Mazur, N A; Zhukov, V N
The study was conducted in the course of 2 years in accordance with the programme of myocardial infarction register of all mortality cases among the inhabitants of one of the Moscow districts. In conformity with the criteria recommended by the WHO Expert Committee, general figures of sudden death incidence at the age of 20 to 64 years comprised 80.3--76.2 and 32.7--34.5 per 100,000 males and females, respectively, during the 1st and 2nd year of observation. Autopsies performed in 89.5% of the mortality cases established that only in 39.8% of the cases death ensued in the presence of fresh foci of necrosis in the myocardium, while in the rest no myocardial infarction was found. In an overwhelming majority of the dying patients severe stenoses or occlusions of the coronary arteries were seen, and only 13% had no stenoses. However, the latter group showed fresh necroses or postinfarction cicatrices in the myocardium. The obtained data indicate that sudden death occupies an important place in the structure of mortality in ischaemic heart disease. It has been demonstrated that no reduction of general mortality due to myocardial infarction is possible without effective measures against this kind of death.
... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Death due to pneumoconiosis. 718.205 Section... DEATH DUE TO PNEUMOCONIOSIS Determining Entitlement to Benefits § 718.205 Death due to pneumoconiosis. (a) Benefits are provided to eligible survivors of a miner whose death was due to pneumoconiosis. In...
... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Death due to pneumoconiosis. 718.205 Section... OR DEATH DUE TO PNEUMOCONIOSIS Determining Entitlement to Benefits § 718.205 Death due to pneumoconiosis. (a) Benefits are provided to eligible survivors of a miner whose death was due to pneumoconiosis...
... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Death due to pneumoconiosis. 718.205 Section... OR DEATH DUE TO PNEUMOCONIOSIS Determining Entitlement to Benefits § 718.205 Death due to pneumoconiosis. (a) Benefits are provided to eligible survivors of a miner whose death was due to pneumoconiosis...
... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false Death due to pneumoconiosis. 718.205 Section... OR DEATH DUE TO PNEUMOCONIOSIS Determining Entitlement to Benefits § 718.205 Death due to pneumoconiosis. (a) Benefits are provided to eligible survivors of a miner whose death was due to pneumoconiosis...
... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false Death due to pneumoconiosis. 718.205 Section... OR DEATH DUE TO PNEUMOCONIOSIS Determining Entitlement to Benefits § 718.205 Death due to pneumoconiosis. (a) Benefits are provided to eligible survivors of a miner whose death was due to pneumoconiosis...
Azad, Kishwar; Mathews, Jiji
Preterm births (PTBs), defined as births before 37 weeks of gestation account for the majority of deaths in the newborn period. Prediction and prevention of PTB is challenging. A history of preterm labour or second trimester losses and accurate measurement of cervical length help to identify women who would benefit from progesterone and cerclage. Fibronectin estimation in the cervicovaginal secretions of a symptomatic woman with an undilated cervix can predict PTB within 10 days of testing. Antibiotics should be given to women with preterm prelabour rupture of membranes but tocolysis has a limited role in the management of preterm labour. Antenatal corticosteroids to prevent complications in the neonate should be given only when gestational age assessment is accurate PTB is considered imminent, maternal infection and the preterm newborn can receive adequate care. Magnesium sulphate for fetal neuroprotection should be given when delivery is imminent. After birth, most babies respond to simple interventions essential newborn care, basic care for feeding support, infections and breathing difficulties. Newborns weighing 2000 g or less, benefit from KMC. Babies, who are clinically unstable or cannot be given KMC may be nursed in an incubator or under a radiant warmer. Treatment modalities include oxygen therapy, CPAP, surfactant and assisted ventilation. Copyright © 2016. Published by Elsevier Ltd.
Nadesan, K; Beng, O B
Deaths due to plastic bag suffocation or plastic bag asphyxia are not reported in Malaysia. In the West many suicides by plastic bag asphyxia, particularly in the elderly and those who are chronically and terminally ill, have been reported. Accidental deaths too are not uncommon in the West, both among small children who play with shopping bags and adolescents who are solvent abusers. Another well-known but not so common form of accidental death from plastic bag asphyxia is sexual asphyxia, which is mostly seen among adult males. Homicide by plastic bag asphyxia too is reported in the West and the victims are invariably infants or adults who are frail or terminally ill and who cannot struggle. Two deaths due to plastic bag asphyxia are presented. Both the autopsies were performed at the University Hospital Mortuary, Kuala Lumpur. Both victims were 50-year old married Chinese males. One death was diagnosed as suicide and the other as sexual asphyxia. Sexual asphyxia is generally believed to be a problem associated exclusively with the West. Specific autopsy findings are often absent in deaths due to plastic bag asphyxia and therefore such deaths could be missed when some interested parties have altered the scene and most importantly have removed the plastic bag. A visit to the scene of death is invariably useful.
Lehtonen, Liisa; Gimeno, Ana; Parra-Llorca, Anna; Vento, Máximo
Early neonatal death (ENND), defined as the death of a newborn between zero and seven days after birth, represents 73% of all postnatal deaths worldwide. Despite a 50% reduction in childhood mortality, reduction of ENND has significantly lagged behind other Millennium Developmental Goal achievements and is a growing contributor to overall mortality in children aged <5 years. The etiology of ENND is closely related to the level of a country's industrialization. Hence, prematurity and congenital anomalies are the leading causes in high-income countries. Furthermore, sudden unexpected early neonatal deaths (SUEND) and collapse have only recently been identified as relevant and often preventable causes of death. Concomitantly, perinatal-related events such as asphyxia and infections are extremely relevant in Africa, South East Asia, and Latin America and, together with prematurity, are the principal contributors to ENND. In high-income countries, according to current research evidence, survival may be improved by applying antenatal and perinatal therapies and immediate newborn resuscitation, as well as by centralizing at-risk deliveries to centers with appropriate expertise available around the clock. In addition, resources should be allocated to the close surveillance of newborn infants, especially during the first hours of life. Many of the conditions leading to ENND in low-income countries are preventable with relatively easy and cost-effective interventions such as contraception, vaccination of pregnant women, hygienic delivery at a hospital, training health care workers in resuscitation practices, simplified algorithms that allow for early detection of perinatal infections, and early initiation of breastfeeding and skin-to-skin care. The future is promising. As initiatives undertaken in previous decades have led to substantial reduction in childhood mortality, it is expected that new initiatives targeting the perinatal/neonatal periods are bound to reduce ENND and
Pedrosa, Linda Délia Carvalho de Oliveira; Sarinho, Silvia Wanick; Ximenes, Ricardo Arraes de Alencar; Ordonha, Manoelina R
To investigate the quality of official neonatal death data in Maceió, Alagoas. A descriptive study was conducted on early neonatal deaths in hospitals between January 1, 2001, and December 31, 2002, to compare data entry in the Death Certificate (DC) and Mortality Information System (MIS) with a standardized form filled out with data of medical files from the mothers and newborn. The frequency with which the following variables failed to be recorded in the DC and SIM was studied: type of death, address, age of mother, gender, birth weight, and delivery type, age at death and gestational age. MIS reliability was verified using simple concordance, sensitivity and Kappa indicator. MIS recorded 451 deaths, of which 50 were excluded. Mother's age was omitted from MIS in 44.1% of cases. 85.7% to 100% of the variables not filled in for the DC were recovered from the medical files. There was good concordance between DC and medical files for type of delivery, weight and age. Birth weight and age of mother presented the least concordance between medical files and MIS. MIS presented 69.2% sensitivity for weight and 36.3% for age of mother, thus demonstrating little capability to correctly supply information to generate perinatal health indicators. Because of incomplete filling out, quality of the DC becomes precarious and makes the MIS inadequate, even though it covers 100% of neonatal deaths in Maceió. Inefficiency of the system is increased by failure of MIS technicians to correct errors found and input all the information available.
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Death due to pneumoconiosis, including... Death Due to Pneumoconiosis § 410.450 Death due to pneumoconiosis, including statutory presumption... at the time of his death, or whose death is determined to have been due to pneumoconiosis. (For...
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Death due to pneumoconiosis, including... Death Due to Pneumoconiosis § 410.450 Death due to pneumoconiosis, including statutory presumption... at the time of his death, or whose death is determined to have been due to pneumoconiosis. (For...
Wei, Dengming; Yuan, Xiaogang; Yang, Tiantong; Chang, Lin; Zhang, Xiang; Burke, Allen; Fowler, David; Li, Ling
We report a case of a 30-year-old woman who suddenly collapsed after having a physical altercation with her husband. Despite immediate resuscitation, she died on arrival at the hospital. The victim's parents requested an autopsy because they believed that their daughter was killed by her husband. Postmortem examination revealed that the victim had a diffusely enlarged thyroid gland and cardiomegaly with left ventricular hypertrophy. There was no evidence of significant trauma on the body. Further postmortem thyroid function tests and review of her medical history indicated that her death was due to Graves' disease. To the best of our knowledge, this is the first case reported of sudden death due to cardiac arrhythmia from Graves' disease induced by physical and emotional stress associated with the criminal activity of another person. The autopsy findings are described. In addition, the literature is reviewed and the significance of postmortem evaluation of thyroid hormones in the cases of sudden death is discussed. © 2013 American Academy of Forensic Sciences.
Starzyk, Patricia M.
This paper discusses data on the deaths of children aged 1-4 years in Washington State. A two-fold approach was used in the analysis. First, Washington State death certificate data for 1979-85 were used to characterize the deaths and identify hazardous situations. Second, death certificates were linked to birth certificates of children born in…
Carter, A O; Millson, M E; Allen, D E
A case-control study, using both matched and unmatched controls, was carried out on individuals who were injured or killed by a series of tornadoes that passed through Ontario, Canada, on May 31, 1985. Many serious injuries (25%) and almost all (83%) deaths were the result of becoming airborne, while most minor injuries (94%) were due to being struck by objects. Head injury was the most common injury type. Few (21%) of those in buildings chose the recommended location, and most (61%) were not in the least damaged part. Most (91%) had less than one minute's warning, and only 47% had a functioning radio at the time the tornado hit. The following risk factors for injury and death were identified: poor building anchorage; location other than in a basement, especially outdoors; age over 70 years; and high wind strength. These findings support previous findings and point to measures which have potential for preventing death or serious injury in future tornadoes: adequate warning systems and public education to ensure that individuals understand the warning and respond by seeking appropriate shelter. Those in adequately anchored buildings should shelter in an interior room or basement. Those who are outdoors, in poorly anchored buildings, mobile homes, or portable classrooms require access to an adequately anchored building, preferably with a basement, during severe storm warnings. This should be arranged by local authorities.
Li, Wenhe; Zhang, Lin; Liang, Yue; Tong, Fang; Zhou, Yiwu
Abstract Introduction: Atrioventricular node (AVN) contusion usually results in cardiogenic shock and arrhythmia and is a rare but fatal condition. The condition is difficult to diagnose and easily overlooked because it develops rapidly and is asymptomatic. We here report 3 cases that demonstrate blunt chest impact and hemorrhages of the posterior atrioventricular junction, eventually result in death. Clinical Findings: Autopsy and histological examination were performed on all cases. External inspection revealed bruises in the hearts and fractures in the sternum and ribs. However, histological examinations were conclusive and showed cardiac contusion on the surface of the posterior atrioventricular junction of the individuals, and the death was due to the AVN contusion. The position of the AVN on the heart surface is determined by detailed examinations via an autopsy and microscopic, both of which are critical in the certification of cause of death. Conclusion: The report is intended to raise our understanding and make forensic pathologists aware of the surface of the posterior atrioventricular junction. PMID:28072704
Martínez, María Antonia; Ballesteros, Salomé; Alcaraz, Rafael
The investigation of uncertain fatalities requires accurate determination of the cause of death, with assessment of all factors that may have contributed to it. Gasoline is a complex and highly variable mixture of aliphatic and aromatic hydrocarbons that can lead to cardiac arrhythmias due to sensitization of the myocardium to catecholamines or acts as a simple asphyxiant if the vapors displace sufficient oxygen from the breathing atmosphere. This work describes a sudden occupational fatality involving gasoline. The importance of this petroleum distillate detection and its quantitative toxicological significance is discussed using a validated analytical method. A 51 year-old Caucasian healthy man without significant medical history was supervising the repairs of the telephone lines in a manhole near to a gas station. He died suddenly after inhaling gasoline vapors from an accidental leak. Extensive blistering and peeling of skin were observed on the skin of the face, neck, anterior chest, upper and lower extremities, and back. The internal examination showed a strong odor of gasoline, specially detected in the respiratory tract. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography with flame ionization detector and confirmation was performed using gas chromatography-mass spectrometry. Disposition of gasoline in different tissues was as follows: heart blood, 35.7 mg/L; urine, not detected; vitreous humor, 1.9 mg/L; liver, 194.7 mg/kg; lung, 147.6 mg/kg; and gastric content, 116,6 mg/L (2.7 mg total). Based upon the toxicological data along with the autopsy findings, the cause of death was determined to be gasoline poisoning and the manner of death was accidental. We would like to alert on the importance of testing for gasoline, and in general for volatile hydrocarbons, in work-related sudden deaths involving inhalation of hydrocarbon vapors and/or exhaust fumes. Copyright © 2011 Elsevier Ireland Ltd. All rights
Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta
In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded.
Arróspide, Nancy; Espinoza, Máximo Manuel; Miranda-Choque, Edwin; Mayta-Tristán, Percy; Legua, Pedro; Cabezas, César
Here we describe the case of a 19-year-old woman, in her 29th week of gestation, who was from Llumpe (Ancash, Peru) and had a history of traveling to Chanchamayo (Junín, Peru) and Rinconada (Ancash, Peru). The patient presented at Chacas Hospital (Chacas, Ancash, Peru) with general malaise, dehydration, respiratory distress, jaundice, the sensation of thermal rise, and abdominal pain. Analysis of blood smears revealed 60% hemoparasites. She was transferred to Ramos Guardia Hospital (Huaraz, Peru) where she presented increasing respiratory distress, choluria, hematuria, and decreased urine output, moreover she was positive for Plasmodium. From there she was transferred to Cayetano Heredia Hospital (Lima, Peru), where she was admitted to the intensive care unit (ICU) with multiple organ failure, stillbirth, and leading to death. She underwent mechanical ventilation, was administered clindamycin, and was prescribed quinine, which she did not received due a lack by availability. The evolution of the illness was torpid, and she ultimately developed multiple organ failure and died. Plasmodium vivax infection was confirmed. Accordingly, we emphasize the importance of improving our diagnostic capabilities and management techniques to enable clinicians to provide adequate and timely treatment.
Wigle, D T; Collishaw, N E; Kirkbride, J; Mao, Y
Recently published evidence indicates that involuntary smoking causes an increased risk of lung cancer among nonsmokers. Information was compiled on the proportion of people who had never smoked among victims of lung cancer, the risk of lung cancer for nonsmokers married to smokers and the prevalence of such exposure. On the basis of these data we estimate that 50 to 60 of the deaths from lung cancer in Canada in 1985 among people who had never smoked were caused by spousal smoking; about 90% occurred in women. The total number of deaths from lung cancer attributable to exposure to tobacco smoke from spouses and other sources (mainly the workplace) was derived by applying estimated age- and sex-specific rates of death from lung cancer attributable to such exposure to the population of Canadians who have never smoked; about 330 deaths from lung cancer annually are attributable to such exposure. PMID:3567810
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Irrebuttable presumption of death due to... FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Total Disability or Death Due to Pneumoconiosis § 410.458 Irrebuttable presumption of death due to pneumoconiosis—survivor's...
Kinney, Hannah C.; Willinger, Marian
In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Disability or death due... Benefits § 3.800 Disability or death due to hospitalization, etc. This section applies to claims received... 3.363. (a) Where disease, injury, death or the aggravation of an existing disease or injury occurs...
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Termination due to death of recipient. 416... FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1334 Termination due to death of... effective with the month after the month of death. ...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Disability or death due... Benefits § 3.800 Disability or death due to hospitalization, etc. This section applies to claims received... 3.363. (a) Where disease, injury, death or the aggravation of an existing disease or injury occurs...
... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Termination due to death of recipient. 416... FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1334 Termination due to death of... effective with the month after the month of death. ...
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Termination due to death of recipient. 416... FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1334 Termination due to death of... effective with the month after the month of death. ...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Disability or death due... Benefits § 3.800 Disability or death due to hospitalization, etc. This section applies to claims received... 3.363. (a) Where disease, injury, death or the aggravation of an existing disease or injury occurs...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Disability or death due... Benefits § 3.800 Disability or death due to hospitalization, etc. This section applies to claims received... 3.363. (a) Where disease, injury, death or the aggravation of an existing disease or injury occurs...
Wareham, N. J.; Harrison, B. D.; Jenkins, P. F.; Nicholls, J.; Stableforth, D. E.
BACKGROUND--The aim was to establish a continuing district based confidential enquiry into deaths from asthma. METHODS--A confidential enquiry was conducted in an English health district. Subjects comprised 24 residents of the Norwich health district aged between 16 and 65 years who had died between 1988 and 1991 with asthma as the principal cause of death. RESULTS--Twenty one of the patients (88%) died away from hospital. Overall the routine asthma management was appropriate in all respects in only four patients. In five cases the drug treatment was considered inappropriate, in 10 cases (42%) there was no written evidence that the patient had received advice and education, and only six cases had a written management plan. In 17 patients (71%) the fatal attack of asthma developed rapidly (in under three hours). The medical care during the final attack was found to have been inappropriate in six cases. Seventeen cases (71%) had psychological or social factors that were considered to have been of potential importance. CONCLUSIONS--This study has shown the feasibility of organising a confidential enquiry into asthma deaths within a health district. The distinguishing features of such an enquiry are that it is continuing, that the quality of care given to those patients who died is compared against a recognised standard, and that there is a structured system for feeding back the conclusions of the enquiry to the local medical community. PMID:8296254
Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.
Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746
Douglas, Mbuyiselo; Maluleke, Thelmah Xavela
Deaths of initiates occurring in the circumcision initiation schools are preventable. Current studies list dehydration as one of the underlying causes of deaths among traditional male circumcision initiates in the Eastern Cape, a province in South Africa, but ways to prevent dehydration in the initiation schools have not been adequately explored. The goals of this study were to (a) explore the underlying determinants of dehydration among initiates aged from 12 to 18 years in the traditional male circumcision initiation schools and (b) determine knowledge of participants on the actions to be taken to prevent dehydration. The study was conducted at Libode, a rural area falling under Nyandeni municipality. A simple random sampling was used to select three focus group discussions with 36 circumcised boys. A purposive sampling was used to select 10 key informants who were matured and experienced people with knowledge of traditional practices and responsible positions in the communities. The research findings indicate that the practice has been neglected to inexperienced, unskillful, and abusive traditional attendants. The overall themes collated included traditional reasons for water restriction, imbalanced food nutrients given to initiates, poor environmental conditions in the initiation hut, and actions that should be taken to prevent dehydration. This article concludes with discussion and recommendation of ways to prevent dehydration of initiates in the form of a comprehensive circumcision health promotion program.
Douglas, Mbuyiselo; Maluleke, Thelmah Xavela
Deaths of initiates occurring in the circumcision initiation schools are preventable. Current studies list dehydration as one of the underlying causes of deaths among traditional male circumcision initiates in the Eastern Cape, a province in South Africa, but ways to prevent dehydration in the initiation schools have not been adequately explored. The goals of this study were to (a) explore the underlying determinants of dehydration among initiates aged from 12 to 18 years in the traditional male circumcision initiation schools and (b) determine knowledge of participants on the actions to be taken to prevent dehydration. The study was conducted at Libode, a rural area falling under Nyandeni municipality. A simple random sampling was used to select three focus group discussions with 36 circumcised boys. A purposive sampling was used to select 10 key informants who were matured and experienced people with knowledge of traditional practices and responsible positions in the communities. The research findings indicate that the practice has been neglected to inexperienced, unskillful, and abusive traditional attendants. The overall themes collated included traditional reasons for water restriction, imbalanced food nutrients given to initiates, poor environmental conditions in the initiation hut, and actions that should be taken to prevent dehydration. This article concludes with discussion and recommendation of ways to prevent dehydration of initiates in the form of a comprehensive circumcision health promotion program. PMID:26833781
Marín-Huerta, E; Peinado, R; Asso, A; Loma, A; Villacastín, J P; Muñiz, J; Brugada, J
Since most sudden cardiac death victims show neither symptoms before the event nor other signs or risk factors that would have identified them as a high risk population before their cardiac arrest, emergency out-of-hospital medical services must be improved in order to obtain a higher survival in these patients. Early defibrillation is an essential part of the chain of survival that also includes the early identification of the victim, activation of the emergency medical system, immediate arrival of trained personnel who can perform basic cardiopulmonary resuscitation and early initiation of advanced cardiac life support that would raise the survival rate for sudden cardiac arrest victims. Many studies have demonstrated the enormous importance of early defibrillation in patients with a cardiac arrest due to ventricular fibrillation. The most important predictor of survival in these individuals is the time that elapses until electric defibrillation, the longer the time to defbrillation the lower the number of patients who are eventually discharged. Multiple studies have demonstrated that automatic external defibrillation will reduce the time elapsed to defibrillation and thus improve survival. For these reason, public access defibrillation to allow the use of automatic external defibrillators by minimally trained members of the lay public, has received increasing interest on the part of a groving number of companies, cities or countries. The automatic external defibrillaton, as performed by a lay person is being investigated. The liberalization of its application, if is demonstrated to be effective, will need to be accompanied by legal measures to endorse it and appropriate health education, probably during secondary education.
Sejben, István; Som, Zoltán; Cserni, Gábor
Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.
Ogden, Emily; Schandl, Cynthia; Tormos, Lee Marie
Ectodermal dysplasia comprises a group of disorders affecting ectodermal tissues. Severity depends on the genetic aberration; hyperpyrexia secondary to absence of sweat glands is a common complication. Treatment is supportive. This case report describes a 1-month, 27-day-old male infant with a diagnosis of X-linked recessive anhidrotic ectodermal dysplasia. On the day of his death, his mother swaddled him in a blanket and placed him on the couch at 5:30 am. When she picked him up at 8:00 am, he was unresponsive. At the emergency department, his rectal temperature was 40°C. Postmortem blood culture was positive for group B streptococcus, a possible etiology for fever. It is vital to teach parents that close monitoring of children with ectodermal dysplasia is necessary, as an increase in body temperature can become life threatening. © 2014 American Academy of Forensic Sciences.
Rigouzzo, A; Tessier, V; Zieleskiewicz, L
Over the period 2010-2012, maternal mortality from infectious causes accounted for 5% of maternal deaths by direct causes and 16% of maternal deaths by indirect causes. Among the 22 deaths caused by infection occurred during this period, 6 deaths were attributed to direct causes from genital tract origin, confirming thus the decrease in direct maternal deaths by infection during the last ten years. On the contrary, indirect maternal deaths by infection, from extragenital origin, doubled during the same period, with 16 deaths in the last triennium, dominated by winter respiratory infections, particularly influenza: the 2009-2010 influenza A (H1N1) virus pandemic was the leading cause of indirect maternal mortality by infection during the studied period. The main infectious agents involved in maternal deaths from direct causes were Streptococcus A, Escherichia Coli and Clostridium perfringens: these bacterias were responsible for toxic shock syndrome, severe sepsis, secondary in some cases to cellulitis or necrotizing fasciitis. Of the 6 deaths due to direct infection, 4 were considered avoidable because of inadequate management: delayed or missed diagnosis, delayed or inadequate initiation of a specific medical and/or surgical treatment. Of the 16 indirect maternal deaths due to infection causes, the most often involved infectious agents were influenza A (H1N1) virus and Streptococcus pneumonia with induced purpura fulminans: the absence of influenza vaccination during pregnancy, delayed diagnosis and emergency initiation of a specific treatment, were the main contributory factors to these deaths and their avoidability in 70% of the cases analyzed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Barbería, Eneko; Suelves, Josep M; Xifró, Alexandre; Medallo, Jordi
To study immediate (same day of the collision) and delayed (within 30 days of the collision) deaths due to traffic injuries in Catalonia (Spain) according to forensic sources and to assess the differences between the two kinds of deaths. An observational study was conducted of all the traffic accident deaths registered in the Institute of Legal Medicine of Catalonia between January 1(st) 2005 and December 31(st) 2014. Data analysis was performed using the SPSS v.18.0 statistical package. Comparisons of proportions were based on the χ(2) test. During the study period, 4044 deaths due to traffic injuries were recorded. Deaths within 30 days included more women, minors, elderly people, and pedestrians than immediate deaths. Traffic injury deaths in the 30 days following a crash differ from immediate deaths. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.
Vander Stoep, Ann; McCauley, Elizabeth; Flynn, Cynthia; Stone, Andrea
The prevalence and persistence of thoughts of death and suicide during early adolescence were estimated in a community-based cohort. A latent class approach was used to identify distinct subgroups based on endorsements to depression items administered repeatedly over 24 months. Two classes emerged, with 75% in a low ideation class across four…
... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false When does SVB entitlement end due to death... CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Termination § 408.816 When does SVB entitlement end due to death? Your SVB entitlement ends with the month in which you die. Payments are terminated...
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false When does SVB entitlement end due to death... CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Termination § 408.816 When does SVB entitlement end due to death? Your SVB entitlement ends with the month in which you die. Payments are terminated...
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false When does SVB entitlement end due to death... CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Termination § 408.816 When does SVB entitlement end due to death? Your SVB entitlement ends with the month in which you die. Payments are terminated...
... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false When does SVB entitlement end due to death... CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Termination § 408.816 When does SVB entitlement end due to death? Your SVB entitlement ends with the month in which you die. Payments are terminated...
... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false When does SVB entitlement end due to death... CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Termination § 408.816 When does SVB entitlement end due to death? Your SVB entitlement ends with the month in which you die. Payments are terminated...
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Irrebuttable presumption of death due to pneumoconiosis-survivor's claim. 410.458 Section 410.458 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Total Disability or Death Due to Pneumoconiosis § 410.458...
Dokoupil, Marek; Marecová, Klára; Handlos, Petr; Březina, Petr
A young adult black female, known to be a prostitute and suspected of smuggling narcotics, was found dead in her apartment in a state of early decomposition. Oval-shaped gray-white masses of exogenous origin protruded from the anus. The autopsy showed dilatation of the folds of the large intestine, which were almost completely filled with these oval-shaped gray-white masses of foreign material. The uterus was enlarged with multiple large leiomyomas. Toxicological tests of blood and the foreign material revealed no toxicologically relevant substances. Kaolin was detected in a sample of the foreign material from the large intestine. The immediate cause of death was intestinal obstruction due to the formation of a kaolin bezoar with simultaneous compression of the large intestine by the enlarged myomatous uterus. Subsequent revelation of a habit the deceased had brought from her native country led to the conclusion that this exotic custom was responsible for her death. © 2018 American Academy of Forensic Sciences.
Sampath, Amitha; Maduro, Gil; Schillinger, Julia A
Neonatal infection with herpes simplex virus (HSV) is not a nationally reportable disease; there have been few population-based measures of HSV-related infant mortality. We describe infant death rates due to neonatal HSV as compared with congenital syphilis (CS) and HIV, 2 reportable, perinatally transmitted diseases, in New York City from 1981 to 2013. We identified neonatal HSV-, CS-, and HIV-related deaths using International Classification of Diseases (ICD) codes listed on certificates of death or stillbirth issued in New York City. Deaths were classified as HSV-related if certificates listed (1) any HSV ICD-9/ICD-10 codes for deaths ≤42 days of age, (2) any HSV ICD-9/ICD-10 codes and an ICD code for perinatal infection for deaths at 43 to 365 days of age, or (3) an ICD-10 code for congenital HSV. CS- and HIV-related deaths were those listing any ICD code for syphilis or HIV. There were 34 deaths due to neonatal HSV (0.82 deaths per 100 000 live births), 38 from CS (0.92 per 100 000), and 262 from HIV (6.33 per 100 000). There were no CS-related deaths after 1996, and only 1 HIV-related infant death after 2004. The neonatal HSV-related death rate during the most recent decade (2004-2013) was significantly higher than in previous years. The increasing neonatal HSV-related death rate may reflect increases in neonatal herpes incidence; an increasing number of pregnant women have never had HSV type 1 and are therefore at risk of acquiring infection during pregnancy and transmitting to their infant. Copyright © 2016 by the American Academy of Pediatrics.
Pikala, Malgorzata; Bryla, Marek; Bryla, Pawel; Maniecka-Bryla, Irena
Background The aim of the study is the analysis of years of life lost due to external causes of death, particularly due to traffic accidents and suicides. Materials and Methods The study material includes a database containing information gathered from 376,281 death certificates of inhabitants of the Lodz province who died between 1999 and 2010. The Lodz province is characterized by the highest mortality rates in Poland. The SEYLLp (Standard Expected Years of Life Lost per living person) and the SEYLLd (per death) indices were used to determine years of life lost. Joinpoint models were used to analyze time trends. Results In 2010, deaths due to external causes constituted 6.0% of the total number of deaths. The standardized death rate (SDR) due to external causes was 110.0 per 100,000 males and was five times higher than for females (22.0 per 100,000 females). In 2010, the SEYLLp due to external causes was 3746 per 100,000 males and 721 per 100,000 females. Among males, suicides and traffic accidents were the most common causes of death (the values of the SEYLLp were: 1098 years and 887 years per 100,000 people, respectively). Among females, the SEYLLp values were 183 years due to traffic accidents and 143 years due to suicides (per 100,000 people). Conclusions A decrease in the number of years of life lost due to external causes is much higher among females. The authors observe that a growing number of suicides contribute to an increase in the value of the SEYLLp index. This directly contributes to over-mortality of males due to external causes. The analysis of the years of life lost focuses on the social and economic aspects of premature mortality due to external causes. PMID:24810942
Halder, Amal K.; Gurley, Emily S.; Naheed, Aliya; Saha, Samir K.; Brooks, W. Abdullah; Arifeen, Shams El; Sazzad, Hossain M. S.; Kenah, Eben; Luby, Stephen P.
Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD±7.3). Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006–2007. The leading cause of under-five death was respiratory infections (22%). The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year) were similar (36 versus 32). The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years. PMID:19997507
Koch, Abigail R; Geller, Stacie E
Homicide, suicide, and substance abuse accounted for nearly one fourth of all pregnancy-associated deaths in Illinois from 2002 through 2013. Maternal mortality review in Illinois has been primarily focused on obstetric and medical causes and little is known about the circumstances surrounding deaths due to homicide, suicide, and substance abuse, if they are pregnancy related, and if the deaths are potentially preventable. To address this issue, we implemented a process to form a second statewide maternal mortality review committee for deaths due to violence in late 2014. We convened a stakeholder group to accomplish 3 tasks: (1) identify appropriate committee members; (2) identify potential types and sources of information that would be required for a meaningful review of violent maternal deaths; and (3) revise the Maternal Mortality Review Form. Because homicide, suicide, and substance abuse are closely linked to the social determinants of health, the review committee needed to have a broad membership with expertise in areas not required for obstetric maternal mortality review, including social service and community organizations. Identifying additional sources of information is critical; the state Violent Death Reporting System, case management data, and police and autopsy reports provide contextual information that cannot be found in medical records. The stakeholder group revised the Maternal Mortality Review Form to collect information relevant to violent maternal deaths, including screening history and psychosocial history. The form guides the maternal mortality review committee for deaths due to violence to identify potentially preventable factors relating to the woman, her family, systems of care, the community, the legal system, and the institutional environment. The committee has identified potential opportunities to decrease preventable death requiring cooperation with social service agencies and the criminal justice system in addition to the physical
Zhang, M Z; Li, B X; Zhao, R; Guan, D W; Zhang, G H; Wu, X; Zhu, B L; Li, R B
To analyse the cases of sudden death due to hyperthyroid heart disease, and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases. Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine, China Medical University. The general information （gender and age）, clinical manifestations, medical history, anatomical and histopathological findings, biochemical parameters and cause of death were analysed retrospectively. Most of the 6 patients had definite history of hyperthyroidism, and they all showed certain degrees of symptoms of cardiovascular disease; had obvious incentive factors of death; histopathological examination of thyroid conformed to the performances of diffuse toxic goiter; with increase of cardiac weight, dilatation of cardiac chambers, myocardial hypertrophy and focal necrosis; postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease. The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy, histopathological examination, postmortem toxicology tests. The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary. Copyright© by the Editorial Department of Journal of Forensic Medicine
Teplin, Linda A; McClelland, Gary M; Abram, Karen M; Mileusnic, Darinka
Youth processed in the juvenile justice system are at great risk for early violent death. Groups at greatest risk, ie, racial/ethnic minorities, male youth, and urban youth, are overrepresented in the juvenile justice system. We compared mortality rates for delinquent youth with those for the general population, controlling for differences in gender, race/ethnicity, and age. This prospective longitudinal study examined mortality rates among 1829 youth (1172 male and 657 female) enrolled in the Northwestern Juvenile Project, a study of health needs and outcomes of delinquent youth. Participants, 10 to 18 years of age, were sampled randomly from intake at the Cook County Juvenile Temporary Detention Center in Chicago, Illinois, between 1995 and 1998. The sample was stratified according to gender, race/ethnicity (African American, non-Hispanic white, Hispanic, or other), age (10-13 or > or =14 years), and legal status (processed as a juvenile or as an adult), to obtain enough participants for examination of key subgroups. The sample included 1005 African American (54.9%), 296 non-Hispanic white (16.2%), 524 Hispanic (28.17%), and 4 other-race/ethnicity (0.2%) subjects. The mean age at enrollment was 14.9 years (median age: 15 years). The refusal rate was 4.2%. As of March 31, 2004, we had monitored participants for 0.5 to 8.4 years (mean: 7.1 years; median: 7.2 years; interquartile range: 6.5-7.8 years); the aggregate exposure for all participants was 12944 person-years. Data on deaths and causes of death were obtained from family reports or records and were then verified by the local medical examiner or the National Death Index. For comparisons of mortality rates for delinquents and the general population, all data were weighted according to the racial/ethnic, gender, and age characteristics of the detention center; these weighted standardized populations were used to calculate reported percentages and mortality ratios. We calculated mortality ratios by comparing our
Teplin, Linda A.; McClelland, Gary M.; Abram, Karen M.; Mileusnic, Darinka
Objective Youth processed in the juvenile justice system are at great risk for early violent death. Groups at greatest risk, ie, racial/ethnic minorities, male youth, and urban youth, are overrepresented in the juvenile justice system. We compared mortality rates for delinquent youth with those for the general population, controlling for differences in gender, race/ethnicity, and age. Methods This prospective longitudinal study examined mortality rates among 1829 youth (1172 male and 657 female) enrolled in the Northwestern Juvenile Project, a study of health needs and outcomes of delinquent youth. Participants, 10 to 18 years of age, were sampled randomly from intake at the Cook County Juvenile Temporary Detention Center in Chicago, Illinois, between 1995 and 1998. The sample was stratified according to gender, race/ethnicity (African American, non-Hispanic white, Hispanic, or other), age (10–13 or ≥14 years), and legal status (processed as a juvenile or as an adult), to obtain enough participants for examination of key subgroups. The sample included 1005 African American (54.9%), 296 non-Hispanic white (16.2%), 524 Hispanic (28.17%), and 4 other-race/ethnicity (0.2%) subjects. The mean age at enrollment was 14.9 years (median age: 15 years). The refusal rate was 4.2%. As of March 31, 2004, we had monitored participants for 0.5 to 8.4 years (mean: 7.1 years; median: 7.2 years; interquartile range: 6.5–7.8 years); the aggregate exposure for all participants was 12 944 person-years. Data on deaths and causes of death were obtained from family reports or records and were then verified by the local medical examiner or the National Death Index. For comparisons of mortality rates for delinquents and the general population, all data were weighted according to the racial/ethnic, gender, and age characteristics of the detention center; these weighted standardized populations were used to calculate reported percentages and mortality ratios. We calculated mortality
Barrera, Maru; O'connor, Kathleen; D'Agostino, Norma Mammone; Spencer, Lynlee; Nicholas, David; Jovcevska, Vesna; Tallet, Susan; Schneiderman, Gerald
This study comprehensively explored parental bereavement and adjustment at 6 months post-loss due to childhood cancer. Interviews were conducted with 18 mothers and 13 fathers. Interviews were transcribed verbatim and analyzed based on qualitative methodology. A model describing early parental bereavement and adaptation emerged with 3 domains:…
Giugliano, Pasquale; Massoni, Francesco; Crisci, Antonello; Ricci, Serafino
Lesions of the digestive tract due to barotrauma resulting from compressed air application are not common, are rarely lethal, and largely affect the sigmoid and descending colon. Moreover, their pathogenic mechanism is a topic of discussion because these lesions have multiple characteristics. Here, the authors describe an autoptic case of death from lesions of the ascending and transverse segments, with perforations and bleeding suffusions as well as ischemic areas covered the colonic wall that was extremely thinned, congested, and hemorrhagic, with considerable flattening leading to disappearance of the mucosal folds and with numerous petechial hemorrhages. The pathological framework of lung congestion made it possible to identify the mechanism responsible for this death as depletion of the heart's pumping function, which contributed significantly to the acute respiratory failure due to respiratory distress as well as to reduced mobility of the diaphragm due to intestinal distension. Acute heart failure played an important role in this death. © 2016 American Academy of Forensic Sciences.
... Customs Broker Licenses Due to Death of the License Holder AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: Customs broker license cancellation due to death of the broker... without prejudice due to the death of the license holders. SUPPLEMENTARY INFORMATION: Notice is hereby...
Ruszkiewicz, A; de Boer, B; Robertson, S
Two cases are reported representing opposite ends of the spectrum of death as a result of carbon monoxide poisoning from car exhaust fumes. In one case, a women was reported to be found dead in bed early in the morning by her husband. The cause of her death, established by autopsy, was carbon monoxide poisoning. Toxicology examination indicated a car engine as the possible source of carbon monoxide. The mode of administration was never established. In the second case, a women was found in a car located in her garage with a hose leading from the exhaust pipe to the interior of the sealed vehicle. Autopsy revealed negligible carboxyhemoglobin saturation of the blood, bilateral infarction of the globus pallidus, and extensive bronchopneumonia. It was concluded that inhalation of carbon monoxide resulted in sublethal hypoxia with subsequent exhalation of carbon monoxide and a delayed death.
Pridemore, William Alex; Chamlin, Mitchell B; Kaylen, Maria T; Andreev, Evgeny
To determine the impact of a suite of 2006 Russian alcohol control policies on deaths due to traffic accidents in the country. We used autoregressive integrated moving average (ARIMA) interrupted time-series techniques to model the impact of the intervention on the outcome series. The time-series began in January 2000 and ended in December 2010. The alcohol policy was implemented in January 2006, providing 132 monthly observations in the outcome series, with 72 months of pre-intervention data and 60 months of post-intervention data. The outcome variables were the monthly number of male- and female-specific deaths of those aged 15+ years due to transport accidents in Russia. The 2006 set of alcohol policies had no impact on female deaths due to traffic accidents (ω0 = -50.31, P = 0.27). However, the intervention model revealed an immediate and sustained monthly decrease of 203 deaths due to transport accidents for males (ω0 = -203.40, P = 0.04), representing an 11% reduction relative to pre-intervention levels. The implementation of the suite of 2006 Russian alcohol control policies is partially responsible for saving more than 2400 male lives annually that would otherwise have been lost to traffic accidents. © 2013 Society for the Study of Addiction.
Madanat-Harjuoja, Laura-Maria; Lähteenmäki, Päivi M; Dyba, Tadeusz; Gissler, Mika; Boice, John D; Malila, Nea
Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.
Mendez, L C; Moraes, F Y; Fernandes, G Dos S; Weltman, E
Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Thousands of cancer patients requiring
... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...
... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...
... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...
Watanabe-Suzuki, K; Nozawa, H; Ishii, A; Seno, H; Suzuki, O
We report a rare case of death due to rescue using a power shovel. A 41-year-old female was accidentally buried alive by a landslide of the earth and sand upon working at a construction site. One of her colleagues started to save her using a power shovel. However, she was dug out dead at the spot about 10 min after the accident with marked head and face injuries. The autopsy disclosed that there was extensive laceration across the face and head with marked skull bone fractures. Around these injuries, extensive hemorrhage could be observed as a vital reaction. Asphyxial death had to be taken into consideration, because she was buried under the earth and sand for about 10 min; but we finally judged that the cause of her death was head injury by the power shovel inflicted during the attempted rescue.
Long, G.; Bakos, G.; Shires, P. K.; Gritter, L.; Crissman, J. W.; Harris, J. L.; Clymer, J. W.
Irreversible electroporation (IRE) has been shown to be an effective method of killing cells locally. In contrast to radiofrequency ablation, the mechanism by which cells are thought to die via IRE is the creation of pores in cell membranes, without substantial increase in tissue temperature. To determine the degree to which cell death is non-thermal, we evaluated IRE in porcine hepatocytes in vivo. Using pulse widths of 10μs, bursts of 3 kV square-wave pulses were applied through a custom probe to the liver of an anesthetized pig. Affected tissue was evaluated histologically via stainings of hematoxylin & eosin (H&E), nitroblue tetrazolium (NBT) to monitor cell respiration and TUNEL to gauge apoptosis. Temperature was measured during the application of electroporation, and heat transfer was modeled via finite element analysis. Cell death was calculated via Arrhenius kinetics. Four distinct zones were observed within the ring return electrode; heat-fixed tissue, coagulation, necrotic, and viable. The Arrhenius damage integral estimated complete cell death only in the first zone, where the temperature exceeded 70°C, and partial or no cell death in the other zones, where maximum temperature was approximately 45°C. Except for a limited area near the electrode tip, cell death in IRE is predominantly due to a non-thermal mechanism. PMID:24000980
Kara, I; Pampal, H K; Yildirim, F; Dilekoz, E; Emmez, G; U, F P; Kocabiyik, M; Demirel, C B
Increased intracranial pressure following trauma and subsequent possible development of brain death are important factors for morbidity and mortality due to ischemic changes. We aimed to establish the role of ischemic modified albumin (IMA) in the early diagnosis of the process, starting with increased intracranial pressure and ending with brain death. Eighteen Wistar-Albino rats were divided into three groups; control (CG, n = 6), increased intracranial pressure (ICPG, n = 6), and brain death (BDG, n = 6). Intracranial pressure elevation and brain death were constituted with the inflation of a balloon of a Fogarty catheter in the epidural space. In all three groups, blood samples were drawn before the procedure, and at minutes 150 and 240 for IMA and malondialdehyde (MDA) analysis. Serum IMA levels at 150 and 240 minutes were higher in ICPG than in CG (p < 0.05). IMA levels were similar in ICPG and BDG. Serum MDA levels at 150 and 240 minutes increased in ICPG and BDG groups compared to CG (p < 0.05). MDA levels were similar in ICP and BD groups. IMA should be considered as a biochemical parameter in the process starting from increased intracranial pressure elevation and ending at brain death (Tab. 3, Fig. 5, Ref. 31).
Barrera, Maru; O'Connor, Kathleen; D'Agostino, Norma Mammone; Spencer, Lynlee; Nicholas, David; Jovcevska, Vesna; Tallet, Susan; Schneiderman, Gerald
This study comprehensively explored parental bereavement and adjustment at 6 months post-loss due to childhood cancer. Interviews were conducted with 18 mothers and 13 fathers. Interviews were transcribed verbatim and analyzed based on qualitative methodology. A model describing early parental bereavement and adaptation emerged with 3 domains: (1) Perception of the Child, describing bereavement and adjustment prior to and after the loss; (2) Perception of Others, including relationships with partners, surviving children, and their social network; and (3) Perception of the World, exploring parents' perceived meanings of the experience in the context of their worldview. Domains are illustrated by quotes. Profiles of parental bereavement emerged.
Basu, Millie Nguyen; Johnsen, Iben Birgit Gade; Wehberg, Sonja; Sørensen, Rikke Guldberg; Barington, Torben; Nørgård, Bente Mertz
We examined the causes of death amongst full term stillbirths and early neonatal deaths. Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.
Cubí-Mollá, Patricia; Peña-Longobardo, Luz María; Casal, Bruno; Rivera, Berta; Oliva-Moreno, Juan
To estimate the years of potential life lost, years of potential productive life lost and the labor productivity losses attributable to premature deaths due to traffic injuries between 2002 and 2012 in Spain. Several statistical sources were combined (Spanish Registry of Deaths, Labor Force Survey and Wage Structure Survey) to develop a simulation model based on the human capital approach. This model allowed us to estimate the loss of labor productivity caused by premature deaths following traffic injuries from 2002 to 2012. In addition, mortality tables with life expectancy estimates were used to compute years of potential life lost and years of potential productive life lost. The estimated loss of labour productivity caused by fatal traffic injuries between 2002 and 2012 in Spain amounted to 9,521 million euros (baseline year 2012). The aggregate number of years of potential life lost in the period amounted to 1,433,103, whereas the years of potential productive life lost amounted to 875,729. Throughout the period analyzed, labor productivity losses and years of life lost diminished substantially. Labor productivity losses due to fatal traffic injuries decreased throughout the period analyzed. Nevertheless, the cumulative loss was alarmingly high. Estimation of the economic impact of health problems can complement conventional indicators of distinct dimensions and be used to support public policy making. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.
Binder, Nadine; Herrnböck, Anne-Sophie; Schumacher, Martin
In clinical and epidemiological studies information on the primary outcome of interest, that is, the disease status, is usually collected at a limited number of follow-up visits. The disease status can often only be retrieved retrospectively in individuals who are alive at follow-up, but will be missing for those who died before. Right-censoring the death cases at the last visit (ad-hoc analysis) yields biased hazard ratio estimates of a potential risk factor, and the bias can be substantial and occur in either direction. In this work, we investigate three different approaches that use the same likelihood contributions derived from an illness-death multistate model in order to more adequately estimate the hazard ratio by including the death cases into the analysis: a parametric approach, a penalized likelihood approach, and an imputation-based approach. We investigate to which extent these approaches allow for an unbiased regression analysis by evaluating their performance in simulation studies and on a real data example. In doing so, we use the full cohort with complete illness-death data as reference and artificially induce missing information due to death by setting discrete follow-up visits. Compared to an ad-hoc analysis, all considered approaches provide less biased or even unbiased results, depending on the situation studied. In the real data example, the parametric approach is seen to be too restrictive, whereas the imputation-based approach could almost reconstruct the original event history information. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Channa Perera, S D; Pollanen, Michael S
We report a case of vaso-occlusive sickle cell crisis in a young schizophrenic man with undiagnosed sickle cell trait who was restrained. Prior to being restrained he had locked himself in his apartment for two days without food or water. He was subsequently restrained, and transferred to hospital while handcuffed to the stretcher. He died suddenly during restraint. At autopsy, there was acute vaso-occlusive sickle cell crisis associated with hypernatremic dehydration. There were no injuries present. We conclude that the death was due to vaso-occlusive sickle cell crisis secondary to dehydration. It is important for the forensic pathologist to remember that death may occur suddenly during restraint from an unexpected mechanism other than excited delirium leading to cardiac arrhythmia or restraint asphyxia.
