Unexpected Natural Death Research Articles

Heart Failure Predictive Analysis Using Decision Tree Classification

With an average age of 28 compared to Western countries, India's young population accounts for half of heart attacks in South Asia, which happen to people under 52. Autopsy reports, which identify the actual cause of death, frequently concentrate on sudden deaths in young adults that have no apparent reason or warning signs. Fat accumulation in the blood vessels of the heart is the cause of abrupt, unexpected natural deaths. The heart stops beating and loses blood as a result of these arteries narrowing or blocking. The body may exhibit subtle symptoms prior to abrupt death, such as shortness of breath, palpitations, tightness in the chest, and chest discomfort. A decision tree classification is a death dataset model that generates labelled classes at leaf nodes and makes judgments at edges to predict class labels for subsequent records. The purpose of the proposed paper study is to predict abrupt natural deaths, which are frequently brought on by smoking, by using regression analysis, a statistical technique that establishes the relationship between independent and dependent variables. The experiment's outcome, which looks at how Artificial Neural Networks (ANN) may be used to forecast heart failure, shows five records out of 50,000 patients from different hospitals. Perceptron’s, both single- and multi-layer, were used to gather patient information. Keywords: Artificial Neural Network, Linear Regression Analysis, Sudden and Unexpected Natural Deaths etc.

Trends in Admissions and Outcomes at a British Wildlife Rehabilitation Centre over a Ten-Year Period (2012-2022).

Millions of animals pass through wildlife rehabilitation centres (WRCs) globally each year, some dying in captivity, others euthanised, and some released into the wild. Those caring for these animals are generally well-intentioned, but skills, knowledge, and resources may be limited, potentially compromising animal welfare. WRC databases provide an opportunity to provide an evidence base for treatment and conservation efforts. 42,841 records of animals admitted over a 10-year period to a British WRC were analysed. More birds (69.16%) were admitted than mammals (30.48%) and reptiles and amphibians (0.36%). Most admissions were in the summer (48.8%) and spring (26.0%) months. A total of 9 of the 196 species seen made up 57% of admissions, and hedgehogs were the most common species admitted (14% of all admissions and 20% of mammals). Juvenile animals (35.5%) were admitted more frequently than 'orphans' (26.0%) or adults (26.4%). 'Orphaned' was also the predominant reason for admission (28.3%), followed by 'injured' (25.5%). 42.6% of animals were eventually released back to the wild, 19.2% died in captivity, and 37.2% were euthanised; 1% of outcomes were unknown. The prognosis was better for orphaned animals than for those admitted because of injury. Unexpected natural deaths in captivity were found to decline over the period of study, consistent with improved early triage. These findings can be used to focus veterinary and WRC training and seasonal resources on the species and case types most likely to be successfully rehabilitated and released. The findings also have the potential to contribute to our understanding of anthropogenic impacts, historical and regional variations in ecosystem health, and resultant implications for animal welfare.

A Genome-Wide Analysis of a Sudden Cardiac Death Cohort: Identifying Novel Target Variants in the Era of Molecular Autopsy.

Sudden cardiac death (SCD) is an unexpected natural death due to cardiac causes, usually happening within one hour of symptom manifestation or in individuals in good health up to 24 h before the event. Genomic screening has been increasingly applied as a useful approach to detecting the genetic variants that potentially contribute to SCD and helping the evaluation of SCD cases in the post-mortem setting. Our aim was to identify the genetic markers associated with SCD, which might enable its target screening and prevention. In this scope, a case-control analysis through the post-mortem genome-wide screening of 30 autopsy cases was performed. We identified a high number of novel genetic variants associated with SCD, of which 25 polymorphisms were consistent with a previous link to cardiovascular diseases. We ascertained that many genes have been already linked to cardiovascular system functioning and diseases and that the metabolisms most implicated in SCD are the lipid, cholesterol, arachidonic acid, and drug metabolisms, suggesting their roles as potential risk factors. Overall, the genetic variants pinpointed herein might be useful markers of SCD, but the novelty of these results requires further investigations.

