The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

This corrects the article DOI: 10.1038/onc.2015.168.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

Longevity-dependent organ-specific accumulation of DNA damage in two closely related murine species.

To measure directly the accumulation of DNA damage with age, and to understand better the effect of modulators of DNA damage in vivo, the DNA of brain, liver, and kidney of two mice from different families, Mus musculus and Peromyscus leucopus, have been examined for age-dependent accumulation of single-strand breaks plus alkali-labile bonds, by the alkaline sucrose sedimentation method. These two species of small rodents are closely related taxonomically, yet differ significantly in maximum achievable lifespan. Using the reciprocal of the number average molecular weight for estimation of DNA size, these analyses indicate that: (a) DNA damage does not measurably accumulate in brain tissue; (b) the accumulation of DNA damage was more pronounced in hepatic DNA than other tissue DNA; and (c) the rate of accumulation of DNA damage in liver and kidney cells with age was greater in the shorter-lived species (M. musculus) and was inversely proportional to maximum achievable lifespan. There are suggestions that a similar threshold might exist for tolerance of DNA damage in the two species in specific organs, and that these species differ in the rate at which this threshold is reached as a function of maximum achievable lifespan.

Induction of single-strand breaks plus alkali-labile bonds by N-nitrosoureas in rat tissues in vivo: ethylnitrosourea versus benzylnitrosourea.

Alkaline sucrose sedimentation procedures were used to quantitate the amount of single-strand breaks plus alkali-labile bonds (SSB + ALB) induced and repaired following a single intraperitoneal injection of the neurocarcinogen N-ethyl-N-nitrosourea (ENU) and its non-neurocarcinogenic analog N-benzyl-N-nitrosourea (BNU) in the brain, liver and kidney of female Sprague-Dawley rats. SSB + ALB were measured and used as an indicator of apurinic/apyrimidinic sites, phosphotriesters and in situ breaks. ENU induced a dose-dependent increase in the number of SSB + ALB at the doses studied (0, 0.39, 0.77, 1.54 mmoles/kg) in all 3 tissues. At 1 h postinjection with 0.77 mmoles/kg of these compounds there were 50-70% fewer breaks induced by BNU than ENU. The SSB + ALB induced by ENU persisted over a 7-day period, while those induced by BNU did not. Thus, these studies showed that 2 homologues of nitrosoureas, ENU and BNU, exhibited different potentials to induce and to persist SSB + ALB in vivo.

Late skin damage in rabbits and monkeys after exposure to particulate radiations.

Skin biopsies were taken from the central regions of the ears of New Zealand white rabbits following localized exposure of one ear of each rabbit to 530 MeV/amu Ar or 365 MeV/amu Ne ions. The unirradiated ears served as controls. Biopsies were taken also from the chests and inner thighs of rhesus monkeys after whole-body exposure to 32 MeV protons and from unirradiated control animals. The linear energy transfers (LET infinity's) for the radiations were 90 +/- 5, 35 +/- 3, and approximately 1.2 keV/micrometer, respectively. In the rabbit studies, explants were removed with a 2 mm diameter dermal punch at post-irradiation times up to five years after exposure. Similar volumes of monkey tissue were taken from skin samples excised surgically 16-18 years following proton irradiation. Fibroblast cultures were initiated from the explants and were propagated in vitro until terminal senescence (cessation of cell division) occurred. Cultures from irradiated tissue exhibited decreases in doubling potential that were dependent on radiation dose and LET infinity and seemed to reflect damage to stem cell populations. The implications of these results for astronauts exposed to heavy ions and/or protons in space include possible manifestations of residual effects in the skin many years after exposure (e.g. unsatisfactory responses to trauma or surgery).

The experiences of non-operative treatment in patients with bacterial brain abscess.

Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.

Fluid flow structure in arterial bypass anastomosis.

