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BMC Infectious Diseases Jun 2024Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the...
BACKGROUND
Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated.
METHODS
There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis.
RESULTS
Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result.
CONCLUSION
This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.
Topics: Humans; HIV Infections; Viral Load; Tertiary Care Centers; Male; Female; Adult; Beijing; Middle Aged; HIV-1; RNA, Viral; HIV Antibodies; Young Adult; China; Early Diagnosis; Adolescent
PubMed: 38879487
DOI: 10.1186/s12879-024-09486-8 -
European Journal of Radiology Jun 2024Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted... (Review)
Review
The clinical utility of diffusion-weighted imaging in diagnosing and predicting treatment response of laryngeal and hypopharyngeal carcinoma: A systematic review and meta-analysis.
PURPOSE
Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC.
METHODS
A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies.
RESULTS
A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 10 mm/s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes.
CONCLUSION
DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI's reliability in predicting prognosis and treatment response in patients with LC/HPC.
PubMed: 38878501
DOI: 10.1016/j.ejrad.2024.111550 -
Nature Communications Jun 2024Spatial attention is critical for recognizing behaviorally relevant objects in a cluttered environment. How the deployment of spatial attention aids the hierarchical...
Spatial attention is critical for recognizing behaviorally relevant objects in a cluttered environment. How the deployment of spatial attention aids the hierarchical computations of object recognition remains unclear. We investigated this in the laminar cortical network of visual area V4, an area strongly modulated by attention. We found that deployment of attention strengthened unique dependencies in neural activity across cortical layers. On the other hand, shared dependencies were reduced within the excitatory population of a layer. Surprisingly, attention strengthened unique dependencies within a laminar population. Crucially, these modulation patterns were also observed during successful behavioral outcomes that are thought to be mediated by internal brain state fluctuations. Successful behavioral outcomes were also associated with phases of reduced neural excitability, suggesting a mechanism for enhanced information transfer during optimal states. Our results suggest common computation goals of optimal sensory states that are attained by either task demands or internal fluctuations.
Topics: Visual Cortex; Attention; Male; Animals; Macaca mulatta; Photic Stimulation; Visual Perception; Neurons
PubMed: 38877026
DOI: 10.1038/s41467-024-49144-w -
Nature Communications Jun 2024The capacity of HIV-1 to replicate during optimal antiretroviral therapy (ART) is challenging to assess directly. To gain greater sensitivity to detect evolution on ART,...
The capacity of HIV-1 to replicate during optimal antiretroviral therapy (ART) is challenging to assess directly. To gain greater sensitivity to detect evolution on ART, we used a nonhuman primate (NHP) model providing precise control over the level of pre-ART evolution and more comprehensive analyses than are possible with clinical samples. We infected 21 rhesus macaques (RMs) with the barcoded virus SIVmac239M and initiated ART early to minimize baseline genetic diversity. RMs were treated for 285-1200 days. We used several tests of molecular evolution to compare 1352 near-full-length (nFL) SIV DNA single genome sequences from PBMCs, lymph nodes, and spleen obtained near the time of ART initiation and those present after long-term ART, none of which showed significant changes to the SIV DNA population during ART in any animal. To investigate the possibility of ongoing replication in unsampled putative tissue sanctuaries during ART, we discontinued treatment in four animals and confirmed that none of the 336 nFL SIV RNA sequences obtained from rebound plasma viremia showed evidence of evolution. The rigorous nature of our analyses reinforced the emerging consensus of a lack of appreciable ongoing replication on effective ART and validates the relevance of this NHP model for cure studies.
Topics: Animals; Simian Immunodeficiency Virus; Simian Acquired Immunodeficiency Syndrome; Macaca mulatta; Virus Replication; Anti-Retroviral Agents; Evolution, Molecular; RNA, Viral; Viral Load; Viremia; DNA, Viral; Male
PubMed: 38877003
DOI: 10.1038/s41467-024-49369-9 -
The Lancet. Global Health Jul 2024Cost-effectiveness analyses have been conducted for many interventions for HIV/AIDS, malaria, syphilis, and tuberculosis, but they have not been conducted for all... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cost-effectiveness analyses have been conducted for many interventions for HIV/AIDS, malaria, syphilis, and tuberculosis, but they have not been conducted for all interventions that are currently recommended in all countries. To support national decision makers in the effective allocation of resources, we conducted a meta-regression analysis of published incremental cost-effectiveness ratios (ICERs) for interventions for these causes, and predicted ICERs for 14 recommended interventions for Global Fund-eligible countries.
