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The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings.

Background/Objectives: There is a gap between the very positive opinion of patients and doctors regarding knee viscosupplementation (VS) and the contrasting results of controlled studies. The objective of this study was to evaluate the overall satisfaction and predictors of satisfaction with VS in patients with knee osteoarthritis treated with VS. Methods : Post-hoc analysis of a cross-sectional study in patients with knee OA treated with one injection of a mannitol-modified cross-linked HA (HANOX-M-XL). The primary outcome was satisfaction, self-assessed semi-quantitatively by the patients. Demographics, radiological features, comorbidities, OA and comorbidities treatments, and lifestyle associated with satisfaction were studied in bivariate and multivariate analysis. Results : 89 patients (124 knees) were analyzed. A total of 88.7% were satisfied with the treatment. Satisfaction was correlated with duration of effectiveness (DoE) and negatively correlated with BMI. Satisfaction was higher in active versus sedentary patients, in tibiofemoral involvement, in Kellgren-Lawrence grade 1-3 versus 4, and in subjects not requiring intraarticular corticosteroid (IACS) concomitantly to VS. Satisfied subjects were older than dissatisfied ones. In multivariate analysis, older age, K-L grade < 4, absence of IACS, and longer DoE were associated with higher rates of satisfaction. Conclusions : We identified several predictive factors of patient satisfaction after VS of the knee. Alongside these objective factors, there are probably subjective factors linked to patient beliefs, fears, and expectations impacting satisfaction.

Introduction: Claw lesions significantly contribute to lameness, greatly affecting sow welfare. This study investigated different factors that would impact the severity of claw lesions in the sows of Brazilian commercial herds., Methods: A total of 129 herds ( n = 12,364 sows) were included in the study. Herds were in the Midwest, Southeast, or South regions of Brazil. Inventory sizes were stratified into 250-810 sows, 811-1,300 sows, 1,301-3,000 sows, and 3,001-10,000 sows. Herds belonged to Cooperative (Coop), Integrator, or Independent structures. The herd management was conducted either maintaining breeds from stock on-site (internal), or through purchase of commercially available genetics (external). Herds adopted either individual crates or group housing during gestation. Within each farm, one randomly selected group of sows was scored by the same evaluator (two independent experts evaluated a total of 129 herds) from 0 (none) to 3 (severe) for heel overgrowth and erosion (HOE), heel-sole crack (HSC), separation along the white line (WL), horizontal (CHW) and vertical (CVW) wall cracks, and overgrown toes (T), or dewclaws (DC) in the hind legs after parturition. The study assessed differences and similarities between herds using Principal Component Analysis (PCA) and Hierarchical Agglomerative Clustering (HAC) analysis. The effects of factors (i.e., production structure, management, housing during gestation, and region) were assessed using the partial least squares method (PLS)., Results and Discussion: Heel overgrowth and erosion had the highest prevalence, followed by WL and CHW, while the lowest scores were observed for T, DC, and CVW. Herds were grouped in three clusters (i.e., C1, C2, and C3). Heel overgrowth and erosion, HSC, WL, CHW, CVW, and T were decreased by 17, 25, 11, 25, 21, and 17%, respectively, in C3 compared to C1 and 2 combined. Independent structure increased the L-Index in all three clusters. Furthermore, individual housing increased the L-Index regardless of the cluster. The results suggest that shifting toward larger, more technologically advanced herds could potentially benefit claw health. Additionally, adopting group gestation housing appears to mitigate the adverse effects on claw health, although further validation is necessary, as Brazil has only recently transitioned from individual housing practices., Competing Interests: TK, AC, AK, MS, CR, and LR are employees of Zinpro. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kramer, Cornelison, Klein, Socha, Rapp, Rodrigues and Alberton.)

Understanding enzyme catalysis as connected to protein motions is a major challenge. Here, based on temperature kinetic studies combined with isotope effect measurements, we obtain energetic description of C-H activation in NAD-dependent UDP-glucuronic acid C4 epimerase. Approach from the ensemble-averaged ground state (GS) to the transition state-like reactive conformation (TSRC) involves, alongside uptake of heat ( Δ H ‡  = 54 kJ mol -1 ), significant loss in entropy ( - T Δ S ‡  = 20 kJ mol -1 ; 298 K) and negative activation heat capacity ( Δ C p ‡  = -0.64 kJ mol -1 K -1 ). Thermodynamic changes suggest the requirement for restricting configurational freedom at the GS to populate the TSRC. Enzyme variants affecting the electrostatic GS preorganization reveal active-site interactions important for precise TSRC sampling and H-transfer. Collectively, our study captures thermodynamic effects associated with TSRC sampling and establishes rigid positioning for C-H activation in an enzyme active site that requires conformational flexibility in fulfillment of its natural epimerase function., (© 2024. The Author(s).)

Background: An advanced radiological stage and obesity are predictive of poorer and shorter responses to viscosupplementation in patients with knee osteoarthritis (OA). Very little is known regarding the impact of other factors such as sport practice, comorbidities, or anatomical features of OA. Methods: This study aimed to investigate patients' and OA characteristics associated with the duration of the effectiveness (DE) of viscosupplementation in patients with knee OA. It was a cross-sectional, single-centre clinical trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigators collected data regarding demographic and radiographic features (Kellgren-Lawrence grade and involved knee compartments), dosing regimen (single or repeat injections), the presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, the number of previous viscosupplementations, and comorbidities. Patients completed a questionnaire including the self-assessment of DE (the number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, or athletic), and the level of sport activity (light, moderate, or intensive). Predictors of the DE were studied in bivariate and multivariate analyses. Results: In total, 105 patients (149 knees) were analysed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m 2 ). The mean DE was 48.2 ± 24.8 weeks. In bivariate analysis, the predictors of a shorter DE were BMI > 27.5 kg/m 2 , more than three previous viscosupplementations, Kellgren-Lawrence grade 4, sedentary patients, and multicompartmental involvement. In the multivariate analysis, four independent factors remained associated with a shorter DE: BMI > 27.5 kg/m 2 , multicompartmental knee involvement, number of viscosupplementations >3, and sedentary lifestyle. A statistically significant association between a longer DE and arterial hypertension was found, suggesting a beneficial effect of certain antihypertensive medications. Conclusions: This study confirms that being overweight significantly reduces the duration of the effectiveness of viscosupplementation. It also shows that viscosupplementation is more lastingly effective in unicompartmental OA and among active or athletic patients. The duration of effectiveness decreases when the treatment is repeated more than three times.

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1 + vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1 + vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1 and balancing VIT deficiency., Competing Interests: Disclosure Statement J.C.S. received fees for lectures from Boehringer Ingelheim and Kinevant, all outside the present study. T.W. declares funding by the German Ministry of Research and Education. M.M.H. received fees for lectures and consultations from Acceleron, Actelion, AOP, Bayer, Janssen, MSD, and Pfizer, all outside the present study. J.F. received personal fees/speaker honoraria from AstraZeneca, outside the submitted work. M.G. received fees for lectures from Boehringer Ingelheim, participates in an adjudication board in a nintedanib clinical trial, and received a research grant from Boehringer Ingelheim. D.D.J. received fees for lectures from Boehringer Ingelheim and declares a research contract with Boehringer Ingelheim (contract number 43099358). All other authors declare no existing conflicts of interest., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)