Health Literacy as a Social Determinant of Health in Asian American Immigrants: Findings from a Population-Based Survey in California

Background

Asian American immigrants have a lower level of health literacy than non-Latino whites, but their level of health literacy and its impact on health outcomes may differ among subgroups.

Objective

We investigated the level of health literacy across five subgroups of Asian American immigrants and explored the association between health literacy and self-rated health status and symptoms of depression.

Design

We utilized a cross-sectional survey research design and a population-based sampling strategy using the 2007 California Health Interview Survey (CHIS).

Participants

We sampled 30,615 non-Latino whites and 3,053 Asian American immigrants (1,058 Chinese, 598 Koreans, 534 Filipinos, 416 South Asians, and 447 Vietnamese).

Main Measures

We used two questions as proxy measures to assess the level of health literacy in non-Latino whites and in both aggregated and disaggregated Asian American immigrant groups. We then investigated the effect of health literacy on two main health outcomes: self-rated health status and depression symptoms.

Key Results

The level of health literacy varied across the five subgroups of Asian American immigrants. Chinese, Korean, and Vietnamese groups had the lowest levels of health literacy, while Filipinos showed the highest level. Health literacy was positively correlated with health status in Chinese and Korean immigrants, and negatively correlated with depression symptoms in Korean and South Asian immigrants.

Conclusion

We found heterogeneity in health literacy among Asian American immigrants and found that health literacy had varying associations with health outcomes. The aggregated Asian American immigrant group results may mask the true health disparities that each Asian American immigrant group faces. Koreans were the only group found to have a significant association between the proxy for health literacy and both health outcomes. Further research is needed to better understand the causes of heterogeneity and to investigate health literacy as a critical determinant of immigrant health.KEY WORDS: health literacy, health status, depression, Asian American immigrants, health disparity     

Feasibility and Diagnostic Yield of Endoscopic Ultrasonography-Guided Fine Needle Biopsy With a New Core Biopsy Needle Device in Patients With Gastric Subepithelial Tumors

As treatment decisions for patients with gastric subepithelial tumors (SETs) largely depend on the histopathologic diagnosis, noninvasive and effective tissue acquisition methods are definitely required for proper management of gastric SETs. Recently, a new endoscopic ultrasonography-guided fine needle biopsy (EUS-FNB) device with ProCore reverse bevel technology was developed. We aimed to elucidate the feasibility and diagnostic yield of EUS-FNB with this new core biopsy needle device in patients with gastric SETs.A prospectively maintained database was retrospectively reviewed to identify consecutive patients who underwent EUS-FNB with a 22-gauge ProCore needle for gastric SETs 2 cm or larger. The main outcome measurement was the diagnostic yield of EUS-FNB. Procedure results were categorized into diagnostic, suggestive, or nondiagnostic.Of the 43 patients, needle punctures were successful in all cases irrespective of tumor location. EUS-FNB procedure results were diagnostic in 86.0%, suggestive in 4.7%, and nondiagnostic in 9.3% of cases, respectively. The diagnostic yield was the highest in fundus (100.0%), followed by body (89.5%), cardia (83.3%), and antrum (50.0%). All 18 patients with cardiac SET were finally diagnosed to have leiomyoma, and 16 patients with diagnostic or suggestive results avoided surgery. A heterogeneous echo pattern on EUS was found in 33.3% of cases with nondiagnostic or suggestive results and in 5.4% with diagnostic results. In multivariate analysis, no independent predictor of unsuccessful EUS-FNB with nondiagnostic or suggestive results was identified. Agreement between EUS-FNB and surgical pathology was 100% with respect to the diagnosis of gastrointestinal stromal tumor. However, there was a significant discrepancy in mitotic counts observed between the EUS-FNB and surgical specimens in patients with gastrointestinal stromal tumor. There were no significant procedure-related adverse events during and after the procedures.EUS-FNB with a 22G ProCore needle is a technically feasible, safe, and effective procedure for pathologic diagnosis of gastric SETs. This procedure can help refine surgical indications and facilitate a proper treatment decisions for gastric SETs, especially in the cardia.     

Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells

Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR [endosomal sorting complex required for transport (ESCRT) and ALIX-binding region] of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55–TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx₃Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx₃YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx₃Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells.Intercellular bridges are a distinct feature of spermatogenesis in mammalian germ cells. Although observations of intercellular bridges were reported more than 100 y ago, their molecular function is largely unknown and we have only recently begun to learn how they form at the molecular level. Interestingly, stable bridges have recently been recognized as providing a unique means of intercellular communication, because cytoplasmic molecules can pass through them (1). The loss of germ cell intercellular bridges disrupts spermatogenesis and causes sterility (2).The most direct method of cell-to-cell communication is to connect the separate cytosols of cells using a tunnel that allows macromolecules to pass from one cell to another. Various organisms achieve this type of direct intercellular transfer using tunneling nanotubes (3), intercellular bridges (also called ring canals) (1), and bacterial intercellular nanotubes (4). Somatic ring canals have also been found to equilibrate the levels of some proteins between connected cells in invertebrates such as Drosophila (5). Among these mechanisms, it has been shown that intercellular bridges having channels that are 0.5–3 μm in diameter are formed by the arrest of cell abscission at the final stage of cytokinesis in the germ cells of vertebrates (1).Whether the process of cell abscission is completed or not depends on the cell type. In the somatic cells of vertebrates, cell abscission occurs at the midbody (6), a structure that tethers two daughter cells. The midbody protein CEP55 plays a key role in recruiting the ALIX–endosomal sorting complex required for transport (ESCRT) I complex to the midbody (7, 8). After this event, ESCRT-III subunits, which have a membrane scission activity, are recruited (9–13). Alternatively, to inactivate cell abscission, TEX14, a testis-expressed gene and germ cell-specific component, is recruited to the midbody. It is essential for intercellular bridges and fertility in male mice (2), and has recently been identified as one of the susceptibility genes for testicular germ cell tumors (14).In germ cells, intercellular bridges are formed throughout spermatogenesis and the arrest of cell abscission is controlled precisely by a sophisticated interplay among the proteins TEX14, ALIX, TSG101 (expressed by tumor susceptibility gene 101; TSG101), and CEP55. Therefore, it is important to investigate how TEX14 safeguards intercellular bridges from the potentially damaging membrane scissor in germ cells. To understand the molecular mechanisms involved in this process, we have performed both structural and functional analyses of the CEP55–TEX14 interaction.     

Targeted disruption of PDE3B,but not PDE3A,protects murine heart from ischemia/reperfusion injury

Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B^−/− heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B^−/− mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B^−/− mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca²⁺-induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B^−/− heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3–enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies.The two cyclic nucleotide phosphodiesterase type 3 (PDE3) subfamilies PDE3A and PDE3B are products of separate but homologous genes. PDE3 isoforms hydrolyze both cAMP and cGMP with high affinity (K_m <1 μM) in a mutually competitive manner and are important regulators of cyclic nucleotide signaling pathways and responses in cardiomyocytes and vascular smooth muscle (1). PDE3A and PDE3B exhibit different patterns of expression. PDE3A is more abundant in platelets, airway and vascular smooth muscle, and cardiovascular tissues, whereas PDE3B is relatively more highly expressed in tissues that are important in regulating energy metabolism, including liver, pancreatic β cells, brown adipose tissue (BAT), and white adipose tissue (WAT) (2). Little is known about their differential localization and functions when PDE3A and PDE3B are present in the same cell. To gain further insight into specific PDE3A and PDE3B functions in physiological contexts, we have generated and studied PDE3A^−/− and PDE3B^−/− mice (3, 4).PDE3 inhibitors, e.g., milrinone, are thought to enhance myocardial inotropic responses via cAMP/PKA regulation of Ca²⁺ cycling in the sarcoplasmic reticulum (SR) (1, 5). The PDE3 inhibitor cilostazol (6–9) and the PDE5 inhibitor sildenafil (10, 11) have been reported to protect hearts against ischemia/reperfusion (I/R) injury in various species. Fukasawa et al. (8) have suggested that cilostazol exerts its cardioprotective effect by activating mitochondrial Ca²⁺-activated K⁺ (mitoK_Ca) channels, whose opening protects hearts against infarction (12). Furthermore, studies have shown that the opening of mitoK_Ca channels is potentiated by cAMP-dependent PKA signaling (13), whereas PKC potentiates mitochondrial ATP-sensitive K⁺ (mitoK_ATP) channel activation (14). Kukreja and his associates have suggested that the cardioprotective effects of sildenafil are mediated by activation of both mitoK_ATP (10) and mitoK_Ca channels (11).Ischemic preconditioning (PreC), a process in which brief intermittent episodes of ischemia and reperfusion protect the heart from subsequent prolonged ischemic injury (15), initiates a number of cardioprotective signaling pathways at the plasma membrane, which are transduced to mitochondria (16). According to the “signalosome” hypothesis, cardioprotective [e.g., G protein-coupled receptor (GPCR)-induced or ouabain-induced] signals are delivered to mitochondria by specialized caveolae-derived vesicular structures, signalosomes, which contain a wide variety of receptors (e.g., GPCRs) and signaling molecules (e.g., Akt, Src, eNOS, and PKCε) that are assembled in lipid rafts and caveolae (17). In recent years, the role of lipid rafts and caveolae in cardiovascular signaling has attracted much attention (18), and adenylyl cyclases and PDEs have emerged as key players in shaping and organizing intracellular signaling microdomains (19–21).Accumulating evidence implicates the mitochondrial permeability transition (MPT) pore as a key effector of cardioprotection against I/R injury, and reperfusion-induced elevation of reactive oxygen species (ROS) can trigger the opening of the MPT pore, resulting in ischemic injury, apoptosis, and cell death (16). A wide range of cardioprotective signaling pathways converge on glycogen synthase kinase-3β (GSK-3β), and its inhibition directly and/or indirectly regulates MPT pore-regulatory factors (e.g., cyclophilin D and voltage-dependent anion channels) and antiapoptotic Bcl-2 family members (22). Physical association between mitochondria and the endoplasmic reticulum (ER) [via mitochondria-associated ER membranes (MAMs)] (23) or the SR (24) also may reduce reperfusion-induced mitochondrial Ca²⁺ overload and consequent oxidative stress and thus block MPT pore opening (25).In this study, we report that, 24 h after in vivo coronary artery ligation, I/R or, in a Langendorff cardiac I/R model system, infarct size is reduced in PDE3B^−/− heart, but not in PDE3A^−/− heart, compared with WT heart. This protective effect is most likely caused by reduced production of ROS and reduced Ca²⁺-induced MPT pore opening in PDE3B^−/− mitochondria. The mechanism(s) for cardioprotection in PDE3B^−/− mice may be related to cAMP/PKA-induced opening of mitoK_Ca channels and assembly of ischemia-induced caveolin-3–enriched fraction (ICEF) signalosomes in which various cardioprotective molecules accumulate, resulting in functional cardiac preconditioning. Our results also suggest that the increased physical interaction between mitochondria and transverse tubules (T-tubules) (indirectly via the SR at dyads or directly) in PDE3B^−/− heart may be involved in ICEF/signalosome delivery of cardioprotective molecules to mitochondria, leading to reduced ROS generation and increased resistance to Ca²⁺-induced MPT pore opening in PDE3B^−/− mitochondria. Although PDE3A is more highly expressed than PDE3B in cardiovascular tissues, our findings of cardioprotection against I/R injury in PDE3B^−/− mice but not in PDE3A^−/− mice and the different subcellular locations of PDE3A and PDE3B in cardiomyocytes [PDE3A colocalizes with sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) on SR membranes, and PDE3B localizes with caveolin-3 in T-tubules along Z-lines] may reflect an important example of individual PDEs at distinct subcellular sites regulating the compartmentalization of specific cAMP/PKA-signaling pathways (19, 21). In this case, PDE3B, located in regions where cardiomyocyte mitochondria, T-tubules, and SR may be in close proximity, may regulate stress responses and/or the assembly of ICEF signalosomes or other specific cardioprotective pathways.     

Translating What Works: A New Approach to Improve Diabetes Management

Background:

The most efficacious strategies to improve diabetes control include case management, health care team changes, patient education, and facilitated transmission of patient data to clinicians (“facilitated relay”), but these strategies have not been translated to permit general use in clinical practice.

