Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Value-added switchgrass extractives for reduction of Escherichia coli O157:H7 and Salmonella Typhimurium populations on Formica coupons.

Recurring outbreaks linked to Escherichia coli O157:H7-contaminated lettuce and Salmonella enterica-contaminated sprouts highlight the need for improved food safety measures. The aim of this study was to determine the ability of a bio-based antimicrobial extract prepared from switchgrass, a dedicated energy crop, to reduce E. coli O157:H7 and S. Typhimurium populations on Formica coupons, a model food-contact surface. Overnight cultures of ~7 log CFU/mL E. coli O157:H7 and S. Typhimurium, air-dried on Formica coupons were treated with 0.625% NaClO, 70% ethanol, sterile water or different batches of switchgrass extractives (SE1, SE2, and SE3) for up to 30 min. E. coli O157:H7 was reduced by 4.43 log CFU/mL after 1 min by SE3, and to non-detectable levels after 1 min by all other treatments. Populations of S. Typhimurium LT2 (15-min drying) were reduced by 3.30 log CFU/mL with 70% ethanol, 5.38 log CFU/mL with SE1, and to non-detectable levels with 0.625% NaClO after 1 min, while S. Typhimurium ATCC 23564 (1-h drying) was non-detectable after 1 min by all treatments. Under soiled conditions, 10-min treatment with SE1 and 70% ethanol reduced both bacteria to non-detectable levels. Studies with concentrated switchgrass extractives combined with various other natural disinfectants or in hurdle approaches warrant further investigation.

Peri-ampullary duodenal diverticulum: effect on extrahepatic bile duct dilatation after cholecystectomy.

AIM: To investigate the effect of peri-ampullary duodenal diverticula (PAD) on extrahepatic bile duct (EHBD) dilatation before and after cholecystectomy. MATERIALS AND METHODS: During a 5-year period, a total of 860 consecutive patients with prior cholecystectomy were examined using abdominal computed tomography (CT). After exclusion of those with other obstructive EHBD lesions, 61 patients with PAD were recruited for evaluation of EHBD dilatation before and after cholecystectomy and were compared with a randomly sampled control group (n=113) without PAD. EHBD diameter was measured on coronal reconstruction CT using electronic callipers on the picture archiving and communication system monitors by two reviewers in consensus. RESULTS: There was no significant difference in EHBD diameter between PAD and non-PAD groups (8.2±2.8 versus 7.8±2.3 mm; p=0.276) before cholecystectomy. Compared with preoperative diameter, EHBD was significantly dilated after cholecystectomy (7.9±2.5 versus 9.8±3.4 mm, p<0.001), regardless of the presence of PAD; the degree of change was more prominent in the PAD group than in the non-PAD group (3.3±2.4 versus 1.1±1.6 mm; p<0.001) after surgery. The size of PAD did not affect the degree of EHBD dilatation after cholecystectomy (p=0.522). In the non-PAD group, the degree of EHBD dilatation was positively correlated with the follow-up interval after cholecystectomy (r=0.298; p=0.002), while the PAD group showed no significant correlation (r=-0.036; p=0.797). In patients with ≥2 mm postoperative EHBD dilatation, PAD incidence was higher than that in other patients (odds ratio, 8.739; p<0.001). CONCLUSION: Regardless of their size or postoperative follow-up duration, PAD induce marked post-cholecystectomy biliary dilatation.

Anakinra Protects Against Serum Deprivation-Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates.

We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/- ) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1ß, IL-6, and tumor necrosis factor-α in hIAPP+/- mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.

Improved revascularization of islet grafts using an angiogenic monocyte subpopulation derived from spheroid culture of bone marrow mononuclear cells.

The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and non-endocrine tissue, and ß cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.

Clinical association between serum γ-glutamyltransferase levels and the development of insulin resistance in Korean men: a 5-year follow-up study.

