Implementation of an Enhanced Recovery after Surgery Pathway to Reduce Inpatient Opioid Consumption after Cesarean Delivery.

OBJECTIVE: Opioid prescription after cesarean delivery is excessive and can lead to chronic opioid use disorder. We assessed the impact of an enhanced recovery after surgery (ERAS) pathway on inpatient opioid consumption after cesarean delivery. STUDY DESIGN: An ERAS pathway was implemented as a quality improvement initiative in December 2019. Preintervention (PRE) data were collected from March to May 2019 to assess baseline opioid consumption. Postintervention (POST) data were collected from January to March 2020. The primary outcome was inpatient postoperative opioid consumption in morphine milligram equivalents (MME). Secondary outcomes included the consumption of any opioids, postpartum length of stay, and opioid prescription at discharge. RESULTS: A total of 92 women were in the PRE group and 91 were in the POST group. Inpatient opioid consumption decreased by 87.3% from PRE to POST, from 124.7 (interquartile range [IQR]: 10-181.6) MME to 15.8 (IQR: 0-75) MME (p < 0.001). There was no difference in median postpartum length of stay (3.4 days PRE vs. 3.3 days POST; p = 0.12). The proportion of women who did not consume any opioids increased by 75.4% from PRE to POST (p = 0.02). The proportion of women discharged with an opioid prescription decreased by 25.6% from PRE to POST (p = 0.007), despite no formal change to prescribing practices. After adjustment for differences in race/ethnicity and gravidity, there was still a reduction in total inpatient opioid consumption (p < 0.001) and an increase in the proportion of women not consuming any opioids (adjusted relative risk (RR): 2.14, 95% confidence interval [CI]: 1.18-3.87), but the difference in rate of prescription of opioids at discharge was no longer statistically significant (adjusted RR: 0.70, 95% CI: 0.48-1.02). CONCLUSION: Adoption of an ERAS pathway for cesarean delivery resulted in a marked reduction in inpatient opioid consumption. Such a pathway can be implemented across institutions and may be a powerful tool in combating the opioid epidemic. KEY POINTS: · ERAS after cesarean reduces inpatient opioid consumption.. · ERAS after cesarean increases the proportion of women not consuming any opioids.. · This pathway can be feasibly adopted elsewhere..

Acute lymphoblastic leukemia-derived extracellular vesicles affect quiescence of hematopoietic stem and progenitor cells.

Patient-derived xenografted (PDX) models were generated through the transplantation of primary acute lymphoblastic leukemia (ALL) cells into immunodeficient NSG mice. We observed that ALL cells from mouse bone marrow (BM) produced extracellular vesicles (EVs) with specific expression of inducible heat shock protein HSP70, which is commonly activated in cancer cells. Taking advantage of this specific expression, we designed a strategy to generate fluorescent HSP70-labeled ALL EVs and monitor the impact of these EVs on endogenous murine BM cells ex vivo and in vivo. We discovered that hematopoietic stem and progenitor cells (HSPC) were mainly targeted by ALL EVs, affecting their quiescence and maintenance in the murine BM environment. Investigations revealed that ALL EVs were enriched in cholesterol and other metabolites that contribute to promote the mitochondrial function in targeted HSPC. Furthermore, using CD34+ cells isolated from cord blood, we confirmed that ALL EVs can modify quiescence of human HSPC. In conclusion, we have discovered a new oncogenic mechanism illustrating how EVs produced by proliferative ALL cells can target and compromise a healthy hematopoiesis system during leukemia development.

Therapist Adherence to Two Treatments for Adolescent Suicide Risk: Association to Outcomes and Role of Therapeutic Alliance.

In psychotherapy research, adherence refers to the extent to which therapists deliver a treatment as intended. This study examined whether therapist adherence to two different manualized treatments was associated with improved client outcomes and whether the association was moderated by therapeutic alliance. The study sample included 320 video recordings of therapy sessions from 118 cases in a randomized controlled trial (RCT) comparing attachment-based family therapy (ABFT) with family-enhanced nondirective supportive therapy (FE-NST). Recordings were selected from early, middle, and late stages of treatment. The adherence measure consisted of 24 items representing essential therapist interventions from both treatments. Trained raters coded tapes from both therapies. Adolescent self-report of alliance was measured at session 4. Adherence to ABFT was associated with a significant increase in family cohesion at mid-treatment but not at posttreatment. Adherence to FE-NST was significantly associated with an increase in suicide ideation posttreatment. Using therapeutic alliance as a moderator, adherence to ABFT was significantly associated with a reduction in suicide ideation, family conflict, and higher client satisfaction posttreatment. Alliance did not positively affect the association of FE-NST adherence to outcomes. Findings suggest that adherence to ABFT interventions may be better linked to treatment outcomes when adolescents feel a strong alliance with their therapist. Implications for future research and therapist training are explored.

