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Poultry Science Jun 2024Spotty Liver Disease (SLD), caused by Campylobacter hepaticus or C. bilis infection in adult female chickens continues to emerge as a major disease problem in cage-free...
Spotty Liver Disease (SLD), caused by Campylobacter hepaticus or C. bilis infection in adult female chickens continues to emerge as a major disease problem in cage-free production systems. Free range production has become the predominant system in Australian egg production and SLD is widespread in these farms. Previous studies have identified having a scratch area as a key determinant for SLD occurrence. An Australia-wide survey of egg production flocks with scratch areas was conducted regarding SLD including 48 individual flocks. Descriptive information on the facilities and flock management practices was reported. The incidence of SLD, age of first outbreak, initial mortality rate, duration of elevated mortality, and magnitude and duration of any associated egg production decline are described. Recurrence of SLD in the same flock was also reported and discussed. Therapies applied were recorded and assessed across SLD severity and duration. SLD occurred in 66.7% of layer flocks whose facility included a scratch area. Recurrent SLD outbreaks occurred in 31% of flocks experiencing SLD. Antibiotic medication reduced duration of mortality and egg production decline. Antibiotic therapy was associated with reduced duration of mortality and a less severe and shorter duration of egg production drops compared to untreated flocks. PCR detection of C. hepaticus in cloacal swabs and house dust samples and a serological ELISA test were compared and evaluated as diagnostic aids or as possible predictors of SLD outbreaks. The ELISA showed substantial agreement with detection of C. hepaticus in cloacal swabs by PCR. Examining composite house dust samples by PCR for C. hepaticus DNA appeared to be the most convenient and cost-effective aid to diagnosis and as a putative predictor for SLD outbreaks.
PubMed: 38917603
DOI: 10.1016/j.psj.2024.103941 -
PloS One 2024This paper studied an integrated process planning and scheduling problem from a machining workshop for large-size valves in a valve manufacturing plant. Large-size...
This paper studied an integrated process planning and scheduling problem from a machining workshop for large-size valves in a valve manufacturing plant. Large-size valves usually contain several key parts and are generally produced in small-series production. Almost all the parts need to be manufactured in the same workshop at the same time in the plant. Facilities have to handle various items in one order, including different models, sizes, and types. It is a classical NP-hard problem on a large scale. An improved NSGA-II algorithm is suggested to obtain satisfactory solutions for makespan and manufacturing costs, which involve large optimization parameters and interactions. A two-section encoding method and an inserting greedy decoding method are chosen to enable the algorithm. The dynamic population update strategy based on dynamic population update and the adaptive mutation technique depending on the population entropy changing rate are selected for enhancing both the solution quality and population diversity. The methodology was successfully implemented in a real-life case at a major valve machining workshop operated by Yuanda Valve Company in China. By taking into account realistic factors and restrictions that have been identified from a real-world manufacturing setting, this technique aids in bridging the knowledge gap between present IPPS research and practical valve production implementations.
Topics: Algorithms; Humans; China; Manufacturing Industry
PubMed: 38917183
DOI: 10.1371/journal.pone.0306024 -
PloS One 2024We construct a model to investigate HIV/AIDS dynamics in real cases and study its mathematical analysis. The study examines the qualitative outcomes and confirms the...
We construct a model to investigate HIV/AIDS dynamics in real cases and study its mathematical analysis. The study examines the qualitative outcomes and confirms the local and global asymptotic stability of both the endemic equilibrium and the disease-free equilibrium. The model's criteria for exhibiting both local and global asymptotically stable behavior are examined. We compute the endemic equilibria and obtain the existence of a unique positive endemic equilibrium. The data is fitted to the model using the idea of nonlinear least-squares fitting. Accurate parameter values are achieved by fitting the data to the model using a 95% confidence interval. The basic reproduction number is computed using parameters that have been fitted or estimated. Sensitivity analysis is performed to discover the influential parameters that impact the reproduction number and the eradication of the disease. The results show that implementing preventive measures can reduce HIV/AIDS cases.
