Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia.

Schizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal immune activation and neuroinflammation, we studied NLRP1 expression and content in the postmortem brain tissue of 10 schizophrenia and 10 control subjects. In the medial orbitofrontal cortex (Brodmann's area 11/12) and dorsolateral prefrontal cortex (area 46) from both hemispheres of six schizophrenia subjects, the NLRP1 mRNA expression was significantly higher than in six control brains (p < 0.05). As the expression difference was highest for the medial orbitofrontal cortex in the right hemisphere, we assessed NLRP1-immunoreactive pyramidal neurons in layers III, V, and VI in the medial orbitofrontal cortex in the right hemisphere of seven schizophrenia and five control brains. Compared to controls, we quantified a significantly higher number of NLRP1-positive pyramidal neurons in the schizophrenia brains (p < 0.01), suggesting NLRP1 inflammasome activation in schizophrenia subjects. Layer III pyramidal neuron dysfunction aligns with working memory deficits, while impairments of pyramidal neurons in layers V and VI likely disrupt predictive processing. We propose NLRP1 inflammasome as a potential biomarker and therapeutic target in schizophrenia.

Death by accidental intravenous administration of gasoline.

Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline.

Accidental death from a fall from height at workplace turned out to be a COVID-19 death.

Coronavirus 2019 disease (COVID-19) has rapidly evolved into a pandemic during the first months of 2020. The general extent of organ involvement, as well as microscopic changes in the organs of the diseased remains insufficiently documented so far. Herein we are reporting the case of a Caucasian male who apparently died in a workplace allegedly by a fall from height and was found to be SARS-CoV-2 positive just prior to the autopsy. The circumstances of his death required a medicolegal investigation. Gross autopsy findings included minor external injuries and focal subarachnoid hemorrhage together with ribs and sternum fractures resulting from resuscitation attempt. In addition, visceral congestion was noticed, especially visible in lungs. Traumatic findings suitable to explain sudden death were absent. However, lungs histopathology analysis revealed diffuse alveolar damage with massive capillary congestion. Pathology in other organs included myocardial fibrosis, left ventricular hypertrophy, severe generalized atherosclerosis, glomerulosclerosis, focal liver necrosis, liver microabscesses and intrahepatal cholestasis. Lab test confirmed the presence of SARS-CoV-2 in nasopharygeal swab taken postmortem. Only afterwards, the investigation brought out that he was suffering complaints consistent with respiratory infection in the days before death. Based on all findings, the death was ruled as natural, caused by COVID-19. Learnings from this case urge medical staff in the autopsy suite to consider the presence of SARS-CoV-2 in sudden deaths during the pandemic, to enable adequate personal protection gear is worn and to ensure the proper cause of death is determined where misleading circumstances exist.

Liver re-transplantation for donor-derived neuroendocrine tumor: A case report.

BACKGROUND: Donor-origin cancer is a well-recognized but rare complication after liver transplantation (LT). The rise in the use of extended criteria donors due to the current shortage of organs increases the risk. Data on donor-origin neuroendocrine neoplasms (NENs) and the most appropriate treatment are scarce. Here, we report a case of a patient who developed a NEN confined to the liver after LT and was treated with liver re-transplantation (re-LT). CASE SUMMARY: A 49-year-old man with no other medical co-morbidities underwent LT in 2013 for alcoholic liver cirrhosis. The donor was a 73-year-old female with no known malignancies. Early after LT, a hypoechogenic (15 mm) lesion was detected in the left hepatic lobe on abdominal ultrasound. The lesion was stable for next 11 mo, when abdominal magnetic resonance identified two hypovascular lesions (20 and 11 mm) with atypical enhancement pattern. Follow-up abdominal ultrasound revealed no new lesions for the next 2.5 years, when magnetic resonance showed a progression in size and number of lesions, also confirmed by abdominal computed tomography. Liver biopsy proved a well-differentiated NEN. Genetic analysis of the NEN confirmed donor origin of the neoplasm. As NEN was confined to liver graft only, in 2018, the patient underwent his second LT. At 12 mo after re-LT the patient is well with no signs of NEN dissemination. CONCLUSION: The benefits of graft explantation should be weighed against the risks of re-LT and the likelihood of NEN dissemination beyond the graft.

Fatal motorcycle crashes in wide urban area of Zagreb, Croatia-A 10-year review.

