Assessing Children's Autonomic Nervous System Activity During Structured Tasks: A Feasibility and Reliability Study in Ghana.

The significance of physiological regulation in relation to behavioral and emotional regulation is well documented, but primarily in economically advantaged contexts. Few studies have been conducted in low- and middle-income countries. We investigated the feasibility and reliability of measuring autonomic nervous system (ANS) activity and behavior during challenge tasks in 30 children aged 8-10 years in Ghana during two visits, 1 week apart. Completeness of ANS data ranged from 80% to 100% across all tasks. There was low-to-moderate test-retest reliability of video mood induction (VMI) emotion ratings and balloon analog risk task (BART) pumps (r = 0.34-0.52). VMI elicited higher targeted emotion ratings in Visit 2 than Visit 1. Respiratory sinus arrhythmia (RSA) was higher, and pre-ejection period (PEP) was longer at Visit 2 than Visit 1 for baseline and both tasks. RSA was higher at baseline than during the VMI anger scene at Visit 1, whereas PEP was shorter at baseline than during all VMI emotion scenes at Visit 2. RSA was higher at baseline than during BART at both visits. In conclusion, ANS data collection within evocative and arousing challenge tasks was feasible in Ghana, and the tasks were generally reliable and effective in eliciting target emotions and risk-taking behavior in this sample.

A practice already in use: a snapshot survey on the use of doxycycline as a preventive strategy (Doxy-PEP and Doxy-PrEP) in the GBMSM population in Spain.

PURPOSE: . While doxycycline shows promise as a preventative measure against certain STIs (post-exposure prophylaxis or PEP, and pre-exposure prophylaxis or PrEP), very few medical and scientific associations favor its community use. Nevertheless, sexual health organizations for gay, bisexual and other men who have sex with men (GBMSM) community have noticed an increase in requests of its use. METHODS: . The sexual health organization "Stop Sida" in Spain launched an anonymous snapshot survey to evaluate the current use of doxycycline as prevention strategy (both PEP and PrEP) in Spain through its social networks and its support groups in telegram. RESULTS: . 150 valid answers were obtained from different parts of Spain. 82 respondents (54,6% of total) had ever taken doxycycline, out of which 29 (35,4%) indicated the use as doxy-PEP and 7 (8,5%) as doxy-PrEP. The self-reported rate of STI diagnoses (mainly of syphilis and chlamydia) in the past 12 months was lower among those participants who reported having used doxy-PEP compared with those who did not report using doxy-PEP. The most common ways to obtain the doxycycline were telling a specialist that they have had a risky contact or by using leftover pills from a previous treatment. CONCLUSION: The current study is the first study to describe the use of doxycycline as a preventive strategy among the GBMSM community in Spain, and the first designed, launched and analyzed entirely by an NGO dealing with sexual health for the GBMSM community. The results obtained are aligned with other studies in other parts of Europe, such as Germany.

In Vitro Comparison of Aerosol Delivery in High-Frequency Assisted Airway Clearance Devices With Integrated Nebulizers.

BACKGROUND: High-frequency assisted airway clearance systems combine positive expiratory pressure or oscillatory positive airway pressure with integrated nebulizers to improve the delivery of aerosols and assist with airway clearance. This aerosol study evaluated lung delivery efficiency during positive expiratory pressure and oscillatory positive airway pressure therapy of 2 high-frequency assisted airway clearance/nebulizer systems. METHODS: Aerosol delivery was evaluated during positive expiratory pressure therapy of 10 cm H2O and oscillatory positive airway pressure therapy of 20 cm H2O with the BiWaze Clear and the Volara high-frequency assisted airway clearance/nebulizer systems. The handset and nebulizer were attached to an anatomic upper-airway model via a mouthpiece and placed into a plethysmograph. A tracheal filter was placed to capture the inhaled aerosol. A vacuum filter entrained fugitive aerosols from the plethysmograph. After nebulization of technetium in 3.0 mL normal saline solution, the components were scanned by using scintigraphy and the decay-corrected radiation counts were referenced to the initial nebulizer technetium charges. RESULTS: Aerosol delivery during positive expiratory pressure therapy of 10 cm H2O resulted in higher lung deposition with the BiWaze Clear versus the Volara (28 vs 6.2%; P < .001; 95% CI 16.5-27.7), and higher fugitive losses (23.7 vs 2.8%; P = .004) and nebulizer losses (55 vs 3.3%; P < .001) with the Volara than with the BiWaze Clear. Aerosol delivery during oscillatory positive airway pressure of 20 cm H2O resulted in a higher lung deposition with the BiWaze Clear versus the Volara (16.3 vs 7.3%; P = .005; 95% CI 3.3-15) and higher fugitive (22.3 vs 3.8%; P = .02) and nebulizer (58.8 vs 7.2%; P = .004) losses with the Volara. There were no differences at the other locations during testing. CONCLUSIONS: The BiWaze Clear system showed greater delivery efficiency than did the Volara during positive expiratory pressure and oscillatory positive airway pressure. The high residual nebulizer dose and fugitive aerosol losses through the handset leak valve contributed to the lower delivery efficiency observed with the Volara. The nebulizer type, circuit design, and handset are important factors when targeting effective aerosol delivery to the lungs with high-frequency assisted airway clearance therapy.

