Teaching forensic pathology to undergraduates at Zhongshan School of Medicine.

Producing qualified forensic pathological practitioners is a common difficulty around the world. In China, forensic pathology is one of the required major subspecialties for undergraduates majoring in forensic medicine, in contrast to forensic education in Western countries where forensic pathology is often optional. The enduring predicament is that the professional qualities and abilities of forensic students from different institutions vary due to the lack of an efficient forensic pedagogical model. The purpose of this article is to describe the new pedagogical model of forensic pathology at Zhongshan School of Medicine, Sun Yat-sen University, which is characterised by: (a) imparting a broad view of forensic pathology and basic knowledge of duties and tasks in future careers to students; (b) educating students in primary skills on legal and medical issues, as well as advanced forensic pathological techniques; (c) providing students with resources to broaden their professional minds, and opportunities to improve their professional qualities and abilities; and (d) mentoring students on occupational preparation and further forensic education. In the past few years, this model has resulted in numerous notable forensic students accomplishing achievements in forensic practice and forensic scientific research. We therefore expect this pedagogical model to establish the foundation for forensic pathological education and other subspecialties of forensic medicine in China and abroad.

Course constructions: A case-base of forensic toxicology.

Forensic toxicology education in China is limited by insufficient teaching methods and resources, resulting in students with adequate theoretical principles but lacking practice experience. Typical cases used as teaching materials vividly represent intoxication and provide students with an opportunity to practice and hone resolving skills. In 2013, the Department of Forensic Pathology at Zhongshan School of Medicine began to construct top-quality courses in forensic toxicology, with its first step, creating a base containing typical cases of intoxication. This essay reviews the construction process of said cases-base, which is intended to set an example of forensic toxicology education.

An East Asian Common Variant Vinculin P.Asp841His Was Associated With Sudden Unexplained Nocturnal Death Syndrome in the Chinese Han Population.

BACKGROUND: We have identified the cardiomyopathy-susceptibility gene vinculin (VCL) mutation M94I may account for a sudden unexplained nocturnal death syndrome (SUNDS) case. We addressed whether VCL common variant D841H is associated with SUNDS. METHODS AND RESULTS: In 8 of 120 SUNDS cases, we detected an East Asian common VCL variant p.Asp841His (D841H). Comparing the H841 allele frequency of the general population in the local database (15 of 1818) with SUNDS victims (10 of 240) gives an odds ratio for SUNDS of 5.226 (95% CI, 2.321, 11.769). The VCL-D841H variant was engineered and either coexpressed with cardiac sodium channel (SCN5A) in HEK293 cells or overexpressed in human induced pluripotent stem-cell-derived cardiomyocytes to examine its effects on sodium channel function using the whole-cell patch-clamp method. In HEK293 cells, under physiological pH conditions (pH 7.4), D841H caused a 29% decrease in peak INa amplitude compared to wild type (WT), whereas under acidotic conditions (pH 7.0), D841H decreased further to 43% along with significant negative shift in inactivation compared to WT at pH 7.4. In induced pluripotent stem-cell-derived cardiomyocytes, similar effects of D841H on INa were observed. VCL colocalized with SCN5A at the intercalated disk in human cardiomyocytes. VCL was also confirmed to directly interact with SCN5A, and VCL-D841H did not disrupt the association of VCL and SCN5A. CONCLUSIONS: A VCL common variant was genetically and biophysically associated with Chinese SUNDS. The aggravation of loss of function of SCN5A caused by VCL-D841H under acidosis supports that nocturnal sleep respiratory disorders with acidosis may play a key role in the pathogenesis of SUNDS.

The biophysical characterization of the first SCN5A mutation R1512W identified in Chinese sudden unexplained nocturnal death syndrome.

Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease. To test our hypothesis that slight acidosis conditions may contribute to the significant loss of function of mutant cardiac sodium channels underlying SUNDS, the biophysical characterization of SCN5A mutation R1512W was performed under both extracellular and intracellular slight acidosis at pH 7.0. The cDNA of R1512W was created using site-directed mutagenesis methods in the pcDNA3 plasmid vector. The wild type (WT) or mutant cardiac sodium channel R1512W was transiently transfected into HEK293 cells. Macroscopic voltage-gated sodium current (INa) was measured 24 hours after transfection with the whole-cell patch clamp method at room temperature in the HEK293 cells. Under the baseline conditions at pH 7.4, R1512W (-175 ±â€Š15 pA/pF) showed about 30% of reduction in peak INa compared to WT (-254 ±â€Š23 pA/pF, P < 0.05). Under the acidosis condition at pH 7.0, R1512W (-130 ±â€Š17 pA/pF) significantly decreased the peak INa by nearly 50% compared to WT (-243 ±â€Š23 pA/pF, P < 0.005). Compared to baseline condition at pH 7.4, the acidosis at pH 7.0 did not affect the peak INa in WT (P > 0.05) but decreased peak INa in R1512W (P < 0.05). This initial functional study for SCN5A mutation in the Chinese SUNDS victim revealed that the acidosis aggravated the loss of function of mutant channel R1512W and suggested that nocturnal sleep disorders-associated slight acidosis may trigger the lethal arrhythmia underlying the sudden death of SUNDS cases in the setting of genetic defect.

