Reliability Testing of a Low-Cost, Multi-Purpose Arduino-Based Data Logger Deployed in Several Applications Such as Outdoor Air Quality, Human Activity, Motion, and Exhaust Gas Monitoring.

This contribution shows the possibilities of applying a low-cost, multi-purpose data logger built around an Arduino Mega 2560 single-board computer. Most projects use this kind of hardware to develop single-purpose data loggers. In this work, a data logger with a more general hardware and software architecture was built to perform measurement campaigns in very different domains. The wide applicability of this data logger was demonstrated with short-term monitoring campaigns in relation to outdoor air quality, human activity in an office, motion of a journey on a bike, and exhaust gas monitoring of a diesel generator. In addition, an assessment process and corresponding evaluation framework are proposed to assess the credibility of low-cost scientific devices built in-house. The experiences acquired during the development of the system and the short measurement campaigns were used as inputs in the assessment process. The assessment showed that the system scores positively on most product-related targets. However, unexpected events affect the assessment over the longer term. This makes the development of low-cost scientific devices harder than expected. To assure stability and long-term performance of this type of design, continuous evaluation and regular engineering corrections are needed throughout longer testing periods.

The complementarity of phosphatidylethanol in whole blood and ethyl glucuronide in hair as biomarkers for the monitoring of alcohol use.

Monitoring long-term alcohol use and/or abstinence is essential in clinical and medico-legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2-4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth-NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2-4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.

Air bubble artifact: why postmortem brain MRI should always be combined with postmortem CT.

Forensic pathology increasingly uses postmortem magnetic resonance imaging (PMMRI), particularly in pediatric cases. It should be noted that each (sudden and unexpected) death of an infant or child should have a forensic approach as well. Current postmortem imaging protocols do not focus adequately on forensic queries. First, it is important to demonstrate or rule out bleeding, especially in the brain. Thus, when incorporating PMMRI, a blood sensitive sequence (T2* and/or susceptibility weighted imaging (SWI)) should always be included. Secondly, as intracranial air might mimic small focal intracerebral hemorrhages, PMMRI should be preceded by postmortem CT (PMCT) since air is easily recognizable on CT. This will be illustrated by a case of a deceased 3-week-old baby. Finally, note that postmortem scans will often be interpreted by clinical radiologists, sometimes with no specific training, which makes this case report relevant for a broader audience.

The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution.

AIMS: Severe acute respiratory syndrome coronavirus-2 infection causes COVID-19, which in severe cases evokes life-threatening acute respiratory distress syndrome (ARDS). Transcriptome signatures and the functional relevance of non-vascular cell types (e.g. immune and epithelial cells) in COVID-19 are becoming increasingly evident. However, despite its known contribution to vascular inflammation, recruitment/invasion of immune cells, vascular leakage, and perturbed haemostasis in the lungs of severe COVID-19 patients, an in-depth interrogation of the endothelial cell (EC) compartment in lethal COVID-19 is lacking. Moreover, progressive fibrotic lung disease represents one of the complications of COVID-19 pneumonia and ARDS. Analogous features between idiopathic pulmonary fibrosis (IPF) and COVID-19 suggest partial similarities in their pathophysiology, yet, a head-to-head comparison of pulmonary cell transcriptomes between both conditions has not been implemented to date. METHODS AND RESULTS: We performed single-nucleus RNA-sequencing on frozen lungs from 7 deceased COVID-19 patients, 6 IPF explant lungs, and 12 controls. The vascular fraction, comprising 38 794 nuclei, could be subclustered into 14 distinct EC subtypes. Non-vascular cell types, comprising 137 746 nuclei, were subclustered and used for EC-interactome analyses. Pulmonary ECs of deceased COVID-19 patients showed an enrichment of genes involved in cellular stress, as well as signatures suggestive of dampened immunomodulation and impaired vessel wall integrity. In addition, increased abundance of a population of systemic capillary and venous ECs was identified in COVID-19 and IPF. COVID-19 systemic ECs closely resembled their IPF counterparts, and a set of 30 genes was found congruently enriched in systemic ECs across studies. Receptor-ligand interaction analysis of ECs with non-vascular cell types in the pulmonary micro-environment revealed numerous previously unknown interactions specifically enriched/depleted in COVID-19 and/or IPF. CONCLUSIONS: This study uncovered novel insights into the abundance, expression patterns, and interactomes of EC subtypes in COVID-19 and IPF, relevant for future investigations into the progression and treatment of both lethal conditions.