Puppies as the primary causal animal for human rabies cases: three-year prospective study of human rabies in the Philippines.

Introduction: While rabies remains a global concern, detailed studies on human rabies, particularly regarding causal animals and the reasons for not receiving postexposure prophylaxis (PEP), are lacking. Methods: We conducted a 3-year prospective study (October 2019-September 2022) at the Philippines' largest rabies referral center. We interviewed patients with suspected rabies and their families. We used LN34 qRT-PCR and rapid fluorescent focus inhibition test on saliva samples. We also compared our findings with two retrospective studies at the same hospital. Results: We enrolled 151 patients, including 131 with potential rabies exposure. Similar to retrospective studies, the participants were predominantly males (75.5%), adults (76.8%), low-income individuals (91.4%), and rural dwellers (62.3%). The causal animals were mainly dogs (97.0%), with similar incubation periods, clinical symptoms, and a high proportion not receiving vaccines or immunoglobulins (93.2%). Most causal animals were owned by either the patients' households or their neighbors (60.2%), with a significant proportion being puppies (58.8%). Most patients had knowledge of rabies; however, reasons for not seeking PEP included misconceptions about minor bites not causing rabies (51.3%), beliefs in traditional healers (33.9%), and economic constraints (22.6%). Despite completing the WHO regimen, two PEP failures were observed. LN34 qRT-PCR detected 98 positive cases (sensitivity, 64.9%; 95% CI 56.7-72.5). These strains belong to the Southeast Asia 4 subclade. Discussion: In conclusion, this study highlights the role of puppies as primary causal animals and the presence of misconceptions that preclude patients from acquiring PEP.

Is doxycycline post-exposure prophylaxis being utilised in Germany? Insights from an online survey among German men who have sex with men.

PURPOSE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.

The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach.

We propose a detailed computational beta cell model that emphasizes the role of anaplerotic metabolism under glucose and glucose-glutamine stimulation. This model goes beyond the traditional focus on mitochondrial oxidative phosphorylation and ATP-sensitive K+ channels, highlighting the predominant generation of ATP from phosphoenolpyruvate in the vicinity of KATP channels. It also underlines the modulatory role of H2O2 as a signaling molecule in the first phase of glucose-stimulated insulin secretion. In the second phase, the model emphasizes the critical role of anaplerotic pathways, activated by glucose stimulation via pyruvate carboxylase and by glutamine via glutamate dehydrogenase. It particularly focuses on the production of NADPH and glutamate as key enhancers of insulin secretion. The predictions of the model are consistent with empirical data, highlighting the complex interplay of metabolic pathways and emphasizing the primary role of glucose and the facilitating role of glutamine in insulin secretion. By delineating these crucial metabolic pathways, the model provides valuable insights into potential therapeutic targets for diabetes.

Influence of Anode Immersion Speed on Current and Power in Plasma Electrolytic Polishing.

Plasma electrolytic polishing (PeP) is mainly used to improve the surface quality and thus the performance of electrically conductive parts. It is usually used as an anodic process, i.e., the workpiece is positively charged. However, the process is susceptible to high current peaks during the formation of the vapour-gaseous envelope, especially when polishing workpieces with a large surface area. In this study, the influence of the anode immersion speed on the current peaks and the average power during the initialisation of the PeP process is investigated for an anode the size of a microreactor mould insert. Through systematic experimentation and analysis, this work provides insights into the control of the initialisation process by modulating the anode immersion speed. The results clarify the relationship between immersion speed, peak current, and average power and provide a novel approach to improve process efficiency in PeP. The highest peak current and average power occur when the electrolyte splashes over the top of the anode and not, as expected, when the anode touches the electrolyte. By immersion of the anode while the voltage is applied to the anode and counterelectrode, the reduction of both parameters is over 80%.

