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47 ud af 47 tidsskrifter valgt, søgeord (urin) valgt, emner højest 180 dage gamle, sorteret efter nyeste først.
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Dipak Kathayat, Brian C. VanderVen
Trends in Microbiology, 15.02.2024
Tilføjet 15.02.2024
Mycobacterium tuberculosis (Mtb) replicates within host macrophages by adapting to the stressful and nutritionally constrained environments in these cells. Exploiting these adaptations for drug discovery has revealed that perturbing cAMP signaling can restrict Mtb growth in macrophages. Specifically, compounds that agonize or stimulate the bacterial enzyme, Rv1625c/Cya, induce cAMP synthesis and this interferes with the ability of Mtb to metabolize cholesterol. In murine tuberculosis (TB) infection models, Rv1625c/Cya agonists contribute to reducing relapse and shortening combination treatments, highlighting the therapeutic potential for this class of compounds. More recently, cAMP signaling has been implicated in regulating fatty acid utilization by Mtb. Thus, a new model is beginning to emerge in which cAMP regulates the utilization of host lipids by Mtb during infection, and this could provide new targets for TB drug development. Here, we summarize the current understanding of cAMP signaling in Mtb with a focus on our understanding of how cAMP signaling impacts Mtb physiology during infection. We also discuss additional cAMP-related drug targets in Mtb and other bacterial pathogens that may have therapeutic potential.
Læs mere Tjek på PubMedMalaria Journal, 15.02.2024
Tilføjet 15.02.2024
Abstract Background South Africa set a target to eliminate malaria by 2023, with KwaZulu-Natal (KZN) Province the malaria-endemic province closest to achieving this goal. Objective two of the National Malaria Elimination Strategic Plan (NMESP) focused on strengthening surveillance systems to support the country’s elimination efforts. Regular evaluations of the malaria surveillance systems against the targets of the NMESP objective are crucial in improving their performance and impact. This study aimed to assess whether the malaria surveillance system in KwaZulu-Natal Province meets the NMESP surveillance objective and goals. Methods A mixed-methods cross-sectional study design was used to evaluate the malaria surveillance system, focusing on the District Health Information System 2 (DHIS2). The study assessed the data quality, timeliness, simplicity, and acceptability of the system. Key personnel from KZN’s Provincial malaria control programme were interviewed using self-administered questionnaires to evaluate their perception of the system\'s simplicity and acceptability. Malaria case data from January 2016 to December 2020 were extracted from the DHIS2 and evaluated for data quality and timeliness. Results The survey respondents generally found the DHIS2-based surveillance system acceptable (79%, 11/14) and easy to use (71%, 10/14), stating that they could readily find, extract, and share data (64%, 9/14). Overall data quality was good (88.9%), although some variables needed for case classification had low completeness and data availability. However, case notifications were not timely, with only 61% (2 622/4 329) of cases notified within 24 h of diagnosis. During the 5-year study period, the DHIS2 captured 4 333 malaria cases. The majority of cases (81%, 3 489/4 330) were categorized as imported, and predominately in males (67%, 2 914/4 333). Conclusion While the malaria surveillance system in KZN Province largely met the NMESP surveillance strategic goals, it failed to achieve the overarching surveillance objective of 100% notification of cases within 24 h of diagnosis. The majority of reported cases in KZN Province were classified as imported, emphasizing the importance of complete data for accurate case classification. Engaging with healthcare professionals responsible for case notification and disseminating aggregated data back to them is needed to encourage and improve notification timeliness.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
Journal of Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
Abstract Background Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens.Methods In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd, bo′, or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects.Results The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli “bd-I only” strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus “bd only” strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli.Conclusions Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.
Læs mere Tjek på PubMedCamacho-Dominguez, L., Rojas, M., Herran, M., Rodriguez, Y., Beltran, S., Galindo, P. S., Aguirre-Correal, N., Espitia, M., Garcia, S., Bejarano, V., Morales-Gonzalez, V., Covaleda-Vargas, J. E., Rodriguez-Jimenez, M., Zapata, E., Monsalve, D. M., Acosta-Ampudia, Y., Anaya, J.-M., Ramirez-Santana, C.
BMJ Open, 15.02.2024
Tilføjet 15.02.2024
BackgroundA paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. ObjectivesTo determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DesignA case–control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SettingHigh-complexity centre above 2640 m above sea level (masl) in Colombia. ParticipantsA population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. Main outcome measureMortality during hospitalisation. Main resultsAfter the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). ConclusionsThis study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
Abstract Background Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models. Methods We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (e.g. test number, vaccine coverage). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios. Results At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12–50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts was more stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics. Discussion Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.
Læs mere Tjek på PubMedAlana Rosenberg, Lisa B. Puglisi, Kathryn A. Thomas, Alexandra A. Halberstam, Rosemarie A. Martin, Lauren Brinkley-Rubinstein, Emily A. Wang
PLoS One Infectious Diseases, 14.02.2024
Tilføjet 14.02.2024
by Alana Rosenberg, Lisa B. Puglisi, Kathryn A. Thomas, Alexandra A. Halberstam, Rosemarie A. Martin, Lauren Brinkley-Rubinstein, Emily A. Wang For the millions of people incarcerated in United States’ prisons and jails during the COVID-19 pandemic, isolation took many forms, including medical isolation for those sick with COVID-19, quarantine for those potentially exposed, and prolonged facility-wide lockdowns. Incarcerated people’s lived experience of isolation during the pandemic has largely gone undocumented. Through interviews with 48 incarcerated people and 27 staff at two jails and one prison in geographically diverse locations in the United States, we document the implementation of COVID-19 isolation policies from the perspective of those that live and work in carceral settings. Incarcerated people were isolated from social contact, educational programs, employment, and recreation, and lacked clear communication about COVID-19-related protocols. Being isolated, no matter the reason, felt like punishment and was compared to solitary confinement—with resultant long-term, negative impacts on health. Participants detailed isolation policies as disruptive, detrimental to mental health, and dehumanizing for incarcerated people. Findings point to several recommendations for isolation policy in carceral settings. These include integrating healthcare delivery into isolation protocols, preserving social relationships during isolation, promoting bidirectional communication about protocols and their effect between facility leadership and incarcerated people. Most importantly, there is an urgent need to re-evaluate the current approach to the use of isolation in carceral settings and to establish external oversight procedures for its use during pandemics.
