navigation system that allows visualization of conventional catheters for diagnostic and ablative purposes and uses them to create a three-dimensional (3D) geometry of the heart. NavX is particularly suitable for ablation procedures utilizing an anatomic approach, as in the setting of common-type atrial flutter (AFL). The aim of this study was to compare NavX-guided and conventional ablation procedures for AFL. METHODS AND RESULTS: Forty consecutive patients (32 male, 59 +/- 12 years) with documented AFL were randomized to undergo fluoroscopy-guided (group I, 20 patients) or NavX-guided (group II, 20 patients) ablation, including 3D isthmus reconstruction. The same catheter setup was used in both groups. The endpoint of bidirectional isthmus block was obtained in all patients. Compared to conventional approaches, NavX-guided procedures significantly reduced fluoroscopy time (5.1 +/- 1.4 min vs 20 +/- 11 min, P < 0.01) and total x-ray exposure (5.1 +/- 3.1 Gycm2 vs 24.9 +/- 1.6 Gycm2, P < 0.01). Isthmus geometry reconstruction could be performed in all patients of group II. In 4 patients (20%) of group II, anatomic isthmus variations were detected by NavX. No significant differences in radiofrequency current applications and procedural times were found between the two groups. CONCLUSION: NavX technology allows geometry reconstruction of the cavotricuspid isthmus. NavX-guided ablation of AFL reduces total x-ray exposure compared to the fluoroscopy-guided approach but does not prolong procedure time. 相似文献
Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1(wt)) reduced resting tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1(H208A)) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1(wt)) was functionally antagonized by coexpression with SPP1(wt) but not SPP1(H208A). SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P(2) inhibition by antisense oligonucleotides and 1 mumol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1(wt) overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1(wt) and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure. 相似文献