METHODS
In the meta-regression analysis, we used data from the Tufts University Center for the Evaluation of Value and Risk in Health (Boston, MA, USA) Cost-Effectiveness Registries (the CEA Registry beginning in 1976 and the Global Health CEA registry beginning in 1995) up to Jan 1, 2018. To create analysis files, we standardised and mapped the data, extracted additional data from published articles, and added variables from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Then we selected ratios for interventions with a minimum of two published articles and three published ICERs that mapped to one of five GBD causes (HIV/AIDS, malaria, syphilis, drug-susceptible tuberculosis, or multi-drug resistant tuberculosis), and to a GBD country; reported a currency year during or after 1990; and for which the comparator intervention was defined as no intervention, standard of care, or placebo. Our meta-regression analysis used all available data on 25 eligible interventions, and quantified the association between ICERs and factors at country level and intervention level. We used a five-stage statistical model that was developed to synthesise evidence on cost-effectiveness analyses, and we adapted it for smaller sample sizes by grouping interventions by cause and type (ie, prevention, diagnostics, and treatment). Using the meta-regression parameters we predicted country-specific median ICERs, IQRs, and 95% uncertainty intervals in 2019 US$ per disability-adjusted life-year (DALY) for 14 currently recommended interventions. We report ICERs in league tables with gross domestic product (GDP) per capita and country-specific thresholds.
FINDINGS
The sample for the analysis was 1273 ratios from 144 articles, of which we included 612 ICERs from 106 articles in our meta-regression analysis. We predicted ICERs for antiretroviral therapy for prevention for two age groups and pregnant women, pre-exposure prophylaxis against HIV for two risk groups, four malaria prevention interventions, antenatal syphilis screening, two tuberculosis prevention interventions, the Xpert tuberculosis test, and chemotherapy for drug-sensitive tuberculosis. At the country level, ranking of interventions and number of interventions with a predicted median ICER below the country-specific threshold varied greatly. For instance, median ICERs for six of 14 interventions were below the country-specific threshold in Sudan, whereas 12 of 14 were below the country-specific threshold in Peru. Antenatal syphilis screening had the lowest median ICER among all 14 interventions in 81 (63%) of 128 countries, ranging from $3 (IQR 2-4) per DALY averted in Equatorial Guinea to $3473 (2244-5222) in Ukraine. Pre-exposure prophylaxis for HIV/AIDS for men who have sex with men had the highest median ICER among all interventions in 116 (91%) countries, ranging from $2326 (1077-4567) per DALY averted in Lesotho to $53 559 (23 841-108 534) in Maldives.
INTERPRETATION
Country-specific league tables highlight the interventions that offer better value per DALY averted, and can support decision making at a country level that is more tailored to available resources than GDP per capita and country-specific thresholds. Meta-regression is a promising method to synthesise cost-effectiveness analysis results and transfer them across settings.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; Cost-Benefit Analysis; Malaria; HIV Infections; Tuberculosis; Regression Analysis; Syphilis; Global Health; Acquired Immunodeficiency Syndrome
PubMed: 38876762
DOI: 10.1016/S2214-109X(24)00181-5 -
Experimental Neurology Jun 2024Interictal epileptiform discharges refer to aberrant brain electrographic signals between seizures and feature intermittent interictal spikes (ISs), sharp waves, and/or...
Development of spontaneous recurrent seizures accompanied with increased rates of interictal spikes and decreased hippocampal delta and theta activities following extended kindling in mice.
Interictal epileptiform discharges refer to aberrant brain electrographic signals between seizures and feature intermittent interictal spikes (ISs), sharp waves, and/or abnormal rhythms. Recognition of these epileptiform activities by electroencephalographic (EEG) examinations greatly aids epilepsy diagnosis and localization of the seizure onset zone. ISs are a major form of interictal epileptiform discharges recognized in animal models of epilepsy. Progressive changes in IS waveforms, IS rates, and/or associated fast ripple oscillations have been shown to precede the development of spontaneous recurrent seizures (SRS) in various animal models. IS expressions in the kindling model of epilepsy have been demonstrated but IS changes during the course of SRS development in extended kindled animals remain to be detailed. We hence addressed this issue using a mouse model of kindling-induced SRS. Adult C57 black mice received twice daily hippocampal stimulations until SRS occurrence, with 24-h EEG monitoring performed following 50, 80, and ≥ 100 stimulations and after observation of SRS. In the stimulated hippocampus, increases in spontaneous ISs rates, but not in IS waveforms nor IS-associated fast ripples, along with decreased frequencies of hippocampal delta and theta rhythms, were observed before SRS onset. Comparable increases in IS rates were further observed in the unstimulated hippocampus, piriform cortex, and entorhinal cortex, but not in the unstimulated parietal cortex and dorsomedial thalamus. These data provide original evidence suggesting that increases in hippocampal IS rates, together with reductions in hippocampal delta and theta rhythms are closely associated with development of SRS in a rodent kindling model.
PubMed: 38876195
DOI: 10.1016/j.expneurol.2024.114860 -
Microbiology Spectrum Jun 2024The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as , is largely unexplored. In this study, our findings...
The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as , is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in . Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of .IMPORTANCE is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in . Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of . Moreover, Set302 regulates the pathogenicity and colonization ability of in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in .
PubMed: 38874428
DOI: 10.1128/spectrum.04202-23 -
Annals of Clinical and Translational... Jun 2024Conventionally, MRI aids in differentiating acute unilateral peripheral vestibulopathy/vestibular neuritis (AUPV/VN) from mimickers. Meanwhile, the diagnostic utility of...
OBJECTIVE
Conventionally, MRI aids in differentiating acute unilateral peripheral vestibulopathy/vestibular neuritis (AUPV/VN) from mimickers. Meanwhile, the diagnostic utility of MRIs dedicated to the inner ear remains to be elucidated for diagnosing AUPV/VN.
METHODS
We prospectively recruited 53 patients with AUPV/VN (mean age ± SD = 60 ± 15 years, 29 men). Initial MRIs were performed with a standard protocol, and an additional axial 3D-fluid-attenuated inversion recovery (3D-FLAIR) sequence was obtained 4 h after intravenous injection of gadoterate meglumine. Abnormal enhancement was defined as a signal intensity that exceeded the mean + 2SD value on the healthy side. The findings of neurotologic evaluation and MRIs were compared.
RESULTS
Overall, the inter-rater agreement for gadolinium enhancement was 0.886 (Cohen's kappa coefficient). Enhancement was observed in 26 patients (49%), most frequently in the vestibule (n = 20), followed by the anterior (n = 12), horizontal (HC, n = 8), posterior canal (n = 5), and superior (n = 3) and inferior (n = 1) vestibular nerves. In multivariable logistic regression analysis, the enhancement was associated with decreased HC gain in video head-impulse tests (p = 0.036), increased interaural difference in ocular vestibular-evoked myogenic potentials (p = 0.001), and a longer onset-to-MRI time span (p = 0.024). The sensitivity and specificity were 92.3% and 81.5%, respectively, with an area under the curve of 0.90 for predicting gadolinium enhancement.
INTERPRETATION
Robust gadolinium enhancement was observed on 4-hour-delayed 3D-FLAIR images in nearly half of the patients with AUPV/VN, with a good correlation with the results of neurotologic evaluation. The positivity may be determined by the extent of vestibular deficit, timing of imaging acquisition, and possibly by the underlying etiology causing AUPV/VN. MRIs may aid in delineating the involved structures in AUPV/VN.