Topics: Humans; Acquired Immunodeficiency Syndrome; Computer Simulation; HIV Infections; Basic Reproduction Number; Models, Theoretical
PubMed: 38917173
DOI: 10.1371/journal.pone.0304735 -
BioRxiv : the Preprint Server For... Jun 2024The fungus is an opportunistic pathogen of people that reprograms its translatome to facilitate adaptation and virulence within the host. We studied the role of...
UNLABELLED
The fungus is an opportunistic pathogen of people that reprograms its translatome to facilitate adaptation and virulence within the host. We studied the role of Hog1/p38 in reprogramming translation during thermal stress adaptation, and found that this pathway acts on translation via crosstalk with the Gcn2 pathway, a well-studied regulator of general translation control. Using a combination of molecular assays and phenotypic analysis, we show that increased output from the Gcn2 pathway in a Hog1 deletion mutant is associated with rescue of thermal stress adaptation at both molecular and phenotypic scales. We characterize known outputs of the Hog1 pathway during thermal stress as either Gcn2-dependent or Gcn2-independent, and demonstrate that Hog1 activation regulates the Gcn2 pathway even in the absence of thermal stress. Finally, we implicate this phenomenon in another Hog1-regulated process, morphogenesis, and recapitulate Hog1-Gcn2 crosstalk in the distantly related fungal pathogen, Our results point to an important link between the stress response machinery and translation control, and clarify the etiology of phenotypes associated with Hog1 deletion. More broadly, this study highlights complex interplay between core conserved signal transduction pathways and the utility of molecular assays to better understand how these pathways are connected.
IMPORTANCE
is an opportunistic pathogen of people that causes deadly cryptococcal meningitis, which is is responsible for an estimated 19% of AIDS-related mortality. When left untreated, cryptococcal meningitis is uniformly fatal, and in patients receiving the most effective antifungal regimens, mortality remains high. Thus, there is a critical need to identify additional targets that play a role in adaptation to the human host and virulence. This study explores the role of the stress response kinases Hog1 and Gcn2 in thermoadaptation, which is pre-requisite for virulence. Our results show that compensatory signaling occurs via the Gcn2 pathway when Hog1 is deleted, and that disruption of both pathways increases sensitivity to thermal stress. Importantly, our study highlights the insufficiency of using single gene deletion mutants to study gene function, since many phenotypes associated with Hog1 deletion were driven by Gcn2 signaling in this background, rather than loss of direct Hog1 activity.
PubMed: 38915642
DOI: 10.1101/2024.06.11.598457 -
BioRxiv : the Preprint Server For... Jun 2024The global burden of infections due to the pathogenic fungus is substantial in persons with low CD4 T cell counts. Previously, we deleted three chitin deacetylase...
UNLABELLED
The global burden of infections due to the pathogenic fungus is substantial in persons with low CD4 T cell counts. Previously, we deleted three chitin deacetylase genes from to create a chitosan-deficient, avirulent strain, designated which, when used as a vaccine, protected mice from challenge with virulent strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8 T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4 T cells. Moreover, CD4 T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4 T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4 T cells after vaccination, but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in IFNγ, TNFα, or IL-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4 T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8 T cells are dispensable, IFNγ and CD4 T cells have overlapping roles in generating protective immunity prior to vaccination. However, once vaccinated, protection becomes less dependent on CD4 T cells, suggesting a strategy for vaccinating HIV persons prior to loss of CD4 T cells.
IMPORTANCE
The fungus is responsible for >100,000 deaths annually, mostly in persons with impaired CD4 T cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of , designated . When used as a vaccine, protects mice against a subsequent challenge with a virulent strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8 T cells were dispensible, protection was lost in mice genetically deficient in CD4 T cells, and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4 T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4 T cells following vaccination, suggesting a strategy to protect persons who are at risk for future CD4 T cell dysfunction.
PubMed: 38915489
DOI: 10.1101/2024.06.12.598760 -
AIDS Research and Therapy Jun 2024Ethiopia's viral suppression rate was less than 90% by 2020, and more than 10% of adult clients on ART in Woliso Town were unsuppressed at the end of March 2022. This...
