BACKGROUND: The COVID-19 pandemic may have caused an underestimation of cardiovascular disease (CVD) mortality, as COVID-19 was predominantly recorded as the underlying cause of death. This study investigates CVD-related excess mortality and recording of CVD on the death certificates during 2020-2021, considering underlying (underlying causes of death (UCD)), immediate and contributory causes. METHODS: We utilize US Multiple-Cause-of-Death Mortality Data. Excess deaths are assessed by comparing actual 2020-2021 deaths with Seasonal Autoregressive Integrated Moving Average model predictions. To understand changes in cause-of-death recording, we use the standardized ratio of multiple to underlying causes (SRMU). RESULTS: Excess CVD mortality is most prominent in contributory causes, including hypertensive disease, essential hypertension, and acute myocardial infarction. While excess of contributory CVDs generally decreased in 2021, acute myocardial infarction, pulmonary heart diseases and other circulatory diseases showed a continual increase. Changes in SRMU from 2020 to 2021, compared to 2010-2019, reveal shifts in coding practices, particularly for pulmonary heart, cerebrovascular diseases, non-rheumatic valve disorders and heart failure. CONCLUSIONS: The COVID-19 pandemic has significantly increased CVD-related mortality, which is not fully captured in conventional analyses based solely on the UCD. The trend of coding CVDs as non-underlying causes of death accelerated during 2020-2021. Multiple-causes-of-death should be employed to evaluate mortality when new leading cause of death emerges.

• MeSH
• COVID-19 * MeSH
• Myocardial Infarction * MeSH
• Cardiovascular Diseases * MeSH
• Causality MeSH
• Humans MeSH
• Mortality MeSH
• Pandemics MeSH
• Cause of Death MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• United States MeSH

INTRODUCTION: The impact of conditions that partly or indirectly contribute to drinking-related mortality is usually underestimated. We investigate all alcohol-related multiple (underlying and contributory) causes of death and compare mortality distributions in countries with different levels and patterns of drinking. METHOD: Analysis of population-level mortality data for persons aged 20 and over in Austria, Czechia, Poland and Spain. Age-standardised death rates and standardised ratios of multiple to underlying cause were calculated for alcohol-related causes of death. RESULTS: Multiple-cause mortality ranged from 20 to 58 deaths per 100,000 for men and from 5 to 16 per 100,000 for women. Liver diseases were the most common underlying and multiple causes, but mental and behavioural disorders were the second or third, depending on country and sex, most prevalent multiple mentions. Two distinct age patterns of alcohol-related mortality were observed: in Czechia and Poland an inverted-U distribution with a peak at the age of 60-64, in Austria and Spain a distribution increasing with age and then levelling off for older age groups. DISCUSSION AND CONCLUSION: The importance of alcohol-related conditions that indirectly impact mortality can be re-assessed with the use of contributory mentions. The multiple-cause-of-death approach provides convergent results for countries characterised by similar patterns of alcohol consumption. Multiple-cause mortality was almost double the level of mortality with alcohol as the underlying cause, except in Poland. Mental and behavioural disorders were mostly certified as contributory to other, non-alcohol-related underlying causes of death.

• MeSH
• Adult MeSH
• Humans MeSH
• Mortality * MeSH
• Alcohol Drinking * MeSH
• Cause of Death MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Poland MeSH

OBJECTIVES: The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. DESIGN: Cohort study. SETTING: Swedish Dementia Registry (SveDem), 2007-2012. PARTICIPANTS: Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%). MEASUREMENTS: Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia (AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes (P-values from t-tests). RESULTS: The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD (HR = 1.82, 95% CI = 1.64-2.02). Respiratory death was higher in individuals with Lewy body dementia (LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71-2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD (HR = 2.86, 95% CI = 1.53-5.32). CONCLUSION: Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD.

• MeSH
• Alzheimer Disease mortality   MeSH
• Lewy Body Disease mortality   MeSH
• Cardiovascular Diseases mortality   MeSH
• Cohort Studies MeSH
• Humans MeSH
• Respiratory Tract Diseases mortality   MeSH
• Cause of Death * MeSH
• Registries MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Death Certificates * MeSH
• Dementia, Vascular mortality   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Sweden epidemiology   MeSH

• MeSH
• Delivery of Health Care MeSH
• Primary Health Care MeSH
• Health Care Reform MeSH
• Health Services Needs and Demand MeSH
• Publication type
• Review MeSH
• News MeSH
• Geographicals
• Colombia MeSH

• Conspectus
• Veřejné zdraví a hygiena
• NML Fields
• veřejné zdravotnictví
• NML Publication type
• studie

Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1-c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD.

