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Ayumi Hirao, Yasushi Hojo, Gen Murakami, Rina Ito, Miki Hashizume, Takayuki Murakoshi, Naonori Uozumi
PLoS One Infectious Diseases, 4.05.2024
Tilføjet 4.05.2024
by Ayumi Hirao, Yasushi Hojo, Gen Murakami, Rina Ito, Miki Hashizume, Takayuki Murakoshi, Naonori Uozumi Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 μg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance. The power of kainic acid (KA)-induced network oscillation in the ACC Cg1 region slice preparation increased in LPS-treated mice. Notably, histamine, which was added in vitro, increased the oscillation power in the brain slices from LPS-untreated mice; for the LPS-treated mice, however, the effect of histamine was suppressive. In the open field test, frequency of entries into the center area showed a negative correlation with the power of network oscillation (0.3 μM of KA, theta band (3–8 Hz); 3.0 μM of KA, high-gamma band (50–80 Hz)). These results suggest that LPS-induced systemic inflammation results in increased network oscillation and a drastic change in histamine sensitivity in the ACC, accompanied by the robust production of systemic pro-inflammatory cytokines in the periphery, and that these alterations in the network oscillation and animal behavior as an acute phase reaction relate with each other. We suggest that our experimental setting has a distinct advantage in obtaining mechanistic insights into inflammatory cognitive impairment through comprehensive analyses of hormonal molecules and neuronal functions.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 3.05.2024
Tilføjet 3.05.2024
Abstract We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV pre-exposure prophylaxis (PrEP) during pregnancy and postpartum and compared hair levels with tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). Overall, 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster randomized trial. Having a partner known to be living with HIV was associated with higher hair TFV levels (p
Læs mere Tjek på PubMedAmerican Journal of Tropical Medicine and Hygiene, 2.05.2024
Tilføjet 2.05.2024
Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 110 Issue: 5 Pages: 953-960
Læs mere Tjek på PubMedSaraiva, I. E., Hamahata, N., Huang, D. T., Kane-Gill, S. L., Rivosecchi, R. M., Shiva, S., Nolin, T. D., Chen, X., Minturn, J., Chang, C.-C. H., Li, X., Kellum, J., Gomez, H.
BMJ Open, 1.05.2024
Tilføjet 1.05.2024
IntroductionAcute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. Methods and analysisBlind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. Ethics and disseminationThis study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. Trial registration numberNCT05900284.
Læs mere Tjek på PubMedJeffrey V. Lazarus, Trenton M. White, Katarzyna Wyka, Scott C. Ratzan, Kenneth Rabin, Heidi J. Larson, Federico Martinon-Torres, Ernest Kuchar, Salim S. Abdool Karim, Tamara Giles-Vernick, Selina Müller, Carolina Batista, Nellie Myburgh, Beate Kampmann, Ayman El-Mohandes
Nature, 30.04.2024
Tilføjet 30.04.2024
Murphy, Matthew; Rogers, Brooke; Galipeau, Drew; Toma, Emily; Almonte, Alexi; Napoleon, Siena; Schmid, Christopher H.; Ahluwalia, Jasjit S.; Chan, Philip
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Pre-exposure prophylaxis (PrEP) is an effective approach to preventing HIV acquisition and is recommended for populations overrepresented in carceral systems given the overlap with populations disproportionately impacted by HIV. However, few studies have focused on PrEP initiation outcomes in a carceral setting to maximize public health impact. Setting: This study was conducted in a unified jail/prison system within the state of Rhode Island located in the United States. Methods: A prospective observational cohort of men initiating PrEP within a jail setting were enrolled in this trial. Men were referred by providers, staff, or after self-presenting for HIV preventive care, these individuals were offered enrollment in the study which involved evaluation for clinical PrEP eligibility, PrEP initiation while incarcerated, continuation upon community re-entry and linkage to a community PrEP provider post-release. Results: A total of (N=100) men in the jail facility (e.g. “intake”) were enrolled in the cohort. Of the 100 men enrolled, 83% were determined to be PrEP eligible through standard clinical evaluation, 37% were prescribed PrEP, and 26% initiated PrEP while incarcerated. In total, 5% of enrolled individuals were linked successfully to PrEP care in the community. Conclusion: Our findings suggest preliminary feasibility and acceptability of initiating PrEP within a jail setting. There were significant challenges across the PrEP care continuum that can be used to inform future studies and practice. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedWhite, Douglas AE; Godoy, Ashley; Jewett, Montana; Burns, Molly; Pinto, Cinthya Mujica; Packel, Laura J; Garcia-Chinn, Maria; Anderson, Erik S; McCoy, Sandra I
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Emergency departments (ED) provide care to patients at increased risk for acquiring HIV and for many of them, the ED serves as their sole point of entry into the healthcare system. We implemented the HIV PreventED Program to increase access to HIV prevention services for ED patients. Setting: Emergency department in Oakland, CA with an annual census of 57,000 visits. Methods: This cross-sectional study evaluated the first 9 months of the HIV PreventED Program. In this program, a navigator surveyed adult HIV negative ED patients to determine their risk for acquiring HIV infection, incorporating HIV prevention counseling into their assessments. Patients at higher risk for acquiring HIV were referred to outpatient prevention services, if interested. The primary outcome measure was the number and proportion of ED patients at higher risk for acquiring HIV that followed up for outpatient prevention services. Results: There were 1,233 HIV negative patients assessed by the navigator and who received ED-based HIV prevention counseling. Of these, 193 (15.7%) were identified at higher risk and offered an outpatient referral for prevention services, of which 104 accepted (53.9%), 23 (11.9%) attended the referral, and 13 (6.7%) were prescribed pre-exposure prophylaxis (PrEP). The median time to linkage was 28 days (interquartile range 15 to 41 days). Conclusion: A navigator focused on providing ED-based HIV prevention counseling and linkage to outpatient services is feasible. Strategies to more efficiently identify ED patients at higher risk for HIV acquisition, such as automated identification of risk data from the electronic health record, and policies to improve follow up and the receipt of PrEP, such as same-day PrEP initiation, should be prospectively evaluated. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedBMC Infectious Diseases, 27.04.2024
Tilføjet 27.04.2024
Abstract Introduction Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. Methods A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. Key findings Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. Conclusion Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources– such as upscaled screening– to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.
