Randomized controlled trial of a lay-facilitated angina management programme

furze g., cox h., morton v., chuang l.-h., lewin r.j.p., nelson p., carty r., norris h., patel n. & elton p. (2012)?Randomized controlled trial of a lay-facilitated angina management programme. Journal of Advanced Nursing68(10), 2267-2279. ABSTRACT: Aims. This article reports a randomized controlled trial of lay-facilitated angina management (registered trial acronym: LAMP). Background. Previously, a nurse-facilitated angina programme was shown to reduce angina while increasing physical activity, however most people with angina do not receive a cardiac rehabilitation or self-management programme. Lay people are increasingly being trained to facilitate self-management programmes. Design. A randomized controlled trial comparing a lay-facilitated angina management programme with routine care from an angina nurse specialist. Methods. Participants with new stable angina were randomized to the angina management programme (intervention: 70 participants) or advice from an angina nurse specialist (control: 72 participants). Primary outcome was angina frequency at 6?months; secondary outcomes at 3 and 6?months included: risk factors, physical functioning, anxiety, depression, angina misconceptions and cost utility. Follow-up was complete in March 2009. Analysis was by intention-to-treat; blind to group allocation. Results. There was no important difference in angina frequency at 6?months. Secondary outcomes, assessed by either linear or logistic regression models, demonstrated important differences favouring the intervention group, at 3?months for: Anxiety, angina misconceptions and for exercise report; and at 6?months for: Anxiety; Depression; and angina misconceptions. The intervention was considered cost-effective. Conclusion. The angina management programme produced some superior benefits when compared to advice from a specialist nurse.     

Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic

ABSTRACT: BACKGROUND: CCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS and countries in Subsahara Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of country circulating HIV strains to guide the impending use of CCR5 antagonists. Objectives: To determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya METHODS: Blood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIV env fragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of the env sequences was done using Geno2pheno [co-receptor]. and. phylogenetic relationships determined using CLUSTAL W and Neighbor Joining method. RESULTS: A total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistically significant associations were observed between cell tropism and CD4+ status, patient gender, age, or type of treatment regimen. There was a tendency for more X4 tropic strains being in the treatment experienced than the naive group 14/18 (78%), though not statistically significant (p=0.31). However, a strong association was observed between subtype D and CXCR4 co-receptor usage (p=0.015). CONCLUSION: HIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.     

Molecular cytogenetic characterization of an interstitial deletion of chromosome 21 (21q22.13q22.3) in a patient with dysmorphic features, intellectual disability and severe generalized epilepsy

We report on a de novo interstitial deletion of chromosome 21q in a patient presenting with characteristic facial features, intellectual disability, and epilepsy. The deletion extent was about 4.9 Mb from position 37713441 bp (21q22.13) to position 42665162 bp (21q22.3) (NCBI36/hg18 map).Patients with partial monosomy 21 are quite rare; this anomaly has been associated with a wide spectrum of clinical signs, ranging from very mild to quite severe phenotypes. This variability results from variability in the deleted regions, thus accurate molecular definition of the chromosomal breakpoints is necessary to make better genotype-phenotype correlations.We compared our patient's phenotype with the few other patients reported in the literature and found to have similar deletion when analyzed by array CGH. The minimal overlapping region contains only two genes, DYRK1A and KCNJ6, which may play a major role in these patients' phenotype.     

Breakthrough Pain in Patients Referred to Pain Clinics: The Italian Pain Network Retrospective Study

Introduction

Despite breakthrough pain (BTP) being one of the most severe forms of pain, there are no definitive data on its prevalence.

Methods

The authors performed a retrospective survey of the prevalence of BTP in consecutive patients in four Italian pain clinics, subsequent to application of an Italian law mandating detailed clinical records on pain characteristics, treatment, and results. Mean pain intensity was assessed with a numerical rating scale from 0 to 10.