Methods:

A web-based decision support program was developed to include these features, and assessed in patients who had A1c ≥7.0% despite using metformin with/without sulfonylureas or insulin. Staff entered patients’ glucose data, obtained management recommendations, reviewed the plan with a clinician, and discussed the new plan with patients.

Results:

113 subjects were 96% male and 32% black, with average age 65.6 years and BMI 32.8. During prior primary care, A1c averaged 8.32 ± 0.16% (SEM). In all patients, baseline A1c was 8.18 ± 0.11%, and decreased to 7.54 ± 0.12%, 7.16 ± 0.13%, and 7.54 ± 0.16% at 3, 6, and 12 months, respectively, all P < .001. In 42 subjects who provided glucose data and made requested changes in medications, A1c was 8.12 ± 0.09% at baseline and fell to 7.29 ± 0.11%, 6.98 ± 0.10%, and 7.05 ± 0.10% at 3, 6, and 12 months, respectively, all P < .001. Chart review of 16 subjects followed for 12 months demonstrated that hypoglycemia (symptoms and/or glucose <70 mg/dl) averaged less than 1 episode/patient/month, and there was no severe hypoglycemia.

Conclusions:

A novel decision support program improved A1c with little hypoglycemia. Use of this approach should allow primary care teams to keep patients well controlled, and reduce the need for specialist referrals.     

Percutaneous Thrombectomy of AVF: Immediate Success and Long‐term Patency Rates

The purpose of this study was to report the results obtained in a cohort of 520 cases of thrombosed arteriovenous fistulas (AVF) treated by percutaneous intervention over a period of 8 years. The methods used varied according to the individual characteristics of the case. A clinical success rate of 91.1% was obtained with no significant difference being noted among radial‐cephalic, brachial‐cephalic, and brachial‐basilic AVFs. The mean primary patency for this group was 227.3 ± 14.6 days, and the mean assisted primary patency was 677.2 ± 44.6 days. The lower arm AVFs had both a primary patency and an assisted primary patency that were significantly better than the upper arm cases (p = 0.006 and 0.002, respectively). The primary patency for radial‐cephalic AVFs was significantly better than that for brachial‐cephalic AVFs (p = 0.021), but not for brachial‐basilic cases (p = 0.122). Assisted primary patency for radial‐cephalic cases was significantly superior to the values for either patients with a brachial cephalic (p = 0.046) or a brachial‐basilic (p = 0.004). Complications occurred in seven cases (1.3%), all of which were venous ruptures. Blood flow was affected in four cases. Only one of these was salvaged with angioplasty balloon tamponade. In the remaining three cases, the AVF was lost.     

Metformin improves performance in high‐intensity exercise,but not anaerobic capacity in healthy male subjects

The aim of this study was to determine the ergogenic effects of metformin in high‐intensity exercise, as well as its effects on anaerobic capacity, in healthy and physically active men. Ten subjects (mean (± standard deviation) maximal oxygen uptake (_2max) 38.6 ± 4.5 mL/kg per min) performed the following tests in a cycle ergometer: (i) an incremental test; (ii) six submaximal constant workload tests at 40%–90% (_2max); and (iii) two supramaximal tests (110% (_2max). Metformin (500 mg) or placebo was ingested 60 min before the supramaximal test. There were no significant differences between the placebo and metformin groups in terms of maximum accumulated oxygen deficit (2.8 ± 0.6 vs 3.0 ± 0.8 L, respectively; P = 0.08), lactate concentrations (7.8 ± 2.6 vs 7.5 ± 3.0 mmol/L, respectively; P = 0.75) or O₂ consumed in either the last 30 s of exercise (40.4 ± 4.4 vs 39.9 ± 4.0 mL/kg per min, respectively; P = 0.35) or the first 110 s of exercise (29.0 ± 2.5 vs 29.5 ± 3.0 mL/kg per min, respectively; P = 0.42). Time to exhaustion was significantly higher after metformin than placebo ingestion (191 ± 33 vs 167 ± 32 s, respectively; P = 0.001). The fast component of recovery was higher in the metformin than placebo group (12.71 vs 12.18 mL/kg per min, respectively; P = 0.025). Metformin improved performance and anaerobic alactic contribution during high‐intensity exercise, but had no effect on overall anaerobic capacity in healthy subjects.