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AIDS Research and Therapy Jun 2024The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030,...
INTRODUCTION
The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030, which refers to 95% of patients living with HIV knowing their HIV status, 95% of patients living with HIV receiving continual care and medication, and 95% of patients living with HIV exhibiting viral suppression. However, how to measure the status of viral suppression varies, and it is hard to indicate the quality of HIV care. The study aimed to examine the long-term viral load suppression in these cases and explore potential factors affecting the control of long-term viral load.
METHODS
This study analyzed viral load testing data from HIV patients who are still alive during the period from notification up to 2019-2020. Three indicators were calculated, including durable viral suppression, Viremia copy-years, and Viral load > 1,500 copies/ml, to assess the differences between them.
RESULTS
Among the 27,706 cases included in the study, the proportion of persistent viral load suppression was 87%, with 4% having viral loads exceeding 1,500 copies/ml. The average duration from notification to viral load suppression was 154 days, and the geometric mean of annual viral replication was 90 copies*years/ml. Regarding the last available viral load measurement, 96% of cases had an undetectable viral load. However, we observed that 9.3% of cases, while having an undetectable viral load for their last measurement, did not show consistent long-term viral load suppression. An analysis of factors associated with non-persistent viral load suppression revealed higher risk in younger age groups, individuals with an educational level of high school or below, injection drug users, cases from the eastern region, those seeking care at regional hospitals, cases with drug resistance data, individuals with lower healthcare continuity, and those with an initial CD4 count below 350 during the study period.
CONCLUSIONS
The recommendation is to combine it with the indicator of sustained viral load suppression for a more accurate assessment of the risk of HIV transmission within the infected community.
Topics: Humans; Viral Load; HIV Infections; Male; Female; Adult; Taiwan; Middle Aged; Anti-HIV Agents; Young Adult; Aged; Adolescent; HIV-1; Sustained Virologic Response
PubMed: 38902777
DOI: 10.1186/s12981-024-00626-3 -
BMC Genomics Jun 2024Autophagy is a conserved catabolic process in eukaryotes that contributes to cell survival in response to multiple stresses and is important for organism fitness....
BACKGROUND
Autophagy is a conserved catabolic process in eukaryotes that contributes to cell survival in response to multiple stresses and is important for organism fitness. Extensive research has shown that autophagy plays a pivotal role in both viral infection and replication processes. Despite the increasing research dedicated to autophagy, investigations into shrimp autophagy are relatively scarce.
RESULTS
Based on three different methods, a total of 20 members of the ATGs were identified from F. chinensis, all of which contained an autophagy domain. These genes were divided into 18 subfamilies based on their different C-terminal domains, and were found to be located on 16 chromosomes. Quantitative real-time PCR (qRT-PCR) results showed that ATG genes were extensively distributed in all the tested tissues, with the highest expression levels were detected in muscle and eyestalk. To clarify the comprehensive roles of ATG genes upon biotic and abiotic stresses, we examined their expression patterns. The expression levels of multiple ATGs showed an initial increase followed by a decrease, with the highest expression levels observed at 6 h and/or 24 h after WSSV injection. The expression levels of three genes (ATG1, ATG3, and ATG4B) gradually increased until 60 h after injection. Under low-salt conditions, 12 ATG genes were significantly induced, and their transcription abundance peaked at 96 h after treatment.
CONCLUSIONS
These results suggested that ATG genes may have significant roles in responding to various environmental stressors. Overall, this study provides a thorough characterization and expression analysis of ATG genes in F. chinensis, laying a strong foundation for further functional studies and promising potential in innate immunity.
Topics: Animals; Stress, Physiological; Penaeidae; Autophagy; Gene Expression Profiling; Phylogeny; Autophagy-Related Proteins; Transcriptome
PubMed: 38902611
DOI: 10.1186/s12864-024-10529-2 -
Psychology of Addictive Behaviors :... Jun 2024Alcohol use is an important, but understudied, risk factor for nonsuicidal self-injury (NSSI), defined as deliberate physical harm to oneself without intent to die....
Alcohol use prior to episodes of nonsuicidal self-injury in women with borderline personality disorder participating in a randomized clinical trial of dialectical behavior therapy.
OBJECTIVE
Alcohol use is an important, but understudied, risk factor for nonsuicidal self-injury (NSSI), defined as deliberate physical harm to oneself without intent to die. Alcohol use may facilitate engagement in NSSI by increasing impulsivity and physical pain tolerance. Limited data also suggest that people engage in more medically severe NSSI under the influence of alcohol.