Results

The authors analyzed records of 1,401 patients (58% women, 33.1% patients with cancer). Transient episodes of severe pain or BTP were referred by 790 patients (56.4%), including 58.2% of the men (342 of 588) and 55.1% of the women (448 of 813). Among the 464 patients with cancer, 70.3% reported daily exacerbation of pain. The mean BTP intensity was 8.31 ± 1.58 and 31.1% of patients reported experiencing three episodes per day.

Conclusion

Despite some limitations of the study, the authors show that transient episodes of severe pain or BTP are significantly present both in cancer and other diseases, and that many patients are not yet receiving appropriate opioid therapy. The authors need validated tools at international level for the diagnosis and treatment of BTP in patients with cancer and for transitory and patients with severe non-cancer pain. A survey at national level is needed to estimate the prevalence of BTP in different settings, to plan specific medical education.     

Interaction between NH(2)-tau fragment and Aβ in Alzheimer's disease mitochondria contributes to the synaptic deterioration

Although amyloid beta (Aβ) peptide can promote tau pathology and its toxicity is concurrently tau-dependent, the underlying mechanisms of the in vivo interplay of these proteins remain unsolved. Structural and functional mitochondrial alterations play an early, precipitating role in synaptic failure of Alzheimer's disease (AD) pathogenesis and an aggravated mitochondrial impairment has been described in triple APP/PS/tau transgenic mice carrying both plaques and tangles, if compared with mice overexpressing tau or amyloid precursor protein (APP) alone. Here, we show that a neurotoxic aminoterminal (NH(2))-derived tau fragment mapping between 26 and 230 amino acids of the human tau40 isoform (441 amino acids)-but not the physiological full-length protein-preferentially interacts with Aβ peptide(s) in human AD synapses in association with mitochondrial adenine nucleotide translocator-1 (ANT-1) and cyclophilin D. The two peptides-Aβ 1-42 and the smaller and more potent NH(2)-26-44 peptide of the longest 20-22 kDa NH(2)-tau fragment-inhibit the ANT-1-dependent adenosine diphosphate-adenosine triphosphate (ADP/ATP) exchange in a noncompetitive and competitive manner, respectively, and together further aggravate the mitochondrial dysfunction by exacerbating the ANT-1 impairment. Taken together, these data establish a common, direct and synergistic toxicity of pathological APP and tau products on synaptic mitochondria and suggest potential, new pathway(s) and target(s) for a combined, more efficient therapeutic intervention of early synaptic dysfunction in AD.     

Soluble TRAIL is elevated in recurrent miscarriage and inhibits the in vitro adhesion and migration of HTR8 trophoblastic cells