Changing diagnostic patterns in cases of sudden and unexpected natural death in infants and young children: 1994-2018.

To determine whether there has been a change in the incidence and type of conditions causing sudden and unexpected natural death in infants and young children in recent years. A search was undertaken of pathology records at Forensic Science SA in Adelaide, Australia for all cases of sudden and unexpected natural death in children aged less than 10 years at the time of death over two time periods: 1994-1998 and 2014-2018. Overall, 136 cases were identified consisting of 81 boys and 55 girls (M:F=16:11; age range 0-9 years). No difference was shown in the numbers of sudden unexplained deaths in infants and young children between the two time periods (80 vs. 56; p=0.18). A trend was shown for a prominent decrease in SIDS cases (55 vs. 12) with an increase in undetermined cases, <1 year (5 vs. 18). However, when the two categories were combined there was no statistical difference between the two periods (60/80 vs. 30/56) (p= 0.26), although a decrease in numbers had occurred. Analysis of numbers of fatalities reported from medicolegal institutes should be undertaken with an awareness of the potential effect of diagnostic shift.

A postmortem study of unexpected natural pediatric deaths in Egypt

BackgroundIdentifying the causes of unexpected pediatric deaths is a clinical, medicolegal, and humanitarian requirement. This study included autopsied children aged < 18 years who suddenly died due to natural causes and excluded nonnatural deaths. The study was performed over 5 years in the Egyptian Forensic Medical Authority.ResultsThe study included 244 cases, consisting of 51.6% of neonates (< 1 month), 18% of infants (1–12 months), and 30.3% of children (1–18 years). The cause of death in neonates and children was “explained natural diseases” in 73.8% and 91.9%, respectively, while it was only 45.5% in infants. Infection-related deaths account for 30.4% of all explained natural deaths. Infections were responsible for 11.8% of explained deaths in neonates, while 55% and 48.5% were in infants and children, respectively. Of the fatal infections, 60% occurred at the age of > 1 year. Pneumonia accounted for 61.8% of infection-related deaths, followed by myocarditis (12.7%) and septicemia (12.7%). Regarding systems that had fatal pathologies, respiratory causes were responsible for 64% of explained natural deaths, whereas cardiovascular and central nervous system diseases accounted for 11% and 7.7% of explained natural deaths, respectively. Considering prodromes, alarming symptoms were reported before death in 51.2% of cases, whereas death occurred without alarming manifestations in 29.9% of cases. The rest of the cases (18.9%) were abandoned children with unavailable antemortem data.ConclusionsPresent results serve as a valuable reference dataset for deaths in developmental stages in Egypt that guides forensic practitioners in managing child deaths.

Epidemiology of sudden unexpected natural medicolegal deaths in Jammu region of union territory of Jammu and Kashmir

Background: Medicolegal autopsies are conducted in cases of sudden and unexpected deaths primarily to establish the cause of death in cases where such deaths have occurred in apparently healthy individuals under suspicious circumstances. Aims and Objectives: The current study was done to analyze autopsies of individuals dying of sudden death. Materials and Methods: A retrospective, case record study on cases of natural deaths brought for medicolegal autopsies to the mortuary was studied. The findings were statistically analyzed using descriptive statistics to find out the mean, percentage, and frequencies. Results: In the present study, a total of 70 sudden unexpected natural medicolegal deaths were studied. Male (92.86%) was more than females (7.14%) and male: female ratio was 13:1. The most common age group was 51–60 years (40%) followed by 41–50 years (35.71%). System-wise cardiovascular system involvement was most common (54.29%), followed by respiratory system (14.29%), central nervous system (10%), gastrointestinal tract (8.57%), genitourinary system (2.86%), septicemia (2.86%), and miscellaneous (7.14%) were noted. Coronary artery disease (51.43%) was most common disease noted, followed by tuberculosis (10%), intraventricular hemorrhage (10%), cirrhosis (7.14%), pneumonia/bronchiolitis (4.29%), cardiomyopathy (2.86%), septicemia (2.86%), ruptured ectopic pregnancy (1.43%), and chronic pyelonephritis (1.43%) were noted as cause of death. Conclusion: Cardiovascular disease accounts for the maximum number of sudden deaths, in which coronary artery disease is the main cause of sudden deaths.

Study of an ocular ptosis in a 13th century illuminated manuscript

The finding of an eyelid ptosis in a manuscript of the xiii century raises the differential diagnosis of injury to the third cranial nerve. This nerve was not differentiated from the other oculomotors until the xvi century and only in the xix century a clinicopathological correlation was established for its paralysis. Describe the characteristics and differential diagnoses of an eyelid ptosis illustrated in the Book of Divine Works (1173) by Hildegard of Bingen. In the mentioned work the nun Richardis of Stade is portrayed with her left eyelid drooping. Two conspicuous signs are described, ptosis and corresponding raising of the eyebrow. The deviation of the eye downward and outward is inferred from the shape that adopts the eyelid by the position of the eye and the curvature of the cornea. The picture is consistent with an isolated paralysis of the oculomotor nerve. The causes of ptosis are discussed: aponeurotic due to levator palpebrae dehiscence; myogenic, congenital and acquired; of the neuromuscular junction, and neuropathic, the latter being the most probable in this case and of a compressive mechanism. The nun's unexpected natural death suggests a ruptured brain aneurysm. Richardis of Stade's portrait shows an oculomotor paralysis centuries before its anatomy, function, and clinicopathological expression were known. Credit for this original description must go to Hildegard, whose medical vocation has long been recognized.

Cardiomyocytes calpain 2 expression: Diagnostic forensic marker for sudden cardiac death caused by early myocardial ischemia and an indicator of the duration of myocardial agonal period?

Sudden cardiac death (SCD) is an unexpected natural death of cardiac etiology and occurs within one hour of the onset of cardiac symptoms in an apparently healthy subject or within 24 h if death is not witnessed. The diagnosis of early myocardial ischemia (EMI) or acute myocardial infarction (AMI) after death is a challenge for forensic pathologists especially when death occurs in a short period of time after the onset of myocardial ischemia. Disorder of cardiomyocytes Ca2+ homeostasis caused by myocardial ischemia during SCD can lead to the activation of calcium-activated non-lysosomal cysteine protease, including calpains. They serve as a proteolytic unit for cell balance and also participate in the processes of apoptosis and necrosis.Agony is a period that precedes somatic death that differs from cellular agony which may evolve for hours after somatic death lasting differently depending on the cell type and mechanism of death.We hypothesize that the expression of calpain 2 in cardiomyocytes could be a specific and sensitive diagnostic forensic marker for SCD caused by EMI and an indicator of the duration of myocardial agonal period. We will conduct a retrospective study that will prove this hypothesis on the respondents who died of SCD by EMI and AMI, instant death by head gunshot and hanging. There is no data on such an analysis in the available literature. The standard hematoxylin-eosin staining will be used to detect cardiac tissue damage. The expression of calpain 2 in cardiomyocytes will be analyzed immunohistochemically.In SCD caused by EMI we expect lower level of calpain 2 expressionin comparison to AMI due to shorter duration of dying. Similar, we predict in the remote region lower calpain 2 expression than in the region of ischemia for both EMI and AMI. In instant death caused by perforating traumatic brain injury we expect mild or no calpain 2 expression throughout the whole myocardium because of very short (immediate) duration of dying. In death caused by hanging calpain 2 expression throughout the whole myocardium should be strong because of longer cellular agonal period.We expect that our results would indicate the immediate activation of calpain 2 in different causes of cardiomyocytes death. From the degree of expression of calpain 2 we could conclude about the duration of cardiomyocytes agony so calpain 2 could be used as a marker for the assessment the duration of somatic and cellular agony.