Læs mere Tjek på PubMedInfection, 14.02.2024
Tilføjet 14.02.2024
Abstract Purpose Liver transplant (LT) recipients have an increased risk of tuberculosis (TB), which is associated with higher mortality rates. This retrospective cohort study assessed the outcome and tolerability of screening and treatment of latent tuberculosis infection (LTBI) in LT recipients. Methods Between March 2020 and February 2022, all adult LT candidates at our institution were screened for LTBI. The candidates who tested positive for interferon-γ-releasing assay or met epidemiological or clinical-radiological criteria for LTBI were treated and monitored. Results Among the 857 LT recipients, 199 (23.2%) were diagnosed with LTBI, of which 171 (85.9%) initiated LTBI treatment. The median duration of follow-up was 677 days. Adequate LTBI treatment occurred in 141/171 (82.5%) patients and was discontinued prematurely in 30/171 (17.5%) patients. The most common reason for discontinuation was liver enzyme elevation (11/30, 36.7%), although only five discontinued treatment due to suspicion of isoniazid-associated hepatotoxicity. None of the LTBI-treated patients developed active TB during the follow-up period, while 3.6% (1/28) of untreated LTBI patients and 0.6% (4/658) of patients without LTBI developed TB. Conclusion These findings demonstrate that LTBI screening and treatment is a safe and effective strategy to prevent TB in LT recipients. However, monitoring for adverse events and liver enzyme elevation is recommended.
Læs mere Tjek på PubMedInfection, 14.02.2024
Tilføjet 14.02.2024
Abstract Purpose This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. Methods People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. Results The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. Conclusions IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.02.2024
Tilføjet 14.02.2024
Abstract Background Drug-resistant tuberculosis (DR-TB) is a major public health threat in Hunan Province, with an increasing clinical burden in recent years. This study aimed to identify socio-demographic and clinical factors associated with DR-TB in Hunan province, China. Methods A case-control study was conducted in Hunan province. Cases were all DR-TB patients who were confirmed by culture and Drug susceptibility testing (DST) and enrolled at the DR-TB treatment center of Hunan Chest Hospital from 2013 to 2018. Controls were all Drug Susceptible TB (DS-TB) patients confirmed by DST and enrolled at the same hospital during the same period. A multivariable logistic regression model was fitted to identify factors significantly associated with DR-TB. Results A total of 17,808 patients (15,534 DS-TB controls and 2274 DR-TB cases) were included in the study, with a mean age of 42.5 years (standard deviation (SD) ± 17.5 years) for cases and 46.1 years (SD ± 19.1 years) for controls. Age 15-64 years (Adjusted odds ratio (AOR = 1.5, 95% CI; 1.4, 1.8)), ethnic minorities (AOR = 1.5; 95% CI; 1.4, 1.8), and a history of previous TB treatment (AOR) = 1.84; 95% CI: 1.57, 2.15) was significantly associated with DR-TB. Being resident in a province outside Hunan was also a significant risk factor (AOR = 1.67; 1.27, 2.21) for DR-TB. Conclusion and recommendations To prevent the occurrence of DR-TB in Hunan Province, interventions should be targeted at high-risk demographic groups such as ethnic minorities, individuals of productive age, and residents living outside the province. Interventions must also be targeted to previously treated cases, suggesting the appropriateness of diagnosis, treatment, and follow-up. Understanding the risk factors at the province level helps design strategies for controlling DR-TB due to variations by socioeconomic differences, quality of health care, and healthcare access.
Læs mere Tjek på PubMedShuai WangQin-Yi MaJuan DuTing-Ting WeiWan-Xue ZhangPeng WangYiguo ZhouMing WeiLi GuFuqiang CuiQing-Bin Lua Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of Chinab Department of Laboratorial of Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, People’s Republic of Chinac Center for Infectious Disease and Policy Research & Global Health and Infectious Diseases Group, Peking University, Beijing, People’s Republic of Chinad Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, People’s Republic of Chinae Ministry of Education, Key Laboratory of Epidemiology of Major Diseases (Peking University), Beijing, People’s Republic of China
Emerg Microbes Infect, 13.02.2024
Tilføjet 13.02.2024
Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek
PLoS One Infectious Diseases, 13.02.2024
Tilføjet 13.02.2024
by Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2–22% in symptomatic individuals and 2–14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p
Læs mere Tjek på PubMedJournal of Infectious Diseases, 13.02.2024
Tilføjet 13.02.2024
Abstract Background Unlike influenza, information on the burden of human metapneumovirus (HMPV) as a cause of hospitalizations in adults with acute respiratory illness (ARI) is limited.Methods We compared the population-based incidence, seasonality, and clinical characteristics of these two viral infections among adults aged 20 years and over with ARI hospitalisations in Auckland, New Zealand, during 2012-2015 through the Southern Hemisphere Influenza Vaccine Effectiveness Research and Surveillance (SHIVERS) project.Results Of the 14,139 ARI hospitalisations, 276 (4.3%) of 6484 tested positive for HMPV and 1342 (19.1%) of 7027 tested positive for influenza. Crude rates of 9.8 (95% CI: 8.7-11.0) HMPV and 47.6 (95% CI: 45.1-50.1) influenza-associated ARI hospitalisations were estimated for every 100,000 adult residents annually. The highest rates for both viruses were in those aged 80 years or older, of Māori or Pacific ethnicity, or living in low socioeconomic status (SES) areas. HMPV infections were more common than influenza in those with chronic medical conditions.Conclusions Although HMPV infections accounted for fewer hospitalisations than influenza in adults aged 20 years and over, HMPV-associated ARI hospitalisation rates were higher than influenza in older adults, Maori and Pacific people and those of low SES. This highlighted a need for vaccine/antiviral development.
Læs mere Tjek på PubMedJelen, A., Rodin, G., Graham, L., Goldfarb, R., Mah, K., Satele, D. V., Elliot, M., Krzyzanowska, M. K., Rubin, B. B.
BMJ Open, 13.02.2024
Tilføjet 13.02.2024
ObjectivesTo assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work–life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic. DesignCross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021. SettingCardiovascular and oncology care settings at a Canadian quaternary hospital network. Participants261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480). Outcome measuresSurvey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors. ResultsAmong 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p
Læs mere Tjek på PubMedKeil, V., Schaumburg, T., Buchta, F., Luz, J. K., Kolbe-Busch, S., Chaberny, I. F., von Lengerke, T.
BMJ Open, 13.02.2024
Tilføjet 13.02.2024
IntroductionInfection prevention and control (IPC) teams are routinely confronted with intense emotions in their daily work, as they are involved in many change processes with front-line medical staff, for example, when promoting compliance with basic IPC measures. In addition, they are confronted with challenges due to their role as intermediaries. Based on former research, this study aims to empower IPC teams to promote clinicians’ compliance through interventions focusing on the IPC teams’ leadership skills. Methods and analysisThe IP-POWER study (Infection Prevention with head and heart: Psychological empowerment of IPC teams), a multicentre, two-arm, non-blinded, cluster-randomised controlled trial with a parallel waiting control group, is planned to be conducted in Germany as of February to November 2024. A group of 10 voluntary hospitals is going to participate in a multistage intervention programme, including 2 days of intense psychological training; 5 hospitals will be randomly assigned to the waiting control group. After the workshops, there will be a 12-week follow-up period during which the contents learnt within the workshops can be applied and internalised into IPC practice. The proposed outcomes (both self-assessed and other-assessed leadership competencies of IPC team members and their task profiles, perceived workload, motivation to act in order to implement IP measures and goal attainment) are going to be collected with an online questionnaire, followed by an analysis with IBM SPSS (Statistics 29 (or later)) using descriptive analyses and multiple linear regressions. Additionally, as external data sources, hand hygiene compliance rates from the study hospitals’ monitoring systems will be analysed using ² tests. Ethics and disseminationThis study was reviewed and approved by the ethics committee of the University of Leipzig (184/23-ek; vote from 4 July 2023). Findings will be disseminated via peer-review publications, and national and international conference presentations. Trial registration numberDRKS00031879.
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.02.2024
Tilføjet 13.02.2024
Abstract Background Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. Methods Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. Findings Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. Interpretation Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks Funding Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044)
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.02.2024
Tilføjet 13.02.2024
Abstract Background The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. Methods Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan–Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. Results Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan–Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. Conclusions This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.
Læs mere Tjek på PubMedTing-Li Chen, Elizabeth P. Chou, Min-Yi Chen, Fushing Hsieh
PLoS One Infectious Diseases, 12.02.2024
Tilføjet 12.02.2024
by Ting-Li Chen, Elizabeth P. Chou, Min-Yi Chen, Fushing Hsieh We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nation’s population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.
Læs mere Tjek på PubMedAbraham Teka Ajema, Yilkal Simachew, Meiraf Daniel Meshesha, Taye Gari
PLoS One Infectious Diseases, 12.02.2024
Tilføjet 12.02.2024
by Abraham Teka Ajema, Yilkal Simachew, Meiraf Daniel Meshesha, Taye Gari Objectives To assess the incidence and predictors of time to Tuberculosis (TB) development among Human Immunodeficiency Virus (HIV) positive patients attending follow-up care in health facilities of Hawassa, Ethiopia. Methods We conducted a retrospective cohort study from April 1–30, 2023. A total of 422 participants were selected using a simple random sampling method. Data was collected from the medical records of patients enrolled between January 1, 2018 –December 31, 2022, using the Kobo toolbox. We used Statistical Package for Social Studies (SPSS) version 26.0 for data analysis. To estimate the duration of TB-free survival, we applied the Kaplan-Meier survival function and fitted Cox proportional hazard models to identify the predictors of time to TB development. Adjusted hazard ratios (AHR) with 95% confidence intervals were calculated and statistical significance was declared at a P-value of 0.05. Results The overall incidence rate of TB among HIV-positive patients was 6.26 (95% CI: 4.79–8.17) per 100 person-years (PYs). Patients who did not complete TB Preventive Therapy (TPT) were more likely to have TB than those who did (AHR = 6.2, 95% CI: 2.34–16.34). In comparison to those who began antiretroviral therapy (ART) within a week, those who began after a week of linkage had a lower risk of TB development (AHR = 0.44, 95% CI: 0.21–0.89). Patients who received ART for six to twelve months (AHR = 0.18, 95% CI: 0.05–0.61) and for twelve months or longer (AHR = 0.004, 95% CI: 0.001–0.02) exhibited a decreased risk of TB development in comparison to those who had ART for less than six months. Conclusion The incidence of TB among HIV-positive patients is still high. To alleviate this burden, special attention should be given to regimen optimization and provision of adherence support for better completion of TPT, sufficient patient preparation, thorough clinical evaluation for major (Opportunistic Infections) OIs prior to starting ART, and ensuring retention on ART.