STUDY QUESTION: What is the potential physiopathological role of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in recurrent miscarriage (RM), characterized by at least three consecutive pregnancy losses. SUMMARY ANSWER: The levels of serum TRAIL immediately after miscarriage in RM patients are significantly elevated with respect to that in first-trimester normal pregnant women, and recombinant TRAIL inhibits the adhesion and migration of HTR8 trophoblastic cells in vitro. WHAT IS KNOWN ALREADY: Both TRAIL and its trans-membrane receptors (TRAIL-R1, TRAIL-R2, TRAIL-R3?and TRAIL-R4) have been documented in the placenta, but their physiopathological role is incompletely understood. STUDY DESIGN, SIZE, DURATION: The study populations consisted of RM patients (n = 80) and first-trimester normal pregnant women (n = 80). Blood samples were obtained within 24 h after abortion (RM) or at gestational 12-week (normal pregnant women). As additional controls, third-trimester normal pregnant women (n = 28) were examined before (within 72 h) and after (within 24 h) partum. PARTICIPANTS/MATERIALS, SETTING, METHODS: The concentrations of TRAIL were analysed in serum samples by ELISA. In parallel, the effect of soluble recombinant TRAIL (0.1-1000 ng/ml) was analysed on the survival of primary extravillus trophoblasts (EVTs) and on the survival, proliferation, adhesion and migration of trophoblastic HTR8 cells. MAIN RESULTS AND THE ROLE OF CHANCE: The circulating levels of TRAIL in RM women (median: 52.5 pg/ml; mean and SD: 55.5 ± 24.4 pg/ml) were significantly higher with respect to first-trimester normal pregnant women (median: 44.9 pg/ml; mean and SD: 47 ± 15.1 pg/ml) and third-trimester normal pregnant women, as assessed before (median: 45.1 pg/ml; mean and SD: 46 ± 12.4 pg/ml) and after partum (median: 35.4 pg/ml; mean and SD: 38 + 17.5 pg/ml). Both primary EVT and HTR8 cells expressed detectable levels of TRAIL death receptors, but exposure to soluble recombinant TRAIL did not induce cell death of trophoblastic cells. On the other hand, TRAIL dose-dependently inhibited the adhesion of HTR8 cells to decidual endothelial cells (DEC) as well as the migration of HTR8 in transwell assays using either fibronectin or DEC. LIMITATIONS, REASONS FOR CAUTION: Although this study suggests that TRAIL might have a pathogenic role in RM by inhibiting both the adhesion and migration capabilities of first trimester trophoblastic cells, there is a possibility that the elevated serum levels of TRAIL in RM are not cause but rather the result of RM. WIDER IMPLICATIONS OF THE FINDINGS: Our current findings together with data of other authors suggest that circulating TRAIL should be further analysed as a potential important biomarker in different physiopathological settings. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by FIRB projects (RBAP11Z4Z9_002 to Giorgio Zauli and RBAP10447J_002 to Paola Secchiero). The authors have no competing interests to declare.     

Error-related negativity in individuals with obsessive-compulsive symptoms: toward an understanding of hoarding behaviors

The error-related negativity (ERN), an event-related potential component elicited by error responses in cognitive tasks, has been shown to be abnormal in most, but not all, studies of obsessive-compulsive disorder or obsessive-compulsive symptoms (OCD/S); these inconsistencies may be due to task selection, symptom subtype, or both. We used meta-analysis to further characterize the ERN in OCD/S, and pooled data across studies to examine the ERN in OCD/S with hoarding. We found an enhanced ERN in OCD/S relative to controls, as well as heterogeneity across tasks. When stratified, OCD/S showed a significantly enhanced ERN only in response conflict tasks. However, OCD/S + hoarding showed a marginally larger ERN than OCD/S-hoarding, but only for probabilistic learning tasks. These results suggest that abnormal ERN in OCD/S is task-dependent, and that OCD/S + hoarding show different ERN activity from OCD/S − hoarding perhaps suggesting different pathophysiological mechanisms of error monitoring.     

Distinctive features of classic and nonclassic (Th17 derived) human Th1 cells

T helper17 (Th17) lymphocytes represent a third arm of the CD4⁺ T‐cell effector responses, in addition to Th1 and Th2 cells. Th17 cells have been found to exhibit high plasticity because they rapidly shift into the Th1 phenotype in inflammatory sites. In humans, Th1 cells derived from Th17 cells express CD161, whereas classic Th1 cells do not; these Th17‐derived Th1 cells have been termed nonclassic Th1 cells. In this study, we examined similarities and differences between classic and nonclassic human Th1 cells by assessing a panel of T‐cell clones, as well as CD161⁺ or CD161^? CD4⁺ T cells derived ex vivo from the circulation of healthy subjects or the synovial fluid of patients with juvenile idiopathic arthritis. The results show that nonclassic Th1 cells can be identified based on CD161 expression, as well as the consistent expression of retinoic acid orphan receptor C, IL‐17 receptor E, CCR6, and IL‐4‐induced gene 1, which are all virtually absent in classic Th1 cells. The possibility to distinguish these two‐cell subsets by using such a panel of markers may allow the opportunity to better establish the respective pathogenic roles of classic and nonclassic (Th17 derived) Th1 cells in different chronic inflammatory disorders.