Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort.

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.

Benefits and challenges of a community-based programme for women living with HIV in Mali.

Gundo-So is a community-based programme developed by and for women living with HIV (WLHIV) in Mali through the ARCAD-Santé-PLUS association. It provides support, co-constructed with WLHIV, to develop strategies on whether or not to disclose their status. The aim of the ANRS-12373 research is to evaluate the impact of this programme in the short and medium term. As part of this research, semi-structured interviews were conducted with participants (14). These interviews were analysed thematically. Three themes are presented here: positive feedback from the programme, which enabled them to be listened to and supported them both psychologically and financially. The impact of the programme on the participants' social network is also described, in terms of the links made with peers met during the programme. Finally, a new perspective on issues such as disease management, which improved through the contribution of knowledge, and also through the development of psychosocial resources. The programme enabled participants to acquire psychosocial skills, the ability to effectively self-manage their condition, and strategies on whether or not to disclose their HIV status. Participants' empowerment and social support in relation to the disease were developed through the programme, particularly through the links created with other women living with HIV.

Benefits and costs of immune memory in Rhodnius prolixus against Trypanosoma cruzi.

There is increasing evidence supporting the immune memory in invertebrates, but the studies are relatively neglected in insect vectors other than mosquitoes. Therefore, we tested two hypotheses: 1) Rhodnius prolixus insects possess immune memory against Trypanosoma cruzi, and 2) their immune memory is costly. The Dm28c and Y strains of T. cruzi were used, the former being more infective than the latter. On the one hand, the triatomines subjected to dual challenges with the Dm28c strain did not show significant differences in survival than those of the heterologous challenge groups control-Dm28c and Y-Dm28c. On the other hand, the insects survived longer after a dual Y-Y challenge than after the corresponding heterologous challenge (control-Y). The Y-Y, Dm28c-Y, and naïve groups showed similar survival. There was more prolonged survival following the Y-Y versus Dm28c-Dm28c dual challenge. The Dm28c-Dm28c group exhibited moulting sooner than the control-Dm28c or naïve group. In contrast, there were no differences in the probability of moulting between the Y-Y and naïve groups. The results suggest that triatomines have immune memory against the Y but not the Dm28c strain. Further investigation on triatomine and T. cruzi interaction is needed to determine if infectivity accelerates or delay growth due to innate immune memory.

Evidence for a spinon Fermi surface in a triangular-lattice quantum-spin-liquid candidate.

A quantum spin liquid is an exotic quantum state of matter in which spins are highly entangled and remain disordered down to zero temperature. Such a state of matter is potentially relevant to high-temperature superconductivity and quantum-information applications, and experimental identification of a quantum spin liquid state is of fundamental importance for our understanding of quantum matter. Theoretical studies have proposed various quantum-spin-liquid ground states, most of which are characterized by exotic spin excitations with fractional quantum numbers (termed 'spinons'). Here we report neutron scattering measurements of the triangular-lattice antiferromagnet YbMgGaO4 that reveal broad spin excitations covering a wide region of the Brillouin zone. The observed diffusive spin excitation persists at the lowest measured energy and shows a clear upper excitation edge, consistent with the particle-hole excitation of a spinon Fermi surface. Our results therefore point to the existence of a quantum spin liquid state with a spinon Fermi surface in YbMgGaO4, which has a perfect spin-1/2 triangular lattice as in the original proposal of quantum spin liquids.

Female sex workers and police violence during the Covid-19 health crisis in 2020-2021: results from the EPIC multi-country community-based research program in Argentina.

