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Objectives: Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.Design: Cross-sectional analysis of 134 PLWH on suppressive ARV therapy, 79 lifestyle-comparable HIV-negative controls aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors (BD).Methods: Biological age was estimated using a validated algorithm based on ten biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression.Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6, 14.9) years] and HIV-negative [5.5 (3.8, 7.2) years] COBRA participants compared to BD [-7.0 (-4.1, -9.9) years, both p's < 0.001)], but also in HIV-positive compared to HIV-negative participants (p < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1, 6.8) years among those with nadir CD4+ < 200 cells/μL and by 0.1 (0.06, 0.2) years for each additional month of exposure to saquinavir.Conclusions: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared to BD, to which persistent CMV, HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure. published

Background: HIV-infected individuals may be at risk for the premature onset of age-associated noncommunicable comorbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, comorbidities and age on HRQL and depression. Methods: HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of comorbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent comorbidities, aging and HIV infection were independently associated with HRQL and depression. Results: HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of comorbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of comorbidities or with higher age. Conclusion: In a cohort of largely well suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of comorbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of comorbidities as the HIV-infected population continues to age.

Background The aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified. Methods A wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers’ D statistic was applied to identify patterns of comorbidities. Results PCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47–59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48–59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = –.02; P = .64). Conclusions Comorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.

The efficacy and pharmacokinetics of the aqueous co-formulation contents of the Trobigard™ (atropine sulfate, obidoxime chloride) auto-injector were evaluated in a sarin exposed guinea pig model. Two subcutaneous (sc) sarin challenge doses were evaluated in guinea pigs instrumented with brain and heart electrodes for electroencephalogram (EEG) and electrocardiogram (ECG). Sarin challenge doses were chosen to reflect exposure subclasses with sublethal (moderate to severe clinical signs) and lethal consequences. The level of protection of intramuscular human equivalent doses of the co-formulation was defined by (1) the mitigation of signs and symptoms at a sublethal level and (2) the increase of survival time at the supralethal sarin dose levels. Pharmacokinetics of both atropine sulfate and obidoxime were proportional at 1 and 3 human equivalent doses, and only a small increase in heart rate was observed briefly as a side effect. At both sarin challenge doses, 54 μg/kg and 84 μg/kg, the co-formulation treatment was effective against sarin-induced effects. Survival rates were improved at both sarin challenge levels, whereas clinical signs and changes in EEG activity could not in all cases be effectively mitigated, in particular at the supralethal sarin challenge dose level. Reactivation of sarin inhibited cholinesterase was observed in blood, and higher brain cholinesterase activity levels were associated with a better clinical condition of the co-formulation treated animals. Although the results cannot be directly extrapolated to the human situation, pharmacokinetics and the effects over time related to plasma levels of therapeutics in a freely moving guinea pig could aid translational models and possibly improve prediction of efficacy in humans. © 2018 Elsevier B.V.

We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine (PC), Sphingomyelin (SPM) and Triacylglycerols (TG's) for liver tissue while for brain tissue we had an extra lipid compound the Plasmalogens. In addition, dynamics of hepatic steatosis were determined in an in vivo mouse model with localized non-invasive Magnetic Resonance Spectroscopy (1H-MRS) techniques. In the experimental design Male C57bl6 mice (age 8-12 weeks) were exposed to three treatments: A: They were fed a chow Diet for a period of approximately 40 days (Control group); B: They were fed a High-Fat Diet, containing 0.25% cholesterol (Ch) and 24% energy from bovine lard for a period of approximately 40 days, C: Or they were exposed to 48 hours of starvation. For whole brain tissue of these mice groups the LC-MS techniques indicated that the brain was rather invulnerable to Dietary intervention. The (phospho-) lipid-composition of the brain was unchanged in the starvation group but the cholesterol-ester content was significantly increased in the high High-Fat Diet group. These observations suggest that the brain lipid composition is insensitive to starvation but can be affected by a high High-Fat Diet. In contrast, for liver tissue both 24 h starvation and the 40 day High-Fat Diet resulted in exponential hepatic fat accumulation, although their time course (measured with 1H MRS) techniques was distinctly different. Mass spectrometry (LC-MS) demonstrated for liver tissue remarkable differences in lipid profiles between treatments. 1H-MRS proved to be a reliable method for frequent, repetitive determination of hepatic fat in vivo and a noninvasive alternative to biopsy. Moreover, LC-MS and Principal Component Analysis (PCA) demonstrated that in liver tissue different lipid end products are formed as result of Dietary composition Apparently, for liver tissue starvation and a High-Fat Diet result in a process called hepatic steatosis which is regulated under both conditions via different metabolic pathways. In addition, 1H-MRS techniques demonstrated for liver that the relative amount of unsaturated bindings is significantly higher in the High-Fat Diet group (P≤0.001), which can be deducted from the relative intensities of the (CH=CH) elements and their conjugated unsaturated elements (C-CCH2C=C). We conclude, comparing brain vs. liver tissue that both tissues have a totally different metabolic response to both treatments. The brain is insensitive to starvation but can be affected by a High-Fat Diet while in liver tissue both treatments result paradoxically in a hepatic steatosis. However, for the liver, the dynamics and the lipid profiles of this process of this hepatic steatosis under starvation or a High-Fat Diet are totally different. © 2010 Nova Science Publishers, Inc. All rights reserved.

An analysis of collections of nongeniculate Corallinales (Rhodophyta) in the Onderzoekinstituut Rijksherbarium/Hortus Botanicus, Rijksuniversiteit Te Leiden (abbreviated L) has revealed the presence of type material for 114 species and infraspecific taxa. These include 35 holotypes, 21 lectotypes, 1 neotype, 15 isotypes, 25 isolectotypes, 12 syntypes and 4 paratypes. Type material of 25 authors is represented and includes taxa described by F.T. Kützing, M.H. Foslie, F.R. Kjellman, R.A. Philippi, F. Hauck, and F. Heydrich. Lectotypes have been newly designated for Lithophyllum crassum, L. crispatum, Lithothamnion macquariensis, and L. mamillosum. For each taxon, information on the protologue, nature of the type material, type locality, references to typification and published illustrations and pertinent nomenclatural and other comments are provided.

A new species of coralline algae, Spongites sulawesiensis. is described. Its relationship to other species belonging to the genus Spongites is discussed. Also a new combination is made in the genus Mesophyllum, M. funafutiense.

Eleven seagrass species were found in South Sulawesi, Indonesia. Seagrasses occurred in five different habitats, i.e. intertidal terrigenous mudflats, shallow terrigenous sandy bays, coastal reef flats, reef flats of patch reefs, and sandy reef bases, from the intertidal to a maximum depth of 35 m. Thalassia hemprichii and Enhalus acoroides were the dominant constant species of stable environments (permanently present in climax vegetations). Cymodocea rotundata, Halodule uninervis and Halophila ovalis were the dominant pioneering species in the area. A considerable number (117) of macroalgal taxa were found associated with seagrass vegetation, but only 13 of these were found exclusively in association with seagrasses. Macroalgal biomass in the seagrass beds was usually low (< 5 g AFDW m-2). However, in stressed habitats macroalgae may contribute up to 50% to the total biomass, notably during periods of occasional blooming. Species diversity of seagrasses and associated macroalgae was much lower in stressed habitats, which are characterized by heavy sedimentation, physical instability of the substratum, or high turbidity.