Objective: The objective of our study was to determine the prevalence of alcohol and drug intoxication among fatally injured motorcyclists in a wide urban area of Zagreb, Croatia. Methods: We conducted a single-center observational retrospective study over a 10-year period (2007-2016) in 3 counties covering an area including 1.2 million residents. We reviewed the records on fatally injured motorcyclists, collecting information relating to sex, age, cause of death, time of death in relation to the time of the crash, and the circumstances of the crash (time of day, day of the week, season). Blood alcohol concentration (BAC) and toxicology analysis results were collected and analyzed. Results: We identified 163 deaths (95.7% males, 4.3% females). Overall, 64.2% of the victims were 20 to 39 years old. The majority (50.9%) of those fatally injured were responsible for causing the traffic crash; the rest were determined not to be responsible or the responsibility could not be determined. The most frequent causes of death were multiple injuries (55.8%) and isolated head trauma (23.3%). The rider's BAC was above the legal limit for driving (>0.50 g/kg) in 53.8% of cases, with a mean BAC of 1.91 g/kg. There was no difference in riding a motorcycle with a BAC above the legal limit between groups defined as younger (≤39 years of age) and older (≥40 years of age). The number of people with an illegal BAC was significantly higher during weekends than during the work week. The BAC of riders who were responsible for the crash was significantly higher than that of those who were not responsible or whose responsibility could not be determined. Use of illegal drugs or nontherapeutic use of legal drugs was not common and was detected in 10.4% of fatally injured riders. Conclusions: Alcohol intoxication has a major role in motorcycle crash-related mortality. A significant difference in BAC between fatally injured riders responsible for the accident and those who were not responsible implies that measures directed toward prevention of drinking and driving behavior could lower the number of fatal motorcycle crashes. Weekend measures, especially during spring and summer, could have particularly significant effects.

Acetabular osteometric standards for sex estimation in contemporary Croatian population.

AIM: To determine the sexual dimorphism of acetabular measurements in contemporary Croatian population and to provide a discriminant function equation for sex estimation. METHODS: The sample consisted of 200 adult pelvic bones (100 male and 100 female) from positively identified victims of Croatian War of Independence. In total, 96 left (48 male and 48 female) and 104 right (52 male and 52 female) acetabula were measured. One author measured two acetabular parameters using a sliding caliper: acetabular diameter (AD) and transverse acetabular diameter (TAD). Another author re-measured the acetabula of 40 randomly selected individuals to determine the inter-observer error. RESULTS: Both measured variables showed significant sexual dimorphism. Men had significantly higher values for AD and TAD than women. Receiver operating characteristic curve analysis showed that the cut-off point for prediction of male sex when using acetabular diameter was higher than 54 mm. For transverse acetabular diameter it was higher than 52 mm. The discriminant function was generated by using both acetabular variables, with 88% of accuracy in sex estimation. Inter-observer error was not significant. CONCLUSION: The acetabular measurements can be used for sex estimation in contemporary Croatian population with high accuracy.

Case of Fatal Starvation: Can Stable Isotope Analysis Serve to Support Morphological Diagnosis and Approximate the Length of Starvation?

The diagnosis of death as a result of starvation is established on anthropological measurements, visual appearance of the deceased on external and internal examination, microscopic analysis, laboratory testing, and exclusion of other causes of death. Herein, we present our findings on a case of 95-year-old man who died of starvation. After the diagnosis of starvation was established by traditional forensic medicine methods, we have conducted retrospective segmental analysis of stable carbon (δ13 C) and nitrogen (δ15 N) isotope ratios in hair sample. This method reveals periods of starvation through decrease in δ13 C and increase in δ15 N along the strand of hair. Our analysis revealed the decrease of 0.6 ‰ in δ13 C during the last 10-12 weeks prior to death, similar as reported in other investigations. Also, a decrease of 0.7 ‰ in δ15 N during the last 8-10 weeks prior to death was determined that was different than observed in previous studies.

Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia.

Schizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46), and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12), in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes: SART1, KAT7, C1D, NPM1, EVI2A, XGY2, and TTTY15. As the differentially expressed genes only partially overlap with previous studies that analyzed other brain regions, our findings indicate the importance of considering prefrontal cortical regions, especially those in the left hemisphere, for obtaining disease-relevant insights.

Suicidal chemistry: combined intoxication with carbon monoxide and formic acid.

Herein, we present a rare case of suicidal intoxication with carbon monoxide produced via reaction of formic and sulphuric acid with additional toxic effect of formic acid. The deceased was a 22-year-old men found dead in the bathroom locked from the inside. A bucket filled with liquid was found next to him, together with an almost empty canister labeled "formic acid" and another empty unlabeled canister. The postmortem examination revealed corrosive burns of the face, neck and chest, cherry-pink livor mortis, corrosive injury to the oropharyngeal area and trachea, subpleural petechiae, 100 mL of blood in stomach and superficial erosions of stomach mucosa. Toxicology analysis revealed 30% of carboxyhemoglobin in the femoral blood and the presence of the formic acid in various samples. Quantitative analysis of formic acid was performed by measuring methyl ester derivative of formic acid by using headspace gas chromatography with flame ionization detection. The highest concentration of formic acid was measured in the lungs (0.55 g/kg), gastric content (0.39 g/L), and blood (0.28 g/L). In addition, it was established that content of the unlabeled canister had a pH value of 0.79 and contained sulphuric ions. Morphological and toxicology findings suggested that the main route of exposure to formic acid was inhalation of vapors with a possible ingestion of only small amount of liquid acid. The cause of death was determined to be combined intoxication with carbon monoxide and formic acid.

Death by band-aid: fatal misuse of transdermal fentanyl patch.