Study of Histopathological Findings in Sudden Unexpected Natural Deaths in a Tertiary Care Hospital

Introduction: Sudden death (SD) is defined by World Health Organization (WHO) as ‘death within 24 hours from onset of the symptoms’.1 It is by definition natural and it excludes all deaths due to poison and trauma. The incidence of sudden cardiac death has been steadily increasing all over the world. When SD occurs in adults and elderly persons, coronary atherosclerosis is the usual cause. These diseases are frequently concealed and discovered with surprise only at post mortem using macroscopic and microscopic examination of heart. Methods: Present study is a retrospective study, conducted in the department of Pathology, Vydehi Institute of Medical Sciences and Research Centre Bengaluru from July 2016 to June 2020. Patients of all age groups who died within 24 hours from the onset of symptoms were included. Results: A total of 483 autopsy cases were received for histopathological examination, among which there were 134 cases with history of sudden death during the study period. Age distribution ranged from 6 days to 86 years. In our study we observed male preponderance. Maximum number of cases was observed in 31 to 40 years of age. Major causes for sudden deaths observed were coronary artery diseases in 98 cases (73%) followed by pulmonary causes in 12 cases (8.96%). Conclusion: Present study highlighted the presence of increasing cases of sudden deaths among young males compared to developed countries. This will emphasize the need for research studies to find out the cause and early interventional measures to prevent the same.

Evaluation of histopathological findings of cardiac deaths in forensic autopsies.

The vast majority of sudden and unexpected natural deaths are related to cardiovascular diseases, especially coronary artery diseases. In this study, we aimed to reveal the epidemiological differences between men and women and to investigate the most common pathologies that cause cardiac deaths. Five thousand seven hundred sixty-eight autopsy cases that were done in 2016 were reviewed for the autopsy information and histopathological findings. Of the 5768 autopsies performed, 866 were due to cardiac causes. Eight hundred thirty-two cases were reviewed due to lack of autopsy information in 34 cases. One hundred sixteen (13.9%) were female, and 716 (86.1%) were male. Coronary artery disease was detected in 760 of 832 cases. There were findings of acute or previous myocardial infarction in 595 (71.5%), perivascular and interstitial fibrosis in 159 (19.1%), myocardial rupture and tamponade in 31 (%3.7), valvular disease in 6 (0.7%), cardiomyopathy in 4 (0.5%), and congenital heart disease in 3 (0.4%). In the study, it was observed that the mean age of death due to cardiac pathology other than coronary artery disease was significantly lower than deaths due to coronary artery disease (p < 0.05). The presence of coronary artery disease in men was found to be significantly higher than in women (p < 0.001). In our study, it was found that deaths due to coronary artery disease are seen at an older age than cardiac deaths other than coronary artery disease. In addition, in line with current knowledge, it has been confirmed that the mortality rate of coronary artery disease is higher in men than in women.

Cardiac and coronary artery study on sudden death cases in Hospital Canselor Tuanku Muhriz

Background: Sudden death (SD) is defined as an unexpected natural death within an hour onset of symptoms or unwitnessed death that occurs within 24 hours, which accounts for most cardiovascular deaths in Malaysia. This study aimed to evaluate the extent of histopathological changes in the heart and to study the demographic trend in SD cases in Kuala Lumpur, Malaysia. Methods: Specimens from all SD cases were received from 2017 to 2018 by the Forensic Unit, Hospital Canselor Tuanku Mukhriz (HCTM) were studied. The specimens were the left ventricular myocardium and left anterior descending artery (LAD), which were fixed in 10% formalin with haematoxylin and eosin staining. The tissues were graded histologically based on changes such as arterial occlusion, myocardial infarction, and/or thrombus formation. Results: Out of 545 medicolegal deaths, only 25 cases (4.6%) had samples available for analysis. Among these 25 patients, 24 (96%) were male patients and only one (4%) was a female patient. The available samples were from patients aged between 30 to 79 years old. In terms of ethinicity, Malays (40%) were the most numerous, followed by patients of Chinese and Indian ethnicities.The majority of the SD cases had a body mass index (BMI) that ranged between underweight (56%) and obese (40%). Besides, there were 10 (40%) cases of coronary artery with atheroma and 15 (60%) cases of myocardial infarction. The most common presentation of atherosclerosis was grade III and IV, and acute MI was the most common presentation at death, followed by healed infarcts and old infarcts. Discussion and Conclusion: Our findings reflect worsening risk factor levels in cardiovascular diseases, compounded by demographic trends. Further studies on biomarkers specific for cardiac diseases are warranted to understand imminent sudden cardiac death.