Terzich, M; Quarles, C; Goodwin, M A; Brown, J
The purposes of this study were to determine the effect of Poultry Litter Treatment (PLT) on levels of litter moisture, litter nitrogen, atmospheric ammonia, and death due to ascites. Data were collected from chicks raised in containment conditions that resembled commercial settings. The ascites death rate (5.9%) in broiler chicks on PLT-treated litter was significantly (chi 2 = 15.5, df = 1, P = 0.0001) lower than that (31.5%) in broiler chicks raised on untreated litter. Likewise, atmospheric ammonia levels in pens that had been treated with PLT were significantly (P < 0.05) lower than those in pens that received no treatment. Under the conditions of the present study, litter moisture and litter nitrogen levels were not different (P > 0.05) among treatments at any sample interval.
... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Notice of Cancellation of Customs Broker Licenses Due to Death of the License Holder AGENCY: U.S. Customs and Border Protection, U.S... broker licenses and any and all permits have been cancelled due to the death of the broker: Name License...
... DEPARTMENT OF HOMELAND SECURITY Customs and Border Protection Notice of Cancellation of Customs Broker Licenses Due to Death of the License Holder AGENCY: U.S. Customs and Border Protection, U.S... broker licenses and any and all permits have been cancelled due to the death of the broker: License Name...
... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Notice of Cancellation of Customs Broker Licenses Due to Death of the License Holder AGENCY: U.S. Customs and Border Protection, DHS... have been cancelled due to the death of the broker: Name License No. Port name Leandro U. Guevarra...
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Behera, Chittaranjan; Bodwal, Jatin; Sikary, Asit K; Chauhan, Mohit Singh; Bijarnia, Manjul
In an air-conditioning system, the compressor is a large electric pump that pressurizes the refrigerant gas as part of the process of turning it back into a liquid. The explosion of an air conditioner (AC) compressor is an uncommon event, and immediate death resulted from the blast effect is not reported in forensic literature. We report three such cases in which young AC mechanics were killed on the spot due to compressor blast, while repairing the domestic split AC unit. The autopsy findings, the circumstances leading to the explosion of the compressor, are discussed in this study. © 2016 American Academy of Forensic Sciences.
Leitner, Jordan B; Hehman, Eric; Ayduk, Ozlem; Mendoza-Denton, Rodolfo
Perceptions of racial bias have been linked to poorer circulatory health among Blacks compared with Whites. However, little is known about whether Whites' actual racial bias contributes to this racial disparity in health. We compiled racial-bias data from 1,391,632 Whites and examined whether racial bias in a given county predicted Black-White disparities in circulatory-disease risk (access to health care, diagnosis of a circulatory disease; Study 1) and circulatory-disease-related death rate (Study 2) in the same county. Results revealed that in counties where Whites reported greater racial bias, Blacks (but not Whites) reported decreased access to health care (Study 1). Furthermore, in counties where Whites reported greater racial bias, both Blacks and Whites showed increased death rates due to circulatory diseases, but this relationship was stronger for Blacks than for Whites (Study 2). These results indicate that racial disparities in risk of circulatory disease and in circulatory-disease-related death rate are more pronounced in communities where Whites harbor more explicit racial bias.
Barranco, Rosario; Lo Pinto, Sara; Cuccì, Maria; Caputo, Fiorella; Fossati, Francesca; Fraternali Orcioni, Giulio; Ventura, Francesco
Cysts of the pineal gland are benign lesions. Often asymptomatic, in the majority of cases they are discovered incidentally during brain magnetic resonance imaging or autopsy. Sporadically, however, they may cause such symptoms as chronic headache, loss of consciousness, corticospinal and sensory impairment, and, in some cases, even sudden death. A 45-year-old woman, in apparently good health, collapsed and died suddenly, after reaching orgasm while engaged in sexual intercourse. According to the circumstantial account of her relatives, the woman suffered from severe headaches, which were exacerbated by certain types of physical strain, such as sexual activity. Postmortem examination revealed no external injuries or internal diseases except for a cystic lesion of the pineal gland. Microscopically, the wall of the cyst consisted of a layer of glial tissue surrounded by an area of pineal elements. A complete forensic approach concluded that the cause of death was fatal cardiorespiratory failure resulting from midbrain compression due to a nonneoplastic pineal gland cyst, exacerbated by sexual activity. In this case, the intracranial pressure increase, secondary to Valsalva maneuver during climax, may further aggravate compression on the brainstem, thus concurring to determine the death.
Chaudhari, Vinod Ashok; Ghodake, Dattatray G; Kharat, Rajesh D
Death due to a head-down position with hyperflexion of the neck is a rare event. A person accidentally falling into a narrow space and remaining in an upside-down position with no timely recovery may experience positional or postural asphyxia. It is a critical condition arising out of particular body positions, leading to mechanical obstruction of respiration. The precipitating factors are intoxication due to alcohol, drugs, obesity, psychiatric illnesses, and injuries. A 30-year-old unmarried woman, weighing 82 kg and with a body mass index of 31.24, was found in a narrow space between the bed and the wall in a naked state and in a head-down position with hyperflexion of the neck. The distribution of lividity was consistent with the position of the body at the scene. Blood was oozing from the mouth and nostrils, and signs of asphyxia were present. The toxicological analyses of viscera, blood, and urine were negative for alcohol, drugs, and poisons. Glucose levels in the blood (86 mg/dL) as well as urine and vitreous humor levels (68 mg/dL) were within normal limits. On microscopic examination, there were no findings of coronary atherosclerosis, whereas the brain and lung were edematous. After meticulous examination, we ruled out sexual assault, autoerotic asphyxia, epilepsy, psychiatric illness, diabetes, toxicity, and coronary artery disease. Death was attributed to the accidental fall of the obese individual being stuck in a narrow space, resulting in positional asphyxia. It is imperative to recognize the precipitating or risk factors before labeling positional asphyxia as a cause of death.
Slaughter, Virginia; Lyons, Michelle
Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which "life" or "life-force" is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death.…
Lemez, S; Wattie, N; Baker, J
The objective of the study was to examine mortality trends and causes of death among professional athletes from the four major sports in North America who died during their playing careers. 205 deceased athletes who were registered as active when they died from the National Basketball Association (NBA), National Football League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were examined. Results were compared with the Canadian and U.S. general population. The leading causes of death in players reflected the leading causes of death in the Canadian and U.S. general population (i.e., car accidents). Descriptively, NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75, 95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA players had a significantly higher likelihood of dying from a cardiac-related illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to team size. Overall, death in active athletes is low. Out of 53 400 athletes who have historically played in the four leagues, only 205 died while active (0.38%). Future examinations into the trends and causes of mortality in elite athlete populations will create a better understanding of health-related risks in elite sport. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
de Araújo, Valdelaine Etelvina Miranda; Morais, Maria Helena Franco; Reis, Ilka Afonso; Rabello, Ana; Carneiro, Mariângela
Background In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). Methodology The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002–2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. Principal Findings Model 1 (period 2002–2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007–2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3–6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2–4.8) and age ≥60 years (OR 2.5; 95%CI 1.5–4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2–10.3), other associated infections (OR 3.2; 95%CI 1.3–7.8), jaundice (OR 10.1; 95%CI 3.7–27.2) and age ≥60 years (OR 3.1; 95%CI 1.4–7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). Conclusions Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute
Watanabe, Shinya; Nagai, Takashi
To obtain the data concerning death losses due to stillbirth, neonatal death and diseases in cloned cattle derived from somatic cell nuclear transfer (SCNT) and their progeny produced by Japanese institutions, a nationwide survey was carried out in July-August, 2006. As a result, lifetime data concerning 482 SCNT cattle (97.5% of cattle produced in the country at that time) and 202 progeny of SCNT cattle were accumulated and the death loss of these cattle was analyzed. Although 1/3 of delivered SCNT calves died during the perinatal period due to stillbirth and neonatal death, incidence of death loss due to diseases in SCNT cattle surviving more than 200 days after birth seems to be the same as these in conventionally bred cattle. In contrast, progeny of SCNT cattle showed the same level in death loss as observed in conventionally bred cattle throughout their lifetime. These results suggest that robust health would be expected in SCNT cattle surviving to adulthood and their progeny.
Arslan, M N; Kertmen, Ç; Esen Melez, I; Melez, D O
Traumatic asphyxia is a rare clinical syndrome usually caused by sudden and severe thoracic and/or thoracoabdominal compression. It presents with craniofacial cyanosis, petechiae, and subconjunctival haemorrhages. The present study employed a postmortem retrospective methodology to analyse autopsy findings and accompanying injuries in cases of death due to traumatic asphyxia. Four years of case files from a morgue department at a forensic medicine institute were searched and 53 cases of lethal traumatic asphyxia were found. These cases were then classified into groups and compared using the Injury Severity Score (ISS) and New Injury Severity Score (NISS) indices to measure trauma. The individuals had died due to occupational (n = 28; 52.8%), farm (n = 10; 18.9%), traffic (n = 9; 17.0%) or household (n = 6; 11.3%) accidents. At the external examination, conjunctival petechiae (60.4%) and petechiae on the face/neck (52.8%); at the autopsy, subpleural petechiae (58.5%) and petrous ridge hemorrgahe (without skull base fracture) (56.6%) were the most common findings. A finding of petrous ridge hemorrgahe was very common in the cases without any accompanying injuries (Group A in which mean Injury Severity Score was 0.83 ± 0.98). Traumatic asphyxia is usually suspected from the given circumstances before an autosopy is performed. In cases without hospitalisation, any of the following signs may lead the physician to diagnose traumatic asphyxia as the cause of death: petechiae on the upper parts of the body and conjunctiva, petechiae on serous membranes (including subpleural regions), signs of petrous ridge haemorrhage without skull base fracture. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Salim, Mubadda A.; Alpert, Bruce S.
Physicians who work with athletes play an important role in preventing sudden death related to physical activity in people who have Marfan syndrome. Flagging those who have the physical stigmata and listening for certain cardiac auscultation sounds are early diagnostic keys that can help prevent deaths. People with Marfan syndrome should be…
Doberentz, E; Genneper, L; Böker, D; Lignitz, E; Madea, B
The expression of heat shock proteins (hsp) increases in case of variable types of endogenous and exogenous cellular stress, as for example thermal stress. Immunohistochemical staining with hsp antibodies can visualize these stress proteins. Fifty-three cases of death due to heat and a control group of 100 deaths without any antemortem thermic stress were examined regarding hsp27 and hsp70 expression in myocardial, pulmonary, and renal tissues. The results revealed a correlation between hsp expression, survival time, and cause of death. In cases of death due to fire, the expression of hsp is more extensive than in the control group, especially in pulmonary and renal tissues. The immunohistochemical investigation of an hsp expression can support the proof of vitality in cases of death related to fire.
López, Cristina; Masiá, Mar; Padilla, Sergio; Aquilino, Ana; Bas, Cristina; Gutiérrez, Félix
The objective of this study was to analyze the deaths caused by non-AIDS diseases in a cohort of HIV-infected patients treated between 1998 and 2011. Information on the causes of death was collected retrospectively, and then classified according to the deaths code (CoDe) algorithm. Patient characteristics and causes of death were compared for two periods: 1998-2004 and 2005-2011. A total of 159 out of the 1070 patients cared for in study period died, 56 (35%) due to AIDS events and 86 (54%) due to non-AIDS events (NAEs); in 17 (11%) the cause of death could not be determined. Overall, the main causes of death were infections (32%), cancer (17%), and unnatural deaths (17%). There was lower mortality from AIDS-related conditions during the second period (18.5% vs 47%; P<.001) and higher mortality from NAEs (68% vs 45%; P=.006). There was a very sharp increase in non-AIDS-defining cancers (18.5% vs 2.1%, p=001), and increased deaths from cardiovascular disease (9.2% vs 2.1%, P=.06). Patients who died in the second period were older, and had a better immunological and virological status at cohort entry and before death. They received antiretroviral therapy (ART) more often and were more often virologically suppressed before death (61.5% vs 24%; P=.001). Non-AIDS-defining cancers, unnatural deaths, and cardiovascular diseases are now major causes of death in patients with HIV. In recent years the majority of deceased patients are on ART and with virological suppression. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Ellis, Jennifer A; Mays, Darren; Huang, An-Tsun
Abstract Objective To evaluate the global impact of adopting highest-level MPOWER tobacco control policies in different countries and territories from 2007 to 2010. Methods Policy effect sizes based on previously-validated SimSmoke models were applied to determine the reduction in the number of smokers as a result of policy adoption during this period. Based on previous research suggesting that half of all smokers die from smoking, we also derived the estimated smoking-attributable deaths (SADs) averted due to MPOWER policy implementation. The results from use of this simple yet powerful method are consistent with those predicted by using previously validated SimSmoke models. Findings In total, 41 countries adopted at least one highest-level MPOWER policy between 2007 and 2010. As a result of all policies adopted during this period, the number of smokers is estimated to have dropped by 14.8 million, with a total of 7.4 million SADs averted. The largest number of SADs was averted as a result of increased cigarette taxes (3.5 million), smoke-free air laws (2.5 million), health warnings (700 000), cessation treatments (380 000), and bans on tobacco marketing (306 000). Conclusion From 2007 to 2010, 41 countries and territories took action that will collectively prevent nearly 7.5 million smoking-related deaths globally. These findings demonstrate the magnitude of the actions already taken by countries and underscore the potential for millions of additional lives to be saved with continued adoption of MPOWER policies. PMID:23825878
Rana, Abbas; Kaplan, Bruce; Jie, Tun; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G
The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality. © 2013 John Wiley & Sons A/S.
Mauritz, Walter; Brazinova, Alexandra; Majdan, Marek; Rehorcikova, Veronika; Leitgeb, Johannes
To investigate changes in TBI mortality in Austria during 1980-2012 and to identify causes for these changes. Statistik Austria provided data (from death certificates) on all TBI deaths from January 1980-December 2012. Data included year/month of death, age, sex, residency of the cases and mechanism of accident. Data regarding the size of the age groups was obtained from Statistik Austria. Mortality rates (MR; deaths/10(5) population/year) were calculated for male vs. female patients and for different age groups. Changes in mechanisms of TBI were evaluated. The MR decreased from 28.1 to 11.8 deaths/10(5) population/year. Traffic-related TBI deaths decreased from 62% to 9%. This caused a significant decrease in TBI deaths in younger age groups. Fall-related TBI deaths (mostly geriatric cases) remained unchanged. Falls became the leading cause; its rate increased from 22% to 64% of all TBI deaths. Thus, the mean age of fatal TBI cases increased by 20 years and the rate of cases aged <60 years decreased from 71% to 28%. Another important cause was suicide by firearms; its rate increased from 10% to 23% of all TBI deaths. These findings warrant better prevention of falls in the elderly and of suicides.
Fujisawa, Rina; Shibuya, Hitoshi; Harata, Naoki; Yuasa-Nakagawa, Keiko; Toda, Kazuma; Hayashi, Keiji
Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.
Hayashizaki, Yoshie; Usui, Kiyotaka; Moriya, Takuya; Hashiyada, Masaki; Usui, Akihito; Hosokai, Yoshiyuki; Kawasumi, Yusuke; Saito, Haruo; Funayama, Masato
A female infant was found unresponsive at home. The mother alleged that she delivered the baby at home 13 days prior to the death. The mother did not have any prenatal examinations during the pregnancy and the infant was not examined by a doctor until death. The autopsy revealed that the cause of death was hypoplastic left heart syndrome (HLHS) and the infant's chest showed bilateral breast enlargement. Forensic pathologists may encounter very rare pathological findings with unexpected infant deaths. Some, like HLHS, are serious congenital heart defects related to the cause of death, and others are unique phenomena unrelated to the cause of death such as breast swelling and discharge called "witch's milk." In this case, we observed both findings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Spoonamore, Katherine G; Ware, Stephanie M
Sudden cardiac death due to heritable ventricular arrhythmias is an important cause of mortality, especially in young healthy individuals. The identification of the genetic basis of Mendelian diseases associated with arrhythmia has allowed the integration of this information into the diagnosis and clinical management of patients and at-risk family members. The rapid expansion of genetic testing options and the increasing complexity involved in the interpretation of results creates unique opportunities and challenges. There is a need for competency to incorporate genetics into clinical management and to provide appropriate family-based risk assessment and information. In addition, disease-specific genetic knowledge is required to order and correctly interpret and apply genetic testing results. Importantly, genetic diagnosis has a critical role in the risk stratification and clinical management of family members. This review summarizes the approach to genetic counseling and genetic testing for inherited arrhythmias and highlights specific genetic principles that apply to long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Cupper, Matthew L.; Duncan, Jacqui
The Tedford subfossil locality at Lake Menindee preserves a diverse assemblage of marsupials, monotremes and placental rodents. Of the 38 mammal taxa recorded at the site, almost a third are of extinct megafauna. Some of the bones are articulated or semi-articulated and include almost complete skeletons, indicating that aeolian sediments rapidly buried the animals following death. New optical ages show the site dates to the early part of the last glacial (55,700 ± 1300 yr weighted mean age). This is close to the 51,200-39,800 yr Australia-wide extinction age for megafauna suggested by Roberts et al. [2001, Science 292:1888-1892], but like all previous researchers, we cannot conclusively determine whether humans were implicated in the deaths of the animals. Although an intrusive hearth at the site dating to 45,100 ± 1400 yr ago is the oldest evidence of human occupation of the Darling River, no artifacts were identified in situ within the sub-fossil-bearing unit. Non-anthropogenic causes, such as natural senescence or ecosystem stress due to climatic aridity, probably explain the mortality of the faunal assemblage at Lake Menindee.
Umarova, Gulmira; Mamyrbayev, Аrstan; Bermagambetova, Saule; Baspakova, Akmaral; Satybaldieva, Umyt; Sabyrakhmetova, Valentina; Abilov, Talgar; Sultanova, Gulnar; Uraz, Raisa
Objective: The dynamics of morbidity, disability and death rates due to malignant neoplasms in the population in Uralsk city of the Republic of Kazakhstan were studied for 2011-2015, with a focus on age and sex, as well as tumor location. Methods: Statistics for total morbidity, primary disability and mortality from cancer in the adult population of the city of Uralsk for 2011-2015 were calculated per 100 thousand. Estimation of morbidity was based on data from form - №12 «Report on the number of diseases registered in patients living in the area of health care organizations and patient population under medical observation”. Evaluation of primary disability was based on form №7 «The distribution of newly recognized disabled by disease class, age, sex and disability groups” for 2011-2015 in Ural city and analysis of cancer was carried out using annual form 7 “Report on the sick, and diseases of malignant neoplasms”. Result: The most common localizations of cancer were the trachea, bronchi, lungs, stomach and mammary glands. High death rates were noted for patients with cancer of the trachea, bronchi, lung, as compared to stomach and esophagus. Conclusion: The results of our investigation and data in the literature indicate that regional characteristics influence the impact of risk factors associated with cancer. An unfavorable environmental background contributes to ill health of urban populations, contributing to development of cancer. Moreover behavioral risk factors are very important, such as smoking, alcohol drinking, and an unhealthy diet. All these factors require urgent adoption of a package of measures for prevention, early detection and timely treatment. Detailed study of cancer is necessary to develop national programs and activities for prevention and control. Creative Commons Attribution License
Hardelid, Pia; Davey, Jonathan; Dattani, Nirupa; Gilbert, Ruth
Background Injuries are an increasingly important cause of death in children worldwide, yet injury mortality is highly preventable. Determining patterns and trends in child injury mortality can identify groups at particularly high risk. We compare trends in child deaths due to injury in four UK countries, between 1980 and 2010. Methods We obtained information from death certificates on all deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and resident in England, Scotland, Wales or Northern Ireland. Injury deaths were defined by an external cause code recorded as the underlying cause of death. Injury mortality rates were analysed by type of injury, country of residence, age group, sex and time period. Results Child mortality due to injury has declined in all countries of the UK. England consistently experienced the lowest mortality rate throughout the study period. For children aged 10 to 18 years, differences between countries in mortality rates increased during the study period. Inter-country differences were largest for boys aged 10 to 18 years with mortality rate ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91) for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England (the baseline) in 2006–10. The decline in mortality due to injury was accounted for by a decline in unintentional injuries. For older children, no declines were observed for deaths caused by self-harm, by assault or from undetermined intent in any UK country. Conclusion Whilst child deaths from injury have declined in all four UK countries, substantial differences in mortality rates remain between countries, particularly for older boys. This group stands to gain most from policy interventions to reduce deaths from injury in children. PMID:23874585
Husemoen, Lise Lotte N; Osler, Merete; Godtfredsen, Nina S; Prescott, Eva
Smoking is the most important single preventable cause of a variety of common diseases, and a considerable share of premature death is attributable to smoking. Although the effects of smoking on morbidity and mortality are widely recognized, little is known about the impact of smoking on early retirement due to chronic disease. The objective of the study is to determine the effects of smoking behaviour on early retirement due to permanent disability in a large sample of the general population. Follow-up study based on data from three longitudinal population studies conducted in the Copenhagen area. The final study population comprised 9,053 persons, 5,623 men and 3,430 women. Endpoint was grant of disability pension in the period 1980-1985. Baseline information was obtained from a self-administered questionnaire. Information about disability pensions was obtained from Statistics Denmark. Data analysis was performed by univariate and multiple logistic regression analyses. Smoking was found to be strongly associated with the risk of being granted a disability pension after adjustment for various confounders. The risk increased with daily consumption reaching a maximum odds ratio of 5.66 (1.88-17.00) and 5.61 (2.11-14.92) in heavily smoking men and women, respectively, who were below age 60. Smokers are at considerably higher risk of early retirement due to chronic disease. In addition to the burden of disease, this leads to social and economic problems for the individual and has a significant economic impact on society.
Rodríguez-Otero, Paula; Mateos, María Victoria; Martínez-López, Joaquín; Martín-Calvo, Nerea; Hernández, Miguel-Teodoro; Ocio, Enrique M; Rosiñol, Laura; Martínez, Rafael; Teruel, Ana-Isabel; Gutiérrez, Norma C; Bargay, Joan; Bengoechea, Enrique; González, Yolanda; de Oteyza, Jaime Pérez; Gironella, Mercedes; Encinas, Cristina; Martín, Jesús; Cabrera, Carmen; Palomera, Luis; de Arriba, Felipe; Cedena, María Teresa; Paiva, Bruno; Puig, Noemí; Oriol, Albert; Bladé, Joan; Lahuerta, Juan José; San Miguel, Jesús F
Although survival of elderly myeloma patients has significantly improved there is still a subset of patients who, despite being fit and achieving optimal responses, will die within 2 years of diagnosis due to myeloma progression. The objective of this study was to define a scoring prognostic index to identify this group of patients. We have evaluated the outcome of 490 newly diagnosed elderly myeloma patients included in two Spanish trials (GEM2005-GEM2010). Sixty-eight patients (13.8%) died within 2 years of diagnosis (early deaths) due to myeloma progression. Our study shows that the use of simple scoring model based on 4 widely available markers (elevated LDH, ISS 3, high risk CA or >75 years) can contribute to identify up-front these patients. Moreover, unsustained response (<6 months duration) emerged as one important predictor of early myeloma-related mortality associated with a significant increase in the risk of death related to myeloma progression. The identification of these patients at high risk of early death is relevant for innovative trials aiming to maintain the depth of first response, since many of them will not receive subsequent lines of therapy.
Almeida, Milena Cristina da Silva; Gomes, Camila de Moraes Santos; Nascimento, Luiz Fernando Costa
Alzheimer's disease is a common cause of dementia and identifying possible spatial patterns of mortality due to this disease may enable preventive actions. The objective of this study was to identify spatial distribution patterns of mortality due to Alzheimer's disease in the state of São Paulo. Ecological and exploratory study conducted in all municipalities in the state of São Paulo. Data on Alzheimer's disease mortality in the state of São Paulo between 2004 and 2009 were obtained from DATASUS (the Department of Informatics in the Brazilian Ministry of Health). Death rates per 100,000 inhabitants were then calculated and spatial analysis was performed by constructing a death rate map, global Moran index and local Moran index, which were used to obtain the Moran map. The kernel technique was also applied. The Terra View 4.0.0 software was used. 13,030 deaths due to Alzheimer were reported in the state of São Paulo (rate of 5.33 deaths/100,000 inhabitants). São José do Rio Preto, Ribeirão Preto, Bauru and Araçatuba had higher rates. The Moran index was I = 0.085 (P < 0.002). The Moran map identified 42 municipalities that merit intervention and the kernel estimator identified a high density of deaths in the northwestern region of the state. Higher densities of deaths due to Alzheimer were concentrated more to the north and northwest of the state of São Paulo. It was possible to identify municipalities that have priority for interventions to reduce the death rates due to this disease.
Forrester, Joseph D; Kugeler, Kiersten J; Perea, Anna E; Pastula, Daniel M; Mead, Paul S
Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.
Bandele, E.O.; Olude, I.O.
An analysis was made of deaths from tuberculosis in the Lagos University Teaching Hospital from 1976 to 1980. Of the 320 patients assessed, 240 were determined to have died from tuberculosis. Tuberculous meningitis was the main cause of death. Forty-two percent of the deaths occurred in the age group of 0 to 10 years old, and 47.5 percent of the patients died within one week of diagnosis. Potentially avoidable factors contributing to death include late reporting by patients to medical personnel, lack of bacillus of Calmette and Guerin (BCG) vaccine, irregular taking of medications by patients, and late referral of patients to specialized hospitals. There is a need for improved education of patients and medical personnel about the management of tuberculosis in Lagos. PMID:4046063
Mordovsky, E A; Soloviev, A G; Sannikov, A L
To reveal the specific features of marital status and educational level in people who have died of leading circulatory diseases (CDs) in Arkhangelsk in relation to the place of death, alcohol anamnesis, and demographic characteristics (gender, life span). Materials and methods. Data on the diagnosed underlying cause of death, marital status, educational level, and place of death were copied from 4137 medical death certificates (form 106/y-08) of all those who had died in Arkhangelsk in 1 July to 30 June 2012. Data on patients registered at a psychoneurology dispensary as having a diagnosis of alcohol-induced mental and behavioral disorders (F10) were copied. The data were statistically processed using the procedures of binary and multinomial logistic regression analysis. A total of 2101 people (50.8% of the total number of deaths) died of CDs (ICD-10 Class IX) in the study period. Male sex and a compromised alcohol anamnesis were associated with untimely death (less than 60 years of age) from acute conditions in ICD-10 Class IX. Male sex, a compromised alcohol anamnesis, and negative characteristics of marital and educational statuses were related to untimely death from chronic conditions in ICD-10 Class IX. Single people having a lower educational level and a compromised alcohol anamnesis statistically more frequently died of CDs outside a health care facility. The results of the investigation suggest that there is inequality in the excess risk of death from leading CDs among the representatives of different social population groups in Arkhangelsk, as well as nonequivalence in their interaction with the public health system.
Richardson, Joseph B.; Brown, Jerry; Van Brakle, Michelle
Quantitative studies have uncovered factors associated with early violent death among youth offenders detained in the juvenile justice system, but little is known about the contextual factors associated with pathways to early violent death among youths detained in adult jails. We interviewed young Black male serious violent youth offenders detained in an adult jail to understand their experience of violence. Their narratives reveal how the code of the street, informal rules that govern interpersonal violence among poor inner-city Black male youths, increases the likelihood of violent victimization. Youth offenders detained in adult jails have the lowest rate of service provision among all jail populations. We have addressed how services for youth offenders can be improved to reduce the pathways to early violent death. PMID:23678923
Richardson, Joseph B; Brown, Jerry; Van Brakle, Michelle
Quantitative studies have uncovered factors associated with early violent death among youth offenders detained in the juvenile justice system, but little is known about the contextual factors associated with pathways to early violent death among youths detained in adult jails. We interviewed young Black male serious violent youth offenders detained in an adult jail to understand their experience of violence. Their narratives reveal how the code of the street, informal rules that govern interpersonal violence among poor inner-city Black male youths, increases the likelihood of violent victimization. Youth offenders detained in adult jails have the lowest rate of service provision among all jail populations. We have addressed how services for youth offenders can be improved to reduce the pathways to early violent death.
Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki
We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.
Fais, Paolo; Pigaiani, Nicola; Cecchetto, Giovanni; Montisci, Massimo; Gottardo, Rossella; Viel, Guido; Pascali, Jennifer Paola; Tagliaro, Franco
Many homemade tamper processes of medical codeine formulations are available on selected "forums" on the Internet, where recreational codeine users claim to be able to purify codeine by removing additives, such as acetaminophen, to avoid or limit adverse effects. In this work, it is reported and discussed a fatal case of codeine intoxication. The findings of objects such as jars, filters, and tablets, and amounts of unknown liquid material at the death scene investigation suggested a fatal codeine intoxication after the tampering procedure called "cold water extraction." Toxicological results obtained from the analysis of both the nonbiological material and the body fluids of the decedent integrated with the information collected at the death scene investigation confirmed the above-mentioned hypothesis. This report underlines the importance of a tight interconnection between criminalistics and legal medicine to strengthen the identification of the cause of death and the reconstruction of the event. © 2017 American Academy of Forensic Sciences.
Yilmaz, Riza; Yilmaz, Eyyüp; Ozdemir, Veli; Can, Muhammet; Pakis, Isil; Piskin, Ibrahim E; Dokgoz, Halis; Ozer, Erdal; Numanoglu, Kemal V
Yellow phosphorus (YP) is a powerful protoplasmic poison used in the manufacturing of matches, pest poisons, firecrackers, firework cracker, lights for watches, military ammunition, and agriculture fertilizer. YP is extremely flammable and toxic and easily absorbed from the gastrointestinal tract. In this study, we examined childhood deaths from 1997 to 2012 resulting from the ingestion of firecrackers. The patients ranged from 2 to 15 years of age and were admitted to the hospital with a variety of symptoms. Those that presented with nausea, vomiting, and hypotension rapidly deteriorated and entered a coma. An autopsy was performed in all but one of the 16 cases reviewed. Macroscopically, the livers had a yellowish discoloration with petechial bleeding. Histopathologic examination revealed acute toxic hepatitis. In conclusion, these firecrackers are found in corner shops throughout Turkey, may cause death in children with little warning, and should be banned to prevent further deaths. © 2015 American Academy of Forensic Sciences.
Na, Joo-Young; Lee, Kyung-Hwa; Kim, Hyung-Seok; Park, Jong-Tae
Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.
Moreschi, Carlo; Da Broi, Ugo; Fanzutto, Antonia; Cividino, Sirio; Gubiani, Rino; Pergher, Gianfranco
Farm tractors are large, heavy, powerful vehicles with a high center of gravity. When driven carelessly on sloping, irregular, or slippery ground, tractors can overturn sideways and cause the death by crush asphyxia of the driver or passengers, especially if appropriate safety equipment is not fitted or used. The aim of this review is to focus on the diagnostic difficulties with which coroners and forensic pathologists have to cope when a confirmation of crush asphyxia after tractor side rollover is required by judicial authorities. Forensic investigations in such cases must involve the meticulous analysis of the death scene and the mechanical characteristics of the vehicle together with accurate postmortem and toxicological examination.
Abouk, Rahi; Grosse, Scott D; Ailes, Elizabeth C; Oster, Matthew E
In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after
Amancio, Camila Trolez; Nascimento, Luiz Fernando
Little has been discussed about the increased risk of stroke after exposure to air pollutants, particularly in Brazil. The mechanisms through which air pollution can influence occurrences of vascular events such as stroke are still poorly understood. The aim of this study was to estimate the association between exposure to some air pollutants and risk of death due to stroke. Ecological time series study with data from São José dos Campos, Brazil. Data on deaths due to stroke among individuals of all ages living in São José dos Campos and on particulate matter, sulfur dioxide and ozone were used. Statistical analysis was performed using a generalized additive model of Poisson regression with the Statistica software, in unipollutant and multipollutant models. The percentage increase in the risk of increased interquartile difference was calculated. There were 1,032 deaths due to stroke, ranging from 0 to 5 per day. The statistical significance of the exposure to particulate matter was ascertained in the unipollutant model and the importance of particulate matter and sulfur dioxide, in the multipollutant model. The increases in risk were 10% and 7%, for particulate matter and sulfur dioxide, respectively. It was possible to identify exposure to air pollutants as a risk factor for death due to stroke, even in a city with low levels of air pollution.
Lawn, Joy E; Mwansa-Kambafwile, Judith; Horta, Bernardo L; Barros, Fernando C; Cousens, Simon
Background ‘Kangaroo mother care’ (KMC) includes thermal care through continuous skin-to-skin contact, support for exclusive breastfeeding or other appropriate feeding, and early recognition/response to illness. Whilst increasingly accepted in both high- and low-income countries, a Cochrane review (2003) did not find evidence of KMC’s mortality benefit, and did not report neonatal-specific data. Objectives The objectives of this study were to review the evidence, and estimate the effect of KMC on neonatal mortality due to complications of preterm birth. Methods We conducted systematic reviews. Standardized abstraction tables were used and study quality assessed by adapted GRADE methodology. Meta-analyses were undertaken. Results We identified 15 studies reporting mortality and/or morbidity outcomes including nine randomized controlled trials (RCTs) and six observational studies all from low- or middle-income settings. Except one, all were hospital-based and included only babies of birth-weight <2000 g (assumed preterm). The one community-based trial had missing birthweight data, as well as other limitations and was excluded. Neonatal-specific data were supplied by two authors. Meta-analysis of three RCTs commencing KMC in the first week of life showed a significant reduction in neonatal mortality [relative risk (RR) 0.49, 95% confidence interval (CI) 0.29–0.82] compared with standard care. A meta-analysis of three observational studies also suggested significant mortality benefit (RR 0.68, 95% CI 0.58–0.79). Five RCTs suggested significant reductions in serious morbidity for babies <2000 g (RR 0.34, 95% CI 0.17–0.65). Conclusion This is the first published meta-analysis showing that KMC substantially reduces neonatal mortality amongst preterm babies (birth weight <2000 g) in hospital, and is highly effective in reducing severe morbidity, particularly from infection. However, KMC remains unavailable at-scale in most low-income countries. PMID:20348117
... at the time of death, if such miner is suffering or suffered from a chronic dust disease of the lung... Classification of the Pneumoconioses of the Union Internationale Contra Cancer/Cincinnati (1968) (which may be..., yields massive lesions in the lung; or (c) When diagnosed by means other than those specified in...
Twentieth-century tobacco control programs and policies were responsible for preventing more than 795,000 lung cancer deaths in the United States from 1975 through 2000. If all cigarette smoking in this country had ceased following the release of the firs
Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L; Golstein, Pierre
Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of "paddle" cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells.
Objective Whether bereaved relatives should be encouraged to view the body after a traumatic death is uncertain. This analysis of narrative interviews interprets people’s accounts of why and how they decided whether to view the body and their emotional reactions to this, immediately and at a later stage. Design In depth interviews with qualitative analysis. Participants A maximum variation sample of 80 people bereaved because of suicide or other traumatic death. Setting Most people were interviewed in their homes. Results For those who had the option, decisions about seeing the body varied. Some wanted someone else to identify the body, because they feared how it might look or preferred to remember their relative as they had been in life. Those who had wanted to see the body gave various reasons beyond the need to check identity. Some felt they ought to see the body. Others felt that the body had not lost its social identity, so wanted to make sure the loved one was “being cared for” or to say goodbye. Some people wanted to touch the body, in privacy, but the coroner sometimes allowed this only after the postmortem examination, which made relatives feel that the body had become police property. Seeing the body brought home the reality of death; it could be shocking or distressing, but, in this sample, few who did so said they regretted it. Conclusions Even after a traumatic death, relatives should have the opportunity to view the body, and time to decide which family member, if any, should identify remains. Officials should prepare relatives for what they might see, and explain any legal reasons why the body cannot be touched. Guidelines for professional practice must be sensitive to the needs and preferences of people bereaved by traumatic death. The way that relatives refer to the body can be a strong indication for professionals about whether the person who died retains a social identity for the bereaved. PMID:20435644
Mental diseases such as schizophrenia and depression put patients at risk for suicide. It is extremely important to understand that one way of preventing suicide is to determine the actual mental state of the individual. The purpose of this study was to analyze the true mental state of suicide victims reported in the vital statistics. This study investigated the vital statistics of 30,299 suicide victims in Japan in 2008. The use of these basic statistics for non-statistical purposes was approved by the Japanese Ministry of Health, Labour and Welfare. The method involved reviewing the Vital Statistics Survey Death Form at the Ministry of Health, Labour and Welfare as well as analyzing their Online Reporting of Vital Statistics. Furthermore, this study was able to validate 29,799 of the 30,299 suicides (98.3%) that occurred in 2008. Mental diseases were validated not only from the "Cause of death" section as marked on the death certificate, but also by information found in sections for "Additional items for death by external cause" and "Other special remarks." RESULTS; From the Vital Statistics Survey Death Form and Online Reporting of Vital Statistics, 2964 individuals with either a mental disease or mental disorder were identified. Of the 2964 identified individuals, 55 had dementia (of which 13 were dementia in Alzheimer's disease), 116 had alcohol dependence/psychotic disorder, 550 had schizophrenia, 101 had bipolar affective disorder, 1,913 has had a depressive episode, 13 had obsessive-compulsive disorder, 22 had adjustment disorders, 14 had eating disorders, 49 had nonorganic sleep disorders, 24 had personality disorder, and 6 had pervasive developmental disorders. In addition, 125 individuals had more than one mental disease. The national police statistics from 2008 show that 1,368 suicide victims had schizophrenia and 6,490 had depression. These figures show quite a difference between the results of this study and the police statistics. Further, there have
DeGue, Sarah; Fowler, Katherine A; Calkins, Cynthia
Several high-profile cases in the U.S. have drawn public attention to the use of lethal force by law enforcement (LE), yet research on such fatalities is limited. Using data from a public health surveillance system, this study examined the characteristics and circumstances of these violent deaths to inform prevention. All fatalities (N=812) resulting from use of lethal force by on-duty LE from 2009 to 2012 in 17 U.S. states were examined using National Violent Death Reporting System data. Case narratives were coded for additional incident circumstances. Victims were majority white (52%) but disproportionately black (32%) with a fatality rate 2.8 times higher among blacks than whites. Most victims were reported to be armed (83%); however, black victims were more likely to be unarmed (14.8%) than white (9.4%) or Hispanic (5.8%) victims. Fatality rates among military veterans/active duty service members were 1.4 times greater than among their civilian counterparts. Four case subtypes were examined based on themes that emerged in incident narratives: about 22% of cases were mental health related; 18% were suspected "suicide by cop" incidents, with white victims more likely than black or Hispanic victims to die in these circumstances; 14% involved intimate partner violence; and about 6% were unintentional deaths due to LE action. Another 53% of cases were unclassified and did not fall into a coded subtype. Regression analyses identified victim and incident characteristics associated with each case subtype and unclassified cases. Knowledge about circumstances of deaths due to the use of lethal force can inform the development of prevention strategies, improve risk assessment, and modify LE response to increase the safety of communities and officers and prevent fatalities associated with LE intervention. Copyright © 2016. Published by Elsevier Inc.
Zavala-Zegarra, Diego E; López-Charneco, Magdalena; Garcia-Rivera, Enid J; Concha-Eastman, Alberto; Rodriguez, José F; Conte-Miller, María
To raise awareness of the impact of homicides in Puerto Rico based on the findings of the spatial and temporal distribution of homicides and the use of firearms, by age and gender, using reports of interpersonal violent deaths from the Institute of Forensic Science (IFS) headquartered in San Juan, Puerto Rico. This was a descriptive study of all homicide incidents in Puerto Rico reported by the IFS for the period 2001-2010. For each of the 8 542 cases, data analyzed included age, sex, municipality of incident, date of death, and mechanism. Crude sex- and age-specific mortality rates for Puerto Rico and for each municipality per year and for the 10-year period were calculated. Cumulative rate and cumulative risks were estimated and defined as lifetime risk. The relative distribution of cumulative rates for each municipality was categorized into quartiles of highest to lowest risk and displayed as a map. The risk of homicide death among males is 13 times greater than among females. The highest rates were observed among males 20-24 years of age (198.4 homicides per 100 000). In any given year, firearms were used in at least 80% of homicides. The average lifetime risk of homicide death for males is 1 in 34. Young adult males with access to firearms are at greatest risk of homicide in Puerto Rico. Also, highly urbanized municipalities are at highest risk; however, certain non-urban municipalities along the coast also have a very high homicide risk. Top priorities should be applying the WHO "ecological model" for violent injury prevention and establishing a surveillance system that will assist in identifying the role that socioeconomics, illegal firearms trade, and drug trafficking are playing.
McCann, Stewart J H
The precocity-longevity hypothesis that those who reach career milestones earlier in life have shorter life spans was tested with the 430 men elected to serve in the House of Representatives for the 71st U.S. Congress in 1929-1930 who were alive throughout 1930. There was no tendency for those first serving at an earlier age to die sooner or those serving first at a later age to die later than expected based on individual life expectancy in 1930. Although age at first serving was correlated with death age, the correlation was not significant when expected death age was controlled. The results cast serious doubt on the contention of the precocity-longevity hypothesis that the developmental aspects of the prerequisites, concomitants, and consequences of early career achievement peaks actively enhance the conditions for an earlier death.
Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon
Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.
Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increasse of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death. PMID:19127326
Bengtsson, Tommy; Nilsson, Anton
This paper considers the long-term effects of smoking on disability retirement in Sweden. Smoking is known to have damaging effects on health, but there is limited evidence on how the effects of smoking translate into worse labour market outcomes, such as the inability to work. In contrast to the few previous studies on smoking and disability retirement, we use a large population sample with registry information on smoking, which is recorded for all women who give birth in Sweden. Thanks to these comprehensive data, we are able to account for a much broader range of potential confounders. In particular, by the use of sibling and twin fixed effects, we account for unobserved heterogeneity in childhood environment and family characteristics. Given that smoking is often initiated in adolescence, one would suspect such factors to play important roles. Among individuals aged 50-64 in 2011, a simple model suggested smokers to have a 5 percentage point higher probability of receiving (full) disability pension, making them more than twice as likely as non-smokers to receive this. However, in a model with sibling fixed effects, the size of the effect was reduced by more than a third. The results point to the importance of confounders, such as childhood circumstances or behaviours, which were not accounted for by previous studies. We also consider effects on disability due to different health conditions. In relative terms, effects are the largest for circulatory conditions and tumours. Results are largely driven by health problems severe enough to merit hospitalization, and there is no evidence of a role played by financial incentives. Copyright © 2018 Elsevier B.V. All rights reserved.
Lee, Hyun-Pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon
Neuronal cell cycle activation has been implicated in neurodegenerative diseases such as Alzheimer's disease, while the initiating mechanism of cell cycle activation remains to be determined. Interestingly, our previous studies have shown that cell cycle activation by c-Myc (Myc) leads to neuronal cell death which suggests Myc might be a key regulator of cell cycle re-entry mediated neuronal cell death. However, the pattern of Myc expression in the process of neuronal cell death has not been addressed. To this end, we examined Myc induction by the neurotoxic agents camptothecin and amyloid-β peptide in a differentiated SH-SY5Y neuronal cell culture model. Myc expression was found to be significantly increased following either treatment and importantly, the induction of Myc preceded neuronal cell death suggesting it is an early event of neuronal cell death. Since ectopic expression of Myc in neurons causes the cell cycle activation and neurodegeneration in vivo, the current data suggest that induction of Myc by neurotoxic agents or other disease factors might be a key mediator in cell cycle activation and consequent cell death that is a feature of neurodegenerative diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Kennedy, Hannah; Haack, Tobias B; Hartill, Verity; Mataković, Lavinija; Baumgartner, E Regula; Potter, Howard; Mackay, Richard; Alston, Charlotte L; O'Sullivan, Siobhan; McFarland, Robert; Connolly, Grainne; Gannon, Caroline; King, Richard; Mead, Scott; Crozier, Ian; Chan, Wandy; Florkowski, Chris M; Sage, Martin; Höfken, Thomas; Alhaddad, Bader; Kremer, Laura S; Kopajtich, Robert; Feichtinger, René G; Sperl, Wolfgang; Rodenburg, Richard J; Minet, Jean Claude; Dobbie, Angus; Strom, Tim M; Meitinger, Thomas; George, Peter M; Johnson, Colin A; Taylor, Robert W; Prokisch, Holger; Doudney, Kit; Mayr, Johannes A
We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Kłys, Małgorzata; Kowalski, Piotr; Rojek, Sebastian; Gross, Adam
To our knowledge, the majority of evidence supporting the relationship between the serotonin syndrome and medications that effect 5HT is based on case reports. The justification for taking up this subject has been a fatal outcome of a 21 year-old female following an administration of toxic doses of moclobemide (MAOI) and venlafaxine (SNRI). As a result of complex toxicological investigations including antemortem and postmortem material, antemortem clinical observations and postmortem examinations, the cause of death was identified as overdose with antidepressants--moclobemide and venlafaxine--in the mechanism of the clinically fully developed severe toxic serotonin syndrome. The analysis of a hair strand collected from the victim documented the use of the above-mentioned drugs simultaneously with cocaine in the period of at least 20 months preceding death. The fact is a matter of considerable interest in view of the employed pharmacotherapy, giving rise to suspicion that the woman had not developed the serotonin syndrome during the almost 2-year antemortem period until she took toxic doses of both medications.
Wolff-Maras, R; Klintschar, M
Death during an operation represents a severe event for physicians and family of the deceased. A further difficulty arises when certifying the cause and manner of death because medical staff are often afraid that they will incriminate themselves when declaring an unnatural death or an unclear manner of death but are also afraid to issue a false statement by declaring a natural death. In such cases of mors in tabula it is recommended to declare an unclear manner of death because this leads to police investigations and in the majority of the cases to exoneration of the medical staff.
Lagunes, Leonel; Len, Oscar; Sandiumenge, Alberto; Martínez-Saez, Elena; Pumarola, Tomás; Bodro, Marta; Macías, Antonio; Silva, Jose T; Nuvials, F Xavier; Charco, Ramon; Moreso, Francesc; Pont, Teresa
The increasing gap between availability of solid organs for transplantation and the demand has led to the inclusion of donor organs that, according to current guidelines, may be discarded, some of them because of the possibility for transmission of infection to the recipients. We present the first report, to the best of our knowledge, of a case of a brain-dead donor with a localized and treated Actinomyces israelii central nervous system infection who, after a thorough evaluation, provided organs for successful transplant procedures in four recipients. There was no evidence of transmission of infection within a 6-month follow-up. Relative contraindications must be individualized in order to expand the number of real organ donors, emphasizing caution in rare causes for brain death in which patients should be thoroughly evaluated for possible donation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Galanakis, E; Dimoliatis, I D K
Eugenios Voulgaris (Corfu, Greece, 1716; St Petersburg, Russia, 1806) was an eminent theologian and scholar, and bishop of Kherson, Ukraine. He copiously wrote treatises in theology, philosophy and sciences, greatly influenced the development of modern Greek thought, and contributed to the perception of Western thought throughout the Eastern Christian world. In his Treatise on euthanasia (1804), Voulgaris tried to moderate the fear of death by exalting the power of faith and trust in the divine providence, and by presenting death as a universal necessity, a curative physician and a safe harbour. Voulgaris presented his views in the form of a consoling sermon, abundantly enriched with references to classical texts, the Bible and the Church Fathers, as well as to secular sources, including vital statistics from his contemporary England and France. Besides euthanasia, he introduced terms such as dysthanasia, etoimothanasia and prothanasia. The Treatise on euthanasia is one of the first books, if not the very first, devoted to euthanasia in modern European thought and a remarkable text for the study of the very early European attitudes towards "good death". In the Treatise, euthanasia is clearly meant as a spiritual preparation and reconciliation with dying rather than a physician-related mercy killing, as the term progressed to mean during the 19th and the 20th centuries. This early text is worthy of study not only for the historian of medical ethics or of religious ethics, but for everybody who is trying to courageously confront death, either in private or in professional settings.
Webb, Roger T; Pickles, Andrew R; Appleby, Louis; Mortensen, Preben B; Abel, Kathryn M
Offspring of psychiatric inpatients are at higher risk of death from all causes, but their cause-specific risks have not been quantified. To investigate cause-specific deaths at 1 to 25 years in offspring of parents previously admitted as psychiatric inpatients. Population-based cohort study. The entire Danish population. All singleton births (N = 1.38 million) from January 1, 1973, to December 31, 1997, with follow-up to January 1, 1999. Linkage to the national psychiatric register identified all previous parental admissions. Deaths from all natural causes and all unnatural causes, specifically, accidents, homicides, suicides, and undetermined causes. The highest observed relative risk (RR) was for homicide in young and older children with affected mothers or fathers. Homicides were between 5 and 10 times more likely to occur in this group, according to child's age and whether the mother or father had been admitted. There was previous parental admission in approximately one third of all child homicides. We found no evidence of increased risk of homicide in exposed young adults, but this group had a 2-fold to 3-fold higher risk of suicide. In almost one fourth of the suicides, there was a history of parental admission. Young adults with 2 previously admitted parents were 6 times more likely to kill themselves than were their peers in the general population. Relative risk of suicide or open-verdict deaths by poisoning were higher than for such deaths occurring by other means. Almost 99% of children studied survived to their mid-20s. However, they were more vulnerable to death from unnatural causes, notably, homicide during childhood and suicide in early adulthood. Further research is needed to establish how parental psychopathology contributes to increased risk of premature death in these offspring.
Welch, K D; Lee, S T; Panter, K E; Gardner, D R
Numerous plants are known to be teratogenic in livestock. In addition to causing malformations, several plants can also cause embryonic death. These losses decrease the reproductive efficiency of animals exposed to these plants. The aim of this study was to determine if teratogenic plants such as lupines or tobaccos cause embryonic losses. A goat model using the plant Nicotiana glauca was used in this study, as this model has been used to characterize the mechanism of Lupinus, Conium, and Nicotiana-induced terata. Four groups of goats were dosed from gestational day 1-10, 11-20, 21-30, and 31-40. Goats were evaluated via ultrasound imaging for pregnancy after completion of the dosing regimen and kids were evaluated for malformations at the time of parturition. Overall, there was no evidence from this study that N. glauca (anabasine) at this dose (2 g/kg/day) would cause embryonic losses in goats. However, the dose of N. glauca used in this study was at the lower threshold that would be expected to produce terata. Therefore it is possible that higher doses of anabasine could cause embryonic loss. Further work is also needed to characterize the kinetic profile of anabasine, and other teratogenic alkaloids, in the fetal compartments. Published by Elsevier Ltd.
Bilukha, Oleg O; Leidman, Eva Z; Sultan, Abdul-Salam Saleh; Jaffar Hussain, Syed
The aim of this study was to describe the most recent trends and epidemiologic patterns of fatal injuries resulting from explosions in Iraq, one of the countries most affected by violence from explosive devices. Iraqi Ministry of Health (MoH) routine prospective injury surveillance collects information on all fatal injuries recorded by coroners from physical examinations, police reports, and family members in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. This study analyzed explosive-related fatal injuries that occurred from January 1, 2010 through December 31, 2013. Analysis included 2,803 fatal injuries. The number of fatal injuries declined from 2010 through 2012, followed by an increase in 2013. One-thousand one-hundred and one explosion-related fatalities were documented in 2013, more than twice as many as in 2012 or in 2011. Most fatalities were among men aged 20-39 years. Of all causalities, 194 (6.9%) were among females and 302 (10.8%) were among children aged less than 18 years. The majority of fatalities were caused by improvised explosive devices (IEDs): car bombs (15.3%), suicide bombs (4.0%), and other IEDs (29.6%). The highest number of fatalities occurred in streets and roads. Of all deaths, 95.6% occurred in three governorates: Baghdad, Ninevah, and Al-Anbar. Explosives continue to result in a high number of fatal injuries in Iraq. Following a period of declining violence from explosives, in 2013, fatalities increased. Most explosion-related injuries resulted from IEDs; males aged 20-39 years were at greatest risk.
Hirano, André Carramenha de Góes; Targueta, Eduardo Pelegrineti; Martines, João Augusto dos Santos; Andrade, Dafne; Lovisolo, Silvana Maria; Felipe-Silva, Aloisio
In 2005, the combined pulmonary fibrosis and emphysema (CPFE) was first defined as a distinct entity, which comprised centrilobular or paraseptal emphysema in the upper pulmonary lobes, and fibrosis in the lower lobes accompanied by reduced diffused capacity of the lungs for carbon monoxide (DLCO). Recently, the fibrosis associated with the connective tissue disease was also included in the diagnosis of CPFE, although the exposure to tobacco, coal, welding, agrochemical compounds, and tire manufacturing are the most frequent causative agents. This entity characteristically presents reduced DLCO with preserved lung volumes and severe pulmonary hypertension, which is not observed in emphysema and fibrosis alone. We present the case of a 63-year-old woman with a history of heavy tobacco smoking abuse, who developed progressive dyspnea, severe pulmonary hypertension, and cor pulmonale over a 2-year period. She attended the emergency facility several times complaining of worsening dyspnea that was treated as decompensate chronic obstructive pulmonary disease (COPD). The imaging examination showed paraseptal emphysema in the upper pulmonary lobes and fibrosis in the middle and lower lobes. The echo Doppler cardiogram revealed the dilation of the right cardiac chambers and pulmonary hypertension, which was confirmed by pulmonary trunk artery pressure measurement by catheterization. During this period, she was progressively restricted to the minimal activities of daily life and dependent on caregivers. She was brought to the hospital neurologically obtunded, presenting anasarca, and respiratory failure, which led her to death. The autopsy showed signs of pulmonary hypertension and findings of fibrosis and emphysema in the histological examination of the lungs. The authors highlight the importance of the recognition of this entity in case of COPD associated with severe pulmonary hypertension of unknown cause. PMID:28740835
Hauser, Robert G.; Katsiyiannis, William T.; Gornick, Charles C.; Almquist, Adrian K.; Kallinen, Linda M.
Aims An estimated 10 000–15 000 pacemaker and implantable cardioverter–defibrillator (ICD) leads are extracted annually worldwide using specialized tools that disrupt encapsulating fibrous tissue. Additional information is needed regarding the safety of the devices that have been approved for lead extraction. The aim of this study was to determine whether complications due to device-assisted lead extraction might be more hazardous than published data suggest, and whether procedural safety precautions are effective. Methods and results We searched the US Food and Drug Administration's (FDA) Manufacturers and User Defined Experience (MAUDE) database from 1995 to 2008 using the search terms ‘lead extraction and death’ and ‘lead extraction and injury’. Additional product specific searches were performed for the terms ‘death’ and ‘injury’. Between 1995 and 2008, 57 deaths and 48 serious cardiovascular injuries associated with device-assisted lead extraction were reported to the FDA. Owing to underreporting, the FDA database does not contain all adverse events that occurred during this period. Of the 105 events, 27 deaths and 13 injuries occurred in 2007–2008. During these 2 years, 23 deaths were linked with excimer laser or mechanical dilator sheath extractions. The majority of deaths and injuries involved ICD leads, and most were caused by lacerations of the right atrium, superior vena cava, or innominate vein. Overall, 62 patients underwent emergency surgical repair of myocardial perforations and venous lacerations and 35 (56%) survived. Conclusion These findings suggest that device-assisted lead extraction is a high-risk procedure and that serious complications including death may not be mitigated by emergency surgery. However, skilled standby cardiothoracic surgery is essential when performing pacemaker and ICD lead extractions. Although the incidence of these complications is unknown, the results of our study imply that device-assisted lead
Goldberg, David; French, Benjamin; Trotter, James; Shetty, Kirti; Schiano, Thomas; Reddy, K Rajender; Halpern, Scott D
Few studies have evaluated the accuracy of United Network for Organ Sharing (UNOS) or Scientific Registry of Transplant Recipients data among patients listed for liver transplantation. Of particular importance for transplant policy and practice is whether patients' outcomes are coded properly. Using data from four transplant centers, we identified all liver transplant candidates removed from the waitlist from February 27, 2002 to July 24, 2010, with a specific focus the removal code of "other." Among nontransplanted patients at these centers, 2206 patients were removed for death or clinical deterioration. Of these, 8.6% (189 of 2206) were misclassified; they were assigned the UNOS removal code of "other." Among these 189 misclassified patients, 128 became medically unsuitable, 35 died, and 26 became too sick to transplant. Nearly one-half (46.8%) of misclassified patients were removed due to advanced hepatocellular carcinoma. Among true waitlist removals for death, only 35 of 1593 (2.2%) were misclassified. Conversely, of true removals for clinical deterioration, 154 of 612 (25.2%) were misclassified, with significant (P < 0.001) center variation: 4.4% (Baylor), 8.0% (Georgetown), 32.6% (University of Pennsylvania), and 45.0% (Mount Sinai). Extrapolating these data to the entire United States, if "other" patients who truly died or clinically deteriorated were recoded appropriately, there would be an additional 2525 (95% confidence interval, 2046-3102) patients removed from the waitlist due to death (331) or clinical deterioration (2194) since 2002. A substantial proportion of patients truly removed from the waitlist for death or clinical deterioration were misclassified as "other." Thus, analyses using the UNOS or the Scientific Registry of Transplant Recipients database may underestimate the true proportion of patients removed from the waitlist for clinical deterioration.
Paciej, Paulina; Ciabiada, Beata; Maniecka-Bryła, Irena
In order to evaluate the health status of a population, besides indicators measuring the incidence of diseases and deaths, potential measures are becoming more frequently used, ie. measures that take into account life-time potential of the individuals in the population. They can particularly by applied to analyse the problem of premature mortality, which is measured by lost life years. The aim of the study was to evaluate life years lost due to diseases of digestive system in Polish population in 2013. The study was based on a dataset containing 387,312 death certificates of Poles who died in 2013, provided by the Central Statistical Office in Poland. Data on deaths caused by diseases of digestive system (K00-K93 by ICD-10) were used in the study – that were 16,543 records (4.3% of all the deaths). Lost life years were assessed with the measures: SEYLL (Standard Expected Years of Life Lost), SEYLLp (Standard Expected Years of Life Lost per living person), SEYLLd (Standard Expected Years of Life Lost per death). In the analysed year among men there were 9,275 deaths caused by diseases of digestive system and in women 7,268 deaths. SEYLL in the group of men amounted to 102 230.7 and in the group of women it was 53,475.5. The number of lost life years calculated per 10 000 male inhabitants was 54.9, and for 10,000 females it was 26.9. The highest share in lost life years had alcoholic liver disease (SEYLLp for men – 20.87, for women – 6.1), fibrosis and cirrhosis of the liver (SEYLLp for men- 9.7, for women- 5.6) and acute pancreatitis (SEYLLp for men – 5.3, for women – 2.1). The results of the study indicate that diseases of digestive system have an important contribution to the loss of life-time potential in Polish population (6.6% of all SEYLL in 2013). The dominant role in this class of diseases played alcoholic liver disease – K70, fibrosis and cirrhosis of the liver – K74 and acute pancreatitis – K85.
Inoue, Takako; Tamiya, Motohiro; Tamiya, Akihiro; Nakahama, Kenji; Taniguchi, Yoshihiko; Shiroyama, Takayuki; Isa, Shin-Ichi; Nishino, Kazumi; Kumagai, Toru; Kunimasa, Kei; Kimura, Madoka; Suzuki, Hidekazu; Hirashima, Tomonori; Atagi, Shinji; Imamura, Fumio
The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting. The medical records of patients with NSCLC who started receiving nivolumab between December 17, 2015 and July 31, 2016 in 3 Japanese institutes were collected. Early death was defined as any death within 3 months from the start of nivolumab treatment, irrespective of its cause. Treatment response was evaluated using the Response Evaluation Criteria In Solid Tumors criteria, version 1.1. A total of 201 patients with NSCLC were enrolled, and 38 (18.9%) died within the first 3 months. Thirty-one (81.6%) patients who experienced early death developed progressive disease, whereas 14 (36.8%) patients who experienced early death demonstrated nivolumab-induced immune-related adverse events, which required corticosteroid intervention, including interstitial lung disease in 7 (18.4%) patients. Multivariate logistic regression demonstrated that an Eastern Cooperative Oncology Group performance status score ≥ 2 (odds ratio [OR], 5.66; 95% confidence interval [CI], 2.01-15.61; P < .001), C-reactive protein-to-albumin ratio > 0.3 (OR, 10.56; 95% CI, 3.61-30.86; P < .001), and the response to prior treatment (OR, 2.07; 95% CI, 1.03-4.14; P = .041) were independent predictors for early death. Disease progression and immune-related adverse events are 2 major causes of early death with nivolumab in patients with NSCLC. An Eastern Cooperative Oncology Group performance status score ≥ 2, pretreatment C-reactive protein-to-albumin ratio > 0.3, and poor response to prior treatment were associated with early death. Copyright © 2017 Elsevier Inc. All rights reserved.
Colzani, Edoardo; Clements, Mark; Johansson, Anna L V; Liljegren, Annelie; He, Wei; Brand, Judith; Adolfsson, Jan; Fornander, Tommy; Hall, Per; Czene, Kamila
Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ⩾1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.
Colzani, Edoardo; Clements, Mark; Johansson, Anna L V; Liljegren, Annelie; He, Wei; Brand, Judith; Adolfsson, Jan; Fornander, Tommy; Hall, Per; Czene, Kamila
Background: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. Methods: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. Results: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23–1.28) and 1.18 (95% CI: 1.14–1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ⩾1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98–2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50–2.22) compared with those without bone fracture. Conclusions: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities. PMID:27701383
Tan, X; He, J; Li, L; Yang, G; Liu, H; Tang, S; Wang, Y
Stroke is often accompanied by hyperglycaemia, and this has an important impact on prognosis. The aim of this study was to investigate the relationship between early hyperglycaemia and the outcome of spontaneous intracerebral haemorrhage (sICH). A systematic literature search on PubMed, Embase, Cochran, WANFANG DATA, VIP and CNKI databases was conducted, and eight eligible studies were retrieved. Relative risks and 95% confidence interval (CI) in the hyperglycaemia group compared with the non-hyperglycaemia group were calculated and meta-analysed when possible. Eight controlled trials and cohort studies totalling 3756 patients addressing early hyperglycaemia and the outcome of sICH were compiled for this meta-analysis. Cut-off points for defining hyperglycaemia was 6.1-8.3 mmol/L, and the median cut-off value was 7.5 mmol/L. Studies were assigned to one of the two subgroups: the group A (for studies with the values of glucose concentrations above the median cut-off) and the group B (for studies with the values of glucose concentrations below the median cut-off). The RR for short-term death associated with hyperglycaemia was 3.65 (95% confidence interval (CI) (3.08, 4.33); P < 0.0001). In the subgroup analysis, the relative risk values were 3.46 (95% CI (1.66, 7.20); P = 0.0009) and 3.53 (95% CI (2.92, 4.26); P < 0.00001) for the groups A and B respectively. The publication bias showed that Egger's test (P > 0.1), Begg's test (P > 0.05) and Nfs0.05 exceeded included studies. Early hyperglycaemia can significantly increase the rate of early-term death in patients with sICH, independent of the cut-off points for hyperglycaemia. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.
Marchesi, Matteo; Boracchi, Michele; Gentile, Guendalina; Maghin, Francesca; Zoja, Riccardo
Congenital diverticula of the left ventricle, very rare malformations, are determined by an abnormal embryonic development of the ventricular wall and can be isolated or associated to other cardiac anomalies. In most of the cases, these pathologies are not symptomatic and in some patients can be associated to ventricular arrhythmia, cardiac rupture with tamponade and sudden death. Authors are presenting the case of a sudden death in an 8-weeks-old newborn due to rupture of a cardiac congenital diverticulum of the left ventricle, discovered only at the moment of the autopsic examination. The parents of the victim pressed charges against the medical staff that was appointed to the cares, blaming them with malpractice. The missed diagnosis of a cardiac congenital diverticulum of the left ventricle, a rare pathology, reflects the trickiness of the medical management that can lead to medico-legal controversies and, even though such rare conditions must be always taken into consideration when investigating possible dysfunction causing the death, diagnostic difficulties, in the case in exam, justify the missed diagnosis intra-vitam of cardiac ventricular diverticulum. Copyright © 2017 Elsevier B.V. All rights reserved.
Cousens, Simon; Blencowe, Hannah; Gravett, Michael; Lawn, Joy E
In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM. To review the evidence for and estimate the effect on neonatal mortality due to pre-term birth complications or infection, of administration of antibiotics to women with pPROM, in low and middle-income countries. We performed a systematic review to update a Cochrane review. Standardized abstraction forms were used. The quality of the evidence provided by individual studies and overall was assessed using an adapted GRADE approach. Eighteen RCTs met our inclusion criteria. Most were from high-income countries and provide strong evidence that antibiotics for pPROM reduce the risk of respiratory distress syndrome [risk ratio (RR) = 0.88; confidence interval (CI) 0.80, 0.97], and early onset postnatal infection (RR = 0.61; CI 0.48, 0.77). The data are consistent with a reduction in neonatal mortality (RR = 0.90; CI 0.72, 1.12). Antibiotics for pPROM reduce complications due to pre-term delivery and post-natal infection in high-income settings. There is moderate quality evidence that, in low-income settings, where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of those due to infection.
Shimura, Mai; Ishikawa, Hiroshi; Nagase, Hiromi; Mochizuki, Akihiko; Sekiguchi, Futoshi; Koshimizu, Naho; Itai, Toshiyuki; Odagami, Mizuha
We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult. © 2018 Japanese Teratology Society.
Finsterer, Josef; Stöllberger, Claudia
Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance.
Ngallaba, S E; Majinge, C; Gilyoma, J; Makerere, D J; Charles, E
Sixty percent of the global deaths and injuries occur in the developing world and mostly are due to Road traffic accidents (RTAs. looking at the etiological related factors which include, carelessness of the driver, condition of the vehicle or motorcycle, poor condition of roads, risky behavior of the driver, most of these factors can be prevented to some extent. This study therefore, determined the pattern of cases and deaths due to traffic road accidents in Mwanza City Tanzania. In this retrospective study, records, registers and case notes In the surgical ward and causality, medical records and central police station from 2008 to 2011 were used. The study focused on the two referral hospitals (Sekouture regional hospital and Bugando Medical Center). There were 3450 cases due to accidents reported at both centers (Sekouture regional hospital and Bugando Medical Center of which 3224 (93.4%) had complete information for analysis.2225 (69%) were male and 999 (31%) were female, and the most affected group were male. Among the RTAs2809 cases (87%) were due to motor cycle accidents which were the leading cause of RTAs with case fatality rate of 5% while motor vehicle has case fatality rate of 24% which is 5 times that of motor cycle. Among all RTAs the leading cause of injuries is Motor cycle traffic accidents followed by motor vehicle. RTAs are on increase particularly the motor cycle traffic accidents and has claimed a good number of innocent people's lives however most of them are preventable, therefore driving course to be introduced to motor cycle drivers with emphasize on the road posters signal, rules and regular checkup of their motor cycles especially commercial motor cycle.
Ward, Michael M
To determine if socioeconomic status, as measured by education level, is associated with mortality due to systemic lupus erythematosus (SLE), and to determine if these associations differ among ethnic groups. Sex- and race-specific mortality rates due to SLE by education level were computed for persons age 25-64 years using US Multiple Causes of Death data from 1994 to 1997. SLE-specific mortality rates were compared with all-cause mortality rates in 1997 to determine if the association between education level and mortality in SLE was similar to that in other causes of death. Among whites, the risk of death due to SLE was significantly higher among those with lower levels of education, and the risk gradient closely paralleled the 1997 all-cause mortality risks by education level. However, in African American women and men and Asian/Pacific Islander women, the risk of death due to SLE was lower among those with lower education levels, contrary to the associations between education level and all-cause mortality in these groups. Comparing the distribution of education levels among deaths due to SLE and all deaths in 1997, persons with lower education levels were underrepresented among deaths due to SLE in African Americans and Asian/Pacific Islanders. Among whites, higher education levels are associated with lower mortality due to SLE. These associations were not present in ethnic minorities, likely due to underascertainment of deaths due to SLE in less-well educated persons. This underascertainment may be due to underreporting of SLE on death certificates, but may also represent underdiagnosis of SLE in ethnic minorities with low education levels.
Macdonald, Stuart W S; Hultsch, David F; Dixon, Roger A
Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least 1 occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the 3 cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. (c) 2008 APA, all rights reserved
MacDonald, Stuart W.S.; Hultsch, David F.; Dixon, Roger A.
Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least one occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the three cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. PMID:18808249
Colangelo, Michele; Ripullone, Francesco; Julio Camarero, Jesus; De Micco, Veronica; Gazol, Antonio; Gentilesca, Tiziana; Borghetti, Marco
In recent decades, forest dieback episodes have been recorded worldwide affecting different tree species. In particular, several cases of widespread dieback and increased mortality rates have been described for Mediterranean oak (Quercus spp.) species. These dieback cases are revealing the high vulnerability of Mediterranean oaks, manifested as a loss in tree vigour (leaf shedding, canopy and shoot dieback), growth decline and sometimes tree death, as a consequence of temperatures rising at unprecedented rates and drying trends. However, in the wake of the so-called 'oak decline phenomenon', the attention on these species has generally been limited, perhaps because they are often regarded as well-adapted to the dry conditions typical of Mediterranean areas. Indeed, according to recent studies, the reduced size, the ability to sprout and the anisohydric behavior of Mediterranean oak species (reduced control of water loss and high stomatal conductance rates) would make them better adapted to withstand heat and drought stress then taller and non-sprouting isohydric species (e.g. conifer, with strict control of water loss by closing stomata). Here, we investigated the vulnerability of Mediterranean oaks by comparing neighboring living and recently dead trees in species with low (Q. pubescens), intermediate (Q. cerris, Q. frainetto) and high (Q. robur) sensitivity to water shortage. We analysed changes in tree vigour using tree-ring width and functional wood anatomical traits as proxies to search for early-warning signals of dieback, in connection with the main proposed dieback mechanisms (hydraulic failure and/or carbon starvation). We also modeled the probability of tree death as a function of tree size (diameter, height) by quantifying recent changes in growth and wood anatomy along tree-ring series. Contrary to the general concept that trees tend to experience increasing cavitation risk with increasing height, our studies show that smaller oaks are more prone to die
Atanasijević, Tatjana; Jovanović, Aleksandar A; Nikolić, Slobodan; Popović, Vesna; Jasović-Gasić, Miroslava
A case is reported of a 36-year-old male, found dead in his locked room, lying on a bed, dressed in his mother's clothes, with a plastic bag over his head, hands tied and with a barrel wooden cork in his rectum. Two pornographic magazines were found on a chair near the bed, so that the deceased could see them well. Asphyxia was controlled with a complex apparatus which consisted of two elastic luggage rack straps, the first surrounding his waist, perineum, and buttocks, and the second the back of his body, and neck. According to the psychological autopsy based on a structured interview (SCID-I, SCID-II) with his father, the deceased was single, unemployed and with a part college education. He had grown up in a poor family with a reserved father and dominant mother, and was indicative of fulfilling DSM-IV diagnostic criteria for alcohol dependence, paraphilia involving hypoxyphilia with transvestic fetishism and anal masturbation and a borderline personality disorder. There was no evidence of previous psychiatric treatment. The Circumstances subscale of Beck's Suicidal Intent Scale (SIS-CS) pointed at the lack of final acts (thoughts or plans) in anticipation of death, and absence of a suicide note or overt communication of suicidal intent before death. Integration of the crime scene data with those of the forensic medicine and psychological autopsy enabled identification of the event as an accidental death, caused by neck strangulation, suffocation by a plastic bag, and vagal stimulation due to a foreign body in the rectum.
Jeon, Hee-Yeon; Lee, Hyunsook
Aurora-A is a serine/threonine mitotic kinase that is required for centrosome maturation. Many cancer cells over-express Aurora-A, and several reports have suggested that Aurora-A has prognostic value in the clinical treatment of cancer. Therefore, inhibitors for Aurora-A kinase have been developed. However, studies on Aurora-A are largely performed in cancer cell lines and are sometimes controversial. For effective evaluation of Aurora-A inhibitors in cancer treatment, it is essential to understand its function at the organism level. Here, we report the crucial functions of Aurora-A in homeostasis of spindle organization in mitosis using zebrafish embryogenesis as a model system. Using morpholino technology, we show that depletion of Aurora-A in zebrafish embryogenesis results in short bent trunks, accompanied by growth retardation and eventual cell death. Live-imaging and immunofluorescence analyses of the embryos revealed that the developmental defects are due to problems in mitosis, manifested through monopolar and disorganized spindle formation. Aurora-A-depleted cells exhibited mitotic arrest with congression failure, leading to activation of the spindle assembly checkpoint. Cell death in the absence of Aurora-A was partially rescued by co-injection of the p53 morpholino, suggesting that apoptosis after Aurora-A depletion is p53-dependent. The clinical implications of these results relate to the indication that Aurora-A inhibitors may be effective towards cancers with intact p53. © 2013 The Authors Journal compilation © 2013 FEBS.
Lee, Gyunghee; Wang, Zixing; Sehgal, Ritika; Chen, Chun-Hong; Kikuno, Keiko; Hay, Bruce; Park, Jae H
A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.
Hansen, James E.; Stringer, William W.
Background: The responses of oxygen uptake efficiency (ie, oxygen uptake/ventilation = V˙o2/V˙e) and its highest plateau (OUEP) during incremental cardiopulmonary exercise testing (CPET) in patients with chronic left heart failure (HF) have not been previously reported. We planned to test the hypothesis that OUEP during CPET is the best single predictor of early death in HF. Methods: We evaluated OUEP, slope of V˙o2 to log(V˙e) (oxygen uptake efficiency slope), oscillatory breathing, and all usual resting and CPET measurements in 508 patients with low-ejection-fraction (< 35%) HF. Each had further evaluations at other sites, including cardiac catheterization. Outcomes were 6-month all-reason mortality and morbidity (death or > 24 h cardiac hospitalization). Statistical analyses included area under curve of receiver operating characteristics, ORs, univariate and multivariate Cox regression, and Kaplan-Meier plots. Results: OUEP, which requires only moderate exercise, was often reduced in patients with HF. A low % predicted OUEP was the single best predictor of mortality (P < .0001), with an OR of 13.0 (P < .001). When combined with oscillatory breathing, the OR increased to 56.3, superior to all other resting or exercise parameters or combinations of parameters. Other statistical analyses and morbidity analysis confirmed those findings. Conclusions: OUEP is often reduced in patients with HF. Low % predicted OUEP (< 65% predicted) is the single best predictor of early death, better than any other CPET or other cardiovascular measurement. Paired with oscillatory breathing, it is even more powerful. PMID:22030802
Pereira, Mariana; Johnsen, Iren; Hauken, May Aa; Kristensen, Pål; Dyregrov, Atle
Previous meta-analyses examined the effectiveness of interventions for bereaved children showing small to moderate effect sizes. However, no mixed methods systematic review was conducted on bereavement interventions following the loss of a parent focusing on the time since death in regard to the prevention of grief complications. The overall purpose of the review is to provide a rigorous synthesis of early intervention after parental death in childhood. Specifically, the aims are twofold: (1) to determine the rationales, contents, timeframes, and outcomes of early bereavement care interventions for children and/or their parents and (2) to assess the quality of current early intervention studies. Quantitative, qualitative, and mixed methods intervention studies that start intervention with parentally bereaved children (and/or their parents) up to 6 months postloss will be included in the review. The search strategy was based on the Population, Interventions, Comparator, Outcomes, and Study Designs (PICOS) approach, and it was devised together with a university librarian. The literature searches will be carried out in the Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Excerpta Medica Database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The Mixed Methods Appraisal Tool will be used to appraise the quality of eligible studies. All data will be narratively synthetized following the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. The systematic review is ongoing and the data search has started. The review is expected to be completed by the end of 2017. Findings will be submitted to leading journals for publication. In accordance with the current diagnostic criteria for prolonged grief as well as the users' perspectives literature, this systematic review outlines a possible sensitive period for early intervention following the death of a parent. The hereby presented protocol ensures
LEE, Seung-Hun; PARK, Sang-Joon; KWAK, Dongmi; KIM, Kyoo-Tae
A 16-year-old female Indian peafowl (Pavo cristatus) died two days after recognition of conjunctivitis in the right eye, anorexia and depression. Gross necropsy revealed a thick pseudomembrane under the eyelid and hydropericardium. Histopathological examination revealed hepatocellular necrosis, sinusoidal and vascular congestion and infiltrated inflammatory cells. Infiltration by inflammatory cells was noted in the epicardium. The lungs had mild interstitial pneumonia with the extensive congestion within the capillaries of the air sacs. Tubular interstitial congestion and necrosis was noted in the kidneys. Bacterial culture and nucleotide sequencing of the inflammatory specimens identified the causative agent as Serratia marcescens, an uncommon bacterium in birds. In summary, this study describes the sudden death of an Indian peafowl due to S. marcescens infection, which is rarely seen in animals. PMID:29081475
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Does every employee's death due to injuries incurred in connection with his or her service with an Armed Force in a contingency operation qualify for... connection with his or her service with an Armed Force in a contingency operation qualify for the death...
To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.
Malkan, Umit Yavuz; Ozcebe, Osman Ilhami
Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm 3 in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL. Twenty-eight de novo patients with AML, diagnosed with HL between 2002 and 2015 at the Hacettepe Hematology Department, were analyzed retrospectively. Leukapheresis was performed in 10 patients, and the mean WBC decrease with leukapheresis was 57.4×10 3 /μl which accounts for 31% of the initial WBC count. The indications for leukapheresis were hyperviscosity and prophylaxis in four and six patients, respectively. In the group of patients who received leukapheresis, three of four patients who had hyperviscosity symptoms died, and three of six patients died who did not have symptoms. In our study, we observed that the leukapheresis procedure is highly effective in reducing plasma WBC levels. However, although it is statistically insignificant, our findings also revealed that there is a much higher rate of death in patients who were treated with leukapheresis. Therefore we conclude that leukapheresis does not lower rates of early death; nevertheless, this finding should be confirmed by prospective studies with larger cohorts. Copyright © 2017 Elsevier Ltd. All rights reserved.
Stark, Ann R.; Carlo, Waldemar A.; Vohr, Betty R; Papile, Lu Ann; Saha, Shampa; Bauer, Charles R.; Donovan, Edward F.; Oh, William; Shankaran, Seetha; Tyson, Jon E.; Wright, Linda L.; Poole, W. Kenneth; Das, Abhik; Stoll, Barbara J.; Fanaroff, Avroy A.; Korones, Sheldon B.; Ehrenkranz, Richard A.; Stevenson, David K.; Peralta-Carcelen, Myriam; Adams-Chapman, Ira; Wilson-Costello, Deanne E.; Bada, Henrietta S.; Heyne, Roy J.; Johnson, Yvette R.; Lee, Kimberly Gronsman; Steichen, Jean J.; Hintz, Susan R.
Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. Methods Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment. Results Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group. PMID:23992673
Binswanger, Ingrid A; Blatchford, Patrick J; Lindsay, Rebecca G; Stern, Marc F
High mortality rates after release from prison have been well-documented, particularly from overdose. However, little is known about the risk factors for death after release from prison. Therefore, the objective of this study was to determine the demographic and incarceration-related risk factors for all-cause, overdose and early mortality after release from prison. We conducted a retrospective cohort study of inmates released from a state prison system from 1999 through 2003. The cohort included 30,237 who had a total of 38,809 releases from prison. Potential risk factors included gender, race/ethnicity, age, length of incarceration, and community supervision. Cox proportional hazards regression was used to determine risk factors for all-cause, overdose and early (within 30 days of release) death after release from prison. Age over 50 was associated with an increased risk for all-cause mortality (hazard ratio [HR] 2.67 for each decade increase, 95% confidence interval [CI] 2.23, 3.20) but not for overdose deaths or early deaths. Latinos were at decreased risk of death compared to Whites only for all-cause mortality (HR 0.61, 95% CI 0.42, 0.87). Increasing years of incarceration were associated with a decreased risk of all-cause mortality (HR 0.95, 95% CI 0.91, 0.99) and overdose deaths (HR 0.80, 95% CI 0.68, 0.95), but not early deaths. Gender and type of release were not significantly associated with all-cause, overdose or early deaths. Age, ethnicity and length of incarceration were associated with mortality after release from prison. Interventions to reduce mortality among former inmates are needed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Mwansa-Kambafwile, Judith; Cousens, Simon; Hansen, Thomas; Lawn, Joy E
In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. However, although >1 million deaths due to preterm birth occur annually, antenatal steroids are not routine practice in low-income countries where most of these deaths occur. To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries. We conducted systematic reviews using standardized abstraction forms. Quality of evidence was assessed using an adapted GRADE approach. Existing meta-analyses were reviewed for relevance to low/middle-income countries, and new meta-analysis was performed. We identified 44 studies, including 18 randomised control trials (RCTs) (14 in high-income countries) in a Cochrane meta-analysis, which suggested that antenatal steroids decrease neonatal mortality among preterm infants (<36 weeks gestation) by 31% [relative risk (RR) = 0.69; 95% confidence interval (CI) 0.58-0.81]. Our new meta-analysis of four RCTs from middle-income countries suggests 53% mortality reduction (RR = 0.47; 95% CI 0.35-0.64) and 37% morbidity reduction (RR = 0.63; 95% CI 0.49-0.81). Observational study mortality data were consistent. The control group in these equivalent studies was routine care (ventilation and, in many cases, surfactant). In low-income countries, many preterm babies currently receive little or no medical care. It is plausible that antenatal steroids may be of even greater effect when tested in these settings. Based on high-grade evidence, antenatal steroid therapy is very effective in preventing neonatal mortality and morbidity, yet remains at low coverage in low/middle-income countries. If fully scaled up, this intervention could save up to 500 000 neonatal lives annually.
Kobek, M; Jankowski, Z; Chowaniec, C; Chowaniec, M; Jabłoński, C; Skowronek, R
Postmortem diagnostics of anaphylactic and anaphylactoid reaction as the cause of death in cases of sudden deaths without witnesses, as well as those in which circumstances of sudden disease and then death are known, seems to be very difficult. This is caused by the lack of characteristic macro- or microscopic changes to internal organs resulting from a short, or even very short time, that elapses from the action of the etiological factor till death. In the above mentioned cases it is often impossible to establish univocally the cause of death, despite considering information on the cause of disease and its clinical symptoms. On the basis of 2 cases of sudden deaths resulted from the intake of hazel nuts, and the administration of contrast agent before radiological examination, the authors discuss the usefulness of postmortem determinations of tryptase and IgE in blood for diagnostics of deaths resulting from anaphylactic and anaphylactoid reaction, respectively.
Bedzhov, Ivan; Zernicka-Goetz, Magdalena
Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. PMID:25640415
Bedzhov, Ivan; Zernicka-Goetz, Magdalena
Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.
Al-Shahrani, S; Naidoo, V
Florfenicol, a commonly used veterinary antibiotic, was reported to have caused a severe drop in egg hatchability following its off-label use on a broiler breeder farm in South Africa. According to the pharmacovigilance report, hatchability dropped by 80 % for up to a week following a five day course at 10 mg/kg (both males and females treated metaphylactically) to manage an Escherichia coli infection. While mammalian toxicity studies indicate the potential for early embryonic death in utero or testicular damage, no literature is available on the avian toxicity of florfenicol. For this study we investigated the effects of florfenicol at various doses from 10 to 90 mg/kg on the egg hatchability in a breeder flock we kept and established under controlled conditions, with the same cockerels and hens being exposed in a phased manner. Following five days of oral exposure, no toxic signs were evident in any of the cockerels or hens treated at doses up to 90 mg/kg. Treatment of only the cockerels had no effect on egg hatchability, while treatment of only the hens at doses of 60 and 90 mg/kg resulted in decreased hatchability of 0 % in comparison to 70 % of the control as early 24 h after treatment. In all cases, decreased hatchability was associated with embryonic death at 5 days of development. The toxic effects of florfenicol were completely reversible with comparable hatchability being present by day 4 post-treatment withdrawal. Toxicity correlated with total egg florfenicol concentrations with an LC50 of 1.07 μg/g. Florfenicol appears to be toxic to the developing chick embryo at around day 5 of incubation, in the absence of related toxicity in the hen or cockerel.
Shi, J R; Tian, C J; Zeng, Q; Guo, X J; Lu, J; Gao, C R
To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting. Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （ P <0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （ P <0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （ P >0.05）. The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine
Imai, Kosuke; Jiang, Zhichao
The matched-pairs design enables researchers to efficiently infer causal effects from randomized experiments. In this paper, we exploit the key feature of the matched-pairs design and develop a sensitivity analysis for missing outcomes due to truncation by death, in which the outcomes of interest (e.g., quality of life measures) are not even well defined for some units (e.g., deceased patients). Our key idea is that if 2 nearly identical observations are paired prior to the randomization of the treatment, the missingness of one unit's outcome is informative about the potential missingness of the other unit's outcome under an alternative treatment condition. We consider the average treatment effect among always-observed pairs (ATOP) whose units exhibit no missing outcome regardless of their treatment status. The naive estimator based on available pairs is unbiased for the ATOP if 2 units of the same pair are identical in terms of their missingness patterns. The proposed sensitivity analysis characterizes how the bounds of the ATOP widen as the degree of the within-pair similarity decreases. We further extend the methodology to the matched-pairs design in observational studies. Our simulation studies show that informative bounds can be obtained under some scenarios when the proportion of missing data is not too large. The proposed methodology is also applied to the randomized evaluation of the Mexican universal health insurance program. An open-source software package is available for implementing the proposed research. Copyright © 2018 John Wiley & Sons, Ltd.
Banaschak, Sibylle; Janßen, Katharina; Schulte, Babette; Rothschild, Markus A
In recent years, increasing attention has been paid to the issue of (fatal) child abuse and neglect, largely due to the media attention garnered by some headline-grabbing cases. If media statements are to be believed, such cases may be an increasing phenomenon. With these published accounts in mind, publicly available statistics should be analysed with respect to the question of whether reliable statements can be formulated based on these figures. It is hypothesised that certain data, e.g., the Innocenti report published by UNICEF in 2003, may be based on unreliable data sources. For this reason, the generation of such data, and the reliability of the data itself, should also be discussed. Our focus was on publicly available German mortality and police crime statistics (Polizeiliche Kriminalstatistik). These data were classified with respect to child age, data origin, and cause of death (murder, culpable homicide, etc.). In our opinion, the available data could not be considered in formulating reliable scientific statements about fatal child abuse and neglect, given the lack of detail and the flawed nature of the basic data. Increasing the number of autopsies of children 0-3 years of age should be considered as a means to ensure the capture of valid, practical, and reliable data. This could bring about some enlightenment and assist in the development of preemptive strategies to decrease the incidence of (fatal) child abuse and neglect.
Lauer, Jeremy A; Betrán, Ana Pilar; Barros, Aluísio J D; de Onís, Mercedes
We estimate attributable fractions, deaths and years of life lost among infants and children < or = 2 years of age due to suboptimal breast-feeding in developing countries. We compare actual practices to a minimum exposure pattern consisting of exclusive breast-feeding for infants < or = 6 months of age and continued breast-feeding for older infants and children < or = 2 years of age. For infants, we consider deaths due to diarrhoeal disease and lower respiratory tract infections, and deaths due to all causes are considered in the second year of life. Outcome measures are attributable fractions, deaths, years of life lost and offsetting deaths potentially caused by mother-to-child transmission of HIV through breast-feeding. Developing countries. Infants and children < or = 2 years of age. Attributable fractions for deaths due to diarrhoeal disease and lower respiratory tract infections are 55% and 53%, respectively, for the first six months of infancy, 20% and 18% for the second six months, and are 20% for all-cause deaths in the second year of life. Globally, as many as 1.45 million lives (117 million years of life) are lost due to suboptimal breast-feeding in developing countries. Offsetting deaths caused by mother-to-child transmission of HIV through breast-feeding could be as high as 242,000 (18.8 million years of life lost) if relevant World Health Organization recommendations are not followed. The size of the gap between current practice and recommendations is striking when one considers breast-feeding involves no out-of-pocket costs, that there exists universal consensus on best practices, and that implementing current international recommendations could potentially save 1.45 million children's lives each year.
Pina, J M; Domínguez, A; Alcaide, J; Alvarez, J; Camps, N; Díez, M; Godoy, P; Jansá, J M; Minquell, S; Arias, C
To calculate excess mortality in an annual cohort of tuberculosis patients and study the factors associated with death. Cases of tuberculosis reported in Catalonia (May 1996-April 1997). Patients were classified as completed treatment/cured (compliant), non-compliant, failures, transfers out and deaths. Excess mortality was defined as the ratio actual deaths/expected deaths (according to general mortality figures for Catalonia, May 1996-April 1997). Factors associated with death were determined by a comparative study of variables (demographic, substance abuse, comorbidity, tuberculosis-related disease) in deaths after diagnosis and survivors. Time from diagnosis to death was recorded. Patients included: 2,085. Patients classified as: completed treatment/cured (compliant), 1,406 (67.43 %); noncompliant, 165 (7, 91%); failures, 5 (0.24%); transfers out, 25 (1.21%); deaths, 133 (6.38%), 28 of which occurred before diagnosis and 105 after diagnosis. Insufficient data in medical record for classification, 351 (16.83%) patients. Excess mortality: 5.98 (95% CI: 4.96-7.0). Factors associated with death: treatment with non-standardized guidelines, 46%; OR: 10.3 (6.2-17.4); HIV infection, 40%; OR: 13.0 (6.6-25.8); age greater than 64 years, 40%; OR: 14.6 (3.0-69.8); alcoholism, 25%; OR: 2.0 (1.1-3.6); neoplasm, 16%; OR: 3.9 (1.8-8.6; renal failure, 8%; OR: 10.1 (3.1-32.3). The shortest time from diagnosis to death was in patients with only one risk factor, except for HIV infection, where the time passed was the longest observed. We found substantial excess mortality in tuberculosis patients. Death was associated with the efficacy of treatment, HIV coinfection, advanced age, alcoholism and the coexistence of neoplasms or renal failure.
Lee, David D; Singh, Amandeep; Burns, Justin M; Perry, Dana K; Nguyen, Justin H; Taner, C Burcin
Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. © 2014 American Association for the Study of Liver Diseases.
Two hundred venirepersons from the 12th Judicial Circuit in Bradenton, Florida completed the following measures: (1) one question that measured their level of support for the death penalty; (2) one question that categorized their death-qualification status; (3) 23 questions that measured their attitudes toward the death penalty (ATDP); (4) 22 questions that assessed their attitudes toward women (ATW); (5) 25 questions that measured their level of homophobia (H); (6) seven questions that assessed their level of modern racism (MR); (7) eight questions that measured their level of modern sexism (MS); and (8) standard demographic questions. Results indicated that as death-penalty support increased participants exhibited more positive attitudes toward the death penalty, more negative attitudes toward women, and higher levels of homophobia, modern racism, and modern sexism. Findings also suggested that death-qualified venirepersons exhibited more positive attitudes toward the death penalty and higher levels of homophobia, modern racism, and modern sexism. Finally, more positive attitudes toward the death penalty were correlated with more negative attitudes toward women and higher levels of homophobia, modern racism, and modern sexism. Legal implications are discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.
Jochems, Arthur; El-Naqa, Issam; Kessler, Marc; Mayo, Charles S; Jolly, Shruti; Matuszak, Martha; Faivre-Finn, Corinne; Price, Gareth; Holloway, Lois; Vinod, Shalini; Field, Matthew; Barakat, Mohamed Samir; Thwaites, David; de Ruysscher, Dirk; Dekker, Andre; Lambin, Philippe
Early death after a treatment can be seen as a therapeutic failure. Accurate prediction of patients at risk for early mortality is crucial to avoid unnecessary harm and reducing costs. The goal of our work is two-fold: first, to evaluate the performance of a previously published model for early death in our cohorts. Second, to develop a prognostic model for early death prediction following radiotherapy. Patients with NSCLC treated with chemoradiotherapy or radiotherapy alone were included in this study. Four different cohorts from different countries were available for this work (N = 1540). The previous model used age, gender, performance status, tumor stage, income deprivation, no previous treatment given (yes/no) and body mass index to make predictions. A random forest model was developed by learning on the Maastro cohort (N = 698). The new model used performance status, age, gender, T and N stage, total tumor volume (cc), total tumor dose (Gy) and chemotherapy timing (none, sequential, concurrent) to make predictions. Death within 4 months of receiving the first radiotherapy fraction was used as the outcome. Early death rates ranged from 6 to 11% within the four cohorts. The previous model performed with AUC values ranging from 0.54 to 0.64 on the validation cohorts. Our newly developed model had improved AUC values ranging from 0.62 to 0.71 on the validation cohorts. Using advanced machine learning methods and informative variables, prognostic models for early mortality can be developed. Development of accurate prognostic tools for early mortality is important to inform patients about treatment options and optimize care.
Azevedo, L D; Stucchi, R S; de Ataíde, E C; Boin, I F S F
Graft dysfunction after liver transplantation is a serious complication that can lead to graft loss and patient death. This was a study to identify risk factors for early death (up to 30 days after transplantation). It was an observational and retrospective analysis at the Liver Transplantation Unit, Hospital de Clinicas, State University of Campinas, Brazil. From July 1994 to December 2012, 302 patients were included (>18 years old, piggyback technique). Of these cases, 26% died within 30 days. For analysis, Student t tests and chi-square were used to analyze receptor-related (age, body mass index, serum sodium, graft dysfunction, Model for End-Stage Liver Disease score, renal function, and early graft dysfunction [EGD type 1, 2, or 3]), surgery (hot and cold ischemia, surgical time, and units of packed erythrocytes [pRBC]), and donor (age, hypotension, and brain death cause) factors. Risk factors were identified by means of logistic regression model adjusted by the Hosmer-Lemeshow test with significance set at P < .05. We found that hyponatremic recipients had a 6.26-fold higher risk for early death. There was a 9% reduced chance of death when the recipient serum sodium increased 1 unit. The chance of EGD3 to have early death was 18-fold higher than for EGD1 and there was a 13% increased risk for death for each unit of pRBC transfused. Donor total bilirubin, hyponatremia, massive transfusion, and EGD3 in the allocation graft should be observed for better results in the postoperative period. Copyright © 2015 Elsevier Inc. All rights reserved.
Norton, Maria C.; Smith, Ken R.; Østbye, Truls; Tschanz, JoAnn T.; Schwartz, Sarah; Corcoran, Chris; Breitner, John C. S.; Steffens, David C.; Skoog, Ingmar; Rabins, Peter V.; Welsh-Bohmer, Kathleen A.