Bat Bites and Rabies PEP in the Croatian Reference Centre for Rabies 1995-2020.

Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995-2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts.

"Something Like That": Awareness and Acceptability of HIV PrEP and PEP Among Kenyan Adolescents.

BACKGROUND: Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but uptake is low among adolescents, particularly in resource-limited settings. We assessed awareness and acceptability of PrEP and PEP among Kenyan adolescents. METHOD: Focus group discussions were conducted with 120 adolescent boys and girls ages 15 to 19 in Kisumu. Data were analyzed using the Framework Approach. RESULTS: Adolescent participants often had not heard of or could not differentiate between PrEP and PEP. They also confused these HIV prevention tools with emergency contraceptives. Taking a daily pill to prevent HIV was perceived as analogous to taking a pill to treat HIV. Boys were aware of and willing to consider using PrEP and PEP due to their dislike for using condoms. Adolescents identified insufficient information, cost, and uncomfortableness speaking with healthcare workers about their HIV prevention needs due to sexuality stigma as barriers to using PrEP and PEP. CONCLUSION: Low awareness and poor understanding of PrEP and PEP among adolescents reveal the need for increased education and sensitization about these HIV prevention options. Expanding access to sexual and reproductive health services that are tailored to the needs of adolescents and staffed with non-judgmental providers could help reduce sexuality stigma as a barrier to accessing care. New HIV prevention approaches such as long-acting injectables or implants, on-demand regimens, and multipurpose prevention technologies may encourage increased uptake of PrEP and PEP by adolescents.

Spatial accessibility and inequality analysis of rabies-exposed patients to rabies post-exposure prophylaxis clinics in Guangzhou City, China.

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.

The clinical effects of Orff music therapy on children with autism spectrum disorder: a comprehensive evaluation.

Objective: This study aimed to investigate the clinical effects of Orff music therapy on children with Autism Spectrum Disorder (ASD) from the perspectives of parents, evaluators, and therapists. Methods: 93 children with ASD aged 3-6 years participated in the study. They were divided into an observation group (n = 48) receiving comprehensive rehabilitation intervention including Orff music therapy, and a control group (n = 45) receiving only comprehensive rehabilitation intervention. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Psycho-educational Profile-3rd edition (PEP-3) were used for assessments before and after the intervention. Results: There were no significant demographic differences between the two groups. Both groups showed significant improvements in Sensory, Relating, Language, CVP, EL, RL, VMI, AE, SR, and CARS scores at T1, T2, and T3 (T1 vs. T2, T2 vs. T3, T1 vs. T3) (all p < 0.05). The observation group demonstrated significant changes in Body and Object use and FM, while the control group showed some changes in these domains. Social and self-help, GM, CMB, and CVB also significantly improved in both groups after 6 months of intervention (all p < 0.05). In terms of different time intervals, the observation group showed greater improvements in Sensory, Relating, Language, CARS scores, EL, RL, and SR compared to the control group (all p < 0.05). The improvement levels in Body and Object use, CVP, FM, VMI, and AE did not differ significantly between the two groups in the T1-T2 interval, but were significantly higher in the observation group in the T2-T3 and T1-T3 intervals (all p < 0.05). The magnitude of changes in Social and self-help, GM, CMB, and CVB did not differ significantly between the groups. Conclusion: Orff music therapy showed significant improvements in language expression, language comprehension, social skills, cognitive abilities, imitation abilities, emotional expression and fine motor in children with ASD. These findings provide support for the use of Orff music therapy as an effective intervention for children with ASD.

Identification of the potato (Solanum tuberosum L.) P-type ATPase gene family and investigating the role of PHA2 in response to Pep13.

