Parvovirus 4 in French in-patients: a study of haemodialysis and lung transplant cohorts

International audienceThe epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French haemodialysis and lung transplant patients. Plasma samples (n=289) were tested for PARV4 by real-time PCR assay (ORF2), and amplification products selected at random were sequenced. Analysis of available serological and biological markers was also undertaken. Fifty-seven samples out of 185 (30.8%) were positive for PARV4 DNA in the cohort of haemodialysis patients. A higher prevalence of the virus was identified in individuals with markers of HBV infection. PARV4 was also identified in 14 out of 104 samples (13.5%) from lung transplant recipients, with no clear-cut association with available clinical markers. Point mutations located on the zone of real-time detection were identified for some amplification products. This study describes the detection of PARV4 in the blood of haemodialysis and lung transplanted patients with significant difference in prevalence in these two cohorts. Further studies will be needed in order to understand better both the potential implication in host health and the natural history of this virus

Assessments of productive performance, eggshell quality, excreta moisture, and incubation traits of laying breeder hens fed a proprietary blend of Quillaja and Yucca

A study was conducted to evaluate performance, eggshell quality, nutrient metabolizability, and incubation traits of laying breeder hens fed diets supplemented with an additive containing polyphenols and saponins of a proprietary blend from Quillaja saponaria and Yucca schidigera (QY) biomass. Hens were fed 4 feeds in 5 periods of 28 days each from 30 to 49 weeks of age. Experimental feeds were a Control diet; Control + virginiamycin (33 g/ton); Control + QY (250 g/ton) and Control + virginiamycin + QY. A total of 40 White Plymouth Rock and 44 Rhode Island Red breeder hens were allocated in individual cages using a completely randomized block design with 21 replicates. Performance parameters, evaluated per period, were egg production, egg weight, FCR, egg mass, and culled eggs. All eggs were collected in the last 4 days of each period to evaluate specific egg weight, percentage of albumen, yolk and shell, and Haugh unit as well as cuticle quality, shell strength, and shell thickness. At the end of the experiment, nutrient metabolizability assessment and four incubations were conducted. There were no interactions between diet and period in all evaluated responses (P > 0.05). Experimental diets did not affect daily egg production, egg weight, and egg mass as well as Haugh unit, yolk and albumen percentage, and yolk color (P > 0.05). However, hens fed Control + QY produced eggs with better shell strength, shell thickness, and cuticle quality than hens fed the Control (P < 0.05). Hens fed Control + QY or Control + virginiamycin + QY had lower culled eggs, better FCR and higher egg specific weight, shell percentage, and yolk strength compared to breeder hens fed the Control (P < 0.05). In general, hens fed QY achieved enhanced performance and egg quality compared to virginiamycin. In conclusion, laying breeder hens fed diets supplemented with Quillaja and Yucca additive, from 30 to 49 weeks of age, maintained their productive performance, had improved eggshell and cuticle quality and reduced culled, dirty and contaminated eggs

Martian Atmospheric Aerosols Composition and Distribution Retrievals During the First Martian Year of NOMAD/TGO Solar Occultation Measurements: 2. Extended Results, End of MY 34 and First Half of MY 35

This is the second part of Stolzenbach et al. (2023, https://doi.org/10.1029/2022JE007276), named hereafter Paper I, extends the period to the end of MY 34 and the first half of MY 35. This encompasses the end phase of the MY 34 Global Dust Storm (GDS), the MY 34 C-Storm, the Aphelion Cloud Belt (ACB) season of MY 35, and an unusual early dust event of MY 35 from L$_S$ 30° to L$_S$ 55°. The end of MY 34 overall aerosol size distribution shows the same parameters for dust and water ice to what was seen during the MY 34 GDS. Interestingly, the layered water ice vertical structure of MY 34 GDS disappears. The MY 34 C-Storm maintains condition like the MY 34 GDS. A high latitude layer of bigger water ice particles, close to 1 μm, is seen from 50 to 60 km. This layered structure is linked to an enhanced meridional transport characteristic of high intensity dust event which put the MY 34 C-Storm as particularly intense compared to non-GDS years C-Storms as previously suggested by Holmes et al. (2021, https://doi.org/10.1016/j.epsl.2021.117109). Surprisingly, MY 35 began with an unusually large dust event (Kass et al., 2020, https://ui.adsabs.harvard.edu/abs/2020AGUFMP039…01K) found in the Northern hemisphere during L$_S$ 35° to L$_S$ 50°. During this dust event, the altitude of aerosol first detection is roughly equal to 20 km. This is close to the values encountered during the MY 34 GDS, its decay phase and the C-Storm of the same year. Nonetheless, no vertical layered structure was observed

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach

Low Rates of Both Lipid-Lowering Therapy Use and Achievement of Low-Density Lipoprotein Cholesterol Targets in Individuals at High-Risk for Cardiovascular Disease across Europe

Aims To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Methods and Results Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients’ 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE 5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE 10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels ( 2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as 1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72%and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin 40 mg/day or rosuvastatin 20 mg/day). Among veryhigh- risk patients, this figure was 8.4%. Conclusions There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in EuropeWriting support was provided by Oxford PharmaGenesis Ltd, Oxford, UK, and was funded by AstraZenec

Martian Atmospheric Aerosols Composition and Distribution Retrievals During the First Martian Year of NOMAD/TGO Solar Occultation Measurements: 2. Extended Results, End of MY 34 and First Half of MY 35

This is the second part of Stolzenbach et al. (2023, https://doi.org/10.1029/2022JE007276), named hereafter Paper I, extends the period to the end of MY 34 and the first half of MY 35. This encompasses the end phase of the MY 34 Global Dust Storm (GDS), the MY 34 C‐Storm, the Aphelion Cloud Belt (ACB) season of MY 35, and an unusual early dust event of MY 35 from LS 30° to LS 55°. The end of MY 34 overall aerosol size distribution shows the same parameters for dust and water ice to what was seen during the MY 34 GDS. Interestingly, the layered water ice vertical structure of MY 34 GDS disappears. The MY 34 C‐Storm maintains condition like the MY 34 GDS. A high latitude layer of bigger water ice particles, close to 1 μm, is seen from 50 to 60 km. This layered structure is linked to an enhanced meridional transport characteristic of high intensity dust event which put the MY 34 C‐Storm as particularly intense compared to non‐GDS years C‐Storms as previously suggested by Holmes et al. (2021, https://doi.org/10.1016/j.epsl.2021.117109). Surprisingly, MY 35 began with an unusually large dust event (Kass et al., 2020, https://ui.adsabs.harvard.edu/abs/2020AGUFMP039…01K) found in the Northern hemisphere during LS 35° to LS 50°. During this dust event, the altitude of aerosol first detection is roughly equal to 20 km. This is close to the values encountered during the MY 34 GDS, its decay phase and the C‐Storm of the same year. Nonetheless, no vertical layered structure was observed

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor–specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor–specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade–mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors