Effect of HIV-exposure and timing of antiretroviral treatment initiation in children living with HIV on antibody persistence and memory responses to Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines

BackgroundWe investigated the effect of in utero HIV-exposure, timing of antiretroviral treatment (ART) initiation, and ART interruption on memory responses and persistence of immunity induced by pneumococcal (PCV) and Haemophilus influenzae type b (HibCV) polysaccharide-protein conjugate vaccines.MethodsChildren were enrolled (6–12 weeks of age), and vaccinated with a three-dose primary series of 7-valent PCV (PCV7) and HibCV at 6, 10 and 14 weeks of age. Study groups included infants infected with HIV perinatally with CD4+ ≥ 25% initiating ART following immunological or clinical deterioration (ART-Def), or immediately upon enrolment followed by interruption at 40 (ART-Immed/40w) or 96 weeks (ART-Immed/96w); and HIV-uninfected infants with (HEU), and without HIV (HIV-unexpsoed) exposure in utero. Within each group, children were randomized to receive either a booster dose of PCV7 or HibCV at 15 months of age. PCV serotype-specific and polyribosyl ribitol phosphate (PRP) IgG were measured pre-boost, two-weeks post-boost and at two-years of age. Opsonophagocytic activity (OPA) to serotypes 9V, 19F and 23F was measured post-booster dose.ResultsPersistence of IgG to PCV vaccine–serotypes and anti-PRP was similar in all groups of children living with HIV (CLWH) compared to HIV-unexposed children. Anamnestic responses to PCV and HibCV were also similar in all three groups of CLWH compared to HIV-unexposed children. CLWH, however, tended to have lower functional antibody (OPA) titers than HIV-unexposed children after the PCV booster dose for some serotypes. Immunity to PCV and HibCV was similar between the ART-Immed/40w and ART-Immed-96w groups. There were no differences in IgG kinetics between HEU and HIV-unexposed children.ConclusionsA three dose primary series, with or without PCV or HibCV booster doses in CLWH initiated on ART during infancy, would likely be similarly effective in preventing invasive bacterial disease as in HIV-unexposed children.     

Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine,and responses to a booster vaccination

BackgroundIn a multi-center extension study, children 2–10 years of age, initially vaccinated with one or two doses (2–5 year-olds) or one dose (6–10 year-olds) of quadrivalent meningococcal CRM₁₉₇-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA).MethodsChildren 7–10 and 11–15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later.ResultshSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7–22% for A, 32–57% for C, 74–83% for W, and 48–54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised.ConclusionsApproximately half the children vaccinated as 2–10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations.     

Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv) regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.     

Persistence of blood (DNA/RNA) on shoe soles under varying casework related conditions

Blunt force traumas by footwear can result in severe and even fatal head and upper body injuries. Oftentimes, footwear impressions are only partially available and evidential value is limited. DNA evidence on shoe soles could provide crucial evidence helping to solve crimes by linking target DNA to the activity of interest. Little is known about the persistence and detectability of biological material post such offenses and the interplay of factors affecting the analytical success. In this study, we assessed the persistence of blood on shoe soles under varying parameters such as blood location, different sneakers, weather condition, gait, amount of blood, underground and step count. We applied an optimized DNA/RNA workflow adapted to micro-traces without constraints for the primary DNA pipeline. There is a high probability to link donor DNA to the shoe sole for up to 300–400 steps, regardless of the underground, blood location, and amount of blood. Depending on the sole material and the degree of abrasion of the sole, a longer blood persistence can be observed. Considering blood, 98.2% of the initial DNA amount (1 μl initial blood volume) was lost after 100 steps walked on sole areas that are in constant contact with the ground. Proportion of foreign DNA was marginal (avg. 4.4 alleles), minimizing the probability of unintentional DNA transfer in this context. RNA typing showed high specificity but lower sensitivity than presumptive tests used for body fluid identification (BFI). Luminol is essential for targeted sampling on shoe soles, as latent blood traces (>100–200 steps) provided sufficient biological material for DNA/RNA typing. The generated data help to address the activity of interest and evaluate probabilities about prevalence of target DNA important for casework implications and assessments on activity level.     

Building trophic modules into a persistent food web

Understanding what maintains species and perpetuates their coexistence in a network of feeding relationships (the food web) is of great importance for biodiversity conservation. A food web can be viewed as consisting of a number of simple subunits called trophic modules. Intraguild predation (IGP), in which a prey and its predator compete for the same resource, is one of the best-studied trophic modules. According to theory, there are two ways to yield a large persistent system from such modules: (i) to use persistent subunits as building blocks or (ii) to arrange the subunits in a way that externally supports the nonpersistent subunits. Here, I show that the complex food web of the Caribbean marine ecosystem is constructed in both ways. I show that IGP modules, which convey internal persistence because of the fact that prey are superior competitors for the resources, are overrepresented in the Caribbean ecosystem. The other modules, consisting of competitively inferior prey, are not persistent in isolation. However, competitively inferior prey in these modules tend to receive more advantage from extra-module interactions, which allows persistence of the IGP module. In addition, those exterior interactions tend to be provided by intrinsically persistent IGP modules to prevent cascading extinction of interacting IGP modules. The food web can be viewed as a set of interacting modules, nonrandomly arranged to enhance the maintenance of biodiversity.     

Blunted cardiovascular reactivity to acute psychological stress predicts low behavioral but not self‐reported perseverance: A replication study

Emerging evidence suggests that individuals with poor behavioral perseverance show low or blunted physiological responses to acute psychological stress. For example, a recent preliminary laboratory study demonstrated that blunted responders give up sooner and take fewer attempts when endeavoring to complete an impossible puzzle, but do not self‐report poor perseverance. This present research is a replication of the previous study with an increased sample size, longer recovery periods between tasks and addition of social evaluation to the cold pressor. Participants (147) completed a self‐report perseverance questionnaire (Short Grit Scale) and behavioral perseverance tasks (impossible Euler puzzle and socially evaluated cold‐pressor (SECPT)). The number of attempts and time spent trying to complete the unsolvable puzzle, and duration of hand submergent during the SECPT, were recorded as behavioral perseverance measures. Difference in blood pressure (BP) and pulse rate (PR) from baseline to a 10‐min paced auditory serial addition task (PASAT) were computed as reactivity. As previously, reactivity did not relate to self‐reported perseverance and blunted BP reactivity to the PASAT was associated with less time persevering at the unsolvable puzzle. Additionally, blunted BP and PR reactivity to the PASAT related to poorer perseverance during the SECPT. These findings, replicating the previous study, increase confidence that blunted reactivity is a physiological marker of poor behavioral perseverance. Moreover, given that self‐reported perseverance does not relate to reactivity, this suggests that blunted responders are not conscious of this detriment in perseverance, but likely need additional support when persistence is critical (e.g., during behavior change).