P-type ATPase family members play important roles in plant growth and development and are involved in plant resistance to various biotic and abiotic factors. Extensive studies have been conducted on the P-type ATPase gene families in Arabidopsis thaliana and rice but our understanding in potato remains relatively limited. Therefore, this study aimed to screen and analyze 48 P-type ATPase genes from the potato (Solanum tuberosum L.) genome database at the genome-wide level. Potato P-type ATPase genes were categorized into five subgroups based on the phylogenetic classification of the reported species. Additionally, several bioinformatic analyses, including gene structure analysis, chromosomal position analysis, and identification of conserved motifs and promoter cis-acting elements, were performed. Interestingly, the plasma membrane H+-ATPase (PM H+-ATPase) genes of one of the P3 subgroups showed differential expression in different tissues of potato. Specifically, PHA2, PHA3, and PHA7 were highly expressed in the roots, whereas PHA8 was expressed in potatoes only under stress. Furthermore, the small peptide Pep13 inhibited the expression of PHA1, PHA2, PHA3, and PHA7 in potato roots. Transgenic plants heterologously overexpressing PHA2 displayed a growth phenotype sensitive to Pep13 compared with wild-type plants. Further analysis revealed that reducing potato PM H+-ATPase enzyme activity enhanced resistance to Pep13, indicating the involvement of PM H+-ATPase in the physiological process of potato late blight and the enhancement of plant disease resistance. This study confirms the critical role of potato PHA2 in resistance to Pep13.

Post-endoscopic Retrograde Cholangiopancreatography Hemorrhagic Pancreatitis in a Young Female: A Case Report.

Hemorrhagic pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is an adverse event that has received limited attention in medical studies. We describe a 28-year-old female who was admitted with symptoms of abdominal pain, nausea, and vomiting, along with tenderness in the right upper quadrant upon physical examination. CT abdomen revealed the presence of a gallstone obstructing the common bile duct. The patient underwent an ERCP procedure, which included a biliary sphincterotomy and the balloon-assisted removal of the obstructing stone. Unfortunately, the procedure was complicated with acute pancreatitis characterized by fluid accumulation in the abdomen, suggestive of hemorrhagic pancreatitis. There was a notable decrease in hemoglobin levels and hypotension, indicating the need for a higher level of care. Patients were managed conservatively with hydration and pain control. Follow-up in the clinic confirmed the resolution of symptoms and stabilization of the hemoglobin. Prompt recognition of post-ERCP hemorrhagic pancreatitis is crucial and warrants a high index of suspicion. Furthermore, the discussion explored the various risk factors and pathological events behind post-ERCP pancreatitis to understand the mechanisms of the disease. Various previously used intervention and prevention strategies were critically discussed for the awareness of future researchers and healthcare practitioners.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

One-step high efficiency separation of prolyl endopeptidase from Aspergillus niger and its application.

Prolyl endopeptidase from Aspergillus niger (An-PEP) is an enzyme that recognizes C-terminal peptide bonds of amino acid chains and cleaves them by hydrolysis. An aqueous two-phase system (ATPS) was used to separate An-PEP from fermentation broth. Through single factor experiments, the ATPS containing 16 % (w/w) PEG2000 and 15 % (w/w) (NH4)2SO4 at pH 6.0 obtained the recovery of 79.74 ± 0.16 % and the purification coefficient of 7.64 ± 0.08. It was then used to produce soy protein isolate peptide (SPIP) by hydrolysis of soy protein isolate (SPI), and SPIP-Ferrous chelate (SPIP-Fe) was prepared with SPIP and Fe2+. The chelation conditions were optimized by RSM, as the chelation time was 30 min, chelation temperature was 25 °C, SPIP mass to VC mass was two to one and pH was 6.0. The obtained chelation rate was 82.56 ± 2.30 %. The change in the structures and functional features of SPIP before and after chelation were investigated. The FTIR and UV-Vis results indicated that the chelation of Fe2+ and SPIP depended mainly on the formation of amide bonds. The fluorescence, SEM and amino acid composition analysis results indicated that Fe2+ could induce and stabilize the surface conformation and change the amino acid distribution on the surfaces of SPIP. The chelation of SPIP and Fe2+ resulted in the enhancement of radical scavenging activities and ACE inhibitory activities. This work provided a new perspective for the further development of peptide-Fe chelates for iron supplement.

