SH3BP2-related fibro-osseous disorders of the maxilla and mandible: A systematic review.

Cherubism is a disorder of bony overgrowth of the jaws that manifests in childhood. SH3BP2 gene variants have been associated with cherubism; this gene plays a major role in bone homeostasis. Due to its rare occurrence, there is as yet no comprehensive understanding of the natural history and clinical course of the disease. The aim of this review was to compile and analyze all cases of SH3BP2-related cherubism and cherubism-like disorders. Thirty publications were identified, including 92 individuals from 34 families, who were diagnosed with SH3BP2-related fibro-osseous lesions of the jaw. Only 15% of cases included in this review had no known family history of the disease. The distribution of cherubism was equal with respect to biological sex. Missing teeth were reported in 38% of cases. Lesions were restricted to the mandible in 36% of cases and involved both the maxilla and mandible in 54% of cases. The clinical phenotypes reported in the articles analyzed varied greatly in detail, making comparisons between studies and conclusive analysis difficult. Further work is necessary to describe the connection between SH3BP2 gene variants and cherubism in order to advance its diagnosis and treatment.

Low rate of local recurrence detection by rectoscopy in follow-up of rectal cancer.

AIM: The main aim of this study was to examine the effectiveness of rectoscopy for detecting local recurrence of rectal cancer in patients following low anterior resection. METHOD: This was a retrospective study of 201 patients, who underwent low anterior resection for rectal or rectosigmoid cancer between 2007 and 2009 and who were followed up with rigid rectoscopy and imaging. A total of 91 patients were excluded from the analysis for various reasons, leaving 110 patients eligible for analysis. RESULTS: A total of 613 rectoscopies were performed, and 48 biopsies taken. Six local recurrences were detected in the 110 patients, three of which were first detected by rectoscopy and three by CT. Two of the local recurrences were detected outside the follow-up programme because of symptoms: one by rectoscopy and one by CT. Three of 613 (0.5%) rectoscopies led to detection of local recurrence. The sensitivity and specificity of rectoscopy to detect local recurrence was 0.50 and 0.93, respectively. Nineteen distant metastases were detected, and two patients had both local recurrence and distant metastasis. All local recurrences and distant metastases were detected within 48 months of surgery. CONCLUSION: Rigid rectoscopy is poor at detecting local recurrence. Only 3 out of 613 rectoscopies (0.5%) detected local recurrence. Due to extramural growth of some recurrences, the sensitivity is also very low. Based on our results, routine rectoscopy in the surveillance of asymptomatic patients cannot be recommended.

Rate of Anastomotic Leakage After Rectal Anastomosis Depends on the Definition: Pelvic Abscesses are Significant.

BACKGROUND AND AIMS: The International Study Group of Rectal Cancer has proposed that a pelvic abscess in the proximity of the anastomosis is considered an anastomotic leak, whether or not its point of origin is detectable. This study describes how the inclusion of pelvic abscesses alters the leakage rate. MATERIAL AND METHODS: Risk factors and postoperative complications in patients with visible anastomotic leakage ("direct leakage"), pelvic abscesses alone in the vicinity of a visibly intact anastomosis ("abscess leakage"), and no leakage were retrospectively evaluated. RESULTS: In total, 341 patients operated with anterior resections and who received an anastomosis within 15 cm as measured from the anal verge were included. A total of 37 patients (10.9%) had direct leakage, 13 (3.8%) had abscess leakage, and 291 (85.3%) had no leakage. The overall anastomotic leakage rate was 14.7% (50 patients). In accordance with the grading system outlined by International Study Group of Rectal Cancer, 7 patients (2.1%) experienced Grade A leakage, 19 (5.6%) Grade B, and 24 (7.0%) Grade C. Direct leak patients had more often a reoperation due to anastomotic complications (odds ratio = 19.7, p = 0.001), a permanent stoma (odds ratio = 28.5, p = 0.001), and a longer hospital stay than abscess leak patients (29.0 vs 15.5 days, p = 0.030). CONCLUSION: Abscess leakage accounted for over one-fourth of the overall leakage rate, raising the leakage rate. Direct leak patients were at a higher risk of requiring a reoperation, permanent stoma, and longer hospital stay than abscess leak patients. Abscess leak patients were at a greater risk for a urinary tract infection, wound infection, and postoperative intestinal obstruction than non-leak patients.