Objectives Early parental death is associated with lifelong tendencies toward depression and chronic stress. We tested the hypothesis that, early parental death is associated with higher risk for Alzheimer’s disease (AD) in offspring. Design A population-based epidemiological study of dementia with detailed clinical evaluations, linked to one of the world’s richest sources of objective genealogical and vital statistics data. Setting Home visits with residents of a rural county in northern Utah. Participants 4,108 subjects, aged 65-105. Measurements Multi-stage dementia ascertainment protocol implemented in four triennial waves, yielding expert consensus diagnoses of 570 participants with AD and 3,538 without dementia. Parental death dates, socioeconomic status and parental remarriage after widowhood were obtained from the Utah Population Database, a large genealogical database linked to statewide birth and death records. Results Mother’s death during subject’s adolescence was significantly associated with higher rate of AD in regression models that included age, gender, education, APOE genotype, and socioeconomic status. Father’s death before subject age 5 showed a weaker association. In stratified analyses, associations were significant only when the widowed parent did not remarry. Parental death associations were not moderated by gender or APOE genotype. Findings were specific to AD and not found for non-AD dementia. Conclusions Parental death during childhood is associated with higher prevalence of AD, with different critical periods for father’s vs. mother’s death, with strength of these associations attenuated by remarriage of the widowed parent. PMID:21873837
Ajetunmobi, Omotomilola; Taylor, Mark; Stockton, Diane; Wood, Rachael
To compare the mortality in those previously hospitalised for mental disorder in Scotland to that experienced by the general population. Population-based historical cohort study using routinely available psychiatric hospital discharge and death records. All Scotland. Individuals with a first hospital admission for mental disorder between 1986 and 2009 who had died by 31 December 2010 (34 243 individuals). The main outcome measure was death from any cause, 1986-2010. Excess mortality was presented as standardised mortality ratios (SMRs) and years of life lost (YLL). Excess mortality was assessed overall and by age, sex, main psychiatric diagnosis, whether the psychiatric diagnosis was 'complicated' (ie, additional mental or physical ill-health diagnoses present), cause of death and time period of first admission. 111 504 people were included in the study, and 34 243 had died by 31 December 2010. The average reduction in life expectancy for the whole cohort was 17 years, with eating disorders (39-year reduction) and 'complicated' personality disorders (27.5-year reduction) being worst affected. 'Natural' causes of death such as cardiovascular disease showed modestly elevated relative risk (SMR1.7), but accounted for 67% of all deaths and 54% of the total burden of YLL. Non-natural deaths such as suicide showed higher relative risk (SMR5.2) and tended to occur at a younger age, but were less common overall (11% of all deaths and 22% of all YLL). Having a 'complicated' diagnosis tended to elevate the risk of early death. No worsening of the overall excess mortality experienced by individuals with previous psychiatric admission over time was observed. Early death for those hospitalised with mental disorder is common, and represents a significant inequality even in well-developed healthcare systems. Prevention of suicide and cardiovascular disease deserves particular attention in the mentally disordered.
Bachilova, Sophia; Czuzoj-Shulman, Nicholas; Abenhaim, Haim Arie
The prevalence of home birth in the United States is increasing, although its safety is undetermined. The objective of this study was to investigate the effects of obstetrical risk factors on early neonatal death in planned home births delivering at home. The authors conducted a retrospective 3-year cohort study consisting of planned home births that delivered at home in the United States between 2011 and 2013. The study excluded infants with congenital and chromosomal anomalies and infants born at ≤34 weeks' gestation. Multivariate logistic regression models were used to estimate the adjusted effects of individual obstetrical variables on early neonatal deaths within 7 days of delivery. During the study period, there were 71 704 planned and delivered home births. The overall early neonatal death rate was 1.5 deaths per 1000 planned home births. The risks of early neonatal death were significantly higher in nulliparous births (OR 2.71; 95% CI 1.71-4.31), women with a previous CS (OR 2.62, 95% CI 1.25-5.52), non-vertex presentations (OR 4.27; 95% CI 1.33-13.75), plural births (OR 9.79; 95% CI 4.25-22.57), preterm births (OR 4.68; 95% CI 2.30-9.51), and births at ≥41 weeks of gestation (OR 1.76; 95% CI 1.09-2.84). Early neonatal deaths occur more commonly in certain obstetrical contexts. Patient selection may reduce adverse neonatal outcomes among planned home births. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.
Pamoukdjian, F; Lévy, V; Sebbane, G; Boubaya, M; Landre, T; Bloch-Queyrat, C; Paillaud, E; Zelek, L
To assess the predictive value of gait speed for early death in older outpatients with cancer. Prospective bicentric observational cohort study. The Physical Frailty in Elder Cancer patients (PF-EC) study (France). One hundred and ninety outpatients with cancer during the first 6 months of follow up in the PF-EC study. The association between usual gait speed over 4 m alone (GS) or included in the short physical performance battery (SPPB) and overall survival within 6 months following a comprehensive geriatric assessment (CGA). A Cox proportional-hazard regression model was performed in non-survivors for clinical factors from the CGA, along with c reactive protein (CRP). Two models were created to assess GS alone and from inclusion in the SPPB. The mean age was 80.6 years, and 50.5% of the participants were men. Death occurred in 11% (n=22) of the participants within the 6 month follow up period. Of these participants, 98% had solid cancers, and 33% had a metastatic disease. A GS < 0.8 m/s (HR=5.6, 95%CI=1.6-19.7, p=0.007), a SPPB < 9 (HR=5.8, 95%CI=1.6-20.9, p=0.007) and a CRP of 50 mg/l or greater (p<0.0001) were significantly associated with early death in the two multivariate analyses. Cancer site and extension were not significantly associated with early death. Walking tests are associated with early death within the 6 month follow up period after a CGA independent of cancer site and cancer extension. GS alone < 0.8 m/s is at least as efficacious as the SPPB in predicting this outcome. GS alone could be used routinely as a marker of early death to adapt oncologic therapeutics. Further studies are needed to validate these preliminary data.
Link, M S; Wang, P J; Pandian, N G; Bharati, S; Udelson, J E; Lee, M Y; Vecchiotti, M A; VanderBrink, B A; Mirra, G; Maron, B J; Estes, N A
The syndrome of sudden death due to low-energy trauma to the chest wall (commotio cordis) has been described in young sports participants, but the mechanism is unknown. We developed a swine model of commotio cordis in which a low-energy impact to the chest wall was produced by a wooden object the size and weight of a regulation baseball. This projectile was thrust at a velocity of 30 miles per hour and was timed to the cardiac cycle. We first studied 18 young pigs, 6 subjected to multiple chest impacts and 12 to single impacts. Of the 10 impacts occurring within the window from 30 to 15 msec before the peak of the T wave on the electrocardiogram, 9 produced ventricular fibrillation. Ventricular fibrillation was not produced by impacts at any other time during the cardiac cycle. Of the 10 impacts sustained during the QRS complex, 4 resulted in transient complete heart block. We also studied whether the use of safety baseballs, which are softer than standard ones, would reduce the risk of arrhythmia. A total of 48 additional animals sustained up to three impacts during the T-wave window of vulnerability to ventricular fibrillation with a regulation baseball and safety baseballs of three degrees of hardness. We found that the likelihood of ventricular fibrillation was proportional to the hardness of the ball, with the softest balls associated with the lowest risk (two instances of ventricular fibrillation after 26 impacts, as compared with eight instances after 23 impacts with regulation baseballs). This experimental model of commotio cordis closely resembles the clinical profile of this catastrophic event. Whether ventricular fibrillation occurred depended on the precise timing of the impact. Safety baseballs, as compared with regulation balls, may reduce the risk of commotio cordis.
Osman, Rim; Tacnet-Delorme, Pascale; Kleman, Jean-Philippe; Millet, Arnaud; Frachet, Philippe
Calreticulin (CRT) is a well-known “eat-me” signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes. We observed that exogenous CRT is endocytosed by THP1 macrophages through macropinocytosis and that internalization is associated with a particular phenotype characterized by an increase of cell spreading and migration, an upregulation of CD14, an increase of interleukin-8 release, and a decrease of early apoptotic cell uptake. Importantly, CRT-induced pro-inflammatory phenotype was confirmed on human monocytes-derived macrophages by the overexpression of CD40 and CD274, and we found that monocyte-derived macrophages exposed to CRT display a peculiar polarization notably associated with a downregulation of the histocompatibility complex of class II molecules hampering its description through the classical M1/M2 dichotomy. Altogether our results highlight the role of soluble CRT with strong possible consequences on the macrophage-mediated immune response to dying cell. PMID:28878781
O'Dowd, Emma L; McKeever, Tricia M; Baldwin, David R; Anwar, Sadia; Powell, Helen A; Gibson, Jack E; Iyen-Omofoman, Barbara; Hubbard, Richard B
The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. Of 20,142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65-69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Esmaeili, Mohammad A; Panahi, Marzieh; Yadav, Shilpi; Hennings, Leah; Kiaei, Mahmoud
Abnormal distribution, modification and aggregation of transactivation response DNA-binding protein 43 (TDP-43) are the hallmarks of multiple neurodegenerative diseases, especially frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Transgenic mouse lines overexpressing wild-type or mutant TDP-43 exhibit ALS-like symptom, motor abnormalities and early paralysis followed by death. Reports on lifespan and phenotypic behaviour in Prp-TDP-43 (A315T) vary, and these animals are not fully characterized. Although it has been proposed that the approximate 20% loss of motor neurons at end stage is responsible for the severe weakness and death in TDP-43 mice, this degree of neurologic damage appears insufficient to cause death. Hence we studied these mice to further characterize and determine the reason for the death. Our characterization of TDP-43 transgenic mice showed that these mice develop ALS-like symptoms that later become compounded by gastrointestinal (GI) complications that resulted in death. This is the first report of a set of pathological evidence in the GI track that is strong indicator for the cause of death of Prp-hTDP-43 (A315T) transgenic mice. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.
Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel
Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.
Tolppanen, Anna-Maija; Koponen, Marjaana; Tanskanen, Antti; Lavikainen, Piia; Sund, Reijo; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi
The use of antipsychotic agents has been associated with increased pneumonia risk, but although people with dementia are particularly susceptible to pneumonia, only one small study has assessed the risk of pneumonia in relation to the use of antipsychotic agents among people with Alzheimer disease (AD). We investigated whether the incident use of antipsychotic agents, or specific antipsychotic agents, are related to a higher risk of hospitalization or death due to pneumonia in the Medication and Alzheimer Disease (MEDALZ) cohort. The cohort includes all individuals with AD who received a clinically verified AD diagnosis in Finland in 2005 to 2011 (N = 60,584; incident pneumonia, n = 12,225). A matched comparison cohort without AD (N = 60,584; incident pneumonia, n = 6,195) was used to compare the magnitude of risk. Results were adjusted for a propensity score derived from comorbidities, concomitant medications, and sociodemographic characteristics. Sensitivity analyses with case-crossover design were conducted. The use of antipsychotic agents was associated with a higher risk of pneumonia (adjusted hazard ratio [HR], 2.01; 95% CI, 1.90-2.13) in the AD cohort and a somewhat higher risk in the non-AD cohort (adjusted HR, 3.43; 95% CI, 2.99-3.93). Similar results were observed with case-crossover analyses (OR, 2.02; 95% CI, 1.75-2.34 in the AD cohort and OR, 2.59; 95% CI, 1.77-3.79 in the non-AD cohort). The three most commonly used antipsychotic agents (quetiapine, risperidone, haloperidol) had similar associations with pneumonia risk. Regardless of applied study design, treatment duration, or the choice of drug, the use of antipsychotic agents was associated with a higher risk of pneumonia. With observational data, we cannot fully rule out a shared causality between pneumonia and the use of antipsychotic agents, but the risk to benefit balance should be considered when antipsychotic agents are prescribed. Copyright Â© 2016 American College of Chest
Bryła, Marek; Maniecka-Bryła, Irena; Burzyńska, Monika; Pikala, Małgorzata
External causes of death are the third most common causes of death, after cardiovascular diseases and malignant neoplasms, in inhabitants of Poland. External causes of death pose the greatest threat to people aged 5-44, which results in a great number of years of life lost. The aim of the study is the analysis of years of life lost due to external causes of death among rural inhabitants in Poland, particularly due to traffic accidents and suicides. The study material included a database created on the basis of 2,100,785 certificates of rural inhabitants in Poland in the period 1999-2012. The SEYLL p (Standard Expected Years of Life Lost per living person) and the SEYLL d (per death) indices were used to determine years of life lost due to external causes of death. Joinpoint models were used to analyze time trends. In the period 1999-2012, 151,037 rural inhabitants died due to external causes, including 27.2% due to traffic accidents and 25.2% due to suicides. In 2012, the SEYLL p was 1,817 per 100,000 males and 298 per 100,000 females. Among males, suicides (SEYLL p = 633 years per 100,000) and traffic accidents (SEYLL p = 473 years per 100,000) contributed to the largest number of years of life lost. Among females, SEYLLp values were: 109 years due to traffic accidents and 69 years due to suicides (per 100,000). Among males, SEYLL p values started to decrease in 2008 at the average annual rate of 3.2%. In the group of females in the period 1999-2012, SEYLL p values were decreasing by 2.4% per year. The decreasing trend of the number of lost years of life due to external causes among rural inhabitants does not apply to suicides among men. The SEYLL p due to this group of causes has been steadily increasing since 1999. Analysis of the years of life lost focuses on the social and economic aspects of premature mortality due to external causes.
Borlase, B C; Baxter, J T; Benotti, P N; Stone, M; Wood, E; Forse, R A; Blackburn, G L; Steele, G
The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU.
Howland, J; Hingson, R
The findings in 32 studies on alcohol and injuries and deaths attributed to fires and burns were analyzed in detail. The studies, all in English, were published between 1947 and 1986. Most of them were descriptive and reported on the percent of the victims who were exposed to alcohol. Eight of the nine best descriptive studies indicated that alcohol exposure was more likely among those who died in fires ignited by cigarettes than those attributable to other causes. It can be concluded that there is substantial, although not definitive, evidence that alcohol plays a role in the etiology of fire and burn injuries and deaths. PMID:3116577
Lemez, Srdjan; Wattie, Nick; Lawler, Tyler; Baker, Joseph
While empirical evidence suggests that elite athletes have superior lifespan outcomes relative to the general population, less is known regarding their causes of death. The purpose of this study was to critically examine the mortality outcomes of deceased National Basketball Association and American Basketball Association players. Death data were collected from publicly available sources until 11 December 2015, and causes of death were categorized using the International Classification of Diseases, Tenth Revision (ICD). Mortality was measured through: i) cause-specific crude death rates (CDR), ii) estimates of death rates per athlete-year (AY), and iii) binary and multinomial regression analyses. We identified 514 causes of death from 787 deceased players (M = 68.1 y ± 16.0) from 16 different ICD groups, 432 of which were from natural causes. Findings showed similar leading causes of death and CDRs to sex- and race-matched controls, higher death rate differences per AY within time-dependent variables (i.e., birth decade, race, and height), and a higher likelihood of dying below the median age of death for black and taller players, although this was highly confounded by birth decade. More complete knowledge of mortality outcomes would provide broad public health applications and disarm harmful stereotypes of elite athlete health.
Rosbottom, Anne; Gibney, E. Helen; Guy, Catherine S.; Kipar, Anja; Smith, Robert F.; Kaiser, Pete; Trees, Alexander J.; Williams, Diana J. L.
The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle. PMID:18362132
Chomba, Elwyn; Carlo, Wally A; Goudar, Shivaprasad S; Jehan, Imtiaz; Tshefu, Antoinette; Garces, Ana; Parida, Sailajandan; Althabe, Fernando; McClure, Elizabeth M; Derman, Richard J; Goldenberg, Robert L; Bose, Carl; Krebs, Nancy F; Panigrahi, Pinaki; Buekens, Pierre; Wallace, Dennis; Moore, Janet; Koso-Thomas, Marion; Wright, Linda L
Infants of women with lower education levels are at higher risk for perinatal mortality. We explored the impact of training birth attendants and pregnant women in the Essential Newborn Care (ENC) Program on fresh stillbirths (FSBs) and early (7-day) neonatal deaths (END) by maternal education level in developing countries. A train-the-trainer model was used with local instructors in rural communities in six countries (Argentina, Democratic Republic of the Congo, Guatemala, India, Pakistan, and Zambia). Data were collected using a pre-/post-active baseline controlled study design. A total of 57,643 infants/mothers were enrolled. The follow-up rate at 7 days of age was 99.2%. The risk for FSB and END was higher for mothers with 0-7 years of education than for those with ≥8 years of education during both the pre- and post-ENC periods in unadjusted models and in models adjusted for confounding. The effect of ENC differed as a function of maternal education for FSB (interaction p = 0.041) without evidence that the effect of ENC differed as a function of maternal education for END. The model-based estimate of FSB risk was reduced among mothers with 0-7 years of education (19.7/1,000 live births pre-ENC, CI: 16.3, 23.0 vs. 12.2/1,000 live births post-ENC, CI: 16.3, 23.0, p < 0.001), but was not significantly different for mothers with ≥8 years of education, respectively. A low level of maternal education was associated with higher risk for FSB and END. ENC training was more effective in reducing FSB among mothers with low education levels. © 2016 S. Karger AG, Basel.
Alam, Rifat; Barrera, Maru; D'Agostino, Norma; Nicholas, David B.; Schneiderman, Gerald
The authors investigated longitudinally bereavement in mothers and fathers whose children died of cancer. Thirty-one parents were interviewed 6 and 18 months post-death. Analyses revealed parental differences and changes over time: (a) employment--fathers were more work-focused; (b) grief reactions--mothers expressed more intense grief reactions…
Background The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory. Methods Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared. Results Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed). Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5) were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06). Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%), hypotension (N = 4, 80%), and renal failure (N = 4, 80%). All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivax-associated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment. Conclusion Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of malaria deaths in Sabah
Zhang, Sui-Liang; Chen, Ting-Song; Ma, Chen-Yun; Meng, Yong-Bin; Zhang, Yu-Fei; Chen, Yi-Wei; Zhou, Yu-Hao
Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98-1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90-1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94-1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23-0.94; P = 0.032). Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers.
Malhotra, Konark; Gornbein, Jeffrey; Saver, Jeffrey L
Since large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death. To delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3-6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset. Among 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3-6) within 3-6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53-5.63, p < 0.0001). Mortality within 3-6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5-6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8-55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8-81.3%) of poststroke dependence or death and 95.6% (CI: 89.0-98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality. LVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.
Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia
Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.
Tummolo, Albina; Favia, Vito; Bellantuono, Rosa; Bellino, Vito; Ranieri, Antonio; Morrone, Amelia; De Palo, Tommaso; Papadia, Francesco
Ornithine transcarbamylase deficiency (OTC-D) is a urea cycle disorder caused by dysfunction of ornithine transcarbamylase, which frequently leads to hyperammonemia. Hyperammonemia represents a medical emergency requiring prompt treatment to reduce plasma ammonia levels and prevent severe neurological damage, coma, and death, particularly in patients with acute decompensation-related coma. The clinical symptoms of OTC-D can manifest themselves either at an early stage, which is often associated with severe symptoms, or in later life (late-onset OTC-D), when symptoms may be less severe. There is currently little agreement over diagnostic signs of the condition or the most appropriate therapeutic approach. Hyperammonemia is usually treated with ammonia scavengers, continuous venovenous hemodialysis, and dietary changes. N-carbamylglutamate is approved for the treatment of hyperammonemia in N-acetylglutamate synthetase deficiency and may have efficacy in other urea cycle disorders. Here, we report a 13-year-old girl who was diagnosed with OTC-D at the age of 3 years. On this occasion, the patient presented with vomiting, lethargy, and mental confusion. Despite biochemical parameters being within normal ranges, she was comatose within a few hours. She was promptly treated with a combined therapy of continuous venovenous hemodialysis and N-carbamylglutamate, resulting in a gradual normalization of clinical symptoms within 30 hours. No neurological damage was apparent at 18 months after treatment. This case demonstrates that clinical benefits can be obtained by beginning aggressive treatment of OTC-D within a few hours of the onset of severe neurological symptoms even in the absence of altered biochemical markers.
Nickel, Katelin B; Marsden-Haug, Nicola; Lofy, Kathryn H; Turnberg, Wayne L; Rietberg, Krista; Lloyd, Jennifer K; Marfin, Anthony A
This study evaluated risk factors for intensive care unit (ICU) admission or death among people hospitalized with 2009 pandemic influenza A (pH1N1) virus infection. We based analyses on data collected in Washington State from April 27 to September 18, 2009, on deceased or hospitalized people with laboratory-confirmed pH1N1 infection reported by health-care providers and hospitals as part of enhanced public health surveillance. We used bivariate analyses and multivariable logistic regression to identify risk factors associated with ICU admission or death due to pH1N1. We identified 123 patients admitted to the hospital but not an ICU and 61 patients who were admitted to an ICU or died. Independent of high-risk medical conditions, both older age and delayed time to hospital admission were identified as risk factors for ICU admission or death due to pH1N1. Specifically, the odds of ICU admission or death were 4.44 times greater among adults aged 18-49 years (95% confidence interval [CI] 1.97, 10.02) and 5.93 times greater among adults aged 50-64 years (95% CI 2.24, 15.65) compared with pediatric patients < 18 years of age. Likewise, hospitalized cases admitted more than two days after illness onset had 2.17 times higher odds of ICU admission or death than those admitted within two days of illness onset (95% CI 1.10, 4.25). Although certain medical conditions clearly influence the need for hospitalization among people infected with pH1N1 virus, older age and delayed time to admission each played an independent role in the progression to ICU admission or death among hospitalized patients.
Wilcox, Holly C; Mittendorfer-Rutz, Ellenor; Kjeldgård, Linnea; Alexanderson, Kristina; Runeson, Bo
This study addresses the burden of grief after the death of an adolescent or young adult offspring. Parental bereavement following the death of an adolescent or young adult offspring is associated with considerable psychiatric and somatic impairment. Our aim is to fill a research gap by examining offspring death due to suicide, accidents, or natural causes in relation to risk of parental sickness absence with psychiatric or somatic disorders. This whole population-based prospective study included mothers and fathers of all offspring aged 16-24 years in Sweden on December 31, 2004 (n = 1,051,515). This study had no loss to follow-up and exposure, confounders, and the outcome were recorded independently of each other. Cox survival analysis was used to model time to sickness absence exceeding 30 days, adjusting for parental demographic characteristics, previous parental sickness absence and disability pension, and inpatient and outpatient psychiatric and somatic healthcare prior to offspring death in 2001-2004. This large study population provided satisfactory statistical power for stratification by parents' sex and adolescent and young adults' cause of death. Mothers and fathers of offspring suicide and accident decedents both had over tenfold higher risk for psychiatric sickness absence exceeding 30 days as compared to parents of live offspring. Fathers of suicide decedents were at 40 % higher risk for somatic sickness absence. This is the largest study to date of parents who survived their offspring's death and the first study of work-related outcomes in bereaved parents. This study uses a broad metric of work-related functional impairment, sickness absence, for capturing the burden of sudden offspring death.
Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy
Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.
Xie, Xinmin; Dumas, Theodore; Tang, Lamont; Brennan, Thomas; Reeder, Thadd; Thomas, Winston; Klein, Robert D; Flores, Judith; O'Hara, Bruce F; Heller, H Craig; Franken, Paul
The Na(+)-independent alanine-serine-cysteine transporter 1 (Asc-1) is exclusively expressed in neuronal structures throughout the central nervous system (CNS). Asc-1 transports small neutral amino acids with high affinity especially for D-serine and glycine (K(i): 8-12 microM), two endogenous glutamate co-agonists that activate N-methyl-D-aspartate (NMDA) receptors through interacting with the strychnine-insensitive glycine binding-site. By regulating D-serine (and possibly glycine) levels in the synaptic cleft, Asc-1 may play an important role in controlling neuronal excitability. We generated asc-1 gene knockout (asc-1(-/-)) mice to test this hypothesis. Behavioral phenotyping combined with electroencephalogram (EEG) recordings revealed that asc-1(-/-) mice developed tremors, ataxia, and seizures that resulted in early postnatal death. Both tremors and seizures were reduced by the NMDA receptor antagonist MK-801. Extracellular recordings from asc-1(-/-) brain slices indicated that the spontaneous seizure activity did not originate in the hippocampus, although, in this region, a relative increase in evoked synaptic responses was observed under nominal Mg(2+)-free conditions. Taken together with the known neurochemistry and neuronal distribution of the Asc-1 transporter, these results indicate that the mechanism underlying the behavioral hyperexcitability in mutant mice is likely due to overactivation of NMDA receptors, presumably resulting from elevated extracellular D-serine. Our study provides the first evidence to support the notion that Asc-1 transporter plays a critical role in regulating neuronal excitability, and indicate that the transporter is vital for normal CNS function and essential to postnatal survival of mice.
Jyot, Jeevan; Balloy, Viviane; Jouvion, Gregory; Verma, Amrisha; Touqui, Lhousseine; Huerre, Michel; Chignard, Michel; Ramphal, Reuben
The role of toxins secreted by the type II secretion system (T2SS) of Pseudomonas aeruginosa during lung infection has been uncertain despite decades of research. Using a model of pneumonia in Toll-like receptor (TLR) 2,4(-/-) mice, we reexamined the role of the T2SS system. Flagellin-deficient mutants of P. aeruginosa, with mutations in the T2SS and/or T3SS, were used to infect mice. Mice were followed up for survival, with some killed at different intervals to study bacterial clearance, inflammatory responses, and lung pathology. Strains carrying either secretion system were lethal for mice. Double mutants were avirulent. The T3SS(+) strains killed mice within a day, and the T2SS(+) strains killed them later. Mice infected with a strain that had only the T2SS were unable to eradicate the organism from the lungs, whereas those infected with a T2SS-T3SS double deletion were able to clear this mutant. Death caused by the T2SS(+) strain was accompanied by a >50-fold increase in bacterial counts and higher numbers of viable intracellular bacteria. The T2SS of P. aeruginosa may play a role in death from pneumonia, but its action is delayed. These data suggest that antitoxin strategies against this organism will require measures against the toxins secreted by both T2SS and T3SS.
Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J.
Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as “apoptosis-necrosis continuum.” To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. PMID:26124276
Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J
Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as "apoptosis-necrosis continuum." To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. © 2015 by The American Society for
Nezis, Ioannis P; Lamark, Trond; Velentzas, Athanassios D; Rusten, Tor Erik; Bjørkøy, Geir; Johansen, Terje; Papassideri, Issidora S; Stravopodis, Dimitrios J; Margaritis, Lukas H; Stenmark, Harald; Brech, Andreas
Autophagy is a physiological and evolutionarily conserved process maintaining homeostatic functions, such as protein degradation and organelle turnover. Accumulating data provide evidence that autophagy also contributes to cell death under certain circumstances, but how this is achieved is not well known. Herein, we report that autophagy occurs during developmentally-induced cell death in the female germline, observed in the germarium and during middle developmental stages of oogenesis in Drosophila melanogaster. Degenerating germline cells exhibit caspase activation, chromatin condensation, DNA fragmentation and punctate staining of mCherry-DrAtg8a, a novel marker for monitoring autophagy in Drosophila. Genetic inhibition of autophagy, by removing atg1 or atg7 function, results in significant reduction of DNA fragmentation, suggesting that autophagy acts genetically upstream of DNA fragmentation in this tissue. This study provides new insights into the mechanisms that regulate cell death in vivo during development.
Nagar, Himanshu; Yan, Weisi; Christos, Paul; Chao, K S Clifford; Nori, Dattatreyudu; Ravi, Akkamma
Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0
Alam, Rifat; Barrera, Maru; D'Agostino, Norma; Nicholas, David B; Schneiderman, Gerald
The authors investigated longitudinally bereavement in mothers and fathers whose children died of cancer. Thirty-one parents were interviewed 6 and 18 months post-death. Analyses revealed parental differences and changes over time: (a) employment--fathers were more work-focused; (b) grief reactions--mothers expressed more intense grief reactions that lessened over time; (c) coping--mothers were more child-focused, fathers more task-focused; (d) relationship with bereaved siblings-mothers actively nurtured relationship with child; (e) spousal relationship--parents reported diversity in their relationship over time; and (f) relationship with extended family--mothers maintained contact with extended family more. Findings illustrate parental differences in bereavement over time that might be partly socially determined. These findings emphasize the need for tailoring bereavement support services in the family.
Nait Amor, Samir; Ghalila, Hassen; Bouderba, Yasmina
Early events are a Very Low Frequencies (VLF) signal perturbations recorded during a lightning activity. The properties of these signal perturbations and their association to the lightning peak current and/or Transient Luminous Events (TLEs) were widely studied. In a recently analysis a new early signal perturbations whose recovery time persists for several minutes were discovered. The underlying cause of these events is still unclear. In a recently published work, these events were attributed to the lightning peak current and the type of associated TLE. In others, and newly published papers, analyzes were done where all kind of early events were considered. Statistical results showed that the occurrence of long recovery events is independent of the lightning current amplitude and/or TLEs type. To understand which is the main cause of these events, we analyzed two types of early signal perturbations: One was a typical event (~200s time duration) in association with a Gigantic Jet and the second was a long recovery event in association with an elve recorded on December 12 2009 during the EuroSprite campaign. In addition to the VLF signal analysis, we used the Long Wave Propagation Capability (LWPC) code to simulate the unperturbed and perturbed signal parameters (amplitude and phase), to determine the signal modes attenuation coefficient and then to infer the electron density increases in the disturbed region. The results showed that the reference height was reduced from its ambient value (87km) to 66.4 km in the case of the GJ and 74.3 km for the elve. These reference heights decreases affected the propagating signal at the disturbed region by increasing the modes attenuation coefficient. Effectively, the number of modes was reduced from 28 at ambient condition to 9 modes (in the case of GJ) and 17 (in the case of elve). This high attenuation of modes leads to the appearance of null signal perturbations positions due to the interferences. Between two null positions
Sibonga, Jean D.
Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition
Kawase, Koya; Azuma, Eiichi; Ohshita, Hironori; Tanaka, Tatsushi; Hanada, Yu; Sasaki, Tomoaki; Sugimoto, Mari; Togawa, Takao; Kouwaki, Masanori; Ito, Tsuyoshi; Hirayama, Masahiro; Koyama, Norihisa
Not only in newborns with Down syndrome, but newborns without phenotypic features of Down syndrome also develop transient myeloproliferative disorder (TMD). In these cases, trisomy 21 and related chromosomal abnormalities are either constitutionally mosaic or limited to blood cells. Risk factors for early death of these patients are unknown so far. We here report a fatal case of TMD without phenotypic features of Down syndrome and review literature to identify risk factors associated with early death. Not only are gestational age and white blood cell count risk factors for early death in TMD with Down syndrome, but they also appear to be risk factors in TMD without Down syndrome.
Motoyama, M.; Tsunakawa, H.; Takahashi, F.
The ocean tide is one of the most important factors affecting the Earth's surface environment and the evolution of the Earth-Moon system (e.g. Goldreich, 1966). According to the Giant Impact hypothesis, the Moon was formed very near the Earth 4.6 billion years ago (Hartmann and Davis, 1979). At that time, the tidal force would be about several thousand times as strong as the present. However previous studies pointed out that significant attenuation of tidal waves might have occurred due to mechanical response of water motion (e.g. Hansen, 1982; Abe and Ooe, 2001), resulting in relatively calm state like the present ocean.In the present study, we analyze tidal response of the ocean on the early Earth using a model of constant-depth ocean covering all the surface of the rigid Earth. The examined modes of response are not only M2 corresponding to spherical harmonics Y22 but also others such as Y21, since the lunar orbital plane would be inclined.First, estimated is an ocean depth for possible resonance of the individual mode. Eigen frequencies of the fluid on a rotating sphere with no friction are calculated on the basis of previous study (Longuet-Higgins, 1968). These frequencies depend on the Earth's rotation rate and the ocean depth. The Earth's rotation period is assumed to have changed from 5 hours to 24 hours for the past 4.6 billion years (e.g. Mignard, 1980; Stacey and Davis, 2008). It is found that resonance could occur for diurnal modes of Y21 and Y31 with reasonable depths of the ancient ocean (1300 - 5200 m).Then we obtain a 2D response function on a sphere with friction in order to estimate the tidal amplitude of the ocean for main modes . The response function in the present study shows good agreement with the numerical simulation result of the tidal torque response of M2 (Abe et al., 1997). The calculation results suggest that diurnal modes of Y21 and Y31 would grown on the early Earth, while the other modes would fairly be attenuated. In particular
White, Helene Raskin; Widom, Cathy Spatz
This study compared mortality data and causes of death in a sample of 908 abused and/or neglected individuals and 667 matched controls followed for 25 years into young adulthood. The study found no significant differences in rates of mortality for the two groups and victims of child abuse and neglect were not more likely to experience a violent…
V& aacute; clavík Tom& aacute; & scaron;
Phytophthora ramorum was first discovered in forests of southwestern Oregon in 2001. Despite intense eradication efforts, disease continues to spread from initially infested sites because of the late discovery of disease outbreaks and incomplete detection. Here we present two GIS predictive models of sudden oak death (SOD) establishment and spread...
Pealing, Louise; Perel, Pablo; Prieto-Merino, David; Roberts, Ian
Background Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. Methods and Findings We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) . We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001). Conclusions Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients. PMID:23251374
Friberg, Emilie; Rosenhall, Ulf; Alexanderson, Kristina
It is estimated that hearing difficulties will be one of the top ten leading burdens of disease by 2030. Knowledge of mortality among individuals on sick leave or disability pension due to hearing diagnoses is virtually non-existent. We aimed prospectively to examine the associations of diagnosis-specific sick leave and disability pension due to different otoaudiological diagnoses with risks of all-cause and cause-specific mortality. A cohort, based on Swedish registry data, including all 5,248,672 individuals living in Sweden in 2005, aged 20-64, and not on old-age pension, was followed through 2010. Otoaudiological diagnoses were placed in the following categories: otological, hearing, vertigo, and tinnitus. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models; individuals on sick leave or disability pension due to different otoaudiological diagnoses during 2005 were compared with those not on sick leave or disability pension. In multivariable models, individuals with sickness absence due to otoaudiological diagnoses showed a lower risk of mortality, while individuals on disability pension due to otoaudiological diagnoses showed a 14% (95% CI 1-29%) increased risk of mortality, compared with individuals not on sick leave or disability pension. The risk increase among individuals on disability pension was largely attributable to otological (HR 1.56; 95% CI = 1.04-2.33) and hearing diagnoses (HR 1.20; 95% CI = 1.00-1.43). This large nationwide population-based cohort study suggests an increased risk of mortality among individuals on disability pension due to otoaudiological diagnoses.
Background It is estimated that hearing difficulties will be one of the top ten leading burdens of disease by 2030. Knowledge of mortality among individuals on sick leave or disability pension due to hearing diagnoses is virtually non-existent. We aimed prospectively to examine the associations of diagnosis-specific sick leave and disability pension due to different otoaudiological diagnoses with risks of all-cause and cause-specific mortality. Methods A cohort, based on Swedish registry data, including all 5 248 672 individuals living in Sweden in 2005, aged 20–64, and not on old-age pension, was followed through 2010. Otoaudiological diagnoses were placed in the following categories: otological, hearing, vertigo, and tinnitus. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models; individuals on sick leave or disability pension due to different otoaudiological diagnoses during 2005 were compared with those not on sick leave or disability pension. Results In multivariable models, individuals with sickness absence due to otoaudiological diagnoses showed a lower risk of mortality, while individuals on disability pension due to otoaudiological diagnoses showed a 14% (95% CI 1-29%) increased risk of mortality, compared with individuals not on sick leave or disability pension. The risk increase among individuals on disability pension was largely attributable to otological (HR 1.56; 95% CI = 1.04-2.33) and hearing diagnoses (HR 1.20; 95% CI = 1.00-1.43). Conclusion This large nationwide population-based cohort study suggests an increased risk of mortality among individuals on disability pension due to otoaudiological diagnoses. PMID:24507477
Alonso-Alconada, Daniel; Hilario, Enrique; Álvarez, Francisco José; Álvarez, Antonia
Despite advances in neonatology, the hypoxic-ischemic injury in the perinatal period remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Using a sheep model of intrauterine asphyxia, we evaluated the correlation between reactive oxygen species (ROS) overproduction, cytokine expression, and apoptotic cell death. Fetal lambs were assigned to sham group, nonasphyctic animals; and hypoxia-ischemia (HI) group, lambs subjected to 60 minutes of HI) by partial cord occlusion and sacrificed 3 hours later. Different brain regions were separated to quantify the number of apoptotic cells and the same territories were dissociated for flow cytometry studies. Our results suggest that the overproduction of ROS and the early increase in cytokine production after HI in fetal lambs correlate in a significant manner with the apoptotic index, as well as with each brain region evaluated.
Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.
An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.
Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François
Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.
Monetti, Emanuela; Kadono, Takashi; Bouteau, François
Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571
Antonelli, Francesca; Esposito, Giuseppe; Dini, Valentina; Belli, Mauro; Campa, Alessandro; Sorrentino, Eugenio; Antonella Tabocchini, Maria; Lobascio, Cesare; Berra, Bruno
HZE particles from space radiation raise an important protection concern during long-term astronauts' travels. As high charge, high energy particles interact with a shield, both projec-tile and target fragmentation may occurs, so that the biological properties of the emerging radiation field depend on the nature and energy of the incident particles, and on the nature and thickness of the shield. We have studied the influence of PMMA and Kevlar shielding as well as the antioxidant compounds Rosmarinic acid or Resveratrol on DNA damage induction and processing (as evaluated by the g-H2AX phosphorylation assay) and on early and delayed cell death in AG01522 human fibroblasts irradiated with Fe ions of 595 MeV/u at the NASA Space Radiation Laboratory (NSRL), Brookhaven National Laboratory (BNL, Upton, USA). Insertion of PMMA or Kevlar shields (10 g/cm2 thick) gave no substantial change in the bio-logical effect per unit dose on the sample for all the end points studied. When irradiation was performed in the presence of 300 mM Rosmarinic acid or Resveratrol no difference were found for both early and delayed cell death, while a slight protective effect was observed for the initial and residual DNA damage. For both early and delayed cell death, Fe-ions are more effective than g-rays. The number of Fe-ion induced g-H2AX foci is instead lower than that induced by g-rays, due to the presence of multiple DSB within a single focus induced by Fe-ions. From a comparison of the g-H2AX data with the results on DNA fragmentation obtained with 414 MeV/u Fe ions at the Heavy Ions Medical Accelerator (HIMAC, Chiba, Japan) and with 1 GeV/u Fe ions at BNL, in the absence or in the presence of PMMA shields (Esposito et al, Advance in Space Research 2004) we speculate that the overall effect of the shield is a balance between the contributions due to the slowing down of the primary particles and that due to the nuclear fragmentation. Acknowledgment: Financial support from ASI project
Liu, Ruiling; Bohac, David L; Gundel, Lara A; Hewett, Martha J; Apte, Michael G; Hammond, S Katharine
Background Despite efforts to reduce exposure to secondhand smoke (SHS), only 5% of the world's population enjoy smoke-free restaurants and bars. Methods Lifetime excess risk (LER) of cancer death, ischaemic heart disease (IHD) death and asthma initiation among non-smoking restaurant and bar servers and patrons in Minnesota and the US were estimated using weighted field measurements of SHS constituents in Minnesota, existing data on tobacco use and multiple dose-response models. Results A continuous approach estimated a LER of lung cancer death (LCD) of 18×10−6(95% CI 13 to 23×10−6) for patrons visiting only designated non-smoking sections, 80×10−6(95% CI 66 to 95×10−6) for patrons visiting only smoking venues/sections and 802×10−6(95% CI 658 to 936×10−6) for servers in smoking-permitted venues. An attributable-risk (exposed/non-exposed) approach estimated a similar LER of LCD, a LER of IHD death about 10−2 for non-smokers with average SHS exposure from all sources and a LER of asthma initiation about 5% for servers with SHS exposure at work only. These risks correspond to 214 LCDs and 3001 IHD deaths among the general non-smoking population and 1420 new asthma cases among non-smoking servers in the US each year due to SHS exposure in restaurants and bars alone. Conclusions Health risks for patrons and servers from SHS exposure in restaurants and bars alone are well above the acceptable level. Restaurants and bars should be a priority for governments’ effort to create smoke-free environments and should not be exempt from smoking bans. PMID:23407112
Campbell, R; Weis, M A; Millet, L; Powell, V; Hull-Jilly, D; Hackman, H
Drawing from the experiences of individual state programs that currently participate in the National Violent Death Reporting System (NVDRS), this article reviews some of the practical benefits that may accrue from the introduction of violent death surveillance systems. As a state-based surveillance system that uses multiple data sources and relies upon multiple stakeholders, the NVDRS program has fostered an array of initiatives within and among individual state programs. State-based initiatives highlighted in this article were selected on the basis of a purposive sampling strategy intended to illustrate key aspects of program development. The NVDRS state programs are in Alaska, California, Colorado, Georgia, Kentucky, Maryland, Massachusetts, New Jersey, New Mexico, North Carolina, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin. The NVDRS has helped to build alliances and collaborative efforts between key stakeholders, facilitated the recognition of violent death as a public health problem through outreach and media attention, acted as a catalyst for new projects, enhanced surveillance of special populations and utility for evaluation, and identified key circumstances that will target interventions in state prevention planning. The NVDRS has implemented data collection efforts and is beginning to produce and analyze findings. In the process of implementing the data collection system and publicizing findings, state NVDRS programs are realizing other gains that strengthen their surveillance efforts. The use of data for prevention purposes will be the ultimate indicator of program success.
Fluschnik, Nina; Ojeda, Francisco; Zeller, Tanja; Jørgensen, Torben; Kuulasmaa, Kari; Becher, Peter Moritz; Sinning, Christoph; Blankenberg, Stefan; Westermann, Dirk
Growth differentiation factor-15 (GDF-15), Cystatin C and C-reactive protein (CRP) have been discussed as biomarkers for prediction of cardiac diseases. The aim of this study was to investigate the predictive value of single and repeated measurements of GDF-15 compared to Cystatin C and CRP for incidence of heart failure (HF) and death due to coronary heart disease (CHD) in the general population. Levels of GDF-15, CRP and Cystatin C were determined in three repeated measurements collected 5 years apart in the DAN-MONICA (Danish-Multinational MONitoring of trends and determinants in Cardiovascular disease) cohort (participants at baseline n = 3785). Cox regression models adjusted for cardiovascular risk factors revealed significantly increased hazard ratios (HR) for GDF-15 for incident HF 1.36 (HR per interquartile range (IQR) increase, 95% confidence interval (CI): 1.16; 1.59) and for death from CHD 1.51 (HR per IQR increase, 95% CI: 1.31, 1.75) (both with p<0.001). Joint modeling of time-to-event and longitudinal GDF-15 over a median 27-year follow-up period showed that the marker evolution was positively associated with death of CHD (HR per IQR increase 3.02 95% CI: (2.26, 4.04), p < 0.001) and HF (HR per IQR increase 2.12 95% CI: (1.54, 2.92), p<0.001). However using Cox models with follow-up time starting at the time of the third examination, serial measurement of GDF-15, modeled as changes between the measurements, did not improve prediction over that of the most recent measurement. GDF-15 is a promising biomarker for prediction of HF and death due to CHD in the general population, which may provide prognostic information to already established clinical biomarkers. Repeated measurements of GDF-15 displayed only a slight improvement in the prediction of these endpoints compared to a single measurement.
Bloch, Miki; Peleg, Ido; Koren, Danny; Aner, Hamotal; Klein, Ehud
We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (p<0.03). Group by time effect reached a trend level (p<0.06). A correlation was found between psychiatric symptomatology and PBI scores; however, both parameters did not correlate with HPA axis activity. A significant correlation was found between DAS scores and ACTH. A regression model revealed a contributing effect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.
Dean, Dylan; Wetzel, Brian; White, Nathan; Kuppermann, Nathan; Wang, Nancy Ewen; Haukoos, Jason S; Hsia, Renee Y; Mann, N Clay; Barton, Erik D; Newgard, Craig D
This study aimed to characterize initial clinical presentations of patients served by emergency medical services (EMS) who die following injury, with particular attention to patients with occult ("talk-and-die") presentations. This was a population-based, multiregion, mixed-methods retrospective cohort study of fatally injured children and adults evaluated by 94 EMS agencies transporting to 122 hospitals in seven Western US regions from 2006 to 2008. Fatalities were divided into two main groups: occult injuries (talk-and-die; Glasgow Coma Scale [GCS] score ≥ 13, no cardiopulmonary arrest, and no intubation) versus overt injuries (all other patients). These groups were further subdivided by timing of death: early (<48 hours) versus late (>48 hours). We then compared demographic, physiologic, procedural, and injury patterns using descriptive statistics. We also used qualitative methods to analyze available EMS chart narratives for contextual information from the out-of-hospital encounter. During the 3-year study period, 3,358 persons served by 9-1-1 EMS providers died, with 1,225 (37.1%) in the field, 1,016 (30.8%) early in the hospital, and 1,060 (32.1%) late in the hospital. Of the 2,133 patients transported to a hospital, there were 612 (28.7%) talk-and-die patients, of whom 114 (18.6%) died early. Talk-and-die patients were older (median age, 81 years; interquartile range, 67-87 years), normotensive (median systolic blood pressure, 138 mm Hg; interquartile range, 116-160 mm Hg), commonly injured by falls (71.3%), and frequently (52.4%) died in nontrauma hospitals. Compared with overtly injured patients, talk-and-die patients had relatively fewer serious head injuries (13.7%) but more frequent extremity injuries (20.3% vs. 10.6%) and orthopedic interventions (25.3% vs. 5.0%). EMS personnel often found talk-and-die patients lying on the ground with hip pain or extremity injuries. Patients served by EMS who "talk-and-die" are typically older adults with falls
Resnick, Shelby; Seamon, Mark J; Holena, Daniel; Pascual, Jose; Reilly, Patrick M; Martin, Niels D
Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation. Using data over a 5-year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs , kidneys , liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t-test. Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (±16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates. A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed. Copyright © 2017 Elsevier Inc. All rights
Hess, C; Unger, M; Madea, B; Stratmann, B; Tschoepe, D
Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death. To describe a concentration range in clinical samples after chronic use of metformin, metformin serum concentrations were determined in serum samples of 95 diabetic patients receiving daily doses of 500mg-3000mg of metformin. The analyses of metformin was carried out using a validated high performance liquid chromatograph coupled to triple quadrupole mass spectrometry (LC-QQQ-MS). On average, metformin concentrations were 1846ng/mL (
Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E
We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
Nisar, Yasir Bin; Dibley, Michael J.
Introduction Early neonatal deaths account for 75% of neonatal deaths globally. Antenatal iron-folic acid (IFA) supplementation has significantly reduced the risk of early neonatal deaths in China and Indonesia. We investigated the impact of antenatal IFA supplements on the risk of early neonatal deaths in Nepal and Pakistan during the last decade. Methods Data from the most recent singleton live-births of 8,186 from two Nepal Demographic and Health Surveys (DHS) and 13,034 from two Pakistan DHS were selected for the current study. The primary outcome was early neonatal deaths and the main study variable was antenatal IFA supplementation. Analyses used multivariate Cox proportional regression, adjusted for the cluster sampling design and for 18 potential confounders. Findings The adjusted risk of early neonatal deaths was significantly reduced by 51% (aHR = 0.49, 95% CI = 0.32–0.75) in Nepal and 23% (aHR = 0.77, 95% CI = 0.59–0.99) in Pakistan with any use of IFA compared to none. When IFA supplementation started at or before the 5th month of pregnancy, the adjusted risk of early neonatal mortality was significantly reduced by 53% in Nepal, and 28% in Pakistan, compared to no IFA. When >90 IFA supplements were used and started at or before 5th months, the adjusted risk of early neonatal deaths was significantly reduced by 57% in Nepal, and 45% in Pakistan. In Nepal 4,600 and in Pakistan 75,000 early neonatal deaths could be prevented annually if all pregnant women used >90 IFA supplements and started at or before the 5th month of pregnancy. Conclusions Any use of IFA supplements was significantly associated with reduced risk of early neonatal deaths in Nepal and Pakistan. The greatest mortality sparing effect of IFA on early neonatal deaths in both countries was with early initiation and use of a greater number of supplements. PMID:25398011
Yamada, Takahisa; Muramatsu, Youji; Taniguchi, Yukio; Sasaki, Yoshiyuki
Our previous study detected 291 and 77 genes showing early embryonic death-associated elevation and reduction of expression, respectively, in the fetal placenta of the cow carrying somatic nuclear transfer-derived cloned embryo. In this study, we mapped the 10 genes showing the elevation and the 10 genes doing the reduction most significantly, using somatic cell hybrid and bovine draft genome sequence. We then compared the mapped positions for these genes with the genomic locations of bovine quantitative trait loci for still-birth and/or abortion. Among the mapped genes, peptidylglycine alpha-amidating monooxygenase (PAM), spectrin, beta, nonerythrocytic 1 (SPTBNI), and an unknown novel gene containing AU277832 expressed sequence tag were intriguing, in that the mapped positions were consistent with the genomic locations of bovine still-birth and/or abortion quantitative trait loci, and thus identified as positional candidates for bovine placental genes responsible for the early embryonic death during the pregnancy attempted by somatic nuclear transfer-derived cloning.
