Binge Drinking among Economically Disadvantaged African American Older Adults with Diabetes.

Purpose. This study investigated the effect of demographic, socioeconomic, and psychological factors as well as the role of health determinants on alcohol consumption and binge drinking among economically disadvantaged African American older adults with type 2 diabetes mellites (T2DM). Methods. This survey recruited 231 African Americans who were older adults (age 65+ years) and had T2DM. Participants were selected from economically disadvantaged areas of South Los Angeles. A structured face-to-face interview was conducted to collect data on demographic factors, objective and subjective socioeconomic status (SES) including education and financial difficulty, living arrangement, marital status, health, and drinking behaviors (drinking and binge drinking). Results. Age, gender, living alone, pain, comorbid conditions, and smoking were associated with drinking/binge drinking. Male gender, pain, and being a smoker were associated with higher odds of drinking/binge drinking, while individuals with more comorbid medical conditions had lower odds of binge drinking. Conclusion. In economically constrained urban environments, gender, pain, and smoking but not age, SES, depression, and health may predict binge drinking for African American older adults with T2DM. African Americans older adult men with T2DM with comorbid pain should be screened for binge drinking.

Chronic Respiratory Disease and Health-Related Quality of Life of African American Older Adults in an Economically Disadvantaged Area of Los Angeles.

Background. Most of the attention of policy makers, program planners, clinicians, and researchers in the area of physical health disparities among African American older adults has been traditionally focused on cardiometabolic disease and cancer. Among a long list of chronic medical conditions, chronic respiratory conditions (CRCs), such as asthma, chronic bronchitis, and emphysema, have received less attention. Purpose. This study investigated whether CRCs contribute to physical and mental health-related quality of life (HRQoL) of African American older adults who live in economically disadvantaged urban areas, and whether these effects are due to demographic factors, socioeconomic status (SES), health behaviors, and comorbid medical and mental conditions. Methods. This community-based study recruited 617 African American older adults (age ≥ 65 years) from Service Planning Areas (SPA) 6, an economically disadvantaged area in South Los Angeles. Structured face-to-face interviews were used to collect data on demographic factors (age and gender), SES (educational attainment and financial difficulty), living arrangements, marital status, health behaviors (cigarette smoking and alcohol drinking), health (CRC, number of comorbid medical conditions, depressive symptoms, and pain intensity), and physical and mental HRQoL (Physical and Mental Component Summary Scores; PCS and MCS; SF-12). Linear regressions were used to analyze the data. Results. The presence of CRCs was associated with lower PCS and MCS in bivariate analysis. The association between CRCs and PCS remained significant above and beyond all confounders. However, the association between CRCs and MCS disappeared after controlling for confounders. Conclusion. For African American older adults living in economically disadvantaged urban areas, CRCs contribute to poor physical HRQoL. Evaluation and treatment of CRCs in African American older adults may be a strategy for reduction of disparities in HRQoL in this population. As smoking is the major modifiable risk factor for CRCs, there is a need to increase accessibility of smoking cessation programs in economically disadvantaged urban areas. More research is needed on the types, management, and prognosis of CRCs such as asthma, chronic bronchitis, and emphysema in African American older adults who reside in low-income and resource limited urban areas.

Cigarette Smoking among Economically Disadvantaged African-American Older Adults in South Los Angeles: Gender Differences.

The current study aims to explore gender differences in the risk of cigarette smoking among African-American (AA) older adults who live in economically disadvantaged urban areas of southern Los Angeles. This cross-sectional study enrolled 576 older AA adults (age range between 65 and 96 years) who were residing in Service Planning Area 6 (SPA 6), one of the most economically challenged areas in southern Los Angeles. All participants had cardiometabolic disease (CMD). Data were collected using structured face-to-face interviews. Demographic factors (age and gender), socioeconomic status (educational attainment and financial difficulty), health (number of comorbid medical conditions and depressive symptoms), and health behaviors (current alcohol drinking and current smoking) were measured. Logistic regressions were used to analyze the data without and with interaction terms between gender and current drinking, depressive symptoms, and financial difficulty. AA men reported more smoking than AA women (25.3% versus 9.3%; p < 0.05). Drinking showed a stronger association with smoking for AA men than AA women. Depressive symptoms, however, showed stronger effects on smoking for AA women than AA men. Gender did not interact with financial difficulty with regard to current smoking. As AA older men and women differ in psychological and behavioral determinants of cigarette smoking, gender-specific smoking cessation interventions for AA older adults who live in economically deprived urban areas may be more successful than interventions and programs that do not consider gender differences in determinants of smoking. Gender-tailored smoking cessation programs that address drinking for AA men and depression for AA women may help reduce the burden of smoking in AA older adults in economically disadvantaged urban areas. Given the non-random sampling, there is a need for replication of these findings in future studies.

Potentially inappropriate medication use among hypertensive older African-American adults.

BACKGROUND: Inappropriate use of medications, particularly among minority older adults with co-morbidity, remains a major public health concern. The American Geriatrics Society (AGS) reports that Potentially Inappropriate Medication (PIM) continues to be prescribed for older adults, despite evidence of poor outcomes. The main objective of this study was to examine the prevalence of PIM use among underserved non-institutionalized hypertensive older African-American adults. Furthermore, this study examines potential correlations between PIM use and the number and type of chronic conditions. METHODS: This cross-sectional study is comprised of a convenience sample of 193 hypertensive non-institutionalized African-American adults, aged 65 years and older recruited from several senior housing units located in underserved areas of South Los Angeles. The updated 2015 AGS Beers Criteria was used to identify participants using PIMs. RESULTS: Almost one out of two participants had inappropriate medication use. While the average number of PIMs taken was 0.87 drugs, the range was from one to seven medications. Almost 23% of PIMs were due to drugs with potential drug-drug interactions. The most common PIM was the use of proton pump inhibitors (PPI) and Central Nervous System (CNS) active agents. Nearly 56% of PIMs potentially increased the risk of falls and fall-associated bone fractures. The use of PIMs was significantly higher among participants who reported a higher number of chronic conditions. Nearly 70% of participants with PIM use reported suffering from chronic pain. CONCLUSIONS: The major reason for high levels of polypharmacy, PIMs, and drug interactions is that patients suffer from multiple chronic conditions. But it may not be possible or necessary to treat all chronic conditions. Therefore, the goals of care should be explicitly reviewed with the patient in order to determine which of the many chronic conditions has the greatest impact on the life goals and/or functional priorities of the patient. Those drugs that have a limited impact on the patient's functional priorities and that may cause harmful drug-drug interactions can be reduced or eliminated, while the remaining medications can focus on the most important functional priorities of the patient.

Using Gas Phase Reactions of Hexamethylene Triperoxide Diamine (HMTD) to Improve Detection in Mass Spectrometry.

Our efforts to lower the detection limits of hexamethylene triperoxide diamine (HMTD) have uncovered previously unreported gas-phase reactions of primary and secondary amines with one of the six methylene carbons. The reaction occurs primarily in the atmospheric pressure chemical ionization (APCI) source and is similar to the behavior of alcohols with HMTD [1]. However, unlike alcohols, the amine reaction conserves the hydrogen peroxide on the intact product. Furthermore, with or without amines, HMTD is oxidized to tetramethylene diperoxide diamine dialdehyde (TMDDD) in a temperature-dependent fashion in the APCI source. Synthesized TMDDD forms very strong adducts (not products) to ammonium and amine ions in the electrospray ionization (ESI) source. Attempts to improve HMTD detection by generating TMDDD in the APCI source with post-column addition of amines were not successful. Signal intensity of the solvent related HMTD product in methanol, [HMTD+MeOH2-H2O2]+ (m/z 207.0975), was understandably related to the amount of methanol in the HMTD environment as it elutes into the source. With conditions optimized for this product, the detection of 100 pg on column was accomplished with a robust analysis of 300 pg (1.44 pmol) routinely performed on the Orbitrap mass spectrometers. Graphical Abstract ᅟ.

Gas-phase reactions of alcohols with hexamethylene triperoxide diamine (HMTD) under atmospheric pressure chemical ionization conditions.

