Use of software applications to improve medication adherence and achieve more integrated disease management in heart failure

The treatment and management of heart failure is associated with high mortality rates and treatment costs. Poor medication adherence is a major barrier to improving care and traditional interventions addressing non-adherence have not consistently demonstrated improvement in health care outcomes like readmission. The reasons for non-adherence are complicated and illustrate the broader challenges patients face when managing a complex disease like heart failure. In this review, a digitally enabled heart failure management platform consisting of medical digital tools and software solutions that are designed to be patient-facing and continuously accessed is explored as a way to integrate the multiple components of heart failure care and deliver personalized patient management tools.     

Problems in screening colorectal cancer in the elderly

AIM: To explore the problems in the screening of colorectal carcinoma in the elderly. METHODS: Three models of colorectal cancer prevention were examined: standard screening, active check-up of suspected cases and summons to have endoscopic check-up for previously diagnosed colorectal polyps. The study was performed among three groups of elderly individuals:Group 1 (167 cases), hospitalized asymptomatic individuals without symptoms in large intestines. Group 2 (612 cases):old individuals at home for the aged, out of which 32 showed symptoms of colon disorders; Group 3 (44 cases): elderlypeople with diagnosed polyps. As a result of 1788 rectosigmoidoscopies, we identified 61 individuals with polyps, out of which 44 patients were over 65 years old.However, only 9 of these 44 individuals agreed to have the endoscopy performed again.RESULTS: One cancer and 13 polyps were detected in Group 1, and two polyps in Group 2. However, it should be noted that only eleven individuals from Group 2 agreed to have the endoscopy. In Group 3, there were no relapses of the polyps among the nine individuals who came back for the endoscopy.CONCLUSION: Poor understanding of the screening procedures is one of the greatest problems in early detection of the cancer in the aged. Paradoxically, the cooperation is better with hospitalized patients, than with “successfully old“persons.     

Cytotoxicity, cellular uptake, and DNA interactions of new monodentate ruthenium(II) complexes containing terphenyl arenes

We have compared the cancer cell cytotoxicity, cell uptake, and DNA binding properties of the isomeric terphenyl complexes [(eta(6)-arene)Ru(en)Cl](+), where the arene is ortho- (2), meta- (3), or para-terphenyl (1) (o-, m-, or p-terp). Complex 1, the X-ray crystal structure of which confirms that it has the classical "piano-stool" geometry, has a similar potency to cisplatin but is not cross-resistant and has a much higher activity than 2 or 3. The extent of Ru uptake into A2780 or A2780cis cells does not correlate with potency. Complex 1 binds to DNA rapidly and quantitatively, preferentially to guanine residues, and causes significant DNA unwinding. Circular and linear dichroism, competitive binding experiments with ethidium bromide, DNA melting, and surface-enhanced Raman spectroscopic data are consistent with combined intercalative and monofunctional (coordination) binding mode of complex 1. This unusual DNA binding mode may therefore make a major contribution to the high potency of complex 1.     

Neurohormonal risk stratification for sudden death and death owing to progressive heart failure in chronic heart failure

BACKGROUND: This study tested various neurohormones for prediction of heart failure death (death owing to progressive deterioration of ventricular function; HFD). Moreover, B-type natriuretic peptide (BNP) as a predictor of sudden death (SD; as reported previously) and the best predictor of HFD were combined for a simple risk stratification model. DESIGN: BNP, the N-terminal fragment of BNP (N-BNP), and of the atrial natriuretic peptide (N-ANP) and big endothelin levels were obtained from 452 patients with a left ventricular ejection fraction 130 pg mL(-1) and N-ANP < 6300 fmol mL(-1) (Group B, n = 177; 18%; P = 0.0001) and patients with BNP > 130 pg mL(-1) and N-ANP > 6300 fmol mL(-1) (Group C, n = 50; 19%; P = 0.0001). Analyzing 293 survivors and 31 patients with HFD, fewer patients died in Group A (n = 109; 0%; P = 0.0001) and Group B (n = 153; 6%; P = 0.0001) as compared with patients of Group C (n = 62; 34%). CONCLUSION: Prognostic power of neurohormones depends on the mode of death. The combined determination of BNP and N-ANP identifies patients with minimal risk of death, elevated SD but low HFD risk as well as elevated SD and HFD risk.     

Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice

Expression levels of the papain-like cysteine protease cathepsin B (Ctsb) have been positively correlated with mammary tumour progression and metastasis; however, its roles in the hallmark processes of malignant growth remain poorly defined. Using Ctsb-deficient mice we investigated tumour cell differentiation, proliferation and apoptosis in the Tg(MMTV-PyMT) mouse mammary cancer model. Absence of Ctsb significantly impaired development of high-grade invasive ductal carcinomas and reduced the metastatic burden in the lungs. Mice lacking Ctsb exhibited reduced cell proliferation in mammary carcinomas and their lung metastases. Notably, intravenous injection of primarily isolated, Ctsb-expressing tumour cells into congenic Ctsb-deficient mice revealed impaired cell proliferation in the resulting experimental lung metastases, providing evidence for the involvement of Ctsb in paracrine regulation of cancer cell proliferation. No Ctsb genotype-dependent difference in tumour cell death was observed in vivo or by treatment of isolated PyMT cancer cells with tumour necrosis factor-alpha. However, cancer cells lacking Ctsb exhibited significantly higher resistance to apoptosis induction by the lysosomotropic agent Leu-Leu-OMe. Thus, our results indicate an in vivo role for Ctsb in promoting cellular anaplasia in mammary cancers and proliferation in lung metastases.     

3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis,and dismantling mitochondria in a syngeneic mouse model

Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. The majority of patients with locally advanced pancreatic cancer undergo chemotherapy and/or radiation therapy (RT). However, current treatments are inadequate and novel strategies are desperately required. 3-Bromopyruvate (3-BP) is a promising anticancer drug against pancreatic cancer. It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells. 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein. Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells. We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female mice. Immunohistochemistry data showed complete inhibition of hexokinase II (HK2) and TGFβ, in animals treated with 3-BP drug. We also observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death. Flow Cytometry analysis showed significant inhibition in MDSC (CD11b) population in treated tumor which may have allowed infiltration of CD8+ T cells and inhibited tumor growth. Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP. Importantly, we also observed inhibition in lactic acid production responsible for tumor aggression. These results provide new evidence that 3-BP severely inhibit glucose metabolism in cancer cells by blocking hexokinase II, and disrupting mitochondria by suppressing BCL2L1 in pancreatic cancer.     

Assessment of Maize Hybrids Resistance to Aspergillus Ear Rot and Aflatoxin Production in Environmental Conditions in Serbia

Aflatoxin, a naturally occurring toxin produced by the fungus Aspergillus flavus, is the most economically important mycotoxin in the world, with harmful effects on human and animal health. Preventive measures such as irrigation and planting dates can minimize aflatoxin contamination most years. However, no control strategy is completely effective when environmental conditions are extremely favorable for growth of the fungus. The most effective control method is growing maize hybrids with genetic resistance to aflatoxin contamination. The aim of this research was to evaluate the sensitivity of different maize hybrids to A. flavus infection and aflatoxin accumulation. Twenty commercial maize hybrids were evaluated in field trials with artificial inoculations using the colonized toothpicks method. The mycotoxin production potential of A. flavus isolates was confirmed by cluster amplification patterns (CAPs) analysis. The results of this research indicated the existence of significant differences in maize hybrids susceptibility to Aspergillus ear rot and aflatoxin B₁ accumulation. No hybrid included in this research showed complete resistance in all conditions, but some hybrids showed partial resistance. Different hybrids also responded differently depending on the sowing date. This research showed that infection intensity is not always consistent with aflatoxin levels, and therefore visual evaluation is not enough to assess maize safety.     

Tumor microvasculature supports proliferation and expansion of glioma‐propagating cells

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The identification of ‘cancer stem cells’ (CSC) has shed new light on the potential mechanism of therapy resistance of these tumors. Because these cells appear to be more resistant to conventional treatments, they are thought to drive tumor regrowth after therapy. Therefore, novel therapeutic approaches that target these cells are needed. Tumor cells interact with their microenvironment. It has been reported that close contact between CSCs and tumor microvascular endothelium in GBM is important for CSCs to preserve their undifferentiated state and self‐renewal ability. However, our understanding of this interaction is still rudimentary. This is in part due to a lack of suitable in vitro models that accurately represent the in vivo situation. Therefore, we set up a co‐culture system consisting of primary brain tumor microvascular endothelial cells (tMVECs) and glioma propagating cells (GPCs) derived from biopsies of GBM patients. We found that tMVECs support the growth of GPCs resulting in higher proliferation rates comparing to GPCs cultured alone. This effect was dependent on direct contact between the 2 cell types. In contrast to GPCs, the FCS‐cultured cell line U87 was stimulated by culturing on tMVEC‐derived ECM alone, suggesting that both cell types interact different with their microenvironment. Together, these results demonstrate the feasibility and utility of our system to model the interaction of GPCs with their microenvironment. Identification of molecules that mediate this interaction could provide novel targets for directed therapy for GBM. © 2009 UICC