Does the Production of Isoprene Affect the Productivity of Poplars?

Poplar trees are known to produce a chemical called isoprene that plays a complex, and not fully understood, role in the chemical process of photosynthesis. Understanding why plants produce isoprene and under what conditions will help scientists make more accurate predictions about poplars’ photosynthetic capabilities in future climates. What benefit could isoprene provide a plant? The literature suggests its production could help plants tolerate heat stress. We studied two genetic lines of trees in a common garden of Populus, one line with the gene for producing isoprene and a second line without that gene. We subjected some trees of each line to low water conditions to investigate if isoprene played a role in allowing plants to cope with water stress. We then compared the ability of these 4 treatment groups of poplars to photosynthesize over a range of temperatures. Poplars with and without isoprene showed similar rates of photosynthesis over the range of temperatures measured. Poplars subjected to low water conditions and poplars with normal water conditions also recorded similar rates of photosynthesis. This suggests that isoprene does not offer a photosynthetic benefit, and also that the low water conditions may not have triggered a water stressed state in the poplars. However, the poplars’ rate of photosynthesis differed between morning and afternoon, suggesting that time of day could play a role in photosynthesis. Future work is needed to understand how the influence of time of day on photosynthesis may overshadow any differences due to isoprene production

Safety and Tolerability of Antiretrovirals during Pregnancy

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs

Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics

HIV Continuum of Care for Youth in the United States

BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among the youth: engagement, treatment, and viral load (VL) suppression. Youth aged 13-24 who were behaviorally infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had 1 year of available data. Most were aged 22-24 (57%), male (79%), and black/non-Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the 3 months before enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved VL suppression. Sustained VL suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for the prevalence of adherence counseling (100%), case management (100%), clinic-based mental health (93%), and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained VL suppression may be an important step to add to the Continuum of Care for youth

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial

Introduction Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed

Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir

Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission. To investigate safety, we compared adverse events (AE) among infants exposed to different maternal cART regimens. We reviewed 158 HIV-uninfected infants born between 1997 and 2009, using logistic regression to model grade ≥1 AE and grade ≥3 AE as a function of maternal cART and confounding variables (preterm, C-section, illicit drug use, race, ethnicity, infant antiretrovirals, and maternal viremia). Frequently used cART regimens included zidovudine (63%), lamivudine (80%), ritonavir-boosted lopinavir (37%), nelfinavir (26%), and atazanavir (10%). At birth, anemia occurred in 13/140 infants (9%), neutropenia in 27/107 (25%), thrombocytopenia in 5/133 (4%), and liver enzyme elevation in 21/130 (16%). Corresponding rates of AE at 4 weeks were 59/141 (42%), 54/130 (42%), 3/137 (2%), and 3/104 (3%), respectively. Serious AE (grade ≥ 3) exceeded 2% only for neutropenia (13% at birth; 9% at 4 weeks). Compared with infants exposed to maternal lopinavir/ritonavir, infants exposed to nelfinavir and atazanavir had a 5-fold and 4-fold higher incidence of AE at birth, respectively. In conclusion, hematologic and hepatic AE were frequent, but rarely serious. In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE

Prion-like α-synuclein pathology in the brain of infants with Krabbe disease

Krabbe disease is an infantile neurodegenerative disorder resulting from pathogenic variants in the GALC gene that causes accumulation of the toxic sphingolipid psychosine. GALC variants are also associated with Lewy body diseases, an umbrella term for age-associated neurodegenerative diseases in which the protein α-synuclein aggregates into Lewy bodies. To explore whether α-synuclein in Krabbe disease has pathological similarities to that in Lewy body disease, we performed an observational post-mortem study of Krabbe disease brain tissue (n = 4) compared to infant controls (n = 4) and identified widespread accumulations of α-synuclein. To determine whether α-synuclein in Krabbe disease brain displayed disease-associated pathogenic properties we evaluated its seeding capacity using the real-time quaking-induced conversion assay in two cases for which frozen tissue was available and strikingly identified aggregation into fibrils similar to those observed in Lewy body disease, confirming the prion-like capacity of Krabbe disease-derived α-synuclein. These observations constitute the first report of prion-like α-synuclein in the brain tissue of infants and challenge the putative view that α-synuclein pathology is merely an age-associated phenomenon, instead suggesting it results from alterations to biological pathways, such as sphingolipid metabolism. Our findings have important implications for understanding the mechanisms underlying Lewy body formation in Lewy body disease

HIV monoclonal antibodies: a new opportunity to further reduce mother-to-child HIV transmission.

Yegor Voronin and colleagues explore how monoclonal antibodies against HIV could provide a new opportunity to further reduce mother-to-child transmission of HIV and propose that new interventions should consider issues related to implementation, feasibility, and access. Please see later in the article for the Editors' Summary

Inducing behavioural change in society through communication and education in sustainable manufacturing

The United Nations considers the mobilization of the broad public to be the essential requirement for achieving a shift towards a more sustainable development. Science can play a vital role in Education for Sustainable Development (ESD) by contributing to ESD-related research and development on the one hand, and by becoming active awareness raisers themselves in education and multiplier networks. Specifically, the use of special Learnstruments, and investment inOpen Educationformats among other educational tools, may pave the way for accelerated apprehension and appreciation of sustainable manufacturing topics among the greater populace