Kirk, Diana K.; Gopalakrishnan, Sandeep; Schmitt, Heather; Abroe, Betsy; Stoehr, Michele; Dubis, Adam; Carroll, Joseph; Stone, Jonathan; Valter, Krisztina; Eells, Janis
Irradiation by light in the far-red to near-infrared (NIR) region of the spectrum (photobiomodulation, PBM) has been demonstrated to attenuate the severity of neurodegenerative disease in experimental and clinical studies. The purpose of this study was to test the hypothesis that 670 nm PBM would protect against the loss of retinal function and improve photoreceptor survival in a rodent model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated once per day with a 670 nm LED array (180 sec treatments at 50 mW/cm2; fluence 9 joules/cm2) (Quantum Devices Inc., Barneveld WI) from postnatal day (p) 16-20 or from p10-20. Sham-treated rats were restrained, but not exposed to NIR light. The status of the retina was determined at p22 by assessment of mitochondrial function, oxidative stress and cell death. In a second series of studies, retinal status was assessed at p30 by measuring photoreceptor function by ERG and retinal morphology by Spectral Domain Optical Coherence Tomography (SD-OCT). 670 nm PBM increased retinal mitochondrial cytochrome oxidase activity and upregulated the retina's production of the key mitochondrial antioxidant enzyme, MnSOD. PBM also attenuated photoreceptor cell loss and improved photoreceptor function. PBM protects photoreceptors in the developing P23H retina, by augmenting mitochondrial function and stimulating antioxidant protective pathways. Photobiomodulation may have therapeutic potential, where mitochondrial damage is a step in the death of photoreceptors.
Szymczak, Wiesław; Sobala, Wojciech; Wilczyńska, Urszula; Szeszenia-Dabrowska, Neonila
The main goal of the study was to analyze thoroughly the results of a cohort study. Such an analysis renders it possible to eliminate certain neoplasms as those not related to the observed exposure. The cohort study was carried out in a group of workers, covering 11,342 persons (5472 men and 5870 women), employed for at least one year during the years 1945-1985 in a rubber footwear plant. The cohort study was continued until the end of December 1997. Of all the sites of malignant neoplasms observed in the cohort, significant, exposure-related excess mortality was found to be due to malignant neoplasms of larynx and lung in men, and malignant neoplasms of gallbladder and lung in women. For these neoplasms, the values of observed risk among those exposed were significantly higher than among non-exposed. Moreover, in a certain interval of employment duration, an increase in risk rates with increasing duration of employment under exposure was observed, which suggests the presence of dose-response relationship. For all these sites, a relevant trend was shown by the RR values calculated in relation to the group of persons non-exposed but employed in the same plant. The internal reference group used to calculate RR values allowed to eliminate the effect of confounding variables, which is not always possible when the general population is used as the reference group.
Dubey, J P
Six does serologically negative to toxoplasma gondii were vaccinated with 1 million oocysts of the nonpathogenic coccidiym Hammondia hammondi 17 to 73 days before breeding. Two does were not inoculated with H hammondi. All does were mated with a T gondii-free buck. Between the 51st and 119th days of their pregnancies, 5 of the 6 Hammondia-vaccinated does and the 2 controls were each inoculated orally with 1,000 infective oocysts of the GT-1 strain of T gondii. Four of the 5 Toxoplasma-inoculated vaccinated does gave birth to 8 apparently healthy kids at the expected gestation period. The 5th vaccinated doe gave birth to 3 kids that died during delivery or were born dead. Toxoplasma gondii was isolated in mice inoculated with tissues of all kids born to vaccinated does. The vaccinated doe which was not inoculated with T gondii gave birth to 2 healthy noninfected kids. Of the 2 control pregnant does (not vaccinated, but inoculated with T gondii), 1 aborted due to toxoplasmosis 17 days after inoculation. The other control doe had 2 dead fetuses and retained fetal membranes in uterus when necropsied at the expected parturition time. the results indicate that it might be possible to develop a vaccine against toxoplasmic abortions in animals.
Mishra, Shikha; Guan, Jian; Plovie, Eva; Seldin, David C; Connors, Lawreen H; Merlini, Giampaolo; Falk, Rodney H; MacRae, Calum A; Liao, Ronglih
Systemic amyloid light-chain (AL) amyloidosis is associated with rapidly progressive and fatal cardiomyopathy resulting from the direct cardiotoxic effects of circulating AL light chain (AL-LC) proteins and the indirect effects of AL fibril tissue infiltration. Cardiac amyloidosis is resistant to standard heart failure therapies, and, to date, there are limited treatment options for these patients. The mechanisms underlying the development of cardiac amyloidosis and AL-LC cardiotoxicity are largely unknown, and their study has been limited by the lack of a suitable in vivo model system. Here, we establish an in vivo zebrafish model of human AL-LC-induced cardiotoxicity. AL-LC isolated from AL cardiomyopathy patients or control nonamyloidogenic LC protein isolated from multiple myeloma patients (Con-LC) was directly injected into the circulation of zebrafish at 48 h postfertilization. AL-LC injection resulted in impaired cardiac function, pericardial edema, and increased cell death relative to Con-LC, culminating in compromised survival with 100% mortality within 2 wk, independent of AL fibril deposition. Prior work has implicated noncanonical p38 MAPK activation in the pathogenesis of AL-LC-induced cardiotoxicity, and p38 MAPK inhibition via SB-203580 rescued AL-LC-induced cardiac dysfunction and cell death and attenuated mortality in zebrafish. This in vivo zebrafish model of AL-LC cardiotoxicity demonstrates that antagonism of p38 MAPK within the AL-LC cardiotoxic signaling response may serve to improve cardiac function and mortality in AL cardiomyopathy. Furthermore, this in vivo model system will allow for further study of the molecular underpinnings of AL cardiotoxicity and identification of novel therapeutic strategies.
Ellis, Jackie; Dowrick, Chris; Lloyd-Williams, Mari
Objective To explore the individual experiences of those who had experienced the death of a parent(s) before the age of 18, and investigate how such experiences were perceived to impact on adult life. Design An exploratory qualitative design using written (n = 5) and oral (n = 28) narratives and narrative analysis was adopted to explore the experiences 33 adults (7 men and 26 women) who had experienced parental death during childhood. Setting UK Participants Individuals living in the North West of England who had lost a parent(s) before the age of 18. Main outcome measures Views of adults bereaved of a parent before the age of 18 of impact of parental loss in adult life. Results While individual experiences of bereavement in childhood were unique and context bound, the narratives were organized around three common themes: disruptions and continuity, the role of social networks and affiliations and communication and the extent to which these dynamics mediated the bereavement experience and the subsequent impact on adult life. Specifically they illustrate how discontinuity (or continuity that does not meet the child's needs), a lack of appropriate social support for both the child and surviving parent and a failure to provide clear and honest information at appropriate time points relevant to the child's level of understanding was perceived to have a negative impact in adulthood with regards to trust, relationships, self-esteem, feeling of self-worth loneliness and isolation and the ability to express feelings. A model is suggested for identifying and supporting those that may be more vulnerable to less favourable outcomes in adult life. Conclusions The findings suggest that if the negative consequences are to be minimized it is crucial that guidelines for ‘best practice’ that recognize the complex nature of the bereavement experience are followed. PMID:23392851
Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Castro-Obregón, Susana; Massieu, Lourdes
Autophagy is triggered during nutrient and energy deprivation in a variety of cells as a homeostatic response to metabolic stress. In the CNS, deficient autophagy has been implicated in neurodegenerative diseases and ischemic brain injury. However, its role in hypoglycemic damage is poorly understood and the dynamics of autophagy during the hypoglycemic and the glucose reperfusion periods, has not been fully described. In the present study, we analyzed the changes in the content of the autophagy proteins BECN1, LC3-II and p62/SQSTM1 by western blot, and autophagosome formation was followed through time-lapse experiments, during glucose deprivation (GD) and glucose reintroduction (GR) in cortical cultures. According to the results, autophagosome formation rapidly increased during GD, and was followed by an active autophagic flux early after glucose replenishment. However, cells progressively died during GR and autophagy inhibition reduced neuronal death. Neurons undergoing apoptosis during GR did not form autophagosomes, while those surviving up to late GR showed autophagosomes. Calpain activity strongly increased during GR and remained elevated during progressive neuronal death. Its activation led to the cleavage of LAMP2 resulting in lysosome membrane permeabilization (LMP) and release of cathepsin B to the cytosol. Calpain inhibition prevented LMP and increased the number of neurons containing lysosomes and autophagosomes increasing cell viability. Taken together, the present results suggest that calpain-mediated lysosome dysfunction during GR turns an adaptive autophagy response to energy stress into a defective autophagy pathway, which contributes to neuronal death. In these conditions, autophagy inhibition results in the improvement of cell survival.
Calderón-Garcidueñas, Ana Laura; Piña-Osuna, Karina; Leal-Moreno, Ana María; López-Cárdenas, Adriana; Cerda-Flores, Ricardo M
1. To describe clinical and pathologic characteristics of patients with coccidioidomycosis (CM) who died from 1983-2000 at a hospital in northeastern Mexico, and 2, to know distribution of number of deaths due to CM per year and month. From 4598 autopsies, 31 cases of CM were selected. Clinical chart and autopsy protocols were examined. Distribution of cases was analyzed by contingence table and Kolmogorov-Smirnov tests. There were 10 women and 21 men (aged 4 months to 60 years). In women, pregnancy was present in 40% of cases. In men, chronic renal failure (CRF) (38%) and AIDS (19%) were the pathologic conditions most frequently observed. Variation in distribution of cases throughout 18 years was not observed (p > 0.05). Mortality due to CM was 0.67% and variation in number of deaths was not found. In this endemic area, CM must be included in differential diagnosis of patients with risk factors such as pregnancy, CRF, and AIDS, especially if associated with pneumonia with miliary pattern or septicemia with splenomegaly.
Xu, Haiqing; Dai, Qiong; Xu, Yusong; Gong, Zhengtao; Dai, Guohong; Ding, Ming; Duggan, Christopher; Hu, Zubin; Hu, Frank B
The nutrition and epidemiologic transition has been associated with an increasing incidence of preterm birth in developing countries, but data from large observational studies in China have been limited. Our study was to describe the trends and factors associated with the incidence of preterm birth and infant mortality due to prematurity in Hubei Province, China. We conducted a population-based survey through the Maternal and Child Health Care Network in Hubei Province from January 2001 to December 2012. We used data from 16 monitoring sites to examine the trend and risk factors for premature birth as well as infant mortality associated with prematurity. A total of 818,481 live births were documented, including 76,923 preterm infants (94 preterm infants per 1,000 live births) and 2,248 deaths due to prematurity (2.75 preterm deaths per 1,000 live births). From 2001 to 2012, the incidence of preterm birth increased from 56.7 to 105.2 per 1,000 live births (P for trend < 0.05), while the infant mortality rate due to prematurity declined from 95.0 to 13.4 per 1,000 live births (P for trend < 0.05). Older maternal age, lower maternal education, use of assisted reproductive technology (ART), higher income, residence in urban areas, and infant male sex were independently associated with a higher incidence of preterm birth (all p values < 0.05). Shorter gestation, lower birth weight, and lower income were associated with a higher mortality rate, while use of newborn emergency transport services (NETS) was associated with a lower preterm mortality rate (all p values < 0.05). An increasing incidence of preterm birth and a parallel reduction in infant mortality due to prematurity were observed in Hubei Province from 2001 to 2012. Our results provide important information for areas of improvements in reducing incidence and mortality of premature birth.
Hata, Yukiko; Yoshida, Koji; Kinoshita, Koshi; Nishida, Naoki
A 64-year-old woman was found dead in her home. At autopsy, although relatively fresh bruises were found on her body, no lethal injury was observed in an internal observation. Mild edematous swelling of the right half of the medulla oblongata was observed. There was acute medial medullary infarction (MMI), which mainly involved the nucleus hypoglossi, medial lemniscus, hypoglossal root, inferior olivary nucleus, and pyramidal tract. Subacute infarction of the lower part of the cerebellum was also found, and severe atherosclerosis of the right vertebral artery containing thrombi was found as the culprit lesion. Immunohistochemistry using amyloid precursor protein (APP) was positive in neuronal tissue in the nucleus ambiguus, despite not showing coagulative necrosis in the nucleus. Therefore, acute ischemic necrosis of the nucleus ambiguus, which is considered to be a component of the dorsal respiratory group, may be a significant finding for her expected death. Immunohistochemistry of APP may be useful for confirming the precise extent of acute ischemia in brain stem infarction, such as unilateral MMI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa
Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675
Raczkowska, Zuzanna; Samojłowicz, Dorota
Nitrogen causes environmental asphyxia by displacing oxygen in the air leading to death. The study presents a case of a death of a driver death who was transporting flasks with liquid nitrogen that depressurized during an accident. The mechanism and cause of death were determined based on the result of the autopsy and histopathologic examination. The authors emphasize the relevance of accident scene inspection during establishing the cause of death in similar cases.
Nieder, Carsten; Dalhaug, Astrid; Pawinski, Adam; Aandahl, Gro; Norum, Jan
In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer) in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years). Actuarial survival analyses were performed. During the first 3 years, two patients (1.1%) died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4%) was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI) scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition). The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis). However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis. PMID:21666987
Huynh, Quan; Negishi, Kazuaki; De Pasquale, Carmine; Hare, James; Leung, Dominic; Stanton, Tony; Marwick, Thomas H
To investigate whether enrolment of patients in management programs after hospitalisation for heart failure (HF) reduces the likelihood of post-hospital adverse outcomes. Cohort study in which associations between adverse outcomes at 30 and 90 days for people hospitalised for HF and baseline clinical, socio-demographic and blood pathology factors, and with post-discharge management strategies, were assessed. Setting, participants: 906 patients with HF were prospectively enrolled in five Australian states at cardiology departments with expertise in treating people with HF. All-cause re-admissions and deaths at 30 and 90 days after discharge from the index admission. 58% of patients were men; the mean age was 72.5 years (SD, 13.9 years). By hospital, 30-day re-admission rates ranged from 17% to 33%, and 90-day rates from 40% to 55%; 30-day mortality rates were 0-13%, 90-day rates 4-24%. Factors associated with increased odds of re-admission or death at 30 or 90 days included living alone, cognitive impairment, depression, NYHA classification, left atrial volume index, and Charlson index score. Nurse-led disease management programs and reviews within 7 days were associated with reduced odds of re-admission (but not of death) at 30 and 90 days; exercise programs were associated with reduced odds at 90 days. Significant between-hospital differences in re-admission rates were reduced after adjustment for post-discharge management programs, and abolished by further adjustment for echocardiography findings. Between-hospital differences in mortality were largely explained by differences in echocardiographic findings. Differences in early re-admission rates after hospitalisation for HF are primarily explained by differences in post-discharge management.
López-Fernández, Teresa; Thavendiranathan, Paaladinesh
The undeniable advances in the field of oncology have finally led to a decrease in overall cancer-related mortality. However, this population of long-term cancer survivors is now facing a shift toward a substantial increase in cardiovascular morbidity and mortality. Because the development of overt cardiotoxicity can be associated with poor outcomes, preclinical identification of cardiac toxicity is important. This will promote early instauration of treatments to prevent overt heart dysfunction and allow oncologists to continue cancer therapy in an uninterrupted manner. Surveillance strategies for the early detection of cardiac injury include cardiac imaging and biomarkers during treatment. In this review, we outline existing cardiac imaging modalities to detect myocardial changes in patients undergoing cancer treatment and in survivors, and their strengths and limitations. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
O'Toole, D; Chase, C C L; Miller, M M; Campen, H Van
The inaugural issue of Pathologia Veterinaria in 1964 contained the first detailed account of lesions in aborted fetuses following natural, experimental, and postvaccinal infection with bovine herpesvirus 1 (BoHV-1). The article, written by pathologists Kennedy and Richards, described diagnostic gross and histologic features in 13 bovine fetuses. The authors provided clinical and epidemiologic features of 1 postvaccination outbreak, including the absence of clinical signs in infected dams and the propensity for abortions to occur after 6 months' gestation. Subsequent field and experimental studies corroborated and expanded these observations. As a result of this and later reports, veterinarians became alert to the association between infectious bovine rhinotracheitis and abortion, including the risks of exposing pregnant cattle to live vaccinal BoHV-1. Methods were developed to corroborate a morphologic diagnosis of herpetic abortion in cattle, including immunofluorescence, immunohistochemistry, and polymerase chain reaction methods. Outbreaks of postvaccinal BoHV-1 abortion in the United States began to be reported with apparently increased frequency in the early 2000s. This coincided with licensure in 2003 of modified live BoHV-1 vaccines intended for use in pregnant cattle, which are now sold by 3 manufacturers. Ten recent herd episodes of postvaccinal BoHV-1 abortion are reported. All 10 BoHV-1 isolates had single-nucleotide polymorphism (SNPs) profiles previously identified in a group of BoHV-1 isolates that contains vaccine strains, based on a BoHV-1 SNP classification system. They lacked SNP features typical of those in characterized field-type strains of BoHV-1. © The Author(s) 2014.
Higuchi, Fumito; Tajima, Michio; Ogura, Atsushi
To analyze the early stage of oxygen precipitation in n-type multicrytalline Si, the spectral change of photoluminescence (PL) induced by thermal treatment at 450-650 °C was investigated in relation to the changes in excess donor and interstitial oxygen concentrations. We observed the characteristic PL bands in the near-band-edge region and sharp lines in the deep-level region in correspondence with the generation of thermal donors and new donors. The observed PL spectral variation is essentially the same as that in Czochralski-grown Si annealed at 450-650 °C.
Busardò, Francesco Paolo; Portelli, Francesca; Montana, Angelo; Rotolo, Maria Concetta; Pichini, Simona; Maresi, Emiliano
We here report a case involving a 21-year-old female, found dead in a central square of a city in the south of Italy. Initial evidences and circumstances were suggestive of a death associated with a sexual assault. Two peripheral blood and two vitreous humor samples were collected for the purpose of gamma-hydroxybutyric acid (GHB) testing from the dead body at two different post-mortem intervals (PMIs): approximately 2 (t 0 ) and 36 (t 1 ) hours. The obtained results showed that, between t 0 and t 1, there was an increase of GHB concentrations in peripheral blood and vitreous humor of 66.3% and 8.1%, respectively. This case was the first evidence of GHB post mortem production in a dead body and not in vitro, showing that vitreous humor is less affected than peripheral blood in GHB post-mortem production. The value detected at t 1 in peripheral blood (53.4µg/mL) exceeded the proposed cut-off and if interpreted alone would have led to erroneous conclusions. This was not the case of vitreous humor GHB, whose post-mortem increase was minimal and it allowed to exclude a GHB exposure. Only after a broad forensic investigation including a complete autopsy, serological, histological, toxicological and haematology analyses, a diagnosis of idiopathic hypereosinophilic syndrome, a myeloproliferative disorder characterized by persistent eosinophilia associated with damage to multiple organs, was made and the cause of death was due to a pulmonary eosinophilic vasculitis responsible for an acute respiratory failure. Copyright © 2017 Elsevier B.V. All rights reserved.
Hassan, Inaam Bashir; Zaabi, Mariam R Al; Alam, Arif; Hashim, Mohammed Jawad; Tallman, Martin S; Kristensen, Jorgen
Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0.030), WBC count >20 × 10 9 /L (P = 0.010), the breakpoints other than bcr1 (P = 0.043) and fibrinogen level <1.5 g/L (P = 0.025). Delay in ATRA administration beyond 24 h from admission and fibrinogen <150 mg/dL were also significant predictors of ED, but only among high-risk patients (P = 0.035 and P = 0.033, respectively). WBC count >10 × 10 9 /L and expression of HLA-DR (P = 0.018) or CD2 (P = 0.017) were significant predictors for differentiation syndrome (DS) which was found to be a predictor of ED (P = 0.002). Reducing the APL related ED rate in centers with limited resources is feasible provided early initiation of ATRA administration and early correction of coagulopathy in high-risk patients in addition to prompt treatment of DS. To our knowledge this is the first report from the Arabian Gulf describing ED in APL.
Weischer, Maren; Nordestgaard, Børge G.; Pharoah, Paul; Bolla, Manjeet K.; Nevanlinna, Heli; van't Veer, Laura J.; Garcia-Closas, Montserrat; Hopper, John L.; Hall, Per; Andrulis, Irene L.; Devilee, Peter; Fasching, Peter A.; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G.; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J.; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M.; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M.; Wang, Qin; Muranen, Taru A.; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C.; Czene, Kamila; Knight, Julia A.; Tollenaar, Rob A.E.M.; Beckmann, Matthias W.; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W.R.; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E.; Kosma, Veli-Matti; Kristensen, Vessela N.; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B.; Leunen, Karin; Kriege, Mieke; Cross, Simon S.; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F.; Schmidt, Marjanka K.; Bojesen, Stig E.
Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer–specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer–specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor–positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer–specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor–positive first breast cancer only. Conclusion Among women with estrogen receptor–positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer–specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer. PMID:23109706
Lee, Who-Seung; Monaghan, Pat; Metcalfe, Neil B
Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence.Using three-spined sticklebacks ( Gasterosteus aculeatus ), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish caught up in size with controls.However, this growth acceleration influenced swimming endurance and its decline over the course of the breeding season, with a faster decline in fish that had undergone faster growth compensation.Similarly, accelerated growth led to a more pronounced reduction in the breeding period (as indicated by the duration of sexual ornamentation) over the following two breeding seasons, suggesting faster reproductive senescence. Parallel experiments showed a heightened effect of accelerated growth on these age-related declines in performance if the fish were under greater time stress to complete their compensation prior to the breeding season.Compensatory growth led to a reduction in median life span of 12% compared to steadily growing controls. While life span was independent of the eventual adult size attained, it was negatively correlated with the age-related decline in swimming endurance and sexual ornamentation.These results, complementary to those found when growth trajectories were altered by temperature rather than dietary manipulations, show that the costs of accelerated growth can last well beyond the time over which growth rates differ and are affected by the time available until an approaching life-history event such as reproduction.
Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey
Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113
Gioia, Sara; Bacci, Mauro; Lancia, Massimo; Carlini, Luigi; Suadoni, Fabio
We present a peculiar autopsy case of a transorbital penetrating head injury, in a male worker, after an accidental fall onto a screw not completely stuck into a wooden board. A 13-cm screw entered the cranium 9.5 cm deep, penetrating with the flat end, a condition defined in literature as "reverse penetration." The death was instantaneous and caused by a neurogenic shock due to injuries to the brain stem and the right cerebellar hemisphere. These injuries, enabled by the length of the screw, are generally described in literature as due to nontransorbital penetrations, frequently associated with posterior entry and a large intracranial injury. The ocular globe has been, furthermore, perfectly preserved thanks to its mobility in the orbit. Even the dynamic of the incident is peculiar because of the stationary nature of the penetrating object, which the victim actively fell on by accident. To the best of our knowledge, the matter is therefore a very peculiar mortal case of transorbital intracranial penetration, whose verified injuries and dynamics are absolutely atypical. The case is now under discussion, and a review of pertinent literature is performed.
Nowacki, Laetitia; Follet, Julie; Vayssade, Muriel; Vigneron, Pascale; Rotellini, Laura; Cambay, Florian; Egles, Christophe; Rossi, Claire
Since a few years, the acoustic sensing of whole cell is the focus of increasing interest for monitoring the cytoskeletal cellular response to morphological modulators. We aimed at illustrating the potentialities of the quartz crystal microbalance with dissipation (QCM-D) technique for the real-time detection of the earliest morphological changes that occur at the cell-substrate interface during programmed cell death. Human breast cancer cells (MCF-7) grown on serum protein-coated gold sensors were placed in dynamic conditions under a continuous medium flow. The mass and viscoelasticity changes of the cells were tracked by monitoring the frequency and dissipation shifts during the first 4h of cell exposure to staurosporine, a well-known apoptosis inducer. We have identified a QCM-D signature characteristic of morphological modifications and cell detachment from the sensing surface that are related to the pro-apoptotic treatment. In particular, for low staurosporine doses below 1 µM, we showed that recording the dissipation shift allows to detect an early cell response which is undetectable after the same duration by the classical analytical techniques in cell biology. Furthermore, this sensing method allows quantifying the efficiency of the drug effect in less than 4h without requiring labeling and without interfering in the system, thus preventing any loss of information. In the actual context of targeted cancer therapy development, we believe that these results bring new insights in favor of the use of the non invasive QCM-D technique for quickly probing the cancer cell sensitivity to death inducer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.
Davis, Jeremy L; Langan, Russell C; Panageas, Katherine S; Zheng, Junting; Postow, Michael A; Brady, Mary S; Ariyan, Charlotte; Coit, Daniel G
Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma. Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray's test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors. Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (≥3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD. NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.
Harrison, Gordon A; Jacques, Theresa; McLaws, Mary-Louise; Kilborn, Gabrielle
Medical emergency team (MET) call criteria are late signs of a deteriorating clinical condition. Some early signs predict in-hospital death but have a high prevalence so their use as single sign call criteria could be wasteful of resources. This study searched a large database to explore the association of combinations of recordings of early signs (ES), or early with late signs (LS) with in-hospital death. A cross-sectional survey was undertaken of 3046 non-do not attempt resuscitation adult admissions in 5 hospitals without MET over 14 days. The medical records were reviewed for recordings of 26 ES and 21 LS and in-hospital death. Combinations of ES with or without LS were examined as predictors of death. Global modified early warning scores (GMEWS) were calculated. ES with LS, plus LS only, had higher odd ratios than ES alone. Four combinations of ES were strongly associated with death: cardiovascular plus respiratory with decrease in urinary output, cardiovascular plus respiratory with a decrease in consciousness, respiratory with decrease in urinary output, and cardiovascular plus respiratory. In other combinations, recordings of SpO2 90-95%, systolic blood pressure 80-100 mmHg or decrease in urinary output in turn occurring with one or more disturbed blood gas variable were associated with death. Compared with admissions whose GMEWS were 0-2, admissions with GMEWS 5-15 were 27.1 times more likely to die while those with GMEWS 3-4 were 6.5 times more likely. The results support the inclusion of early signs of a deteriorating clinical condition in sets of call criteria.
WANG, L.; Yu, J. Y.; Paek, H.
The El Niño-Southern Oscillation (ENSO) and Pacific subtropical highs (PSHs) have major impacts on social and ecological systems through their influences on severe natural hazards including tropical storms, coastal erosions, droughts and floods. The ability to forecast ENSO and PSHs requires an understanding of the underlying physical mechanisms that drive their variability. Here we present an Atlantic capacitor effect mechanism to suggest the Atlantic as a key pacemaker of the biennial variability in the Pacific including ENSO and PSHs in recent decades, while the pacemaker was previously considered to be mainly lied within the Pacific or Indian Oceans. The "charging" (i.e., ENSO imprinting the North Tropical Atlantic (NTA) sea surface temperature (SST) via an atmospheric bridge mechanism) and "discharging" (i.e., the NTA SST triggering the following ENSO via a subtropical teleconnection mechanism) process works alternately, generating the biennial rhythmic changes in the Pacific. After the early-1990s, the positive phase of the Atlantic Multidecadal Oscillation and global warming provides more favorable background states over the NTA that enable the Atlantic capacitor effect to operate more efficiently, giving rise to enhanced biennial variability in the Pacific which may increase the occurrence frequency of severe natural hazard events. The results highlight the increasing important role of the Atlantic-Pacific coupling as an important pacemaker of the ENSO cycle in recent decades.
Yang, T.; Poovaiah, B. W.
35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.
Abrams, Robert C
An appraisal of the last ten days of Queen Victoria's life, viewed primarily from the perspective of her personal physician, Sir James Reid, is presented. Sir James' clinical encounters with his patient and the Royal Family are examined to reveal his strategic and medical thinking and gauge his level of success in basic palliative aims. It was found that the lack of effective medical interventions, tensions within the Royal Family, the importance of his post to Sir James' professional career, and the political ramifications unavoidably connected with the illness of a head of state, all presented challenges to Reid's efforts to ease the physical and emotional pain of Queen Victoria's dying. Key features of Sir James' approach included reliance on physician-patient and physician-family relationships, emphasis on emotional support for the patient, and the careful selection of interventions for the family. In the first years of the 20th century, an era when the contemporary concepts of palliative care, hospice, and family dynamics did not exist, Sir James' management of the Queen's final illness suggested an early model for end-of-life care. By the end of Queen Victoria's life, Sir James was seen to have preserved his patient's comfort and dignity, at the same time advancing family and societal acceptance of the death of this matriarchal figure. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: email@example.com.
Zhao, Hongli; Zhao, Yanqiu; Zhang, Yingmei; Hou, Jinxiao; Yang, Huiyuan; Cao, Fenglin; Yang, Yiju; Hou, Wenyi; Sun, Jiayue; Jin, Bo; Fu, Jinyue; Li, Haitao; Wang, Ping; Ge, Fei; Zhou, Jin
Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 10 9 /L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 10 9 /L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.
Hayashi, Terumasa; Kimura, Tomonori; Yasuda, Keiko; Sasaki, Koichi; Obi, Yoshitsugu; Nagayama, Harumi; Ohno, Motoki; Uematsu, Kazusei; Tamai, Takehiro; Nishide, Takahiro; Rakugi, Hiromi; Isaka, Yoshitaka
There is a paucity of studies on whether early referral (ER) to nephrologist could reduce cardiovascular mortality on dialysis, and the length of pre-dialysis nephrological care needed to reduce mortality on dialysis. A total of 604 consecutive patients who started dialysis between 2001 and 2009 in Senshu region, Osaka, Japan were analyzed. Non-linear associations between mortality and pre-dialysis duration of nephrological care were assessed using restricted cubic spline function, and predictors for death analyzed on Cox modeling. A total of 31.6%, 18.2%, 11.3% and 6.1% of patients had >12, 24, 36 and 48 months of pre-dialysis care, respectively. A total of 258 patients (42.7%) were categorized as ER (≥6 months pre-dialysis duration). During the follow-up period (median, 31.1 months), 218 patients died (cardiovascular, n=70; infection, n=69). Although patients with late referral (LR) had a proxy of inappropriate pre-dialysis care compared with the ER group, Cox multivariate analysis failed to show a favorable association between ER and cardiovascular outcome. In contrast, a deleterious effect of LR on overall survival was observed but was limited only to the first 12 months of dialysis (HR, 1.957; 95% CI: 1.104-3.469; P=0.021), but not observed thereafter. Current pre-dialysis nephrological care may reduce short-term mortality but may not improve cardiovascular mortality after dialysis initiation.
Wijesinghe, Printha; Gorrie, Catherine; Shankar, S K; Chickabasaviah, Yasha T; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo-Hun; Steinbusch, H W M; De Silva, K Ranil D
There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years). This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population. Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used. There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging - Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex ( P < 0.05). However, associations obtained for other dementia-related pathologies were not statistically important. Our findings suggest that early Alzheimer stages may be a contributing factor to injury deaths caused by traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths.
Zhou, Minghai; Ottenberg, Gregory; Sferrazza, Gian Franco; Hubbs, Christopher; Fallahi, Mohammad; Rumbaugh, Gavin; Brantley, Alicia F.
The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD+) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD+ followed by decreased ATP production, and are completely rescued by treatment with NAD+ or its precursor nicotinamide because of restoration of physiological NAD+ levels. Toxic prion protein-induced NAD+ depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD+. Intranasal NAD+ treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD+ starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD+ replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases. PMID:25678560
Langley, Gayle; Hao, Yongping; Pondo, Tracy; Miller, Lisa; Petit, Susan; Thomas, Ann; Lindegren, Mary Louise; Farley, Monica M; Dumyati, Ghinwa; Como-Sabetti, Kathryn; Harrison, Lee H; Baumbach, Joan; Watt, James; Van Beneden, Chris
Invasive group A Streptococcus (iGAS) infections cause significant morbidity and mortality worldwide. We analyzed whether obesity and diabetes were associated with iGAS infections and worse outcomes among an adult US population. We determined the incidence of iGAS infections using 2010-2012 cases in adults aged ≥ 18 years from Active Bacterial Core surveillance (ABCs), a population-based surveillance system, as the numerator. For the denominator, we used ABCs catchment area population estimates from the 2011 to 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. The relative risk (RR) of iGAS was determined by obesity and diabetes status after adjusting for age group, gender, race, and other underlying conditions through binomial logistic regression. Multivariable logistic regression was used to determine whether obesity or diabetes was associated with increased odds of death due to iGAS compared to normal weight and nondiabetic patients, respectively. Between 2010 and 2012, 2927 iGAS cases were identified. Diabetes was associated with an increased risk of iGAS in all racial groups (adjusted risk ratio [aRR] ranged from 2.71 to 5.08). Grade 3 obesity (body mass index [BMI] ≥ 40) was associated with an increased risk of iGAS for whites (aRR = 3.47; 95% confidence interval [CI], 3.00-4.01). Grades 1-2 (BMI = 30.0-<40.0) and grade 3 obesity were associated with an increased odds of death (odds ratio [OR] = 1.55, [95% CI, 1.05, 2.29] and OR = 1.62 [95% CI, 1.01, 2.61], respectively) when compared to normal weight patients. These results may help target vaccines against GAS that are currently under development. Efforts to develop enhanced treatment regimens for iGAS may improve prognoses for obese patients. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta
The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1+∕+-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca2+ sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady-state and
Guha-Sapir, Debarati; Schlüter, Benjamin; Rodriguez-Llanes, Jose Manuel; Lillywhite, Louis; Hicks, Madelyn Hsiao-Rei
Since March, 2011, the Syrian civil war has lowered life expectancy by as much as 20 years. We describe demographic, spatial, and temporal patterns of direct deaths of civilians and opposition combatants from conflict-related violence in 6 years of war. We analysed conflict-related violent deaths with complete information on date, place, and cause of death and demographic group occurring from March 18, 2011, to Dec 31, 2016, recorded by the Violation Documentation Center (VDC). We included civilian and combatant deaths in all Syrian governorates, excluding government-controlled areas. We did not include detainees and missing persons, nor deaths from siege conditions or insufficient medical care. We categorised deaths based on VDC weapon type. We used χ 2 testing to compare deaths from different weapons in civilian men, women, boys, and girls and adult and child combatants. We analysed deaths by governorate and over time. The VDC recorded 143 630 conflict-related violent deaths with complete information between March 18, 2011, and Dec 31, 2016. Syrian civilians constituted 101 453 (70·6%) of the deaths compared with 42 177 (29·4%) opposition combatants. Direct deaths were caused by wide-area weapons of shelling and air bombardments in 58 099 (57·3%) civilians, including 8285 (74·6%) civilian women and 13 810 (79·4%) civilian children, and in 4058 (9·6%) opposition combatants. Proportions of children among civilian deaths increased from 8·9% (388 of 4254 civilian deaths) in 2011 to 19·0% (4927 of 25 972) in 2013 and to 23·3% (2662 of 11 444) in 2016. Of 7566 deaths from barrel bombs, 7351 (97·2%) were civilians, of whom 2007 (27·3%) were children. Of 20 281 deaths by execution, 18 747 (92·4%) were civilians and 1534 (7·6%) were opposition combatants. Compared with opposition child soldiers who were male (n=333), deaths of civilian male children (n=11 730) were caused more often by air bombardments (39·2% vs 5·4%, p<0·0001) and
Cao, Siqi; Smith, Laura L; Padilla-Lopez, Sergio R; Guida, Brandon S; Blume, Elizabeth; Shi, Jiahai; Morton, Sarah U; Brownstein, Catherine A; Beggs, Alan H; Kruer, Michael C; Agrawal, Pankaj B
Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development and function is unclear. There have been several reports linking de novo dominant EEF1A2 mutations to neurological issues in humans. We report a pair of siblings carrying a homozygous missense mutation p.P333L in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation. Functional genomic analysis was performed in S. cerevisiae and zebrafish. In S. cerevisiae, there was no evidence for a dominant-negative effect. Previously identified putative de novo mutations failed to complement yeast strains lacking the EEF1A ortholog showing a major growth defect. In contrast, the introduction of the mutation seen in our family led to a milder growth defect. To evaluate its function in zebrafish, we knocked down eef1a2 expression using translation blocking and splice-site interfering morpholinos. EEF1A2-deficient zebrafish had skeletal muscle weakness, cardiac failure and small heads. Human EEF1A2 wild-type mRNA successfully rescued the morphant phenotype, but mutant RNA did not. Overall, EEF1A2 appears to be critical for normal heart function in humans, and its deficiency results in clinical abnormalities in neurologic function as well as in skeletal and cardiac muscle defects. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
van Vugt, Jeroen L A; Gaspersz, Marcia P; Vugts, Jaynee; Buettner, Stefan; Levolger, Stef; de Bruin, Ron W F; Polak, Wojciech G; de Jonge, Jeroen; Willemssen, François E J A; Groot Koerkamp, Bas; IJzermans, Jan N M
Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death. © 2018 The Author(s) Published by S. Karger AG, Basel.
Hanefeld, C; Kloppe, C; Breger, W; Kloppe, A; Mügge, A; Wiemer, M
There is a comprehensive early defibrillation program in Bochum (Germany); since 2003 a total of 175 automated external defibrillators (AEDs) have been installed in urban areas by the city of Bochum and private companies. These were preferably installed in places with high foot traffic, e.g., public buildings, companies, and event/shopping centers. Approximately 15,000 laypeople who work in the vicinity of the AED locations were trained in the use of defibrillators and in basic resuscitation. In addition, rescue workers on fire trucks and medically trained personnel in physicians' medical practices were equipped as "first responders" with AEDs. After an initiation phase, all available information after each AED use since August 2004 has been collected by the project coordinator. During the period of data collection (August 2004 to August 2013), an AED was used in a total of 17 patients who had suffered sudden cardiac death (SCD) under the project in Bochum. Eleven patients had primary ventricular fibrillation (VF). Six of these survived without neurological deficit. In another 6 patients, a nondefibrillatable rhythm disorder was diagnosed. The AEDs are reliable and showed impeccable rhythm analysis before the instructions to provide any necessary shock. Compared to the number of existing units and an estimated number of 37-100 SCD/100,000, the use of the AEDs only 17 times appears relatively small. To improve the effectiveness of the AED program in Bochum, an analysis of the emergency service responses, which were necessary because of sudden circulatory collapse, is currently being performed. This will allow areas with an increased incidence of SCD to be identified and a plan for the strategic placement of AED and emergency services can be made.
...) Care, treatment, or examination. To establish that carelessness, negligence, lack of proper skill... additional disability or death (as explained in paragraph (c) of this section); and (i) VA failed to exercise...
Shiri, Rahman; Kausto, Johanna; Martimo, Kari-Pekka; Kaila-Kangas, Leena; Takala, Esa-Pekka; Viikari-Juntura, Eira
Previously we reported that early part-time sick leave enhances return to work (RTW) among employees with musculoskeletal disorders (MSD). This paper assesses the health-related effects of this intervention. Patients aged 18-60 years who were unable to perform their regular work due to MSD were randomized to part- or full-time sick leave groups. In the former, workload was reduced by halving working time. Using validated questionnaires, we assessed pain intensity and interference with work and sleep, region-specific disability due to MSD, self-rated general health, health-related quality of life (measured via EuroQol), productivity loss, depression, and sleep disturbance at baseline, 1, 3, 8, 12, and 52 weeks. We analyzed the repeated measures data (171-356 observations) with the generalized estimating equation approach. The intervention (part-time sick leave) and control (full-time sick leave) groups did not differ with regard to pain intensity, pain interference with work and sleep, region-specific disability, productivity loss, depression, or sleep disturbance. The intervention group reported better self-rated general health (adjusted P=0.07) and health-related quality of life (adjusted P=0.02) than the control group. In subgroup analyses, the intervention was more effective among the patients whose current problem began occurring <6 weeks before baseline and those with ≤30% productivity loss at baseline. Our findings showed that part-time sick leave did not exacerbate pain-related symptoms and functional disability, but improved self-rated general health and health-related quality of life in the early stage of work disability due to MSD.
Fink, Günther; Peet, Evan; Danaei, Goodarz; Andrews, Kathryn; McCoy, Dana Charles; Sudfeld, Christopher R; Smith Fawzi, Mary C; Ezzati, Majid; Fawzi, Wafaie W
The growth of >300 million children <5 y old was mildly, moderately, or severely stunted worldwide in 2010. However, national estimates of the human capital and financial losses due to growth faltering in early childhood are not available. We quantified the economic cost of growth faltering in developing countries. We combined the most recent country-level estimates of linear growth delays from the Nutrition Impact Model Study with estimates of returns to education in developing countries to estimate the impact of early-life growth faltering on educational attainment and future incomes. Primary outcomes were total years of educational attainment lost as well as the net present value of future wage earnings lost per child and birth cohort due to growth faltering in 137 developing countries. Bootstrapped standard errors were computed to account for uncertainty in modeling inputs. Our estimates suggest that early-life growth faltering in developing countries caused a total loss of 69.4 million y of educational attainment (95% CI: 41.7 million, 92.6 million y) per birth cohort. Educational attainment losses were largest in South Asia (27.6 million y; 95% CI: 20.0 million, 35.8 million y) as well as in Eastern (10.3 million y; 95% CI: 7.2 million, 12.9 million y) and Western sub-Saharan Africa (8.8 million y; 95% CI: 6.4 million, 11.5 million y). Globally, growth faltering in developing countries caused a total economic cost of $176.8 billion (95% CI: $100.9 billion, $262.6 billion)/birth cohort at nominal exchange rates, and $616.5 billion (95% CI: $365.3 billion, $898.9 billion) at purchasing power parity-adjusted exchange rates. At the regional level, economic costs were largest in South Asia ($46.6 billion; 95% CI: $33.3 billion, $61.1 billion), followed by Latin America ($44.7 billion; 95% CI: $19.2 billion, $74.6 billion) and sub-Saharan Africa ($34.2 billion; 95% CI: $24.4 billion, $45.3 billion). Our results indicate that the annual cost of early
Tomas Vaclavik; Alan Kanaskie; Everett M. Hansen; Janet L. Ohmann; Ross K. Meentemeyer
An isolated outbreak of the emerging forest disease sudden oak death was discovered in Oregon forests in 2001. Despite considerable control efforts, disease continues to spread from the introduction site due to slow and incomplete detection and eradication. Annual field surveys and laboratory tests between 2001 and 2009 confirmed a total of 802 infested locations. Here...
Brennan, Andrew J. J.
Health professionals and educators should develop their abilities to educate about death and to comfort the bereaved. Due to lower death rates, the lack of philosophical religious views, and distorted perceptions of death contributed by television, death has become a mystery instead of a segment of the common experience. Particularly when a child…
Haws, Rachel A; Mashasi, Irene; Mrisho, Mwifadhi; Schellenberg, Joanna Armstrong; Darmstadt, Gary L; Winch, Peter J
Little research in low-income countries has compared the social and cultural ramifications of loss in childbearing, yet the social experience of pregnancy loss and early neonatal death may affect demographers' ability to measure their incidence. Ninety-five qualitative reproductive narratives were collected from 50 women in rural southern Tanzania who had recently suffered infertility, miscarriage, stillbirth or early neonatal death. An additional 31 interviews with new mothers and female elders were used to assess childbearing norms and social consequences of loss in childbearing. We found that like pregnancy, stillbirth and early neonatal death are hidden because they heighten women's vulnerability to social and physical harm, and women's discourse and behaviors are under strong social control. To protect themselves from sorcery, spiritual interference, and gossip--as well as stigma should a spontaneous loss be viewed as an induced abortion--women conceal pregnancies and are advised not to mourn or grieve for "immature" (late-term) losses. Twelve of 30 respondents with pregnancy losses had been accused of inducing an abortion; 3 of these had been subsequently divorced. Incommensurability between Western biomedical and local categories of reproductive loss also complicates measurement of losses. Similar gender inequalities and understandings of pregnancy and reproductive loss in other low-resource settings likely result in underreporting of these losses elsewhere. Cultural, terminological, and methodological factors that contribute to inaccurate measurement of stillbirth and early neonatal death must be considered in designing surveys and other research methods to measure pregnancy, stillbirth, and other sensitive reproductive events. Copyright © 2010 Elsevier Ltd. All rights reserved.
Viikari-Juntura, Eira; Kausto, Johanna; Shiri, Rahman; Kaila-Kangas, Leena; Takala, Esa-Pekka; Karppinen, Jaro; Miranda, Helena; Luukkonen, Ritva; Martimo, Kari-Pekka
The purpose of this study was to assess the effects of early part-time sick leave on return to work (RTW) and sickness absence among patients with musculoskeletal disorders. A randomized controlled trial was conducted in six occupational health units of medium- and large-size enterprises. Patients aged 18-60 years with musculoskeletal disorders (N=63) unable to perform their regular work were randomly allocated to part- or full-time sick leave. In the former group, workload was reduced by restricting work time by about a half. Remaining work tasks were modified when necessary, as specified in a "fit note" from the physician. The main outcomes were time to return to regular work activities and sickness absence during 12-month follow-up. Time to RTW sustained for ≥4 weeks was shorter in the intervention group (median 12 versus 20 days, P=0.10). Hazard ratio of RTW adjusted for age was 1.60 [95% confidence interval (95% CI) 0.98-2.63] and 1.76 (95% CI 1.21-2.56) after further adjustment for pain interference with sleep and previous sickness absence at baseline. Total sickness absence during the 12-month follow-up was about 20% lower in the intervention than the control group. Compliance with the intervention was high with no discontinuations of part-time sick leave due to musculoskeletal reasons. Early part-time sick leave may provide a faster and more sustainable return to regular duties than full-time sick leave among patients with musculoskeletal disorders. This is the first study to show that work participation can be safely increased with early part-time sick leave.
Wijesinghe, Printha; Gorrie, Catherine; Shankar, S. K.; Chickabasaviah, Yasha T.; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K. Sunil; Samarasinghe, Kamani; Suh, Yoo-Hun; Steinbusch, H. W. M.; De Silva, K. Ranil D.