Læs mere Tjek på PubMedMpirirwe, R., Segawa, I., Ojiambo, K. O., Kamacooko, O., Nangendo, J., Semitala, F. C., Kyambadde, P., Kalyango, J. N., Kiragga, A., Karamagi, C., Katahoire, A., Kamya, M., Mujugira, A.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectiveTo evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DesignSystematic review and meta-analysis. Data sourcesWe searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. Eligibility criteria for studiesRandomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. Data extraction and synthesisSeven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. ResultsOf 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). ConclusionsA hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO registration numberCRD42020219363.
Læs mere Tjek på PubMedAmbrosio, L., Faulkner, J., Morris, J. H., Stuart, B., Lambrick, D., Compton, E., Portillo, M. C.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectiveTo understand the physical activity and mental health of individuals living with long-term conditions during the COVID-19 pandemic. DesignA sequential explanatory mixed-methods study with two phases: phase 1: quantitative survey and phase 2: qualitative follow-up interviews. SettingFor the quantitative phase, an online survey was launched in March 2021, using Microsoft Forms. For the qualitative phase, in-depth semistructured interviews were conducted via online. Participants368 adults over 18 years old living in the UK with at least one long-term condition completed the survey. Interviews were conducted in a subsample of participants from the previous quantitative phase, with 26 people. Data were analysed using thematic analysis. ResultsResponses from the survey showed that people with one long-term condition were significantly more physically active and spent less time sitting, than those with two or more conditions, presenting with significantly higher well-being (p
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Background Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, often harboring resistance-associated mutations to azithromycin (AZM). Global surveillance has been mandated to tackle the burden caused by MG, yet no data are available for Austria. Thus, we aimed to investigate the prevalence of MG, disease characteristics, and treatment outcomes at the largest Austrian HIV—and STI clinic. Methods All MG test results at the Medical University of Vienna from 02/2019 to 03/2022 were evaluated. Azithromycin resistance testing was implemented in 03/2021. Results Among 2671 MG tests, 199 distinct and mostly asymptomatic (68%; 135/199) MG infections were identified, affecting 10% (178/1775) of all individuals. This study included 83% (1479/1775) men, 53% (940/1775) men who have sex with men (MSM), 31% (540/1754) HIV+, and 15% (267/1775) who were using HIV pre-exposure prophylaxis (PrEP). In logistic regression analysis, ‘MSM’ (aOR 2.55 (95% CI 1.65–3.92)), ‘use of PrEP’ (aOR 2.29 (95% CI 1.58–3.32)), and ‘history of syphilis’ (aOR 1.57 (95% CI 1.01–2.24) were independent predictors for MG infections. Eighty-nine percent (178/199) received treatment: 11% (21/178) doxycycline (2 weeks), 52% (92/178) AZM (5 days), and 37% ( 65/178) moxifloxacin (7–10 days) and 60% (106/178) had follow-up data available showing negative tests in 63% (5/8), 76% (44/58) and 85% (34/40), respectively. AZM resistance analysis was available for 57% (114/199)) and detected in 68% (78/114). Resistance-guided therapy achieved a cure in 87% (53/61), yet, empiric AZM-treatment (prior to 03/2021) cleared 68% (26/38). Conclusions Mycoplasma genitalium was readily detected in this Austrian observational study, affected predominantly MSM and often presented as asymptomatic disease. We observed a worryingly high prevalence of AZM resistance mutations; however, empiric AZM treatment cleared twice as many MG infections as expected.
Læs mere Tjek på PubMedCole, S. W., Glick, J. L., Campoamor, N. B., Sanchez, T. H., Sarkar, S., Vannappagari, V., Rinehart, A., Rawlings, K., Sullivan, P. S., Bridges, J. F. P.
BMJ Open, 23.04.2024
Tilføjet 23.04.2024
IntroductionCabotegravir long-acting injectable HIV pre-exposure prophylaxis (LA-PrEP) was shown to be safe and effective in multiple clinical trials. Increasing uptake and persistence among populations with elevated risk for HIV acquisition, especially among men who have sex with men (MSM), is critical to HIV prevention. ObjectiveThis analysis aims to understand potential users’ preferences for LA-PrEP, with audience segmentation. DesignWillingness to use and preferences for LA-PrEP were measured in HIV-negative, sexually active MSM in the 2020 American Men’s Internet Survey. Respondents answered a discrete choice experiment with paired profiles of hypothetical LA-PrEP characteristics with an opt-out option (no LA-PrEP). Conditional and mixed logit models were run; the final model was a dummy-coded mixed logit that interacted with the opt-out. SettingUS national online sample. ResultsAmong 2506 MSM respondents, most (75%) indicated a willingness to use LA-PrEP versus daily oral PrEP versus no PrEP. Respondents were averse to side effects and increasing costs and preferred increasing levels of protection. Respondents preferred a 2-hour time to obtain LA-PrEP vs 1 hour, with a strong aversion to 3 hours. Overall, there was an aversion to opting out of LA-PrEP, with variations: those with only one partner, no/other insurance or who were Black, Indigenous or People of Colour were significantly less likely to prefer LA-PrEP, while those who were Hispanic/Latino, college educated and
Læs mere Tjek på PubMed