Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.

Sudden infant death syndrome (SIDS) represents a significant cause of post-neonatal mortality, yet its underlying mechanisms remain unclear. The triple-risk model of SIDS proposes that intrinsic vulnerability, exogenous triggers, and a critical developmental period are required for SIDS to occur. Although case-control studies have identified potential risk factors, no in vivo model fully reflects the complexities observed in human studies. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide with diverse physiological functions, including metabolic and thermal regulation, cardiovascular adaptation, breathing control, stress responses, sleep-wake regulation and immunohomeostasis, has been subject to early animal studies, which revealed that the absence of PACAP or its specific receptor (PAC1 receptor: PAC1R) correlates with increased neonatal mortality similar to the susceptible period for SIDS in humans. Recent human investigations have further implicated PACAP and PAC1R genes as plausible contributors to the pathomechanism of SIDS. This mini-review comprehensively synthesizes all PACAP-related research from the perspective of SIDS and proposes that PACAP deficiency might offer a promising avenue for studying SIDS.

Application of 3D printing in assessment and demonstration of stab injuries.

In stabbing related fatalities, the forensic pathologist has to assess the direction of wound track (thus, the direction of the stabbing) and the weapon's possible characteristics by examining the stab wound. The determination of these characteristics can be made only with a high level of uncertainty, and the precise direction of the stabbing is often difficult to assess if only soft tissues are injured. Previously reported techniques used for the assessment of these wound characteristics have substantial limitations. This manuscript presents a method using today's easily accessible three-dimensional (3D) printing technology for blade-wound comparison and wound track determination. Scanning and 3D printing of knives is a useful method to identify weapons and determine the precise stabbing direction in a stabbing incident without compromising the trace evidence or the autopsy results. Ballistic gel experiment, and dynamic stabbing test experiments prove the method can be applied in safety, without compromising the autopsy results. Identification of the exact knife is not possible with complete certainty but excluding certain knives will decrease the number of necessary DNA examinations, hence it can lower the burden on forensic genetic laboratories. The method addresses many of the shortcomings of previously used methods of probe insertion or post-mortem CT. Insertion of the printed knife into the wound gives a good visual demonstration of the stabbing direction, thus easing the forensic reconstruction of the stabbing incident. After combining the 3D printing with photogrammetry, the achieved 3D visualization is useful for courtroom demonstration and educational purposes.

The effect of steatosis and fibrosis on blunt force vulnerability of the liver.

The aim of our study was to examine the possible effect of steatosis and fibrosis on the blunt force vulnerability of human liver tissue. 3.5 × 3.5 × 2-cm-sized liver tissue blocks were removed from 135 cadavers. All specimens underwent microscopical analysis. The tissue samples were put into a test stand, and a metal rod with a square-shaped head was pushed against the capsular surface. The force (Pmax) causing liver rupture was measured and registered with a Mecmesin AFG-500 force gauge. Six groups were formed according to the histological appearance of the liver tissue: intact (group 1), mild steatosis (group 2), moderate steatosis (group 3), severe steatosis (group 4), fibrosis (group 5), and cirrhosis (group 6). The average Pmax value was 34.1 N in intact liver samples (range from 18.1 to 60.8 N, SD ± 8.7), 45.1 N in mild steatosis (range from 24.2 to 79.8 N SD ± 12.6), 55.4 N in moderate steatosis (range from 28.9 to 92.5 N, SD ± 16.0), 57.6 N in severe steatosis (range from 39.8 to 71.5 N, SD ± 11.9), 63.7 N in fibrosis (range from 37.8 to 112.2 N, SD ± 19.5), and 87.1 N in the case of definite cirrhosis (range from 52.7 to 162.7 N, 30.3). The Pmax values were significantly higher in samples with visible structural change than in intact liver sample (p = 0.023, 0.001, 0.009, 0.0001, 0.0001 between group 1 and groups 2 to 6 respectively). Significant difference was found between mild steatosis (group 2) and cirrhosis (group 6) (p = 0.0001), but the difference between mild, moderate, and severe steatosis (groups 2, 3, and 4) was not significant. Our study demonstrated that contrary to what is expected as received wisdom dictates, the diseases of the parenchyma (steatosis and presence of fibrosis) positively correlate with the blunt force resistance of the liver tissue.