Cardiac and coronary artery study on sudden death cases in Hospital Canselor Tuanku Muhriz

Background: Sudden death (SD) is defined as an unexpected natural death within an hour onset of symptoms or unwitnessed death that occurs within 24 hours, which accounts for most cardiovascular deaths in Malaysia. This study aimed to evaluate the extent of histopathological changes in the heart and to study the demographic trend in SD cases in Kuala Lumpur, Malaysia. Methods: Specimens from all SD cases were received from 2017 to 2018 by the Forensic Unit, Hospital Canselor Tuanku Mukhriz (HCTM) were studied. The specimens were the left ventricular myocardium and left anterior descending artery (LAD), which were fixed in 10% formalin with haematoxylin and eosin staining. The tissues were graded histologically based on changes such as arterial occlusion, myocardial infarction, and/or thrombus formation. Results: Out of 545 medicolegal deaths, only 25 cases (4.6%) had samples available for analysis. Among these 25 patients, 24 (96%) were male patients and only one (4%) was a female patient. The available samples were from patients aged between 30 to 79 years old. In terms of ethinicity, Malays (40%) were the most numerous, followed by patients of Chinese and Indian ethnicities.The majority of the SD cases had a body mass index (BMI) that ranged between underweight (56%) and obese (40%). Besides, there were 10 (40%) cases of coronary artery with atheroma and 15 (60%) cases of myocardial infarction. The most common presentation of atherosclerosis was grade III and IV, and acute MI was the most common presentation at death, followed by healed infarcts and old infarcts. Discussion and Conclusion: Our findings reflect worsening risk factor levels in cardiovascular diseases, compounded by demographic trends. Further studies on biomarkers specific for cardiac diseases are warranted to understand imminent sudden cardiac death.

Myoglobin and C5b9 immunohistochemistry studies in heart tissue from sudden unexpected natural death cases

ABSTRACT The post-mortem diagnosis for acute myocardial infarction is one of the most challenging because acute myocardial infarction in the first 4 hours does not provide specific changes. Hence, this research evaluated the effectiveness of immunohistochemistry staining for detecting early myocardial infarction. Immunohistochemical staining for myoglobin and C5b9 were conducted on myocardial tissue from four groups with the following criteria: 1. Acute myocardial infarction cases (18 cases, positive control), 2. Severe coronary atherosclerosis cases (19 cases), 3. Natural deaths with unknown cause of death (12 cases), 4. Negative control. The results were that myoglobin staining was found positive in 17 cases of group 1 (94.4%), 13 cases of group 2 (68.4%), 3 cases of group 3 (25%), and 6 cases of group 4 (60%). C5b9 staining was found positive in 18 cases of group 1(100%), 10 cases of group 2 (52.6%), 4 cases of group 3 (33.3%), and 7 cases of group 4 (70%). The results showed that no statistical significance was found in a comparative analysis between group 4 and group 2. Hence, the results of staining for C5b9 and myoglobin conflict with the findings of prior research because the specificity in identifying acute myocardial infarction was low.

Hirtelen szívhalál

A hirtelen szívhalál (HSZH) klinikai szind-róma, amely a legáltalánosabban elfogadott definíció szerint: szívbetegen vagy ismert szívbetegség nélküli személyen cardiogenok miatt bekövetkező, váratlan, idő előtti, természetes halál, amelyet az öntudat hirtelen elvesztése előz meg és az akut tünetek kialakulásától számított egy órán belül bekövetkezik. (3). A hirtelen szívhalál incidenciája a publikált irodalom szerint igen széles tartományban mozog (15-48%), mely függ a földrajzi és demográfi ai mutatóktól.

Increased Platelet-Derived Growth Factor and Cytokine Levels in the Cerebrospinal Fluid of Patients of Sudden Unexpected Death with or without Viral Infection.

