The study of the microbiome in forensic investigations on pediatric deaths.

Background: Sudden infant death syndrome (SIDS) is a tragic and devastating condition whose causes remain largely unknown. Recent studies have shown that the composition of a child's gut flora can play a significant role in the development of SIDS. Methods: This work aims to research those factors that influence the composition of the intestinal flora, the role they have in the development of SIDS and the new strategies for preventing SIDS showing a new interpretation through a detailed review of the literature. The gut in physiological conditions is mainly composed of Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria, but when there is the presence of dysbiotic or different microbial communities, the onset of the disease is more likely as an altered microbial community can lead to an interruption of the gut-brain axis and an increased risk of SIDS. Conclusions: All this implies that the composition of the microbiome can be modified to reduce the risk of sudden death in newborns. The results of the literature provide valuable information on the potential role of the intestinal microbiome in SIDS even if not all mechanisms are yet clear, especially in the mechanisms of death. Therefore, it is necessary in cases of SIDS when carrying out an autopsy to also investigate this area; to this end, we suggest a questionnaire to be administered to family members to understand the eating habits of the newborn and the family and integrate with microbiological investigations to explore every possible hypothesis.

Asphyxia with a blunt instrument: which forensic evidence to use in complex cases of murder.

Background: The blunt injuries may be heterogeneous. Due to the diversity, it is often difficult to establish the type of weapon used. Particular attention must be paid to the circumstantial data and previous diseases because the injuries often could not correspond to the presumed instruments used. Case Report: A man was found dead in his bedroom wearing pajamas. On the bed there was a blanket with visible traces of blood, which had dried. There were around 10 dogs in the house, poor hygienic and sanitary conditions, widespread excrements and unbreathable air. Testimonies from general practitioner, neighbors and the partner were collected. An autopsy, histological and toxicological examination was performed. On external examination the face showed blood smearing down the nose, subconjunctival hemorrhages, and labial cyanosis. Mo-reover, a hypochromic skin area was present on the right lateral region of the neck. The inguinal region showed large de-epithelized areas with multiple purplish red ecchymoses which were histologically analyzed. These areas showed hemorrhagic infiltration in the superficial and deep dermis up to the adipose tissue due to traumatic action. Conclusion: The reconstruction of the case allowed us to state a strangulation probably attributable to a belt. The discovery of intradermal hemorrhagic infiltrations, supported by histopathological investigations, confirmed the diagnosis of blunt force injuries, excluding other type of non-violent causes of lesions. Therefore, we recommended the use of experimental methods and procedures to evaluate the harmful suitability on biological matrices.

The experimental reconstruction of a complicated case of work accident due to a scraper.

Background: Workplace safety is a global public health issue. Re-constructing an accident can prove extremely complicated, especially when the event occurs without direct witnesses or when the scene is altered. In these cases, it is essential to adopt proper investigation pro-tocols in order to ensure the correct reconstruction of the dynamics. Case report: A man was found unconscious on the ground, having fallen from a height of approximately 2 meters, where there was a cabin in which a conveyor belt of raw materials for the production of cement ran. At the end of the path of this belt a scraper was found. An autopsy was carried out and the scraper present at the scene was examined and compared with the injuries on the victim. After the autopsy, the investigators returned to the scene and collected the traces found in the cabin. At the end of collecting the traces, the investigators simulated the dynamics of the event by turning on the conveyor belt and placing a scraper of the same dimensions and characteristics as the one found at the scene inside the cabin. Conclusion: The autopsy showed a maxillofacial trauma with multiple bruises on the face and a serious fracture of the epistropheus tooth. This trauma was therefore incompatible with a simple fall from 2 meters. The investigators created an experimental model that demonstrated a very high energy rebound of the tape when placed in contact with the scraper. This reconstruction made it possible to carry out a single report with the data collected by the medical examiner and the investigators, which was effective and exhaustive, allowing the Authority to be provided with the evidence to continue the investigations about the responsibilities of the worker and the employer.

Autoptic aspects in a case of autosomal dominant polycystic kidney disease.

