Forensic DNA phenotyping: Canis familiaris breed classification and skeletal phenotype prediction using functionally significant skeletal SNPs and indels.

This review highlights a novel application of breed identification and prediction of skeletal traits in forensic investigations using canine DNA evidence. Currently, genotyping methods used for canine breed classification involve the application of highly polymorphic short tandem repeats in addition to larger commercially available SNP arrays. Both applications face technical challenges. An additional approach to breed identification could be through genotyping SNPs and indels that characterise the array of skeletal differences displayed across domestic dog populations. Research has shown that a small number of genetic variants of large effect drive differences in skeletal phenotypes among domestic dog breeds. This feature makes functionally significant canine skeletal variants a cost-effective target for forensic investigators to classify individuals according to their breed. Further analysis of these skeletal variants would enable the prediction of external appearance. To date, functionally significant genes with genetic variants associated with differences in size, bulk, skull shape, ear shape, limb length, digit type, and tail morphology have been uncovered. Recommendations of a cost-effective genotyping method that can be readily designed and applied by forensic investigators have been given. Further advances to improve the field of canine skeletal forensic DNA phenotyping include the refinement of phenotyping methods, further biological validation of the skeletal genetic variants and establishing a publicly available database for storage of allele frequencies of the skeletal genetic variants in the wider domestic dog population.

ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR). MWS is caused by de novo heterozygous mutations in the ZEB2 gene. The majority of mutations lead to haplo-insufficiency through premature stop codons or large gene deletions. Only three missense mutations have been reported so far; none of which resides in a known functional domain of ZEB2. In this study, we report and analyze the functional consequences of three novel missense mutations, p.Tyr1055Cys, p.Ser1071Pro and p.His1045Arg, identified in the highly conserved C-zinc-finger (C-ZF) domain of ZEB2. Patients' phenotype included the facial gestalt of MWS and moderate ID, but no microcephaly, heart defects or HSCR. In vitro studies showed that all the three mutations prevented binding and repression of the E-cadherin promoter, a characterized ZEB2 target gene. Taking advantage of the zebrafish morphant technology, we performed rescue experiments using wild-type (WT) and mutant human ZEB2 mRNAs. Variable, mutation-dependent, embryo rescue, correlating with the severity of patients' phenotype, was observed. Our data provide evidence that these missense mutations cause a partial loss of function of ZEB2, suggesting that its role is not restricted to repression of E-cadherin. Functional domains other than C-ZF may play a role in early embryonic development. Finally, these findings broaden the clinical spectrum of ZEB2 mutations, indicating that MWS ought to be considered in patients with lesser degrees of ID and a suggestive facial gestalt, even in the absence of congenital malformation.

Surgical management of mandibular cherubism in an adolescent: integration of virtual surgical planning.

Cherubism, also known as familial fibrodysplasia of the jaw, is an autosomal dominant disorder with variable penetrance. The disease process is characterised by painless and progressive bilateral enlargement of the maxillofacial skeleton. We present an adolescent female with a family history of cherubism who presented to the Oral and Maxillofacial Surgery clinic with progressive bilateral swelling of the mandible. The diagnosis of cherubism was established through a thorough history which was confirmed with an incisional biopsy. The progressive swelling negatively affected her appearance and psychosocial well-being. The patient opted for surgical intervention after a course of conservative management. Although there is often resolution of these lesions into adulthood, surgical intervention may be considered when managing this condition in adolescence. Integration with virtual surgical planning can aid in obtaining desired postoperative outcomes.

Synchronous oral squamous cell carcinoma and a lymphoproliferative disorder in an adult: a challenge in diagnosis and management.

Synchronous primary malignancies present challenges in diagnosis, treatment sequencing and management. We present a rare case of a synchronous oral cavity and lymphoproliferative malignancy in a middle-age man. Our patient presented with a primary oral cavity squamous cell carcinoma and was subsequently found to have a secondary lymphoproliferative malignancy (chronic lymphocytic leukaemia/small lymphocytic lymphoma). The challenge of staging and sequencing of treatment is discussed. In addition, this case highlights the importance of multidisciplinary consultation, designing a personalised treatment plan that is coincident with the standard of care for each malignancy, and close follow-up.