Læs mere Tjek på PubMedMalaria Journal, 12.02.2024
Tilføjet 12.02.2024
Abstract Background Malaria remains an enduring public health concern in Indonesia, exacerbated by its equatorial climate that fosters the proliferation of Anopheles mosquitoes. This study seeks to assess the performance of the malaria elimination programme comprehensively. Methods Between May and August 2022, a qualitative study was conducted in Muara Enim Regency, South Sumatra Province, involving 22 healthcare professionals from diverse backgrounds. These informants were strategically chosen for their pivotal roles in providing profound insights into various facets of the malaria elimination programme. This encompasses inputs such as human resources, budgetary allocation, and infrastructural support; processes like case identification and management, capacity enhancement, epidemiological surveillance, prevention measures, outbreak control, and enhanced communication and educational initiatives; and, notably, the programme’s outcomes. Data were collected through 3-h Focus Group Discussions (FGDs) divided into two groups, each with 12 participants: healthcare professionals and programme managers. Additionally, in-depth interviews (IDIs) were conducted with ten informants. Employing the Input-Process-Output (IPO) model, this study meticulously analysed the healthcare system dynamics and the interventions’ efficacy. Results The study unveiled many challenges during the input phase, including the absence of entomologists and a shortage of diagnostic tools. Despite these obstacles, it documented remarkable accomplishments in the output domain, marked by significant advancements in the distribution of mosquito nets and the successful implementation of the Early Warning System (EWS). Despite the adversities, the programme has made substantial strides towards malaria elimination. Conclusions Urgent action is imperative to bolster the effectiveness of the malaria elimination programme. Key measures encompass augmenting the entomologist workforce, optimizing resource allocation, and ensuring stringent adherence to regional regulations. Addressing these concerns will enhance programme efficacy, yielding enduring public health benefits. This research substantially contributes to Indonesia’s ongoing malaria elimination endeavours, furnishing actionable insights for programme enhancement. Consequently, this research holds significant importance for the malaria elimination drive.
Læs mere Tjek på PubMedPolo Friz, Melisa; Rezoagli, Emanuele; Safaee Fakhr, Bijan; Florio, Gaetano; Carlesso, Eleonora; Giudici, Riccardo; Forlini, Clarissa; Tardini, Francesca; Langer, Thomas; Laratta, Matteo; Casella, Giampaolo; Forastieri Molinari, Andrea; Protti, Alessandro; Cecconi, Maurizio; Cabrini, Luca; Biagioni, Emanuela; Berselli, Angela; Mirabella, Lucia; Tonetti, Tommaso; De Robertis, Edoardo; Grieco, Domenico Luca; Antonelli, Massimo; Citerio, Giuseppe; Fumagalli, Roberto; Foti, Giuseppe; Zanella, Alberto; Grasselli, Giacomo; Bellani, Giacomo; for the COVID-19 Lombardy ICU Network
Critical Care Explorations, 11.02.2024
Tilføjet 11.02.2024
OBJECTIVES: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN: Retrospective observational cohort study. SETTING: Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION: The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS: Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.
Læs mere Tjek på PubMedTridon, Chloé; Bachelet, Delphine; El Baied, Majda; Eloy, Philippine; Ortuno, Sofia; Para, Marylou; Wicky, Paul-Henri; Vellieux, Geoffroy; de Montmollin, Etienne; Bouadma, Lila; Manceau, Hana; Timsit, Jean-François; Peoc’h, Katell; Sonneville, Romain
Critical Care Explorations, 11.02.2024
Tilføjet 11.02.2024
OBJECTIVES: Neurologic outcomes of patients under venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be worsened by secondary insults of systemic origin. We aimed to assess whether sepsis, commonly observed during ECMO support, is associated with brain injury and outcomes. DESIGN: Single-center cohort study of the “exposed-non-exposed” type on consecutive adult patients treated by VA-ECMO. SETTING: Medical ICU of a university hospital, France, 2013–2020. PATIENTS: Patients with sepsis at the time of VA-ECMO cannulation (“sepsis” group) were compared with patients without sepsis (“no sepsis” group). The primary outcome measure was poor functional outcome at 90 days, defined by a score greater than or equal to 4 on the modified Rankin scale (mRS), indicating severe disability or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included (“sepsis,” n = 128; “no sepsis,” n = 68), of whom 87 (44.4%) had presented cardiac arrest before VA-ECMO cannulation. A poor functional outcome (mRS ≥ 4) was observed in 99 of 128 patients (77.3%) of the “sepsis” group and 46 of 68 patients (67.6%) of the “no sepsis” group (adjusted logistic regression odds ratio (OR) 1.21, 95% CI, 0.58–2.47; inverse probability of treatment weighting (IPTW) OR 1.24; 95% CI, 0.79–1.95). Subsequent analyses performed according to pre-ECMO cardiac arrest status suggested that sepsis was independently associated with poorer functional outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest (adjusted logistic regression OR 3.44; 95% CI, 1.06–11.40; IPTW OR 3.52; 95% CI, 1.68–7.73), whereas no such association was observed in patients without pre-ECMO cardiac arrest (adjusted logistic regression OR 0.69; 95% CI, 0.27–1.69; IPTW OR 0.76; 95% CI, 0.42–1.35). Compared with the “no sepsis” group, “sepsis” patients presented a significant increase in S100 calcium-binding protein beta concentrations at day 1 (0.94 μg/L vs. 0.52 μg/L, p = 0.03), and more frequent EEG alterations (i.e., severe slowing, discontinuous background, and a lower prevalence of sleep patterns), suggesting brain injury. CONCLUSION: We observed a detrimental role of sepsis on neurologic outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest, but not in other patients.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 11.02.2024
Tilføjet 11.02.2024
Abstract Insects are one of the most successful animals in nature, and entomopathogenic fungi play a significant role in the natural epizootic control of insect populations in many ecosystems. The interaction between insects and entomopathogenic fungi has continuously co-evolved over hundreds of millions of years. Many components of the insect innate immune responses against fungal infection are conserved across phyla. Additionally, behavioral responses, which include avoidance, grooming, and/or modulation of body temperature, have been recognized as important mechanisms for opposing fungal pathogens. In an effort to investigate possible crosstalk and mediating mechanisms between these fundamental biological processes, recent studies have integrated and/or explored immune and behavioral responses. Current information indicates that during discrete stages of fungal infection, several insect behavioral and immune responses are altered simultaneously, suggesting important connections between the two systems. This review synthesizes recent advances in our understanding of the physiological and molecular aspects influencing crosstalk between behavioral and innate immune antifungal reactions, including chemical perception and olfactory pathways.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 10.02.2024
Tilføjet 10.02.2024
Abstract Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focusing on elucidating the roles of obesity and GDM to the clinical outcome. Using immunoassays and multicolour flow cytometry, cytokine profiles and immune cell frequencies were measured in maternal circulation and central metabolic tissues (placenta and visceral adipose tissue (VAT)) in GDM-diagnosed (n=28) and normal glucose tolerant (n=32) women undergoing caesarean section. Participants were sub grouped as non-obese (BMI
Læs mere Tjek på PubMedGroele, L., Dzygało, K., Kowalska, A., Szypowska, A.