The fluid flow through a stenosed artery and its bypass graft in an anastomosis can substantially influence the outcome of bypass surgery. To help improve our understanding of this and related issues, the steady Navier-Stokes flows are computed in an idealized arterial bypass system with partially occluded host artery. Both the residual flow issued from the stenosis--which is potentially important at an earlier stage after grafting--and the complex flow structure induced by the bypass graft are investigated. Seven geometric models, including symmetric and asymmetric stenoses in the host artery, and two major aspects of the bypass system, namely, the effects of area reduction and stenosis asymmetry, are considered. By analyzing the flow characteristics in these configurations, it is found that (1) substantial area reduction leads to flow recirculation in both upstream and downstream of the stenosis and in the host artery near the toe, while diminishes the recirculation zone in the bypass graft near the bifurcation junction, (2) the asymmetry and position of the stenosis can affect the location and size of these recirculation zones, and (3) the curvature of the bypass graft can modify the fluid flow structure in the entire bypass system.

Postsynaptic alpha-adrenoceptor characterization and Ca2+ channel antagonist and activator actions in rat tail arteries from normotensive and hypertensive animals.

Postsynaptic alpha-adrenoceptors in the rat tail artery have been examined by determining the pA2 values for antagonists against several alpha-adrenoceptor agonists. In this tissue the alpha-adrenoceptor agonists all produce concentration-dependent mechanical responses with the following rank order of potency: clonidine greater than norepinephrine greater than phenylephrine greater than UK 14304 greater than B-HT 920. Antagonism by prazosin and yohimbine of phenylephrine, norepinephrine, and clonidine responses does not reveal the anticipated discrimination between alpha 1- and alpha 2-adrenoceptors. Thus, pA2 values for prazosin (9.1-9.5), yohimbine (7.2-7.4), and corynanthine (7.0-7.1) and idazoxan (7.6) do not show large differences between these receptor agonists and suggests the predominance of alpha 1-adrenoceptor mediated contractile responses in this preparation. Significant differences between antagonist activities (pA2 values) in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) artery preparations have not been observed. The sensitivity sequence of alpha-adrenoceptor agonist-induced responses to nifedipine and D 600 is B-HT 920 greater than clonidine greater than phenylephrine greater than norepinephrine. Dependence of agonist response upon extracellular Ca2+ parallels the sensitivity to Ca2+ channel antagonists. Sensitivity to D 600 of phenylephrine responses increased with decreasing concentration of phenylephrine or with receptor blockade by phenoxybenzamine: sensitivity of responses to B-HT 920 was not affected by these procedures. Tail artery strips from WKY and SHR do not exhibit major differences in sensitivity to D 600 or to Ca2+ depletion. Bay k 8644, a Ca2+ channel activator, produces concentration-dependent mechanical responses in the tail artery in the presence of modestly elevated K+ concentrations (10-15 mM): these actions of elevated K+ can be mimicked by both alpha 1- and alpha 2-adrenoceptor agonists including methoxamine, St 587, UK 14304, and clonidine. These studies do not provide clear evidence for the existence of discrete postsynaptic alpha 1- and alpha 2-adrenoceptor populations in rat tail artery as indicated by pA2 values or Ca2+ dependence of response.

The effect of indomethacin on acute radiation induced gastrointestinal injury: a morphologic study.

Radiation-induced intestinal injury is a dose limiting factor in the treatment of pelvic, abdominal, and retroperitoneal malignancies with radiation therapy. In experimental models, radiation has been associated with increased intestinal prostaglandin activity and in clinical trials prostaglandin inhibitors have been demonstrated to improve the symptoms of acute radiation enteritis. This study was conducted to determine if the prostaglandin inhibitor indomethacin could prevent the morphologic changes of acute radiation induced intestinal injury. Twenty-four male rats received either parenteral indomethacin at doses of 0.5, 1.0, and 3.0 mg/kg per dose every 12 hours or saline from 24 hours pre-radiation exposure until sacrifice 48 hours later. Twenty-four control animals received identical drug dosages and anesthesia but no radiation. Radiation produced a decreased villus/crypt ratio and increased acute inflammation and degeneration. Indomethacin treated animals demonstrated significantly less polymorphonuclear leukocyte infiltration and decreased degeneration. Villus/crypt ratio was not affected by indomethacin.