BACKGROUND: Female sex workers (FSW) have been disproportionately impacted by the Covid-19 crisis. Data show increases of police violence toward key populations (KP), likely a consequence of their role in enforcing health government measures. This study aimed to identify factors associated with police violence experienced by FSW during the Covid-19 crisis in Argentina. METHODS: EPIC is a multi-country, cross-sectional, community-based research program evaluating the impact of Covid-19 among KP. In Argentina, the study was conducted in collaboration with FSW community-based organizations (CBO). Participants completed an online survey (October 2020-April 2021). Police violence was measured as having experienced episodes of violence (physical, verbal, psychological or sexual) by security forces since the start of the health crisis. Factors associated with police violence were assessed in logistic regression models. RESULTS: Among 173 respondents, median age was 34 [IQR 27-42], 39.3% were transgender women (TW), 78.1% declared sex work as their only income and 71.7% mentioned their financial situation has deteriorated with the health crisis. Nearly half of FSW (44.5%) reported experiencing police violence within the first year of the Covid-19 pandemic, and among them, 76.6% declared more frequent violence episodes since the beginning of the health crisis. After adjustment for age, being a TW (aOR [95% CI] = 2.71 [1.21;6.05]), reporting non-injection drug use (2.92 [1.02;8.36]), having a considerably deteriorated financial situation (3.67 [1.47;9.21]), having had a consultation with a CBO worker for medical care/treatments (5.56 [2.15;14.37]) and declaring fear or experiences of discrimination by physicians/other health workers (2.97 [1.21;7.29]), since the beginning of the Covid-19 health crisis, were independently associated with police violence. CONCLUSIONS: FSW in Argentina have experienced an increase in police violence since the beginning of the health crisis. Belonging to multiple KP (FSW, TW, people who use drugs) increases the likelihood of experiencing police violence, highlighting the need of an intersectional approach to develop interventions to reduce stigma and violence against FSW. CBOs have provided essential support and services during the crisis to FSWs, and other KPs, who may have avoided traditional healthcare structures due to fear or experiences of discrimination.

How PrEP users constitute a community in the MSM population through their specific experience and management of stigmatization. The example of the French ANRS-PREVENIR study.

The ANRS-PREVENIR (2017-2020) prospective cohort study aims to reduce the number of new HIV infections in the "Ile-de-France" region in France, by enrolling individuals at high risk of HIV infection and proposing daily and on-demand pre-exposure prophylaxis (PrEP). The qualitative component of the ANRS-PREVENIR study aimed to investigate social and relational evolutions associated with PrEP use in men who have sex with men (MSM). In 2018, 12 focus groups with MSM (n = 68) were conducted by a social sciences researcher in Paris. A thematic analysis was performed. Results showed that stigma concerning PrEP use is a complex issue, with various kinds of stigmatization being practiced, sometimes even by the wider MSM population and PrEP users themselves. All types of stigma identified were expressed in forms of verbal abuse which made PrEP use taboo. Inside the wider MSM population a PrEP-user "community" was identified which shared a certain complicity in terms of values and a positive attitude towards PrEP. The emergence of new intragroup and intergroup social norms should be taken into account by policy makers to promote a more positive image of PrEP users.

Immune gene expression in gilthead seabream (Sparus aurata) after Lymphocystis disease virus (LCDV-Sa) challenge resulting in asymptomatic infection.

AIMS: To determine the immune gene expression response of gilthead seabream (Sparus aurata) that is experimentally infected with the lymphocystivirus LCDV-Sa. METHODS AND RESULTS: Viral DNA and transcripts were detected by qPCR in all samples from fish injected with LCDV-Sa, demonstrating that the virus establish a systemic and asymptomatic infection. The expression of 23 immune-related genes was also analysed by RT-qPCR in the head kidney (HK) and intestine at several times post-infection (dpi). In HK, the expression of five type I interferon (IFN)-related genes (ifn, irf3, mx2, mx3 and isg15), il10 and ck10 was upregulated at 1-3 dpi, while genes related to the inflammation process (tnfα, il1ß, il6, casp1) were not differentially expressed or even downregulated. The expression profile in the intestine was different regarding type I INF-related genes. An upregulated c3 and ighm expression was observed in both HK and intestine at 3-8 dpi. Finally, the transcription of nccrp1 and mhcIIα was induced in HK, whereas tcrß expression was downregulated in both organs. CONCLUSIONS: LCDV-Sa seems to trigger an immune response in gilthead seabream characterized by a partial activation of type I IFN system and a lack of systemic inflammatory response which may be related to viral persistence. SIGNIFICANCE AND IMPACT OF THE STUDY: The immune response observed in gilthead seabream infected by LCDV-Sa could be implicated in the establishment of an asymptomatic persistent infection.

Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice.

Background: Targeted capture sequencing can potentially facilitate precision medicine, but the feasibility of this approach in gastrointestinal (GI) malignancies is unknown. Patients and methods: The FOrMAT (Feasibility of a Molecular Characterisation Approach to Treatment) study was a feasibility study enrolling patients with advanced GI malignancies from February 2014 to November 2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin-embedded diagnostic/resection samples) was carried out to detect mutations, copy number variations and translocations in up to 46 genes which had prognostic/predictive significance or were targets in current/upcoming clinical trials. Results: Of the 222 patients recruited, 215 patients (96.8%) had available tissue samples, 125 patients (56.3%) had ≥16 genes successfully sequenced and 136 patients (61.2%) had ≥1 genes successfully sequenced. Sample characteristics influenced the proportion of successfully sequenced samples, e.g. tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas 27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P ≤ 0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type of sample (resection versus biopsy: 82.4% versus 47.6%, P ≤ 0.001). Currently, actionable alterations were detected in 90 (40.5%) of the 222 patients recruited (66% of the 136 patients sequenced) and 2 patients subsequently received a targeted therapy. The most frequently detected currently actionable alterations were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival samples, the median time to obtain sequencing results was 18.9 weeks, including a median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing. Conclusions: Targeted sequencing detected actionable alterations in formalin-fixed paraffin-embedded samples, but tissue characteristics are of critical importance in determining sequencing success. Routine molecular profiling of GI tumours outside of clinical trials is not an effective use of healthcare resources unless more targeted drugs become available. ClinicalTrials.gov identifier: NCT02112357.

Lessons learned from the experiences of informal PrEP users in France: results from the ANRS-PrEPage study.

Before January 2016, Pre-Exposure Prophylaxis (PrEP), a new biomedical HIV-prevention tool, was only available in France via ANRS-Ipergay clinical study but informal use was reported outside this setting. PrEPage qualitative study reports profiles and experiences of participants who used PrEP outside of a biomedical trial before this prevention method was authorized. Between March 2015 and February 2016, a cross-section of twenty-four informal PrEP users, mostly MSM, was recruited to complete in-depth semi-structured interviews. While ANRS-Ipergay was still ongoing (2012-2016), participants described their initiation to PrEP, the way they used it and the difficulties they faced to acquire antiretroviral drugs in an environment where PrEP was still not widely known and often criticized . Through the testimonies, different user profiles and motivation toward informal PrEP use emerged: (a) participants who have increasing difficulties using condoms, (b) "opportunists" who tried PrEP without the intention of using it regularly and (c) participants with a risk aversion who sought additional protection against HIV. Participants chose to use PrEP and/or their usual prevention strategies depending on available supplies, type of partners and individual attitudes toward risk. The feeling of living a safer sex life helped participants to outweigh the fear of possible toxicity and drug resistance. Participants' needs and expectations about PrEP implementation in France were also presented.

Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.

INTRODUCTION: Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. AIMS: We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. METHODS: We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. RESULTS: Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. CONCLUSIONS: Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative.

Search and analysis of genes involved in antibiotic resistance in Chilean strains of Piscirickettsia salmonis.