RATIONALE: Hexamethylene triperoxide diamine (HMTD) is a sensitive peroxide explosive first synthesized in 1885. HMTD exhibits an unusual gas-phase phenomenon in the presence of alcohols that has been previously observed, but incorrectly resolved. We are attempting to determine this specific mechanism. METHODS: We used positive ion mode atmospheric pressure chemical ionization (APCI) as the interface to the mass spectrometer. HMTD was infused with various solvents including (18) O- and (2) H-labeled methanol in order to determine gas-phase reaction mechanisms. RESULTS: Based on these labeled experiments, it was determined that, under APCI conditions, the alcohol oxygen attacks a methylene carbon of HMTD and releases H2 O2 . This was attempted with nine different alcohols and, in each case, the alcohol is fully incorporated into the molecule with the peroxide release. A mechanism for this reaction has been proposed. CONCLUSIONS: This work appears to have confirmed the gas-phase reaction mechanism of HMTD with alcohols. As we continue efforts to characterize this unusual molecule, the information may prove useful in determining formation and degradation mechanism(s). In addition, this property of HMTD may find use in other fields of science.

Effect of cardiorespiratory fitness on short-term morbidity and mortality after coronary artery bypass grafting.

Although preoperative risk assessment for coronary artery bypass grafting (CABG) has been evaluated with multiple predictive models, none have incorporated a low level of cardiorespiratory fitness, which represents one of the strongest predictors of all-cause and cardiovascular mortality in subjects with and without heart disease. The aim of the present study was to evaluate preoperative cardiorespiratory fitness, expressed as METs (1 MET = 3.5 ml O2/kg/min), and short-term morbidity and mortality after CABG. The Society of Thoracic Surgeons database was queried for patients who underwent CABG from January 2002 to December 2010 at Beaumont Health Systems. Electronic medical records were reviewed for peak or symptom-limited exercise testing <90 days before CABG. Peak METs were estimated from the achieved treadmill speed, grade, and duration or the cycle ergometer workload, corrected for body weight. Patients who met eligibility criteria (n = 596) were categorized into 2 groups: those with reduced aerobic capacity (<5 METs [n = 78]) and those achieving ≥5 METs (n = 518). Fisher's exact tests were used to compare preoperative aerobic capacity and short-term postoperative morbidity and mortality between the 2 groups. After adjusting for potential confounding variables, an inverse relation was found between cardiorespiratory fitness and complications after CABG. Specifically, low preoperative cardiorespiratory fitness (<5 METs) was associated with higher operative and 30-day mortality after CABG (p <0.05). In conclusion, these data suggest that preoperative cardiorespiratory fitness provides an independent and additive marker for mortality after CABG.

How does Listeria monocytogenes combat acid conditions?

Listeria monocytogenes, a major foodborne pathogen, possesses a number of mechanisms that enable it to combat the challenges posed by acidic environments, such as that of acidic foods and the gastrointestinal tract. One mechanism employed by L. monocytogenes for survival at low pH is the adaptive acid tolerance response (ATR) in which a short adaptive period at a nonlethal pH induces metabolic changes that allow the organism to survive a lethal pH. Overcoming acid conditions by L. monocytogenes involves a variety of regulatory responses, including the LisRK 2-component regulatory system, the SOS response, components of the σ(B) regulon, changes in membrane fluidity, the F0F1-ATPase proton pump, and at least 2 enzymatic systems that regulate internal hydrogen ion concentration (glutamate decarboxylase and arginine deiminase). It is not clear if these mechanisms exert their protective effects separately or in concert, but it is probable that these mechanisms overlap. Studies using mutants indicate that the glutamate decarboxylase system can protect L. monocytogenes when the organism is present in acidic juices, yogurt, salad dressing, mayonnaise, and modified CO2 atmospheres. The glutamate decarboxylase system also has a role in protecting L. monocytogenes against the acidic environment of the stomach. There is a need to study other acid resistance mechanisms of L. monocytogenes to determine their effectiveness in protecting the organism in acidic foods or during transit through the acid stomach.

Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL-60 cells.

PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia (APL) involves differentiation therapy with retinoic acid (RA). However, the relapse rates are significant. In the present work we evaluated the effects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF-alpha, IL-8, and MMP-9 expression. This treatment induced higher levels of ICAM-1 endothelial cell expression, and increased cellular mobility. Inhibiting PDGFR enhanced RA-induced expression of integrin. Integrin ligand increased differentiation markers CD11b, inducible oxidative metabolism and PDGFR-beta phosphorylation. While the neutrophil-endothelial cell interactions are strengthened by the combined treatment, the endothelium-substratum interactions are weakened, a situation common in RAS.

An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II.

Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II-targeted lantibiotics are too short to be able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis.