Doxycycline post-exposure prophylaxis for sexually transmitted infections impacts the gut antimicrobial resistome.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. While poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from a randomized clinical trial who either received doxy-PEP as a one-time doxycycline 200 mg taken after condomless sex (DP arm, n = 100) or standard of care treatment (SOC arm, n = 50). From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data was analyzable from 127 samples derived from 89 participants, and RNA-seq data from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. Tetracycline ARGs were detected in all day-0 DNA-seq samples and 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46-51% in the metagenome (p = 0.02) and 4-15% in the metatranscriptome (p < 0.01), but no changes in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman's ρ = 0.23, p < 0.01) and metatranscriptome (Spearman's ρ = 0.55, p < 0.01). Bacterial microbiome alpha diversity, beta diversity, and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome, and an increase in the expression of tetracycline ARGs. Notably, doxy-PEP did not significantly alter alpha diversity or taxonomic composition of the gut microbiome, and did not demonstrate significant increases in non-tetracycline ARG classes. Further studies and population level surveillance are needed to understand the implications of these findings as doxy-PEP is implemented as a public health strategy.

Four recent insights suggest the need for more refined methods to assess the resistogenicity of doxycycline post exposure prophylaxis.

Two recently published randomized trials of doxycycline post exposure prophylaxis (PEP) have concluded that this intervention is highly effective at reducing the incidence of bacterial sexually transmitted infections (STIs) and has little or no risk of promoting the spread of antimicrobial resistance (AMR). In this perspective piece, we review four types of evidence that suggest that the risk of promoting AMR has been inadequately assessed in these studies. 1) The studies have all used proportion resistant as the outcome measure. This is a less sensitive measure of resistogenicity than MIC distribution. 2) These RCTs have not considered population-level pathways of AMR selection. 3) In populations with very high antimicrobial consumption such as PrEP cohorts, the relationship between antimicrobial consumption and resistance may be saturated. 4) Genetic linkage of AMR means that increased tetracycline use may select for AMR to not only tetracyclines but also other antimicrobials in STIs and other bacterial species. We recommend novel study designs to more adequately assess the AMR-inducing risk of doxycycline PEP.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

A cross-sectional investigation of the factors associated with awareness of PEP and PrEP among Queensland university students.

OBJECTIVE: University creates unique social environments for many young people that can result in behaviour changes that can impact sexual health-related risks and facilitate transmission of HIV. Little is known about HIV knowledge, risk, and awareness of pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) among Australian university students. METHODS: A 2019 online survey distributed through Queensland universities, using active recruitment/snowball sampling. Descriptive and logistical regression analysis investigated HIV knowledge/risk and PrEP/PEP awareness. RESULTS: Of the 4,291 responses, 60.4% were 20-29 years old, 57.0% identified as heterosexual, and 31.8% were born-overseas. Mean HIV knowledge score was 9.8/12. HIV risk scores were higher among men-who-have-sex-with-men (MSM) (mean=5.2/40) compared to all other sexual behaviours (mean=3.1/40). Logistic regression indicated PrEP and PEP awareness was associated with older age (p<0.05), being non-binary/gender-diverse (p<0.05), and MSM (p<0.05). Lower odds of PrEP awareness were associated with international student status (p<0.05). CONCLUSION: This study highlights the need for future health promotion targeting younger Australians at risk of HIV to increase uptake of PrEP/PEP, particularly among overseas-born young people and those ineligible for appropriate health care in Australia. IMPLICATIONS FOR PUBLIC HEALTH: Addressing these gaps will improve sexual health outcomes for young Australians at risk of HIV and work towards virtual elimination of HIV transmission in Australia.

Preclinical and Early Clinical Development of Tenofovir Alafenamide/Elvitegravir Topical Inserts for Effective On-Demand Vaginal and Rectal HIV Prevention.

HIV/AIDS remains a global public health issue, and products available for the prevention of HIV infections are limited, especially those for short-acting, on-demand, user-controlled applications. Topical inserts are products that can be applied vaginally or rectally and have been explored as drug delivery systems. To fill the gap in the HIV prevention product pipeline, CONRAD has developed a topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG), two potent and synergistic antiretrovirals, as a simple, low-cost, and discreet option that can be self-administered vaginally and/or rectally, before and after coitus. In this review, we have described the development path of the TAF/EVG insert up to its current point in clinical testing, highlighting findings from acceptability, preclinical safety, pharmacokinetics, and efficacy evaluations and early clinical studies. In summary, the TAF/EVG inserts are stable, easy to manufacture, low-cost, acceptable, and show highly promising preclinical and clinical results for on-demand topical pre- or post-exposure HIV prevention.