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Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-naïve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans

Identification of biallelic loss-of-function PREP variants in three individuals with syndromic intellectual disability.

BACKGROUND: Neurodevelopmental disorders are one of the most prevalent reasons for genetic testing in childhood. Despite the identification of over 1950 associated genes, many proposed candidate genes lack convincing gene-disease validity. The gene PREP encodes the broadly expressed prolyl endopeptidase whose exact function remains largely unknown. A homozygous PREP variant has been reported once as a candidate gene in two siblings with intellectual disability but no functional studies were conducted. METHODS: Exome and trio genome sequencing were performed in two unrelated families as part of larger cohorts. Segregation analysis, RNA sequencing and immunoblots were performed to further examine the pathogenicity of detected PREP variants. RESULTS: We report three individuals from two unrelated families who presented with intellectual disability, behavioural abnormalities, strabismus, generalised muscular hypotonia, dysmorphic facial features and epilepsy. Exome and genome sequencing identified two different homozygous rare PREP variants: c.1570_1573dup, p.(Asn525Thrfs*5) and c.1839-2A>G, p.?. RNA sequencing confirmed the detected intronic variant to result in two aberrant mRNA isoforms. In patient-derived cells immunoblots showed absence of PREP protein. CONCLUSION: Our data suggest PREP deficiency as the underlying cause of a syndromic neurodevelopmental disorder.

Female

Ten years on, still out of reach: barriers to PrEP access and retention in France according to frontline actors (QualiPrEP Study).

Pre-exposure prophylaxis (PrEP) for HIV has been available in France since 2014, and reimbursed since 2016, with general practitioners allowed to prescribe it since 2021. Despite these policy advances, uptake remains low among some of the most affected populations. This community-based qualitative study explored barriers to PrEP access and retention ten years into its implementation.Interviews were conducted with 28 PrEP frontline actors (healthcare professionals and community-based workers involved in promoting, prescribing, or supporting PrEP). The sample included one group discussion (n = 5), two triads (n = 6), two dyads (n = 4), and nine individual interviews (n = 13). Thematic analysis was inductive, with barriers classified across four main domains.Participants were mostly cisgender men, median age 48, born in France and abroad, and employed by NGOs in Paris. Thirteen barriers and four major themes emerged: (1) Internal psychosocial barriers: lack of knowledge, negative health-related reactions; HIV stigma; STI risk perception, taboos; (2) Internal pragmatic barriers: perceived limits of protection, usage and follow-up constraints; (3) External psychosocial barriers: limited physician knowledge and reluctance; (4) External pragmatic barriers: communication failures; structural constraints, lack of human and financial resources.Findings call for more targeted messaging, simplified care models and provider training. They highlight the need to address social and symbolic dimensions of PrEP, with insights from those supporting users to ensure more equitable implementation.

Humans

The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with ≥ 99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20 min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20 min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans

[The prep-trainer--thermal control in the pulp space].

The "Prep-Trainer" was developed as teaching and checking aid in order to enable students and dentists interested in continued education to check themselves. The heat development in the pulp cavity is measured at the model. Measurements made by the author showed that the safest method for maintaining constant temperatures and thus avoiding over-heating of the pulp cavity is the cooling with the air-water spray handpiece by the dental assistant.

Audiovisual Aids

1. Membrane vesicles of Escherichia coli K-12 CS7, a strain gentically derepressed for glutamate permease, maintain low aspartate transport activity, like that of prep.

1. Membrane vesicles of Escherichia coli K-12 CS7, a strain gentically derepressed for glutamate permease, maintain low aspartate transport activity, like that of preparations of the wild-type parent. Growth of the parent CS101 on aspartate as the source of carnon or nitrogen results in derepression of both asparatate and glytamate transport. Growth of strain CS7 on aspartate derepresses aspartate transport to the same extent as in strains CS101, but only slightly increases the derepressed level of glutamate transport activity. 2. The affinity of the membrane transport system for glutamate is enhanced by sodium, while that for asparate is not. 3. Although the affinities for glutamate (23 muM) and aspartate (12 muM) are similar, aspartate does not inhibit glutamate transport, while glutamate competitively inhibits aspartate transport. 4. Aspartate transport, but not glutamate transport, is competitively inhibited by C4 dicarboxylic acids, whereas 2-oxoglutarate competitively inhibits glutamate transport, but not aspartate transport. 5. Competitive inhibition of L-aspartate transport by L-glutamate and by the 5-methyl ester of L-glutamate is abolished in the presence of 2-oxoglutarate. However, 2-oxoglutarate does not affect the competitive inhibition of L-aspartate transport by D-aspartate and by DL-threo-3-hydroxyaspartate. The relationship between the two dicarboxylic amino acid transport systems and the spatial characteristics of the aspartate carrier are discussed in the light of these findings.