Background: There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years). Aim: This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population. Materials and Methods: Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used. Results: There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging – Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex (P < 0.05). However, associations obtained for other dementia-related pathologies were not statistically important. Conclusion: Our findings suggest that early Alzheimer stages may be a contributing factor to injury deaths caused by traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths. PMID:29497190
Gunst, Mark; Ghaemmaghami, Vafa; Gruszecki, Amy; Urban, Jill; Frankel, Heidi
Injury mortality was classically described with a trimodal distribution, with immediate deaths at the scene, early deaths due to hemorrhage, and late deaths from organ failure. We hypothesized that the development of trauma systems has improved prehospital care, early resuscitation, and critical care and altered this pattern. This population-based study of all trauma deaths in an urban county with a mature trauma system reviewed data for 678 patients (median age, 33 years; 81% male; 43% gunshot, 20% motor vehicle crashes). Deaths were classified as immediate (scene), early (in hospital, ≤4 hours from injury), or late (>4 hours after injury). Multinomial regression was used to identify independent predictors of immediate and early versus late deaths, adjusted for age, gender, race, intention, mechanism, toxicology, and cause of death. Results showed 416 (61%) immediate, 199 (29%) early, and 63 (10%) late deaths. Compared with the classical description, the percentage of immediate deaths remained unchanged, and early deaths occurred much earlier (median 52 vs 120 minutes). However, unlike the classic trimodal distribution, the late peak was greatly diminished. Intentional injuries, alcohol intoxication, asphyxia, and injuries to the head and chest were independent predictors of immediate death. Alcohol intoxication and injuries to the chest were predictors of early death, while pelvic fractures and blunt assaults were associated with late deaths. In conclusion, trauma deaths now have a predominantly bimodal distribution. Near elimination of the late peak likely represents advancements in resuscitation and critical care that have reduced organ failure. Further reductions in mortality will likely come from prevention of intentional injuries and injuries associated with alcohol intoxication. PMID:20944754
Fairthorne, Jenny; Hammond, Geoff; Bourke, Jenny; Jacoby, Peter; Leonard, Helen
Introduction Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. Methods The study population comprised all mothers of live-born children in Western Australia from 1983–2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. Results and Discussion During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. Conclusion Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity. PMID:25535971
Kohlsdorf, Katja; Nunziata, Adriana; Funcke, Jan-Bernd; Brandt, Stephanie; von Schnurbein, Julia; Vollbach, Heike; Lennerz, Belinda; Fritsch, Maria; Greber-Platzer, Susanne; Fröhlich-Reiterer, Elke; Luedeke, Manuel; Borck, Guntram; Debatin, Klaus-Michael; Fischer-Posovszky, Pamela; Wabitsch, Martin
To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI trajectories were compared between the groups at selected time points. The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m 2 (27.2-38.4 kg/m 2 ) and %BMI P95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8-198.6%) at the age of 2 years and a BMI > 33 kg/m 2 (33.3-45.9 kg/m 2 ) and %BMI P95 > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p < 0.01). As result of the investigation of early childhood BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m 2 or %BMI P95 > 140% at the age of 2 years and BMI values >33.0 kg/m 2 or %BMI P95 > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.
Baechli, Heidi; Behzad, Melika; Schreckenberger, Matthias; Buchholz, Hans-Georg; Heimann, Axel; Kempski, Oliver; Alessandri, Beat
Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.
... surgical treatment, examination, training and rehabilitation services, or compensated work therapy (CWT... rehabilitation services or CWT program cannot cause the continuance or natural progress of a disease or injury... CWT program proximately caused a veteran's additional disability or death, it must be shown that the...
... surgical treatment, examination, training and rehabilitation services, or compensated work therapy (CWT... rehabilitation services or CWT program cannot cause the continuance or natural progress of a disease or injury... CWT program proximately caused a veteran's additional disability or death, it must be shown that the...
... surgical treatment, examination, training and rehabilitation services, or compensated work therapy (CWT... rehabilitation services or CWT program cannot cause the continuance or natural progress of a disease or injury... CWT program proximately caused a veteran's additional disability or death, it must be shown that the...
Pradhan, Abani K; Ivanek, Renata; Gröhn, Yrjö T; Bukowski, Robert; Geornaras, Ifigenia; Sofos, John N; Wiedmann, Martin
The objective of this study was to estimate the relative risk of listeriosis-associated deaths attributable to Listeria monocytogenes contamination in ham and turkey formulated without and with growth inhibitors (GIs). Two contamination scenarios were investigated: (i) prepackaged deli meats with contamination originating solely from manufacture at a frequency of 0.4% (based on reported data) and (ii) retail-sliced deli meats with contamination originating solely from retail at a frequency of 2.3% (based on reported data). Using a manufacture-to-consumption risk assessment with product-specific growth kinetic parameters (i.e., lag phase and exponential growth rate), reformulation with GIs was estimated to reduce human listeriosis deaths linked to ham and turkey by 2.8- and 9-fold, respectively, when contamination originated at manufacture and by 1.9- and 2.8-fold, respectively, for products contaminated at retail. Contamination originating at retail was estimated to account for 76 and 63% of listeriosis deaths caused by ham and turkey, respectively, when all products were formulated without GIs and for 83 and 84% of listeriosis deaths caused by ham and turkey, respectively, when all products were formulated with GIs. Sensitivity analyses indicated that storage temperature was the most important factor affecting the estimation of per annum relative risk. Scenario analyses suggested that reducing storage temperature in home refrigerators to consistently below 7 degrees C would greatly reduce the risk of human listeriosis deaths, whereas reducing storage time appeared to be less effective. Overall, our data indicate a critical need for further development and implementation of effective control strategies to reduce L. monocytogenes contamination at the retail level.
... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...
Assel, Melissa J; Gerdtsson, Axel; Thorek, Daniel L J; Carlsson, Sigrid V; Malm, Johan; Scardino, Peter T; Vickers, Andrew; Lilja, Hans; Ulmert, David
To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics.
Assel, Melissa J.; Gerdtsson, Axel; Thorek, Daniel L.J.; Carlsson, Sigrid V.; Malm, Johan; Scardino, Peter T.; Vickers, Andrew; Lilja, Hans; Ulmert, David
Objectives To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. PMID:29464033
Aït-Azzouzene, D; Langkopf, A; Cohen, J; Bleux, C; Gendron, M C; Kanellopoulos-Langevin, C
Among the numerous hypotheses proposed to explain the absence of fetal rejection by the mother in mammals, it has been suggested that regulation of expression of the polymorphic major histocompatibility complex (MHC) at the fetal-maternal interface plays a major role. In addition to a lack of MHC gene expression in the placenta throughout gestation, the absence of polymorphic MHC molecules on the early embryo, as well as their low level of expression after midgestation, could contribute to this important biologic phenomenon. In order to test this hypothesis, we have produced transgenic mice able to express polymorphic MHC class I molecules early in embryogenesis. We have placed the MHC class la gene H-2Kb under the control of a housekeeping gene promoter, the hydroxy-methyl-glutaryl coenzyme A reductase (HMG) gene minimal promoter. This construct has been tested for functionality after transfection into mouse fibroblast L cells. The analysis of three founder transgenic mice and their progeny suggested that fetoplacental units that could express the H-2Kb heavy chains are unable to survive in utero beyond midgestation. We have shown further that a much higher resorption rate, on days 11 to 13 of embryonic development, is observed among transgenic embryos developing from eggs microinjected at the one-cell stage with the pHMG-Kb construct than in control embryos. This lethality is not due to immune phenomena, since it is observed in histocompatible combinations between mother and fetus. These results are discussed in the context of what is currently known about the regulation of MHC expression at the fetal-maternal interface and in various transgenic mouse models.
Benavides, Fernando G; Duran, Xavier; Gimeno, David; Vanroelen, Christophe; Martínez, José Miguel
To analyse the impact of labour market trajectory indicators on early retirement, measured by age at onset of permanent disability (PD). Four labour market trajectory indicators were reconstructed in 14 972 new cases of PD recognized between 2004 and 2010: (1) number of employment contracts, (2) number of unemployment periods, (3) number of periods without social security affiliation and (4) percentage of time spent in inactivity. The outcome was measured as the age at onset of PD. Median differences and 95% confidence intervals (95%CI) were compared using a median regression. Analyses were stratified by sex and adjusted for occupational category and total time elapsed between the beginning of working life and the age at onset of PD: separately for each labour market indicator, and adjusted for each other. In men, the age at the onset of PD for workers with 15 or more employment contracts decreased by 4.8 years; and for workers with five or more periods without affiliation it decreased by 4.6 years. In women, the corresponding decreases were 5.8 years for 15 or more contracts and 7.2 years for five or more unaffiliated periods. The results for four indicators slightly changed when they were mutually adjusted. Poor employment conditions, such as having a high number of periods without affiliation, a high number of contracts (in men) and a higher percentage of inactive time (in women) are associated with early retirement due to PD. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
Hunt, G J
First, some of the early work is reviewed on exposure pathways in connection with proposed and early liquid radioactive waste discharges from Sellafield. The main historical features of these discharges, affected by relevant plant operations, are then briefly described. The important radiological exposure pathways resulting from the discharges and people's consumption and occupancy habits are considered. To place the changing scenario onto a consistent basis using present-day methodology, a reconstruction of exposures has been carried out using environmental monitoring data and models. The three major pathways are examined of Porphyra/laverbread consumption in South Wales, fish and shellfish consumption near Sellafield, and external exposure over local and more distant sediments. The results show that over the period 1952 to about 1970 the laverbread pathway was probably critical, taking a cautious approach. Effective dose rates fluctuated at around 1 mSv y(-1) from about 1956 to 1971. From about 1970 to 1985, the fish and shellfish pathway was likely to have been critical, with effective dose rates peaking at about 2 mSv y(-1) in 1975-1976. External exposure was likely to have been of lesser importance than the other two pathways until about 1985, when with the retention of previously-released radiocesium on sediments it has become dominant. This phenomenon applies particularly further afield where radiocesium concentrations have been slower to decline; in the Ribble estuary, houseboat dwellers have been the critical group from about 1985. Effective doses have been at about 0.3 mSv y(-1) and declining; they are due to the effects of radiocesium discharges in earlier years. Dose rates have remained within contemporary ICRP dose limits.
Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakır, Mustafa; Boztug, Kaan; Chatila, Talal A; Barlan, Isil B
Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-γ/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-γ and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-β and -γ-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.
Cao, Xiaodong; MacNaughton, Piers; Laurent, Jose Cedeno; Allen, Joseph G
EPA reported that radon is the second leading cause of lung cancer in the United States, killing 21,100 people per year. EPA relies on the BEIR VI models, based on an evaluation of radon exposure and lung cancer risk in studies of miners. But these models did not account for co-exposure to diesel exhaust, a known human carcinogen recently classified by IARC. It is probable then that a portion of the lung cancer deaths in the miner cohorts are originally attributable to the exposure to diesel rather than radon. To re-evaluate EPA's radon attributable lung cancer estimates accounting for diesel exposure information in the miner cohorts. We used estimates of historical diesel concentrations, combined with diesel exposure-response functions, to estimate the risks of lung cancer attributable to diesel engine exhaust (DEE) exposure in the miner studies. We re-calculated the fatal lung cancer risk attributable to radon after accounting for risk from diesel and re-estimated the number of U.S. deaths associated with radon in the U.S. using EPA's methodology. Considering the probable confounding with DEE exposure and using the same estimate of baseline mortality from 1989-91 that the EPA currently uses in their calculations, we estimate that radon-induced lung cancer deaths per year are 15,600 (95% CI: 14,300, 17,000)- 19,300 (95% CI: 18,800, 20,000) in the U.S. population, a reduction of 9%-26%. The death estimates would be 12,900-15,900 using 2014 baseline vital statistics. We recommend further research on re-evaluating the health effects of exposure to radon that accounts for new information on diesel exhaust carcinogenicity in BEIR VI models, up-to-date vital statistics and new epidemiological evidence from residential studies.
MacNaughton, Piers; Laurent, Jose Cedeno; Allen, Joseph G.
Background EPA reported that radon is the second leading cause of lung cancer in the United States, killing 21,100 people per year. EPA relies on the BEIR VI models, based on an evaluation of radon exposure and lung cancer risk in studies of miners. But these models did not account for co-exposure to diesel exhaust, a known human carcinogen recently classified by IARC. It is probable then that a portion of the lung cancer deaths in the miner cohorts are originally attributable to the exposure to diesel rather than radon. Objective To re-evaluate EPA’s radon attributable lung cancer estimates accounting for diesel exposure information in the miner cohorts. Methods We used estimates of historical diesel concentrations, combined with diesel exposure-response functions, to estimate the risks of lung cancer attributable to diesel engine exhaust (DEE) exposure in the miner studies. We re-calculated the fatal lung cancer risk attributable to radon after accounting for risk from diesel and re-estimated the number of U.S. deaths associated with radon in the U.S. using EPA’s methodology. Results Considering the probable confounding with DEE exposure and using the same estimate of baseline mortality from 1989–91 that the EPA currently uses in their calculations, we estimate that radon-induced lung cancer deaths per year are 15,600 (95% CI: 14,300, 17,000)– 19,300 (95% CI: 18,800, 20,000) in the U.S. population, a reduction of 9%–26%. The death estimates would be 12,900–15,900 using 2014 baseline vital statistics. Conclusions We recommend further research on re-evaluating the health effects of exposure to radon that accounts for new information on diesel exhaust carcinogenicity in BEIR VI models, up-to-date vital statistics and new epidemiological evidence from residential studies. PMID:28886109
Karaismailoğlu, Eda; Dikmen, Zeliha Günnur; Akbıyık, Filiz; Karaağaoğlu, Ahmet Ergun
Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-off values of these biomarkers, which differentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the significant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of significant biomarkers and a combined biomarker during 240 h. The bootstrap method was used to compare statistical significance and the Youden index was used to determine optimal cut-off values. Results : Myoglobin and BNP were significant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the first 180 h. Conclusion: Although myoglobin is not clinically specific to a cardiac event, in our study both myoglobin and BNP were found to be statistically significant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.
Berrut, Sylvie; Richmond, Peter; Roehner, Bertrand M.
After birth, setting up an effective immune system is a major challenge for all living organisms. In this paper we show that this process can be explored by using the age-specific infant death rate as a kind of sensor. This is made possible because, as shown by the authors in Berrut et al. (2016), between birth and a critical age tc, for all mammals the death rate decreases with age as a smooth hyperbolic function. For humans tc is equal to 10 years. It turns out that for some causes of deaths and specific ages the hyperbolic fall displays temporary spikes which, it is assumed, correspond to specific events in the organism's response to exogenous factors. One of these spikes occurs 10 days after birth and there is another at the age of 300 days. It is shown that the first spike is related to viral infections whereas the second is related to bacterial diseases. By going back to former time periods during which infant mortality was much higher than it is currently, one gets a magnified view of these peaks. They give us useful information about how an organism adapts to new conditions. Apart from the reaction to pathogens, the same methodology can be used to study the response to changes in other external conditions, e.g. temperature or oxygen level.
Vilozni, Daphna; Hakim, Fahed; Adler, Adi; Livnat, Galit; Bar-Yishay, Ephraim; Bentur, Lea
In a previous study we assessed the feasibility of measuring bronchial-reactivity (BHR) in young asthmatic children by the determination of PC(20)-FEV(1) along with clinical end-of-test criteria during a methacholine challenge test (MCT). The end-point was associated with a significant reduction in both flow and vital capacity values. The findings could be due to the children's loss of motivation, which may preclude use of this test. Alternatively, if it reflects air trapping during airway obstruction, it might reinforce its applicability in preschool age children. To elucidate the mechanism of low vital capacity at PC(20)-FEV(1) in preschool age children. Twenty-eight children (3.3-6.9 years) with recurrent respiratory symptoms. An MCT was carried out using tripling doses (0.06-13.9 mg/ml) delivered by a dosimeter. Spirometry was measured at baseline and after each inhalation in duplicate sets. Whole body plethysmography was measured at baseline and at end-of-test (defined by clinical criteria) according to the recommendations for older populations. Plethysmography was reliably performed by 20 children before and after MCT. At baseline, lung function was within the healthy range. At end-of-test (PC(20)-FEV(1)=4.02+/-3.47 mg/ml), the spirometry parameters and specific conductance values were markedly reduced in correlation with a significant increase in residual volume and resistance. The study shows that diminished vital capacity is due to the increase in FRC at end-of-test. Our findings support the use of PC(20)-FEV(1) during BHR in young children and suggest that lung volume measurement by a plethysmograph may be feasible in early childhood. Larger studies should be performed to establish the clinical applicability of PC20-FEV1 determination in the preschool age.
Pavlidis, Pavlos; Karakasi, Valeria
This incident concerns the simultaneous death of seven people as a result of the accidental triggering of an antipersonnel landmine during peacetime. The victims were illegal migrants who attempted to cross the Greek-Turkish border zone and accidentally entered a demarcated minefield. This incident is presented because of its rarity and highlights the devastating consequences of the residual mines on the European Union eastern frontiers in peacetime. It also showcases the difficulties and risks that arise during the identification process in illegal migration issues. The victims' positions at the moment of explosion are indicated by the detailed forensic examination and comparison of the injuries' anatomical dispersion and their severity.
Zhang, Wenxia; Zhou, Tianjun; Zhang, Lixia
Known as the "the world water tower", the Tibetan Plateau (TP) is the origin of the ten largest rivers in Asia, breeding more than 1.4 billion people, and exerts substantial influences on water resources, agriculture, and ecosystems in downstream countries. This region is one of the most susceptible areas around the world to changing climate due to the high elevation. Observed evidence have shown significant climate changes over the TP, including surface air warming and moistening, glaciers shrinking, winds stilling, solar dimming, and atmospheric heat source weakening. However, as an essential part of the hydrological cycle, precipitation changes on the TP remain an ambiguous picture. Changes in precipitation vary largely with different seasons, time periods and climate zones considered. This study shows a robust increase in precipitation amount over the TP in May, when the rainy season starts, over the period 1979-2014 (31% relative to the climatology). The wetting trend is spatially consistent over the south-eastern TP, to which both precipitation frequency and intensity contribute. Circulation trends show that the wetting TP in May is resulted from the advanced onset of Asian summer monsoon, which onsets 1~2 pentads earlier since 1979. It intensified water vapor transport from the Bay of Bengal (BOB) to south of the TP in May and local anomalous convection. This relationship is further validated by the significant correlation coefficient (0.47) between the onset dates of Asian summer monsoon (particularly the BOB summer monsoon, 0.68) and precipitation over the south-eastern TP in May. The wetting TP in May has further exerted profound impacts on the hydrological cycle and ecosystem, such as moistening the soil and animating vegetation activities throughout early summer. Both decadal variations of soil moisture (from May to June) and Normalized Difference Vegetation Index (NDVI) (from May to July) coincide well with that of precipitation over the south
Fenske, Annabelle E; Glaesener, Stephanie; Bokemeyer, Carsten; Thomale, Juergen; Dahm-Daphi, Jochen; Honecker, Friedemann; Dartsch, Dorothee C
To identify factors involved in cisplatin (CDDP) resistance of germ cell tumours (GCTs), we exposed NTERA-2 cells, and the platinum-adapted subline NTERA-2R to CDDP and compared their response. While both cell lines showed comparable proliferation, NTERA-2R cells were clearly more resistant to the drug than the parental NTERA-2 cell line. Interestingly, the two lines showed identical extent of DNA adduct formation and elimination, indicating that neither changes in CDDP uptake, nor altered drug efflux, DNA binding, or repair caused the difference in resistance. Similarly, no difference occurred in the time-course of γH2AX formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R cells showed a more pronounced dose-dependent S phase delay, a transient G(2)/M-block, and subsequent release into immediate cell death. We thus conclude that the enhanced resistance against CDDP is linked to reduced susceptibility to cell death rather than to an altered DNA adduct formation or adduct removal. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Gagnon, Alain; Acosta, Enrique; Hallman, Stacey; Bourbeau, Robert; Dillon, Lisa Y; Ouellette, Nadine; Earn, David J D; Herring, D Ann; Inwood, Kris; Madrenas, Joaquin; Miller, Matthew S
Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics. IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest
Ardisson-Araújo, Daniel Mendes Pereira; Morgado, Fabrício Da Silva; Schwartz, Elisabeth Ferroni; Corzo, Gerardo; Ribeiro, Bergmann Morais
Baculoviruses are the most studied insect viruses in the world and are used for biological control of agricultural and forest insect pests. They are also used as versatile vectors for expression of heterologous proteins. One of the major problems of their use as biopesticides is their slow speed to kill insects. Thus, to address this shortcoming, insect-specific neurotoxins from arachnids have been introduced into the baculovirus genome solely aiming to improve its virulence. In this work, an insecticide-like toxin gene was obtained from a cDNA derived from the venom glands of the theraphosid spider Brachypelma albiceps. The mature form of the peptide toxin (called Ba3) has a high content of basic amino acid residues, potential for three possible disulfide bonds, and a predicted three-stranded β-sheetDifferent constructions of the gene were engineered for recombinant baculovirus Autographa californica multiple nuclepolyhedrovirus (AcMNPV) expression. Five different forms of Ba3 were assessed; (1) the full-length sequence, (2) the pro-peptide and mature region, (3) only the mature region, and the mature region fused to an (4) insect or a (5) virus-derived signal peptide were inserted separately into the genome of the baculovirus. All the recombinant viruses induced cell death by necrosis earlier in infection relative to a control virus lacking the toxin gene. However, the recombinant virus containing the mature portion of the toxin gene induced a faster cell death than the other recombinants. We found that the toxin construct with the signal peptide and/or pro-peptide regions delayed the necrosis phenotype. When infected cells were subjected to ultrastructural analysis, the cells showed loss of plasma membrane integrity and structural changes in mitochondria before death. Our results suggest this use of baculovirus is a potential tool to help understand or to identify the effect of insect-specific toxic peptides when produced during infection of insect cells. PMID
Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro
Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
This paper presents a verification of the thermodynamic model allowing an estimation of the time of death (TOD) by calculating the post mortem interval (PMI) based on a single eyeball temperature measurement at the death scene. The study was performed on 30 cases with known PMI, ranging from 1h 35min to 5h 15min, using pin probes connected to a high precision electronic thermometer (Dostmann-electronic). The measured eye temperatures ranged from 20.2 to 33.1°C. Rectal temperature was measured at the same time and ranged from 32.8 to 37.4°C. Ambient temperatures which ranged from -1 to 24°C, environmental conditions (still air to light wind) and the amount of hair on the head were also recorded every time. PMI was calculated using a formula based on Newton's law of cooling, previously derived and successfully tested in comprehensive studies on pigs and a few human cases. Thanks to both the significantly faster post mortem decrease of eye temperature and a residual or nonexistent plateau effect in the eye, as well as practically no influence of body mass, TOD in the human death cases could be estimated with good accuracy. The highest TOD estimation error during the post mortem intervals up to around 5h was 1h 16min, 1h 14min and 1h 03min, respectively in three cases among 30, while for the remaining 27 cases it was not more than 47min. The mean error for all 30 cases was ±31min. All that indicates that the proposed method is of quite good precision in the early post mortem period, with an accuracy of ±1h for a 95% confidence interval. On the basis of the presented method, TOD can be also calculated at the death scene with the use of a proposed portable electronic device (TOD-meter). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
van Walraven, Carl; Wong, Jenna; Forster, Alan J
Background Death or urgent readmission after hospital discharge is a common adverse event that can be used to compare outcomes of care between institutions. To accurately adjust for risk and to allow for interhospital comparisons of readmission rates, we used administrative data to derive and internally validate an extension of the LACE index, a previously validated index for 30-day death or urgent readmission. Methods We randomly selected 500 000 medical and surgical patients discharged to the community from any Ontario hospital between 1 April 2003 and 31 March 2009. We derived a logistic regression model on 250 000 randomly selected patients from this group and modified the final model into an index scoring system, the LACE+ index. We internally validated the LACE+ index using data from the remaining 250 000 patients and compared its performance with that of the original LACE index. Results Within 30 days of discharge to the community, 33 825 (6.8%) of the patients had died or had been urgently readmitted. In addition to the variables included in the LACE index (length of stay in hospital [L], acuity of admission [A], comorbidity [C] and emergency department utilization in the 6 months before admission [E]), the LACE+ index incorporated patient age and sex, teaching status of the discharge hospital, acute diagnoses and procedures performed during the index admission, number of days on alternative level of care during the index admission, and number of elective and urgent admissions to hospital in the year before the index admission. The LACE+ index was highly discriminative (C statistic 0.771, 95% confidence interval 0.767–0.775), was well calibrated across most of its range of scores and had a model performance that exceeded that of the LACE index. Interpretation The LACE+ index can be used to predict the risk of postdischarge death or urgent readmission on the basis of administrative data for the Ontario population. Its performance exceeds that of the LACE
Background Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. Results Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43. Conclusions Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death
Hornick, John R; Vangveravong, Suwanna; Spitzer, Dirk; Abate, Carmen; Berardi, Francesco; Goedegebuure, Peter; Mach, Robert H; Hawkins, William G
Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43. Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death following LMP protected by DEVD
Karray, Saoussen; Kress, Chantal; Cuvellier, Sylvain; Hue-Beauvais, Catherine; Damotte, Diane; Babinet, Charles; Lévi-Strauss, Matthieu
To investigate the in vivo function of Fas ligand (FasL), we produced a mouse strain with a FasL gene flanked by loxP sequences. Mice with homozygous floxed FasL gene showed no obvious abnormalities. However, germline deletion of the FasL gene, obtained after mating with mice expressing ubiquitous Cre recombinase, resulted in an unexpectedly severe phenotype. FasL(-/-) mice exhibited an extreme splenomegaly and lymphadenopathy associated with lymphocytic infiltration into multiple organs and autoimmune disease. This severe phenotype led to the premature death at 4 mo of age of >50% of the homozygous mice. It stands in sharp contrast with the milder disease observed in gld (generalized lymphoproliferative disease) mice, indicating that the FasL allele of these mice encodes a protein still able to bind, albeit at a very low level, the Fas receptor.
McComb, Scott; Mulligan, Rebecca; Sad, Subash
Background CD8+ T cell responses develop rapidly during infection and are swiftly reduced during contraction, wherein >90% of primed CD8+ T cells are eliminated. The role of apoptotic mechanisms in controlling this rapid proliferation and contraction of CD8+ T cells remains unclear. Surprisingly, evidence has shown non-apoptotic activation of caspase-3 to occur during in vitro T-cell proliferation, but the relevance of these mechanisms to in vivo CD8+ T cell responses has yet to be examined. Methods and Findings We have evaluated the activity of caspase-3, a key downstream inducer of apoptosis, throughout the entirety of a CD8+ T cell response. We utilized two infection models that differ in the intensity, onset and duration of antigen-presentation and inflammation. Expression of cleaved caspase-3 in antigen specific CD8+ T cells was coupled to the timing and strength of antigen presentation in lymphoid organs. We also observed coordinated activation of additional canonical apoptotic markers, including phosphatidylserine exposure. Limiting dilution analysis directly showed that in the presence of IL7, very little cell death occurred in both caspase-3hi and caspase-3low CD8+ T cells. The expression of active caspase-3 peaked before effector phenotype (CD62Llow) CD8+ T cells emerged, and was undetectable in effector-phenotype cells. In addition, OVA-specific CD8+ cells remained active caspase-3low throughout the contraction phase. Conclusions Our results specifically implicate antigen and not inflammation in driving activation of apoptotic mechanisms without cell death in proliferating CD8+ T cells. Furthermore, the contraction of CD8+ T cell response following expansion is likely not mediated by the key downstream apoptosis inducer, caspase-3. PMID:21203525
Sandmann, W; Dueppers, P; Pourhassan, S; Voiculescu, A; Klee, D; Balzer, K M
This retrospective study presents the early and late results of pediatric patients who underwent reconstructive surgery for renovascular hypertension (RVH) between 1979 and 2009. From 1979 to 2009 44 patients (male 22; mean age 13±5.2 years, range 1-19 years; early childhood 7 [1-6 years], middle childhood 5 [7-10 years]; adolescents 32 [11-19 years]) with renovascular hypertension underwent surgery for abdominal aortic stenoses (n=6), renal artery stenosis (RAS) (n=25) or for combined lesions (n=13). Nineteen aortic stenoses (bypass/interposition 10/5, patch dilatation/thromboendarterectomy 2/2), 51 renal arteries (interposition 36, resection+reimplantation 13, patch dilatation/aneurysmorraphy 1 each), and 10 visceral arteries (resection+reimplantation 6, interposition 3, patch dilatation 1) were reconstructed. Each patient underwent duplex studies and if required intra-arterial digital subtraction angiography. Reoperations within 30 postoperative days were required in four (9%) of the patients for occlusion of four arteries (6%), achieving a combined technical success rate of 94%. After 114±81 months 36 patients were re-examined by duplex and magnetic resonance angiography (2 not surgery-related deaths 7/12 years postoperatively, 8 patients lived abroad). Twelve patients had required a second and three a third procedure. Hypertension was cured early/late postoperatively in 27%/56%, improved in 41%/44%, and remained unchanged in 32%/0%. Best late results were obtained in patients with isolated aortic disease and at the age of middle childhood. Reconstructive surgery for pediatric RVH yields good results at every age and every type of lesion. However, these children should be followed up closely and to avoid early cardiovascular disease and death in later life, surgery should not be delayed. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Damodaran, T.V., E-mail: email@example.com; Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC; Dept of Biology, North Carolina Central University, Durham, NC 27707
quantitative analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: Black-Right-Pointing-Pointer Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. Black-Right-Pointing-Pointer Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. Black-Right-Pointing-Pointer Multiple anomalous cellular (neuronal and astroglial) features were recorded. Black-Right-Pointing-Pointer Anatomical specificity of the neurodegeneration was described.« less
Durán-Carabali, L E; Arcego, D M; Odorcyk, F K; Reichert, L; Cordeiro, J L; Sanches, E F; Freitas, L D; Dalmaz, C; Pagnussat, A; Netto, C A
Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.
Quitian-Reyes, Hoover; Gómez-Restrepo, Carlos; Gómez, Maria Juliana; Naranjo, Salome; Heredia, Patricia; Villegas, John
This study aimed to quantify the number of years of life lost in traffic accidents in Bogota, Colombia. The years of life lost were calculated using the 'age-standardized expected years of life lost' method, the table of Japanese adjusted life expectancy and the database of the Institute of Legal Medicine and Forensic Science between September 2012 and August 2013. During a period of 1 year, 430 people died and 10,056.3 years of life were lost in Bogota due to traffic accidents. The mortality burden of traffic accidents in Bogota is high. Further studies are required in order to characterize the accidents and develop effective policy decisions. Copyright © 2016 Elsevier Inc. All rights reserved.
Miles, Lizzy; Corr, Charles A
This article explains the meaning of the phrase Death Cafe and describes what typically occurs at a Death Cafe gathering. The article traces the history of the Death Cafe movement, explores some reasons why people take part in a Death Cafe gathering, and gives examples of what individuals think they might derive from their participation. In addition, this article notes similarities between the Death Cafe movement and three other developments in the field of death, dying, and bereavement. Finally, this article identifies two provisional lessons that can be drawn from Death Cafe gatherings and the Death Cafe movement itself.
Schrank, Bertold; Götz, Rudolf; Gunnersen, Jennifer M.; Ure, Janice M.; Toyka, Klaus V.; Smith, Austin G.; Sendtner, Michael
Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second most common pediatric neuromuscular disorder. Two candidate genes—survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning. However, the functional impact of these genes and the mechanism leading to a degeneration of motor neurons remain to be defined. To analyze the role of the SMN gene product in vivo we generated SMN-deficient mice. In contrast to the human genome, which contains two copies, the mouse genome contains only one SMN gene. Mice with homozygous SMN disruption display massive cell death during early embryonic development, indicating that the SMN gene product is necessary for cellular survival and function. PMID:9275227
Ahonkhai, Aima A.; Noubary, Farzad; Munro, Alison; Stark, Ruth; Wilke, Marisa; Freedberg, Kenneth A.; Wood, Robin; Losina, Elena
Background Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up. Methods We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes. Results In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39–0.62]. Conclusions In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU. PMID:22427925
Jarvis, Stuart; Kovacs, Caroline; Briggs, Jim; Meredith, Paul; Schmidt, Paul E; Featherstone, Peter I; Prytherch, David R; Smith, Gary B
Although the weightings to be summed in an early warning score (EWS) calculation are small, calculation and other errors occur frequently, potentially impacting on hospital efficiency and patient care. Use of a simpler EWS has the potential to reduce errors. We truncated 36 published 'standard' EWSs so that, for each component, only two scores were possible: 0 when the standard EWS scored 0 and 1 when the standard EWS scored greater than 0. Using 1564,153 vital signs observation sets from 68,576 patient care episodes, we compared the discrimination (measured using the area under the receiver operator characteristic curve--AUROC) of each standard EWS and its truncated 'binary' equivalent. The binary EWSs had lower AUROCs than the standard EWSs in most cases, although for some the difference was not significant. One system, the binary form of the National Early Warning System (NEWS), had significantly better discrimination than all standard EWSs, except for NEWS. Overall, Binary NEWS at a trigger value of 3 would detect as many adverse outcomes as are detected by NEWS using a trigger of 5, but would require a 15% higher triggering rate. The performance of Binary NEWS is only exceeded by that of standard NEWS. It may be that Binary NEWS, as a simplified system, can be used with fewer errors. However, its introduction could lead to significant increases in workload for ward and rapid response team staff. The balance between fewer errors and a potentially greater workload needs further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Walter, Johannes; Unterberg, Andreas W; Zweckberger, Klaus
Approximately 1% of all patients surviving rupture of a cerebral aneurysm suffer from a second aneurysmatic subarachnoid hemorrhage later in their lives, 61% of which are caused by rupture of a de novo aneurysm. Latency between bleedings is usually many years, and younger patients tend to achieve better outcomes from a second subarachnoid hemorrhage. We report an unusual case of lethal ultra-early rupture of a de novo aneurysm of the anterior communicating artery only 5 months after the initial subarachnoid hemorrhage and complete coiling in a young, healthy male patient. Despite complete aneurysm obliteration, young age, and good recovery, patients may be subjected to secondary subarachnoid hemorrhages from de novo aneurysms after only a few months of the initial bleeding. Early-control magnetic resonance angiography might hence be advisable. Copyright © 2018 Elsevier Inc. All rights reserved.
Juranek, Jenifer; Romanowska-Pawliczek, Anna; Hannay, H. Julia; Cirino, Paul T.; Dennis, Maureen; Kramer, Larry A.; Fletcher, Jack M.
Abstract Spina bifida myelomeningocele (SBM) is commonly associated with anomalous development of the corpus callosum (CC) because of congenital partial hypogenesis and hydrocephalus-related hypoplasia. It represents a model disorder to examine the effects of early disruption of CC neurodevelopment and the plasticity of interhemispheric white matter connections. Diffusion tensor imaging was acquired on 76 individuals with SBM and 27 typically developing individuals, aged 8–36 years. Probabilistic tractography was used to isolate the interhemispheric connections between the posterior superior temporal lobes, which typically traverse the posterior third of the CC. Early disruption of CC development resulted in restructuring of interhemispheric connections through alternate commissures, particularly the anterior commissure (AC). These rerouted fibers were present in people with SBM and both CC hypoplasia and hypogenesis. In addition, microstructural integrity was reduced in the interhemispheric temporal tract in people with SBM, indexed by lower fractional anisotropy, axial diffusivity, and higher radial diffusivity. Interhemispheric temporal tract volume was positively correlated with total volume of the CC, such that more severe underdevelopment of the CC was associated with fewer connections between the posterior temporal lobes. Therefore, both the macrostructure and microstructure of this interhemispheric tract were reduced, presumably as a result of more extensive CC malformation. The current findings suggest that early disruption in CC development reroutes interhemispheric temporal fibers through both the AC and more anterior sections of the CC in support of persistent hypotheses that the AC may serve a compensatory function in atypical CC development. PMID:26798959
Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P
Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.
Di Segni, Matteo; Andolina, Diego; Coassin, Alessandra; Accoto, Alessandra; Luchetti, Alessandra; Pascucci, Tiziana; Luzi, Carla; Lizzi, Anna Rita; D'Amato, Francesca R; Ventura, Rossella
Although early aversive postnatal events are known to increase the risk to develop psychiatric disorders later in life, rarely they determine alone the nature and outcome of the psychopathology, indicating that interaction with genetic factors is crucial for expression of psychopathologies in adulthood. Moreover, it has been suggested that early life experiences could have negative consequences or confer adaptive value in different individuals. Here we suggest that resilience or vulnerability to adult cocaine sensitivity depends on a "triple interaction" between genetic makeup x early environment x later experience. We have recently showed that Repeated Cross Fostering (RCF; RCF pups were fostered by four adoptive mothers from postnatal day 1 to postnatal day 4. Pups were left with the last adoptive mother until weaning) experienced by pups affected the response to a negative experience in adulthood in opposite direction in two genotypes leading DBA2/J, but not C57BL/6J mice, toward an "anhedonia-like" phenotype. Here we investigate whether exposure to a rewarding stimulus, instead of a negative one, in adulthood induces an opposite behavioral outcome. To test this hypothesis, we investigated the long-lasting effects of RCF on cocaine sensitivity in C57 and DBA female mice by evaluating conditioned place preference induced by different cocaine doses and catecholamine prefrontal-accumbal response to cocaine using a "dual probe" in vivo microdialysis procedure. Moreover, cocaine-induced c-Fos activity was assessed in different brain regions involved in processing of rewarding stimuli. Finally, cocaine-induced spine changes were evaluated in the prefrontal-accumbal system. RCF experience strongly affected the behavioral, neurochemical and morphological responses to cocaine in adulthood in opposite direction in the two genotypes increasing and reducing, respectively, the sensitivity to cocaine in C57 and DBA mice. Copyright © 2017 Elsevier Ltd. All rights reserved.
Muchtar, Eli; Gertz, Morie A; Kumar, Shaji K; Lacy, Martha Q; Dingli, David; Buadi, Francis K; Grogan, Martha; Hayman, Suzanne R; Kapoor, Prashant; Leung, Nelson; Fonder, Amie; Hobbs, Miriam; Hwa, Yi Lisa; Gonsalves, Wilson; Warsame, Rahma; Kourelis, Taxiarchis V; Russell, Stephen; Lust, John A; Lin, Yi; Go, Ronald S; Zeldenrust, Steven; Kyle, Robert A; Rajkumar, S Vincent; Dispenzieri, Angela
In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone, and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of better than very good partial response (VGPR) was higher in more recent periods (66% vs 58% vs 51%; P = .001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS, 91% compared with 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS, 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the 2 later periods (24% vs 25% vs 37%; P < .001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality, and improved OS. © 2017 by The American Society of Hematology.
Suorsa, Kristina I; Mullins, Alexandria J; Tackett, Alayna P; Reyes, Kristy J Scott; Austin, Paul; Baskin, Laurence; Bernabé, Kerlly; Cheng, Earl; Fried, Allyson; Frimberger, Dominic; Galan, Denise; Gonzalez, Lynette; Greenfield, Saul; Kropp, Bradley; Meyer, Sabrina; Meyer, Theresa; Nokoff, Natalie; Palmer, Blake; Poppas, Dix; Paradis, Alethea; Yerkes, Elizabeth; Wisniewski, Amy B; Mullins, Larry L
We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes. A total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised. A large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged. Although many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł
Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.
de Cosio, Federico G; Jiwani, Safia S; Sanhueza, Antonio; Soliz, Patricia N; Becerra-Posada, Francisco; Espinal, Marcos A
Data on maternal deaths occurring after the 42 days postpartum reference time is scarce; the objective of this analysis is to explore the trend and magnitude of late maternal deaths and deaths from sequelae of obstetric causes in the Americas between 1999 and 2013, and to recommend including these deaths in the monitoring of the Sustainable Development Goals (SDGs). Exploratory data analysis enabled analyzing the magnitude and trend of late maternal deaths and deaths from sequelae of obstetric causes for seven countries of the Americas: Argentina, Brazil, Canada, Colombia, Cuba, Mexico and the United States. A Poisson regression model was developed to compare trends of late maternal deaths and deaths from sequelae of obstetric causes between two periods of time: 1999 to 2005 and 2006 to 2013; and to estimate the relative increase of these deaths in the two periods of time. The proportion of late maternal deaths and deaths from sequelae of obstetric causes ranged between 2.40% (CI 0.85% - 5.48%) and 18.68% (CI 17.06% - 20.47%) in the seven countries. The ratio of late maternal deaths and deaths from sequelae of obstetric causes per 100,000 live births has increased by two times in the region of the Americas in the period 2006-2013 compared to the period 1999-2005. The regional relative increase of late maternal death was 2.46 (p<0.0001) times higher in the second period compared to the first. Ascertainment of late maternal deaths and deaths from sequelae of obstetric causes has improved in the Americas since the early 2000's due to improvements in the quality of information and the obstetric transition. Late and obstetric sequelae maternal deaths should be included in the monitoring of the SDGs as well as in the revision of the International Classification of Diseases' 11th version (ICD-11).
de Cosio, Federico G.; Sanhueza, Antonio; Soliz, Patricia N.; Becerra-Posada, Francisco; Espinal, Marcos A.
Background Data on maternal deaths occurring after the 42 days postpartum reference time is scarce; the objective of this analysis is to explore the trend and magnitude of late maternal deaths and deaths from sequelae of obstetric causes in the Americas between 1999 and 2013, and to recommend including these deaths in the monitoring of the Sustainable Development Goals (SDGs). Methods Exploratory data analysis enabled analyzing the magnitude and trend of late maternal deaths and deaths from sequelae of obstetric causes for seven countries of the Americas: Argentina, Brazil, Canada, Colombia, Cuba, Mexico and the United States. A Poisson regression model was developed to compare trends of late maternal deaths and deaths from sequelae of obstetric causes between two periods of time: 1999 to 2005 and 2006 to 2013; and to estimate the relative increase of these deaths in the two periods of time. Findings The proportion of late maternal deaths and deaths from sequelae of obstetric causes ranged between 2.40% (CI 0.85% – 5.48%) and 18.68% (CI 17.06% – 20.47%) in the seven countries. The ratio of late maternal deaths and deaths from sequelae of obstetric causes per 100,000 live births has increased by two times in the region of the Americas in the period 2006-2013 compared to the period 1999-2005. The regional relative increase of late maternal death was 2.46 (p<0.0001) times higher in the second period compared to the first. Interpretation Ascertainment of late maternal deaths and deaths from sequelae of obstetric causes has improved in the Americas since the early 2000’s due to improvements in the quality of information and the obstetric transition. Late and obstetric sequelae maternal deaths should be included in the monitoring of the SDGs as well as in the revision of the International Classification of Diseases’ 11th version (ICD-11). PMID:27626277
Background Idiopathic portal hypertension (IPH) is a disorder of unknown etiology and is characterized clinically by portal hypertension, splenomegaly, and hypersplenism accompanied by pancytopenia. This study evaluates the pathogenic concept of the disease by a systematic review of the literature and illustrates novel pathologic and laboratory findings. Case Presentation We report the first case of uncontrolled splenic hyperperfusion and enlargement with subsequent hypersplenism leading to life-threatening complications of IPH in infancy and emergent splenectomy. Conclusions Our results suggest that splenic NO and VCAM-1, rather than ET-1, have a significant impact on the development of IPH, even at a very early stage of disease. The success of surgical interventions targeting the splenic hyperperfusion suggests that the primary defect in the regulation of splenic blood flow seems to be crucial for the development of IPH. Thus, beside other treatment options splenectomy needs to be considered as a prime therapeutic option for IPH. PMID:20961440
Langer, Maria; Kühn, Michael
Shallow groundwater resources could be possibly affected by intruding brines, which are displaced along hydraulically conductive faults as result of subsurface activities like CO2 injection. To avoid salinization of potable freshwater aquifers an early detection of intruding saline water is necessary, especially in regions where an initial geogenic salinization already exists. Our study is based on work of Tillner et al.  and Langer et al.  who investigated the influence of permeable fault systems on brine displacement for the prospective storage site Beeskow-Birkholz in the Northeast German Basin. With a 3D regional scale model considering the deep groundwater system, they demonstrated that the existence of hydraulically conductive faults is not necessarily an exclusion criterion for potential injection sites, because salinization of shallower aquifers strongly depends on the effective damage zone volume, the initial salinity distribution and overlying reservoirs , while permeability of fault zones does not influence salinization of shallower aquifers significantly . Here we extracted a 2D cross section regarding the upper 220 m of the study area mainly represented by shallow freshwater aquifers, but also considering an initial geogenic salinization . We took flow rates of the intruding brines from the previous studies  and implemented species transport simulations with the program code SHEMAT . Results are investigated and interpreted with the hydrochemical genesis model GEBAH  which has been already applied as early warning of saltwater intrusions into freshwater aquifers and surface water . GEBAH allows a categorization of groundwater by the ion ratios of the dissolved components and offers a first indicative determination for an existence and the intensity of saline water intrusion in shallow groundwater aquifer, independent of the concentration of the solution. With our model we investigated the migration of saline water through a
Landes, Scott D
Utilizing a particular case study of a woman attempting to come to terms with her death, this article explores the difficult metaphors of death present within the Christian tradition. Tracing a Christian understanding of death back to the work of Augustine, the case study is utilized to highlight the difficulties presented by past and present theology embracing ideas of punishment within death. Following the trajectory of the case study, alternative understandings of death present in recent Christian theology and within Native American spirituality are presented in an attempt to find room for a fuller meaning of death post-reconciliation, but premortem.
Kilany, Yasser Fouad; Abou Holw, Sahar A; Abouel-Nour, Mohamed Fathy; Morsy, Ayman T A
The multifactor outcome of hypoandrogenemia with the impact of oxidative stress induced by glucose intolerance, fascioliasis with or without schistosomiasis and cumulative smoking influence on bone remodeling and the early development of osteoporotic manifestations were studied. The effect on vascular endothelium immune mediated mechanisms and antioxidant capacity were monitored in cases of youth aged selected male smokers involving 20 with hypoandrogenemia who were either subjected to sedentary life style, glucose intolerance fascioliasis hepatic fibrosis (FHF) (G1) or without (G2) and GI after following 6 months therapy (G3). Monitoring of clinical picture and biochemical assessments of osteoporotic indices (osteocolcin, bone alkaline phosphatase, parathyroid hormone, urinary cyclic AMP), hypoandrogenism (dehydroepiandrosterane sulphate or DHEAS & testosterone) glycemic determinant (insulin) immuno-inflammatory response (interleukein-6, tumor necrosis factor alpha, E-selectin, ceruloplasmin) smoking index (serum cotinine), total antioxidant capacity (AOC) and lipid peroxidation (malonedialdehyde) was done before and after 6 months therapeutic program involving supplement of DHEAS, mirazid, chromium picolinate, and megavit zinc alongside smoking cessation and physical exercise daily for at least 30 minutes. Treatment with Mirazid supplied as 10 mg/kg for 6 successive days resulted in 100% cure of fascioliasis whether single or combined with schistosomiasis.
Spakman, W.; Van Hinsbergen, D. J.; Vissers, R.