BACKGROUND
Ethiopia's viral suppression rate was less than 90% by 2020, and more than 10% of adult clients on ART in Woliso Town were unsuppressed at the end of March 2022. This study aims to identify determinants of virologic failure among adult clients on ART at health facilities in Oromia region of Ethiopia.
METHODS
A facility-based unmatched case-control study was conducted at health facilities in Oromia region from August 1 to September 1, 2022. The study cases were clients with virologic-confirmed first-line ART failure, while controls were clients on first-line ART with a suppressed viral load. A total of 135 cases and 268 control participants were selected using simple random sampling techniques, and data were collected by reviewing the client's document. Epi-Info7 was used for data entry and SPSS version 20 for data analysis. Variables having a P-value of less than 0.25 in the bi-variable analysis were included in multivariable logistic regression. Determinants of virologic failure were determined based on an adjusted odds ratio using 95% CI and a P-value of < 0.05.
RESULT
In this study, clients with an age ≥ 35 years (AOR = 3.4, 95% CI: 1.6, 7.0), clients with a baseline regimen of AZT + 3TC + NVP (AOR = 3.5, 95% CI: 1.4, 8.8), clients with a base-line CD4 count < 350 mm (AOR = 2.3, 95% CI: 1.1, 4.5), being single marital status (AOR = 3.7, 95% CI: 1.4, 10.5), TB-HIV coinfection (AOR = 2.58, 95% CI: 1.3, 5.1), and having opportunistic infection other than TB in the last six months (AOR = 3.06, 95% CI: 1.5, 6.3) were factors significantly associated with virologic failure while clients within the appointment spacing model (AOR = 0.05, 95% CI: 0.03, 0.10) is inversely associated with virologic failure.
CONCLUSION
This study showed that age ≥ 35 years, being single, baseline ART regimen with (AZT + 3TC + NVP), baseline CD4 cell count < 350 mm, Tb-co infection, and opportunistic infection in the last 6 months were factors associated with virologic failure. Involvement in the appointment spacing model was found to be protective.
Topics: Humans; Ethiopia; Case-Control Studies; Adult; HIV Infections; Male; Female; Treatment Failure; Viral Load; Anti-HIV Agents; Middle Aged; Young Adult; CD4 Lymphocyte Count; Risk Factors; Adolescent
PubMed: 38915090
DOI: 10.1186/s12981-024-00625-4 -
BMC Infectious Diseases Jun 2024Virological failure, drug resistance, toxicities, and other issues make it difficult for ART to maintain long-term sustainability. These issues would force a...
BACKGROUND
Virological failure, drug resistance, toxicities, and other issues make it difficult for ART to maintain long-term sustainability. These issues would force a modification in the patient's treatment plan. The aim of this research was to determine whether first-line antiretroviral therapy is durable and to identify the factors that lead to patients on HAART changing their first highly active antiretroviral therapy regimen.
METHODS
A retrospective cohort study was conducted from October, 2019-March, 2020 across all regional states including Addis Ababa and Dire Dawa administrative cities. The target population is from all health facilities that have been providing ART service for at least the past 6 months as of October 2019. Multi-stage clustered sampling method was used to select study facilities and participants. Simple random selected ART medical records of patients ever enrolled in ART treatment services. We adopted a multi-state survival modelling (msm) approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another for time to treatment change/switch. We estimated the transition probability, prediction probabilities and length of stay and factor associated with treatment modification of patients to move from one regimen to another.
RESULTS
Any of the six therapy combinations (14.4%) altered their treatment at least once during the follow-up period for a variety of reasons. Of the patients, 4,834 (13.26%) changed their treatments just once, while 371 (1.1%) changed it more than once. For 38.6% of the time, a treatment change was undertaken due to toxicity, another infection or comorbidity, or another factor, followed by New drugs were then made accessible and other factors 18.3% of the time, a drug was out of supply; 2.6% of those instances involved pregnancy; and 43.1% involved something else. Highly active anti-retroviral therapy (HAART) combinations TDF + 3TC + NVP, d4T + 3TC + NVP, and TDF + 3TC + EFV were high to treatment alterations in all reasons of treatment modifications, with 29.74%, 26.52%, and 19.52% treatment changes, respectively. Early treatment modification or regime change is one of the treatment combinations that include the d4T medication that creates major concern. The likelihood of staying and moving at the the start of s = 0 and 30-month transitions increased, but the likelihood of staying were declined. For this cohort dataset, the presence of opportunistic disease, low body weight, baseline CD4 count, and baseline TB positive were risk factors for therapy adjustment.