Piscirickettsia salmonis is the pathogen causing Piscirickettsiosis. For treatment, the industry mainly uses oxytetracycline and florfenicol, so it is essential to understand the degree of susceptibility of this pathogen to these drugs. But this is still unknown for a large number of P. salmonis strains, as are the molecular mechanisms responsible for greater or lesser susceptibility. However, genes that confer resistance to these antimicrobials have been reported and characterized for this and other bacterial species, among which are membrane proteins that take out the drug. Our results identified differences in the degree of susceptibility to both antibiotics among different Chilean isolated of these bacteria. We analysed 10 available genomes in our laboratory and identified ~140 genes likely to be involved in antibiotic resistance. We analysed six specific genes, which suggests that some of them would eventually be relevant in conferring resistance to both antibiotics, as they encode for specific transporter proteins, which increase the number of transcripts when grown in media with these antibiotics. Our results were corroborated with EtBr permeability analysis, which revealed that the LF-89 strain accumulates this compound and has a reduced capacity to expulse it compared with the field strains.

Field-Induced Magnonic Liquid in the 3D Spin-Dimerized Antiferromagnet Sr_{3}Cr_{2}O_{8}.

We report on ultrasound and magnetization studies in three-dimensional, spin-dimerized Sr_{3}Cr_{2}O_{8} as a function of temperature and external magnetic field up to 61 T. It is well established [A. A. Aczel et al., Phys. Rev. Lett. 103, 207203 (2009)] that this system exhibits a magnonic-superfluid phase between 30 and 60 T and below 8 K. By mapping ultrasound and magnetization anomalies as a function of magnetic field and temperature we establish that this superfluid phase is embedded in a domelike phase regime of a high-temperature magnonic liquid extending up to 18 K. Compared to thermodynamic results, our study indicates that the magnonic liquid could be characterized by an Ising-like order but has lost the coherence of the transverse components.

Erratum: Field-Induced Magnonic Liquid in the 3D Spin-Dimerized Antiferromagnet Sr_{3}Cr_{2}O_{8} [Phys. Rev. Lett. 116, 147201 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.116.147201.

Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.

BACKGROUND: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. PATIENTS AND METHODS: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. RESULTS: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). CONCLUSION: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.

High-T(c) Superconductivity at the Interface between the CaCuO2 and SrTiO3 Insulating Oxides.

At interfaces between complex oxides it is possible to generate electronic systems with unusual electronic properties, which are not present in the isolated oxides. One important example is the appearance of superconductivity at the interface between insulating oxides, although, until now, with very low T(c). We report the occurrence of high T(c) superconductivity in the bilayer CaCuO(2)/SrTiO(3), where both the constituent oxides are insulating. In order to obtain a superconducting state, the CaCuO(2)/SrTiO(3) interface must be realized between the Ca plane of CaCuO(2) and the TiO(2) plane of SrTiO(3). Only in this case can oxygen ions be incorporated in the interface Ca plane, acting as apical oxygen for Cu and providing holes to the CuO(2) planes. A detailed hole doping spatial profile can be obtained by scanning transmission electron microscopy and electron-energy-loss spectroscopy at the O K edge, clearly showing that the (super)conductivity is confined to about 1-2 CaCuO(2) unit cells close to the interface with SrTiO(3). The results obtained for the CaCuO(2)/SrTiO(3) interface can be extended to multilayered high T(c) cuprates, contributing to explaining the dependence of T(c) on the number of CuO(2) planes in these systems.

Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients.

BACKGROUND AND OBJECTIVE: Oral mucositis (OM) is considered a painful and debilitating side effect in patients receiving head and neck cancer treatment. Low-level laser therapy (LLLT) proved to be effective to prevent and treat chemoradiotherapy-induced OM. The aim of this study was to evaluate the effect of LLLT in the severity of OM in patients with head and neck cancer and on the release of salivary inflammatory mediators. Clinical (score of OM severity) and biochemical parameters (concentration of inflammatory mediators, growth factors, and enzymes in saliva) were used. MATERIALS AND METHODS: Thirty patients were randomized into two groups: control and laser. LLLT was performed three times a week in the laser group, while control group received sham irradiation. OM severity was assessed according to the World Health Organization (WHO) and National Cancer Institute (NCI) scales. Pro-inflammatory and anti-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-10, TGF-ß), growth factors (EGF, FGF, VEGF), and metalloproteinases (MMP2/TIMP2, MMP9/TIMP2) concentrations were assessed using ELISA test. Saliva samples were collected on admission, and at the 7th, 21st, and 35th sessions of radiotherapy. RESULTS: The laser group showed a reduction in the severity of OM, which coursed with significantly diminished salivary concentration of EGF and VEGF in the 7th radiotherapy session and of IL-6 and FGF in the 35th. There was a trend for reduced levels of IL-1ß, TNF-α, IL-10, TGF-ß, MMP2/TIMP2, MMP9/TIMP2 in the laser group compared to the control, however, no statistically significant differences were found. CONCLUSIONS: These findings demonstrated that LLLT was effective in reducing the severity of chemoradiotherapy-induced OM and was associated with the reduction of inflammation and repair.