Geological studies have shown that Eo-Oligocene subduction related high-pressure, low-temperature metasediments and peridotites of the Alboran region (Spain, Morocco) and the Kabylides (Algeria) experienced a major Early Miocene (~21 Ma) thermal pulse requiring asthenospheric temperatures at ~60 km depth. Despite earlier propositions, the cause of this thermal pulse is still controversial while also the paleogeographic origin of the Alboran and Kabylides units is debated. Here, we relate the thermal pulse to segmentation of the West Alpine-Tethyan slab under the SE Iberian margin (Baleares-Sardinia). We restore the Alboran rocks farther east than previously assumed, to close to the Balearic Islands, adjacent to Sardinia. We identify three major lithosphere faults, the NW-SE trending North Balearic Transform Zone (NBTZ) and the ~W-E trending Emile Baudot and North African transforms that accommodated the Miocene subduction evolution of slab segmentation, rollback, and migration of Alboran and Kabylides rocks to their current positions. The heat pulse occurred S-SE of the Baleares where slab segmentation along the NBTZ triggered radially outgrowing S-SW rollback opening a slab window that facilitated local ascent of asthenosphere below the rapidly extending Alboran-Kabylides accretionary prism. Subsequent slab rollback carried the Kabylides and Alboran domains to their present positions. Our new reconstruction is in line with tomographically imaged mantle structure and focuses attention on the crucial role of evolving subduction segmentation driving HT-metamorphism and subsequent extension, fragmentation, and dispersion of geological terrains.
Weninger, Bernhard; Alram-Stern, Eva; Bauer, Eva; Clare, Lee; Danzeglocke, Uwe; Jöris, Olaf; Kubatzki, Claudia; Rollefson, Gary; Todorova, Henrieta; van Andel, Tjeerd
We explore the hypothesis that the abrupt drainage of Laurentide lakes and associated rapid switch of the North Atlantic thermohaline circulation 8200 yr ago had a catastrophic influence on Neolithic civilisation in large parts of southeastern Europe, Anatolia, Cyprus, and the Near East. The event at 8200 cal yr BP is observed in a large number of high-resolution climate proxies in the Northern Hemisphere, and in many cases corresponds to markedly cold and arid conditions. We identify the relevant archaeological levels of major Neolithic settlements in Central Anatolia, Cyprus, Greece and Bulgaria, and examine published stratigraphic, architectural, cultural and geoarchaeological studies for these sites. The specific archaeological events and processes we observe at a number of these sites during the study interval 8400-8000 cal yr BP lead us to refine some previously established Neolithisation models. The introduction of farming to South-East Europe occurs in all study regions (Thrace, Macedonia, Thessaly, Bulgaria) near 8200 cal yr BP. We observe major disruptions of Neolithic cultures in the Levant, North Syria, South-East Anatolia, Central Anatolia and Cyprus, at the same time. We conclude that the 8200 cal yr BP aridity event triggered the spread of early farmers, by different routes, out of West Asia and the Near East into Greece and Bulgaria.
Osorio-Paz, Ixchel; Uribe-Carvajal, Salvador; Salceda, Rocío
In order to maintain high transmembrane ionic gradients, retinal tissues require a large amount of energy probably provided by a high rate of both, glycolysis and oxidative phosphorylation. However, little information exists on retinal mitochondrial efficiency. We analyzed the retinal mitochondrial activity in ex vivo retinas and in isolated mitochondria from normal rat retina and from short-term streptozotocin-diabetic rats. In normal ex vivo retinas, increasing glucose concentrations from 5.6mM to 30mM caused a four-fold increase in glucose accumulation and CO2 production. Retina from diabetic rats accumulated similar amounts of glucose. However, CO2 production was not as high. Isolated mitochondria from normal rat retina exhibited a resting rate of oxygen consumption of 14.6 ± 1.1 natgO (min.mg prot)-1 and a respiratory control of 4.0. Mitochondria from 7, 20 and 45 days diabetic rats increased the resting rate of oxygen consumption and the activity of the electron transport complexes; under these conditions the mitochondrial transmembrane potential decreased. In spite of this, the ATP synthesis was not modified. GDP, an UCP2 inhibitor, increased mitochondrial membrane potential and superoxide production in controls and at 45 days of diabetes. The role of UCP2 is discussed. The results suggest that at the early stage of diabetes we studied, retinal mitochondria undergo adaptations leading to maintain energetic requirements and prevent oxidative stress. PMID:25951172
Osorio-Paz, Ixchel; Uribe-Carvajal, Salvador; Salceda, Rocío
In order to maintain high transmembrane ionic gradients, retinal tissues require a large amount of energy probably provided by a high rate of both, glycolysis and oxidative phosphorylation. However, little information exists on retinal mitochondrial efficiency. We analyzed the retinal mitochondrial activity in ex vivo retinas and in isolated mitochondria from normal rat retina and from short-term streptozotocin-diabetic rats. In normal ex vivo retinas, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO2 production. Retina from diabetic rats accumulated similar amounts of glucose. However, CO2 production was not as high. Isolated mitochondria from normal rat retina exhibited a resting rate of oxygen consumption of 14.6 ± 1.1 natgO (min.mg prot)(-1) and a respiratory control of 4.0. Mitochondria from 7, 20 and 45 days diabetic rats increased the resting rate of oxygen consumption and the activity of the electron transport complexes; under these conditions the mitochondrial transmembrane potential decreased. In spite of this, the ATP synthesis was not modified. GDP, an UCP2 inhibitor, increased mitochondrial membrane potential and superoxide production in controls and at 45 days of diabetes. The role of UCP2 is discussed. The results suggest that at the early stage of diabetes we studied, retinal mitochondria undergo adaptations leading to maintain energetic requirements and prevent oxidative stress.
Saito, Eiko; Inoue, Manami; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Sasazuki, Shizuka; Noda, Mitsuhiko; Iso, Hiroyasu; Tsugane, Shoichiro
We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale population-based cohort study in Japan. We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders. Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup/day were 0.96 (0.89-1.03) for 1-2 cups/day, 0.88 (0.82-0.95) for 3-4 cups/day, and 0.87 (0.81-0.94) for more than 5 cups/day (P for trend <.001). Corresponding hazard ratios for women were 0.90 (0.81-1.00), 0.87 (0.79-0.96), and 0.83 (0.75-0.91; P for trend <.001). Green tea was inversely associated with mortality from heart disease in both men and women and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality. This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan. Copyright © 2015 Elsevier Inc. All rights reserved.
Addresses the tragedy of crib deaths, giving particular attention to causes, prevention, and medical research on Sudden Infant Death Syndrome (SIDS). Gives anecdotal accounts of coping strategies used by parents and families of SIDS infants. (DT)
Hoyt, Kenneth; Sorace, Anna; Saini, Reshu
Objectives The objective of this study was to determine whether volumetric contrast-enhanced ultrasound (US) imaging could detect early tumor response to anti–death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Methods Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor–bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Results Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone– and TRA-8 + Abraxane–dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Conclusions Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy. PMID:23091246
Shimoyama, Yuichiro; Umegaki, Osamu; Agui, Tomoyuki; Kadono, Noriko; Minami, Toshiaki
Patients with vascular Ehlers-Danlos syndrome (EDS) are susceptible to significant vascular complications, such as aortic and visceral arterial ruptures, aneurysms, and dissection. We describe a case of repeated bleeding in a 57-year-old woman and a case of sudden onset of artery dissection in her daughter, both of whom were previously diagnosed with vascular EDS and managed at our institution. A 57-year-old woman was admitted to our emergency department due to sudden onset of left low back pain. Her past history included vascular EDS. An urgent abdominal computed tomography (CT) scan revealed a left-sided retroperitoneal hematoma and left external iliac artery dissection. Stent graft repair was performed. Five hours postoperatively, cardiac arrest occurred and resuscitation attempts failed. The 32-year-old daughter with genetically diagnosed vascular EDS was notified of the death of her mother during the customary end-of-life conference. Six hours after her mother's death, she was admitted to our emergency department due to sudden onset of left low back pain. On examination, she was not in hypovolemic shock, and weak pulses were palpable in the bilateral dorsalis pedis. An urgent abdominal CT scan revealed a right-sided retroperitoneal hematoma around the right external iliac artery and left external iliac artery dissection. She was admitted to the intensive care unit and underwent conservative therapy consisting of bed rest and antihypertensive therapy with nicardipine. She developed no further vascular complications requiring surgical intervention and was discharged on the 21st hospital day. Vascular rupture can be fatal in patients with vascular EDS. This report underscores the importance of strategic management of vascular complications to prevent rupture, and the importance of psychological care for the bereaved family given the hereditary nature of vascular EDS.
Karemore, Gopal; Nielsen, Mads; Karssemeijer, Nico; Brandt, Sami S.
It is well understood nowadays that changes in the mammographic parenchymal pattern are an indicator of a risk of breast cancer and we have developed a statistical method that estimates the mammogram regions where the parenchymal changes, due to breast cancer, occur. This region of interest is computed from a score map by utilising the anatomical breast coordinate system developed in our previous work. The method also makes an automatic scale selection to avoid overfitting while the region estimates are computed by a nested cross-validation scheme. In this way, it is possible to recover those mammogram regions that show a significant difference in classification scores between the cancer and the control group. Our experiments suggested that the most significant mammogram region is the region behind the nipple and that can be justified by previous findings from other research groups. This result was conducted on the basis of the cross-validation experiments on independent training, validation and testing sets from the case-control study of 490 women, of which 245 women were diagnosed with breast cancer within a period of 2-4 years after the baseline mammograms. We additionally generalised the estimated region to another, mini-MIAS study and showed that the transferred region estimate gives at least a similar classification result when compared to the case where the whole breast region is used. In all, by following our method, one most likely improves both preclinical and follow-up breast cancer screening, but a larger study population will be required to test this hypothesis.
Naoe, T; Tagawa, Y; Kiyoi, H; Kodera, Y; Miyawaki, S; Asou, N; Kuriyama, K; Kusumoto, S; Shimazaki, C; Saito, K; Akiyama, H; Motoji, T; Nishimura, M; Shinagawa, K; Ueda, R; Saito, H; Ohno, R
We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.
Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Kyaw, Khine Wut Yee; Thein, Saw; Si Thu, Aung; Oo, Myo Minn; Htwe, Pyae Sone; Tun, Moe Myint Theingi; Win Maung, Htet Myet; Soe, Kyaw Thu; Aung, Si Thu
death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC “received support” group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in “receiving support” group and therefore similar survival was found when compared to “not receiving support”. Conclusion CBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC. PMID:29261669
The causes of ASD are still relatively unknown. Correlation between clinical status of patients and radiological MRI findings is of primary importance. The radiological classifications proposed by Pfirmann and Oner are most commonly used to assess intradiscal degenerative changes. The aim of the study was to assess the influence of the extension of spine fixation on the risk of developing ASD in a short time after surgery. A total of 332 patients with spinal tumors were treated in our hospital between 2010 and 2013. Of these patients, 287 underwent surgeries. A follow-up MRI examination was performed 12 months after surgical treatment. The study population comprised of 194 patients. Among metastases, breast cancer was predominant (29%); neurological deficits were detected in 76 patients. Metastases were seen in the thoracic (45%) and lumbar (30%) spine; in 25% of cases, they were of multisegmental character. Pathological fractures concerned 88% of the patients. Statistical calculations were made using the χ2 test. Statistical analysis was done using the Statistica v. 10 software. A p value <0.05 was accepted as statistically significant. The study population was divided on seven groups according to applied treatment. Clinical signs of ASD were noted in only seven patients. Two patients had symptoms of nerve root irritation in the lumbar spine. Twenty-two patients (11%) were diagnosed with ASD according to the MRI classifications by Oner, Rijt, and Ramos, while the more sensitive Pfirmann classification allowed to detect the disease in 46 patients (24%). Healthy or almost healthy discs of Oner type I correlated with the criteria of Pfirmann types II and III. The percentage of the incidence of ASD diagnosed 1 year after the surgery using the Pfirmann classifications was significantly higher than diagnosed according to the clinical examination. The incidence of ASD in patients after spine surgeries due to cancer metastases does not differ between the study groups
Holmgren, Kristina; Sandheimer, Christine; Mårdby, Ann-Charlotte; Larsson, Maria E H; Bültmann, Ute; Hange, Dominique; Hensing, Gunnel
Early identification of persons at risk of sickness absence due to work-related stress is a crucial problem for society in general, and primary health care in particular. Tho date, no established method to do this exists. This project's aim is to evaluate whether systematic early identification of work-related stress can prevent sickness absence. This paper presents the study design, procedure and outcome measurements, as well as allocation and baseline characteristics of the study population. The study is a two-armed randomized controlled trial with follow-up at 3, 6 and 12 months. Non-sick-listed employed women and men, aged 18 to 64 years, who had mental and physical health complaints and sought care at primary health care centers (PHCC) were eligible to participate. At baseline work-related stress was measured by the Work Stress Questionnaire (WSQ), combined with feedback at consultation, at PHCC. The preventive intervention included early identification of work-related stress by the WSQ, GP training in the use of WSQ, GP feedback at consultation and finding suitable preventive measures. A process evaluation was used to explore how to facilitate future implementation and structural use of the WSQ at the PHCC. The primary outcome to compare the preventive sick leave intervention by the general practitioner (GP) versus treatment as usual is sick leave data obtained from the Swedish Social Insurance Agency register. Early screening for sick leave due to work-related stress makes it possible not only to identify those at risk for sick leave, but also to put focus on the patient's specific work-related stress problems, which can be helpful in finding suitable preventive measures. This study investigates if use of the WSQ by GPs at PHCCs, combined with feedback at consultation, prevents future sickness absence. ClinicalTrials.gov. Identifier: NCT02480855 . Registered 20 May 2015.
Collection of trace evidence of explosive residues from the skin in a death due to a disguised letter bomb. The synergy between confocal laser scanning microscope and inductively coupled plasma atomic emission spectrometer analyses.
Turillazzi, Emanuela; Monaci, Fabrizio; Neri, Margherita; Pomara, Cristoforo; Riezzo, Irene; Baroni, Davide; Fineschi, Vittorio
In most deaths caused by explosive, the victim's body becomes a depot for fragments of explosive materials, so contributing to the collection of trace evidence which may provide clues about the specific type of device used with explosion. Improvised explosive devices are used which contain "homemade" explosives rather than high explosives because of the relative ease with which such components can be procured. Many methods such as chromatography-mass spectrometry, scanning electron microscopy, stereomicroscopy, capillary electrophoresis are available for use in the identification of explosive residues on objects and bomb fragments. Identification and reconstruction of the distribution of explosive residues on the decedent's body may give additional hints in assessing the position of the victim in relation to the device. Traditionally these residues are retrieved by swabbing the body and clothing during the early phase, at autopsy. Gas chromatography-mass spectrometry and other analytical methods may be used to analyze the material swabbed from the victim body. The histological examination of explosive residues on skin samples collected during the autopsy may reveal significant details. The information about type, quantity and particularly about anatomical distribution of explosive residues obtained utilizing confocal laser scanning microscope (CLSM) together with inductively coupled plasma atomic emission spectrometer (ICP-AES), may provide very significant evidence in the clarification and reconstruction of the explosive-related events. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Érlikh, A D
Independent predictors of death and death or myocardial infarction (MI) during initial hospitalization of patients with acute coronary syndromes (ACS) were determined using database of Russian independent ACS registry RECORD. These predictors (admission Killip class II, ST-segment elevation 1 mm, systolic blood pressure 100 mm Hg, hemoglobin <110 g/L, age 65 years, history of diabetes) were attributed equal weight (1 point) and combined in a prognostic scale for assessment of risk of inhospital death and death or MI. The scale did not include markers of necrosis, and the most time consuming component was measurement of hemoglobin. Sensitivity and specificity of risk scores for prediction of death were 78.5%. The use of GRACE score in this group of patients gave similar results. These preliminary data require confirmation on larger populations of patients with ACS.
Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L.; Golstein, Pierre
Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of “paddle” cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells. PMID:12654899
Al-Hilli, Ali Bakir; Salih, Dheyaa Saeed
Background Compound limb fractures due to high-velocity missiles are complex and usually associated with multiple other injuries. These can occur in both military and civilian settings. Highvelocity missiles are presently used by terrorists worldwide. Early surgical debridement and skeletal fixation are the gold standards in managing these injuries, but data supporting these recommendations are lacking. Aim of the study Our aim was to determine the relationship between time (the time of injury to the time of surgical treatment) and the rate of deep infection in patients treated in Medical City, Baghdad, Iraq due to terrorist activity from 2004-2008. Design This is a retrospective review of a series of open limb fractures. Patients and method A total of 102 civilian patients with 114 limb fractures due to high-velocity missile injuries were selected for this study from Medical City records. Patients were followed in the outpatient department in Medical City Teaching Complex both clinically and radiologically. Results Surgical treatment was accomplished in less than six hours from time of injury in group A (55 fractures, 48.4%) and more than six hours in group B (59 fractures, 51.7%). The infection rate for group A was 30.9% and group B was 23.7%. Conclusion A very high infection rate was noted for these injuries, and there was no increase in the rate of deep infection in patients treated more than six hours after the injury. PMID:21045979
Al-Hilli, Ali Bakir; Salih, Dheyaa Saeed
Compound limb fractures due to high-velocity missiles are complex and usually associated with multiple other injuries. These can occur in both military and civilian settings. High-velocity missiles are presently used by terrorists worldwide. Early surgical debridement and skeletal fixation are the gold standards in managing these injuries, but data supporting these recommendations are lacking. Our aim was to determine the relationship between time (the time of injury to the time of surgical treatment) and the rate of deep infection in patients treated in Medical City, Baghdad, Iraq due to terrorist activity from 2004-2008. This is a retrospective review of a series of open limb fractures. A total of 102 civilian patients with 114 limb fractures due to high-velocity missile injuries were selected for this study from Medical City records. Patients were followed in the outpatient department in Medical City Teaching Complex both clinically and radiologically. Surgical treatment was accomplished in less than six hours from time of injury in group A (55 fractures, 48.4%) and more than six hours in group B (59 fractures, 51.7%). The infection rate for group A was 30.9% and group B was 23.7%. A very high infection rate was noted for these injuries, and there was no increase in the rate of deep infection in patients treated more than six hours after the injury.
Garcia, Santiago; Drexel, Todd; Bekwelem, Wobo; Raveendran, Ganesh; Caldwell, Emily; Hodgson, Lucinda; Wang, Qi; Adabag, Selcuk; Mahoney, Brian; Frascone, Ralph; Helmer, Gregory; Lick, Charles; Conterato, Marc; Baran, Kenneth; Bart, Bradley; Bachour, Fouad; Roh, Steven; Panetta, Carmelo; Stark, Randall; Haugland, Mark; Mooney, Michael; Wesley, Keith; Yannopoulos, Demetris
In 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis-St. Paul. Eleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and <76 and presumed cardiac etiology. Patients with other rhythms, known do not resuscitate/do not intubate, noncardiac etiology, significant bleeding, and terminal disease were excluded. The primary outcome was survival to hospital discharge with favorable neurological outcome. Patients (315 out of 331) who were resuscitated from VT/VF and transferred alive to the Emergency Department had complete medical records. Of those, 231 (73.3%) were taken to the CCL per the Minnesota Resuscitation Consortium protocol while 84 (26.6%) were not taken to the CCL (protocol deviations). Overall, 197 (63%) patients survived to hospital discharge with good neurological outcome (cerebral performance category of 1 or 2). Of the patients who followed the Minnesota Resuscitation Consortium protocol, 121 (52%) underwent percutaneous coronary intervention, and 15 (7%) underwent coronary artery bypass graft. In this group, 151 (65%) survived with good neurological outcome, whereas in the group that did not follow the Minnesota Resuscitation Consortium protocol, 46 (55%) survived with good neurological outcome (adjusted odds ratio: 1.99; [1.07-3.72], P=0.03). Early access to the CCL after cardiac arrest due to a shockable rhythm in a selected group of patients is feasible in a large metropolitan area in the United States and is associated with a 65% survival
Gajek, Arkadiusz; Denel-Bobrowska, Marta; Rogalska, Aneta; Bukowska, Barbara; Maszewski, Janusz; Marczak, Agnieszka
The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline,?WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the
Krug, Utz; Röllig, Christoph; Koschmieder, Anja; Heinecke, Achim; Sauerland, Maria Cristina; Schaich, Markus; Thiede, Christian; Kramer, Michael; Braess, Jan; Spiekermann, Karsten; Haferlach, Torsten; Haferlach, Claudia; Koschmieder, Steffen; Rohde, Christian; Serve, Hubert; Wörmann, Bernhard; Hiddemann, Wolfgang; Ehninger, Gerhard; Berdel, Wolfgang E; Büchner, Thomas; Müller-Tidow, Carsten
About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged >60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2
Introduction Inefficient clearance of copious respiratory secretion is a cause of non-invasive positive pressure ventilation (NPPV) failure, especially in chronic respiratory patients with community-acquired-pneumonia (CAP) and impaired consciousness. We postulated that in such a clinical scenario, when intubation and conventional mechanical ventilation (CMV) are strongly recommended, the suction of secretions with fiberoptic bronchoscopy (FBO) may increase the chance of NPPV success. The objective of this pilot study was, firstly, to verify the safety and effectiveness of early FBO during NPPV and, secondly, to compare the hospital outcomes of this strategy versus a CMV-based strategy in patients with decompensated chronic obstructive pulmonary disease (COPD) due to CAP who are not appropriate candidates for NPPV because of inefficient mucous clearance and hypercapnic encephalopathy (HE). Methods This is a 12-month prospective matched case-control study performed in one respiratory semi-intensive care unit (RSICU) with expertise in NPPV and in one intensive care unit (ICU). Fifteen acutely decompensated COPD patients with copious secretion retention and HE due to CAP undergoing NPPV in RSICU, and 15 controls (matched for arterial blood gases, acute physiology and chronic health evaluation score III, Kelly-Matthay scale, pneumonia extension and severity) receiving CMV in the ICU were studied. Results Two hours of NPPV significantly improved arterial blood gases, Kelly and cough efficiency scores without FBO-related complications. NPPV avoided intubation in 12/15 patients (80%). Improvement in arterial blood gases was similar in the two groups, except for a greater PaO2/fraction of inspired oxygen ratio with CMV. The rates of overall and septic complications, and of tracheostomy were lower in the NPPV group (20%, 20%, and 0%) versus the CMV group (80%, 60%, and 40%; P < 0.05). Hospital mortality, duration of hospitalisation and duration of ventilation were similar
Scala, Raffaele; Naldi, Mario; Maccari, Uberto
Inefficient clearance of copious respiratory secretion is a cause of non-invasive positive pressure ventilation (NPPV) failure, especially in chronic respiratory patients with community-acquired-pneumonia (CAP) and impaired consciousness. We postulated that in such a clinical scenario, when intubation and conventional mechanical ventilation (CMV) are strongly recommended, the suction of secretions with fiberoptic bronchoscopy (FBO) may increase the chance of NPPV success. The objective of this pilot study was, firstly, to verify the safety and effectiveness of early FBO during NPPV and, secondly, to compare the hospital outcomes of this strategy versus a CMV-based strategy in patients with decompensated chronic obstructive pulmonary disease (COPD) due to CAP who are not appropriate candidates for NPPV because of inefficient mucous clearance and hypercapnic encephalopathy (HE). This is a 12-month prospective matched case-control study performed in one respiratory semi-intensive care unit (RSICU) with expertise in NPPV and in one intensive care unit (ICU). Fifteen acutely decompensated COPD patients with copious secretion retention and HE due to CAP undergoing NPPV in RSICU, and 15 controls (matched for arterial blood gases, acute physiology and chronic health evaluation score III, Kelly-Matthay scale, pneumonia extension and severity) receiving CMV in the ICU were studied. Two hours of NPPV significantly improved arterial blood gases, Kelly and cough efficiency scores without FBO-related complications. NPPV avoided intubation in 12/15 patients (80%). Improvement in arterial blood gases was similar in the two groups, except for a greater PaO2/fraction of inspired oxygen ratio with CMV. The rates of overall and septic complications, and of tracheostomy were lower in the NPPV group (20%, 20%, and 0%) versus the CMV group (80%, 60%, and 40%; P < 0.05). Hospital mortality, duration of hospitalisation and duration of ventilation were similar in the two groups. In patients
... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Death from a respirable disease. 718.303... OR DEATH DUE TO PNEUMOCONIOSIS Presumptions Applicable to Eligibility Determinations § 718.303 Death... death was due to pneumoconiosis. (2) Under this presumption, death shall be found due to a respirable...
Clozapine protects PC-12 cells from death due to oxidative stress induced by hydrogen peroxide via a cell-type specific mechanism involving inhibition of extracellular signal-regulated kinase phosphorylation.
Magliaro, Brian C; Saldanha, Colin J
Recent evidence suggests that some atypical antipsychotic drugs may protect against oxidative stress and consequent neurodegeneration by mechanisms that remain unclear. Using the neuron-like rat pheochromocytoma (PC-12) cell line, Clozapine and N-desmethylclozapine were tested for their ability to protect against cell death due to oxidative stress induced by hydrogen peroxide (H(2)O(2)). These drugs demonstrated significant protection of PC-12 cells, as measured by both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) and Alamar Blue cell viability assays. However, neither viability assay detected a protective effect of Clozapine on human embryonic kidney (HEK293), rat primary cortical neurons, or human neuroblastoma (SH-SY5Y) exposed to H(2)O(2) treatment. The mechanism of protection involves a PC-12 cell-specific differential response to H(2)O(2) treatment vs. the other cell lines. Pre-treatment with 250 microM or 125 microM diethyldithiocarbamate (DETC), a superoxide dismutase (SOD) inhibitor, unexpectedly showed protection of the PC-12 cells from H(2)O(2) treatment. Western blots revealed that Clozapine, N-desmethylclozapine, and DETC reduce the phosphorylation of extracellular signal-regulated kinase (ERK) that is caused by H(2)O(2) exposure in PC-12 cells. In both HEK293 and SH-SY5Y cells, H(2)O(2) exposure did not increase ERK phosphorylation over control, demonstrating a different response to H(2)O(2) vs. PC-12 cells, and explaining why Clozapine could not protect these cells. Also, U0126, a specific MEK inhibitor, was able to protect PC-12 cells from H(2)O(2) exposure, showing that inhibiting ERK phosphorylation is sufficient to provide protection. Cumulatively, these results indicate that Clozapine, N-desmethylclozapine, DETC, and U0126 protect PC-12 cells by blocking the cell-type specific H(2)O(2) induced increase in ERK phosphorylation.
Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer
The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies
Karagic, Nidal; Härer, Andreas; Meyer, Axel; Torres-Dowdall, Julián
During early ontogeny, visual opsin gene expression in cichlids is influenced by prevailing light regimen. Red light, for example, leads to an early switch from the expression of short-wavelength sensitive to long-wavelength sensitive opsins. Here, we address the influence of light deprivation on opsin expression. Individuals reared in constant darkness during the first 14 days post-hatching (dph) showed a general developmental delay compared with fish reared under a 12:12 hr light-dark cycle (control group). Several characters including pigmentation patterns and eye development, appeared later in dark-reared individuals. Quantitative real-time PCR and fluorescent in situ hybridization at six time points during the 14 days period revealed that fish from the control group expressed opsin genes from 5 dph on and maintained a short-wavelength sensitive phenotype (sws1, rh2b, and rh2a). Onset of opsin expression in dark-reared Midas cichlids was delayed by 4 days and visual sensitivity rapidly progressed toward a long-wavelength sensitive phenotype (sws2b, rh2a, and lws). Shifts in visual sensitivities toward longer wavelengths are mediated by thyroid hormone (TH) in many vertebrates. Compared to control fish, dark-reared individuals showed elevated dio3 expression levels - a validated proxy for TH concentration - suggesting higher circulating TH levels. Despite decelerated overall development, ontogeny of opsin gene expression was accelerated, resulting in retinae with long-wavelength shifted predicted sensitivities compared to light-reared individuals. Indirect evidence suggests that this was due to altered TH metabolism. © 2018 Wiley Periodicals, Inc.
Fick, J M; P Ronkainen, A; Madden, R; Sawatsky, A; Tiitu, V; Herzog, W; Korhonen, R K
We determined the biomechanical responses of chondrocytes to indentation at specific locations within the superficial zone of cartilage (i.e. patellar, femoral groove, femoral condylar and tibial plateau sites) taken from female New Zealand white rabbits three days after a partial meniscectomy in the lateral compartment of a knee joint. Confocal laser scanning microscopy combined with a custom indentation system was utilized to image chondrocyte responses at sites taken from ten contralateral and experimental knee joints. Cell volume, height, width and depth changes, global, local axial and transverse strains and Young׳s moduli were determined. Histological assessment was performed and proteoglycan content from the superficial zone of each site was determined. Relative to contralateral group cells, patellar, femoral groove and lateral femoral condyle cells in the experimental group underwent greater volume decreases (p < 0.05), due to smaller lateral expansions (with greater decreases in cell height only for the lateral femoral condyle cells; p < 0.05) whereas medial femoral and medial tibial plateau cells underwent smaller volume decreases (p < 0.05), due to less deformation in cell height (p < 0.05). Proteoglycan content was reduced in the patellar (p > 0.05), femoral groove, medial femoral condyle and medial tibial plateau experimental sites (p < 0.05). The findings suggest: (i) cell biomechanical responses to cartilage loading in the rabbit knee joint can become altered as early as 3 days after a partial meniscectomy, (ii) are site-specific, and (iii) occur before alterations in tissue mechanics or changes detectable with histology. Copyright © 2016 Elsevier Ltd. All rights reserved.
Baker, Bridget B; Yee, Jeremiah S; Meyer, Danielle N; Yang, Doris; Baker, Tracie R
We have shown that zebrafish (Danio rerio) are an excellent model for evaluating the link between early life stage exposure to environmental chemicals and disease in adulthood and subsequent unexposed generations. Previously, we used this model to identify transgenerational effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on skeletal development, sex ratio, and reproductive capacity. Transgenerational inheritance of TCDD toxicity, notably decreased reproductive capacity, appears to be mediated through the male germ line. Thus, we examine testicular tissue for structural and gene expression changes using histology, microarray, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Histological analysis revealed decreased spermatozoa with concurrent increase in spermatogonia, and decreased germinal epithelium thickness in TCDD-exposed males compared with controls. We also identified altered expression of genes associated with testis development, steroidogenesis, spermatogenesis, hormone metabolism, and xenobiotic response. Altered genes are in pathways involving lipid metabolism, molecular transport, small molecule biochemistry, cell morphology, and metabolism of vitamins and minerals. These data will inform future investigations to elucidate the mechanism of adult-onset and transgenerational infertility due to TCDD exposure in zebrafish.
Lv, Yong-Gang; Liu, Jing; Zhang, Jun
A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.
The causa mortis of Napoleon Bonaparte has been vexata quaestio for a long time. The author tries to outline a picture of Napoleon from a sanitary point of view. From the report of doctor Francesco Antonmarchi who performed the autopsy, the author tries to understans the cause of death: gastric perforation due to malignant ulcer and subsequent peritonitis with pulmonary tubercolosis.
Singh, Ajai R.; Bagadia, V.N.; Pradhan, P.V.; Acharya, V.N.
SUMMARY Psychology of deaths due to acute medical emergencies is under-researched. Most studies till now have concentrated on extended-death situations like malignancy. This open pilot study of twenty five patients examines the psychological state of patients during a life threatening acute medical illness (Group A, ten patients) and of those who survive such an experience (Group B, fifteen patients). The study finds psychological exploration both possible and necessary if carried out in a discreet manner. Salient features of the interview technique are discussed. The study finds out whether patients are aware of the possibility of terminality. The psychological disturbances manifest and nature of care expected are also discussed. Near Death Experiences of those who acknowledge their occurence are reported. Some nuances of thanatological research are high-lighted: What are the abilities needed in an interviewer? Can such exploration increase psychological distress in a patient already prone to it because of serious medical sickness? What impact such research can have on the interviewer himself? The paper answers some of these common questions while developing the method of thanatological study in acute medical death-situations. PMID:21927325
Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S; Dong, Zheng; Smith, Sylvia; Zhang, Ming
The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3-/-) and Rip3+/+ control mice. Rip3-/- and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3-/- mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3-/- eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3-/- mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3-independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor-κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3-/- eyes. Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor-κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.
Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S.; Dong, Zheng; Smith, Sylvia
Purpose The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3−/−) and Rip3+/+ control mice. Methods Rip3−/− and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Results Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3−/− mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3−/− eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3−/− mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3–independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor–κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3−/− eyes. Conclusions Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor–κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.
Nabhani, Schafiq; Hönscheid, Andrea; Oommen, Prasad T; Fleckenstein, Bernhard; Schaper, Jörg; Kuhlen, Michaela; Laws, Hans-Jürgen; Borkhardt, Arndt; Fischer, Ute
We report a novel type of mutation in the death ligand FasL that was associated with a severe phenotype of the autoimmune lymphoproliferative syndrome in two patients. A frameshift mutation in the intracellular domain led to complete loss of FasL expression. Cell death signaling via its receptor and reverse signaling via its intracellular domain were completely abrogated. In vitro lymphocyte proliferation induced by weak T cell receptor stimulation could be blocked and cell death was induced by engagement of FasL in T cells derived from healthy individuals and a heterozygous carrier, but not in FasL-deficient patient derived cells. Expression of genes implicated in lymphocyte proliferation and activation (CCND1, NFATc1, NF-κB1) was increased in FasL-deficient T cells and could not be downregulated by FasL engagement as in healthy cells. Our data thus suggest, that deficiency in FasL reverse signaling may contribute to the clinical lymphoproliferative phenotype of ALPS. Copyright © 2014 Elsevier Inc. All rights reserved.
Goldenberg, Robert L.; McClure, Elizabeth M.; Kodkany, Bhala; Wembodinga, Gilbert; Pasha, Omrana; Esamai, Fabian; Tshefu, Antoinette; Patel, Archana; Mabaye, Hillary; Goudar, Shivaparasad; Saleem, Sarah; Waikar, Manjushri; Langer, Ana; Bose, Carl L.; Rubens, Craig E.; Wright, Linda L.; Moore, Janet; Blanc, Ann
Objective To determine the feasibility of introducing a simple indicator of quality of obstetric and neonatal care and to determine the proportion of potentially avoidable perinatal deaths in hospitals in low-income countries. Methods Between September 1, 2011, and February 29, 2012, data were collected from women who had a term pregnancy and were admitted to the labor ward of 1 of 6 hospitals in 4 low-income countries. Fetal heart tones on admission were monitored, and demographic and birth data were recorded. Results Data were obtained for 3555 women and 3593 neonates (including twins). The doptone was used on 97% of women admitted. The overall perinatal mortality rate was 34 deaths per 1000 deliveries. Of the perinatal deaths, 40%–45% occurred in the hospital and were potentially preventable by better hospital care. Conclusion The results demonstrated that it is possible to accurately determine fetal viability on admission via a doptone. Implementation of doptone use, coupled with a concise data record, might form the basis of a low-cost and sustainable program to monitor and evaluate efforts to improve quality of care and ultimately might to help to reduce the in-hospital component of perinatal mortality in low-income countries. PMID:23796259
Schoeps, Daniela; Lefevre, Fernando; Silva, Zilda Pereira; Novaes, Hillegonda Maria Dutilh; Raspantini, Priscila Ribeiro; de Almeida, Márcia Furquim
The insatisfactory completeness of the variables in the Death Certificate (DC) makes it difficult to obtain specific perinatal mortality indicators. To assess the social representation of physicians about the perinatal DC. Twenty-five physicians were interviewed in 15 hospitals in the city of São Paulo, in 2009. Qualitative analysis was performed with the Collective Subject Discourse technique. The DC is primarily considered according to its legal aspect. Physicians feel responsible for fulfilling the cause of death. The majority of them reported receiving help from other professionals to complete information on maternal characteristics and identification variables. There is lack of information on the mother's pre-natal conditions, which can make it difficult to identify the perinatal cause of death, mainly in the Unified Health System (SUS) hospitals. Some participants received specific DC training only when attending medical schools. The organization of medical work may affect the completion of the DC, especially in hospitals from SUS. Other professionals contributed to this task and their training can improve the quality of information.
Posti, Jussi P; Piitulainen, Jaakko M; Hupa, Leena; Fagerlund, Susanne; Frantzén, Janek; Aitasalo, Kalle M J; Vuorinen, Ville; Serlo, Willy; Syrjänen, Stina; Vallittu, Pekka K
This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial
Troszyński, Michał; Niemiec, Tomasz; Wilczyńska, Anna
The aim of the following work was to assess three-level selective perinatal care in Polish voivodeships in 2008 on the basis of the following parameters: birth rates as well as perinatal death rates, divided into three classes of neonatal weights, in hospitals on each of the three levels. The goal of selective perinatal care is, among other things, to diagnose threats to the mother and/or fetus and direct women with high-risk pregnancies to higher level obstetrics and neonatology clinics and units. The structure of a regional three-level perinatal care, as well as the rules and procedures governing the process of redirecting patients to different levels of perinatal care have been defined in great detail. Perinatal death rates analysis has been carried out on the basis of data received from Voivodeship Public Health Centers in sixteen voivodeships in Poland in 2008. The main document constituted MZ-29 form section X, modified by the authors and subdivided into levels of perinatal care. All data contained in the form have been verified: the numbers concerning birth and death rates as well as perinatal deaths and birth weight subgroups from given voivodeship hospitals. Statistic analysis was limited to the presentation of result tables and graphs within voivodeships. Birth rates and perinatal death rates revealed that in the course of ten years the level of perinatal care, introduced gradually in Poland between the years 1997-1999, resulted in its improvement. Perinatal death rates decreased in the course of ten years from 9.5% in 1999 to 6.45% in 2008, i.e. by 0.3% annually. On the first level, the rate of neonates with very low birth weight, 500-999g, decreased by 5.5% and was 21.1% in 2008 and 36.6% in 1999, whereas on the third level, the birth rate in the same group (500-999g) increased by 12.7% and was 47.7% in 2008 and 35.5% in 1999. There is a growing and alarming tendency to perform cesarean sections. The increase amounted up to 1.2% annually (18.2% in 19999
Ando, Tomo; Takagi, Hisato; Grines, Cindy L
Clinical outcomes of transfemoral-transcatheter aortic valve implantation (TF-TAVI) versus surgical aortic valve replacement (SAVR) or transapical (TA)-TAVI are limited to a few randomized clinical trials (RCTs). Because previous meta-analyses only included a limited number of adjusted studies or several non-adjusted studies, our goal was to compare and summarize the outcomes of TF-TAVI vs SAVR and TF-TAVI vs TA-TAVI exclusively with the RCT and propensity-matched cohort studies with direct and adjusted indirect comparisons to reach more precise conclusions. We hypothesized that TF-TAVI would offer surgical candidates a better outcome compared with SAVR and TA-TAVI because of its potential for fewer myocardial injuries. A literature search was conducted through PUBMED and EMBASE through June 2016. Only RCTs and propensity-matched cohort studies were included. A direct meta-analysis of TF-TAVI vs SAVR, TA-TAVI vs SAVR and TF-TAVI vs TA-TAVI was conducted. Then, the effect size of an indirect meta-analysis was calculated from the direct meta-analysis. The effect sizes of direct and indirect meta-analyses were then combined. A random-effects model was used to calculate the hazards ratio and the odds ratio with 95% confidence intervals. Early (in-hospital or 30 days) and mid-term (≥1 year) all-cause mortality rates were assessed. Our search resulted in 4 RCTs (n = 2319) and 14 propensity-matched cohort (n = 7217) studies with 9536 patients of whom 3471, 1769 and 4296 received TF, TA and SAVR, respectively. Direct meta-analyses and combined direct and indirect meta-analyses of early and mid-term deaths with TF-TAVI and SAVR were similar. Early deaths with TF-TAVI vs TA-TAVI were comparable in direct meta-analyses (odds ratio 0.64, P = 0.35) and direct and indirect meta-analyses combined (odds ratio 0.73, P = 0.24). Mid-term deaths with TF-TAVI vs TA-TAVI were increased (hazard ratio 0.83, P = 0.07) in a direct meta-analysis and became significant
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Niwinska, Anna, E-mail: firstname.lastname@example.org; Tacikowska, Malgorzata; Murawska, Magdalena
Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Groupmore » II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.« less
Na, Rong; Zheng, S. Lilly; Han, Misop; Yu, Hongjie; Jiang, Deke; Shah, Sameep; Ewing, Charles M.; Zhang, Liti; Novakovic, Kristian; Petkewicz, Jacqueline; Gulukota, Kamalakar; Helseth, Donald L.; Quinn, Margo; Humphries, Elizabeth; Wiley, Kathleen E.; Isaacs, Sarah D.; Wu, Yishuo; Liu, Xu; Zhang, Ning; Wang, Chi-Hsiung; Khandekar, Janardan; Hulick, Peter J.; Shevrin, Daniel H.; Cooney, Kathleen A.; Shen, Zhoujun; Partin, Alan W.; Carter, H. Ballentine; Carducci, Michael A.; Eisenberger, Mario A.; Denmeade, Sam R.; McGuire, Michael; Walsh, Patrick C.; Helfand, Brian T.; Brendler, Charles B.; Ding, Qiang; Xu, Jianfeng; Isaacs, William B.
Background Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk. Objective To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death. Design, setting, and participants A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes. Outcome measurements and statistical analysis Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher’s exact test and Cox regression analysis, respectively. Results and limitations The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p = 0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤60 yr, 61–65 yr, 66–70 yr, 71–75 yr, and over 75 yr, respectively, p = 0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤5 yr, 6–10 yr, and > 10 yr after a PCa diagnosis, respectively, p = 0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio = 2.13, 95% confidence interval: 1.24–3.66, p = 0.004). A limitation of this study is that other DNA repair genes were not analyzed. Conclusions Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time. Patient summary Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age. PMID
Risse, Manfred; Weilbächer, Nadine; Birngruber, Christoph; Verhoff, Marcel A
There are no verified statistics about deaths occurring in hotels, and only a few cases have been described in the literature. A recent case induced us to conduct a systematic search for deaths in hotels in the autopsy reports of the Institute of Legal Medicine in Giessen for the period from 1968 to 2009. This search yielded 22 evaluable cases in which persons had been found dead or had died in hotels. Data evaluated in the study were sex and age of the deceased, reason for the stay in the hotel and cause of death. Among the deaths, 18 were males and 4 females and the average age was 41 and 40 years respectively. 6 of the male guests had died from a natural and 10 from a non-natural cause. In the remaining two cases, the cause of death could not be determined, but as there was no evidence that another party had been involved, the cases were not further investigated. Of the 4 female guests, 3 had died of a natural cause; in one case, the cause of death remained unclear even after morphological and toxicological investigations. Surprisingly, a third of the men were found to be temporarily living in hotels due to social circumstances. This was not true for any of the women. Our retrospective analysis is based on a comparatively small number of deaths in what were mostly hotels in small to medium-sized towns. Interestingly, the gender ratio of 18:4 for deceased men and women was significantly higher than the usual gender ratio of 2:1 found for forensic autopsies. To be able to draw further conclusions, a greater number of cases would have to be analysed, for example by recruiting additional case files from other institutes of legal medicine. This would also open up the option of investigating possible regional variations.
Johnson, H R
Over a period of 22 years, a number of needless deaths have been investigated in this institution following diagnostic and therapeutic procedures. These include fatalities associated with endoscopic examination and biopsies, complications in relation to indwelling tubes and radiological examinations. It is important that these catastrophies must be fully investigated. In this regard, it is essential to ensure that informed consent has been obtained, that an experienced independent pathologist conduct the investigations and that every effort must be made to get at the truth.
Farag, Tamer H.; Koplan, Jeffrey P.; Breiman, Robert F.; Madhi, Shabir A.; Heaton, Penny M.; Mundel, Trevor; Ordi, Jaume; Bassat, Quique; Menendez, Clara; Dowell, Scott F.
Abstract. Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12–15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality. PMID:28719334
Farag, Tamer H; Koplan, Jeffrey P; Breiman, Robert F; Madhi, Shabir A; Heaton, Penny M; Mundel, Trevor; Ordi, Jaume; Bassat, Quique; Menendez, Clara; Dowell, Scott F
Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.
Sparre-Sørensen, Maja; Kristensen, Gustav N
Studies have shown that malnutrition increases the risk of morbidity, mortality, the length of hospital stay, and costs in the elderly population. Approximately one third of all patients admitted to geriatric wards in Denmark are malnourished according to the Danish Geriatric database. The aim of this study is to describe and examine the sudden increase in deaths due to malnutrition in the elderly population in Denmark from 1999 and, similarly, the sudden decline in malnutrition related deaths in 2007. A descriptive epidemiologic study was performed. All Danes listed in the national death registry who died from malnutrition in the period from 1994 to 2012 are included. The number of deaths from malnutrition increased significantly during the period from 1999 to 2007, especially in the age group 70 years and over. Additionally, we document a surprising similarity between the development in excess mortality from malnutrition in the five Danish regions during the same period. During the period 1999-2007 malnutrition was the direct cause of 340 extra deaths, and probably ten times more registered under other diseases. This development in excess mortality runs parallel in all five Danish regions over time. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Zegers, Richard H C; Weigl, Andreas; Steptoe, Andrew
The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch-Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.
Aissaoui, Nadia; Bougouin, Wulfran; Dumas, Florence; Beganton, Franckie; Chocron, Richard; Varenne, Olivier; Spaulding, Christian; Karam, Nicole; Montalescot, Gilles; Aubry, Pierre; Sideris, Georges; Marijon, Eloi; Jouven, Xavier; Cariou, Alain
Little is known about the association between provision of post-resuscitation care and prognosis of out-of-hospital cardiac arrest (OHCA) in elderly patients. Previous studies have suggested futility after 65 years of age. We aimed to evaluate the association of early coronary angiogram (CAG) followed if necessary by percutaneous coronary intervention (PCI), with favorable outcome after OHCA among elderly patients, compared to younger patients. Using a large French registry, we included all OHCA patients with an initial shockable rhythm, transported to hospital from 2011 to 2015. Favorable outcome was defined as hospital discharge with Cerebral Performance Category (CPC) 1 or 2. and were evaluated by multivariate logistic regression. Subgroup analyses were performed according to age groups: <65, 65-75 and >75 years. Among 1502 included patients, 31% were older than 65 and 12% older than 75 years. An early CAG was performed in 79%, 88% and 76% of patients below 65, between 65 and 75 and above 75, respectively (P = 0.002). The rate of patients discharged with CPC1 or 2 was 42% below 65, 38% between 65 and 75 and 24% above 75 (P < 0.001). Among the whole population, early CAG (OR = 6.4, 95% CI = 3.9-10.5, P < 0.001) was associated with favorable outcome. In subgroups analysis, CAG was associated with favorable outcome among patients <65 and 65-75. In patients >75, there was a trend towards a favorable outcome (OR2.9, 95CI = 0.9-9.1). In a large registry of OHCA survivors, the early CAG use was associated with a better prognosis. This benefit was persistent up to 75 years of age, suggesting that age alone should not guide the decision for early invasive strategy. Copyright © 2018 Elsevier B.V. All rights reserved.
Trnka, J; Gesicki, M; Suslo, R; Siuta, J; Drobnik, J; Pirogowicz, I
Violent asphyxia can be subdivided into various kinds according to the mechanism, so that the resuscitation techniques are different in each case. The purpose of the present article was to analyze the autopsy reports of the Department of Forensic Medicine of the Medical University in Wroclaw, Poland of 2010, in which the established cause of death was violent asphyxia. We found that among the 890 autopsies performed, there were 164 cases of death due to violent asphyxia caused by drowning, choking on food, gastric fluid, or blood, hanging, manual strangulations, immobilization of the chest (positional asphyxia), environmental asphyxia due to substitution of the oxygen-rich air for some other gas, and others. The most common cause of death in the group was hanging, mostly suicidal hangings of alcohol-intoxicated males. Despite an early medical treatment consisting of removing the noose from the neck and suction the fluids from the mouth and bronchial tree to safe the central nervous system from imminent hypoxia, there were negative outcomes in most cases due to the development of critical brain ischemia, with deaths followed after several days spent in the intensive care units. No connection to gender or age of the deceased was noted. We conclude that violent asphyxia remains to be a quite commonly cause of death in the practice of forensic pathologists - among all the autopsies performed in 2010 every sixth was of an asphyxia victim.