Calcium channel activation in vascular smooth muscle by BAY K 8644.

BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate) and CGP 28 392 (ethyl-4(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl-5-++ +oxofuro- [3,4-b]pyridine-3-carboxylate) are closely related in structure to nifedipine and other 1,4-dihydropyridine Ca2+ channel antagonists. However, both BAY K 8644 and CGP 28 392 serve as activators of Ca2+ channels. In the rat tail artery, responses to BAY K 8644 are dependent upon Ca2+ext and prior stimulation by K+ or by the alpha-adrenoceptor agonists, phenylephrine and BHT 920 (6-allyl-2-amino-5,6,7,8,-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). Responses are blocked noncompetitively by the Ca2+ channel antagonists D-600 [-)-D-600 greater than (+)-D-600) and diltiazem, but competitively by nifedipine (pA2 = 8.27). This suggests that activator and inhibitor 1,4-dihydropyridines interact at the same site. BAY K 8644 potentiates K+ responses and Ca2+ responses in K+-depolarizing media. The leftward shift of the K+ dose--response curve produced by BAY K 8644 suggests that this ligand facilitates the voltage-dependent activation of the Ca2+ channel. The pA2 value for nifedipine antagonism of BAY K 8644 responses is significantly lower than that for nifedipine antagonism of Ca2+ responses in K+ (25-80 mM) depolarizing media (9.4-9.6), suggesting that the state of the channel may differ according to the activating stimulus.

Pharmacologic and radioligand binding analysis of the actions of 1,4-dihydropyridine activator-antagonist pairs in smooth muscle.

The actions of the enantiomers of Bay K 8644 and 202-791 were studied in rat tail artery and guinea pig ileal longitudinal smooth muscle using pharmacologic and radioligand binding assays. (-)-(S)-Bay K 8644 (below 10(-7) M in rat tail artery and 3 X 10(-7) M in guinea pig ileum) and (+)-(S)-202-791 (below 10(-6) M) induced contractions and potentiated the responses to KCl depolarization in both smooth muscle preparations. In contrast, (+)-(R)-Bay K 8644 and (-)-(R)-202-791 inhibited the responses to KCl-induced depolarization. At higher concentrations, (-)-(S)-Bay K 8644 (10(-7) to 10(-6) M) and (+)-(S)-202-791 (10(-6) to 3 X 10(-5) M) in rat tail artery, and (-)-(S)-Bay K 8644 (3 X 10(-7) to 3 X 10(-6) M) in guinea pig ileal smooth muscle relaxed the tissues contracted maximally at lower concentrations of the same drug. Cross antagonism between 1,4-dihydropyridine activators was observed when (-)-(S)-Bay K 8644 (10(-7) to 10(-6) M) relaxed the maximum contraction in response to (+)-(S)-202-791. [3H]Nitrendipine bound in a tail arterial microsomal preparation to a single class of site, with KD of 3.63 X 10(-10) M and maximum binding of 552.7 fmol mg-1 protein. In both rat tail artery and guinea pig ileal smooth muscle, (-)-(S)-Bay K 8644, (+)-(R)-Bay K 8644, (+)-(S)-202-791 and (-)-(R)-202-791 inhibited specific [3H]nitrendipine binding competitively; the Kl values correlate well to the pharmacologic EC50 (for activators) or IC50 (for antagonists, measured against 80 mM KCl depolarization) values. The biphasic response to (-)-(S)-Bay K 8644 and (+)-(S)-202-791 suggests that the properties of Ca++ channel activation and antagonism may reside within a single 1,4-dihydropyridine molecule.