BMJ Open, 10.02.2024
Tilføjet 10.02.2024
IntroductionSphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. Methods and analysisA total of 102 children aged 10–17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate Ethics and disseminationThe study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. Trial registration numberEnduraCT 2020-003916-28.
Læs mere Tjek på PubMedLee, A., Shah, S., Atha, K., Indoe, P., Mahmoud, N., Niblett, G., Pradhan, V., Roberts, N., Malouf, R. S., Topiwala, A.
BMJ Open, 10.02.2024
Tilføjet 10.02.2024
ObjectivesPreservation of brain health is an urgent priority for the world’s ageing population. The evidence base for brain health optimisation strategies is rapidly expanding, but clear recommendations have been limited by heterogeneity in measurement of brain health outcomes. We performed a scoping review to systematically evaluate brain health measurement in the scientific literature to date, informing development of a core outcome set. DesignScoping review. Data sourcesMedline, APA PsycArticles and Embase were searched through until 25 January 2023. Eligibility criteria for selecting studiesStudies were included if they described brain health evaluation methods in sufficient detail in human adults and were in English language. Data extraction and synthesisTwo reviewers independently screened titles, abstracts and full texts for inclusion and extracted data using Covidence software. ResultsFrom 6987 articles identified by the search, 727 studies met inclusion criteria. Study publication increased by 22 times in the last decade. Cohort study was the most common study design (n=609, 84%). 479 unique methods of measuring brain health were identified, comprising imaging, cognitive, mental health, biological and clinical categories. Seven of the top 10 most frequently used brain health measurement methods were imaging based, including structural imaging of grey matter and hippocampal volumes and white matter hyperintensities. Cognitive tests such as the trail making test accounted for 286 (59.7%) of all brain health measurement methods. ConclusionsThe scientific literature surrounding brain health has increased exponentially, yet measurement methods are highly heterogeneous across studies which may explain the lack of clinical translation. Future studies should aim to develop a selected group of measures that should be included in all brain health studies to aid interstudy comparison (core outcome set), and broaden from the current focus on neuroimaging outcomes to include a range of outcomes.
Læs mere Tjek på PubMedBMC Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Background An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. Methods We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020–May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. Results After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11–1.23]; children: aOR, 1.18[95% CI, 1.08–1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38–1.63]; children: aOR, 1.40[95% CI, 1.15–1.70]) 31–150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17–1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11–1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30–1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. Conclusions Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.
Læs mere Tjek på PubMedBMC Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Background An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. Methods We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020–May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. Results After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11–1.23]; children: aOR, 1.18[95% CI, 1.08–1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38–1.63]; children: aOR, 1.40[95% CI, 1.15–1.70]) 31–150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17–1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11–1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30–1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. Conclusions Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 10.02.2024
Tilføjet 10.02.2024
Abstract One continuous companion and one of the major players in the human blood virome are members of the Anelloviridae family. Anelloviruses are probably found in all humans, infection occurs early in life and the composition (anellome) is thought to remain stable and personal during adulthood. The stable anellome implies a great balance between the host immune system and the virus. However, the lack of a robust culturing system hampers direct investigation of interactions between virus and host cells. Other techniques however, including next generation sequencing, AnelloScan-antibody tests, evolution selection pressure analysis and virus protein structures, do provide new insights into the interactions between anelloviruses and the host immune system. This review aims at providing an overview of the current knowledge on the immune mechanisms acting on anelloviruses and the countering viral mechanisms allowing immune evasion.
Læs mere Tjek på PubMedClinical Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Background Pre-diabetes is associated with proteinuria, a risk factor for chronic kidney disease. While people living with HIV (PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among pre-diabetic persons.Methods Urine protein-to-creatinine ratio (PCR) was measured at semi-annual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of anti-diabetic medications were included. Pre-diabetes was defined as fasting glucose (FG) of 100-125 mg/dL confirmed within a year by a repeat FG or hemoglobin A1c 5.7–6.4%. Incident proteinuria was defined as PCR > 200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-diabetes differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria.Results Between 2006 and 2019, among 1276 men with pre-diabetes, 128/613 PWH (21%) and 50/663 PWOH (8%) developed proteinuria over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-diabetes was 3.3 times [95% CI: 2.3–4.8 times] greater than in PWOH (p
Læs mere Tjek på PubMedClinical Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Background Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success.Methods Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data.Results A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%.Conclusion Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era.