To clarify the pathogenesis of sudden unexpected natural death (SUD) as well as biomarkers to differentiate the underlying diseases, by performing cytokine analysis in the acute phase of pediatric patients in whom viral infection led to SUD. An acute phase cytokine analysis of pediatric patients in whom viral infection led to SUD was performed, and the data obtained were compared with those from SUD patients not associated with viral infections. Subjects included 4 boys aged 1-16 mo who died of cardiopulmonary arrest associated with viral infections. The causative viruses were identified as enterovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus. The 4 other infants/children (aged 2-12 mo) died of non-infectious episodes, i.e., 1, 2, and 1 died of drowning, falling, and a traffic accident, respectively. Cerebrospinal fluid samples (CSF) of the subjects were collected during cardiopulmonary resuscitation or within 24h of the events. The infection-induced sudden death group showed elevated CSF levels of inflammatory cytokines and chemokines. No increase was observed in interleukin-10 levels. Furthermore, in the infection-induced sudden death group, platelet-derived growth factor levels correlated with inflammatory cytokine levels. Infection-associated SUD may be differentiated from noninfectious SUD by measuring the levels of acute phase-inflammatory cytokines and chemokines at the onset of SUD.

An autopsy study of sudden natural deaths conducted at Govt hospital

Background: Many cases of sudden unexpected natural deaths occur in individuals without known medical diseases. Sudden natural death (SND) remains an important worldwide public health problem. The incidence of sudden natural deaths and causes vary in different societies, and these differences are influenced by many demographic factors. Objectives: To assess the frequency of sudden natural deaths among the autopsies, study the demographic profile and causes for sudden natural deaths. Methods: The study period was from 1st January 2015 to 31st July 2017 during which 760 autopsies were conducted, out of which, 88 cases were sudden natural deaths. Among them 60 cases of sudden natural deaths were selected for the study based on purposive sampling. Results: Incidence of sudden natural death was 11.57% out of all autopsies. The maximum number of cases (28.3%) was in the age group of 41-50 years, males constituting 81.7%. Out of 60 cases, more than half of the deaths (63.3%) accounted from cardiovascular diseases, 23.3% were due to respiratory diseases, 10% due to central nervous system diseases and 3.3% due to gastrointestinal diseases. Majority were Hindus (86.6%), belonged to urban area (83.3%), married (83.3%) and 81.7% were found in people taking mixed diet. In more than half of the cases (53.3%) death took place when the deceased was in his/her residence while resting. More than half of the cases were smokers and alcoholics with 51.7% and 58.3% respectively; drug abuse was seen in 2 cases (3.3%). Diabetes was seen in 11 cases (18.3%) and Hypertension in 15 cases (25%). 41.7% were found dead and 33.3% were brought dead to the hospital. Workers in industries, mills, shops, farms and other sectors constituted 16 cases (26.7%). Conclusion: Cardiovascular system pathologies especially coronary artery diseases remain the leading cause of sudden natural deaths in this study. Respiratory system diseases contributed the next major share of diseases. There is clear influence of age, sex, occupation, marital status, food habits, socio- economic status, co-morbid conditions, smoking and alcoholism on the incidence of sudden natural death.

Prevalence of Sudden and Unexpected Natural Death due to Diseases of Central Nervous System

Background: The World Health Organization (WHO) has defined sudden unexpected death as a death, non-violent and not otherwise explained, occurring within 24 hours from the onset of symptoms. This study was performed with the objective to evaluate the different neurological causes of sudden and unexpected death.&#x0D; Methods and materials: this is a cross-sectional analytical study with non-probability consecutive sampling technique over the period of one year. Data were collected, and analyzed using SPSS 20. Data were presented in percentages, and stratifications were used to control the modifiers.&#x0D; Results: There were total 110 autopsies done during the period of one year for sudden and unexpected deaths, among which 19 (17.3%) were deaths due to neurological causes, where 17(89.5%) were males and 2(10.5%) were females. There were 68.43% deaths seen during cold weather. Smoking, alcohol and drug abuse all seems to have higher prevalence among the sudden death due to neurological cause. Most common causes were subarachnoid hemorrhage (58%) followed by ganglionic bleed (26%).&#x0D; Conclusion: Common cause of sudden death due to neurological disease in our study seem to be due to intracerebral hemorrhage where subarachnoid hemorrhage was more common. The deaths were more common during the cold weather and most of them stopped their heart at emergency department during resuscitation.

