Longitudinal Relationships Between Depression and Functioning in People with Type 2 Diabetes

Background

The reciprocal relationship between depression and functioning in people with chronic conditions is poorly understood.

Purpose

The aim of the present study was to analyze the dynamic relationship between depression and functioning in a community sample of people with diabetes.

Methods

Participants with diabetes were assessed at baseline and three yearly follow-up assessments (n?=?1,403). Depression was assessed using the Patient Health Questionnaire. Global functioning was assessed using the World Health Organization Disability Assessment Schedule II.

Results

Path analysis suggested a reciprocal relationship between depression and functioning. Baseline depression was associated with functioning at 3 years follow-up through depression and functioning at 1 and 2 years follow-up assessments.

Conclusions

Depression and functioning might interact with each other in a dynamic way: depression at one assessment point might predict poor functioning at the next assessment point, which in turn might predict depression at the next assessment point. This should be taken into account in both treatment and research programs.     

Patient stratification for risk of readmission due to heart failure by using nationwide administrative data

BackgroundIdentifying patients with heart failure (HF) who are most at risk of readmission permits targeting adapted interventions. The use of administrative data enables regulators to support the implementation of such interventions.Methods and ResultsIn a French nationwide cohort of patients aged 65 years or older, surviving an index hospitalization for HF in 2015 (N = 70,657), we studied HF readmission predictors available in administrative data, distinguishing HF severity from overall morbidity and taking into account the competing mortality risk, over a 1-year follow-up period. We also computed cumulative incidences and daily rates of HF readmission for patient groups defined according to HF severity and overall morbidity. Of the patients, 31.8% (n = 22,475) were readmitted at least once for HF, and 17.6% (n = 12,416) died without any readmission for HF. HF severity and overall morbidity were the strongest readmission predictors were the strongest readmission predictors (subdistribution hazard ratios 2.66 [95% CI: 2.52–2.81] and 1.37 [1.30–1.45], respectively, when comparing extreme categories). Overall morbidity and age were more strongly associated with the rate of death without HF readmission (cause-specific hazard ratios). The difference in observed HF readmission between patient risk groups was approximately 40% (21.9%, n = 2144/9,786 vs 60.4%, n = 618/1023).ConclusionsSegmentation of HF patients into readmission risk groups is possible by using administrative data, and it enables the targeting of preventive interventions.     

Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils

Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration.     

Selective Thymic Localization of Murine Leukemia Virus-Related Antigens in C57BL/Ka Mice after Inoculation with Radiation Leukemia Virus

The tissue distribution and extent of virus-specific antigen expression were studied by immunofluorescence as a function of time and of lymphoma development in adult C57BL/Ka (Fv-1(b)) mice after intravenous injection of radiation leukemia virus, a B-tropic murine leukemia virus. Viral antigens were detected earlier in the thymus (1 week) than in the bone marrow, spleen, or lymph nodes (2-3 weeks). Despite an initial virus-induced thymic involution, the percentage of immunofluorescence-positive cells in the thymus rapidly increased thereafter to 65-80%, at which level it remained until 9 weeks, at which time increases in size and weight, histological changes, and an increased number of blastoid cells indicated the onset of lymphoma development in the thymus. In contrast, the percentage of immunofluorescence-positive cells in the bone marrow, spleen, and nodes remained low, and gradually decreased to zero within 8 weeks after thymectomy. The selective thymic localization of antigens induced by radiation leukemia virus in C57BL/Ka mice is in striking contrast to the previously reported ubiquitous tissue distribution of the Gross-AKR virus, an N-tropic virus, in its natural host, the Fv-1(n), AKR strain with a high incidence of leukemia.     

Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms.

Effects of the stable somatostatin analogue RC-160 on cell proliferation, tyrosine phosphatase activity, and intracellular calcium concentration were investigated in CHO cells expressing the five somatostatin receptor subtypes SSTR1 to -5. Binding experiments were performed on crude membranes by using [125I-labeled Tyr11] somatostatin-14; RC-160 exhibited moderate-to-high affinities for SSTR2, -3, and -5 (IC50, 0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50, 200 and 620 nM, respectively). Cell proliferation was induced in CHO cells by 10% (vol/vol) fetal calf serum, 1 microM insulin, or 0.1 microM cholecystokinin (CCK)-8; RC-160 inhibited serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 (EC50, 53 and 150 pM, respectively) but had no effect on growth of cells expressing SSTR1, -3, or -4. In SSTR2-expressing cells, orthovanadate suppressed the growth inhibitory effect of RC-160. This analogue inhibited insulin-induced proliferation and rapidly stimulated the activity of a tyrosine phosphatase in only this cellular clone. This latter effect was observed at doses of RC-160 (EC50, 4.6 pM) similar to those required to inhibit growth (EC50, 53 pM) and binding to the receptor (IC50, 170 pM), implicating tyrosine phosphatase as a transducer of the growth inhibition signal in SSTR2-expressing cells. In SSTR5-expressing cells, the phosphatase pathway was not involved in the inhibitory effect of RC-160 on cell growth, since this action was not influenced by tyrosine and serine/threonine phosphatase inhibitors. In addition, in SSTR5-expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC50, 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC50, 1.1 nM). This suggests that the inositol phospholipid/calcium pathway could be involved in the antiproliferative effect of RC-160 mediated by SSTR5 in these cells. RC-160 had no effect on the basal or carbachol-stimulated calcium concentration in cells expressing SSTR1 to -4. Thus, we conclude that SSTR2 and SSTR5 bind RC-160 with high affinity and mediate the RC-160-induced inhibition of cell growth by distinct mechanisms.     