We present a case of fatal intoxication by the application of a transdermal fentanyl patch upon a superficial bleeding abrasion of a 2-year-old girl. The grandmother discovered the body of the child in bed at approximately 7 a.m. External examination revealed a properly developed, nourished, and hydrated child, with some vomit in the nostrils and inside the mouth. There was no evidence of trauma besides small contusions and abrasions on the knees, with a patch placed over the largest abrasion. Closer inspection revealed that this was transdermal fentanyl patch. Internal examination and microscopic analysis revealed regurgitation of stomach content, cerebral and pulmonary edema, and liver congestion. Toxicology analysis revealed trace levels of fentanyl in the blood just above the limit of detection (2 ng/mL), while concentrations in the urine, liver, and kidney were approximately 102, 28, and 10 ng/mL, respectively. Investigation discovered that the child injured her knee while playing the evening before. The grandmother applied the patch to cover the injury, unaware that she had used a fentanyl transdermal patch instead of simple band-aid. Although fatal intoxications are uncommon among young children in high-income countries, it is of major interest to raise awareness of such events especially since a great majority of these are preventable. The presented case points at the need for more thorough education of users and more strict rules in prescribing and handling of this potent medicine. As well, we find this case to be a useful contribution to the evaluation of postmortem fentanyl concentrations in fatal intoxication in a small child.

Shot through the heart-firepower and potential lethality of air weapons.

Although certain air weapons attain muzzle velocities comparable to some firearms, their successful use for committing suicide is rarely seen. Herein, we report a case of a young female died shortly after urgent admission to the hospital with penetrating gunshot wound to the chest. The autopsy revealed perforation of the pericardium and two perforative defects to the right heart ventricle. Injury was inflicted by a 0.177 caliber pellet, fired from an air rifle found near her body. Investigation ruled the death as suicide. The used air rifle fired the pellet with the energy density of 1.9 J/mm(2) , substantially above the threshold for inflicting injury. The pellet penetrated through two layers of cotton fabric and several layers of tissue to inflict fatal injury to the heart. In addition, we provide an insight into the wounding potential of air weapons, which illustrates the need for greater caution in handling those devices.

The differences of water diffusion between brain tissue infiltrated by tumor and peritumoral vasogenic edema.

The differences between peritumoral brain tissue infiltrated by tumor and vasogenic edema were prospectively evaluated by comparing the apparent diffusion coefficient (ADC) of peritumoral areas of infiltrative tumors (anaplastic astrocytomas and glioblastomas) to that of peritumoral areas of noninfiltrative tumors (metastatic carcinomas) on 54 patients. Peritumoral ADCs indicated the possibility of differentiation between tumor infiltration and vasogenic edema, as well as between primary gliomas and metastases.

Prediction of stature based on radiographic measurements of cadaver long bones: a study of the Croatian population.

We tested a new approach to the stature prediction that could be used in the identification process of human skeletal remains of unknown identity. The stature of 19 female and 21 male adult cadavers was measured within 24 h after death and considered to be equal to the living stature. The antero-posterior radiographs of all limbs were taken, and the maximum length of the six long bones was measured from radiographs. There was a significant difference in the stature and maximum length of long bones between female and male cadavers (p<0.001 for all). The correlation between the stature and long bone length was the best for the humerus in females (r=0.792) and the tibia in males (r=0.891). Regression equations specific to the Croatian population were computed separately for each long bone in males and females and proven to be reliable in predicting the living stature of the individual.

[Human or animal skeletal remains?]. / Ljudski ili zivotinjski kostani ostatci?

The aim of the article is to provide physicians with guidelines for differentiating human from animal skeletal remains. Morphologic features which clearly distinguish human and nonhuman bones are presented, together with an overview of the methods available for further analysis of bone material. Process of bone identification is exemplified through the case of skeletal remains recovered in Lika district in Croatia. Instructions for the physicians faced with bone material are given in order to better understand their possibilities and limitations when interpreting such findings.

Myasthenia gravis in pregnancy: report on 69 cases.

OBJECTIVE: To review our experience with pregnancies in women with myasthenia gravis (MG). STUDY DESIGN: Sixty nine pregnancies among 65 women with MG patients managed by our department over 28 years were included. The course of the disease in pregnancy, mode of delivery and postpartal period were evaluated. RESULTS: One pregnancy miscarried. In 15% of patients the MG deteriorated in pregnancy a further 16% in the puerperium. 17% of pregnancies were delivered by cesarean section, one due to myasthenia exacerbation. All women with puerperal infections developed exacerbations. One neonatal death, not attributable to myasthenia, was recorded. Transitory neonatal myasthenia gravis (TNMG) was diagnosed in 30% infants. Its incidence was inversely associated with maternal disease duration (P < 0.05). Newborns of thymectomized mothers showed lower rate of neonatal myasthenia compared to those of non-thymectomized women (P < 0.05). CONCLUSIONS: MG patients can have normal pregnancy and delivery but the course is unpredictable. Shorter disease history and infection predispose to puerperal exacerbation. Maternal thymectomy lessens the likelihood of neonatal myasthenia. An interdisciplinary approach is required for managing the pregnant women with MG.