CONCLUSION
Given that the current study took into account a national dataset, it provides a solid basis for ART drug status and management. The patient had a higher likelihood of adjusting their treatment at some point during the follow-up period due to drug toxicity, comorbidity, drug not being available, and other factors, according to the prediction probability once more. Baseline TB positivity, low CD4 count, opportunistic disease, and low body weight were risk factors for therapy adjustment in this cohort dataset.
Topics: Humans; Ethiopia; Retrospective Studies; Female; Male; Adult; HIV Infections; Antiretroviral Therapy, Highly Active; Anti-HIV Agents; Markov Chains; Time-to-Treatment; Middle Aged; Young Adult; Acquired Immunodeficiency Syndrome; Adolescent
PubMed: 38914968
DOI: 10.1186/s12879-024-09469-9 -
BMC Infectious Diseases Jun 2024The pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated...
BACKGROUND
The pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated to be one of the culprits. This notion is derived from studies in HIV-uninfected populations and/or animals while data on HTN and how it relates to IA in PLHIV remains scarce. We determined the relationship between HTN and IA among antiretroviral therapy (ART) naïve PLHIV.
METHODS
We analysed baseline data of 365 out of 430 clinical trial participants whose main aim was to investigate the effect of low-dose aspirin on HIV disease progression in PLHIV starting ART. Soluble CD14 (sCD14), T cells co-expressing CD38 and HLA-DR, and PD-1 were the IA and exhaustion markers, respectively studied and were analysed by flow cytometry. Mann-Whitney U-test was used for comparison of the markers by HTN status. A robust Poisson regression model was used to determine the predictors for HTN.
RESULTS
A quarter of the 365 were hypertensive (25.3%, 95% CI 20.9-29.8%), and, had higher median (IQR) body mass index (kg/m) (23.4 (19.6, 28.0) versus 21.9 (19.3, 25.1)) and lower median (IQR) estimated glomerular filtration rate (mL/min/1.73m) (101.2 (79.4, 126.9) versus 113.6 (92.7, 138.8)) than normotensive participants (p < 0.05). Participants with HTN had higher median frequencies of all markers of IA and exhaustion but lower sCD14 (p > 0.05). None of these markers significantly predicted the occurrence of HTN.
CONCLUSION
Studied markers of IA and exhaustion were higher in PLHIV with HTN than those without but were unpredictive of HTN. Larger multicentre studies with a wider range of markers are needed to confirm the role of IA in HIV-associated HTN.
Topics: Humans; Male; HIV Infections; Female; Adult; Hypertension; Middle Aged; Lipopolysaccharide Receptors; Biomarkers
PubMed: 38914935
DOI: 10.1186/s12879-024-09548-x -
NPJ Vaccines Jun 2024Gammaherpesviruses are oncogenic viruses that establish lifelong infections and are significant causes of morbidity and mortality. Vaccine strategies to limit...