Mandibular odontogenic myxoma in a paediatric patient.

Odontogenic myxoma (OM) are benign, locally aggressive tumours that are rarely found in the paediatric maxillofacial region. OMs derive from mesenchymal odontogenic tissue. We describe the management of a 3-year-old girl who presented with a large right-sided mandibular lesion. Her treatment included conservative excision, curettage and peripheral ostectomy. A literature review was performed which calls into question the dogmatic practice of resection with 1 to 1.5 cm margins. Treatment approaches to the OM could potentially be altered in the paediatric patient.

Cervicofacial actinomycosis of the mandible in a paediatric patient.

Cervicofacial actinomycosis remains a rare pathogenic finding in the paediatric population. Diagnosis is challenging, as findings are often non-specific and Actinomyces species are generally difficult to culture. Treatment is a prolonged course of antibiotics, either intravenous and oral, often combined with a surgical procedure to remove the lesion. This patient had non-specific intermittent left mandibular pain for 8 months that was eventually attributed to an Actinomyces odontolyticus infection in the mandible. Diagnosis required incisional biopsy, and treatment involved 12 months of oral antibiotics.

Septic arthritis of the temporomandibular joint in an unvaccinated adolescent.

Septic arthritis of the temporomandibular joint (TMJ) is a rare condition, particularly in the paediatric population. Our case involves a 15-year-old unvaccinated Amish man with acute pain and trismus of the TMJ. The diagnosis was reached after history, clinical examination, radiographic and laboratory examinations were performed. The patient improved after a minimally invasive surgical procedure and medical therapy. Failure to recognise and treat septic arthritis in a timely fashion can result in serious sequalae. Infectious aetiologies should be kept on the differential for any patient with acute TMJ pain.

Postoperative metabolic acidosis following the minimally invasive radiofrequency maze procedure.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia treated in the world. While medical treatment with antiarrhythmic drugs remains the primary treatment modality, symptomatic refractory AF often requires treatment with a catheter or surgical ablation. One minimally invasive therapy is the Mini-Maze procedure, which utilizes epicardial radiofrequency ablation via a subxiphoid approach to rid the heart of arrhythmogenic atrial foci without a median sternotomy or cardiopulmonary bypass. The goal of this retrospective cohort study was to identify clinical factors associated with metabolic acidosis following the Mini-Maze procedure. MATERIALS AND METHODS: After Institutional Review Board approval, we studied patients undergoing the Mini-Maze procedure, off-pump coronary artery bypass grafting or patients conventional Cox-Maze on cardiopulmonary bypass. The first base deficit value obtained in the Intensive Care Unit was used as a measure of metabolic acidosis. Using logistic regression with Akaike information criteria, we analyzed preoperative, intraoperative, and postoperative data to determine the factors associated with changes in base deficit. RESULTS: A multivariable model using stepwise selection demonstrated that diabetes mellitus and weight were associated with a decrease in the base deficit by 2.87 mEq/L (95% CI: -5.55--0.19) and 0.04 mEq/L (95%CI: -0.08, 0.004), respectively. Furthermore, creatinine was associated with a 1.57 mEq/L (95% CI: 0.14, 2.99) increase in the base deficit. CONCLUSION: The Mini-Maze procedure was not associated with postoperative metabolic acidosis. Instead, nondiabetic patients and patients with higher creatinine were associated with greater base deficits after undergoing cardiac surgery.

Evolution, Not Revolution: Measurement and Management of Health Outcomes in New Zealand through Efficient Use of National Information Systems.

The development of health information systems is not always successful, and there is an emerging perception that money and time that could be better directed to patient care are being wasted on these systems. This paper examines the difficulties faced in creating successful information systems in health services, and suggests strategies for overcoming these difficulties. The development of information systems is a precursor to the use of data in the management of processes which lead towards improved health outcomes. It is argued that before embarking upon difficult and costly new developments, researchers should treat existing sources of data as their first point of call, and New Zealand's existing national data sources are described in detail. Ways in which these data are being used to develop outcome measures are discussed, and it is concluded that through a multidisciplinary approach existing resources could be utilised more efficiently and effectively to achieve this goal.