Leptin, IL-6, and suPAR reflect distinct inflammatory changes associated with adiposity, lipodystrophy and low muscle mass in HIV-infected patients and controls

BACKGROUND: HIV-infected patients could exhibit accelerated ageing, since age-associated complications like sarcopenia; increased inflammation; lipodystrophy with loss of subcutaneous adipose tissue and/or gain of visceral adipose tissue (VAT); and cardiovascular disease occur at an earlier age. Inflammation is involved in age-associated complications. However, it is not understood whether it is the same inflammatory changes that are involved in the various ageing-associated complications. Our objective was to study whether leptin, interleukin 6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) were associated distinctively with adiposity, lipodystrophy and sarcopenia, in HIV-infected patients and healthy Controls. RESULTS: Systemic leptin levels were significantly higher in patients with lipodystrophy than without, whereas there was no difference in IL-6 or suPAR levels. Leptin was significantly positively associated with fat mass index (FMI) and abdominal VAT, but not with lean mass index (LMI). IL-6 was significantly associated with both FMI and VAT, and low LMI. High suPAR was associated with low LMI, and weakly with high FMI and VAT. CONCLUSIONS: Leptin reflected adiposity- and lipodystrophy-related inflammation, but not sarcopenia. IL-6 reflected both adiposity-, but also sarcopenia-related inflammation; and suPAR was a marker of sarcopenia-related inflammation. Our results indicate that different inflammatory processes can be active simultaneously contributing to the systemic low grade inflammatory state. Identifying major contributors to circulating leptin, IL-6, and suPAR levels could levels could therefore improve our understanding of which inflammatory processes are involved in the various age-related complications

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe

Perspectives on menopause and women with HIV

Nisha Andany,1 V Logan Kennedy,2 Muna Aden,2 Mona Loutfy1,2 1Department of Medicine, University of Toronto, Toronto, ON, Canada; 2Women&rsquo;s College Research Institute, Women&rsquo;s College Hospital, Toronto, ON, Canada Abstract: Since the implementation of effective combination antiretroviral therapy, HIV infection has been transformed from a life-threatening condition into a chronic disease. As people with HIV are living longer, aging and its associated manifestations have become key priorities as part of HIV care. For women with HIV, menopause is an important part of aging to consider. Women currently represent more than one half of HIV-positive individuals worldwide. Given the vast proportion of women living with HIV who are, and will be, transitioning through age-related life events, the interaction between HIV infection and menopause must be addressed by clinicians and researchers. Menopause is a major clinical event that is universally experienced by women, but affects each individual woman uniquely. This transitional time in women&rsquo;s lives has various clinical implications including physical and psychological symptoms, and accelerated development and progression of other age-related comorbidities, particularly cardiovascular disease, neurocognitive dysfunction, and bone mineral disease; all of which are potentially heightened by HIV or its treatment. Furthermore, within the context of HIV, there are the additional considerations of HIV acquisition and transmission risk, progression of infection, changes in antiretroviral pharmacokinetics, response, and toxicities. These menopausal manifestations and complications must be managed concurrently with HIV, while keeping in mind the potential influence of menopause on the prognosis of HIV infection itself. This results in additional complexity for clinicians caring for women living with HIV, and highlights the shifting paradigm in HIV care that must accompany this aging and evolving population. Keywords: HIV, women, aging, menopause&nbsp

Infective endocarditis of a native aortic valve due to <i>Pseudomonas aeruginosa</i> complicated by progressive multi-drug resistance

BACKGROUND: Treatment of infective endocarditis secondary to Pseudomonas aeruginosa can be challenging because of this organism’s ability to acquire antimicrobial resistance over time. METHODS: We describe a patient with native aortic valve infective endocarditis due to P. aeruginosa who developed progressive multi-drug resistance while on therapy. The resistance mechanisms were characterized using whole-genome sequencing. RESULTS: We identified two mutations in subsequent isolates ( dacB and OprD) that conferred resistance to anti-pseudomonal penicillins, cephalosporins, and carbapenems. The patient was treated with combination high-dose continuous infusion meropenem and ciprofloxacin therapy, in addition to bioprosthetic aortic valve replacement and repair of ventricular septal wall defect. Antibiotics were continued for 6 weeks post–cardiac surgery and the patient remains infection free 18 months post-completion of antibiotic therapy. CONCLUSION: Clinicians should be aware of the ability of P. aeruginosa to acquire resistance mechanisms in response to selective antibiotic pressures in high-inoculum infections such as infective endocarditis. The mutations identified in this case report correlated well with the evolving antimicrobial resistance profile observed. </jats:p

Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly

AbstractCentrioles are evolutionarily conserved multi-protein organelles essential for forming cilia and centrosomes. Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that scaffolds organelle formation. The importance of this architecture has been difficult to decipher notably because of the lack of precise tools to modulate the underlying assembly reaction. Here, we developed monobodies against Chlamydomonas reinhardtii SAS-6, characterizing three in detail with X-ray crystallography, atomic force microscopy and cryo-electron microscopy. This revealed distinct monobody-target interaction modes, as well as specific consequences on ring assembly and stacking. Of particular interest, monobody MBCRS6-15 induces a conformational change in CrSAS-6, resulting in the formation of a helix instead of a ring. Furthermore, we show that this alteration impairs centriole biogenesis in human cells. Overall, our findings identify monobodies as powerful molecular levers to alter the architecture of multi-protein complexes and tune centriole assembly.</jats:p

Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly

Centrioles are evolutionarily conserved multi-protein organelles essential for forming cilia and centrosomes. Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that scaffolds organelle formation. The importance of this architecture has been difficult to decipher notably because of the lack of precise tools to modulate the underlying assembly reaction. Here, we developed monobodies against Chlamydomonas reinhardtii SAS-6, characterizing three in detail with X-ray crystallography, atomic force microscopy and cryo-electron microscopy. This revealed distinct monobody-target interaction modes, as well as specific consequences on ring assembly and stacking. Of particular interest, monobody MB CRS6 -15 induces a conformational change in CrSAS-6, resulting in the formation of a helix instead of a ring. Furthermore, we show that this alteration impairs centriole biogenesis in human cells. Overall, our findings identify monobodies as powerful molecular levers to alter the architecture of multi-protein complexes and tune centriole assembly.</p