En la investigación sobre psicoterapia, la adhesión se refiere al grado en el cual los terapeutas brindan un tratamiento según lo previsto. Este estudio analizó si la adhesión del terapeuta a dos tratamientos estandarizados diferentes estuvo asociada con mejores resultados en los pacientes y si la asociación estuvo moderada por la alianza terapéutica. La muestra del estudio incluyó 320 videograbaciones de sesiones de terapia de 118 casos en un ensayo aleatorizado controlado donde se comparó la terapia familiar basada en el apego (TFBA) con la terapia de apoyo no directiva optimizada por la familia (TAND-OF). Se eligieron grabaciones de las etapas iniciales, intermedias y finales del tratamiento. El instrumento de medición de la adhesión consistió en 24 ítems que representaban intervenciones esenciales del terapeuta de ambos tratamientos. Un grupo de calificadores capacitados codificaron las grabaciones de ambas terapias. El autoinforme de alianza de los adolescentes se midió en la cuarta sesión. La adhesión a la TFBA estuvo asociada con un aumento considerable de la cohesión familiar en la mitad del tratamiento, pero no después del tratamiento. La adhesión a la TAND-OF estuvo asociada considerablemente con un aumento de la ideación suicida después del tratamiento. Utilizando la alianza terapéutica como moderadora, la adhesión a la TFBA estuvo asociada considerablemente con una reducción de la ideación suicida, el conflicto familiar y una mayor satisfacción del paciente después del tratamiento. La alianza no afectó positivamente la asociación de la adhesión a la TAND-OF con los resultados. Los resultados sugieren que la adhesión a las intervenciones de TFBA puede asociarse mejor con los resultados del tratamiento cuando los adolescentes sienten una alianza fuerte con su terapeuta. Se analizan las implicancias para futuras investigaciones y para la capacitación de los terapeutas.

Exploring the relations between interpersonal risk and adolescent suicidality during treatment.

OBJECTIVE: Despite considerable evidence that supports perceived burdensomeness (PB) and thwarted belongingness (TB) as risk factors for suicidal ideation (SI), far less is known about the direction of effects between these constructs in treatments for suicidal adolescents. The present study examined bidirectional relations between PB, TB, and adolescents' suicidal ideation (SI) during a 16-week randomized clinical trial. METHOD: 129 depressed and suicidal adolescents completed PB, TB, and SI measures at three time points: baseline (T1), mid-treatment (T2), and treatment completion (T3). Random-intercept cross-lagged panel models (RI-CLPM) examined within-subject direction of effects between interpersonal variables (PB & TB) and suicidal ideation (SI) in the first and second halves of treatment. RESULTS: Within-subjects, autoregressive paths indicated significant carryover in PB and SI. In the first half of treatment, a significant cross-lagged path indicated that T1 PB predicted change in T2 SI, and in the last half of treatment change in T2 SI predicted change in T3 PB. There were no significant auto-regressive or cross-lagged effects for TB. CONCLUSIONS: In the first half of treatment, baseline PB predicted fewer reductions in SI suggesting that PB initially moderated adolescents' response to treatment. However, in the last half of treatment, initial reductions in SI predicted subsequent reductions in PB suggesting that adolescents' initial response to treatment decreased their perceptions of burdening others. The clinical and treatment implications of these bidirectional findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Stream Dissolved Organic Matter in Permafrost Regions Shows Surprising Compositional Similarities but Negative Priming and Nutrient Effects.

Permafrost degradation is delivering bioavailable dissolved organic matter (DOM) and inorganic nutrients to surface water networks. While these permafrost subsidies represent a small portion of total fluvial DOM and nutrient fluxes, they could influence food webs and net ecosystem carbon balance via priming or nutrient effects that destabilize background DOM. We investigated how addition of biolabile carbon (acetate) and inorganic nutrients (nitrogen and phosphorus) affected DOM decomposition with 28-day incubations. We incubated late-summer stream water from 23 locations nested in seven northern or high-altitude regions in Asia, Europe, and North America. DOM loss ranged from 3% to 52%, showing a variety of longitudinal patterns within stream networks. DOM optical properties varied widely, but DOM showed compositional similarity based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis. Addition of acetate and nutrients decreased bulk DOM mineralization (i.e., negative priming), with more negative effects on biodegradable DOM but neutral or positive effects on stable DOM. Unexpectedly, acetate and nutrients triggered breakdown of colored DOM (CDOM), with median decreases of 1.6% in the control and 22% in the amended treatment. Additionally, the uptake of added acetate was strongly limited by nutrient availability across sites. These findings suggest that biolabile DOM and nutrients released from degrading permafrost may decrease background DOM mineralization but alter stoichiometry and light conditions in receiving waterbodies. We conclude that priming and nutrient effects are coupled in northern aquatic ecosystems and that quantifying two-way interactions between DOM properties and environmental conditions could resolve conflicting observations about the drivers of DOM in permafrost zone waterways.