Retinoic acid induces expression of SLP-76: expression with c-FMS enhances ERK activation and retinoic acid-induced differentiation/G0 arrest of HL-60 cells.

Retinoic acid (RA) is known to cause MAPK signaling which propels G0 arrest and myeloid differentiation of HL-60 human myeloblastic leukemia cells. The present studies show that RA up-regulated expression of SLP-76 (Src-homology 2 domain-containing leukocyte-specific phospho-protein of 76 kDa), which became a prominent tyrosine-phosphorylated protein in RA-treated cells. SLP-76 is a known adaptor molecule associated with T-cell receptor and MAPK signaling. To characterize functional effects of SLP-76 expression in RA-induced differentiation and G0 arrest, HL-60 cells were stably transfected with SLP-76. Expression of SLP-76 had no discernable effect on RA-induced ERK activation, subsequent functional differentiation, or the rate of RA-induced G0 arrest. To determine the effects of SLP-76 in the presence of a RA-regulated receptor, SLP-76 was stably transfected into HL-60 cells already overexpressing the colony stimulating factor-1 (CSF-1) receptor, c-FMS, from a previous stable transfection. SLP-76 now enhanced RA-induced ERK activation, compared to parental c-FMS transfectants. It also enhanced RA-induced differentiation, evidenced by enhanced paxillin expression, inducible oxidative metabolism and superoxide production. RA-induced RB tumor suppressor protein hypophosphorylation was also enhanced, as was RA-induced G0 cell cycle arrest. A triple Y to F mutant SLP-76 known to be a dominant negative in T-cell receptor signaling failed to enhance RA-induced paxillin expression, but enhanced RA-induced ERK activation, differentiation and G0 arrest essentially as well as wild-type SLP-76. Thus, SLP-76 overexpression in the presence of c-FMS, a RA-induced receptor, had the effect of enhancing RA-induced cell differentiation. This is the first indication to our knowledge that RA induces the expression of an adapter molecule to facilitate induced differentiation via co-operation between c-FMS and SLP-76.

Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels.

Retinoic acid-induced expression of the CD38 ectoenzyme receptor in HL-60 human myeloblastic leukemia cells is regulated by RARalpha and RXR, and enhanced or prevented cell differentiation depending on the level of expression per cell. RARalpha activation caused CD38 expression, as did RXR activation but not as effectively. Inhibition of MAPK signaling through MEK inhibition diminished the induced expression by both RARs and RXRs. Expression of CD38 enhanced retinoic acid-induced myeloid differentiation and G0 cell cycle arrest, but at higher expression levels, induced differentiation was blocked and retinoic acid induced a loss of cell viability instead. In the case of 1,25-dihydroxyvitamin D3, induced monocytic differentiation was also enhanced by CD38 and not enhanced by higher expression levels, but without induced loss of viability. Expression levels of CD38 thus regulated the cellular response to retinoic acid, either propelling cell differentiation or loss of viability. The cellular effects of CD38 thus depend on its expression level.

Novel cell-specific and dominant negative anti-apoptotic roles of p73 in transformed leukemia cells.

Although extensive homology exists between related genes p53 and p73, recent data suggest that the family members have divergent roles. We demonstrate that the differential regulatory roles of p53 family member p73 are highly cell-context and promoter-specific. Full-length p73 expressed in the transformed leukemia cell line Jurkat behaves as a specific dominant negative transcriptional repressor of the cell cycle inhibitor gene p21 and blocks p53-mediated apoptosis. These findings provide evidence for a new mechanism in oncogenesis through which the functional properties of p73 can be altered in an inheritable and cell-specific fashion independent of transcriptional coding.

Cross-regulation of T cell growth factor expression by p53 and the Tax oncogene.

In this study, we demonstrate that p53 directly inhibits expression of the T cell growth factor (IL-2) in activated T cells. This repression is independent of the intrinsic transcriptional activity of p53 and is mediated by the Tax-responsive CD28RE-3'-12-O-tetradecanoylphorbol-13-acetate response element (AP1) element of the IL-2 promoter. Coexpression of the Tax oncogene causes full reversal of this repression through coordinate targeting of p300, CREB, and the NF-kappaB pathways. Paradoxically, IL-2 repression by p53 is not reversed by mdm2. Instead, mdm2 represses the IL-2 promoter by a mechanism that is synergistic with p53 and resistant to Tax reversal. The p300 structure-function studies show that these effects are linked to competitive associations among p53, Tax, and mdm2 with multiple domains of p300. The functional outcome of these antagonistic associations is revealed further by the observation that Tax and p53 induce apoptosis in activated T cells through separate and mutually exclusive pathways. Interestingly, both pathways are abrogated by mdm2. These results provide evidence that a dynamic interplay, between Tax and specific elements of the p53 network, mediates growth factor expression and programmed cell death in activated T cells.

