Impact of COVID-19 & Response Measures on HIV-HCV Prevention Services and Social Determinants in People Who Inject Drugs in 13 Sites with Recent HIV Outbreaks in Europe, North America and Israel.

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.

RESUMEN: La prevención del VIH/VHC entre las personas que se inyectan drogas (PWID) es de vital importancia para la salud pública. Nuestro objetivo fue evaluar el impacto de COVID-19 y las medidas de respuesta asociadas en los servicios de prevención del VIH/VHC y el estado socioeconómico de las PWID en sitios de alto riesgo de VIH. Se contactó con sitios con brotes recientes (2011­2019) de VIH entre PWID en Europa, América del Norte e Israel, que habían sido previamente identificados, a principios de mayo de 2020. De los 17 sitios invitados a participar, 13 aceptaron. Se prepararon informes cualitativos semiestructurados del sitio que cubrían los datos de marzo a mayo de 2020, analizados/codificados y confirmados con un cuestionario estructurado, en el que todos los sitios respondieron explícitamente a los 103 asuntos reportados en los informes cualitativos. El tratamiento de mantenimiento con opiáceos, los programas de agujas/jeringas y el tratamiento antirretroviral/tratamiento de la hepatitis C continuaron, pero con importantes reducciones y cambios operativos. Se reportaron aumentos en las sobredosis, dificultades generalizadas con las necesidades alimentarias y de higiene, interrupciones en el suministro de medicamentos y aumento de personas sin hogar. Los programas de servicios reformaron rápidamente las políticas restrictivas de prestación de servicios, establecidas desde hace mucho tiempo y políticamente arraigadas. Las futuras medidas de control de epidemias deben incluir la mitigación de los efectos secundarios negativos en la prestación de servicios y los determinantes socioeconómicos en las PWID.

Unravelling the origin of SARS-CoV-2: is the model good?

MacLean and colleagues recently published a very elegant analysis demonstrating that SARS-CoV-2 carries signs of positive selection and that it was already adapted to humans prior to the emergence of COVID-19. Using the Spillover theory as a reference model for zoonotic emergence, they conclude that SARS-CoV-2 must have acquired this human adaptation in bats. We reinterpreted the data from MacLean et al. using a different model of zoonotic emergence as reference, the Circulation model. The use of the Circulation model provides a more parsimonious interpretation showing that this adaptation to humans occurs in the human population after primo infection.

Mass culling of minks to protect the COVID-19 vaccines: is it rational?

The Danish Government announced the culling of 17 million minks in rearing after the report of mink-specific mutations of severe acute respiratory syndrome coronavirus 2 in humans. The rationale behind this decision is that these mutations might negatively impact the deployment of anti-coronavirus disease 2019 vaccines. Is it a precautionary attitude or a panic-driven overreaction?

What could explain the late emergence of COVID-19 in Africa?

At the end of November 2019, a novel coronavirus responsible for respiratory tract infections emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in southern Europe and America in spring 2020. Many studies predicted an epidemic in Africa similar to that currently seen in Europe and the USA. However, reported data do not confirm these predictions. Several hypotheses that could explain the later emergence and spread of the coronavirus disease 2019 (COVID-19) pandemic in African countries are being discussed, including the lack of health-care infrastructure capable of clinically detecting and confirming COVID-19 cases, the implementation of social distancing and hygiene, international air traffic flows, the climate, the relatively young and rural population, the genetic polymorphism of the angiotensin-converting enzyme 2 receptor, cross-immunity and the use of antimalarial drugs.

Great apes in the emergence of infectious diseases.

Since the AIDS pandemic and the demonstration that it originated in the accidental transmission of simian retroviruses to humans, no one can ignore the role of nonhuman primates in carrying pathogens that can cross the species barrier to infect humans. In recent decades, viruses as deadly as those for rabies, Herpes B, Marburg hemorrhagic fever, and Ebola have been transferred from monkeys to humans. Because great apes are genetically our closest relatives, the pathogens that colonize these mammals are probably best adapted to pass into humans should accidental exposure occur. This article attempts to evaluate the risks of infection when apes and humans share the same ecosystem.

Ecological speciation in sympatric palms: 2. Pre- and post-zygotic isolation.