Gas chromatography-isotope dilution mass spectrometry method validation for target pesticides in soybeans.

The production of certified reference materials requires the application of highly accurate methods for characterisation. A gas chromatography-isotope dilution mass spectrometry method, setting ambitious performance criteria, was developed for eight selected pesticides in soybeans. Pressurised liquid extraction was followed by automated gel-permeation chromatography and solid-phase extraction clean-up. Pesticides identification respected a Commission Decision and guidelines of the Directorate General for Health and Food Safety (DG SANTE). Reliable quantification involved stable isotopically labelled analogues as internal standards. Validation, according to ISO/IEC 17,025 and DG SANTE guidelines, assessed linearity, LOD/LOQ, trueness, selectivity, precision, stability and robustness. Mean recoveries ranges (83-109%, relative standard deviations < 3%), repeatability (2.2-4.8%), day-to-day variation (0.6-4.2%) and combined uncertainty (1.2-4.2%) were fit for purpose. The method is highly accurate and suitable for certification of the selected pesticides in soybean matrix reference material. Chemical compounds studied in this article: Diazinon (PubChem CID: 3017); malathion (PubChem CID: 4004); chlorpyrifos (PubChem CID: 2730); captan (PubChem CID: 8606); endosulfan (PubChem CID: 3224); tebuconazole (PubChem CID: 86,102); iprodione (PubChem CID: 37,517); cypermethrin (PubChem CID: 2912).

Evidence to support the hypothesis of tuberculosis as a cause of extreme osteonecrosis and osteomyelitis of the mandible in a West African population.

Maxillofacial tuberculosis (TB) is rare. The cases of 19 patients showing extreme bony destruction in the mandible, collected over a 3-month period in West Africa, are presented. Clinical, radiographic, and histological evidence indicated Mycobacterium tuberculosis as a possible cause. Further studies are in progress.

Accurate determination of selected pesticides in soya beans by liquid chromatography coupled to isotope dilution mass spectrometry.

A sensitive, accurate and simple liquid chromatography coupled with mass spectrometry method for the determination of 10 selected pesticides in soya beans has been developed and validated. The method is intended for use during the characterization of selected pesticides in a reference material. In this process, high accuracy and appropriate uncertainty levels associated to the analytical measurements are of utmost importance. The analytical procedure is based on sample extraction by the use of a modified QuEChERS (quick, easy, cheap, effective, rugged, safe) extraction and subsequent clean-up of the extract with C18, PSA and Florisil. Analytes were separated on a C18 column using gradient elution with water-methanol/2.5 mM ammonium acetate mobile phase, and finally identified and quantified by triple quadrupole mass spectrometry in the multiple reaction monitoring mode (MRM). Reliable and accurate quantification of the analytes was achieved by means of stable isotope-labelled analogues employed as internal standards (IS) and calibration with pure substance solutions containing both, the isotopically labelled and native compounds. Exceptions were made for thiodicarb and malaoxon where the isotopically labelled congeners were not commercially available at the time of analysis. For the quantification of those compounds methomyl-(13)C2(15)N and malathion-D10 were used respectively. The method was validated according to the general principles covered by DG SANCO guidelines. However, validation criteria were set more stringently. Mean recoveries were in the range of 86-103% with RSDs lower than 8.1%. Repeatability and intermediate precision were in the range of 3.9-7.6% and 1.9-8.7% respectively. LODs were theoretically estimated and experimentally confirmed to be in the range 0.001-0.005 mg kg(-1) in the matrix, while LOQs established as the lowest spiking mass fractionation level were in the range 0.01-0.05 mg kg(-1). The method reliably identifies and quantifies the selected pesticides in soya beans at appropriate uncertainty levels, making it suitable for the characterization of candidate reference materials.

