Intraocular retinal transplants

Embryonic rat retinae transplanted into the anterior chamber of adult rat eyes of the same or different strain survive and grow. Light and electron microscopic studies show that the transplants undergo histogenetic differentiation, resulting in the development of mature inner and outer layer neurons and Muller glial cells. Vascular connections develop between the host iris and the retinal transplant. These initial observations indicate that retinal transplantation to a recipient eye is a procedure which offers ample opportunities for the study of problems related to neural development, retinal plasticity and repair

A geoarchaeological review of Balzi Rossi, Italy: A crossroad of Palaeolithic populations in the northwest Mediterranean

The Balzi Rossi archaeological complex (comprised of caves, rock shelters, and open-air sites) is a globally significant site for Palaeolithic culture and understanding the transition from Neanderthal to Anatomically Modern Human populations in Europe. It also retains some of the earliest evidence of human interactions with their coastal environment. Balzi Rossi has been subject to excavation for over 150 years - traditionally as individual site locations - with most deposits removed when the discipline of archaeology was nascent, and the science not yet developed. The consequence was the unfortunate loss of materials and critically important stratigraphic context. However, valuable information regarding the Palaeolithic population, their coastal environment, and earlier sea-level change, remains in the literature and in museum repositories. In this work we have compiled and reviewed the extensive resources, available largely in French and Italian, to provide a summary and catalogue for each individual site. These "Site Summaries" are available as appendices to this review, which provides a comprehensive synopsis of the history of excavations conducted at Balzi Rossi, a reconstruction of stratigraphy where possible, the evidence of Palaeolithic occupations, the evidence of Pleistocene sea-level fluctuations, and an assessment of the chronological constraint available for both the Palaeolithic populations and sea level. Finally, this synopsis identifies gaps in knowledge and provides comments on pathways for future research, suggesting a consilient approach that can be applied in other archaeological contexts

The Impact of Nonequilibrium Conditions in Lung Surfactant: Structure and Composition Gradients in Multilamellar Films

The lipid–protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air–liquid interfaces

Bovine Follicular Dynamics, Oocyte Recovery,and Development of Oocytes Microinjected with a Green Fluorescent Protein Construct

The present study was carried out to 1) evaluate the viability of in vitro fertilized zygotes after microinjection of DNA, 2) assess the influence of oocyte quality upon the development rate of embryos when injected with DNA, and 3) determine the integration frequency of green fluorescent protein DNA into microinjected embryos. Oocytes were aspirated from ovaries of nine nonlactating Holsteins and were categorized into grades A, B, C, and D. At 16 h after in vitro fertilization, approximately half of the pronuclear stage presumptive zygotes were classified as having 1 pronucleus or 2 pronuclei, and they were microinjected with DNA constructs. A potential predictor of DNA integration frequency at d 10 was assessment of the incidence of green fluorescing embryos. The proportion of cleaved embryos that developed to morulae or blastocysts was not different between groups with 1 pronucleus injected (45%), 1 pronucleus uninjected (64%), or 2 pronuclei injected (49%). However, the development of morulae or blastocysts was higher in the group with 2 pronuclei uninjected (69%). The overall developmental score of green fluorescent protein-positive embryos was higher for grade A oocytes (1.3 &#;&#;0.1) than for grade B (0.8 &#; 0.1), C (0.6 &#;&#;0.1), or D (0.3 &#;&#;0.1) oocytes. The results show that production of transgenic bovine blastocysts can occur from the microinjection of a presumptive zygote having only one visible pronucleus. Initial oocyte quality is an important factor in selection of oocytes suitable for microinjection of DNA and for preimplantation development to produce bovine transgenic embryos

Deciphering factors linked with reduced SARS-CoV-2 susceptibility in the Swiss HIV Cohort Study

BACKGROUND Factors influencing susceptibility to SARS-CoV-2 remain to be resolved. Using data of the Swiss HIV Cohort Study (SHCS) on 6,270 people with HIV (PWH) and serologic assessment for SARS-CoV-2 and circulating-human-coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS We analyzed SARS-CoV-2 PCR-tests, COVID-19 related hospitalizations, and deaths reported to the SHCS between January 1, 2020 and December 31, 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in pre-pandemic (2019) and pandemic (2020) bio-banked plasma and compared to HIV-negative individuals. We applied logistic regression, conditional logistic regression, and Bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and Ab responses to SARS-CoV-2 in PWH. RESULTS No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High pre-pandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses upon infection. We observed a robust protective effect of smoking on SARS-CoV-2-infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14), which occurred even in previous smokers, and was highest for heavy smokers. CONCLUSIONS Our findings of two independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. METHODS: In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. CONCLUSION: Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION: clinicaltrials.gov NCT00145301

Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

BACKGROUND: The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). METHODS: The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. RESULTS: The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). CONCLUSIONS: In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation

External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV

Post-mortem volatiles of vertebrate tissue

Volatile emission during vertebrate decay is a complex process that is understood incompletely. It depends on many factors. The main factor is the metabolism of the microbial species present inside and on the vertebrate. In this review, we combine the results from studies on volatile organic compounds (VOCs) detected during this decay process and those on the biochemical formation of VOCs in order to improve our understanding of the decay process. Micro-organisms are the main producers of VOCs, which are by- or end-products of microbial metabolism. Many microbes are already present inside and on a vertebrate, and these can initiate microbial decay. In addition, micro-organisms from the environment colonize the cadaver. The composition of microbial communities is complex, and communities of different species interact with each other in succession. In comparison to the complexity of the decay process, the resulting volatile pattern does show some consistency. Therefore, the possibility of an existence of a time-dependent core volatile pattern, which could be used for applications in areas such as forensics or food science, is discussed. Possible microbial interactions that might alter the process of decay are highlighted