We evaluated reproductive isolation in two species of palms (Howea) that have evolved sympatrically on Lord Howe Island (LHI, Australia). We estimated the strength of some pre- and post-zygotic mechanisms in maintaining current species boundaries. We found that flowering time displacement between species is consistent across in and ex situ common gardens and is thus partly genetically determined. On LHI, pre-zygotic isolation due solely to flowering displacement was 97% for Howea belmoreana and 80% for H. forsteriana; this asymmetry results from H. forsteriana flowering earlier than H. belmoreana and being protandrous. As expected, only a few hybrids (here confirmed by genotyping) at both juvenile and adult stages could be detected in two sites on LHI, in which the two species grow intermingled (the Far Flats) or adjacently (Transit Hill). Yet, the distribution of hybrids was different between sites. At Transit Hill, we found no hybrid adult trees, but 13.5% of younger palms examined there were of late hybrid classes. In contrast, we found four hybrid adult trees, mostly of late hybrid classes, and only one juvenile F1 hybrid in the Far Flats. This pattern indicates that selection acts against hybrids between the juvenile and adult stages. An in situ reciprocal seed transplant between volcanic and calcareous soils also shows that early fitness components (up to 36 months) were affected by species and soil. These results are indicative of divergent selection in reproductive isolation, although it does not solely explain the current distribution of the two species on LHI.

Ecological speciation in sympatric palms: 1. Gene expression, selection and pleiotropy.

Ecological speciation requires divergent selection, reproductive isolation and a genetic mechanism to link the two. We examined the role of gene expression and coding sequence evolution in this process using two species of Howea palms that have diverged sympatrically on Lord Howe Island, Australia. These palms are associated with distinct soil types and have displaced flowering times, representing an ideal candidate for ecological speciation. We generated large amounts of RNA-Seq data from multiple individuals and tissue types collected on the island from each of the two species. We found that differentially expressed loci as well as those with divergent coding sequences between Howea species were associated with known ecological and phenotypic differences, including response to salinity, drought, pH and flowering time. From these loci, we identified potential 'ecological speciation genes' and further validate their effect on flowering time by knocking out orthologous loci in a model plant species. Finally, we put forward six plausible ecological speciation loci, providing support for the hypothesis that pleiotropy could help to overcome the antagonism between selection and recombination during speciation with gene flow.

Postoperative discomfort after outpatient anterior cruciate ligament reconstruction: a prospective comparative study.

INTRODUCTION: The principal objective of the present study was to compare rates of postoperative discomfort after anterior cruciate ligament (ACL) reconstruction between inpatient (In) and outpatient (Out) management. PATIENTS AND METHOD: A single-surgeon non-randomized prospective comparative study included patients undergoing primary surgery for isolated ACL tear by short hamstring graft in 2012-13. The Out group comprised patients eligible for and consenting to outpatient surgery and the In group, those not eligible or not consenting. The principal assessment criterion was onset of at least 1 symptom of postoperative discomfort (SPD): anxiety, nausea and vomiting, malaise, vertigo or stomach pain, between postoperative days 0 and 3. Secondary assessment criteria were difficulty in getting to sleep, getting up during the night, regular walking or going out, number of episodes of knee pain and waking because of pain. All criteria were assessed on-line by the patient. RESULTS: One hundred and thirty-three patients filled out the questionnaire, 70 in the Out group and 63 in the In group; 42 females, 91 males; mean age, 30±9 years. Between D0 and D3, the proportion of patients with ≥l SPD was comparable between groups (Out 37% vs In 41%, P=0.62). Out-group patients had significantly less difficulty sleeping the first postoperative night (P=0.01), got up significantly more often during the first night after surgery (P<0.0001), more often walked regularly on day 1 (P=0.03), and were significantly less often woken by pain during the first night (P=0.003). Risk factors for SPD were female gender (OR=4.8±1.9) and postoperative complications (OR=3.8±2.5). CONCLUSION: Patients undergoing ACL reconstruction on an outpatient basis did not show more symptoms of postoperative discomfort than those managed as conventional inpatients. LEVEL OF EVIDENCE: IV; prospective comparative study.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

Outpatient surgery feasibility in anterior cruciate ligament reconstruction: a prospective comparative assessment.

INTRODUCTION: The main objective of this study was to assess the feasibility of outpatient surgery in anterior cruciate ligament (ACL) reconstruction. We hypothesized that if the patient underwent the procedure within a dedicated organization, safety would be ensured. PATIENTS AND METHODS: A non-randomized, prospective, comparative, single-operator study conducted in 2012-2013 included all patients undergoing first-line surgery for ACL arthroscopic reconstruction using a short hamstring graft. The outpatient group (OP) included patients who were eligible for outpatient surgery and provided consent; the conventional hospitalization group (CH) comprised those patients not suitable for outpatient surgery and those who refused it. The main evaluation criterion was failure of the admission modality defined as hospitalization of a patient who had undergone outpatient surgery or rehospitalization in the first week after discharge. The secondary evaluation criteria were the rate of postoperative complications, postoperative pain, use of analgesics, and patient satisfaction. A total of 138 patients were included: 71 in the OP group and 67 in the CH group, with a mean age of 29.6±9 years. Twenty-nine percent of the patients refused outpatient surgery. In the CH group, the mean hospital stay lasted 2.7±0.8 days. RESULTS: One patient in the OP group was hospitalized with localized bleeding and there were no rehospitalizations. Six early postoperative complications were noted in each group. The mean postoperative pain on D0-D4 and patient satisfaction were similar in the two groups. CONCLUSION: This prospective study encountered no serious events after outpatient ACL reconstruction surgery. In a selected population, the risks are comparable to those in conventional hospitalization. LEVEL OF EVIDENCE: Level III, comparative study.