HS-AFM and SERS Analysis of Murine Norovirus Infection: Involvement of the Lipid Rafts.

Studies on human norovirus are severely hampered by the absence of a cell culture system until the discovery of murine norovirus (MNV). The cell membrane domains called lipid rafts have been defined as a port of entry for viruses. This study is conducted to investigate murine norovirus binding on the mouse leukemic monocyte macrophage cell line. Lipid raft related structures are extracted from cells by detergent treatment resulting detergent-resistant membrane (DRMs) domains. The real-time polymerase chain reaction technique is performed to detect the viral genome, thereby the MNV binding on the DRMs. The interactions between MNV and DRMs are investigated by high-speed atomic force microscopy (HS-AFM) combined with surface-enhanced Raman spectroscopy (SERS). The inoculation of the virus onto cells results in the aggregations of detergent-resistant membrane domains significantly. The characteristic Raman band of MNV is found in inoculated samples. To be sure that these results are originated from specific interactions between DRM and MNV, methyl-ß-cyclo-dextrin (MßCD) is applied to disrupt lipid rafts. The MNV binding on DRMs is precluded by the MßCD treatment. The cholesterols chains are defined as a key factor in the interactions between norovirus and DRMs. The authors conclude that the MNV binding involves the presence of DRMs and cholesterol dependent.

Rapid carbon loss and slow recovery following permafrost thaw in boreal peatlands.

Permafrost peatlands store one-third of the total carbon (C) in the atmosphere and are increasingly vulnerable to thaw as high-latitude temperatures warm. Large uncertainties remain about C dynamics following permafrost thaw in boreal peatlands. We used a chronosequence approach to measure C stocks in forested permafrost plateaus (forest) and thawed permafrost bogs, ranging in thaw age from young (<10 years) to old (>100 years) from two interior Alaska chronosequences. Permafrost originally aggraded simultaneously with peat accumulation (syngenetic permafrost) at both sites. We found that upon thaw, C loss of the forest peat C is equivalent to ~30% of the initial forest C stock and is directly proportional to the prethaw C stocks. Our model results indicate that permafrost thaw turned these peatlands into net C sources to the atmosphere for a decade following thaw, after which post-thaw bog peat accumulation returned sites to net C sinks. It can take multiple centuries to millennia for a site to recover its prethaw C stocks; the amount of time needed for them to regain their prethaw C stocks is governed by the amount of C that accumulated prior to thaw. Consequently, these findings show that older peatlands will take longer to recover prethaw C stocks, whereas younger peatlands will exceed prethaw stocks in a matter of centuries. We conclude that the loss of sporadic and discontinuous permafrost by 2100 could result in a loss of up to 24 Pg of deep C from permafrost peatlands.

The Suicide Narrative Interview: adolescents' attachment expectancies and symptom severity in a clinical sample.

Insecure attachment styles have consistently been identified as risk factors for adolescent psychopathology and, more specifically, suicidal ideation. However, much less is known about the mechanisms that account for the relationship between attachment styles and severity of suicidal ideation within clinical samples. In the current study, adolescents' expectancies for caregiver availability and responsiveness were coded from transcripts of the Suicide Narrative Interview in a clinical sample of 129 depressed and suicidal adolescents. Results indicated that negative expectancies for caregiver availability in the Suicide Narrative Interview were associated both with attachment insecurity and with the intensity of adolescents' suicidal ideation. The implications of adolescents' expectancies for caregiver availability as targets for clinical intervention are discussed.

Association between Admission Serum 25-Hydroxyvitamin D Levels and Functional Outcome of Thrombolyzed Stroke Patients.

