Trend (1999–2009) in U.S. death rates from myelodysplastic syndromes: Utility of multiple causes of death in surveillance

BackgroundFor myelodysplastic syndromes (MDS) (formerly known as preleukemia), a diverse group of myeloid neoplasms usually involving anemia in elderly persons, trends in U.S. death rates apparently have not been reported.MethodsTrends in annual age-standardized rates per 100,000 from 1999 to 2009 were examined for MDS using multiple causes vs. underlying cause alone, coded on death certificates for U.S. residents.ResultsThe death rate (all ages combined) for MDS increased from 1999 to 2009, from 1.62 to 1.84 using underlying cause alone and from 2.89 to 3.27 using multiple causes. Rates using multiple causes were about 80% higher than those based on underlying cause alone. From 2001 to 2004 the rate for MDS using underlying cause alone (but not using multiple causes) declined, accompanied by an increase in the rate for deaths from leukemia as underlying cause with mention of MDS; this trend coincided with the advent of the 2001 World Health Organization's reclassification of certain MDS as leukemia. The MDS rate for age 65+ years increased after 2005, whereas the rate for age 25–64 years was low but declined from 2001 to 2003 and then stabilized. For deaths with MDS coded as other than underlying cause, rates did not decline for deaths from each of the two most common causes (i.e., cardiovascular diseases and leukemia).ConclusionsEvidence for decreases in MDS-related mortality rates was limited; the increase at age 65+ years is consistent with increases in incidence rates reported from cancer registries. Using multiple causes of death vs. only the underlying cause results in substantially higher MDS-related death rates, shows the impact of changes in the classification of myeloid neoplasms and emphasizes the importance of reducing cardiovascular disease mortality in MDS patients.     

Cancer mortality in a population-based cohort of American Indians – The strong heart study

BackgroundCancer mortality among American Indian (AI) people varies widely, but factors associated with cancer mortality are infrequently assessed.MethodsCancer deaths were identified from death certificate data for 3516 participants of the Strong Heart Study, a population-based cohort study of AI adults ages 45–74 years in Arizona, Oklahoma, and North and South Dakota. Cancer mortality was calculated by age, sex and region. Cox proportional hazards model was used to assess independent associations between baseline factors in 1989 and cancer death by 2010.ResultsAfter a median follow-up of 15.3 years, the cancer death rate per 1000 person-years was 6.33 (95 % CI 5.67–7.04). Cancer mortality was highest among men in North/South Dakota (8.18; 95 % CI 6.46–10.23) and lowest among women in Arizona (4.57; 95 % CI 2.87–6.92). Factors independently associated with increased cancer mortality included age, current or former smoking, waist circumference, albuminuria, urinary cadmium, and prior cancer history. Factors associated with decreased cancer mortality included Oklahoma compared to Dakota residence, higher body mass index and total cholesterol. Sex was not associated with cancer mortality. Lung cancer was the leading cause of cancer mortality overall (1.56/1000 person-years), but no lung cancer deaths occurred among Arizona participants. Mortality from unspecified cancer was relatively high (0.48/100 person-years; 95 % CI 0.32−0.71).ConclusionsRegional variation in AI cancer mortality persisted despite adjustment for individual risk factors. Mortality from unspecified cancer was high. Better understanding of regional differences in cancer mortality, and better classification of cancer deaths, will help healthcare programs address cancer in AI communities.     

Quantitation of NAD+: Why do we need to measure it?

Background

Nicotinamide adenine dinucleotide (NAD⁺) is an essential pyridine nucleotide that is currently investigated as an important target to extend lifespan and health span. Age-related NAD+ depletion due to the accumulation of oxidative stress is associated with reduced energy production, impaired DNA repair and genomic instability.