Regulation of adipogenesis and osteogenesis in mesenchymal stem cells by vascular endothelial growth factor A.

Understanding the mechanisms by which bone marrow mesenchymal stem cells (BMSCs) differentiate into bone-forming osteoblasts and marrow adipocytes is crucial to develop strategies for the treatment of several bone diseases. Age-related bone loss resulting in osteopenia and osteoporosis has been associated with reduced numbers of osteoblasts and increased numbers of adipocytes, likely originating from differentiation defects in BMSCs. Although many factors involved in the complex regulation of osteoblast and adipocyte cell lineages have previously been identified, their functional interactions in the context of BMSC differentiation and maintenance of bone homeostasis during ageing are unknown. Recent discoveries have provided important new insights into the mechanisms by which the nuclear envelope protein lamin A and vascular endothelial growth factor A (VEGF) mutually control BMSC fate. Particularly interesting is the finding that VEGF in this context functions as an intracellular protein, unaffected by neutralizing antibodies, and not as a secreted growth factor. These insights may not only facilitate the identification of new targets for treating bone diseases but also lead to improved design of tissue engineering approaches aimed at stimulating bone regeneration and repair.

Conservative treatment has comparable outcome with bouquet pinning of little finger metacarpal neck fractures: a multicentre randomized controlled study of 85 patients.

Current literature gives few guidelines regarding indication for operative treatment of little finger metacarpal neck fractures, and some surgeons choose operative treatment when the palmar angulation exceeds 30°. The objective of this study was to determine whether conservative treatment produces comparable outcomes with bouquet pinning in a randomized, controlled trial. Eighty-five patients with little finger metacarpal neck fractures with ≥30° palmar angulation in the lateral view were included. Patients were randomized to two groups: conservative treatment without reduction of the fracture (43 patients); and closed reduction and bouquet pinning (42 patients). After 1 year, there were no statistical differences between the groups in QuickDASH score, pain, satisfaction, finger range of motion, grip strength, or quality of life. There was a trend versus better satisfaction with hand appearance (p = 0.06), but longer sick leave (p < 0.001) and more complications (p = 0.02) in the operative group.

Randomized clinical trial on the postoperative use of an abdominal binder after laparoscopic umbilical and epigastric hernia repair.

PURPOSE: Application of an abdominal binder is often part of a standard postoperative regimen after ventral hernia repair to reduce pain and seroma formation. However, there is lack of evidence of the clinical effects. The aim of the present study was to investigate the pain- and seroma-reducing effect of an abdominal binder in patients undergoing laparoscopic umbilical or epigastric hernia repair. METHODS: Based on power analysis, a minimum of 54 patients undergoing laparoscopic umbilical and epigastric hernia repair were to be included. Patients were randomized to abdominal binders vs. no abdominal binders during the first postoperative week. Standardized surgical technique, anaesthesia, and analgesic regimens were used and study observers were blinded towards the intervention. Postoperative pain (visual analogue score) on day 1 was the primary outcome. In addition, ultrasonographic evaluation of seroma formation and several subjective patient-related parameters were registered. Furthermore, patients in the abdominal binder group were asked to rate benefits or discomforts of wearing the binder. RESULTS: Data from 56 patients (abdominal binder, n = 28; no binder, n = 28) were available for analysis. No significant intergroup differences in postoperative pain or any of the other surgical outcomes, including seroma formation, were found. However, the abdominal binder group reported subjective beneficial effect of wearing the binder in 24 of the 28 patients (86%). No adverse effects of the abdominal binder were found. CONCLUSIONS: There were no effects of an abdominal binder on pain, movement limitation, fatigue, seroma formation, general well-being, or quality of life. However, most patients claimed a subjective beneficial effect of using their abdominal binder.

Microaneurysm count as a predictor of long-term progression in diabetic retinopathy in young patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

PURPOSE: To investigate microaneurysm (MA) count as a predictor of long-term progression of diabetic retinopathy (DR) in young patients with type 1 diabetes mellitus (T1DM). METHODS: We examined 185 patients with T1DM at baseline (1995) and at follow-up (2011). At baseline, mean age and duration of diabetes were 20.6 and 12.9 years, respectively. Two-field (1995) and seven-field (2011) fundus photographs were taken in accordance with the European Diabetes Study Group (EURODIAB) and the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. DR was graded in accordance to the ETDRS protocol, allowing for non-standard photography at baseline. Baseline MAs were counted; patients without DR and those with MAs only were included. Multivariable logistic regressions were performed to investigate MA-count as a predictor of two-step progression, progression to proliferative DR (PDR), and incident diabetic macula edema (DME). RESULTS: We included 138 patients (138 eyes). Of these, 58 had no retinopathy and 80 had MAs only. At follow-up, rates of two-step progression of DR, progression to PDR and incident DME were 52.9, 21.7, and 10.1 %, respectively. In logistic regression models, MA count was able to predict progression to PDR (OR: 1.51 per MA; 95 % CI: [1.04-2.20]) and DME (OR: 1.69 per MA; 95 % CI: [1.05-2.77]), but not two-step progression (OR 0.91 per MA, 95 % CI: [0.64-1.31]). CONCLUSIONS: In younger patients with T1DM, MA count predicts long-term incidence of PDR and DME. This demonstrates that early DR is a warning sign of late retinopathy complications and that the number of MAs is an important factor for long-term outcome.

Outcome, revision rate and indication for revision following resurfacing hemiarthroplasty for osteoarthritis of the shoulder: 837 operations reported to the Danish Shoulder Arthroplasty Registry.

In this study, we evaluated patient-reported outcomes, the rate of revision and the indications for revision following resurfacing hemiarthroplasty of the shoulder in patients with osteoarthritis. All patients with osteoarthritis who underwent primary resurfacing hemiarthroplasty and reported to the Danish Shoulder Arthroplasty Registry (DSR), between January 2006 and December 2010 were included. There were 772 patients (837 arthroplasties) in the study. The Western Ontario Osteoarthritis of the Shoulder (WOOS) index was used to evaluate patient-reported outcome 12 months (10 to 14) post-operatively. The rates of revision were calculated from the revisions reported to the DSR up to December 2011 and by checking deaths with the Danish National Register of Persons. A complete questionnaire was returned by 688 patients (82.2%). The mean WOOS was 67 (0 to 100). A total of 63 hemiarthroplasties (7.5%) required revision; the cumulative five-year rate of revision was 9.9%. Patients aged < 55 years had a statistically significant inferior WOOS score, which exceeded the minimal clinically important difference, compared with older patients (mean difference 14.2 (8.8; 95% CI 19.6; p < 0.001), but with no increased risk of revision. There was no significant difference in the mean WOOS or the risk of revision between designs of resurfacing hemiarthroplasty.

The mouse palate and its cellular responses to midpalatal suture expansion forces.

OBJECTIVES: To investigate the anatomy of the mouse palate, the midpalatal suture, and the cellular characteristics in the sutures before and immediately after midpalatal suture expansion. MATERIALS AND METHODS: Wild-type C57BL/6 male mice, aged between 6 weeks and 12 months, were chosen for all the experiments. The complete palate of the non-operated group and the midpalatal suture-expanded group at different ages was used for histological, micro-CT, immunohistochemistry, and sutural cell analyses. RESULTS: This study documents precise morphological and histological characteristics of the mouse palatal sutures. In addition to the opening of the midpalatal suture caused by expansion, both transverse and interpalatine sutures were also seen to be affected. Cellular density was decreased in different types of sutures following the application of mechanical force. CONCLUSIONS: The detailed morphology and histology of the mouse palate and the cellular changes that occur following midpalatal suture expansion, as described here, will be helpful as a basis for further investigations of palatal suture tissue responses to mechanical force.