Aspartic Acid

Separation of a guanine nucleotide regulatory unit from the adenylate cyclase complex with GTP affinity chromatography.

We studied the relationship between guanine nucleotide binding proteins and adenylate cyclase activity of solubilized turkey erythrocyte membranes with GTP affinity chromatography. Solubilized adenylate cyclase from untreated membranes or membranes pretreated with GMP only (GMP prep) responded poorly to GTP or Gpp(NH)p but were markedly stimulated by fluoride. The solubilized enzyme from membranes pretreated with isoproterenol+GMP (ISO+GMP prep) did not respond to GTP but was markedly stimulated by Gpp(NH)p. Fluoride-stimulated activity of the ISO+GMP prep was reduced by comparison with the GMP prep but could be increased significantly by addition of GTP. GTP hexane agarose (GTP linked to matrix via morpholine derivative of ribose) failed to interact specifically with either the GMP or ISO+GMP prep. Incubation of ISO+GMP prep with GTP-gamma-agarose (GTP linked to matrix via terminal phosphate) reduced the Gpp(NH)p response and the GTP-dependent fraction of the fluoride response. GTP-gamma-agarose did not reduce the fluoride response of the GMP prep. Following incubation with ISO+GMP prep, GTP-gamma-agarose beads were eluted with buffer containing Gpp(NH)p. The eluate had only slight intrinsic adenylate cyclase activity but was able to increase significantly the activity of GTP-gamma-agarose-treated ISO+GMP prep as well as untreated GMP prep. An eluate from GTP-gamma-agarose beads incubated with GMP prep did not possess activity. Our results suggest that the guanine nucleotide-regulatory unit is reversibly associated with the adenylate cyclase complex of turkey erythrocyte membranes.

Adenylyl Cyclases

Same-day initiation of tenofovir alafenamide-based pre-exposure prophylaxis with drug-level feedback for transgender women in Uganda.

OBJECTIVE: To evaluate the feasibility and acceptability of same-day initiation of emtricitabine/tenofovir alafenamide (F/TAF) pre-exposure prophylaxis (PrEP) and test the impact of drug-level feedback on PrEP adherence among transgender women (TGW) in Uganda. DESIGN: Randomized controlled trial. METHODS: HIV-negative TGW were randomly assigned 1 : 1 to intervention (drug-level feedback with tailored adherence counseling) or standard-of-care (SOC), and followed quarterly for 12 months (November 2021-July 2023; NCT04491422). Quarterly clinic visits included demographic and socio-behavioral data collection, PrEP refills, STI testing, and quarterly PrEP adherence assessment using tenofovir levels in dried blood spots (DBS; long-term) and urine (short-term). RESULTS: We enrolled 200 TGW (100 per arm), median age 21 years. Same-day F/TAF PrEP initiation was 100%. Tenofovir detection in urine (intervention arm) was 79, 80, 85, and 70% at the 3, 6, 9, and 12-month visits, respectively. Tenofovir detection in DBS was 46, 40, 35, and 31% at 3, 6, 9, and 12 months, respectively. Median tenofovir DBS concentrations were 40.6 and 47.0 fmol/punch in intervention and SOC arms, respectively. There was no intervention effect on PrEP adherence (DBS tenofovir levels) [adjusted incidence rate ratio (aIRR) 1.06; 95% CI: 0.82-1.37]. Never being harassed by police for being transgender (aIRR 1.66; 95% CI: 1.24-2.23), history of taking daily medication for more than 7 days (aIRR 1.51; 95% CI: 1.18-1.93) and higher monthly income (aIRR 1.44; 95% CI: 1.10-2.04) were associated with PrEP adherence. CONCLUSION: Oral F/TAF PrEP adherence among TGW in Uganda was low and not affected by drug-level feedback or tailored adherence counseling. Long-acting injectable PrEP formulations should be considered for this population.

Humans

"Everybody thinks that it won't happen to them": A mixed-methods study of HIV prevention strategies among people experiencing homelessness who use drugs.

BACKGROUND: HIV disproportionately affects people experiencing homelessness, particularly those who use drugs. Although effective prevention strategies exist, uptake remains suboptimal in high-risk populations. Limited research has examined how this population engages with HIV prevention strategies and the contextual factors shaping behaviors. METHODS: We conducted a mixed-methods study of adults (≥18 years) experiencing homelessness with recent drug use, recruited from three Boston sites (Feb 2024-Jan 2025). Participants completed a survey assessing HIV prevention strategy uptake. A subsample completed in-depth interviews on factors influencing behavior. Guided by the Theoretical Domains Framework, we coded qualitative data and identified themes to help contextualize uptake. RESULTS: Among 196 participants, mean age was 48; 61% identified as male and 44% as non-Hispanic White. Forty-two percent reported condomless sex, and among those who had ever injected drugs (n = 123), 24% reported syringe sharing in the prior three months. Only 9% reported current PrEP use, and 12% had ever used HIV self-tests. Qualitative findings highlighted perceived control as a key facilitator, while low perceived HIV risk hindered uptake across strategies. Additional barriers varied by strategy and included partner dynamics and substance use affecting condom use, structural constraints affecting syringe use, and knowledge, stigma, and cost concerns affecting PrEP and self-testing. CONCLUSION: In this cohort of people experiencing homelessness who use drugs, HIV prevention strategy uptake was suboptimal, with particularly low PrEP and HIV self-testing use. Qualitative findings suggest that interventions to promote HIV prevention strategy uptake in this population should leverage perceived control, address perceived risk, and target strategy-specific interpersonal and structural barriers.