REVIEW ON SUDDEN DEATHS DUE TO CARDIAC ABNORMALITIES

Sudden death is an unexpected natural death within the one-hour onset of a symptom or unwitnessed death that occurs within 24 hours. This definition is most often used to describe death caused by cardiac failure as it is one of the well-known causes of natural death. Various aetiologies are leading to sudden death, and myocardial infarction is reported to be one of the leading causes either due to coronary atherosclerosis and/ or thrombosis. An autopsy is a procedure routinely performed by the pathologist to determine the cause and manner of death which provides valuable information such as, demographic factors comprises gender, age, ethnic and lifestyle that were strongly linked to sudden deaths. This article review will discuss on autopsy in sudden death, as well as the aetiology of sudden death associated with cardiac abnormalities. Further, the contribution of demographic factors to sudden death will also be discussed and highlighted.

May Measurement Month 2017: screening for hypertension in Nigeria-Sub-Saharan Africa.

Hypertension and its complications are now responsible for about a quarter of emergency medical admissions in urban hospitals in Nigeria. It is the commonest risk factor for stroke, heart failure, chronic kidney disease, and dementia. Furthermore, high blood pressure is the commonest cause of sudden unexpected natural death in the country. Regrettably, the rate of awareness, treatment, and control is abysmally low in the country and in many parts of the world. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high blood pressure (BP) and to act as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 19 904 individuals with a mean age of 40.9 years, were screened during MMM17. After multiple imputation, 6709 (36.2%) had hypertension. Of individuals not receiving anti-hypertensive medication, 4140 (25.9%) were found to have hypertension. Of individuals receiving anti-hypertensive medication, 1449 (58.8%) had uncontrolled BP. MMM17 was one of the largest BP screening campaigns undertaken in Nigeria. A significant number of the participants were identified with hypertension (but not on any treatment) and uncontrolled BP despite being treated. These results suggest that opportunistic screening can identify significant numbers with raised BP.

Functional characterization of ABCC9 variants identified in sudden unexpected natural death

BackgroundGenetic variation in ion channel genes (‘channelopathies’) are often associated with inherited arrhythmias and sudden death. Genetic testing (‘molecular autopsies’) of channelopathy genes can be used to assist in determining the likely causes of sudden unexpected death. However, different in silico approaches can yield conflicting pathogenicity predictions and assessing their impact on ion channel function can assist in this regard. Methods and resultsWe performed genetic testing of cases of sudden expected death in the New York City metropolitan area and found four rare or novel variants in ABCC9, which codes for the regulatory SUR2 subunit of KATP channels. All were missense variants, causing amino acid changes in the protein. Three of the variants (A355S, M941V, and K1379Q) were in cases of infants less than six-months old and one (H1305Y) was in an adult. The predicted pathogenicities of the variants were conflicting. We have introduced these variants into a human SUR2A cDNA, which we coexpressed with the Kir6.2 pore-forming subunit in HEK-293 cells and subjected to patch clamp and biochemical assays. Each of the four variants led to gain-of-function phenotypes. The A355S and M941V variants increased in the overall patch current. The sensitivity of the KATP channels to inhibitory ‘cytosolic’ ATP was repressed for the M941V, H1305Y and K1379Q variants. None of the variants had any effect on the unitary KATP channel current or the surface expression of KATP channels, as determined with biotinylation assays, suggesting that all of the variants led to an enhanced open state. ConclusionsAll four variants caused a gain-of-function phenotype. Given the expression of SUR2-containing KATP channels in the heart and specialized cardiac conduction, vascular smooth muscle and respiratory neurons, it is conceivable that electrical silencing of these cells may contribute to the vulnerability element, which is a component of the triple risk model of sudden explained death in infants. The gain-of-function phenotype of these ABCC9 variants should be considered when assessing their potential pathogenicity.