AIMS: In recent years, γ-glutamyltransferase has emerged as a predictor of cardiovascular disease, Type 2 diabetes mellitus, the metabolic syndrome and hypertension. However, it is not yet certain whether γ-glutamyltransferase is a predictor for insulin resistance. The aim of this study was to examine the longitudinal association between baseline γ-glutamyltransferase level and the development of insulin resistance in Korean men. METHODS: We performed a prospective cohort study, involving 22 931 healthy Korean men without baseline insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR < 2.7) for 5 years. We checked the HOMA-IR serially to monitor the development of insulin resistance (incidence of HOMA-IR ≥ 2.7). A Cox proportional hazards model was used to determine hazard ratios for insulin resistance by quartile groups of baseline serum γ-glutamyltransferase levels. RESULTS: During 81 208.6 person-years of follow-up, 3856 (16.8%) cases of insulin resistance developed between 2006 and 2010. After adjusting for multiple covariates, including baseline HOMA-IR, the hazard ratios (95% CI) for incident insulin resistance comparing the second to the fourth quartile of baseline serum γ-glutamyltransferase levels with the first quartile were 1.19 (1.06-1.33), 1.38 (1.23-1.53) and 1.58 (1.41-1.77), respectively (P for trend < 0.001). CONCLUSIONS: Our findings show that serum γ-glutamyltransferase level could be a predictor of the development of insulin resistance in Korean men.

Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice.

BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives. METHODS: To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I(CAP))- and heat (I(heat))-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain. RESULTS: I(CAP) (P<0.01) and I(heat) (P<0.05) of TRPV1 were significantly blocked by 10 µM KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05). CONCLUSIONS: KMS4034 may be an effective analgesic for various pain conditions.

Clinical impact of methicillin-resistant Staphylococcus aureus bacteremia based on propensity scores.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen not only in nosocomial infections, but also in community-associated infections. The aim of this study was to evaluate the impacts of methicillin resistance on mortality, length of hospitalization, and hospital costs via propensity score matching in S. aureus bacteremia. PATIENTS AND METHODS: A propensity-matched case-control study was conducted in a tertiary hospital in Korea from 2003 to 2008. RESULTS: A total of 266 patients who had clinically significant S. aureus bloodstream infections were investigated. Fifty-three propensity-matched case-control pairs with MRSA bacteremia were likely to have stayed in the hospital longer before developing bacteremia (mean 25.0 vs. 6.1 days; P = 0.01). However, after developing bacteremia, the differences in the mean duration of hospital stay was not significant (mean 35.0 vs. 28.7 days; P = 0.33). Similar numbers of MRSA and methicillin-susceptible S. aureus (MSSA) patients died (P = 0.48). The mean total hospital costs after S. aureus bacteremia increased more for MRSA patients compared to MSSA patients. However, this difference was not statistically significant ($9,369.6 vs. $8,355.8; P = 0.62). CONCLUSIONS: This study indicates that MRSA bacteremia is not associated with higher risks of mortality or hospital costs. It is, however, associated with a substantial increase in the length of hospital stay as compared to MSSA bacteremia. This information may help clinicians and policymakers derive methods to control the impacts of MRSA infection.

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells.

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.

The antimicrobial peptide human cationic antimicrobial protein-18/cathelicidin LL-37 as a putative growth factor for malignant melanoma.

BACKGROUND: Recent evidence suggests cathelicidin LL-37 to be a growth factor for various human cancers such as lung cancer, ovarian cancer and breast cancer. However, the effect of LL-37 against malignant skin cancer has not been reported. OBJECTIVES: To investigate whether the human cathelicidin LL-37 is involved in the carcinogenesis of various skin tumours. METHODS: Human cationic antimicrobial protein-18 (hCAP-18)/LL-37 production in several cell lines including HaCaT, a chronic myelogenous leukaemia (CML) cell line and various melanoma cell lines was examined using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Immunohistochemical analysis of melanoma, nonmelanoma skin cancer and precancerous and benign skin lesions was performed. After adding LL-37 to a melanoma cell line, tumour cell proliferation, migration and invasion were investigated. RESULTS: Human malignant melanoma cell lines overexpressed hCAP-18/LL-37 mRNA and peptide compared with HaCaT and CML cell lines. Immunohistochemistry showed that the peptide was strongly expressed in malignant melanoma and moderately expressed in squamous cell carcinoma, whereas basal cell carcinoma, precancerous lesions and seborrhoeic keratosis showed no or weak expression. LL-37 also stimulated melanoma cell proliferation, migration and invasion in vitro. CONCLUSIONS: Cathelicidin LL-37 was primarily expressed in human malignant skin cancer. LL-37 promoted melanoma cell proliferation, migration and invasion in vitro. We report that an increase in the level of LL-37 is associated with malignant skin tumours such as malignant melanoma. These results highlight the importance of LL-37 in the malignant tendency of skin tumours.

