Estimation of Postcardiac Arrest Interval Based on Atrial Cavity Density in Postmortem Computed Tomography

Background: Intracardiac hypostasis is frequently observed in postmortem computed tomography (PMCT) of acute deaths, and it becomes clearer as the postmortem interval increases. To determine the postcardiac arrest interval (PCAI), we evaluated densities of the right and left atria [anterior part of the right atrium (AR) and posterior part of the left atrium (PL)] using postmortem computed tomographic images. Methods: A total of 184 patients were included in the study. Patients with return of spontaneous circulation and those with final alive confirmation time over 1 hour were excluded. We evaluated the density of AR and PL at the level of the right inferior pulmonary vein entry to the left atrium. We defined the interval between the estimated cardiac arrest time and the postmortem CT time as the PCAI. Results: There was a negative correlation between AR and PCAI in 59 patients who died owing to cardiovascular disease. The regression equation (PCAI = −1.725 × AR + 132.95) was obtained based on this result. There was no correlation between PL and PCAI. Conclusion: The result suggests that the density of the anterior part of the right atrium decreases as postcardiac arrest interval increases in the case of cardiovascular disease. The regression equation may be used as an additional method to estimate postcardiac arrest interval

Forensic Medicine in South Asia: Comparison to the Developed Countries

This study attempted to discuss the historical context and current practice of forensic medicine in South Asia. Comparisons within and between countries in South Asia, and between South Asia and the developed countries (represented by Japan and the USA) have been made to provide an insight into their distinct practice of forensic medicine. Though the formal establishment of forensic medicine in South Asia commenced at a comparable period to the developed countries, their pace of development has been considerably slow. Moreover, their ways of practice as well have evolved differently. In effect, South Asian countries follow an ‘integrated service’ system, whilst Japan and the USA practice ‘divided service’ systems to provide forensic medical services. Similarly, regarding the death investigations, most South Asian countries follow a Police-led death investigation system, whereas Japan and the USA follow a hybrid model and the Medical examiner’s system of death investigation, respectively. Indeed, forensic medicine in South Asia is undeniably underdeveloped. In this paper, by highlighting the issues and challenges confronted in South Asia, key actions for prompt redressal are discussed to improve the standard of forensic medical services in South Asia

A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD

Contains fulltext : 69105.pdf (publisher's version ) (Closed access)Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In addition, a broad set of executive/cognitive and motor tests was administered to 350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non-affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5' and two 3') in DAT1 were genotyped. The effect of the polymorphisms on neuropsychological functioning was studied. The review indicated that the majority of studies did not find a relation between DAT1 and neurophysiological or neuropsychological measures. In our sample, several of the polymorphisms of DAT1 were associated with ADHD and ADHD was associated with impaired neuropsychological functioning. However, none of the DAT1 polymorphisms was convincingly associated with neuropsychological dysfunctioning. This suggests that the effect of DAT1 on ADHD was not mediated by neuropsychological performance. However, since DAT1 is mainly expressed in the striatum and not the prefrontal cortex, it may influence striatum-related functions (such as delay aversion) more heavily than prefrontal related functions (such as executive functions). Associations of DAT1 with ADHD were only found in adolescents, which may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having a more persistent form of ADHD may mark a more severe or homogeneous genetic form of the disorder

Early markers for myocardial ischemia and sudden cardiac death.

The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB

Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms

Development of New Formulas for Sex and Age Estimation by Assessing Maxillary Sinus Morphology on CBCT

Background The morphology of the maxillary sinus varies between individuals which could be used in the forensic personal identification process. Methods: In the current study, the CBCT images of the maxillary sinus in 453 patients (217 males, 236 females) aged 14 to 95 years were analyzed. In particular, each left, and right maxillary sinus of the subjects was measured for its maximum height, width, and breadth in 2-D, and volume in 3-D perspectives, and their usefulness for age and sex estimation was examined. Regarding age estimation, because the size of the maxillary sinus increases up to 20s and then decreases over time, two separate age estimation formulas were created, one for subjects in their 14–21 years and the other for those over 22 years old. For each age group, multiple regression formulas were generated using the diameters and volume as explanatory variables and the chronological age as a response variable. This study used 150 cases not included in the study as a validation set for age estimation. Results: Generally, all the diameters and volumes in both sinuses tended to increase till the mid-20s, and then gradually decreased over time. The derived formulas were tested for their accuracy on additional 150 subjects. Plausibly, the model could estimate the age between 14–21 years old with an average accuracy of ± 1.8 years for men and ± 3.2 years for women. Whereas for those over 22 years old, it was possible to estimate the age with an accuracy of ± 11.8 years for males and ± 10.3 years for females, respectively. A comparison of estimated age and chronological age did not show a statistically significant difference(P > 0.05). It was found that the left maxillary sinus had more age groups showing the most significant difference than other measurements between sexes(P < 0.05). The maxillary sinus height may be significantly affected by gender differences. Conclusion: Overall, this study showed the effectiveness of age and sex estimation using the maxillary sinus morphometric analyses

A phase 2 study of a combined diphtheria-tetanus-acellular pertussis vaccine with a Sabin-derived inactivated poliovirus vaccine in children

Background: With the goal of global eradication of poliomyelitis due to wild-type viruses within sight, WHO now recommends that infants receive at least one dose of trivalent inactivated poliovirus vaccine (IPV) with bivalent OPV (types 1 and 3) replacing trivalent OPV. Limited manufacturing capacity and new regulations on manufacturers’ use of wild-type viruses is driving the development of IPV based on attenuated Sabin type polioviruses. Takeda are developing a Sabin-based IPV (sIPV) to augment global capacity and supply. Methods: This study was performed to evaluate three dosages (low, medium and high) of the sIPV when administered as a combination vaccine with diphtheria-tetanus-acellular pertussis antigens (DTaP-sIPV) as a three dose primary series or as booster dose in Japanese infants and toddlers. Results: All formulations were immunogenic and well-tolerated with no safety concerns in either infants or toddlers. There was a dosage-dependent induction of neutralizing antibodies against Sabin polioviruses, the only statistically significant differences being between the low-dose and medium- and high-dose sIPVs. There was good correlation of neutralizing antibodies against Sabin and wild-type polioviruses. No sIPV dose had an observable effect on immune responses to DTaP components or the reactogenicity profile of the combined vaccine. Conclusion: When administered as a DTaP-sIPV combination, Takeda’s sIPV vaccine was well-tolerated and highly immunogenic in infant and toddler schedules. The medium-dose formulation offers the optimal balance between immunogenicity and potential dose-sparing to provide a new source of sIPV to enhance the global supply, while mitigating the environmental risks associated with manufacturing vaccines with wild-type viruses