Background: Polycystic kidney disease is a cystic genetic disease. There are two forms: an autosomal dominant one, more common and typical of adults, and an autosomal recessive one, rarer and present in childhood. The autosomal dominant form is caused by genetic mutations of the PKD1 gene in 85% of cases and of PKD2 in 10-15% of cases. Case Report: We reported a case of 56-year-old woman with ADPKD, who had a kidney transplant and who was hospitalized for respiratory failure from Covid 19 disease. She was intubated, sedated and dialyzed, treated with antibiotics, immunosuppressants, diuretics and heparin. CT scan of the abdomen showed multiple cysts of various sizes in the liver and multiple cysts in the kidneys. The patient died after 20 days because she was unresponsive to therapy. The autopsy showed milky ascitic fluid in the abdomen, massive gastric haemor-rhage, intestinal fungal plaques, hepatic and renal polycystosis. The kidneys measured a total of 27 cm with a total weight of about 9 kg. The liver parenchyma appeared cavernous with multiple cysts. The kidney cysts contained bloody liquid. Conclusions: The case demonstrates how important it is in these subjects to evaluate not only the kidneys but also the liver which could present polycystosis and cause liver failure, affecting the severity of the pathology and death. This data is important to emphasize in the clinical management of these patients a close monitoring of liver function also from a preventative perspective in life.

Desensitization of two young patients with infantile-onset Pompe disease and severe reactions to alglucosidase alfa.

Pompe disease is a metabolic myopathy, due to deficiency of alpha glucosidase, with a wide clinical spectrum. Enzyme replacement therapy is the only available treatment to improve morbidity and mortality, especially in infantile-onset form. However, some patients experience infusion-associated reactions, which may restrict their access to this treatment. We report on two patients (respectively 12 and 3 months old) with infantile-onset Pompe disease and severe cardiomyopathy, that presented with severe reactions during infusion of enzyme replacement therapy and were successfully desensitized with a new individualized protocol. Our protocol, using microdilution and a premedication with antihistamines, corticosteroids, and tranexamic acid, seems safe and effective and it may allow the continuation of therapy in Pompe patients resulting in the reduction of morbidity and mortality related to this disease.

Prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the Risk of Cardiovascular diseases and abdominal aortic Aneurysm in Varese (RoCAV) population based study.

BACKGROUND: Recent meta-analyses suggested that screening program for abdominal aortic aneurysms (AAA) in 65-year old males is cost-effective at prevalence of about 1%. Since some events occur also in females and among the youngers, screening could be feasible among those at higher risk, such as smokers or individuals with a family history of AAA. The RoCAV (Risk of Cardiovascular diseases and abdominal aortic Aneurysms in Varese) Project is a population-based study aimed to evaluate AAA prevalence in Northern Italy in males over-65 years as well as among females and younger males, and to identify new markers for risk stratification by collecting a large set of CVD risk factors. The aims of the project are: (i) cross-sectional evaluation of AAA prevalence (ii); evaluation of standard CVD risk score as criteria for selecting subgroup at higher risk to be included in a screening program; (iii) identification of new risk markers and risk score algorithm for AAA and CVD risk stratification; (iv) cost-effective evaluation during the follow-up. METHODS: Males aged 50-75 years and females aged 60-75 years, resident in the city of Varese (Lombardy Region), were randomly selected from the civil registry. Among 5198 successfully invited, 3777 subjects accepted to participate and were finally recruited (participation rate 63.8%) from June 2013 to May 2016. Trained operators administered a computerized anamnestic questionnaire, measured anthropometric parameters (BMI, body circumferences, skinfolds), blood pressure, ankle-brachial index, pulse wave velocity and performed abdominal aortic ultrasound scan, ECG and spirometry. All methods were internationally validated. A blood sample was collected and stored in biobank. A follow-up will be carried out through linkage with electronic records. DISCUSSION: Participation rate and data quality assessment were as expected and will reasonably allow to reach the project aims. The expected impact in public health of the RoCAV project will be the potential implementation of a AAA screening program to the whole region as well as the formulation of new criteria for risk assessment of AAA and CVD.

Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway hyperreactivity.

To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in vivo and to explore directly its relationship to airway reactivity, we created transgenic mice in which the murine cDNA for IL-4 was regulated by the rat Clara cell 10 protein promoter. Expression was detected only in the lung and not in thymus, heart, liver, spleen, kidney, or uterus. The expression of IL-4 elicited hypertrophy of epithelial cells of the trachea, bronchi, and bronchioles. Hypertrophy is due, at least in part, to the accumulation of mucus glycoprotein. Histologic examination of parenchyma revealed multinucleated macrophages and occasional islands of cells consisting largely of eosinophils or lymphocytes. Analysis of lung lavage fluid revealed the presence of a leukocytic infiltrate consisting of lymphocytes, neutrophils and eosinophils. Mice expressing IL-4 had greater baseline airway resistance but did not demonstrate hyperreactivity to methacholine. Thus, the expression of IL-4 selectively within the lung elicits an inflammatory response characterized by epithelial cell hypertrophy, and the accumulation of macrophages, lymphocytes, eosinophils, and neutrophils without resulting in an alteration in airway reactivity to inhaled methacholine.