[Herpes simplex virus type 1 ICP27 induces apoptotic cell death by increasing intracellular reactive oxygen species].

HSV-1 ICP27, an immediate early protein of herpes simplex virus type 1, is involved in viral replication, transcriptional activation, RNA stability, apoptosis, and reactivation from viral latency. The reactivation from viral latency is closely related to apoptosis and oxidative stress. To understand the effect of ICP27 upon apoptosis, we tested for cell death of ICP27-expressing cells (3-3) in the presence of hydrogen peroxide. Under oxidative stress, 3-3 cells were sensitive to death, displaying typical apoptosis features such as oligonucleosomal DNA fragmentation, chromatin condensation, and G0/G1 accumulation. To dissect the sensitizing mechanism of ICP27 in apoptosis, we analyzed the level of intracellular reactive oxygen species (ROS) in 3-3 cells. We found that 3-3 cells exhibited increased ROS levels compared to Vero cells devoid of ICP27. We also observed that the increased levels of intracellular ROS in 3-3 cells were caused by disturbances in antioxidant enzymes. In 3-3 cells, the elevated ROS increased the AP-1 activity, subsequently the expression of Bax increased, and the expression of Bcl2 was reduced. In addition, 3-3 cells were sensitive to various apoptotic agents. Taken together, these results indicate that HSV-I ICP27 sensitizes the cells to apoptosis by elevating the intracellular levels of ROS.

U-shaped relationship between depression and body mass index in the Korean adults.

BACKGROUND: Although a number of studies have examined the relationship between depression and obesity, it is still insufficient to establish the specific pattern of relationship between depression and body mass index (BMI) categories. Thus, this study was aimed to investigate the relationship between depression and BMI categories. METHODS: A cross-sectional study was conducted for a cohort of 159,390 Korean based on Kangbuk Samsung Health Study (KSHS). Study participants were classified into 5 groups by Asian-specific cut-off of BMI (18.5, 23, 25 and 30kg/m2). The presence of depression was determined by Center for Epidemiologic Studies-Depression scales (CES-D)≥16 and≥25. The adjusted odd ratios (ORs) for depression were evaluated by multiple logistic regression analysis, in which independent variable was 5 categories of BMI and dependent variable was depression. Subgroup analysis was conducted by gender and age. RESULTS: When normal group was set as a reference, the adjusted ORs for depression formed U-shaped pattern of relationship with BMI categories [underweight: 1.31 (1.14-1.50), overweight: 0.94 (0.85-1.04), obese group: 1.01 (0.91-1.12), severe obese group: 1.28 (1.05-1.54)]. This pattern of relationship was more prominent in female and young age group than male and elderly subgroup. BMI level with the lowest likelihood of depression was 18.5kg/m2 to 25kg/m2 in women and 23kg/m2 to 25kg/m2 in men. CONCLUSIONS: There was a U-shaped relationship between depression and BMI categories. This finding suggests that both underweight and severe obesity are associated with the increased risk for depression.

Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia.

This corrects the article DOI: 10.1038/leu.2017.107.

Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia.

Drug resistance to BCR-ABL1 tyrosine kinase inhibitor (TKI) and disease progression to blast crisis (BC) are major clinical problems in chronic myeloid leukemia (CML); however, underlying mechanisms governing this process remain to be elucidated. Here, we report Cordon-bleu protein-like 1 (Cobll1) as a distinct molecular marker associated with drug resistance as well as progression to BC. In detail, Cobll1 increases IKKγ stability, leading to NF-κB activation and reduction of nilotinib-dependent apoptosis, suggesting Cobll1-mediated NF-κB could be involved in drug resistance. Recently, NF-κB signalling has been highlighted as a core mechanism for chronic phase (CP)-BC progression, stem cell survival and tyrosine kinase inhibitor resistance. We also demonstrated that high expression of Cobll1 confers drug resistance to tyrosine kinase inhibitors in CML cell line as well as patient samples. The analysis of large sets of primary CML samples (n=90) shows that Cobll1 expression is dramatically increased in BC but not in CP, which is correlated with a poor survival rate (P=0.002). Moreover, our studies show that Cobll1 is highly expressed in CD34+ primitive stem cell populations, and the zebrafish paralog Cobll1b is important for normal hematopoiesis during embryonic development. Based on these results, we propose that Cobll1 is a novel biomarker and potential therapeutic target for CML-BC.

CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer.

The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.

BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).

Ion-beam-assisted deposition (IBAD) of hydroxyapatite coating layer on Ti-based metal substrate.

A hydroxyapatite layer was formed on the surface of a Ti-based alloy by ion-beam-assisted deposition. The deposition methodology comprised of an electron beam vaporizing a pure hydroxyapatite target, while an Ar ion beam was focused on the metal substrate to assist deposition. All deposited layers were amorphous, regardless of the current level of the ion beam. The bond strength between the layer and the substrate increased steadily with increasing current, while the dissolution rate in a physiological saline solution decreased remarkably. These improvements were attributed to an increase in the Ca/P ratio of the layer. Without ion beam assistance, the Ca/P ratio was much lower than the stoichiometric HAp (Ca/P = 1.67). With ion-beam assistance, the Ca/P ratio of the layer increased presumably due to the high sputtering rate of P compared to that of Ca from the layer being coated.

Involvement of NADH/NADPH oxidase-derived superoxide in experimental vasospasm induced by periarterial blood in rat femoral artery.

To elucidate the mechanism(s) involved in periarterial blood-mediated vasospasm in the rat femoral artery, vascular production of superoxide and related expression of intercellular adhesion molecule-1 (ICAM-1) were assessed with subsequent perivascular mobilization of granulocytes and macrophages. Arterial vasospasm characterized by increased wall thickness and decreased lumen size was observed on the side exposed to blood at 7 to 12 days, and these vascular changes were significantly ameliorated by pretreatment with NADH/NADPH oxidase inhibitor, diphenyleneiodonium (200 microM, locally). Increased mobilization of granulocytes was paralleled with the expression of ICAM-1 in the vessels at 24 hours after periarterial application of blood to the femoral artery, and then both declined. Subsequently, infiltration of macrophage progressively increased at all layers throughout 7 to 12 days. In in vitro study, a large amount of superoxide that was inhibitable by diphenyleneiodonium (20 and 100 microM) was produced at 3 hours upon application of 10% autologous blood to the aortic segments. Furthermore, ICAM-1 expression by autologous blood was well correlated with generation of superoxide anion in the aortic segment (r=0.975, P<0.05). Taken together, it is suggested that NADH/NADPH oxidase-derived superoxide is implicated in periarterial blood-induced vasospasm via increased expression of ICAM-1 with subsequent mobilization of granulocyte/macrophage.

Health, double jeopardy, and culture: the use of institutionalization by African-Americans.

Elderly African-Americans are admitted to nursing homes at between half and three-quarters of the rate of elderly whites. This review examines the theoretical approaches and the nature of the evidence typically brought to bear in addressing this issue. The double jeopardy hypothesis effectively describes but does not explain apparent racial inequities in the use of institutional care. Explanations based on the hypothesized African-American subculture will remain inadequate until they are grounded in data and take into account inequality.