Exposure assessment to heavy metals in general population in an area at high environmental risk through biological monitoring

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Child-Abuse-Related-Deaths, Child Mortality (0-4) & Income Inequality in America and Other Developed Nations 1989-91 v 2012-14: Speaking Truth to Power.

The major concern for social work, namely child abuse‐related deaths (CARD), involves parental neglect. Societal neglect, when measured by child mortality rates (CMR), is considered by bodies such as UNICEF to be indicative of how a nation meets the needs of its children. This population‐based study analyses CARD and CMR for children aged from newborn to four years old between 1989–91 and 2013–15 to identify any relative child neglect in the USA and 20 other developed nations (ODN). World Health Organization data were used for CARD, CMR and undetermined deaths (UnD), a possible source of unreported CARD, juxtaposed against World Bank income inequality data. The USA had the highest number of CARD, the highest CMR and the worst income inequality. Five countries reduced their CARD significantly more than the USA, and 14 countries reduced their CMR more than the USA. Income inequality and CMR were correlated. Had the USA matched the CMR of Japan, where income inequality was narrowest, there would have been on average 16 745 fewer child deaths annually. CARD and UnD correlated, suggesting that UnD may contain unreported CARD. US CMR data indicate that services in the USA are less effective than those in ODN, possibly due to income inequality. These results will be unwelcome but child protection services must dare to speak truth to power. ‘This population‐based study analyses CARD and CMR for children aged from newborn to four years old between 1989–91 and 2013–15 to identify any relative child neglect in the USA and 20 other developed nations’ Key Practitioner Messages The richest country in the world, the USA, has the highest rates of child abuse and total child mortality in the Western world. The USA has the highest income inequality in the West, highlighting the statistical link between child mortality and poverty. Children's services should lead the call for the necessary changes and ‘speak truth to power’

Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma

IntroductionKRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA.MethodsComprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed.Results and discussionOur cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA

Forensic age diagnostics by magnetic resonance imaging of the proximal humeral epiphysis

The most commonly used radiological method for age estimation of living individuals is X-ray. Computed tomography is not commonly used due to high radiation exposure, which raises ethical concerns. This problem can be solved with the use of magnetic resonance imaging (MRI), which avoids the use of ionizing radiation. The purpose of the present study was to evaluate the utility of MRI analysis of the proximal humeral epiphyses for forensic age estimations of living individuals. In this study, 395 left proximal humeral epiphyses (patient age 12-30years) were evaluated with fast-spin-echo proton density-weighted image (FSE PD) sequences in a coronal oblique orientation on shoulder MRI images. A five-stage scoring system was used following the method of Dedouit et al. The intra- and interobserver reliabilities assessed using Cohen's kappa statistic were =0.818 and =0.798, respectively. According to this study, stage five first appeared at 20 and 21years of age in males and females, respectively. These results are not directly comparable to any other published study due to the lack of MRI data on proximal humeral head development. These findings may provide valuable information for legally important age thresholds using shoulder MRI. The current study demonstrates that MRI of the proximal humerus can support forensic age estimation. Further research is needed to establish a standardized protocol that can be applied worldwide

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure

CONTRIBUTION OF ASTHMA IN OPIATE DEATHS

Some studies have shown a connection between asthma deaths and opiate abuse, but the process in which opiates exacerbate asthma is still unclear. Opiates may impair judgment during an acute asthma attack, leading to inadequate treatment. Alterations in mental status may increase aspiration risk. Some studies have also demonstrated an opiate-induced bronchoconstriction. In the present study, data on opiate deaths in the Department of Forensic Sciences of Sapienza University of Rome and in Cook County Medical Examiner’s Office in Chicago (USA) have been collected. A comparison was performed between the opiate users who had a history of asthma and the opiate users who did not, regarding demographic, anamnestic, seasonal, autopsy, histological and toxicological findings. A histological grading of asthma changes was also performed. A history of asthma was found in 78 out of 855 cases of opiate deaths (9.12%). The majority of people who died due to opiate intoxication and had a history of asthma were males and African-American. Among asthma cases, the levels of morphine in blood ranged between 23-1,740 ng/ml (Mean: 209.51 ng/ml), the levels of blood 6-MAM ranged between 12-280 ng/ml (Mean: 80.6 ng/ml) and the levels of blood codeine ranged between 24-34 ng/ml (Mean: 26.6 ng/ml). Regarding the grading of asthma, we found 32 cases with severe asthma, 19 with moderate asthma and 27 with mild asthma. We randomly selected 80 opiate deaths without a history of asthma. The levels of morphine in blood ranged between 1,115-5,280 ng/ml (Mean: 3,450.89 ng/ml), the levels of blood 6-MAM ranged between 70-460 ng/ml (Mean: 321.1 ng/ml) and the levels of blood codeine ranged between 23-52 ng/ml (Mean: 45.7 ng/ml). Preliminary statistical analyses revealed that the levels of blood morphine were significantly higher in non asthma cases compared with asthma cases. These findings may support the hypothesis that the quantity of morphine needed to cause death in asthmatic can be lower than the quantity of morphine needed to cause death in non asthmatic: anatomic and physiologic changes of asthma can play a role in deaths due to opiate, maybe determining a higher susceptibility to the effects of these substances (bronchoconstriction, respiratory depression, etc)

CONTRIBUTION OF ASTHMA IN OPIATE DEATHS

Although some studies have shown a link between asthma deaths and opiate abuse, the process in which opiates exacerbate asthma is still unclear. Opiates may impair judgment during an acute asthma attack, leading to inadequate treatment. Alterations in mental status may increase aspiration risk. Some studies have also demonstrated an opiate-induced bronchoconstriction. In our country, according to the 2015 Annual Report of the Central Directorate for Anti- Drug Services, heroin was the drug that caused the greatest number of deaths, among the drug abuse deaths. The prevalence of asthma in Italy, according to the Italian Statistical Yearbook of 2015 (ISTAT), accounted for the 5.6% of the total population. This study has the aim to provide data on opiate deaths in the Department of Forensic Medicine of Sapienza - University of Rome and in Cook County Medical Examiner’s Office in Chicago (USA) and to compare the demographic, anamnestic, seasonal, autopsy, histological and toxicological findings of opiate users who had a history of asthma with those who did not. A histological grading of asthma changes is performed. At the end of the study, the rate of clinical history of asthma in deaths due to opiates, as well as demographic data and seasonal patterns will be evaluated. Statistical analyses will be performed to compare the toxicological levels of opiates in asthmatic and non asthmatic, to infer the role of asthma in these deaths, also considering the different histological grades of asthma. Our preliminary data (855 cases of opiate deaths) showed that a history of asthma can be present in opiate deaths (it accounted for the 9.12% -78 cases). The majority of people who died of opiate intoxication and had a history of asthma were males and African- American. Deaths usually occurred in winter and in spring, probably because cold air and pollens act as a trigger for exacerbations of asthma, together with the drug. In asthma cases, the level of morphine in blood ranged between 23-1,740 ng/ml (Mean: 209.51 ng/ml), the level of blood 6-MAM ranged between 12-280 ng/ml (Mean: 80.6 ng/ml) and the level of blood codeine ranged between 24-34 ng/ml (Mean: 26.6 ng/ml). In our cases with a history of asthma where the route of administration of the drug was inhalation, the grade of asthma was mild: this can support the hypothesis that inhalation, affecting lung tissue more directly than injection, can lead to death even if preexisting asthma changes are minor