BACKGROUND: 25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer a stroke, and several studies suggested that it may be associated with a poorer prognosis. The aim of this study was to investigate specifically the association between 25(OH)D levels and functional outcome at 3 months in ischemic stroke patients treated with intravenous thrombolysis. METHODS: Consecutive ischemic stroke patients who received intravenous thrombolysis were enrolled between 2010 and 2013. Baseline characteristics were collected, and serum concentrations of 25(OH)D were measured within the first 24 hours after admission and were analyzed according to the quartiles of their distribution (<25 nmol/L versus ≥ 25 nmol/L). Multivariable ordinal logistic regression was used to evaluate the association between 25(OH)D and 3-month functional outcome assessed by the modified Rankin score. RESULTS: Three hundred fifty-two patients were included (mean age 68.6 ± 15.8, 50.7% women, mean 25(OH)D level 45 ± 25 nmol/L). The characteristics of the patients only differed with regard to higher premorbid functional impairment in patients with low 25(OH)D. In univariate analysis, the risk of functional impairment in patients with low 25(OH)D levels was greater than that in patients with higher 25(OH)D levels (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.35-3.27, P = .001). This association was still observed after adjustment for confounding variables (OR 1.70, 95% CI: 1.06-2.71, P = .027). CONCLUSION: A low serum 25(OH)D level is associated with worse functional outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. Further investigations are required to understand the underlying mechanisms of this association.

Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization.

OBJECTIVE: Plasma phospholipid transfer protein (PLTP) is a key determinant of lipoprotein metabolism, and both animal and human studies converge to indicate that PLTP promotes atherogenesis and its thromboembolic complications. Moreover, it has recently been reported that PLTP modulates inflammation and immune responses. Although earlier studies from our group demonstrated that PLTP can modify macrophage activation, the implication of PLTP in the modulation of T-cell-mediated immune responses has never been investigated and was therefore addressed in the present study. Approach and results: In the present study, we demonstrated that PLTP deficiency in mice has a profound effect on CD4+ Th0 cell polarization, with a shift towards the anti-inflammatory Th2 phenotype under both normal and pathological conditions. In a model of contact hypersensitivity, a significantly impaired response to skin sensitization with the hapten-2,4-dinitrofluorobenzene (DNFB) was observed in PLTP-deficient mice compared to wild-type (WT) mice. Interestingly, PLTP deficiency in mice exerted no effect on the counts of total white blood cells, lymphocytes, granulocytes, or monocytes in the peripheral blood. Moreover, PLTP deficiency did not modify the amounts of CD4+ and CD8+ T lymphocyte subsets. However, PLTP-deficiency, associated with upregulation of the Th2 phenotype, was accompanied by a significant decrease in the production of the pro-Th1 cytokine interleukin 18 by accessory cells. CONCLUSIONS: For the first time, this work reports a physiological role for PLTP in the polarization of CD4+ T cells toward the pro-inflammatory Th1 phenotype.

T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1.

T lymphocytes activated by dendritic cells (DC) which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC) are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

[Mass spectrometry and inherited metabolic diseases diagnosis]. / Spectrométrie de masse et diagnostic des maladies héréditaires du métabolisme.

Tandem mass spectrometry is used for the diagnosis and following of metabolic disorders for acylcarnitine profiling and with liquide chromatography to explore creatin metabolism and amino and bile acids disorders. The analysis of organic acids by GC-MS is still the reference method for the diagnosis of inherited disorders of organiques acides and sterols. These techniques are also used to perform "in vitro" functional tests.

Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3-positive CD8+ T lymphocytes.

BACKGROUND: Adoptive transfer of immunosuppressive cells has emerged as a promising strategy for the treatment of immune-mediated disorders. However, only a limited number of such cells can be isolated from in vivo specimens. Therefore efficient ex vivo differentiation and expansion procedures are critically needed to produce a clinically relevant amount of these suppressive cells. OBJECTIVE: We sought to develop a novel, clinically relevant, and feasible approach to generate ex vivo a subpopulation of human suppressor cells of monocytic origin, referred to as human monocyte-derived suppressive cells (HuMoSCs), which can be used as an efficient therapeutic tool to treat inflammatory disorders. METHODS: HuMoSCs were generated from human monocytes cultured for 7 days with GM-CSF and IL-6. The immune-regulatory properties of HuMoSCs were investigated in vitro and in vivo. The therapeutic efficacy of HuMoSCs was evaluated by using a graft-versus-host disease (GvHD) model of humanized mice (NOD/SCID/IL-2Rγc(-/-) [NSG] mice). RESULTS: CD33+ HuMoSCs are highly potent at inhibiting the proliferation and activation of autologous and allogeneic effector T lymphocytes in vitro and in vivo. The suppressive activity of these cells depends on signal transducer and activator of transcription 3 activation. Of therapeutic relevance, HuMoSCs induce long-lasting memory forkhead box protein 3-positive CD8+ regulatory T lymphocytes and significantly reduce GvHD induced with human PBMCs in NSG mice. CONCLUSION: Ex vivo-generated HuMoSCs inhibit effector T lymphocytes, promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an efficient therapeutic tool to prevent GvHD.