The clinical outcomes of mosaicplasty in the treatment of osteochondritis dissecans of the distal humeral capitellum of young athletes.

BACKGROUND: The purpose of this study was to evaluate the clinical outcomes of mosaicplasty in the treatment of osteochondritis dissecans of the distal humeral capitellum. MATERIALS AND METHODS: Between 2003 and 2007, 10 patients (6 female and 4 male patients), with a mean age at surgery of 18 years (range, 13 to 27 years), with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The surgical technique involves transplanting small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint to the defect of the capitellum. At a mean follow-up of 30 months, all elbows were assessed with the Mayo Elbow Performance Score and a modified functional elbow score (Constant). RESULTS: Postoperative radiographs and control magnetic resonance imaging/computed tomography images showed incorporation of the subchondral cortex in all patients. All but 2 patients were completely pain free after surgery. Of the patients, 8 (80%) had no reduction in range of motion. By use of the Mayo Elbow Performance Score, the injured elbow had a preoperative mean score of 71 points (range, 55 to 85 points) and increased significantly to a mean score of 93.5 points (range, 85 to 100 points) postoperatively (P = .0005, paired t test). The nonoperative elbows had a mean score of 100 points, whereas the operated elbows had a mean score of 93.5 points. The functional elbow score showed a mean difference of 7.5 points between the operated and nonoperative elbows. No infection or neurologic deficit developed after surgery in any case. CONCLUSIONS: Autologous osteochondral mosaicplasty for advanced lesions of capitellar osteochondritis dissecans can provide satisfactory clinical and radiographic results.

Regulation of DNA-dependent protein kinase by protein kinase CK2 in human glioblastoma cells.

The DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the nonhomologous end-joining pathway of DNA double-strand breaks repair. Although DNA-PK has been biochemically characterized in vitro, relatively little is known about its functions in the context of DNA repair and how its kinase activity is precisely regulated in vivo. Here, we report that cellular depletion of the individual catalytic subunits of protein kinase CK2 by RNA interference leads to significant cell death in M059K human glioblastoma cells expressing DNA-PKcs, but not in their isogenic counterpart, that is M059J cells, devoid of DNA-PKcs. The lack of CK2 results in enhanced DNA-PKcs activity and strongly inhibits DNA damage-induced autophosphorylation of DNA-PKcs at S2056 as well as repair of DNA double-strand breaks. By the application of the in situ proximity ligation assay, we show that CK2 interacts with DNA-PKcs in normal growing cells and that the association increases upon DNA damage. These results indicate that CK2 has an important role in the modulation of DNA-PKcs activity and its phosphorylation status providing important insights into the mechanisms by which DNA-PKcs is regulated in vivo.

Cyclin D1 positive follicular lymphoma.

This report describes an unusual case of cyclin D1 expression by an otherwise typical follicular lymphoma, of low histological grade. BCL2-IGH and CCND1-IGH fusions were identified by interphase fluorescence in situ hybridisation.

Population-based assessment of Mycoplasma genitalium in Vietnam--low prevalence among married women of reproductive age in a rural area.

OBJECTIVE: To analyse the prevalence of Mycoplasma genitalium infection in a population-based study among married women from a demographic surveillance site in a rural geographical area of Vietnam. MATERIALS AND METHODS: Women, aged 18-49 years, were randomly selected to participate. DNA was isolated from endocervical swabs sampled from 990 participating women. The M. genitalium MgPa adhesion gene was detected using a real-time polymerase chain reaction with TaqMan probe. RESULTS: Eight (0.8%; 95% confidence interval, 0.25-1.35%) of the included women were infected with M. genitalium. Two of these positive women reported clinical symptoms. One additional M. genitalium-positive but symptom-free woman, however, showed clinical signs of vaginitis. None of the M. genitalium-positive women was concomitantly infected with Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis or human immunodeficiency virus (HIV). Furthermore, there was no obvious association between M. genitalium infection and vaginal douching, use of intrauterine device, or occurrence of bacterial vaginosis, candidiasis, or Trichomonas vaginalis. CONCLUSIONS: The prevalence of M. genitalium among married women in Vietnam was relatively low. However, more large, well-designed and appropriately performed studies in other population groups including unmarried women and men, and in other geographical areas, rural as well as urban, are crucial in order to extract any evidence-based conclusions regarding the overall prevalence of sexually transmitted infections (STIs), including M. genitalium infections, in the Vietnamese society. The present study compiled with such future studies may form the basis for a national sexual health strategy for prevention, diagnosis, and surveillance of STIs, including M. genitalium infections, in Vietnam.