Long-Term Consequences of Foodborne Toxoplasmosis: Effects on the Unborn, the Immunocompromised, the Elderly, and the Immunocompetent †.

In immunointact individuals, infection by the ubiquitous protozoan parasite Toxoplasma gondii is common, but clinical disease is rare; however, fetal and immunocompromised populations are at risk for clinical toxoplasmosis. T. gondii organisms persist as quiescent tissue cysts in various tissues of the body with the possibility of tissue cysts reactivating to actively multiplying parasites if there is a decline in the infected individual's immune system. In more recent years, there has been an increase in toxoplasmosis due to a steadily increasing immunocompromised population. T. gondii infections are controlled principally by the cellular immune system. Thus, individuals with defective cell-mediated immunity cannot control a T. gondii infection and if they have been infected previously, reactivation of a previous infection may occur. Congenital toxoplasmosis can cause severe complications in the fetuses of women who are infected with T. gondii during pregnancy. Toxoplasmosis can be serious in individuals with malignancies or AIDS. Since transplant recipients are immunosuppressed by drug treatment, they too are at risk for toxoplasmosis if they receive an organ from an infected donor. Vaccines against T. gondii suitable for human use have not been developed. No drug is available that can eliminate the encysted stage of the parasite; thus, infected individuals are always at risk for reactivation of the parasite if there is a failure of their immune system. More emphasis should be placed on the elimination of T. gondii by development of drugs which can eliminate the cyst stage in tissues and on development of vaccines suitable for protecting humans against infection or reactivation.

Taenia solium Neurocysticercosis 1.

After many years as a relatively rare neurological disorder, Taenia solium (pork tapeworm) neurocysticercosis is now seen more frequently in patients in the United States. Humans are the definitive and only hosts of the tapeworm stage. The larval stage develops in the pig, the intermediate host, following ingestion of tapeworm eggs excreted in the feces of the tapeworm carrier. The larvae invade most tissues of the pig giving rise to a disease termed cysticercosis. When humans ingest raw or undercooked meat from cysticercotic pigs, taeniasis (tapeworm) results. Humans can also act as intermediate hosts if they ingest T. solium eggs present in contaminated food or water; cysticercosis, similar to that seen in pigs, develops. If the larvae invade the central nervous system, neurocysticercosis with ensuing neurological dysfunction results. Cysticercotic pigs are rarely found in the United States. Only three animals out of >88 million federally inspected pigs were diagnosed as cysticercotic in 1990. In the United States, the excellent sewage disposal system prevents access of pigs to human feces and infection of pigs by T. solium eggs is consequently rare. In Mexico, however, the mean rate for cysticercotic pigs in inspected slaughter houses during 1980-1981 was 1.55% and there is little reason to suspect that it has decreased. In rural areas of Mexico and South America where sewage disposal is limited, the number of cysticercotic pigs can be in excess of 5% and neurocysticercosis is a common disease in the human population. In such areas, pigs are not penned or fed but depend on scavenging waste, including human waste, for food. Thus, the cycle of cysticercotic pigs infecting humans and tapeworm carriers infecting both humans and pigs is difficult to break in primitive rural areas. The incidence of neurocysticercosis is increasing in the United States due to an influx of immigrants from areas where T. solium is endemic. Most patients presenting with neurocysticercosis are of Mexican origin and probably acquired their disease in Mexico. However, several cases have been reported in people who have no history of travel to endemic areas and who were probably infected through ingestion of food prepared by an unhygienic food preparer who was also a tapeworm carrier. In this review, the life cycle of T. solium , parasite transmission, incidence of T. solium -related disease in pigs and humans, the disease process, drugs used in treatment, detection T. solium and destruction of T. solium eggs and cysticerci in foods are discussed. Food microbiologists must be aware of the increasing importance of T. solium as a disease agent and how to control T. solium -related diseases.