Overdose of the HIV Medicine Genvoya® in Two Auto-Intoxications.

Toxicological data on overdose with human immunodeficiency virus inhibitors are scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and postmortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time that emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcomes between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.

Ethyl glucuronide and alcohol abstinence: A correlation study in hair and fingernails to establish a cut-off value in fingernails for teetotalers.

INTRODUCTION: Excessive use of alcohol increases the risk to be involved in a road traffic accident. According to many legislations, certain maximal blood-alcohol-concentrations (BAC) have to be respected to be allowed to drive on public roads. Acute alcohol intoxication is evaluated by blood analysis or analysis of the exhaled alveolar air. In many cases, evaluation of the alcohol consumption during the past months can be useful. In this light, ethyl glucuronide (EtG), a direct alcohol biomarker which can be found in keratinized matrices (hair, nails) is valuable and can be used for the long-term follow-up of alcohol consumption. RESEARCH AIM: To compare the EtG concentration in hair and fingernails from teetotalers, and to propose a cut-off value for EtG in fingernails for alcohol abstinence. MATERIAL AND METHODS: Paired samples of hair and nails were collected from participants, with a minimum age of 18 years. They all stated alcohol abstinence for at least 6 months. Participants were asked to complete a questionnaire about age, gender and the use of hair care products and nail polish. Analysis of EtG in the nail and hair samples were conducted following a validated analytical method. RESULTS: From 126 participants a hair and nail sample were collected. Of this group, 15 participants were finally not included in the study because of insufficient amount of hair or nails collected. There were more female participants (65%) and the average age of participants was 39 years. The EtG concentration in hair was below the limit of detection of 2.1 pg/mg in all but 4 samples (2.1, 2.1, 2.9, and 3.5 pg/mg). The EtG concentration in nails was below the limit of detection in 97 of the 111 samples. The concentrations in nails ranged between 2.3 and 23 pg/mg. DISCUSSION AND CONCLUSION: In a population of 111 teetotalers, the 97.5% percentile of EtG concentrations in fingernails is 7.6 pg/mg. The highest EtG concentration observed was 23 pg/mg. These results suggest that the cut-off value for alcohol abstinence may be lower than the previous suggested 59 pg/mg and 37 pg/mg.

Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?

A 22-year-old man was hospitalized after stating he would 'commit suicide in a non-detectable way'. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man's apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.

Stability of phosphatidylethanol 16:0/18:1 in authentic and spiked whole blood.

Phosphatidylethanol 16:0/18:1 (PEth) is the most abundant homologue of the phosphatidylethanol group of phospholipids. Formed only in the presence of ethanol, PEth is used as a biomarker in whole blood to provide information about the consumption of alcohol. As information on the storage life of PEth is essential for its beneficial use as a biomarker, this study investigated the stability of PEth in spiked and authentic whole blood samples stored at 4°C. Human whole blood samples (n = 23) and spiked whole blood samples (n = 7) with a concentration range between 5 and 2000 ng/ml were analysed at specific time intervals, up to 90 days. Differences were evident between the stability of authentic and spiked samples. PEth was stable at 4°C for 60 days (concentrations within 15% of initial concentration) in authentic samples, whereas spiked samples were stable for up to 30 days. This study emphasizes the importance of including authentic samples in stability experiments.

Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome.

BACKGROUND: Although carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy, its pathogenesis remains largely unknown. An estimated heritability index of 0.46 and an increased familial occurrence indicate that genetic factors must play a role in the pathogenesis. METHODS AND RESULTS: We report on a family in which CTS occurred in subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons resulting in toe walking in childhood. Using exome sequencing, we identified a heterozygous variant (c.5009T>G; p.Phe1670Cys) in the fibrillin-2 (FBN2) gene that co-segregated with the phenotype in the family. Functional assays showed that the missense variant impaired integrin-mediated cell adhesion and migration. Moreover, we observed an increased transforming growth factor-ß signalling and fibrosis in the carpal tissues of affected individuals. A variant burden test in a large cohort of patients with CTS revealed a significantly increased frequency of rare (6.7% vs 2.5%-3.4%, p<0.001) and high-impact (6.9% vs 2.7%, p<0.001) FBN2 variants in patient alleles compared with controls. CONCLUSION: The identification of a novel FBN2 variant (p.Phe1670Cys) in a unique family with early onset CTS, together with the observed increased frequency of rare and high-impact FBN2 variants in patients with sporadic CTS, strongly suggest a role of FBN2 in the pathogenesis of CTS.

Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): autopsy reveals a ferroptosis signature.

AIMS: Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID-19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID-19 lethal cardiogenic shock. METHODS AND RESULTS: We report on a 48-year-old male COVID-19 patient with cardiogenic shock; despite extracorporeal life support, dialysis, and massive pharmacological support, this rescue therapy was not successful. Severe acute respiratory syndrome coronavirus 2 RNA was detected at autopsy in the lungs and myocardium. Histopathological examination revealed diffuse alveolar damage, proliferation of type II pneumocytes, lymphocytes in the lung interstitium, and pulmonary microemboli. Moreover, patchy muscular, sometimes perivascular, interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in the cardiac tissue. The lymphocytes 'interlocked' the myocytes, resulting in myocyte degeneration and necrosis. Predominantly, T-cell lymphocytes with a CD4:CD8 ratio of 1.7 infiltrated the interstitial myocardium, reflecting true myocarditis. The myocardial tissue was examined for markers of ferroptosis, an iron-catalysed form of regulated cell death that occurs through excessive peroxidation of polyunsaturated fatty acids. Immunohistochemical staining with E06, a monoclonal antibody binding to oxidized phosphatidylcholine (reflecting lipid peroxidation during ferroptosis), was positive in morphologically degenerating and necrotic cardiomyocytes adjacent to the infiltrate of lymphocytes, near arteries, in the epicardium and myocardium. A similar ferroptosis signature was present in the myocardium of a COVID-19 subject without myocarditis. In a case of sudden death due to viral myocarditis of unknown aetiology, however, immunohistochemical staining with E06 was negative. The renal proximal tubuli stained positively for E06 and also hydroxynonenal (4-HNE), a reactive breakdown product of the lipid peroxides that execute ferroptosis. In the case of myocarditis of other aetiology, the renal tissue displayed no positivity for E06 or 4-HNE. CONCLUSIONS: The findings in this case are unique as this is the first report on accumulated oxidized phospholipids (or their breakdown products) in myocardial and renal tissue in COVID-19. This highlights ferroptosis, proposed to detrimentally contribute to some forms of ischaemia-reperfusion injury, as a detrimental factor in COVID-19 cardiac damage and multiple organ failure.

[Death due to physical restraint in healthcare institutions]. / Overlijden door fysieke fixatie in zorginstellingen.

Physical restraint is frequently used in healthcare institutions, usually in situations where the safety of the person (e.g. fall risk) or that of others (e.g. aggressive behaviour) is compromised, or where essential medical treatment is at stake. The implementation has a major impact with possible psychological consequences, physical injury and even fatal outcomes. In this retrospective study, fifteen deaths due to physical restraint are described. These have been investigated by the Forensic Medicine departments of UZ Leuven (1998 - 2018) and UZ Antwerpen (1999 - 2018). Death was caused by mechanical suffocation in all instances, mainly as a result of inadequate use of bedrails or belt restraint. These avoidable deaths are an urgent plea for a cautious and careful policy on physical restraint. Institutional guidelines and (further) training of health care personnel are of utmost importance. Central aspects are multidisciplinarity (deliberate decision-making), treatment (provoking factors), reticence (search for alternatives), proportionality (least intrusive method), due care (technical implementation), safety (increased supervision), temporality (re-evaluation of moment and duration), registration (accountability and liability) and communication (with all involved).

The optic nerve sheath hemorrhage is a non-specific finding in cases of suspected child abuse.

In young infants, the triad consisting of acute encephalopathy, retinal hemorrhages, and a subdural hematoma is a nonspecific finding. It has traumatic and non-traumatic etiologies. The triad may be found among a vast spectrum of natural diseases. Optic nerve sheath hemorrhage in infants is typically detected at autopsy. It is a nonspecific finding that can be found in traumatic and non-traumatic etiologies. Neither the triad nor the ONSH are pathognomonic for an abusive head injury. Opposite to the triad, the spectrum of non-traumatic etiologies of ONSH is limited. In infants ONSH rarely occurs in spontaneous subarachnoidal hemorrhage or in infectious conditions. Our results show that the clinical significance of the optic nerve sheath hemorrhage in the forensic work-up of fatal cases of alleged abusive head injury is its limited differential diagnosis. Only after careful differential diagnosis ONSH may contribute to the diagnosis of AHT. However, the main limitation of our study is the sampling bias, as the eyes are usually removed when abusive head trauma is suspected.