Læs mere Tjek på PubMedFelix M. Pabon-Rodriguez, Grant D. Brown, Breanna M. Scorza, Christine A. Petersen
PLoS One Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
by Felix M. Pabon-Rodriguez, Grant D. Brown, Breanna M. Scorza, Christine A. Petersen The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time-to-death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model’s ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding of the progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract Background Lipoarabinomannan (LAM) antigen serves as an attractive biomarker to diagnose Tuberculosis (TB). Given the limitations of current diagnostic modalities for Pleural TB, current study evaluated LAM’s potential to serve as a point-of-care test to diagnose pleural TB. Methods A cross sectional, diagnostic accuracy study was conducted during February to November 2021 in a tertiary care hospital in India. LAM antigen detection was performed on pleural fluid as well as early morning urine specimen of suspected pleural TB patients by “Alere/ Abott Determine TB LAM” lateral flow assay (LAM-LFA). The results were compared to microbiological reference standards/MRS (Mycobacterial culture or NAAT) and Composite reference standards/CRS (MRS plus Clinico-radiological diagnosis). Results A total of 170 subjects were included in the analysis, including 26 with Definite TB, 22 with Probable TB, and 122 with No TB. Compared to MRS and CRS, the sensitivity (61.54% & 45.83%) and positive predictive value (PPV) (57.14 & 78.57%) of Pleural LAM-LFA testing were found to be suboptimal, whereas the specificity (91.67% & 95.08%) and negative predictive value (NPV) (92.96% & 81.69%) of the assay were found to be good. Urinary LAM-LFA performed even worse than pleural LAM-LFA, except for its higher specificity against MRS and CRS (97.2% and 98.3%, respectively). Specificity and PPV of pleural LAM detection increased to 100% when analysed in a subgroup of patients with elevated ADA levels (receiver operating curve analysis-derived cut off value > 40 IU/ml). Conclusion Detection of LAM antigen by LFA directly from pleural fluid was found to be a useful test to predict absence of the disease if the test is negative rather than using as a POCT for diagnosis.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract Background During the COVID-19 pandemic swift implementation of research cohorts was key. While many studies focused exclusively on infected individuals, population based cohorts are essential for the follow-up of SARS-CoV-2 impact on public health. Here we present the CON-VINCE cohort, estimate the point and period prevalence of the SARS-CoV-2 infection, reflect on the spread within the Luxembourgish population, examine immune responses to SARS-CoV-2 infection and vaccination, and ascertain the impact of the pandemic on population psychological wellbeing at a nationwide level. Methods A representative sample of the adult Luxembourgish population was enrolled. The cohort was followed-up for twelve months. SARS-CoV-2 RT-qPCR and serology were conducted at each sampling visit. The surveys included detailed epidemiological, clinical, socio-economic, and psychological data. Results One thousand eight hundred sixty-five individuals were followed over seven visits (April 2020—June 2021) with the final weighted period prevalence of SARS-CoV-2 infection of 15%. The participants had similar risks of being infected regardless of their gender, age, employment status and education level. Vaccination increased the chances of IgG-S positivity in infected individuals. Depression, anxiety, loneliness and stress levels increased at a point of study when there were strict containment measures, returning to baseline afterwards. Conclusion The data collected in CON-VINCE study allowed obtaining insights into the infection spread in Luxembourg, immunity build-up and the impact of the pandemic on psychological wellbeing of the population. Moreover, the study holds great translational potential, as samples stored at the biobank, together with self-reported questionnaire information, can be exploited in further research. Trial registration Trial registration number: NCT04379297, 10 April 2020.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract The COVID-19 pandemic has been called the deadliest disease event in history. In this study, we compared the cause specific mortality of the Spanish flu (1918-1920) with the cause specific mortality of COVID-19 (2020-2022) in the Netherlands. During the period of exposure, around 50,000 people died from COVID-19 and 32,000 people from the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates of COVID-19 and Spanish flu were respectively 287 and 486 per 100,000 inhabitants. Compared by an age standardized mortality, there would have been 28 COVID-19 and 194 Spanish flu related deaths in 1918-1920, or there would have been 214 Spanish flu and 98 COVID-19 related deaths in 2020-2022 per 100,000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transport to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular PI3P levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling pre-autophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute UTI.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract This study explores the relationship between influenza infection, both clinically diagnosed in primary-care and laboratory confirmed in hospital, and atherothrombotic events (acute myocardial infarction and ischemic stroke) in Spain. A population-based self-controlled case series design was used with individual-level data from electronic registries (n = 2,230,015). The risk of atherothrombotic events in subjects ≥50 years old increased more than 2-fold during the 14 days after the mildest influenza cases in patients with fewer risk factors and more than 4-fold after severe cases in the most vulnerable patients, remaining in them more than 2-fold for 2 months. The transient increase of the association, its gradient after influenza infection and the demonstration by 4 different sensitivity analyses provide further evidence supporting causality. This work reinforces the official recommendations for influenza prevention in at-risk groups and should also increase the awareness of even milder influenza infection and its possible complications in the general population.
Læs mere Tjek på PubMedClinical Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract Background Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, > 90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs.Methods RCT to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)—amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted.Results Of 284 participants, 72 (25.3%) were deemed high-risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg and 4 (4.2%) after 250 mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics.Conclusion An easy-to-administer risk assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis.
Læs mere Tjek på PubMedMikiko Matsuo, Ayumu Kanbe, Kei Noguchi, Ayumi Niwa, Yuko Imaizumi, Takahito Kuroda, Koki Ichihashi, Takafumi Okubo, Kosuke Mori, Tomohiro Kanayama, Hiroyuki Tomita, Akira Hara
PLoS One Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
by Mikiko Matsuo, Ayumu Kanbe, Kei Noguchi, Ayumi Niwa, Yuko Imaizumi, Takahito Kuroda, Koki Ichihashi, Takafumi Okubo, Kosuke Mori, Tomohiro Kanayama, Hiroyuki Tomita, Akira Hara Galectin-3 is a beta-galactoside-binding lectin that plays important roles in diverse physiological functions, such as cell proliferation, apoptosis, and mRNA splicing. This protein is expressed on inflammatory cells and acts as a local inflammatory mediator. Recently, galectin-3 has been detected in several diseases, such as chronic liver, heart, and kidney diseases, diabetes, viral infection, autoimmune and neurodegenerative diseases, and tumors, and its role as a biomarker has attracted attention. Alpha-galactosylceramide is an artificially synthesized sphingolipid that can induce acute liver injury via the natural killer T pathway. However, the pathophysiological roles and kinetics of galectin-3 in acute liver injury are not fully understood. This study aimed to elucidate the expression and time course of galectin-3 in liver tissues during acute liver injury following alpha-galactosylceramide injection. Animals were histologically examined on days 1, 2, 4, and 7 after intraperitoneal injection of alpha-galactosylceramide, and the expressions of galectin-3 and ionized calcium-binding adaptor molecule 1 were analyzed. Notably, galectin-3 formed characteristic cluster foci, particularly on day 2 after injection. Cluster formation was not observed in chronic liver disease. Simultaneously, ionized calcium-binding adaptor molecule 1-positive cells were observed in the cluster foci. Serum galectin-3 levels increased on day 2 of treatment and correlated well with the number of galectin-3-positive cell clusters in the liver. Moreover, galectin-3 expression was an important mediator of the early phase of liver injury after alpha-galactosylceramide injection. These results suggest that serum galectin-3 may be a biomarker for the early diagnosis of acute liver injury and that clusters of galectin-3-positive cells may be a specific finding in acute liver injury.