Evaluation of the effect of ozone disinfection on forensic identification of blood, saliva, and semen stains.

Good laboratory practice minimizes the biological hazard posed by potentially infectious casework samples. In certain scenarios, when the casework sample is contaminated with highly contagious pathogens, additional safety procedures such as disinfection might be advised. It was previously proven that ozone gas treatment does not hamper STR analysis, but there is no data on how the disinfection affects other steps of the forensic analysis. In this study, we aimed to assess the interference of ozone disinfection with forensic tests used to identify biological stains. A dilution series of blood, saliva, and semen samples were pipetted onto cotton fabric and let completely dry. Half of the samples were subjected to ozone treatment, while the rest served as controls. All the samples were tested with specific lateral flow immunochromatographic assays and for specific RNA markers with quantitative real-time PCR. Additionally, luminol test was carried out on blood spots, Phadebas® Amylase Test on saliva stains, and semen stains were examined with STK Lab kit and light microscope following Christmas Tree or Hematoxylin-Eosin staining. Ozone treatment had no detrimental effect on the microscopic identification of sperm cells. Undiluted blood samples were detected with luminol and immunoassay, but at higher dilution, the sensitivity of the test decreased after disinfection. The same decrease in sensitivity was observed in the detection of semen stains using STK Lab kit from STK® Sperm Tracker, and in the case of the immunoassay specific for prostate-specific antigen (PSA). Ozone treatment almost completely inhibited the enzymatic activity of amylase. The sensitivity of antibody-based detection of amylase was also greatly reduced. RNA markers showed degradation but remained detectable in blood and semen samples after incubation in the presence of ozone. In saliva, the higher Ct values of the mRNA markers were close to the detection limit, even before ozone treatment.

Case Report: A Sudden Thyroid-Related Death of a 15-Year-Old Girl.

A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.

Multicenter retrospective study of patients with PCDH19-related epilepsy: The first Hungarian cohort.

OBJECTIVE: PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated. METHODS: In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19. RESULTS: In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam. SIGNIFICANCE: The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.

Polycyclic aromatic hydrocarbons in surface water and bed sediments of the Hungarian upper section of the Danube River.

This study was performed to elucidate the distribution, concentration trend and possible source of polycyclic aromatic hydrocarbons (PAHs) in surface water and bed sediments of the Hungarian upper section of the Danube River and the Moson Danube branch. A total of 217 samples (water and sediments) were collected from four different sampling sites in the period of 2001-2010 and analysed for the 16 priority US Environmental Protection Agency PAHs. Concentrations of total 16 PAHs (∑PAHs) in water samples ranged from 25 to 1,208 ng/L, which were predominated by two- and three-ring PAHs. The ∑PAH concentrations in sediments ranged from 8.3 to 1,202.5 ng/g dry weight. Four-ring PAHs including fluoranthene and pyrene were the dominant species in sediment samples. A selected number of concentration ratios of specific PAH compounds were calculated to evaluate the possible sources of PAH contamination. The ratios reflected a pattern of pyrogenic input as a major source of PAHs. The levels of PAHs determined were compared with other sections of the Danube and other regions of the world.

Detection of Fatal Potassium Overdose: A Case Report and Review of the Literature.

Potassium overdose usually occurs accidentally, but potassium is also used for judicial executions, assisted death, and, rarely, suicides. In addition to exogenous overdose, various drugs, and renal failure, diabetic ketoacidosis can cause hyperkalemia. Potassium tablets are used in most cases of suicidal potassium overdose. Suicide by intravenous administration of potassium is rare but usually fatal. The author reports a rare case of suicide with potassium infusion. Autopsy and histology findings, along with post-mortem biochemical analysis of different body fluids and fluid from the infusion set, are reported. Previously published reports of potassium overdose were reviewed, and the detection possibilities of potassium overdose are discussed. The detection possibilities of lethal hyperkalemia are very limited since hyperkalemia produces only nonspecific autopsy and histology findings. Post-mortem potassium concentrations are not indicative of ante-mortem potassium concentrations; therefore, post-mortem biochemical analysis has limited value in determining potassium overdose. The best way to prove potassium overdose is via the collection and analysis of circumstantial evidence.