Can post-mortem CT reliably distinguish between drowning and non-drowning asphyxiation?

PURPOSE: The aim of this study is to evaluate whether previously reported post-mortem CT findings in drowning can reliably distinguish drowning from asphyxiation by any other manner. MATERIALS AND METHODS: Cases (n = 14) were corpses with cause of death determined as drowning by concordant autopsy findings and physical and circumstantial evidence. Controls (n = 11) were corpses in which the cause of death was defined as asphyxiation by any other manner than submersion in a liquid. Images were evaluated for the presence of fluid in paranasal sinuses, mastoid air cells and lower airways, frothy foam in the upper airways, ground-glass opacity of the lung parenchyma, the height of the right hemi-diaphragm, the interpulmonary distance at the level of the aortic valve, the mean density of intracardiac blood, and gastric and esophageal contents. Descriptive statistics, Fisher's exact test, and Student's t test were used when appropriate. RESULTS: Only the height of the right hemi-diaphragm differed significantly (p = 0.045) between cases (mean 5.4) and controls (mean 4.3). Other findings were not significantly different between both groups. CONCLUSION: Our results indicate that it is not possible to reliably distinguish drowning from non-drowning asphyxiation on CT, because many findings in drowning were also present in non-drowning asphyxiation. CT indicators for drowning as the cause of death should therefore be defined with great caution, keeping in mind that they are not specific to only a single cause of death.

History of an abusive head trauma including a lucid interval and a retinal hemorrhage is most likely false.

A lucid interval (LI) is the period of time between regaining consciousness after a short period of unconsciousness, resulting from a head injury and deteriorating after the onset of neurologic signs and symptoms caused by that injury. The incentive for this study was the case of a father who left his 14-week-old infant with the nanny in whose custody the infant had collapsed. The nanny denied involvement in the injury, and the father became a suspect. Of 47 abusive head trauma (AHT) cases, 8 were found to have an LI in the past. The history of the cases were thoroughly analyzed and compared with evidence in the literature. An LI is not compatible with an inertial brain injury. Shaking has either an immediate effect or no effect, which means that an LI occurs only in pure impact or blunt injuries. When "shaking lesions" are found including a retinal hemorrhage while the history mentions an LI, the story most likely is false, regardless of whether the perpetrator confesses. The finding of an LI may change the assessment of an AHT case. Lucid interval is a valuable variable in the diagnostic accuracy of an AHT.

Delta-storage pool disease as a mimic of abusive head trauma in a 7-month-old baby: a case report.

A seven-month-old baby was admitted to a hospital emergency department after collapsing suddenly while staying with his nanny. The baby displayed classic symptoms of shaken baby syndrome, including subdural haemorrhage, cytotoxic cerebral oedema, and bilateral retinal hemorrhages. Child protection services were informed, but both the parents and the nanny denied any involvement. In the subsequent weeks, the baby developed three other episodes of new subdural bleeding and a medico-legal investigation was started into the origin of the repeated subdural bleeding. Eventually, platelet aggregation tests and electron microscopy diagnosed a delta-storage pool disease; that is, a haemostatic disorder involving dense granules of the platelets. Initial minor blunt trauma may have resulted in subdural bleeding, while subsequent retinal haemorrhage could have been facilitated by the underlying haemostatic disorder. Delta-storage pool disease should be considered as a possible mimic of abusive head trauma similar to other rare conditions such as Menkes disease and type 1 glutaric aciduria.

Confessed abusive blunt head trauma.

It is generally accepted that terms referring to specific craniocerebral injury mechanisms must be replaced by the more general term abusive head trauma (AHT). Although blunt impact trauma remains an essential part of AHT, it has received far less attention in the literature than shaken-impact injuries. The current article presents 19 confessed cases of a series of 47 highly suspected AHT cases. Of these, 13 were confessed shaken-impact cases, and the other 6 confessed blunt trauma cases. There were no significant differences in the appearance of subdural hematoma, which was present in each case. Retinal hemorrhage, which was present in 10 of the 13 shaken-impact cases in which an ophthalmologic examination was conducted, occurred in 2 of the 6 blunt trauma cases. In 1 case, retinal hemorrhage probably had of metabolic origin. Skull fractures with an overlying subgaleal hematoma and a subdural hematoma below the fracture side were found in 5 of the blunt trauma cases but was also seen in the 2 shaken-impact cases with a skull fracture. The most important finding was a lucid interval (LI) in 3 blunt AHT cases. An LI does not seem to occur in shaking injuries because of the immediate and persistent effect of brain damage that such injuries involve. Therefore, LI makes it important to conduct a detailed investigation of the clinical course in time in suspected AHT cases.

Forensic emergency medicine: old wine in new barrels.

Emergency and forensic physicians may find themselves sometimes on the same medical battleground but with different primary aims and hence often ignore or do not recognize each other's needs. The emergency physician interacts with law enforcement agencies with greater frequency than any other hospital physician and hence needs expertise with legal issues. Awareness of the forensic relevance of certain medical observations by emergency physicians, knowledge of emergency medicine methodology and techniques and of resuscitation-related injuries by forensic physicians may lead to a higher standard in both forensic and emergency medicine, a better serving of the criminal justice system, and most importantly safeguarding the rights of victims of criminal assault. It is this achievable mutual symbiosis that we would like to refer to as the concept of 'forensic emergency medicine'.

Suicidal death after injection of a castor bean extract (Ricinus communis L.).

The castor bean plant (Ricinus communis L.) or wonder tree is cultivated in many countries as an ornamental annual plant in gardens. The highest concentration of the lectin ricin is present in the seeds and pods. Ricin is considered as one of the most toxic natural poisons. Ricinine is a piperidine alkaloidal toxin present in castor bean and is described as a biomarker for the exposure to ricin. A case report is presented of a 49-year-old man who committed suicide by intravenous and subcutaneous injection of a castor bean extract. He was brought to the emergency department 24 h after injecting himself. On admission, the patient was conscious and he presented with a history of nausea, vomiting, diarrhoea, dyspnoea, vertigo and muscular pain. Despite symptomatic and supportive intensive care, the man died 9 h after admission due to multiorgan failure. A body external examination was performed. Blood, urine, vitreous humour and the castor bean extract were submitted to the laboratory for toxicological analysis. The identification of ricinine in the extract was performed by solid phase extraction in combination with full-scan gas chromatography/mass spectrometry, high-performance liquid chromatography with photodiode array detection and liquid chromatography/mass spectrometry operated in the full-scan mode, respectively. An extraction procedure with Oasis HLB solid phase extraction cartridges was applied. Chromatography was achieved using a Symmetry C18 column using a gradient mode with 0.15% formic acid and 0.15% formic acid in acetonitrile as mobile phase. Exposure to the castor bean extract was confirmed by identification of the biomarker ricinine in blood, urine and vitreous humour using solid phase extraction and liquid chromatography tandem mass spectrometry with electro spray source in positive ionization mode. Multiple reaction monitoring was used for specific detection. To the authors' knowledge, it is the first time that ricinine has been identified in vitreous humour in a case of castor bean poisoning. Based on the clinical symptoms and the results of the toxicological analysis, we concluded that death was caused by intoxication with plant toxins originated from R. communis L.

The concept of forensic emergency medicine as illustrated by an unusual complication of pulmonary artery catheterization.

Forensic pathologists are regularly confronted with emergency and invasive medical procedures performed on critically ill or traumatized patients. Basic knowledge of such procedures and their possible complications is therefore mandatory in medico-legal practice. In this article, we describe a very unusual complication of pulmonary artery catheterization: through-and-through perforation of the carotid artery, initially without hemodynamic consequence. Death resulted from an aggravation of the preexisting cerebral edema (secondary to a craniocerebral trauma). The misplacement of the pulmonary artery catheter was clinically missed because the guidewire was initially deflected on the cervical spine towards the subclavian vein where the catheter--by chance--entered the circulatory system and followed its normal route further. The forensic importance of leaving all invasive medical devices in situ on a deceased person when a medico-legal autopsy is to be expected and the mutual interaction between emergency and forensic medicine (forensic emergency medicine) are discussed.