Braun, Anne; Zhang, Songwen; Miettinen, Helena E.; Ebrahim, Shamsah; Holm, Teresa M.; Vasile, Eliza; Post, Mark J.; Yoerger, Danita M.; Picard, Michael H.; Krieger, Joshua L.; Andrews, Nancy C.; Simons, Michael; Krieger, Monty
Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5–6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between ≈3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. PMID:12771386
Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G
Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.
Gowitt, G.T.; Hanzlick, R.L.
So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.
Banerji, John Samuel; Devasia, Antony; Kekre, Nitin Sudhakar; Chacko, Ninan
To study the magnitude of radiation cystitis following radiation therapy for carcinoma cervix, and propose an algorithm to decide on early diversion, with or without vesicovaginostomy. Women who developed radiation cystitis following radiotherapy for carcinoma cervix from January 1998 to December 2011 were included in this retrospective study. Electronic hospital records were analysed to document the presence of radiation cystitis. All women who developed evidence of radiation-induced cystitis, according to the common toxicity and Radiation Therapy Oncology Group criteria, were included in the study. We looked at transfusion requirements, number of hospital admissions, quality of life and cost involved. Chi-square tests were done where applicable. SPSS version 16 was used for analysis. Of the 902 patients who received radiation for carcinoma cervix in the 13-year period, 62 (6.87%) developed grade 3/4 cystitis. Twenty-eight of them underwent ileal conduit diversion, with 18 undergoing concomitant vesicovaginostomy. When compared with the patients who did not have diversion, the transfusion requirements, number of hospital admissions and quality of life had a statistically significant difference. Cost analysis of early diversion too showed a marginal benefit with early diversion. The limitation of the study was that it was retrospective in nature. In radiation cystitis, multiple hospital admissions and consequential increase in cost is the norm. In severe disease, early diversion is a prudent, cost-effective approach with good quality of life and early return to normal activity. © 2014 Royal Australasian College of Surgeons.
Sudden death in young people: Heart problems often blamed Sudden death in young people is rare, but those at ... causes and treatments. By Mayo Clinic Staff Sudden death in people younger than 35, often due to ...
Du, Si-Hao; Tan, Xiao-Hui; Zhao, Rui; Zhao, Dong; Xue, Ye; Wang, Hui-Jun; Xie, Xiao-Li; Wang, Qi
Deaths involved with environmental hazards and intoxication might present with minimal or nonspecific morphological features, which are insufficient to establish a diagnosis. The present study investigated the postmortem brain mRNA and immunohistochemical expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and nuclear factor erythroid-2-related factor-2 (Nrf2) in forensic cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of IL-1β, TNF-α and iNOS, and lower expression of Nrf2 in methamphetamine intoxication and hyperthermia cases, higher expression of iNOS in phenobarbital intoxication cases, and higher expression of Nrf2 in phenobarbital intoxication and hypothermia cases. Immunostaining results showed substantial inter-individual variations in each group, showing no evident differences in distribution or intensity. These findings suggest that different inflammatory and antioxidant responses were involved in deaths from different etiologies, and these markers may be useful for evaluating brain damage and responses.
Solberg, Carl Tollef; Gamlund, Espen
The state of the world is one with scarce medical resources where longevity is not equally distributed. Given such facts, setting priorities in health entails making difficult yet unavoidable decisions about which lives to save. The business of saving lives works on the assumption that longevity is valuable and that an early death is worse than a late death. There is a vast literature on health priorities and badness of death, separately. Surprisingly, there has been little cross-fertilisation between the academic fields of priority setting and badness of death. Our aim is to connect philosophical discussions on the badness of death to contemporary debates in health priorities. Two questions regarding death are especially relevant to health priorities. The first question is why death is bad. Death is clearly bad for others, such as family, friends and society. Many philosophers also argue that death can be bad for those who die. This distinction is important for health priorities, because it concerns our fundamental reasons for saving lives. The second question is, 'When is the worst time to die?' A premature death is commonly considered worse than a late death. Thus, the number of good life years lost seems to matter to the badness of death. Concerning young individuals, some think the death of infants is worse than the death of adolescents, while others have contrary intuitions. Our claim is that to prioritise between age groups, we must consider the question of when it is worst to die. Deprivationism provides a more plausible approach to health priorities than Epicureanism. If Deprivationism is accepted, we will have a firmer basis for claiming that individuals, in addition to having a health loss caused by morbidity, will have a loss of good life years due to mortality. Additionally, Deprivationism highlights the importance of age and values for health priorities. Regarding age, both variants of Deprivationism imply that stillbirths are included in the Global
Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study
Casulo, Carla; Byrtek, Michelle; Dawson, Keith L.; Zhou, Xiaolei; Farber, Charles M.; Flowers, Christopher R.; Hainsworth, John D.; Maurer, Matthew J.; Cerhan, James R.; Link, Brian K.; Zelenetz, Andrew D.; Friedberg, Jonathan W.
Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials. PMID:26124482
Johansson, Per; Lindahl, Erica
Objective: In this article, we estimate the effect of a multidisciplinary collaboration program on the length of sickness absence. The intention with the program was to avoid long-term sickness absence by providing an early and holistic evaluation of the sick-listed individuals' conditions. The target group was individuals who were at risk of…
Thamer, Mae; Kaufman, James S; Zhang, Yi; Zhang, Qian; Cotter, Dennis J; Bang, Heejung
A shared decision-making tool could help elderly patients with advanced chronic kidney disease decide about initiating dialysis therapy. Because mortality may be high in the first few months after initiating dialysis therapy, incorporating early mortality predictors in such a tool would be important for an informed decision. Our objective is to derive and validate a predictive risk score for early mortality after initiating dialysis therapy. Retrospective observational cohort, with development and validation cohorts. US Renal Data System and claims data from the Centers for Medicare & Medicaid Services for 69,441 (aged ≥67 years) patients with end-stage renal disease with a previous 2-year Medicare history who initiated dialysis therapy from January 1, 2009, to December 31, 2010. Demographics, predialysis care, laboratory data, functional limitations, and medical history. All-cause mortality in the first 3 and 6 months. Predicted mortality by logistic regression. The simple risk score (total score, 0-9) included age (0-3 points), low albumin level, assistance with daily living, nursing home residence, cancer, heart failure, and hospitalization (1 point each), and showed area under the receiver operating characteristic curve (AUROC)=0.69 in the validation sample. A comprehensive risk score with additional predictors was also developed (with AUROC=0.72, high concordance between predicted vs observed risk). Mortality probabilities were estimated from these models, with the median score of 3 indicating 12% risk in 3 months and 20% in 6 months, and the highest scores (≥8) indicating 39% risk in 3 months and 55% in 6 months. Patients who did not choose dialysis therapy and did not have a 2-year Medicare history were excluded. Routinely available information can be used by patients with chronic kidney disease, families, and their nephrologists to estimate the risk of early mortality after dialysis therapy initiation, which may facilitate informed decision making
Roberts, Derek J.; Harzan, Christina; Kirkpatrick, Andrew W.; Dixon, Elijah; Grondin, Sean C.; McBeth, Paul B.; Kaplan, Gilaad G.
Summary A wide range of factors have traditionally led to early in-hospital death following severe injury. The primary goal of this commentary was to evaluate the causes of early posttraumatic inpatient deaths over an extended period. Although early posttraumatic in-hospital death remains multifactorial, severe traumatic brain injuries are the dominant cause and have increased in proportion over time. Other traditional causes of death have also decreased owing to improved clinical care. PMID:29806810
Asmundo, A; Aragona, M; Gualniera, P; Aragona, F
The sudden death by hypoglycemia is an aspect of the forensic pathology frequently neglected. Authors initially described the pathogenesis of different hypoglycemia forms, distinguishing the primary ones due to hyperinsulinism and the secondary ones due to functional insufficiency of other organs (hypophysis, thyroid, adrenal gland, liver); after that Authors described three cases of sudden death induced hypoglycemia by hyperinsulinism: two were unweaned with nesidioblastosis and one adolescent. In any form of hypoglycemia the central nervous system damage is present with evident neuronal degenerative-necrotic phenomena, widespread edema with microhemorrhage, swollen and dissociation of myelin sheath, glial cells hyperplasia. Death caused by primary hypoglycemia is histopathologically different from the secondary one because of the maintenance of hepatic glycogen content in the former, that increase in striated muscles, including the heart, in spite of the constant secretion of catecholamine from the adrenal medulla. Glycogen is depleted in secondary hypoglycemia. In the primary form, behind the adrenal medulla hyperfunction, the increased functional activity of the adrenal cortex is moderate, contrasting with the seriousness of the syndrome, due prevalently to inhibit the gluconeogenesis response conditioned by the persistence of stored glycogen in the liver, heart and striated muscles. The rare anoxic processes coming with resynthesis of hepatic glycogen have to be considered in the differential diagnosis. The primary hypoglycemic death, especially in unweaned, is frequently promoted by other processes inducing hypoxia (fetal asphyxia outcome, pneumonia, etc.) or worsening the hypoglycemia (hypothyroidism, etc.). The secondary hypoglycemias are characterized by the normality of exocrine pancreas and by organic alterations that cause glycogen depletion from the liver.
How many cases of Type 2 diabetes mellitus are due to being overweight in middle age? Evidence from the Midspan prospective cohort studies using mention of diabetes mellitus on hospital discharge or death records.
Hart, C L; Hole, D J; Lawlor, D A; Davey Smith, G
To relate body mass index (BMI) in middle age to development of diabetes mellitus. Participants were 6927 men and 8227 women from the Renfrew/Paisley general population study and 3993 men from the Collaborative occupational study. They were aged 45-64 years and did not have reported diabetes mellitus. Cases who developed diabetes mellitus, identified from acute hospital discharge data and from death certificates in the period from screening in 1970-1976 to 31 March 2004, were related to BMI at screening. Of Renfrew/Paisley study men 5.4%, 4.8% of women and 5% of Collaborative study men developed diabetes mellitus. Odds ratios for diabetes mellitus were higher in the overweight group (BMI 25 to < 30 kg/m(2)) than in the normal weight group (BMI 18.5 to < 25 kg/m(2)) and highest in the obese group (BMI >or= 30 kg/m(2)). Compared with the normal weight group, age-adjusted odds ratios for overweight and obese Renfrew/Paisley men were 2.73 [95% confidence interval (CI) 2.05, 3.64] and 7.26 (95% CI 5.26, 10.04), respectively. Further subdividing the normal, overweight and obese groups showed increasing odds ratios with increasing BMI, even at the higher normal level. Assuming a causal relation, around 60% of cases of diabetes could have been prevented if everyone had been of normal weight. Overweight and obesity account for a major proportion of diabetes mellitus, as identified from hospital discharge and death records. With recent increases in the prevalence of overweight, the burden of disease related to diabetes mellitus is likely to increase markedly. Primordial prevention of obesity would be a major strategy for reducing the incidence of diabetes mellitus in populations.
Atrash, Hani K
Reduction of child mortality is a global public health priority. Parents can play an important role in reducing child mortality. The inability of one or both parents to care for their children due to death, illness, divorce or separation increases the risk of death of their children. There is increasing evidence that the health, education, and socioeconomic status of mothers and fathers have significant impact on the health and survival of their children. We conducted a literature review to explore the impact of the death of parents on the survival and wellbeing of their children and the mechanisms through which this impact is mediated. Studies have generally concluded that the death of a mother significantly increased the risk of death of her children, especially during the early years; the effect continues but is significantly reduced with increasing age through the age of 15 years. The effect of the loss of a father had less impact than the effect of losing a mother although it too had negative consequences for the survival prospect of the child. A mother's health, education, socioeconomic status, fertility behavior, environmental health conditions, nutritional status and infant feeding, and the use of health services all play an important role in the level of risk of death of her children. Efforts to achieve the Millennium Development Goal No. 4 of reducing children's under-5 mortality in developing countries by two thirds by 2015 should include promoting the health and education of women.
Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim
Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Martikainen, Janne A; Kautiainen, Hannu; Rantalaiho, Vappu; Puolakka, Kari T
To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.
Cohen, Rony; Basel-Vanagaite, Lina; Goldberg-Stern, Hadassah; Halevy, Ayelet; Shuper, Avinoam; Feingold-Zadok, Michal; Behar, Doron M; Straussberg, Rachel
To characterize a new subset of early myoclonic encephalopathy usually associated with metabolic etiologies with a new genetic entity. We describe two siblings with early myoclonic encephalopathy born to consanguineous parents of Arab Muslim origin from Israel. We used homozygosity mapping and candidate gene sequencing to reveal the genetic basis of the myoclonic syndrome. We found a rare missense mutation in the gene encoding one of the two mitochondrial glutamate/H symporters, SLC25A22. The phenotype of early myoclonic encephalopathy was first linked to the same mutation in 2005 in patients of the same ethnicity as our family. Owing to the devastating nature of this encephalopathy, we focus attention on its clinical history, epileptic semiology, distinct electroencephalography features, and genetic basis. We provide the evidence that an integrated diagnostic strategy combining homozygosity mapping with candidate gene sequencing is efficient in consanguineous families with highly heterogeneous autosomal recessive diseases. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Hauck, Ludger; Stanley-Hasnain, Shanna; Fung, Amelia; Grothe, Daniela; Rao, Vivek; Mak, Tak W.
The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm) mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1. PMID:29267372
Iltis, Ana Smith; Cherry, Mark J
Traditionally, people were recognized as being dead using cardio-respiratory criteria: individuals who had permanently stopped breathing and whose heart had permanently stopped beating were dead. Technological developments in the middle of the twentieth century and the advent of the intensive care unit made it possible to sustain cardio-respiratory and other functions in patients with severe brain injury who previously would have lost such functions permanently shortly after sustaining a brain injury. What could and should physicians caring for such patients do? Significant advances in human organ transplantation also played direct and indirect roles in discussions regarding the care of such patients. Because successful transplantation requires that organs be removed from cadavers shortly after death to avoid organ damage due to loss of oxygen, there has been keen interest in knowing precisely when people are dead so that organs could be removed. Criteria for declaring death using neurological criteria developed, and today a whole brain definition of death is widely used and recognized by all 50 states in the United States as an acceptable way to determine death. We explore the ongoing debate over definitions of death, particularly over brain death or death determined using neurological criteria, and the relationship between definitions of death and organ transplantation.
Bäckström, Björn; Johansson, Bengt; Eriksson, Anders
Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available. © 2015 American Academy of Forensic Sciences.
Abedin, Mohammed Forhad; Hoque, Mohammad Mahfuzul; Md Sadequl Islam, Abu Saleh; Islam Chowdhury, Md Forhadul; Chandra das, Dulal; Begum, Syeda Anwara; Mamun, Ayub Al; Mamun-Al-Mahtab; Rahman, Salimur; Saha, Anup Kumar
In industrialized countries, the audit has become an integral part of medical care. The experience from developing countries like Bangladesh is still inadequate. This study had been carried out to find out relation among some factors like age, sex, causes, diurenal variation, duration of hospital stay with death and errors in certification process. It was a cross-sectional study conducted at the Department of Medicine, Sir Salimullah Medical College (SSMC) and Mitford Hospital from March 2010 to August 2010. Information of consecutive 100 deaths was collected in a predesigned clinical data sheet within half an hour of every occurrence. Necessary data were collected from hospital case records (admission registrar, case files and death certificates) using structured checklist. Patients who were brought dead were excluded from the study. Among 100 deaths, 48% were males (n = 48) and 52% were females (n = 52). Within this group, 66.7% were males and 33.3% were females. First day (within 24 hours of admission) death accounted for 46% (n = 46) of all death and by the second day 23% (n = 23) of all deaths occurred. The highest underlying cause of death was cerebrovascular diseases (29% of total death), infectious disease contributed 20%, chronic liver disease 13%, malignancy 7%, poisoning 6%, cor pulmonale 5%, while others were 20%. In this studychronic liver disease was found to be one of the leading causes of death in our hospital and most of them occurred due to hepatic encephalopathy. So, early detection of hepatic encephalopathy and treatment is necessary to reduce hospital mortality. How to cite this article: Abedin MF, Hoque MM, Islam ASMS, Chowdhury MFI, Das DC, Begum SA, Mamun AA, Mahtab MA, Rahman S, Saha AK. Chronic Liver Disease is One of the Leading Causes of Death in Bangladesh: Experience by Death Audit from a Tertiary Hospital. Euroasian J Hepato-Gastroenterol 2014;4(1):14-17.
Bengsch, Bertram; Johnson, Andy L; Kurachi, Makoto; Odorizzi, Pamela M; Pauken, Kristen E; Attanasio, John; Stelekati, Erietta; McLane, Laura M; Paley, Michael A; Delgoffe, Greg M; Wherry, E John
Dynamic reprogramming of metabolism is essential for T cell effector function and memory formation. However, the regulation of metabolism in exhausted CD8(+) T (Tex) cells is poorly understood. We found that during the first week of chronic lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction develops, virus-specific CD8(+) T cells were already unable to match the bioenergetics of effector T cells generated during acute infection. Suppression of T cell bioenergetics involved restricted glucose uptake and use, despite persisting mechanistic target of rapamycin (mTOR) signaling and upregulation of many anabolic pathways. PD-1 regulated early glycolytic and mitochondrial alterations and repressed transcriptional coactivator PGC-1α. Improving bioenergetics by overexpression of PGC-1α enhanced function in developing Tex cells. Therapeutic reinvigoration by anti-PD-L1 reprogrammed metabolism in a subset of Tex cells. These data highlight a key metabolic control event early in exhaustion and suggest that manipulating glycolytic and mitochondrial metabolism might enhance checkpoint blockade outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Kleyböcker, A; Liebrich, M; Verstraete, W; Kraume, M; Würdemann, H
Early warning indicators for process failures were investigated to develop a reliable method to increase the production efficiency of biogas plants. Organic overloads by the excessive addition of rapeseed oil were used to provoke the decrease in the gas production rate. Besides typical monitoring parameters, as pH, methane and hydrogen contents, biogas production rate and concentrations of fatty acids; carbon dioxide content, concentrations of calcium and phosphate were monitored. The concentration ratio of volatile fatty acids to calcium acted as an early warning indicator (EWI-VFA/Ca). The EWI-VFA/Ca always clearly and reliably indicated a process imbalance by exhibiting a 2- to 3-fold increase 3-7days before the process failure occurred. At this time, it was still possible to take countermeasures successfully. Furthermore, increases in phosphate concentration and in the concentration ratio of phosphate to calcium also indicated a process failure, in some cases, even earlier than the EWI-VFA/Ca. Copyright © 2012 Elsevier Ltd. All rights reserved.
Ratbi, Ilham; Jaouad, Imane Cherkaoui; Elorch, Hamza; Al-Sheqaih, Nada; Elalloussi, Mustapha; Lyahyai, Jaber; Berraho, Amina; Newman, William G; Sefiani, Abdelaziz
Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H
Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. Copyright © 2010 Elsevier Ltd. All rights reserved.
Pinder, Margaret M.; Hayslip, Bert, Jr.
The elderly death rate is somewhat higher than the death rate in general. Numbers of schools with gerontological curricula and frequency of death education courses are positively related to elderly death rates. The contention that elderly deaths have less social impact is not supported. (JAC)
Eastman, Alexander L; Cripps, Michael W; Abdelfattah, Kareem R; Inaba, Kenji; Weiser, Thomas G; Spain, David A; Staudenmayer, Kristan L
Trauma-related deaths remain an important public health problem. One group susceptible to death due to traumatic mechanisms is US law enforcement (LE). We hypothesized that LE officers experienced a higher chance of violent death compared with the general US population and that risks have increased over time. The National Institute on Occupational Safety and Health National Occupational Mortality Surveillance is a population-based survey of occupational deaths. It includes data for workers who died during 1985 to 1998 in one of 30 US states (EARLY period). Additional deaths were added from 23 US states in 1999, 2003 to 2004, 2007 to 2010 (LATE period). Mortality rates are estimated by calculating proportionate mortality ratios (PMR). A PMR above 100 is considered to exceed the average background risk for all occupations. All adults older than 18 years whose primary occupation was listed as "law enforcement worker" were included in the analysis. Law enforcement personnel were more likely to die from an injury compared with the general population (Fig. 1). The overall PMR for injury in EARLY was 111 (95% confidence interval [CI], 108-114; p < 0.01), and for LATE was 118 (95% CI, 110-127; p < 0.01). Four mechanisms of death reached statistical significance: motor vehicle traffic (MVT)-driver, MVT-other, intentional self-harm, and assault/homicide. The highest PMR in EARLY was associated with firearms (PMR, 272; 95% CI, 207-350; p < 0.01). The highest PMR in LATE was associated with death due to being a driver in an MVT (PMR, 194; 95% CI, 169-222; p < 0.01). There were differences in risk of death by race and sex. White females had the highest PMR due to assault and homicide (PMR, 317; 95% CI, 164-554; p < 0.01). All groups had similar risks of death due to intentional self-harm (PMR, 130-171). The risk of death for US LE officers is high and increasing over time, suggesting an at-risk population that requires further interventions. Targeted efforts based on risk
Marcus, Pamela M; Doria-Rose, Vincent Paul; Gareen, Ilana F; Brewer, Brenda; Clingan, Kathy; Keating, Kristen; Rosenbaum, Jennifer; Rozjabek, Heather M; Rathmell, Joshua; Sicks, JoRean; Miller, Anthony B
Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer. Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death. In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as
Higuera Iglesias, Anjarath Lorena; Kudo, Koichiro; Manabe, Toshie; Corcho Berdugo, Alexander Enrique; Baeza, Ariel Corrales; Ramos, Leticia Alfaro; Gutiérrez, René Guevara; Manjarrez Zavala, María Eugenia; Takasaki, Jin; Izumi, Shinyu; Bautista, Edgar; Perez Padilla, José Rogelio
Background Anti-viral treatment has been used to treat severe or progressive illness due to pandemic H1N1 2009. A main cause of severe illness in pandemic H1N1 2009 is viral pneumonia; however, it is unclear how effective antiviral treatment is against pneumonia when administered >48 hours after symptom onset. Therefore, we aimed to determine how time from symptom onset to antiviral administration affected the effectiveness of antiviral treatment against pneumonia due to pandemic (H1N1) 2009. Methods/Principal Findings A retrospective medical chart review of 442 patients was conducted in a hospital in Mexico. Subjects had tested positive for pandemic H1N1 2009 virus by real-time reverse-transcriptase-polymerase-chain-reaction and were administered oseltamivir. Median time from symptom onset to oseltamivir administration was 5.0 days (range, 0–43). 442 subjects, 71 (16.1%) had severe pneumonia which required mechanical ventilation, 191 (43.2%) had mild to moderate pneumonia, and 180 (40%) did not have pneumonia. Subjects were divided into four groups based on time to oseltamivir administration: ≤2, 3–7, 8–14, and >14 days. Severity of respiratory features was associated with time to treatment, and multivariate analysis indicated that time to oseltamivir administration was associated with severity of respiratory features. A proportional odds model indicated that 50% probability for occurrence of pneumonia of any severity and that of severe pneumonia in patients who would develop pneumonia reached at approximately 3.4 and 21 days, respectively, after symptom onset. Patients with a shorter time to oseltamivir administration were discharged earlier from the hospital. Conclusions Earlier initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic H1N1 2009. Even when administered >48 hours after symptom onset, oseltamivir showed considerable potential for
Ledezma, Melissa L.
This paper suggests strategies for helping children understand death. The early experiences of childhood build the foundation on which the child establishes a healthy orientation towards life and living. Grieving parents are often so upset by their own loss that they do not carefully explain death to their children. Parents may feel that the child…
Bode, H; Sauer, M; Pringsheim, W
The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.
Bode, H; Sauer, M; Pringsheim, W
The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination. PMID:3069052
Crib death; SIDS ... However, SIDS is still a major cause of death in infants under 1 year old. Thousands of ... affects boys more often than girls. Most SIDS deaths occur in the winter. The following may increase ...
Shetty, Hemanth Narayan; Koonoor, Vishal
Past research has reported that children with repeated occurrences of otitis media at an early age have a negative impact on speech perception at a later age. The present study necessitates documenting the temporal and spectral processing on speech perception in noise from normal and atypical groups. The present study evaluated the relation between speech perception in noise and temporal; and spectral processing abilities in children with normal and atypical groups. The study included two experiments. In the first experiment, temporal resolution and frequency discrimination of listeners with normal group and three subgroups of atypical groups (had a history of OM) a) less than four episodes b) four to nine episodes and c) More than nine episodes during their chronological age of 6 months to 2 years) were evaluated using measures of temporal modulation transfer function and frequency discrimination test. In the second experiment, SNR 50 was evaluated on each group of study participants. All participants had normal hearing and middle ear status during the course of testing. Demonstrated that children with atypical group had significantly poorer modulation detection threshold, peak sensitivity and bandwidth; and frequency discrimination to each F0 than normal hearing listeners. Furthermore, there was a significant correlation seen between measures of temporal resolution; frequency discrimination and speech perception in noise. It infers atypical groups have significant impairment in extracting envelope as well as fine structure cues from the signal. The results supported the idea that episodes of OM before 2 years of agecan produce periods of sensory deprivation that alters the temporal and spectral skills which in turn has negative consequences on speech perception in noise. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Background While it is known that advanced age alters the recruitment of neutrophils during wound healing, thereby delaying the wound healing process, little is known about prolonged wound healing in advanced ages. Thus, we investigated the correlation of neutrophil recruitment with healing events, and the impact of whey protein (WP) on neutrophil activation. Methods The animals were allocated into wounded young group, wounded older group and wounded older rats with daily treatment of WP at a dose of 100 mg/kg of body weight. Results Our results pointed to a marked deficiency in the number of neutrophils in the wounds of older rats, which was accompanied with impairment of the healing process. In the group of older rats, phagocytic activity, as tested by fluorescence microscopy, declined throughout the first 24 hours after wounding. Both the neutrophil number and the phagocytic activity recovered in older rats which received WP supplementation. Interestingly, WP was found to significantly up-regulate the MIP-1α and CINC-1 mRNA expression in old rats. On the other hand, the wound size in older rats was significantly higher than that in younger ones. Blood angiogenesis was also significantly delayed in the older group as opposed to the young rats. WP, however, was found to return these indices to normal levels in the older rats. Proliferation and epidermal migration of the keratinocytes and the collagen deposition were also returned to the normal rates. Conclusions This data confirms the critical role of neutrophil recruitment in the early inflammatory phase of wound healing in older rats. In addition, WP protein was used to improve neutrophil function in older rats, healing events returned to a more normal profile. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2100966986117779. PMID:24593823
Remond, P; Attyé, A; Lecler, A; Lamalle, L; Boudiaf, N; Aptel, F; Krainik, A; Chiquet, C
A rapid identification of the etiology of anterior ischemic optic neuropathy is crucial because it determines therapeutic management. Our aim was to assess MR imaging to study the optic nerve head in patients referred with anterior ischemic optic neuropathy, due to either giant cell arteritis or the nonarteritic form of the disease, compared with healthy subjects. Fifteen patients with giant cell arteritis-related anterior ischemic optic neuropathy and 15 patients with nonarteritic anterior ischemic optic neuropathy from 2 medical centers were prospectively included in our study between August 2015 and May 2016. Fifteen healthy subjects and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR imaging. The bright spot sign was defined as optic nerve head enhancement with a 3-grade ranking system. Two radiologists and 1 ophthalmologist independently performed blinded evaluations of MR imaging sequences with this scale. Statistical analysis included interobserver agreement. MR imaging scores were significantly higher in patients with giant cell arteritis-related anterior ischemic optic neuropathy than in patients with nonarteritic anterior ischemic optic neuropathy ( P ≤ .05). All patients with giant cell arteritis-related anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic anterior ischemic optic neuropathy presented with the bright spot sign. No healthy subjects exhibited enhancement of the anterior part of the optic nerve. There was a significant relationship between the side of the bright spot and the side of the anterior ischemic optic neuropathy ( P ≤ .001). Interreader agreement was good for observers (κ = 0.815). Here, we provide evidence of a new MR imaging sign that identifies the acute stage of giant cell arteritis-related anterior ischemic optic neuropathy; patients without this central bright spot sign always had a nonarteritic pathophysiology and therefore did not require emergency corticosteroid
Paisán-Ruiz, Coro; Guevara, Rocio; Federoff, Monica; Hanagasi, Hasmet; Sina, Fardaz; Elahi, Elahe; Schneider, Susanne A.; Schwingenschuh, Petra; Bajaj, Nin; Emre, Murat; Singleton, Andrew B.; Hardy, John; Bhatia, Kailash P.; Brandner, Sebastian; Lees, Andrew J.; Houlden, Henry
Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson’s disease including supranu-clear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome. 3 2010 Movement Disorder Society PMID:20669327
Paisán-Ruiz, Coro; Guevara, Rocio; Federoff, Monica; Hanagasi, Hasmet; Sina, Fardaz; Elahi, Elahe; Schneider, Susanne A; Schwingenschuh, Petra; Bajaj, Nin; Emre, Murat; Singleton, Andrew B; Hardy, John; Bhatia, Kailash P; Brandner, Sebastian; Lees, Andrew J; Houlden, Henry
Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome. © 2010 Movement Disorder Society.
Drohan, P J; Brittingham, M; Bishop, J; Yoder, K
Worldwide shale-gas development has the potential to cause substantial landscape disturbance. The northeastern U.S., specifically the Allegheny Plateau in Pennsylvania, West Virginia, Ohio, and Kentucky, is experiencing rapid exploration. Using Pennsylvania as a proxy for regional development across the Plateau, we examine land cover change due to shale-gas exploration, with emphasis on forest fragmentation. Pennsylvania's shale-gas development is greatest on private land, and is dominated by pads with 1-2 wells; less than 10 % of pads have five wells or more. Approximately 45-62 % of pads occur on agricultural land and 38-54 % in forest land (many in core forest on private land). Development of permits granted as of June 3, 2011, would convert at least 644-1072 ha of agricultural land and 536-894 ha of forest land. Agricultural land conversion suggests that drilling is somewhat competing with food production. Accounting for existing pads and development of all permits would result in at least 649 km of new road, which, along with pipelines, would fragment forest cover. The Susquehanna River basin (feeding the Chesapeake Bay), is most developed, with 885 pads (26 % in core forest); permit data suggests the basin will experience continued heavy development. The intensity of core forest disturbance, where many headwater streams occur, suggests that such streams should become a focus of aquatic monitoring. Given the intense development on private lands, we believe a regional strategy is needed to help guide infrastructure development, so that habitat loss, farmland conversion, and the risk to waterways are better managed.
Palacios-Rubio, Julián; Marina-Breysse, Manuel; Quintanilla, Jorge G; Gil-Perdomo, José Miguel; Juárez-Fernández, Miriam; Garcia-Gonzalez, Inés; Rial-Bastón, Verónica; Corcobado, María Carmen; Espinosa, María Carmen; Ruiz, Francisco; Gómez-Mascaraque Pérez, Francisco; Bringas-Bollada, María; Lillo-Castellano, José María; Pérez-Castellano, Nicasio; Martínez-Sellés, Manuel; López de Sá, Esteban; Martín-Benítez, Juan Carlos; Perez-Villacastín, Julián; Filgueiras-Rama, David
Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality and morbidity. Current biological and imaging parameters show significant limitations on predicting cerebral performance at hospital admission. The AWAKE study (NCT03248557) is a multicentre observational study to validate a model based on spectral ECG analysis to early predict cerebral performance and survival in resuscitated comatose survivors. Data from VF ECG tracings of patients resuscitated from SCD will be collected using an electronic Case Report Form. Patients can be either comatose (Glasgow Coma Scale - GCS - ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), or those who regain consciousness (GCS=15) after RoSC; all admitted to Intensive Cardiac Care Units in 4 major university hospitals. VF tracings prior to the first direct current shock will be digitized and analyzed to derive spectral data and feed a predictive model to estimate favorable neurological performance (FNP). The results of the model will be compared to the actual prognosis. The primary clinical outcome is FNP during hospitalization. Patients will be categorized into 4 subsets of neurological prognosis according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. The model-derived categorisation will be also compared with clinical variables to assess model sensitivity, specificity, and accuracy. A model based on spectral analysis of VF tracings is a promising tool to obtain early prognostic data after SCD. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.
Vila, Peter M; Booske, Bridget C; Wegner, Mark V; Remington, Patrick L
While heart disease, cancer, and injuries are leading proximate causes of death, research has demonstrated that about half of all deaths in the United States are actually due to preventable causes, including tobacco use, poor diet, and physical inactivity. Using state vital statistics data and findings from national studies, we report on the trends in the preventable causes of death in Wisconsin from 1992 to 2004. The leading proximate causes of death in Wisconsin were obtained from Wisconsin Interactive Statistics on Health (WISH) data derived from individual death certificates. Information on the preventable causes of death was either obtained from the underlying cause information on the death certificate or from peer-reviewed epidemiologic studies. While the overall age-adjusted death rate declined from 837 to 744 per 100,000 from 1992 to 2004, the top 10 causes of death remain largely unchanged. Nearly half of the deaths in Wisconsin in 2004 resulted from 11 preventable causes, similar to the findings in 1992. Epidemiologic research demonstrates that nearly half of all deaths in Wisconsin are due to preventable causes. Programs and policies must continue to address these preventable causes of disease if Wisconsin is to meet its goal of promoting and protecting population health.
Starnes, Bobby Ann
In this article, the author shares her experience in teaching students with passion. She recalls the time when she was then what most first-year teachers are today: filled with hope and promise, determination and good will, ready to work hard and yearning to soak up the art and craft of teaching and learning. And whenever she gets tired and…
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...
Focardi, Martina; Gualco, Barbara; Norelli, GianAristide
The authors from the Florence Forensic Department present a case that demonstrates the paradigms attached to accidental deaths while performing autoerotic maneuvers. The incidents of such practices are underestimated and are only the tip of the iceberg since they do not represent the cases that are never reported due to successful practice. After analyzing the statistic data, the authors describe the case and discuss about the element that prove the accidental nature of the death and the importance of the correct application of forensic methodology at the scene and in the mortuary.
Neel, E U
Infectious mononucleosis (IM) is usually considered a benign disease. Agranulocytosis developed in a young college student 14 days after the onset of IM. Fulminant staphylococcal pneumonia and bilateral pulmonary infarcts resulted, and the patient died 4 1/2 hours after admission to a hospital. Agranulocytosis secondary to IM may be more prevalent than previously thought. A review of the literature indicated that infection developed in 57.9% of the patients with IM and extreme neutropenia and 45.4% of the infected patients died.
Colombage, Senarath M; Hulathduwa, Sanjaya R
A road traffic accident of an unusual nature is presented. The driver of a pickup cab sustained fatal injuries by a large piece of concrete (missile) set in motion consequent to a car crashing onto the centre island of a highway. Copyright Â© 2010 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Miodrag, Nancy; Silverberg, Sophie E.; Urbano, Richard C.; Hodapp, Robert M.
Background: Although life expectancies in Down syndrome (DS) have doubled over the past 3-4 decades, there continue to be many early deaths. Yet, most research focuses on infant mortality or later adult deaths. Materials and Methods: In this US study, hospital discharge and death records from the state of Tennessee were linked to examine 2046…
Das, Siddhartha; Menezes, Ritesh G
Road traffic accidents are a major cause of fatalities around the world, and a number of deaths are caused by moving traffic on public roads. Deaths from vehicles that are off the highway may be called non-traffic fatalities which can be due to a vehicle reversing, carbon monoxide poisoning, weather-induced over-heating inside the vehicle and electric windows. Children (and animals) are the usual victims. We report a case from India where a man was found lying dead by the roadside with a lorry nearby. The autopsy findings indicated that he had been run over, but as there was no history of a vehicular collision and with no eyewitnesses, the investigators were unsure of the probable sequence of events that led to his death. The autopsy findings, history, circumstantial evidence and chemical analysis enabled us to work out what had happened.
... Kit Read the MMWR Science Clips Preventing Stroke Deaths Progress Stalled Language: English (US) Español (Spanish) Recommend ... states. 80% of strokes are preventable. Problem Stroke deaths have stopped declining. Strokes are common and preventable. ...
Lafrance, Jean-Philippe; Rahme, Elham; Iqbal, Sameena; Leblanc, Martine; Pichette, Vincent; Elftouh, Naoual; Vallée, Michel
Discordance between dialysis registry and death certificate reported death has been demonstrated. Since cause of death is measured using registry data in dialysis patients and death certificate data in the general population, comparisons of cause of death proportions between dialysis patients and the general population may be biased. Our aim was to compare the proportion of deaths attributed to cardiovascular disease (CVD), malignancy, and infections between patients receiving dialysis and the general population using death certificates for both, and to quantify the magnitude of discrepancy between registry and death certificate estimates in dialysis patients. A retrospective cohort study of 5858 patients initiating maintenance dialysis between 2001 and 2007 was conducted. Cause of death was obtained from both registry and death certificate data for dialysis patients, and from death certificate data for the general population. Compared to the general population, use of death certificate data in dialysis patients resulted in smaller differences in the proportion of deaths attributed to CVD or infection than that from the registry. In the general population, the proportion of deaths due to CVD is 29.3% for men and 28.2% for women, and the proportion of deaths due to infection is 3.3% for men and 3.6% for women. For men, the proportion of deaths in dialysis patients due to CVD using registry data is 41.5%, compared with a proportion of 32.1% using death certificate data. Similarly for women, the proportion of deaths due to CVD using registry data is 35.2% and that using death certificate data 24.3%. The proportion of deaths due to infection in dialysis patients follows the same pattern: for men, the proportion of deaths due to infection using registry data is 9.9% and that from death certificate data at 5.0%; while for women the proportions are 11.6% and 4.8%, respectively. While absolute cause-specific mortality rates did differ, evaluation of causes of death using
Aye, Kyi-Phyu; Thanachartwet, Vipa; Soe, Chit; Desakorn, Varunee; Chamnanchanunt, Supat; Sahassananda, Duangjai; Supaporn, Thanom; Sitprija, Visith
Factors predictive for death from snake envenomation vary between studies, possibly due to variation in host genetic factors and venom composition. This study aimed to evaluate predictive factors for death from snake envenomation in Myanmar. A prospective study was performed among adult patients with snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to August 2016. Data including clinical variables and laboratory parameters, management, and outcomes were evaluated. Multivariate regression analysis was performed to evaluate factors predictive for death at the time of presentation to the hospital. Of the 246 patients with snake envenomation recruited into the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake species responsible for a bite was identified in 74 (30%) of the patients; the majority of bites were from Russell's vipers (63 patients, 85%). The independent factors predictive for death included 1) duration from bite to arrival at the hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2; P=0.04); 2) white blood cell counts >20 ×10 3 cells·μL -1 (OR: 8.9, 95% CI: 2.3-33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2-11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death (11/21 deaths). Patients who present with these independent predictive factors should be recognized and provided with early appropriate intervention to reduce the mortality rate among adults with snake envenomation in Myanmar. Copyright © 2018 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
Children's concepts of death grow with their age and development The three-year-old begins to notice that living things move and make sounds. The five-year-old thinks that life and death are reversable, but the six-year-old knows that death is final and brings sorrow. Children from eight through ten are interested in the causes of death and what…
Dunne, J W; Harper, C G; Hilton, J M
Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.
Viringipurampeer, Ishaq A; Gregory-Evans, Cheryl Y; Metcalfe, Andrew L; Bashar, Emran; Moritz, Orson L; Gregory-Evans, Kevin
Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.
... Staying Safe Videos for Educators Search English Español Death and Grief KidsHealth / For Teens / Death and Grief What's in this article? What Is ... the reaction we have in response to a death or loss. Grief can affect our body, mind, ...
Examined frequency and characteristics of overt dreams of dying among healthy young adults. Dreams of dying were found to be rare but distinctive content category, representing overwhelmingly pleasant dreams. Over one-half of death dreams involved lengthy afterlife sequence, remainder focused on process of death. Death dreams of these healthy…
Moody, Raymond A
Near-death experiences are an ancient and very common phenomenon that spans from ancient philosophy, religion and healing to the most modern clinical practice of medicine. Probably we are not much closer to an ultimate explanation of NDEs than were early thinkers like Plato and Democritus. Puzzling cases of near-death experiences continue to come to light and the ancient debate about what they mean continues unabated.
Phillips, Matthew; Pilkington, Ruth; Patterson, Aileen; Hennessy, Martina
Trinity College Dublin remains one of the Medical Schools that uses traditional dissection to teach anatomy, exposing students from the first week of entry to cadavers. This early exposure makes it imperative that issues surrounding death and donor remains are explored early on within the main structure of the curriculum. The School of Medicine began a programme of Medical Humanities student-selected modules (SSMs) in 2010, and the opportunity to offer a module on medical ethics regarding death and dignity was taken. A course was devised that touched only lightly on subjects such as palliative care and the concept of a good death. The course focused much more strongly on the reality of death as part of cultural and societal identity and placement. This was facilitated by field trips to settings where discussions regarding death, dying and dignity were commonplace and authentic experiences, rather than classroom discussions based on theoretical circumstances that may not yet have been experienced by the student. The module ran very well, with students feeling that they had had a chance to think critically about the role of death as an event with significance within society and culture, rather than purely in a medico-legal framework. Options to extend the module to the compulsory element of the course, to be built upon in later years looking at more technical aspects surrounding death, are being explored. © Blackwell Publishing Ltd 2011.
Ogata, Mamoru; Ago, Kazutoshi; Ago, Mihoko; Nakashima, Hiroshi; Hayashi, Takahito
A male in his early seventies complained of abdominal pain and diarrhea at 7h after ingesting a small piece of gratin from a box lunch prepared by a caterer. He was admitted to a hospital, but died 37 h later. Dozens of people who had eaten the same box lunch also complained of diarrhea. All of them recovered after medical treatment. A later investigation demonstrated Salmonella Enteritidis (SE) in the gratin from the box lunch. An autopsy revealed very severe typhloenteritis with edema and submucosal hemorrhage. The digestive tract contained fluid contents without foodstuffs. Bacteriological examination revealed SE in the contents of the lower ileum and large intestine. Based on these findings, we concluded that the cause of death was food poisoning due to SE. In this case, ingesting only a small piece of contaminated food caused fatal food poisoning due to SE. These results emphasize the importance of prevention against food poisoning due to Salmonella, particularly SE.
Glasgow, J F T; Thompson, A J; Ingram, P J
In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (p<0.02), and significantly more common compared to reference deaths (p<0.002). Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI (49%) occurred in the summer months--more than twice the frequency of reference deaths. While sharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.
Bozzay, Melanie L; Liu, Richard T; Kleiman, Evan M
Males are more likely than females to die by all forms of violent death, including suicide. The primary purpose of the present study was to explore whether the gender difference in suicide rates is largely accounted for by males' general greater tendency to experience violent deaths. The current study examined gender and age differences in suicides and other violent deaths, using data from a population-based surveillance system. Pearson's chi-square tests and logistic regression analyses were conducted with data for 32,107 decedents in the 2003-2005 National Violent Death Reporting System (NVDRS). Decedents were categorized by gender, age, and death by suicide versus other violent means. When suicides were examined in the greater context of violent death, the total proportion of violent deaths due to suicide did not differ across gender. When deaths were examined by age group, after controlling for ethnicity, marital status, and U.S. location in which the death occurred, males in early to mid childhood were significantly more likely than same-aged females to die by suicide relative to all other violent deaths. The portion of deaths due to suicide was for the most part equal across both genders in late childhood, young adulthood, and mid-adulthood. Older males were more likely than older females to die by suicide relative to other violent deaths. Our findings suggest that that the risk of dying by suicide relative to other violent deaths may be more pronounced at certain developmental stages for each gender. This knowledge may be valuable in tailoring prevention strategies. Copyright © 2014 Elsevier Inc. All rights reserved.
Alvarez-Lobos, Manuel; Arostegui, Juan I; Sans, Miquel; Tassies, Dolors; Plaza, Susana; Delgado, Salvadora; Lacy, Antonio M; Pique, Josep M; Yagüe, Jordi; Panés, Julián
To study the predictive value of Nod2/CARD15 gene variants along with disease phenotypic characteristics for requirement of initial surgery and for surgical recurrence in Crohn's disease (CD). Nod2/CARD15 gene variants play an important role in the susceptibility to CD. Studies of genotype-phenotype relationship suggest that these variants are associated with development of intestinal strictures. Preliminary reports analyzing the association between these variants and need for surgery have produced inconsistent results. A total of 170 CD patients were included prospectively in the study and followed up regularly for a mean of 7.4 +/- 6.1 years. Clinical characteristics of CD, time and indication for surgery, and recurrence were registered. Nod2/CARD15 gene variants were determined by DNA sequencing analysis. Surgery for stricturing disease was significantly more frequent in patients with Nod2/CARD15 variants in the univariate analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.42-9.27), and it was required at an earlier time (P = 0.004). Only Nod2/CARD15 variants (OR, 3.58; 95% CI, 1.21-10.5) and stricturing phenotype at diagnosis of CD (OR, 9.34; 95% CI, 2.56-33.3) were independent predictive factors of initial surgery for stricturing lesions in the multivariate analysis. Among 70 patients that required surgery, postoperative recurrence was also more frequent in patients with Nod2/CARD15 variants in the univariate and multivariate analysis (OR, 3.29; 95% CI, 1.13-9.56), and reoperation was needed at an earlier time (P = 0.03). Nod2/CARD15 variants are associated with early initial surgery due to stenosis and with surgical recurrence in Crohn's disease. Patients with these variants could benefit from preventive and/or early therapeutic strategies.
... 7 Agriculture 7 2010-01-01 2010-01-01 false Death, incompetency, or disappearance. 701.33 Section... RELATED PROGRAMS PREVIOUSLY ADMINISTERED UNDER THIS PART § 701.33 Death, incompetency, or disappearance. In case of death, incompetency, or disappearance of any participant, any cost-share payment due shall...
... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Death of participant. 21.... Chapter 32 Participation § 21.5067 Death of participant. (a) Disposition of unused contributions. If an.... Educational assistance remaining due and unpaid at the date of the veteran's death is payable under the...
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Death of employee. 335.5 Section 335.5... SICKNESS BENEFITS § 335.5 Death of employee. If an employee dies before filing one or more of the required... due but unpaid as of the date of an employee's death is the same as the order of distribution for...
... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Death from a respirable disease. 718.303... DISABILITY OR DEATH DUE TO PNEUMOCONIOSIS Presumptions Applicable to Eligibility Determinations § 718.303 Death from a respirable disease. (a)(1) If a deceased miner was employed for ten or more years in one or...
... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Death of participant. 21.... Chapter 32 Participation § 21.5067 Death of participant. (a) Disposition of unused contributions. If an.... Educational assistance remaining due and unpaid at the date of the veteran's death is payable under the...
... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Death of participant. 21.... Chapter 32 Participation § 21.5067 Death of participant. (a) Disposition of unused contributions. If an.... Educational assistance remaining due and unpaid at the date of the veteran's death is payable under the...
... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Death of participant. 21.... Chapter 32 Participation § 21.5067 Death of participant. (a) Disposition of unused contributions. If an.... Educational assistance remaining due and unpaid at the date of the veteran's death is payable under the...