Læs mere Tjek på PubMedGiorgia Colombo, Emanuela Pessolano, Maria Talmon, Armando A. Genazzani, Paolo Kunderfranco
PLoS One Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
by Giorgia Colombo, Emanuela Pessolano, Maria Talmon, Armando A. Genazzani, Paolo Kunderfranco Macrophages, key players in the innate immune system, showcase remarkable adaptability. Derived from monocytes, these phagocytic cells excel in engulfing and digesting pathogens and foreign substances as well as contributing to antigen presentation, initiating and regulating adaptive immunity. Macrophages are highly plastic, and the microenvironment can shaper their phenotype leading to numerous distinct polarized subsets, exemplified by the two ends of the spectrum: M1 (classical activation, inflammatory) and M2 (alternative activation, anti-inflammatory). RNA sequencing (RNA-Seq) has revolutionized molecular biology, offering a comprehensive view of transcriptomes. Unlike microarrays, RNA-Seq detects known and novel transcripts, alternative splicing, and rare transcripts, providing a deeper understanding of genome complexity. Despite the decreasing costs of RNA-Seq, data consolidation remains limited, hindering noise reduction and the identification of authentic signatures. Macrophages polarization is routinely ascertained by qPCR to evaluate those genes known to be characteristic of M1 or M2 skewing. Yet, the choice of these genes is literature- and experience-based, lacking therefore a systematic approach. This manuscript builds on the significant increase in deposited RNA-Seq datasets to determine an unbiased and robust murine M1 and M2 polarization profile. We now provide a consolidated list of global M1 differentially expressed genes (i.e. robustly modulated by IFN-γ, LPS, and LPS+ IFN-γ) as well as consolidated lists of genes modulated by each stimulus (IFN-γ, LPS, LPS+ IFN-γ, and IL-4).
Læs mere Tjek på PubMedMalaria Journal, 9.02.2024
Tilføjet 9.02.2024
Abstract Background Malaria is one of the most important vector-borne diseases of humans with an estimated 241 million cases worldwide in 2020. As an urban and periurban mosquito species, Anopheles stephensi is exposed to artificial human stimuli like light that can alter many aspects of mosquito behaviour, physiology and metabolism. Therefore, fluctuations in the light environment may influence the host, parasite and/or mosquito biology and hence modulate risk for disease transmission. In this study, the effect of artifitial light at night on mosquito infectivity by Plasmodium falciparum during the first hours of blood digestion was tested. Methods A total of three independent standard membrane feeding assays were performed to artificially fed septic and aseptic mosquitoes with P. falciparum infected blood. After blood feeding, females were transferred to incubators with different photoperiod cycles, so digestion occurred under day artificial light or dark. At 7 and 16 days post blood feeding, mosquitoes were dissected for midguts and salivary glands, respectively. Percentage of mosquitoes fed, percentage of prevalence and P. falciparum oocyst intensity between septic and aseptic mosquitoes in the two different photoperiod regimes, were compared using a Kruskal-Wallis test followed by a Dunn´s multiple comparison test . Results The exposition of mosquitoes to light after they took an infected blood meal has a negative effect on the successful progression of P. falciparum in the mosquito midgut. Antibiotic treatment significantly incremented the number of oocysts per midgut. Photophase significantly reduced the median oocyst intensity in both septic and aseptic mosquitoes. The percentage of oocyst reduction, understood as the percentage of reduction in the mean oocyst intensity of the parasite in the mosquito midgut between photophase and scotophase, was 51% in the case of aseptic mosquitoes and 80% for septic mosquitoes, both in the photophase condition. Conclusion Although there are still many gaps in the understanding of parasite-mosquito interactions, these results support the idea that light can, not only, influence mosquito biting behaviour but also parasite success in the mosquito midgut. Hence, light can be considered an interesting additional mosquito-control strategy to reduce mosquito-borne diseases.
Læs mere Tjek på PubMedInfection, 9.02.2024
Tilføjet 9.02.2024
Abstract Background Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients’ involvement in the decision process. Methods and Results This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases Conclusions Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients’ care and the needs for future studies in the field of anti-NTM treatments.
Læs mere Tjek på PubMedInfection, 9.02.2024
Tilføjet 9.02.2024
Abstract Purpose Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. Method Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021–May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (
Læs mere Tjek på PubMedKroeze, Stefanie; Kootstra, Neeltje A.; van Nuenen, Ad C.; Rossouw, Theresa M.; Kityo, Cissy M.; Siwale, Margaret; Akanmu, Sulaimon; Mandaliya, Kishor; de Jager, Marleen; Ondoa, Pascale; Wit, Ferdinand W.; Reiss, Peter; Rinke de Wit, Tobias F.; Hamers, Raph L.
AIDS, 9.02.2024
Tilføjet 9.02.2024
Objective: This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4+ T-cell recovery during the first year of ART. Design: MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART. Methods: First, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4+ T-cell recovery (ΔCD4) (N = 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile ΔCD4: n = 61, highest tertile ΔCD4: n = 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls. Results: Poor CD4+ T-cell recovery was associated with higher levels of hsa-miR-199a-3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsa-miR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326, hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and during ART in PWH with poor CD4+ T-cell recovery only. Conclusion: These findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedTingxiu Yang, Jia Li, Yuanyuan Zhang, Zhaohui Deng, Guzhen Cui, Jun Yuan, Jianchao Sun, Xiaojuan Wu, Dengxiong Hua, Song Xiang, Zhenghong Chen
PLoS One Infectious Diseases, 8.02.2024
Tilføjet 8.02.2024
by Tingxiu Yang, Jia Li, Yuanyuan Zhang, Zhaohui Deng, Guzhen Cui, Jun Yuan, Jianchao Sun, Xiaojuan Wu, Dengxiong Hua, Song Xiang, Zhenghong Chen Background Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida. Methods Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity. Results A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive. Conclusion In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.