Microvascular reconstruction of the mandible: an argument for the fibula osteocutaneous free flap / Reconstrucción microvascular de la mandíbula: razones para usar el colgajo libre osteocutáneo de peroné

Introduction/objective: The fibula osteocutaneous free flap has been a workhorse for mandibular reconstruction since Hidalgo's original description for its use for this purpose. The objective of this manuscript is to review the use of the fibula flap in mandibular reconstruction and to answer some of the commonly held misconceptions as to why some surgeons view it as an inferior reconstructive option to the vascularized iliac crest flap. Materials/methods: Review of the literature as it relates to the use of the fibula free flap in mandibular reconstruction and the senior author's experience. Results: The bicortical nature of the fibula provides a stable platform for endosseous implant placement, thus allowing for comprehensive oral rehabilitation and improving the quality of life in reconstructed patients. The fibula osteocutaneous free flap, however, is the longest vascularized bone flap available, allowing for reconstruction of the entire mandible. Given these attributes, it would seem unlikely that doubts regarding the adequacy of the fibula free flap in mandibular reconstruction exists. However, the principal arguments challenging the use of the fibula osteocutaneous free flap are the lack of height of the reconstructed fibula compared to the native mandible, unreliable skin perforators to support a skin paddle, insufficient soft tissue coverage, and the presence of vascular anomalies which may preclude its use. These presumed shortcomings are circumvented with various proven techniques to increase fibular height and anatomic studies demonstrating the cutaneous perforator patterns. Conclusions: With these simple solutions in mind, the fibula osteocutaneous free flap will likely remain a workhorse for mandibular reconstruction, allowing for the reconstruction of virtually any oromandibular defect. It allows for both aesthetic, as well as, functional reconstruction of the mandible (AU)

Introducción/objetivo: Desde la descripción original de Hidalgo sobre su uso con este objetivo, el colgajo libre osteocutáneo de peroné ha sido el factótum para la reconstrucción mandibular. El objetivo de este artículo es revisar el uso del colgajo de peroné en la reconstrucción mandibular y aclarar los conceptos erróneos sostenidos con frecuencia como razón de que algunos cirujanos lo consideren una opción reconstructiva inferior al colgajo vascularizado de cresta ilíaca. Materiales y métodos: Revisión de los estudios publicados sobre el uso del colgajo de peronéen la reconstrucción mandibular y experiencia del primer autor. Resultados: La naturaleza bicortical del peroné ofrece una estructura estable para la colocación de un implante endoóseo, lo que permite una rehabilitación oral integral y mejora la calidad de vida de los pacientes sometidos a reconstrucción. El colgajo libre osteocutáneo de peroné es el colgajo óseo vascularizado de mayor longitud disponible, que permite la reconstrucción de toda la mandíbula. Dadas estas propiedades, parece improbable que suscite dudas su idoneidad en la reconstrucción mandibular. No obstante, la razón principal que pone en duda su uso es la falta de altura del peroné reconstruido, comparado con la mandíbula natural, el número tan variable de perforantes septocutáneos que irrigan la paleta cutánea, una cobertura insuficiente de las partes blandas, y la presencia de anomalías vasculares que pueden impedir su uso. Estas supuestas desventajas se evitan con diversas técnicas de eficacia demostrada para aumentar la altura del peroné al igual que con estudios anatómicos que demuestren los patrones de los perforantes septocutáneos. Conclusiones: Si se tienen en cuenta estas soluciones simples, el colgajo libre osteocutáneo de peroné probablemente seguirá siendo el factótum de la reconstrucción mandibular, ya que permite la reconstrucción de casi cualquier defecto oromandibular. Favorece la reconstrucción tanto estética como funcional de la mandíbula (AU)

Postmortem genetic screening of SNPs in RyR2 gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population.