In vitro and in vivo characterization of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-isothiocyano)phenyl-1,4- dihydropy ridine as a Ca2+ channel antagonist.

The actions of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-isothiocyano)phenyl-1,4- dihydropyridine (o-NCS-DHP), a nifedipine analog bearing a reactive group, have been characterized in vitro by pharmacological and radioligand binding techniques in a number of smooth muscles and in vivo by blood pressure and radioligand binding. o-NCS-DHP exhibits persistent, but slowly reversible, antagonism in guinea pig ileal longitudinal smooth muscle, guinea pig bladder, taenia coli, rat portal vein, and rat tail artery to receptor responses (muscarinic and alpha-adrenoceptor) and K+ depolarization initiated responses. Duration of response was significantly longer than that of equivalent concentrations of nifedipine. In many tissues a component of antagonism produced by o-NCS-DHP was not reversed by repeated washing over the duration of the experiment (up to 2 or 7 h). A comparison of the actions of o-NCS-DHP and its isomers m-NCS-DHP and p-NCS-DHP revealed the former to be significantly longer lasting in rat tail artery against K+ depolarization induced responses. A similar profile was exhibited when the Ca2+ channel activator Bay K 8644 was employed as the stimulant, but the antagonism produced by all three compounds was fully reversed with sufficiently prolonged washing. In vivo administration of o-NCS-DHP (5-25 mg/kg) produced a persistent reduction of [3H]nitrendipine binding in rat brain, gut, and heart characterized as Bmax, but not KD, changes. No effects on [3H]dihydroalprenolol or [3H]quinuclidinyl benzilate binding were detected. Binding site recoveries were characterized by t1/2 values of 35-50 h, and these were significantly prolonged to 91-107 h in animals treated with cycloheximide. Recovery of [3H]nitrendipine binding sites correlated with blood pressure restoration in spontaneously hypertensive rats. These data suggest that o-NCS-DHP possesses both reversible and irreversible actions. The reversible actions are unusually persistent compared with nifedipine and other 1,4-dihydropyridine analogs. This persistent, but reversible component, may be accompanied by an irreversible action particularly at the higher concentrations employed in the in vivo experiments.

Reperfusion-induced accumulation of long-chain acylcarnitines in previously ischemic myocardium.

Long-chain acylcarnitines (LCA) have been shown to accumulate during myocardial ischemia and to contribute to malignant derangements characteristic of ischemia. We detail the time course of the increase in LCA levels during both ischemia and reperfusion. Evidence indicates an additional specific reperfusion-induced increase in LCA that peaks at 2 min and decreases to basal levels by 30 min. This increase in LCA during reperfusion is observed after 2-, 10-, or 20-min ischemia and is inhibited by the presence of the carnitine palmitoyl transferase 1 (CPT1) inhibitor phenyloxirane carboxylic acid (POCA). A role for increased LCA in mediating "reperfusion damage" is not indicated, however, because POCA did not attenuate either the incidence of ventricular fibrillation (VF) during early reperfusion or the survival rate of rats undergoing 24-h reperfusion after 10-min occlusion.

Highly sulfated forms of heparin sulfate are involved in japanese encephalitis virus infection.

Japanese encephalitis virus (JEV) infects a broad range of cell types in vitro, though little is known about the initial events of JEV infection. In the present study, we found that highly sulfated glycosaminoglycans (GAGs) are involved in infection of both neurovirulent (RP-9) and attenuated (RP-2ms) JEV strains. Competition experiments using highly sulfated GAGs, heparin and dextran sulfate, demonstrated an inhibition of JEV's attachment and subsequent infection of BHK-21 cells. Treatment of target cells by a potent sulfation inhibitor, sodium chlorate, greatly reduced viral binding ability as well as infection, suggesting a critical role of GAGs' sulfation status on the cellular surface in JEV infection. This phenomenon was confirmed by the manifestation of a distinct binding efficiency of JEV to the wild-type CHO cell line and its mutants with defects in GAG biosynthesis. We also demonstrated the binding of JEV particles and virus envelope glycoprotein to immobilized heparin beads. Furthermore, the addition of heparin suppressed the cytopathic effects induced by JEV infection in cultured cells. Our results establish that the highly sulfated form of GAGs on cell surfaces plays a determining role in the early stage of in vitro JEV infection.