Misconnected chest tube: An extremely unusual fatal complication of secondary pneumothorax.

A rare and fatal complication of suction drainage of secondary spontaneous pneumothorax is reported. The patient, likely by a mistake, arbitrarily connected the oxygen supply tube to the thoracic drain. The sharp increase of intrapleural pressure combined with the atmospheric intraalveolar environment caused diffuse lung injury and cardiopulmonary collapse without a direct lung injury. The conflicting interests of patient autonomy and patient safety require further consideration.

[The use of lot numbers of surgically implanted devices for forensic identification]. / Mutéti implantátumok tételszáma alapján történo igazságügyi célú személyazonosítás.

The present study aims to discuss two successful identification cases of the search warrants on unknown bodies by the Baranya County Police Department. In both cases, identification was only possible by using lot numbers of the traumatological metal implants removed during exhumation, several years after the bodies had been discovered and the post-mortem investigation was completed. We hope that the cases provided will highlight the importance of secondary identifiers, specifically the lot numbers of medical implants, in forensic identification practice. We would also like to draw attention to the fact that the only way to identify the majority of the over a thousand unknown corpses in Hungary (742 of them have been under warrant for more than ten years) is to re-examine the corpses using recent years' results in technical and technological improvements. The presented cases highlight the importance of documenting the identification numbers of implanted surgical devices during autopsies. Orv Hetil. 2023; 164(23): 911-918.

Simultaneous fatal poisoning of two victims with 4F-MDMB-BINACA and ethanol.

PURPOSE: Methyl-2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (4F-MDMB-BINACA) is a newly emerging synthetic cannabinoid receptor agonists (SCRA) first described in 2018 in both Europe and the United States. Two fatal cases are reported caused by simultaneous consumption of 4F-MDMB-BINACA and ethanol. METHODS: The victims were brothers who were both found deceased after consuming 4F-MDMB-BINACA and ethanol. Post-mortem toxicological analyses of blood and urine were carried out by supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) and headspace gas chromatography with flame ionization detection (HS-GC-FID). RESULTS: The concentration of 4F-MDMB-BINACA in the postmortem blood was 2.50 and 2.34 ng/mL, and blood alcohol concentration was 2.11 and 2.49 g/L, respectively. CONCLUSION: According to the reported cases and reviews of the scientific literature, concurrent ethanol consumption should amplify the toxicity of SCRAs. The threshold SCRA concentration for fatal overdose can be estimated ng/mL level (0.37-4.1 ng/mL according to the reported cases) in cases in which 1.5-2.5 g/L of ethanol is present in the blood.

Fatal Overdose with the Cannabinoid Receptor Agonists MDMB-4en-PINACA and 4F-ABUTINACA: A Case Report and Review of the Literature.

A case of a 26-year-old male who died from consuming synthetic cannabinoid receptor agonists MDMB-4en-PINACA and 4F-ABUTINACA is reported. MDMB-4en-PINACA and 4F-ABUTINACA are potent synthetic cannabinoid receptor agonists (SCRAs). This is the first detailed reporting of MDMB-4-en-PINACA and 4F-ABUTINACA associated fatality, which can help the routine forensic work. The scientific literature on the symptoms associated with these substances are evaluated, along with the pharmacological properties and possible mechanism of death. A forensic autopsy was performed according to Recommendation No. R (99)3 of the Council of Europe on medico-legal autopsies. Histological samples were stained with hematoxylin and eosin (HE). Complement component C9 immunohistochemistry was applied to all heart samples. Toxicological analyses were carried out by supercritical fluid chromatography coupled with tandem mass spectrometry (SFC-MS/MS) and headspace gas chromatography with a flame ionization detector (HS-GC-FID). The literature was reviewed to identify reported cases of MDMB-4en-PINACA and 4F-ABUTINACA use. Autopsy findings included brain edema, internal congestion, petechial bleeding, pleural ecchymoses, and blood fluidity. Toxicological analyses determined 7.2 ng/mL of MDMB-4en-PINACA and 9.1 ng/mL of 4F-ABUTINACA in the peripheral blood. MDMB-4en-PINACA and 4F-ABUTINACA are strong, potentially lethal SCRA, and their exact effects and outcome are unpredictable.

Forensic assessment of a life-threatening penetrating abdominal air gun injury.

Air guns are considered mostly harmless by the public opinion, but projectiles shot from common air guns can penetrate skin and thus able to cause severe, even life-threatening injury. The prevalence of air gun injuries is constantly high, but severe injuries occur rarely. Forensic evaluation of air gun injuries can be challenging since the shot wound characteristics produced by combustion in case of firearm injuries are missing. Despite these difficulties, the topic of air gun injuries is mostly overlooked in forensic literature, and there are no guidelines available which can help the assessment of specific cases. A case of an air gun injury is reported, where the projectile penetrated the abdominal wall and created multiple bowel injury. The complex assessment of all available information (macroscopic and microscopic appearance of entrance wound, types of injuries, CT findings, and crime scene reconstruction) helped to uncover the truth about the circumstances of the injury.

Piercing the surface: A mechanical analysis of stabbing with household tools.

Estimating the applied power during a stabbing incident, or estimating the minimal force necessary to penetrate the body with a certain weapon is a challenging task in forensic practice. A thorough forensic evaluation of stabbing forces needs objective numerical experimental data. Stabbing tests of 12 different weapons - including knives, a pair of scissors, a fork, screwdrivers, a rasp, a corkscrew, and a utility knife blade - were performed with a Mecmesin MultiTest-dV material tester on pork loin and ballistic gel to estimate the stabbing forces and dynamics. Penetration force (Fp ) and maximal force (Fmax ) were recorded, and the registered force curves were analyzed. Fmax was 159.8-212.07 Newton (N), 30.56-30.58 N, 168.9-185.48 N for various knives; 171.39-190.43 N for the pair of scissors, 233.6 N for the fork; 532.65-562.65 N, 370.31-367.19 N and 314.51-432.89 N for various screwdrivers, 44.14-56.62 N for utility knife during pork loin stabbing. The butter knife, corkscrew and rasp were not able to penetrate the pork loin, and the curved fork bent during stabbing. The results prove that weapon characteristics greatly influence the force necessary for penetration. Maximal stabbing force depends mostly on tip sharpness, and the force sharply decreases after penetration occurs, which indicates that edge sharpness is not as important as tip characteristics during stabbing perpendicular to skin surface. The penetration force during stabbing with a pair of scissors is comparable to the penetration force of knives. Stabbing with screwdrivers generally needs larger force than average knives but depends greatly on screwdriver size.

Biomechanical study on the effect of atherosclerosis on the vulnerability of thoracic aorta, and it's role in the development of traumatic aorta injury.

Traumatic aorta injury (TAI) is the second most common traumatic cause of death preceded only by head injuries, being responsible for 5% to 30% of all mortalities in high-speed deceleration injuries. Multiple external factors might play a role such as impact speed, impact direction, occupant location, and presence or lack of restraining safety mechanism. Apart from these external factors, also human biological factors can influence its development. Based on the data of scientific literature, age clearly plays a role in suffering TAI, but the role of atherosclerosis-as a disease affecting the structure of the aorta-is unknown. Biomechanical properties of tissue samples of 104 aorta specimens removed during the autopsy from the posterior (Group 'A') and lateral wall (Group 'B') of descending aorta were analyzed. Specimens were examined by a Zwick/Roell Z5.0 biaxial tester. The Young's modulus (E (MPa)) was calculated using a linear regression procedure where the base of the elongation was the parallel length of the sample, the achieved maximal force (Fmax (N)), the elongation at the time of Fmax (Lmax (mm)), the force at the beginning of rupture (Fbreak (N)), the elongation at the time of Fbreak (Lbreak (mm)) were registered. Specimens were categorized based on macroscopic and microscopic appearance. In the posterior (A) samples the difference between Lbreak (p<0.001) and Lmax (p<0.001) was significant between the macroscopic group. Lbreak (p = 0.009) and Lmax (p = 0.003) showed similar pattern in the lateral (B) samples. Comparing the histological groups by the measured parameters (Fmax, Lmax, Fbreak, Lbreak) showed a significant difference in the means (p<0.001, p = 0.003, p<0.001 respectively). The study demonstrated that atherosclerosis decreases the resistance of the aorta. The rupture occurs at lower force (Fmax and Fbreak), and at shorter elongation (Lmax and Lbreak) in case of the presence of atherosclerosis. This effect is most substantial if calcification is present: the resistance of aorta affected by calcification is only two-thirds on average compared to aorta affected by the early phase of atherosclerosis. This phenomenon can be clearly explained by the weakening structure of the tunica intima.