Læs mere Tjek på PubMedEmily E. Whitaker, Neal E. Mecum, Riley C. Cott, Diana J. Goode
PLoS One Infectious Diseases, 8.02.2024
Tilføjet 8.02.2024
by Emily E. Whitaker, Neal E. Mecum, Riley C. Cott, Diana J. Goode Chemotherapy is often a life-saving treatment, but the development of intractable pain caused by chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity that restricts cancer survival rates. Recent reports demonstrate that paclitaxel (PTX) robustly increases anti-inflammatory CD4+ T cells in the dorsal root ganglion (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. However, the mechanism by which CD4+ T cells are activated, and the extent cytokines released by CD4+ T cells target DRG neurons are unknown. Here, we are the first to detect major histocompatibility complex II (MHCII) protein in mouse DRG neurons and to find CD4+ T cells breaching the satellite glial cell barrier to be in close proximity to neurons, together suggesting CD4+ T cell activation and targeted cytokine release. MHCII protein is primarily expressed in small nociceptive neurons in male and female mouse DRG but increased after PTX in small nociceptive neurons in only female DRG. Reducing one copy of MHCII in small nociceptive neurons decreased anti-inflammatory IL-10 and IL-4 producing CD4+ T cells in naïve male DRG and increased their hypersensitivity to cold. Administration of PTX to male and female mice that lacked one copy of MHCII in nociceptive neurons decreased anti-inflammatory CD4+ T cells in the DRG and increased the severity of PTX-induced cold hypersensitivity. Collectively, our results demonstrate expression of MHCII protein in mouse DRG neurons, which modulates cytokine producing CD4+ T cells in the DRG and attenuates cold hypersensitivity during homeostasis and after PTX treatment.
Læs mere Tjek på PubMedLukas Huber, Benno Kuropka, Pavlos G. Doulidis, Elisabeth Baszler, Lukas Martin, Anda Rosu, Lisa Kulmer, Carolina Frizzo Ramos, Alexandro Rodríguez-Rojas, Iwan A. Burgener
PLoS One Infectious Diseases, 8.02.2024
Tilføjet 8.02.2024
by Lukas Huber, Benno Kuropka, Pavlos G. Doulidis, Elisabeth Baszler, Lukas Martin, Anda Rosu, Lisa Kulmer, Carolina Frizzo Ramos, Alexandro Rodríguez-Rojas, Iwan A. Burgener Acute haemorrhagic diarrhoea is a common complaint in dogs. In addition to causes like intestinal parasites, dietary indiscretion, intestinal foreign bodies, canine parvovirus infection, or hypoadrenocorticism, acute haemorrhagic diarrhoea syndrome (AHDS) is an important and sometimes life-threatening differential diagnosis. There is some evidence supporting the link between Clostridium perfringens toxins and AHDS. These toxins may be partially responsible for the epithelial cell injury, but the pathogenesis of AHDS is still not fully understood. Recent studies have suggested that severe damage to the intestinal mucosa and associated barrier dysfunction can trigger chronic gastrointestinal illnesses. Besides bloodwork and classical markers for AHDS such as protein loss and intestinal bacterial dysbiosis, we focused mainly on the plasma-proteome to identify systemic pathological alterations during this disease and searched for potential biomarkers to improve the diagnosis. To accomplish the goals, we used liquid chromatography-mass spectrometry. We compared the proteomic profiles of 20 dogs with AHDS to 20 age-, breed-, and sex-matched control dogs. All dogs were examined, and several blood work parameters were determined and compared, including plasma biochemistry and cell counts. We identified and quantified (relative quantification) 207 plasmatic proteins, from which dozens showed significantly altered levels in AHDS. Serpina3, Lipopolysaccharide-binding protein, several Ig-like domain-containing proteins, Glyceraldehyde-3-phosphate dehydrogenase and Serum amyloid A were more abundant in plasma from AHDS affected dogs. In contrast, other proteins such as Paraoxonase, Selenoprotein, Amine oxidases, and Apolipoprotein C-IV were significantly less abundant. Many of the identified and quantified proteins are known to be associated with inflammation. Other proteins like Serpina3 and RPLP1 have a relevant role in oncogenesis. Some proteins and their roles have not yet been described in dogs with diarrhoea. Our study opens new avenues that could contribute to the understanding of the aetiology and pathophysiology of AHDS.
Læs mere Tjek på PubMedMeehan, S.-A., Hesseling, A. C., von Delft, A., Marx, F. M., Hughes, J. A., Bock, P., Banke-Thomas, A., Dunbar, R., Phelanyane, F., Smith, M., Osman, M.
BMJ Open, 8.02.2024
Tilføjet 8.02.2024
BackgroundTuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB. MethodsUsing TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing
Læs mere Tjek på PubMedInfection, 8.02.2024
Tilføjet 8.02.2024
Abstract Purpose Gut barrier dysfunction is a pivotal pathophysiological alteration in cirrhosis and end-stage liver disease, which is further aggravated during and after the operational procedures for liver transplantation (LT). In this review, we analyze the multifactorial disruption of all major levels of defense of the gut barrier (biological, mechanical, and immunological) and correlate with clinical implications. Methods A narrative review of the literature was performed using PubMed, PubMed Central and Google from inception until November 29th, 2023. Results Systemic translocation of indigenous bacteria through this dysfunctional barrier contributes to the early post-LT infectious complications, while endotoxin translocation, through activation of the systemic inflammatory response, is implicated in non-infectious complications including renal dysfunction and graft rejection. Bacterial infections are the main cause of early in-hospital mortality of LT patients and unraveling the pathophysiology of gut barrier failure is of outmost importance. Conclusion A pathophysiology-based approach to prophylactic or therapeutic interventions may lead to enhancement of gut barrier function eliminating its detrimental consequences and leading to better outcomes for LT patients.
Læs mere Tjek på PubMedInfection, 8.02.2024
Tilføjet 8.02.2024
Abstract Purpose Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. Methods We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. Results During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15–96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). Conclusion In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.
Læs mere Tjek på PubMed