Isotopic variation in five species of stream fishes under the influence of different land uses.

The aim of this study was to test if changes in land use alter the isotopic signature of fish species, promoting changes in the trophic position and food resource partitioning between these consumers. Three different systems were investigated: pasture streams (n = 3), streams in sugar cane plantations (n = 3) and reference streams (n = 3). Fish species Aspidoras fuscoguttatus, Astyanax altiparanae, Characidium zebra, Hisonotus piracanjuba and Knodus moenkhausii were selected, and their nitrogen and carbon isotopic compositions were estimated to assess changes in the trophic level and partitioning of food items consumed. The composition of δ(13) C (‰) only differed among the land use categories for A. altiparanae, H. piracanjuba and K. moenkhausii. Resource partitioning was different for all species, with changes in the sources or proportions they consumed in each land use category, but only A. altiparanae introduced new food sources in large quantity in altered land uses. It is important to note, however, that the results from the resource partitioning analysis are limited due to large overlapping of isotopic signatures between the analysed food resources. All fish species exhibited variation in δ(15) N (‰), with the highest values found in streams under sugar cane or pasture influence. Despite the variation in nitrogen isotopic values, only C. zebra and H. piracanjuba displayed changes in trophic level. Therefore, it is believed that the increase in the δ(15) N (‰) value of the individuals collected in streams under the influence of sugar cane or pasture was due to the greater influence of livestock dung and chemical and organic fertilizers. The results also highlight the importance of studying consumer species along with all forms of resources available at each location separately, because the signatures of these resources also vary within different land uses.

Denture Adhesives Associated with Silver Vanadate: Antimicrobial Approach Against Multi- Species Biofilms on Acrylic Resin Surfaces.

Alternatives have been sought to add an antimicrobial property to denture adhesives. This study evaluated the antimicrobial potential of adhesives associated with nanostructured silver vanadate decorated with silver nanoparticles (ß-AgVO3). Specimens in acrylic resin were treated with the adhesives associated with ß-AgVO3 (1%, 2.5%, 5% and 10%). As control, specimens treated only with Ultra Corega Cream (UCC) or Ultra Corega Powder (UCP) adhesive were used. Multispecies biofilm of Candida albicans, Candida glabrata, Streptococcus mutans and Staphylococcus aureus was evaluated by counting colony forming units per milliliter (CFU/mL), colorimetric assay and fluorescence microscopy. The data were analyzed using the two-way analysis of variance (ANOVA) and Bonferroni multiple comparisons test (α=0.05). For both adhesives, a small amount of ß-AgVO3 (1%) completely inhibited S. mutans (P⟨0.05). For the other microorganisms, there was a reduction in metabolic activity and complete inhibition in the groups with intermediate or greater amounts of nanomaterial (P⟨0.05), except for C. albicans, which was reduced (P⟨0.05) but not completely inhibited in UCP. Microscopy that showed less biofilm in the groups with ß-AgVO3 and in the UCC than UCP. Denture adhesives in powder and cream form with ß-AgVO3 showed potential antimicrobial activity against multispecies biofilm. Powder adhesive showed higher biofilm formation.