Fatal suicidal injury of a radiocephalic arteriovenous fistula.

A 59-year-old man was found dead in his living room. His body was covered with blood, but the only injury found was a 31-mm-long, transverse incision on the radial surface of the left forearm. Autopsy revealed that the injured vessel was an enlarged cephalic vein from a radiocephalic arteriovenous fistula (RC-AVF) that had been created 23 years before for hemodialysis. Cephalic vein injury is usually not fatal, but circumstantial evidence, autopsy, and histological findings suggested that hemorrhagic shock and death occurred within a short time after the self-inflicted incised wound. This may be explained by the blood flow rate in the RC-AVF, which can reach 12 ml/s; this is 25 times higher than the normal cephalic vein blood flow.

Lethal case of myocardial ischemia following overdose of the synthetic cannabinoid ADB-FUBINACA.

The serious adverse effects of synthetic cannabinoids (SCB), the lack of human pharmacological data on SCBs, and the increasing number of SCBs with diverse structures are growing public health concerns. A fatal case of myocardial ischemia after ADB-FUBINACA overdose is reported. A 41-year-old male died after consuming a brown, powder-like drug. Autopsy revealed pallor in the left ventricle of the subendocardial two-third of the myocardium, and histological examination revealed early signs of myocardial ischemia: few wavy myocardial fibers, contraction band necrosis in the subendocardial region, and patchy subendocardial complement component 9 (C9) positivity. Toxicological analysis detected a high concentration of the indazole carboxamide derivative SCB ADB-FUBINACA (peripheral blood: 105 ng/mL) and a low concentration of the synthetic cathinone (SC) derivative stimulant N-ethylpentylone (NEP). The literature concerning ADB-FUBINCA overdoses is reviewed, and the possible mechanism of death and the cardiac effects of SCBs are discussed. Effects of SCBs are unpredictable, but they are potentially cardiotoxic, capable causing arrhythmias, cardiac hypertrophies, and myocardial ischemia. The cardiotoxicity of SCBs can be attributed to vasospasms, decreased myocardial contractility, and increased cardiac workload and oxygen demand. Based on the autopsy, histology, and toxicology, it could be reasonably suggested, that ADB-FUBINACA have been a significant contributor to the myocardial ischemia seen in histology. The mechanism of death was likely fatal arrhythmia induced by the patchy myocardial ischemia. Due to the low concentration of NEP, it's role in the fatal outcome is improbable.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

An unusual case of suicide: Near decapitation by a modified table saw.

Table saws are dangerous tools able to create severe injuries. In accidental injuries, the most commonly injured body parts are fingers (85.9%) while amputations occur in 10% of cases. Accidental neck or head injuries account for only 3.1% of all injuries. Table saws cause nearly half of all saw-related amputations. There are approximately 30,000 cases of table saw-related injuries in the United States annually, but only a few table saw-related suicides have been reported in the scientific literature. In regard to suicides, usually the head or the neck is targeted. Usually, only the soft tissues of the neck are injured because the blade height limits the cutting depth and the victim falls down from the table saw before complete transection. A rare case of suicide committed by a modified table saw that resulted in near decapitation is presented. Previously reported cases of suicides by table saw are also reviewed.