Constraints imposed by pollinator behaviour on the ecology and evolution of plant mating systems.

Most flowering plants rely on pollinators for their reproduction. Plant-pollinator interactions, although mutualistic, involve an inherent conflict of interest between both partners and may constrain plant mating systems at multiple levels: the immediate ecological plant selfing rates, their distribution in and contribution to pollination networks, and their evolution. Here, we review experimental evidence that pollinator behaviour influences plant selfing rates in pairs of interacting species, and that plants can modify pollinator behaviour through plastic and evolutionary changes in floral traits. We also examine how theoretical studies include pollinators, implicitly or explicitly, to investigate the role of their foraging behaviour in plant mating system evolution. In doing so, we call for more evolutionary models combining ecological and genetic factors, and additional experimental data, particularly to describe pollinator foraging behaviour. Finally, we show that recent developments in ecological network theory help clarify the impact of community-level interactions on plant selfing rates and their evolution and suggest new research avenues to expand the study of mating systems of animal-pollinated plant species to the level of the plant-pollinator networks.

A comparative analysis of the mechanisms underlying speciation on Lord Howe Island.

On Lord Howe Island, speciation is thought to have taken place in situ in a diverse array of distantly related plant taxa (Metrosideros, Howea and Coprosma; Proc. Natl Acad. Sci. USA 108, 2011, 13188). We now investigate whether the speciation processes were driven by divergent natural selection in each genus by examining the extent of ecological and genetic divergence. We present new and extensive, ecological and genetic data for all three genera. Consistent with ecologically driven speciation, outlier loci were detected using genome scan methods. This mechanism is supported by individual-based analyses of genotype-environment correlations within species, demonstrating that local adaptation is currently widespread on the island. Genetic analyses show that prezygotic isolating barriers within species are currently insufficiently strong to allow further population differentiation. Interspecific hybridization was found in both Howea and Coprosma, and species distribution modelling indicates that competitive exclusion may result in selection against admixed individuals. Colonization of new niches, partly fuelled by the rapid generation of new adaptive genotypes via hybridization, appears to have resulted in the adaptive radiation in Coprosma - supporting the 'Syngameon hypothesis'.

High correlation between the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1, v2.0 and the Abbott m2000 RealTime HIV-1 assays for quantification of viral load in HIV-1 B and non-B subtypes.

BACKGROUND: HIV-1 viral load assays are critical tools to monitor antiretroviral therapy efficacy in HIV-infected patients. Two assays based on real-time PCR are available, the Abbott Real-Time HIV-1 assay (Abbott assay) and the new Roche COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 test, v. 2.0 (TaqMan(®) test v2.0). OBJECTIVES: We have compared the performance of the two assays in 546 clinical plasma specimens of group M strains from Luxembourg and Rwanda. STUDY DESIGN: Our analyses focused on subtype inclusivity and platforms accuracy for 328 low level viremia samples. RESULTS: Strong agreement and linear correlation were observed between the two assays (R(2) = 0.95) over a wide dynamic range. Bland-Altman analysis showed a mean difference of 0.04 log 10 indicating minimal overall viral load quantification differences between both platforms. One subtype C was severely underquantified by TaqMan(®) test v2.0 for which sequence analysis revealed multiple mismatches between the viral sequence and the primer/probe regions. A non significant lower quantification of the Abbott assay was shown for subtype A1 with a mean log 10 difference of 0.24. For specimens under 200 cp/mL, the overall agreement was 90% at the cut-off of 50 cp/mL and 67% at assay's lower limit of detection of 20 and 40 cp/mL. 309 samples were retested by the COBAS(®) AMPLICOR(®) HIV-1 MONITOR Test, v. 1.5 and a lack of agreement between the three assays around their lower limit of quantification was revealed. CONCLUSIONS: Both real-time tests were closely comparable in the quantification of viral load specimens of ten HIV-1 subtypes and recombinant forms.

Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA.

OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. RESULTS: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). CONCLUSIONS: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.

In vitro impact of physiological shear stress on endothelial cells gene expression profile.

In the vascular system, the shear applied to the vascular wall activates mechano-sensors located on endothelial cells (ECs) leading to a modification in the gene expression profile. We applied laminar shear stress at 1 Pa on ECs for 6 h and measured by quantitative real time PCR the expression modulation of genes implied in inflammation (ICAM-1 and E-selectin), oxidative stress sensing (HO-1) and vascular tone modulation (eNOS). We showed that all these genes are shear stress inducible. ICAM-1 is more up-regulated than E-selectin suggesting different levels of implication in inflammatory responses and different modes of induction (SSRE, cytokine). Laminar shear stress induces an oxidative stress translated into HO-1 up-regulation, and a possible vasodilatation through the induction of eNOS. Our laminar shear stress system opens a novel and interesting frame in the evaluation of the impact on ECs and blood cells of new pharmacological substances injected in the bloodstream.

Modelling and estimating pollen movement in oilseed rape (Brassica napus) at the landscape scale using genetic markers.

Understanding patterns of pollen movement at the landscape scale is important for establishing management rules following the release of genetically modified (GM) crops. We use here a mating model adapted to cultivated species to estimate dispersal kernels from the genotypes of the progenies of male-sterile plants positioned at different sampling sites within a 10 x 10-km oilseed rape production area. Half of the pollen clouds sampled by the male-sterile plants originated from uncharacterized pollen sources that could consist of both large volunteer and feral populations, and fields within and outside the study area. The geometric dispersal kernel was the most appropriate to predict pollen movement in the study area. It predicted a much larger proportion of long-distance pollination than previously fitted dispersal kernels. This best-fitting mating model underestimated the level of differentiation among pollen clouds but could predict its spatial structure. The estimation method was validated on simulated genotypic data, and proved to provide good estimates of both the shape of the dispersal kernel and the rate and composition of pollen issued from uncharacterized pollen sources. The best dispersal kernel fitted here, the geometric kernel, should now be integrated into models that aim at predicting gene flow at the landscape level, in particular between GM and non-GM crops.

Using a recombinant bispecific antibody to block Na+ -channel toxins protects against experimental scorpion envenoming.

In recent years, several molecular engineering methods of designing bispecific antibodies in various formats have been developed. Tandem-scFvs comprising two scFvs fused together via a peptide are 55-kDa molecules, and are one of the most promising and most straightforward approaches to bispecific antibody production. We report an attempt to design more effective antivenoms to the Androctonus australis scorpion using murine scFvs as building blocks to create a unique bispecific molecule that neutralizes the potent neurotoxins AahI and AahII. The tandem-scFv was produced in recombinant bacteria, purified by immobilized metal ion affinity chromatography, and analyzed by polyacrylamide gel electrophoresis, Western blot, gel filtration, mass spectrometry, and direct and competitive radioimmunoassay. In vivo, it neutralized the binding of the AahI and AahII toxins to their receptor, and protected mice against experimental envenomation. The findings reported here highlight the potential of recombinant antibody fragments for protecting against scorpion venom toxicity.

Significance of phrenic nerve electrophysiological abnormalities in Guillain-Barré syndrome.

The authors investigated whether the amplitude and latency of diaphragm compound muscle action potential helped predict respiratory failure in Guillain-Barré syndrome. Both variables were significantly but weakly correlated with vital capacity (VC) and were similar in unventilated (n = 60) and ventilated (n = 10) patients. In ventilated patients, motor loss severity, progression, and VC reduction were significantly greater, and bulbar dysfunction was more common. Predicting respiratory failure must rely on clinical features and VC.

High diversity of oilseed rape pollen clouds over an agro-ecosystem indicates long-distance dispersal.

Abstract Estimating the frequency of long-distance pollination is important in cultivated species, particularly to assess the risk of gene transfer following the release of genetically modified crops. For this purpose, we estimated the diversity and origin of fertilizing pollen in a 10 x 10 km French oilseed rape production area. First, the cultivar grown in each field was identified through surveys to farmers and using microsatellite markers. Examination of the seed set in fields indicated high rates of seed contamination (8.7%) and pollination from other sources (5%). Then, male-sterile plants were scattered over the study area and their seed genotyped using the same markers. Most pollination was local: 65% of the seeds had a compatible sire in the closest field, i.e. at 50 or 300 m depending on site, but the nearest compatible field was found more than 1000 m away for 13% of the seeds. To assess the diversity of fertilizing pollen, each seed was assigned to the nearest putative siring cultivar. The observed diversity of pollen was then compared to that predicted by simulations using three empirical dispersal models with increasing proportion of long-distance pollination. The diversity was sensitive to the dispersal kernel used in the simulations, fatter-tailed functions predicting higher diversities. The dispersal kernel that was more consistent with our data predicted more long-distance dispersal than the exponential function.