The mitochondrial pathway in yeast apoptosis

Mitochondria are not only important for the energetic status of the cell, but are also the fatal organelles deciding about cellular life and death. Complex mitochondrial features decisive for cell death execution in mammals are present and functional in yeast: AIF and cytochrome c release to the cytosol, mitochondrial fragmentation as well as mitochondrial hyperpolarisation followed by an oxidative burst, and breakdown of mitochondrial membrane potential. The easy accessibility of mitochondrial manipulations such as repression of respiration by growing yeast on glucose or deletion of mitochondrial DNA (rho⁰) on the one hand and the unique ability of yeast cells to grow on non-fermentable carbon sources by switching on mitochondrial respiration on the other hand have made yeast an excellent tool to delineate the necessity for mitochondria in cell death execution. Yeast research indicates that the connection between mitochondria and apoptosis is intricate, as abrogation of mitochondrial function can be either deleterious or beneficial for the cell depending on the specific context of the death scenario. Surprisingly, mitochondrion dependent yeast apoptosis currently helps to understand the aetiology (or the complex biology) of lethal cytoskeletal alterations, ageing and neurodegeneration. For example, mutation of mitochondrial superoxide dismutase or CDC48/VCP mutations, both implicated in several neurodegenerative disorders, are associated with mitochondrial impairment and apoptosis in yeast.     

Studying health histories of cancer: A new model connecting cancer incidence and survival

The results of recent experimental and epidemiological studies provide evidence on the connection between carcinogenesis, cancer progression, and aging. Existing models, however, are traditionally focused only on one of these aspects of health deterioration. In this paper, we derive a new model of cancer, which describes the connection between the ages at disease onset, the duration of disease, and life span of respective individuals. The model combines ideas used in the two hits model of carcinogenesis with those used in the Le Bras multistate model of aging with constant transition intensities. The model is used in the joint analyses of the US demographic mortality data and SEER data for selected cancers. The results show that the developed approach is capable of explaining links among health history data and provides useful insights on mechanisms of cancer occurrence, disease progression, other aging-related changes, and mortality. Further developments of this model are discussed.     

Studies of Lognormality on Mortality Statistics

For the global investigation of the frequencies of the animal or plant species, special methods where worked out decades ago. The authors recommand them for the study of morbidity and mortality statistics. When studying mortality statistics of the United States, they found that the truncated lognormal distribution could be fitted well to the totality of the causes of death frequencies in a sense sketched in the paper. But the logarithmic series was not suitable for fitting.     

Risk stratification for sudden cardiac death

Recent advances in pharmacological and device-based therapies have provided a range of management options for patients at risk of sudden cardiac death (SCD). Since all such interventions come with their attendant risks, however, stratification procedures aimed at identifying those who stand to benefit overall have gained a new degree of importance. This review assesses the value of risk stratification measures currently available in clinical practice, as well as of others that may soon enter the market. Parameters that may be obtained only by performing invasive cardiac catheterisation procedures are considered separately from those that may be derived using more readily available non-invasive techniques. It is concluded that effective stratification is likely to require the use of composite parameters and that invasive procedures might only be justified in specific sub-groups of patients.     

Norepinephrine Induces Apoptosis in Skin Melanophores by Attenuating cAMP‐PKA Signals Via α2‐Adrenoceptors in the Medaka,Oryzias Latipes

The density of skin melanophores in many teleost fish decreases during long‐term adaptation to a white background. Using the medaka, Oryzias latipes, we previously reported that apoptosis is responsible for the decrease in melanophores, and that a sympathetic neurotransmitter, norepinephrine (NE), induces their apoptosis in skin tissue cultures. In this study, we show that NE‐induced apoptosis of melanophores is mediated by the activation of α2‐adrenoceptors. Clonidine, an α2‐adrenoceptor agonist, induced apoptotic melanophore death in skin organ culture, while phenylephrine, an α1‐adrenoceptor agonist, had no effect. NE‐induced apoptosis was diminished by an α2‐adrenoceptor antagonist, yohimbine, but an α1‐adrenoceptor antagonist, prazosin, did not abrogate the effect of NE. Furthermore, forskolin inhibited NE‐induced apoptosis, while an inhibitor of PKA, H‐89, mimicked the effect of NE. These results suggest that NE induces apoptosis in melanophores by attenuating cAMP‐PKA signaling via α2‐adrenoceptors.     

Hazard rates and causes of death in a captive group of crab-eating monkeys (Macaca fascicularis)

In an attempt to examine possible associations between stages of agespecific mortality and various causes of death, vital records of 159 male and 192 female crab-eating monkeys (Macaca fascicularis), housed as a single group, were analyzed. Survival and hazard rates associated with each of five distinct categories of causes of death were estimated for males and females, using the nonparametric kernel method. The obtained overall survival and hazard functions were similar to those reported previously for rhesus monkeys. Among two stages identified in age-specific mortality, the first stage, characterized by rapidly decreasing hazard rates up to about 1.5–2 years of age, was discriminated by the occurrence of deaths due to unfitness for postnatal life. The second stage lasted up to the age of 10–15 years and was largely characterized by a high incidence of violent deaths. The respective hazard rates in males and females attained peaks during the early reproductive period of life and markedly decreased thereafter. This pattern was interpreted to indicate that second stage mortality is unlikely related to senescence, but rather, seems to depend on extrinsic environmental factors. Thus, when considering overall hazard rates in Macaca fascicularis, the onset of senescence, as a result of the specific aspects of simian reproduction, may be hidden from view, and mortality due to aging may only be appreciable after 10 to 15 years of age. © 1993 Wiley-Liss, Inc.     

Prediction of the human life expectancy

We have simulated demographic changes in the human population using the Penna microscopic model, based on the simple Monte Carlo method. The results of simulations have shown that during a few generations changes in the genetic pool of a population are negligible, while improving the methods of compensation of genetic defects or genetically determined proneness to many disorders drastically affects the average life span of organisms. Age distribution and mortality of the simulated populations correspond very well to real demographic data available from different countries. Basing on the comparison of structures of real human populations and the results of simulations it is possible to predict changes in the age structure of populations in the future.     

Immunogenic cell death modalities and their impact on cancer treatment

It is still enigmatic under which circumstances cellular demise induces an immune response or rather remains immunologically silent. Moreover, the question remains open under which circumstances apoptotic, autophagic or necrotic cells are immunogenic or tolerogenic. Although apoptosis appears to be morphologically homogenous, recent evidence suggests that the pre-apoptotic surface-exposure of calreticulin may dictate the immune response to tumor cells that succumb to anticancer treatments. Moreover, the release of high-mobility group box 1 (HMGB1) during late apoptosis and secondary necrosis contributes to efficient antigen presentation and cytotoxic T-cell activation because HMGB1 can bind to Toll like receptor 4 on dendritic cells, thereby stimulating optimal antigen processing. Cell death accompanied by autophagy also may facilitate cross priming events. Apoptosis, necrosis and autophagy are closely intertwined processes. Often, cells manifest autophagy before they undergo apoptosis or necrosis, and apoptosis is generally followed by secondary necrosis. Whereas apoptosis and necrosis irreversibly lead to cell death, autophagy can clear cells from stress factors and thus facilitate cellular survival. We surmise that the response to cellular stress like chemotherapy or ionizing irradiation, dictates the immunological response to dying cells and that this immune response in turn determines the clinical outcome of anticancer therapies. The purpose of this review is to summarize recent insights into the immunogenicity of dying tumor cells as a function of the cell death modality.     

Trends in regional cancer mortality in Taiwan 1992–2014

BackgroundAlthough the cancer mortality rate in Taiwan has been declining in recent years, no study has yet reported any regional differences in cancer mortality rates in Taiwan. We hypothesized that regional cancer mortality rates in Taiwan, an ethnically homogeneous society, exhibited no significant variations.MethodsWe investigated the trends in Taiwan regional cancer mortality between 1992 and 2014. We analyzed regional age-standardized cancer mortality rates for lung, liver, colon, stomach, oral, breast, and prostate cancers using the Taiwan Longitudinal Health Insurance Database and Demographic Database. Furthermore, we applied Joinpoint regression analysis to evaluate the trends across different regions.ResultsThere are clear regional variations in mortality rates for liver, stomach, and oral cancers, but not for lung, colon, breast, and prostate cancers. The regional death rates of oral cancer, especially for eastern Taiwan, not only elevate the fastest (APC = 14.78% per year, P < 0.001) but also show the largest disparities between men and women. Regional death rates for stomach cancer, which declined most rapidly, are converging in both general and gender groups. Liver cancer is the only one with regional variations whose trends do not all go in the same direction. We also demonstrated that northern Taiwan has significant regional advantages with respect to cancer mortality.ConclusionsSome but not all cancers in Taiwan show regional disparities. Liver, stomach, and oral cancers in Taiwan exhibit clear regional variations in mortality rates. In particular, the regional variations in oral cancer mortality rates are consistent with those in alcohol consumption.