PubMed: 38874375
DOI: 10.1002/acn3.52123 -
Euro Surveillance : Bulletin Europeen... Jun 2024Between the start of the Russian Federation's invasion of Ukraine on 24 February 2022 and May 2023, more than 8 million individuals have been displaced from Ukraine....
Refugees from Ukraine receiving antiretroviral therapy in destination countries and territories of the World Health Organization European Region, including EU/EEA countries, February 2022 to March 2023.
Between the start of the Russian Federation's invasion of Ukraine on 24 February 2022 and May 2023, more than 8 million individuals have been displaced from Ukraine. Ukraine has the second-largest HIV epidemic in the World Health Organization (WHO) European Region. From a humanitarian and public health perspective it is critical that Ukrainian refugees living with or at risk of HIV have access to testing, treatment and healthcare in their destination country. To gain better insight on the number of refugees from Ukraine receiving antiretroviral therapy (ART) in destination countries, the WHO Regional Office for Europe and the European Centre for Disease Prevention and Control conducted three surveys in July 2022, November 2022 and March 2023. Among 39 countries that responded to at least one survey, 31 had information on the number of refugees from Ukraine receiving ART in their country. A total of 6,519 refugees (1.5 per 1,000 refugees) received ART, lower than previous estimates by WHO, ECDC and partners of between 0.16% and 1.0%. This discrepancy may suggest a substantial number of undiagnosed and/or diagnosed but untreated HIV infections. Improving access to healthcare for people living with HIV among refugees from Ukraine is vital to ensure quality care.
Topics: Humans; Refugees; HIV Infections; Ukraine; World Health Organization; Male; Female; Adult; Europe; Health Services Accessibility; Anti-Retroviral Agents; Anti-HIV Agents; Middle Aged
PubMed: 38873799
DOI: 10.2807/1560-7917.ES.2024.29.24.2300567 -
Heliyon Jun 2024Greater social capital is associated with positive health outcomes and better HIV management. The ways by which social capital may influence household water insecurity...
The influence of an agricultural intervention on social capital and water insecurity coping strategies: Qualitative evidence from female smallholder farmers living with HIV in western Kenya.
BACKGROUND
Greater social capital is associated with positive health outcomes and better HIV management. The ways by which social capital may influence household water insecurity (HHWI), a critical determinant of health among persons living with HIV, remain underexplored. Further, despite the importance of reliable water access and use for health and agricultural productivity, few studies have described the strategies smallholder farmers living with HIV use to manage water insecurity.
OBJECTIVE
We qualitatively explored how an agricultural intervention (provision of a treadle pump for irrigation) influenced HHWI coping strategies through its impacts on social capital among smallholder farmers living with HIV in western Kenya.
METHOD
In 2018, we purposively recruited participants from the study, a randomized agricultural intervention (NCT02815579) that provided irrigation pumps to improve treatment outcomes and food security among smallholder farmers living with HIV in western Kenya (n = 42). Participants shared their experiences with water insecurity through go-along and photo-elicitation interviews. Data were thematically analyzed using inductively developed codes.
RESULTS
Participants described diverse strategies for coping with agricultural water insecurity. Dimensions of social capital such as feelings of belonging, connectedness, and trust influenced the use of the treadle water pump and other water access behaviors. For instance, participants reported borrowing or sharing water pumps with friends and neighbors if they felt they had a good rapport. In addition, participants indicated a willingness to engage in collective activities, such as supporting the operation of the irrigation pump during planting, when they felt sufficiently connected to a larger group. Overall, individuals in the intervention arm described greater social cohesion, reciprocity, and community connectedness than those in the control arm.
CONCLUSION
The impact of an agricultural intervention on water access and use was described as being modified by social capital among female smallholder farmers living with HIV. Findings suggest that social capital may create an enabling environment for implementing strategies that improve the management and reduce the burden of HIV. Measuring these strategies and their associations with HIV outcomes may strengthen our understanding of resilience among female smallholder farmers living with HIV. The development of a coping strategies index and its use in a longitudinal study could help to identify pathways through which social capital influences health and the effectiveness of livelihood interventions.
PubMed: 38873679
DOI: 10.1016/j.heliyon.2024.e32058