Acute scrotum in Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis with manifestations usually involving the skin, gastrointestinal tract, kidney and joints. Epididymitis is rarely seen as a complication of HSP. It is easily misdiagnosed as testicular torsion, causing the patient to undergo unnecessary surgery, because the patient may have complained of severe scrotal pain and swelling. We report a 5-year-old boy who was suffering from HSP associated with acute scrotal pain and swelling of the left testicle. No gastrointestinal signs were noted but severe joint pain, swelling and palpable skin lesions in the lower limbs and the buttocks were found. Prednisolone was prescribed and the boy recovered without surgical intervention.

Analysis of referral initiatives, severity of illness and return to care of older women with cervical cancer.

BACKGROUND: Cervical cancer is a worldwide malignancy particularly prevalent in older women. Due to the increasing population ratio of older women and their more complicated illnesses, doctors in Taiwan are concerned about the care of older patients with cervical cancer. Few studies have been performed on the association between referral initiative and illness severity upon referral as well as the tendency of older patients with cervical cancer to return to the referring doctor and to the consultant at the medical center for follow-up. The purpose of this study was to investigate the referral association by adjusting for confounding variables. METHODS: This study included 214 women aged 65 years and over with cervical cancer diagnosed between 1987 and 1995. Patients were referred to a tertiary teaching hospital by 71 primary care gynecologists. The International Federation of Gynecology and Obstetrics clinical stage and clinical severity were assessed in each patient. Histopathologic results were reviewed to confirm the diagnosis. RESULTS: Of all the cervical cancer referrals, 20.2% were initiated by patients or families and 79.8% were initiated by primary care doctors. No statistically significant differences were found in the Basic Activities of Daily Living or Instrumental Activities of Daily Living between doctor- and patient-initiated referrals. High Geriatric Depression Scale and low Mini-Mental State Examination were associated with doctor-initiated referrals. Higher cancer stage and greater clinical severity of patients with cervical cancer was found in patient- rather than doctor-initiated referrals. After adjusting for marriage, family type, medical payment, mental status, cancer stage and clinical severity, the data showed that, if the referral was initiated by a primary care doctor, older patients with cervical cancer had a similar likelihood to return to both the primary care doctor and the tertiary teaching hospital for follow-up. CONCLUSIONS: If a referral was initiated by a doctor, older women with cervical cancer were not only likely to return to their consulting physician at the medical center, but also likely to return to their primary care doctor. Continuous care is more likely to occur when the primary care doctor initiated the referral.

Late degeneration in rabbit tissues after irradiation by heavy ions.

In 1974, using the rabbit as a model, we began long-term experiments designed to help in the evaluation of the hazards to man from extended exposure to heavy ions in space. Such exposure would occur, for example, during the construction of solar power stations in stationary orbits or on round trips to Mars. Our experiments with 400 MeV/nucleon Ne ions and 570 MeV/nucleon Ar ions have shown that true late effects of a degenerative nature are manifested only years after irradiation. At the appropriate doses (the high end of the experimental dose range), the magnitudes of the late effects are comparable with those encountered in human patients given radiation therapy with neutrons. Such comparisons show that the rabbit experiments are applicable to man. Given that basis, the results from the low end of the experimental dose range lead to the conclusion that astronauts subjected to the radiation fluxes anticipated during flights of the above duration could experience late radiation effects one or more decades after exposure. Late degenerative changes will occur in tissues of the central nervous system, terminally differentiating systems and stem cell populations. The studies also indicate that individual tissues may be "prematurely aged" by radiation in the sense that the "life spans" of those tissues can be decreased without the appearance of malignancies.