Randomized clinical trial of a community navigation intervention to improve well-being in persons living with HIV and other co-morbidities

Long-term survival of people living with HIV (PLWH) is associated with the development of co-morbid conditions and need for symptom management and other efforts to enhance quality of life. We conducted a longitudinal, randomized trial over 36 months to evaluate the effect of a community-based navigator intervention to provide early palliative care to 179 PLWH and other chronic conditions. Outcomes included quality of life, symptom management, coping ability, social support, self-management, and completion of advance directives. Data were analyzed using SAS mixed effects model repeat measurement. Our navigator program showed variable improvement over time of three outcome variables, self-blame, symptom distress, and HIV self-management. However, the program did not improve overall quality of life, social support, or completion of advance directives.     

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the β₁-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the β₁ adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-β₁ receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.     

Notch signaling is necessary but not sufficient for differentiation of dendritic cells

The Notch family of receptors plays an important role in regulation of cell differentiation via direct contact between hematopoietic progenitor cells (HPCs) and bone marrow stroma (BMS). However the precise contribution of Notch in dendritic cell (DC) differentiation is controversial. In 2 different experimental systems using Notch-1-null embryonic stem cells and Notch-1-deficient HPCs we have found that Notch-1 is necessary for DC differentiation. However, activation of Notch-1 and Notch-2 with cell-bound Notch ligand did not result in differentiation of mature DCs or macrophages. Instead, it caused accumulation of immature myeloid cells. Removal of feeder cells resulted in rapid differentiation of DCs and macrophages. Addition of interleukin 4 (IL-4) into the culture dramatically increased accumulation of functionally potent DCs. Lipopolysaccharide was not able to reproduce this effect. Thus, these data indicate that Notch signaling prevents differentiation of mature myeloid cells. Instead, it results in accumulation of precursors readily able to differentiate into mature DCs once the Notch signal is stopped (eg, after cell emigration from bone marrow) and in the presence of other additional differentiation signals provided by IL-4. Thus, Notch is required but not sufficient for DC differentiation.     

Hydrogen Gas Phase and Electrochemical Hydriding of LaNi5−xMx (M = Sn,Co, Al) Alloys

Hydriding/dehydriding properties of a series of LaNi₅ based alloys were compared by applying both hydrogen gas phase and electrochemical hydrogen charge/discharge methods. The highest hydrogen absorption capacity of 1.4 wt.% H₂ was found for LaNi_4.3Co_0.4Al_0.3, although LaNi_4.8Sn_0.2 also reveals comparable hydrogen capacity (>1.3%). A significant difference in the hydriding kinetics was observed for all studied alloys before and after activation. The activated alloys (5 cycles at 65 °C, 40 atm. H₂) reach their maximum capacities after less than a minute, whereas the pure LaNi₅ alloy needs several minutes for complete hydriding. The electrochemical hydriding/dehydriding behavior of the alloys reveals superior performance of LaNi_4.3Co_0.4Al_0.3 and LaNi_4.8Sn_0.2 compared to the other compositions studied, as the capacity of LaNi_4.8Sn_0.2 decreases by only 10% for 60 charge/discharge cycles at a current density of 100 mA/g. Good agreement between the hydrogen sorption kinetics of the alloys obtained electrochemically and from hydrogen gas phase has also been observed.     

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms

Background

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease.

Methods

Cross-sectional, case–control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication.

Results

The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16–4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24–5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12–3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76–6.36).

Conclusion

Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms.     

Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels

Introduction Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF‐I, GH‐binding protein (GHBP), IGF‐binding proteins (IGFBPs) and acid‐labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. Aim of the study To explore whether GH secretion and/or levels of IGF‐I, IGFBP‐3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. Materials and methods A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age‐ and BMI‐matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF‐I, GHBP, IGFBP‐3, ALS and GH after GHRH and arginine stimulation test. Results As expected, patients with NAFLD had blood glucose, insulin, HOMA‐R significantly higher than controls, indicating a more severe insulin‐resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP‐3 and lower GH peak and IGF‐I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF‐1 was negatively associated with hepatic steatosis. Conclusions This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF‐I axis is significantly altered probably leading to reduced IGF‐I bioavailability at tissue level.     

Metabolic control and risk of hypoglycaemia during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis

Aim: Aim of this study was to analyse clinical correlates of HbA1c, and of overall, nocturnal, and severe hypoglycaemia, through direct‐weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta‐analysis. Methods: Appropriate methodology (PRISMA statement) was used. Sixty‐seven randomized studies, published as full papers were analysed to identify predictors of both HbA1c and hypoglycaemia; studies were included in a meta‐analysis to study the effect of different insulin regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of insulin treatment in type 2 diabetes patients. Results: Final HbA1c, change of HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were associated with intensity of treatment. Final HbA1c was higher with basal than with twice‐a‐day or prandial, and with twice‐a‐day than with prandial regimen, with opposite figures for hypoglycaemia. Within basal regimens, detemir and glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and nocturnal hypoglycaemia; within prandial regimens, new analogues were more effective than regular insulin on HbA1c, and induced less hypoglycaemia. The effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number of insulin injections. Conclusion: Metabolic control and hypoglycaemia are associated with intensity of treatment. Basal regimens have a reduced effect on metabolic control, but are associated with lower frequency of hypoglycaemia. Newer analogues, short‐ and long‐acting, yield better control and less hypoglycaemia than older analogues.