To investigate the genetic variants of the RyR2 gene in sudden unexplained nocturnal death syndrome (SUNDS) in the southern Chinese Han population, we genetically screened 29 of the 105 coding exons of the RyR2 gene associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in sporadic SUNDS victims using polymerase chain reaction (PCR) and direct sequencing methods. Genomic DNA was extracted from blood samples of 127 SUNDS cases and 165 healthy unrelated controls. None of the published or novel RyR2 missense mutations were found in 127 SUNDS cases. A total of sixteen genetic variants of the RyR2 gene were identified, comprised of: one novel synonymous coding mutation (c.13710C>A), one novel synonymous rare polymorphism (c.14871C>T), and fourteen previously reported polymorphisms. The genotype and allele frequency of previously reported missense polymorphism c.5656G>A (G1886S) was of no statistical difference between SUNDS cases and controls (x(2)=0.390, P>0.05; x(2)=0.271, P>0.05). This is the first report of genetic phenotype of RyR2 gene of SUNDS in the southern Chinese Han population. Previously reported plausible pathogenic missense polymorphism G1886S may not be an independent predisposition factor of SUNDS in the southern Chinese Han population. The association of genetic variants of the RyR2 gene with SUNDS needs further elucidation.

Postmortem molecular analysis of KCNQ1, KCNH2, KCNE1 and KCNE2 genes in sudden unexplained nocturnal death syndrome in the Chinese Han population.

The etiology of sudden unexplained nocturnal death syndrome (SUNDS) remains unclear. Previous studies have implicated that SUNDS is probably allelic to cardiac sodium channel diseases such as Brugada syndrome. The variation in cardiac potassium channels is the main genetic cause of inherited long QT syndrome (LQTS), which may manifest as syncope and sudden cardiac death without structural disease. We hypothesized that cardiac potassium channel disease may be responsible for certain Chinese SUNDS cases. Genotyping of 4 main LQTS-susceptibility genes (KCNQ1, KCNH2, KCNE1, and KCNE2) was performed here for the first time in SUNDS victims from the Chinese Han population to address the pathogenic cause of some SUNDS using polymerase chain reaction and direct DNA sequencing. 120 sporadic SUNDS cases were enrolled. Genomic DNA was extracted from blood samples. A total of 2 novel non-synonymous mutations and 3 previously reported arrhythmia susceptibility polymorphisms were identified in KCNQ1, KCNH2, KCNE1, and KCNE2. We concluded that the variants in KCNQ1, KCNH2, KCNE1 and KCNE2 genes may be correlated with the occurrence of part of SUNDS cases in southern China.

Versatility of supraclavicular artery island flap in head and neck reconstruction of vessel-depleted and difficult necks.

PURPOSE: The advent of microvascular free tissue transfer has given reconstructive surgeons a vast repertoire of treatment options for reconstruction of head and neck defects. However, the success of free flaps in head and neck reconstruction depends on the presence and quality of the recipient vessels in the neck for microvascular anastomosis. The supraclavicular artery island flap can be used to reconstruct a variety of head and neck defects, allowing the reconstructive surgeons to circumvent some of the problems inherent in vessel-depleted necks. The present study reports the use of the supraclavicular artery flap (SCAF) in the reconstruction of vessel-depleted neck and in difficult necks. MATERIALS AND METHODS: The present study was a retrospective study of patients who had undergone reconstruction with an SCAF and who also had a difficult neck or vessel-depleted neck in the head and neck surgery section from 2011 to 2012. Our inclusion criteria were patients treated at our institution with an SCAF who also had undergone multiple previous neck surgeries or patients with severely restricted donor options for soft tissue reconstruction. We excluded any patient for whom we did not have adequate follow-up or if the flap procedure was not performed by the faculty of the head and neck section. RESULTS: We identified 8 patients with a total of 9 SCAFs. One patient received bilateral SCAFs. Of the 8 patients, 6 were men and 2 were women. With the exception of 1 patient, all had received previous radiotherapy to the head and neck region. All the patients had undergone multiple surgical procedures. The flap survival was 100%. However, 2 patients had partial loss of the flap, and 2 had partial donor site wound dehiscence. Our overall complication rate was 38%, including dehiscence of the flap and partial loss of the flap. CONCLUSIONS: The SCAF is a sound option for reconstructing defects in the head and neck region in patients with previous radiotherapy and in multiple neck surgeries. The surgeon and patient should be aware of the high incidence of complications associated with this reconstructive option.