Humans

Tissue toxicity of antiseptic solutions. A study of rabbit articular and periarticular tissues.

The gross, histologic, and biochemical effects of four commercially available antiseptic solutions on rabbit knee articular and periarticular connective tissues were investigated. Rabbit knee joints were injected with 2.0 cc of either Betadine prep solution, Betadine scrub solution, pHisohex or 3% hexachlorophene. The opposite knees were injected with sterile saline. All animals were injected three times at 48-hour intervals and sacrificed 10 days after the last injection. The solutions containing detergents, Betadine scrub, and pHisohex caused severe gross and histologic damage to articular cartilage, synovia, and muscle. The hexachlorophene loss solution caused moderate histologic damage, but caused articular cartilage ground substance. Betadine prep solution caused only minimal gross and histologic damage, without any biochemical evidence of articular cartilage damage. If antiseptic solutions are to be used in irrigating or packing joint injuries, the use of Betadine prep is recommended.

Animals

Sequencing the orthologs of human autosomal forensic short tandem repeats provides individual- and species-level identification in African great apes.

BACKGROUND: Great apes are a global conservation concern, with anthropogenic pressures threatening their survival. Genetic analysis can be used to assess the effects of reduced population sizes and the effectiveness of conservation measures. In humans, autosomal short tandem repeats (aSTRs) are widely used in population genetics and for forensic individual identification and kinship testing. Traditionally, genotyping is length-based via capillary electrophoresis (CE), but there is an increasing move to direct analysis by massively parallel sequencing (MPS). An example is the ForenSeq DNA Signature Prep Kit, which amplifies multiple loci including 27 aSTRs, prior to sequencing via Illumina technology. Here we assess the applicability of this human-based kit in African great apes. We ask whether cross-species genotyping of the orthologs of these loci can provide both individual and (sub)species identification. RESULTS: The ForenSeq kit was used to amplify and sequence aSTRs in 52 individuals (14 chimpanzees; 4 bonobos; 16 western lowland, 6 eastern lowland, and 12 mountain gorillas). The orthologs of 24/27 human aSTRs amplified across species, and a core set of thirteen loci could be genotyped in all individuals. Genotypes were individually and (sub)species identifying. Both allelic diversity and the power to discriminate (sub)species were greater when considering STR sequences rather than allele lengths. Comparing human and African great-ape STR sequences with an orangutan outgroup showed general conservation of repeat types and allele size ranges. Variation in repeat array structures and a weak relationship with the known phylogeny suggests stochastic origins of mutations giving rise to diverse imperfect repeat arrays. Interruptions within long repeat arrays in African great apes do not appear to reduce allelic diversity. CONCLUSIONS: Orthologs of most human aSTRs in the ForenSeq DNA Signature Prep Kit can be analysed in African great apes. Primer redesign would reduce observed variability in amplification across some loci. MPS of the orthologs of human loci provides better resolution for both individual and (sub)species identification in great apes than standard CE-based approaches, and has the further advantage that there is no need to limit the number and size ranges of analysed loci.

Animals

Comparative study of a standardized senna liquid and castor oil in preparing patients for radiographic examination of the colon.

X-Prep Liquid, used as a radiologic bowel evacuant, was found to be more effective, better tolerated, and more readily accepted than castor oil. The efficacy of a single full dose of this peristaltic stimulant was confirmed, and a divided dose of X-Prep Liquid was practically as effective and produced less griping and cramping. This less intensive divided-dose approach appears to be appropriate, especially in aged or debilitated patients.

Adult

Chromatographic determination of cis-trans monoethylenic unsaturation in fats and oils--A review.

Chromatographic procedures for the determination of geometric and positional monoethylenic fatty-acid isomers in fats and oils have been reviewed. For the determination of these isomers, the procedure involving prep GLC isolation of the monoethylenic ester fractions on polar stationary phases, further separation and determination of geometric isomers by prep Ag+/TLC, and determination of positional isomers by reductive ozonolysis, is considered to be the most suitable for the analysis of a wide range of oils. Although, in this review, emphasis has been placed on monoethylenic isomers, most of the techniques described are also applicable in the study of polyenoic isomers.

Adsorption