Photodynamic therapy with green light and m-tetrahydroxyphenyl chlorin for intramucosal adenocarcinoma and high-grade dysplasia in Barrett's esophagus

BACKGROUND: The eradication of early stage neoplastic lesions in Barrett's esophagus is imperative to prevent invasive adenocarcinoma. Early stage lesions have an extremely low risk of lymph node metastasis, thereby, making local treatment feasible. Photodynamic therapy destroys malignant cells by a photochemical effect. The aims of this study were to evaluate the efficacy and tolerance of photodynamic therapy with green light and a new photosensitizer, temoporfin or m-tetrahydroxyphenyl chlorin in patients with Barrett's esophagus and early stage neoplastic lesions. METHODS: Four days after injection of m-tetrahydroxyphenyl chlorin, lesions were illuminated at a wavelength of 514 nm through non-circumferential windowed diffusers. Follow-up endoscopy with biopsies was performed at regular intervals. RESULTS: Fourteen lesions (7 high-grade dysplasia, 7 intramucosal adenocarcinoma) in 12 patients were treated. For all lesions, efficacy was 100% and squamous re-epithelialization was complete. Side effects were of moderate severity (one stricture). Mean follow-up was 34 (15) months (range 12-68 months). CONCLUSIONS: Green light photodynamic therapy with m-tetrahydroxyphenyl chlorin can eradicate early stage neoplastic lesions in Barrett's esophagus and may be proposed as an alternative first-line therapy or a second-line therapy after failure of other endoscopic treatments. The efficacy and patient tolerance of the procedure justify further studies of the method in larger groups of patients.     

Diastolic asynchrony is more frequent than systolic asynchrony in dilated cardiomyopathy and is less improved by cardiac resynchronization therapy.

OBJECTIVES: To compare the incidence of diastolic and systolic asynchrony, assessed by tissue Doppler imaging (TDI), in patients with congestive heart failure (CHF) and severe left ventricular (LV) dysfunction, and to assess TDI changes induced by cardiac resynchronization therapy (CRT). BACKGROUND: Thirty percent of CRT candidates are nonresponders. Besides QRS width, the presence of echographic systolic asynchrony has been used to identify future responders. Little is known about diastolic asynchrony and its change after CRT. METHODS: Tissue Doppler imaging was performed in 116 CHF patients (LV ejection fraction 26 +/- 8%). Systolic and diastolic asynchrony was calculated using TDI recordings of right ventricular and LV walls. RESULTS: The CHF group consisted of 116 patients. Diastolic asynchrony was more frequent than systolic, concerning both intraventricular (58% vs. 47%; p = 0.0004) and interventricular (72 vs. 45%; p < 0.0001) asynchrony. Systolic and diastolic asynchrony were both present in 41% patients, but one-third had isolated diastolic asynchrony. Although diastolic delays increased with QRS duration, 42% patients with narrow QRS presented with diastolic asynchrony. Conversely, 27% patients with large QRS had no diastolic asynchrony. Forty-two patients underwent CRT. Incidence of systolic intraventricular asynchrony decreased from 71% to 33% after CRT (p < 0.0001), but diastolic asynchrony decreased only from 81% to 55% (p < 0.0002). Cardiac resynchronization therapy induced new diastolic asynchrony in eight patients. CONCLUSIONS: Diastolic asynchrony is weakly correlated with QRS duration, is more frequent than systolic asynchrony, and may be observed alone. Diastolic asynchrony is less improved by CRT than systolic. Persistent diastolic asynchrony may explain some cases of lack of improvement after CRT despite good systolic resynchronization.     

Surgically created neural pathways mediate visual pattern discrimination

Combined lesions of retinal targets and ascending auditory pathways can induce, in developing animals, permanent retinal projections to auditory thalamic nuclei and to visual thalamic nuclei that normally receive little direct retinal input. Neurons in the auditory cortex of such animals have visual response properties that resemble those of neurons in the primary visual cortex of normal animals. Therefore, we investigated the behavioral function of the surgically induced retino-thalamo-cortical pathways. We showed that both surgically induced pathways can mediate visually guided behaviors whose normal substrate, the pathway from the retina to the primary visual cortex via the primary thalamic visual nucleus, is missing.