METHOD
This secondary analysis study examined the use of alcohol prior to NSSI in a sample of 79 female patients with borderline personality disorder who were enrolled in a randomized clinical trial of dialectical behavior therapy. We used multilevel modeling (MLM) to examine preregistered hypotheses that alcohol use prior to NSSI would be related to the impulsivity of NSSI, physical pain experienced during NSSI, and the medical severity of injuries from NSSI.
RESULTS
Participants endorsed alcohol use prior to 21.96% (47/221) of NSSI episodes, and roughly one third of participants ( = 27) reported at least one episode of NSSI preceded by alcohol use. For NSSI episodes preceded by alcohol use, more than half (52.38%) of participants reported using alcohol up to the moment of initiating NSSI. Alcohol use was significantly associated with higher impulsivity of NSSI episodes ( = 1.16, = .041), but not physical pain from NSSI or medical severity of NSSI.
CONCLUSIONS
Findings need to be replicated but indicate that alcohol use occurs frequently prior to NSSI and could be a target for reducing impulsive episodes of NSSI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38900501
DOI: 10.1037/adb0001016 -
Environmental Monitoring and Assessment Jun 2024The intensive global use of pesticides presents an escalating threat to human health, ecosystems, and water quality. To develop national and local environmental...
The intensive global use of pesticides presents an escalating threat to human health, ecosystems, and water quality. To develop national and local environmental management strategies for mitigating pollution caused by pesticides, it is essential to understand the quantities, timing, and location of their application. This study aims to estimate the spatial distribution of pesticide use in an agricultural region of La Plata River basin in Uruguay. Estimates of pesticide use were made by surveying doses applied to each crop. This information was spatialized through identifying agricultural rotations using remote sensing techniques. The study identified the 60 major agricultural rotations in the region and mapped the use and application amount of the nine most significant active ingredients (glyphosate, 2,4-dichlorophenoxyacetic acid, flumioxazin, S-metolachlor, clethodim, flumetsulam, triflumuron, chlorantraniliprole, and fipronil). The results reveal that glyphosate is the most extensively used pesticide (53.5% of the area) and highest amount of use (> 1.44 kg/ha). Moreover, in 19% of the area, at least seven active ingredients are applied in crop rotations. This study marks the initial step in identifying rotations and estimating pesticide applications with high spatial resolution at a regional scale in agricultural regions of La Plata River basin. The results improve the understanding of pesticide spatial distribution based on data obtained from agronomists, technicians, and producers and provide a replicable methodological approach for other geographic and productive contexts. Generating baseline information is key to environmental management and decision making, towards the design of more robust monitoring systems and human exposure assessment.
Topics: Environmental Monitoring; Uruguay; Pesticides; Rivers; Agriculture; Crops, Agricultural; Water Pollutants, Chemical
PubMed: 38900342
DOI: 10.1007/s10661-024-12759-z -
Environmental Science & Technology Jun 2024Organic molecules in the environment oxidatively degrade by a variety of free radical, microbial, and biogeochemical pathways. A significant pathway is heterogeneous...
Organic molecules in the environment oxidatively degrade by a variety of free radical, microbial, and biogeochemical pathways. A significant pathway is heterogeneous autoxidation, in which degradation occurs via a network of carbon and oxygen centered free radicals. Recently, we found evidence for a new heterogeneous autoxidation mechanism of squalene that is initiated by hydroxyl (OH) radical addition to a carbon-carbon double bond and apparently propagated through pathways involving Criegee Intermediates (CI) produced from β-hydroxy peroxy radicals (β-OH-RO•). It remains unclear, however, exactly how CI are formed from β-OH-RO•, which could occur by a unimolecular or bimolecular pathway. Combining kinetic models and multiphase OH oxidation measurements of squalene, we evaluate the kinetic viability of three mechanistic scenarios. Scenario 1 assumes that CI are formed by the unimolecular bond scission of β-OH-RO•, whereas Scenarios 2 and 3 test bimolecular pathways of β-OH-RO• to yield CI. Scenario 1 best replicates the entire experimental data set, which includes effective uptake coefficients vs [OH] as well as the formation kinetics of the major products (i.e., aldehydes and secondary ozonides). Although the unimolecular pathway appears to be kinetically viable, future high-level theory is needed to fully explain the mechanistic relationship between CI and β-OH-RO• in the condensed phase.
PubMed: 38900151
DOI: 10.1021/acs.est.4c02590 -
Journal of Virology Jun 2024Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the...
Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the present study, we established a mouse model employing a single-cycle infectious virus replicon particle (VRP) system of SARS-CoV-2 that can be safely handled in BSL-2 laboratories. The VRP [ΔS-VRP(G)-Luc] contains a SARS-CoV-2 genome in which the spike gene was replaced by a firefly luciferase (Fluc) reporter gene (Rep-Luci), and incorporates the vesicular stomatitis virus glycoprotein on the surface. Intranasal inoculation of ΔS-VRP(G)-Luc can successfully transduce the Rep-Luci genome into mouse lungs, initiating self-replication of Rep-Luci and, accordingly, inducing acute lung injury mimicking the authentic SARS-CoV-2 pathology. In addition, the reporter Fluc expression can be monitored using a bioluminescence imaging approach, allowing a rapid and convenient determination of viral replication in ΔS-VRP(G)-Luc-infected mouse lungs. Upon treatment with an approved anti-SARS-CoV-2 drug, VV116, the viral replication in infected mouse lungs was significantly reduced, suggesting that the animal model is feasible for antiviral evaluation. In summary, we have developed a BSL-2-compliant mouse model of SARS-CoV-2 infection, providing an advanced approach to study aspects of the viral pathogenesis, viral-host interactions, as well as the efficacy of antiviral therapeutics in the future.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and pathogenic in humans; thus, research on authentic SARS-CoV-2 has been restricted to biosafety level 3 (BSL-3) laboratories. However, due to the scarcity of BSL-3 facilities and trained personnel, the participation of a broad scientific community in SARS-CoV-2 research had been greatly limited, hindering the advancement of our understanding on the basic virology as well as the urgently necessitated drug development. Previously, our colleagues Jin et al. had generated a SARS-CoV-2 replicon by replacing the essential spike gene in the viral genome with a Fluc reporter (Rep-Luci), which can be safely operated under BSL-2 conditions. By incorporating the Rep-Luci into viral replicon particles carrying vesicular stomatitis virus glycoprotein on their surface, and via intranasal inoculation, we successfully transduced the Rep-Luci into mouse lungs, developing a mouse model mimicking SARS-CoV-2 infection. Our model can serve as a useful platform for SARS-CoV-2 pathological studies and antiviral evaluation under BSL2 containment.
PubMed: 38899934
DOI: 10.1128/jvi.00504-24 -
Journal of Cachexia, Sarcopenia and... Jun 2024Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less...
BACKGROUND
Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making.
METHODS
We included 8437 community-dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification.
RESULTS
Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 71 (61-80) and 80 (62-88) μmol/L and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical.
CONCLUSIONS
The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.
PubMed: 38898741
DOI: 10.1002/jcsm.13511 -
Retrovirology Jun 2024Retroviruses exploit host proteins to assemble and release virions from infected cells. Previously, most studies focused on interacting partners of retroviral Gag... (Comparative Study)
Comparative Study
Retroviruses exploit host proteins to assemble and release virions from infected cells. Previously, most studies focused on interacting partners of retroviral Gag proteins that localize to the cytoplasm or plasma membrane. Given that several full-length Gag proteins have been found in the nucleus, identifying the Gag-nuclear interactome has high potential for novel findings involving previously unknown host processes. Here we systematically compared nuclear factors identified in published HIV-1 proteomic studies and performed our own mass spectrometry analysis using affinity-tagged HIV-1 and RSV Gag proteins mixed with nuclear extracts. We identified 57 nuclear proteins in common between HIV-1 and RSV Gag, and a set of nuclear proteins present in our analysis and ≥ 1 of the published HIV-1 datasets. Many proteins were associated with nuclear processes which could have functional consequences for viral replication, including transcription initiation/elongation/termination, RNA processing, splicing, and chromatin remodeling. Examples include facilitating chromatin remodeling to expose the integrated provirus, promoting expression of viral genes, repressing the transcription of antagonistic cellular genes, preventing splicing of viral RNA, altering splicing of cellular RNAs, or influencing viral or host RNA folding or RNA nuclear export. Many proteins in our pulldowns common to RSV and HIV-1 Gag are critical for transcription, including PolR2B, the second largest subunit of RNA polymerase II (RNAPII), and LEO1, a PAF1C complex member that regulates transcriptional elongation, supporting the possibility that Gag influences the host transcription profile to aid the virus. Through the interaction of RSV and HIV-1 Gag with splicing-related proteins CBLL1, HNRNPH3, TRA2B, PTBP1 and U2AF1, we speculate that Gag could enhance unspliced viral RNA production for translation and packaging. To validate one putative hit, we demonstrated an interaction of RSV Gag with Mediator complex member Med26, required for RNA polymerase II-mediated transcription. Although 57 host proteins interacted with both Gag proteins, unique host proteins belonging to each interactome dataset were identified. These results provide a strong premise for future functional studies to investigate roles for these nuclear host factors that may have shared functions in the biology of both retroviruses, as well as functions specific to RSV and HIV-1, given their distinctive hosts and molecular pathology.
Topics: Humans; HIV-1; Gene Products, gag; Cell Nucleus; Nuclear Proteins; gag Gene Products, Human Immunodeficiency Virus; Rous sarcoma virus; Proteomics; Host-Pathogen Interactions; Virus Replication; Host Microbial Interactions; Mass Spectrometry
PubMed: 38898526
DOI: 10.1186/s12977-024-00645-y -
Journal of Geriatric Oncology Jun 2024Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a...
INTRODUCTION
Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status.
MATERIALS AND METHODS
We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry. Frailty and diabetes were captured using a patient-reported geriatric assessment (CARE tool). Frailty was defined using CARE frailty index (CARE-FI) based on principles of deficit accumulation. SMD was calculated from computed tomography scans (L3 vertebrae). Analyses were conducted by sex and diabetes status. Scatterplots and linear regression described crude associations between SMD and frailty score. Classification performance (frail vs. non-frail) was analyzed with (1) area under the receiver operating characteristic curves (AUC) and confidence intervals (CIs); and (2) sensitivity/specificity for sex-specific SMD quartile cut-offs (Q1, median, Q3). Performance was compared between patients with and without diabetes using differences and estimated CIs (2000 bootstrap replicates). We additionally calculated positive and negative likelihood ratios (LR+, LR-).
RESULTS
The analytic cohort included 872 patients (39% female, median age 68 years, 27% with diabetes) with predominately stage III/IV gastrointestinal cancer; >60% planning to initiate first-line chemotherapy. SMD was negatively associated with frailty score; models were best fit in male patients with diabetes. AUC estimates for female (range: 0.58-0.62) and male (0.58-0.68) patients were low. Q3 cut-offs had high sensitivity (range: 0.76-0.89), but poor specificity (0.25-0.34). Diabetes did not impact estimates for female patients. Male patients with diabetes had greater sensitivity estimates compared to those without (sensitivity differences: 0.23 [0.07, 0.38], 0.08 [-0.07, 0.24], and 0.11 [0.00, 0.22] for Q1, median, Q3, respectively). LR estimates were most notable for male patients with diabetes (LR+ = 2.92, Q1 cut-off; LR- = 0.46, Q3 cut-off).
DISCUSSION
Using SMD alone to screen older patients for geriatric assessment requires improvement. High-sensitivity cut-off points could miss 11-24% of patients with frailty, and many non-frail patients may be flagged. Screening with SMD is practical but work is needed to understand clinical andresource impacts of different cut-off points. Future research should evaluate performance with additional clinical data and in subgroups.
PubMed: 38896951
DOI: 10.1016/j.jgo.2024.101815 -
Prosthetics and Orthotics International Jun 2024The selection of the leading limb during gait initiation in individuals with unilateral transtibial amputations can significantly affect various biomechanical...
The selection of the leading limb during gait initiation in individuals with unilateral transtibial amputations can significantly affect various biomechanical parameters. However, there is currently no established recommendation for the suitable leading limb in this population. The systematic review was aimed to propose a preferred leading limb for gait initiation in individuals with unilateral transtibial amputations based on biomechanical parameters. Databases including Google Scholar, PubMed, Science Direct, and ISI Web of Knowledge, were searched. The first selection criterion was based on abstracts and titles to address the research question. A total of seven studies were included in this review, and the Downs and Black's checklist was used by three researchers to assess the risk of bias. The review included a total of 61 adults with unilateral transtibial amputations, with a mean age range of 41 to 64.43 years. The confidence level of the included studies was poor, and the observational cohort was the most common study design (n = 5). Most of the studies were not replicable. Four of the included studies recommended the prosthetic limb as the preferred leading limb. Individuals with unilateral transtibial amputations may experience biomechanical benefits, including a more normal center of pressure path, reduced limb loading, and increased ankle energy generation, when leading with their prosthetic limb during gait initiation. However, further research is necessary to establish a more conclusive recommendation for the preferred leading limb in this population.
PubMed: 38896544
DOI: 10.1097/PXR.0000000000000363