Gammaherpesviruses are oncogenic viruses that establish lifelong infections and are significant causes of morbidity and mortality. Vaccine strategies to limit gammaherpesvirus infection and disease are in development, but there are no FDA-approved vaccines for Epstein-Barr or Kaposi sarcoma herpesvirus. As a new approach to gammaherpesvirus vaccination, we developed and tested a replication-deficient virus (RDV) platform, using murine gammaherpesvirus 68 (MHV68), a well-established mouse model for gammaherpesvirus pathogenesis studies and preclinical therapeutic evaluations. We employed codon-shuffling-based complementation to generate revertant-free RDV lacking expression of the essential replication and transactivator protein encoded by ORF50 to arrest viral gene expression early after de novo infection. Inoculation with RDV-50.stop exposes the host to intact virion particles and leads to limited lytic gene expression in infected cells yet does not produce additional infectious particles. Prime-boost vaccination of mice with RDV-50.stop elicited virus-specific neutralizing antibody and effector T cell responses in the lung and spleen. In contrast to vaccination with heat-inactivated WT MHV68, vaccination with RDV-50.stop resulted in a near complete abolishment of virus replication in the lung 7 days post-challenge and reduction of latency establishment in the spleen 16 days post-challenge with WT MHV68. Ifnar1 mice, which lack the type I interferon receptor, exhibit severe disease and high mortality upon infection with WT MHV68. RDV-50.stop vaccination of Ifnar1 mice prevented wasting and mortality upon challenge with WT MHV68. These results demonstrate that prime-boost vaccination with a gammaherpesvirus that is unable to undergo lytic replication offers protection against acute replication, impairs the establishment of latency, and prevents severe disease upon the WT virus challenge. Our study also reveals that the ability of a gammaherpesvirus to persist in vivo despite potent pre-existing immunity is an obstacle to obtaining sterilizing immunity.
PubMed: 38914546
DOI: 10.1038/s41541-024-00908-x -
Sexually Transmitted Infections Jun 2024Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus...
HIV pre-exposure prophylaxis and opportunities for vaccination against hepatitis A virus, hepatitis B virus and human papillomavirus: an analysis of the Ontario PrEP cohort study.
OBJECTIVES
Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus (HPV). We examined immunity/vaccination against these infections among participants in the Ontario PrEP cohort study (ON-PrEP).
METHODS
ON-PrEP is a prospective cohort of HIV-negative PrEP users from 10 Ontario clinics. We descriptively analysed baseline immunity/vaccination against HAV (IgG reactive), HBV (hepatitis B surface antibody >10) and HPV (self-reported three-dose vaccination). We further performed multivariable logistic regression to identify characteristics associated with baseline immunity/vaccination. We used cumulative incidence functions to describe vaccine uptake among participants non-immune at baseline.
RESULTS
Of 633 eligible participants, 59.1% were white, 85.8% were male and 79.6% were gay. We found baseline evidence of immunity/vaccination against HAV, HBV and HPV in 69.2%, 81.2% and 16.8% of PrEP-experienced participants and 58.9%, 70.3% and 10.4% of PrEP-naïve participants, respectively. Characteristics associated with baseline HAV immunity were greater PrEP duration (adjusted OR (aOR) 1.41/year, 95% CI 1.09 to 1.84), frequent sexually transmitted and bloodborne infection (STBBI) testing (aOR 2.38, 95% CI 1.15 to 4.92) and HBV immunity (aOR 3.53, 95% CI 2.09 to 5.98). Characteristics associated with baseline HBV immunity were living in Toronto (aOR 3.54, 95% CI 1.87 to 6.70) or Ottawa (aOR 2.76, 95% CI 1.41 to 5.40), self-identifying as racialised (aOR 2.23, 95% CI 1.19 to 4.18), greater PrEP duration (aOR 1.39/year, 95% CI 1.02 to 1.90) and HAV immunity (aOR 3.75, 95% CI 2.19 to 6.41). Characteristics associated with baseline HPV vaccination were being aged ≤26 years (aOR 9.28, 95% CI 2.11 to 40.77), annual income between CAD$60 000 and CAD$119 000 (aOR 3.42, 95% CI 1.40 to 8.34), frequent STBBI testing (aOR 7.00, 95% CI 1.38 to 35.46) and HAV immunity (aOR 6.96, 95% CI 2.00 to 24.25). Among those non-immune at baseline, overall cumulative probability of immunity/vaccination was 0.70, 0.60 and 0.53 among PrEP-experienced participants and 0.93, 0.80 and 0.70 among PrEP-naïve participants for HAV, HBV and HPV, respectively.
CONCLUSIONS
Baseline immunity to HAV/HBV was common, and a sizeable proportion of non-immune participants were vaccinated during follow-up. However, HPV vaccination was uncommon. Continued efforts should be made to remove barriers to HPV vaccination such as cost, inclusion in clinical guidelines and provider recommendation.
PubMed: 38914474
DOI: 10.1136/sextrans-2023-055961