Agreement of seven 25-hydroxy vitamin D3 immunoassays and three high performance liquid chromatography methods with liquid chromatography tandem mass spectrometry.

BACKGROUND: Several recent studies have shown some discrepancies between 25-hydroxyvitamin D [25(OH)D] assay methods, despite some improvement in the past few years. The accuracy of 25(OH)D assay methods is still a real challenge for clinical laboratories. The aim of this study was to assess the agreement between a large panel of routine assays and a two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS) method, selected as the reference method. METHODS: Forty-nine human plasma samples with only endogenous 25(OH)D3 were analyzed with 11 different methods, especially with three LC-UV methods that differed in the extraction step. Seven routine immunoassays were also tested: two manual (RIA and EIA from IDS) and five fully-automated methods. The results of the 25(OH)D3 assays were compared with those of the 2D LC-MS/MS method using weighted Deming regression analysis, Bland-Altman plots and concordance correlation coefficient (CCC). The ability of these methods to properly classify patients was evaluated by sorting results depending on vitamin D status. RESULTS: The CCC was >0.90 for the three LC-UV methods and for most of the automated IA, meaning substantial agreement with 2D LC-MS/MS results. The ability to properly classify patients according to their vitamin D status was overall satisfactory for most of the methods tested (concordance >90%). CONCLUSIONS: The immunoassays available on Liaison, Isys, Architect and Elecsys, together with our in-house LC-UV method preceded by an SLE step met the minimum requirements for the assessment of vitamin D status in clinical laboratories.

Development of abdominal aortic aneurysm is decreased in mice with plasma phospholipid transfer protein deficiency.

Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly lower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow-derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.

[Evaluation of the new Hevylite™ IgA assay for the diagnosis and follow-up of monoclonal gammopathies]. / Évaluation du nouveau test Hevylite™ IgA dans le diagnostic et le suivi des gammapathies monoclonales.

Multiple myeloma diagnosis and follow-up are based on monoclonal protein measurement. The estimation of monoclonal immunoglobulin production requires serum protein electrophoresis, immunoelectrophoresis and free light chain assay. However these classical assays have some limitations. Hevylite™ IgA (Binding Site) is a new nephelometric/turbidimetric assay allowing the IgA κ and IgA λ measurement. The aim of this study was to determine the performance of this assay, for the diagnosis and follow-up of myeloma patients at different stages. Sixty seven frozen sera from 26 patients were assayed. Total IgA, IgA κ, IgA λ concentrations, serum protein electrophoresis and serum immunofixation were performed at diagnosis and during follow-up. All myeloma patients had an abnormal IgA κ/IgA λ ratio at diagnosis. During disease monitoring, the IgA κ or IgA λ concentrations correlated well with the electrophoretic estimation of the monoclonal spike and the values of total IgA. Hevylite™ test was more sensitive than serum protein electrophoresis and provided numerical and reproductible assessment of the monoclonal and non-monoclonal isotype. The IgA κ/IgA λ ratio allowed early prediction of disease relapse. Hevylite™ is an interesting assay especially when the monoclonal IgA comigrates on electrophoresis with normal proteins making impossible a reliable densitometric estimation. Hevylite™ might become an important assay in the biological exploration of gammopathies.

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients.

BACKGROUND: Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. METHODS: A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations. RESULTS: Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall). CONCLUSIONS: SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.

Lipid rafts: a signalling platform linking lipoprotein metabolism to atherogenesis.

Lipid rafts are microdomains of the plasma membrane which are enriched in cholesterol and sphingolipids. They serve as a platform for signal transduction, in particular during immune and inflammatory responses. As hypercholesterolemia and inflammation are two key elements of atherogenesis, it is conceivable that the cholesterol and cholesterol oxide content of lipid rafts might influence the inflammatory signalling pathways, thus modulating the development of atherosclerosis. In support of this emerging view, lipid rafts have been shown to be involved in several key steps of atherogenesis, such as the oxysterol-mediated apoptosis of vascular cells, the blunted ability of high density lipoproteins (HDL) to exert anti-inflammatory effects, and the exacerbated secretion of pro-inflammatory cytokines by immune cells. Additional studies are now required to address the relative contribution of lipid raft abnormalities to the pathophysiology of atherosclerosis and cardiovascular disease.