Development and tissue origins of the mammalian cranial base.

The vertebrate cranial base is a complex structure composed of bone, cartilage and other connective tissues underlying the brain; it is intimately connected with development of the face and cranial vault. Despite its central importance in craniofacial development, morphogenesis and tissue origins of the cranial base have not been studied in detail in the mouse, an important model organism. We describe here the location and time of appearance of the cartilages of the chondrocranium. We also examine the tissue origins of the mouse cranial base using a neural crest cell lineage cell marker, Wnt1-Cre/R26R, and a mesoderm lineage cell marker, Mesp1-Cre/R26R. The chondrocranium develops between E11 and E16 in the mouse, beginning with development of the caudal (occipital) chondrocranium, followed by chondrogenesis rostrally to form the nasal capsule, and finally fusion of these two parts via the midline central stem and the lateral struts of the vault cartilages. X-Gal staining of transgenic mice from E8.0 to 10 days post-natal showed that neural crest cells contribute to all of the cartilages that form the ethmoid, presphenoid, and basisphenoid bones with the exception of the hypochiasmatic cartilages. The basioccipital bone and non-squamous parts of the temporal bones are mesoderm derived. Therefore the prechordal head is mostly composed of neural crest-derived tissues, as predicted by the New Head Hypothesis. However, the anterior location of the mesoderm-derived hypochiasmatic cartilages, which are closely linked with the extra-ocular muscles, suggests that some tissues associated with the visual apparatus may have evolved independently of the rest of the "New Head".

The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis.

Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found that CK2beta participates in PLK1-Wee1 complex formation whereas its cellular depletion leads to disruption of PLK1-Wee1 interaction and reduced Wee1 phosphorylation at Ser53 and 121. The data reported here reinforce the notion that CK2beta has functions that are independent of its role as the CK2 regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.

Species diversity of campylobacteria in a wild bird community in Sweden.

AIMS: To analyse the occurrence and host species distribution of campylobacteria species in shorebirds, geese and cattle on grazed coastal meadows in Sweden. METHODS AND RESULTS: Species identification was performed through a polyphasic approach, incorporating Amplified Fragment Length Polymorphism (AFLP) profiling, 16S RNA gene sequence analysis together with extensive phenotypic characterization. From 247 sampled birds and 71 cattle, we retrieved 113 urease positive thermophilic Campylobacter (UPTC) and 16 Campylobacter jejuni ssp. jejuni isolates. Furthermore, 18 isolates of Helicobacter canadensis, and five isolates that potentially represent a new genus of micro-aerophilic, spiral and Gram-negative bacteria were isolated. The distribution of bacterial species on hosts was uneven: all H. canadensis isolates were retrieved from geese, while all but one of the Campylobacter lari UPTC isolates were found in shorebirds. AFLP type distribution of Camp. lari UPTC isolates among individual, resampled and breeding-paired Redshank birds generally indicated a constant shift in strain populations over time and absence of geographical clustering. CONCLUSIONS: The large number of isolated campylobacteria, including species that are zoonotic enteropathogens, indicates that these wild birds potentially may serve as reservoirs of human infections. However, despite a common environment, the different host species largely carried their own campylobacteria populations, indicating that cross-species transmission is rare. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study is one of few that provide data on the occurrence of campylobacteria in wild animals, adding information on the ecology and epidemiology of micro-organisms that are of public health concern.