• MeSH
• Alleles MeSH
• Anemia genetics   MeSH
• Biopsy MeSH
• Chronic Disease MeSH
• Zebrafish embryology   genetics   MeSH
• Child MeSH
• Genes, Dominant MeSH
• Adult MeSH
• Endoplasmic Reticulum metabolism   MeSH
• Exome genetics   MeSH
• Phenotype MeSH
• Golgi Apparatus metabolism   MeSH
• Heterozygote * MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger analysis   genetics   MeSH
• Mutation, Missense genetics   MeSH
• Young Adult MeSH
• Models, Molecular MeSH
• Mutation * MeSH
• Kidney Diseases genetics   pathology   MeSH
• Neutropenia genetics   MeSH
• Infant, Newborn MeSH
• Disease Progression MeSH
• Pedigree MeSH
• Fetal Growth Retardation genetics   MeSH
• Amino Acid Sequence MeSH
• Aged MeSH
• Syndrome MeSH
• SEC Translocation Channels chemistry   genetics   MeSH
• Animals MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Infant, Newborn MeSH
• Aged MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Bylo nashromážděno mnoho důkazů, že infekce zapříčiněná Helicobacter pylori a nesteroidní analgetika jsou hlavními faktory podílejícími se na vzniku vředové nemoci žaludku a dvanáctníku. Autoři referují o 12letém chlapci s recidivami vředové nemoci žaludku a dvanáctníku zapříčiněnými infekcí Helicobacter pylori. Autoři diskutují spojitost mezi vředovou nemocí žaludku a dvanáctníku a silným psychosociálním stresem doprovázeným bolestmi hlavy (rozvod rodičů, konflikty v rodině), který si sám tlumil nekontrolovaným podáváním nesteroidních analgetik.

Evidence has been accumulating on Helicobacter pylori infection and non-steroidal analgesics playing a major contributory role in peptic ulcer disease. We are reporting a 12-year-old boy with recurrent gastric and duodenal ulcers caused by Helicobacter pylori infection. The authors discuss an association between the peptic ulcer disease and a strong psychosocial stress accompanied by headaches (i. e. parental divorce, family conflicts) reduced with the uncontrolled self-administration of non-steroidal analgesics.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal adverse effects   MeSH
• Child MeSH
• Epidemiologic Studies MeSH
• Helicobacter Infections diagnosis   etiology   drug therapy   chemically induced   psychology   MeSH
• Family Conflict MeSH
• Humans MeSH
• Peptic Ulcer * diagnosis   etiology   drug therapy   psychology   therapy   MeSH
• Stress, Psychological pathology   MeSH
• Psychophysiologic Disorders diagnosis   etiology   therapy   MeSH
• Risk Factors MeSH
• Statistics as Topic MeSH
• Parent-Child Relations MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Gastrointestinal Diseases MeSH
• Radiography MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• gastroenterologie
• radiologie, nukleární medicína a zobrazovací metody

PURPOSE: The aim of this study was to assess the diagnostic value of catecholamines and their O-methylated metabolites in vitreous humor samples in identifying antemortem cold exposure and fatal hypothermia in the forensic casework. METHODS: A total of 80 autopsy cases (40 hypothermia fatalities and 40 cases in which hypothermia as the main or contributory cause of death was excluded) were selected for this study. Catecholamines and their O-methylated metabolites were measured in urine and vitreous humor samples collected at autopsy. RESULTS: Urine catecholamine and their O-methylated metabolite concentrations were significantly higher in hypothermia-related deaths. On the other hand, measurements in vitreous humor samples did not reveal statistically significant differences between hypothermia-related deaths and controls. CONCLUSIONS: Globally considered, our findings seem to suggest that, contrary to urine catecholamines and their O-methylated metabolites, vitreous levels of these compounds appear to be of limited value in characterizing human antemortem stress reactions due to cold exposure and can hardly be used in the forensic setting to support the diagnosis of hypothermia.

• MeSH
• Epinephrine metabolism   MeSH
• Dopamine analogs & derivatives   metabolism   MeSH
• Adult MeSH
• Hypothermia diagnosis   metabolism   MeSH
• Catecholamines metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metanephrine metabolism   MeSH
• Young Adult MeSH
• Norepinephrine metabolism   MeSH
• Normetanephrine metabolism   MeSH
• Postmortem Changes MeSH
• Aged MeSH
• Vitreous Body metabolism   MeSH
• Forensic Pathology MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Geocaching is a high-tech treasure-hunt game that uses GPS-enabled devices or smartphone apps to find cleverly hidden treasures marked by GPS coordinates that are shared online. Like any other outdoor activity, geocaching is associated with risks of falls, environmental injuries, asphyxia and natural events. Despite the apparent risk of serious injury and potential death, no relevant reports aiming to identify the characteristics of geocaching-related deaths have appeared in the medical literature to date. We report a case of an experienced geocacher who was found suspended from a bridge pillar with his climbing ropes and helmet straps twisted across his face and neck; he had apparently attempted to rappel from a 30-m-high railway bridge to find a geocache. A recording of the rappelling sequence from the camera found on the chest strap assisted in reconstructing what had actually happened. An autopsy confirmed that the cause of death was asphyxiation due to hanging, with the occlusion of the external airways and positional asphyxia serving as contributory factors. The salient features of this unusual case are discussed, and several forensic issues of geocaching are highlighted.

• MeSH
• Asphyxia etiology   pathology   MeSH
• Smartphone MeSH
• Geographic Information Systems MeSH
• Middle Aged MeSH
• Humans MeSH
• Posture * MeSH
• Recreation * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial K(ATP) opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated.

• MeSH
• Diazoxide pharmacology   therapeutic use   MeSH
• Diabetes Mellitus, Experimental enzymology   MeSH
• Membrane Fluidity drug effects   MeSH
• Mitochondrial Membranes drug effects   MeSH
• Mitochondrial Proton-Translocating ATPases metabolism   MeSH
• Heart Diseases prevention & control   MeSH
• Rats, Wistar MeSH
• Succinate Dehydrogenase antagonists & inhibitors   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH