The Fate of Porous Hydroxyapatite Granules Used in Facial Skeletal Augmentation

Facial appearance is largely determined by the morphology of the underlying skeleton. Hydroxyapatite is one of several materials available to enhance projection of the facial skeleton. This study evaluated the long-term maintenance of augmented bony projection when porous hydroxyapatite granules are used on the facial skeleton. Ten female patients aged 28–58 years were studied following aesthetic augmentation of the facial skeleton at 24 sites using porous hydroxyapatite granules. Postoperative CT scans at 3 months served as the baseline measurement and compared with scans taken at 1 and 2 years, with the thickness of the hydroxyapatite measured in axial and coronal planes. Thickness of original bone plus overlay of hydroxyapatite, thickness of the overlying soft tissue, and the overall projection (bone plus soft tissue) were recorded. It was found that 99.7% of the hydroxyapatite was maintained at 2 years, with no statistical difference (t test) from the baseline measurement. The overall projection (bony and soft tissue) was maintained as there was no evidence of native bone resorption or soft tissue atrophy. Radiographic results confirmed that the use of porous hydroxyapatite granules for enhancement of the facial skeleton is not only a predictable procedure, but maintains full bony projection at 2 years

Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources

BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999–2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Metabolic programming in juveniles of the whiteleg shrimp ( Litopenaeus vannamei ) linked to an early feed restriction at the post-larval stage

In this study, the concept of metabolic programming has been tested for the first time in whiteleg shrimp (L. vannamei). Shrimp were raised under a 70% feed restriction during the post-larval stage over three days and compared to a control group. After 46 days, shrimp were challenged with 3 diets showing different nitrogen free-extract: crude protein ratios (1.5, 1.0 and 0.7) for 70 days. In order to test the existence of metabolic programming, we analyzed shrimp growth performance as well as mRNA levels of different metabolic and digestive actors after the stimulus, and also before and after the challenge. No direct effects of the stimulus were observed for several digestive and metabolic actors, except for the trypsin mRNA (lower in the feed-restricted group, probably linked to a decrease in dietary protein intake). As expected, significant effects associated with the diet challenge were detected for shrimp performance, i.e., growth was lower in shrimp fed with reduced levels of dietary proteins. More interestingly, some effects linked to the nutritional history were also detected showing an improved growth performance for shrimp previously restricted at the post-larvae stage. After the dietary challenge, significantly lower mRNA levels for hepatopancreatic genes involved in digestion (lipase, preamylase and trypsin), amino acid metabolism (gs), energy metabolism (cox VI b) and glucose metabolism (lvglut 1, lvglut 2 and pk) were found in restricted shrimp. The link between an enhanced growth performance and these molecular markers in early feed restricted shrimp requires further studies. Overall, our study has demonstrated for the first time that shrimp can be programmed by an early nutritional stimulus. This will allow the development of new feeding strategies in shrimp for sustainable aquacultur

Long-term impact of a 4-day feed restriction at the protozoea stage on metabolic gene expressions of whiteleg shrimp (Litopenaeus vannamei)

International audienceBased on the ''nutritional programming'' concept, we evaluated the long-term effects of an early four-day caloric restriction (40% reduction in feed allowance compared to a normal feeding level) at the protozoea stage in whiteleg shrimp. We analyzed long-term programming of shrimp by studying metabolism at the molecular level, through RT-qPCR of key biomarkers (involved in intermediary metabolism and digestion). The mRNA levels (extracted from the whole body) were analyzed after the stimulus and after the rearing period, at 20 and 35 days, respectively. At the end of the experimental period, shrimp growth performance was evaluated. There was no difference between normal feed allowance (CTL) and feed-restricted shrimp (RES) for performance parameters (survival, final body weight and the number of post-larvae g −1 or PL g −1). The stimulus directly affected the mRNA levels for only two genes, i.e., preamylase and lvglut 2 which were expressed at higher levels in feed-restricted shrimp. In the long-term, higher levels of mRNAs for enzymes coding for glycolysis and ATP synthesis were also detected. This suggests a possible long-term modification of the metabolism that is linked to the stimulus at the protozoea stage. Overall, further studies are needed to improve nutritional programming in shrimp

Ontogenesis of metabolic gene expression in whiteleg shrimp ( Litopenaeus vannamei ): New molecular tools for programming in the future

Nutritional programming is a very promising strategy for modifying nutrient metabolism to better adapt animals to new diets. Although it is a well-known approach in fish-farmed species, it has never been applied in marine shrimp. A preliminary requirement to perform nutritional programming is to identify the best developmental window for early stimulus. The objective of the present study was to characterize the ontogenesis of the expression of the main genes involved in digestion and metabolism in white shrimp, Litopenaeus vannamei. Four genes involved in digestion, 11 genes in intermediary metabolism (glucose, amino acid and lipid metabolism) and 5 genes in energy metabolism (mitochondria) were studied at 10 different developmental stages (from eggs – 8 h after fertilization - up to post-larval substage 5) using qRT-PCR for measuring mRNA levels. Our data show that almost all of the studied genes present higher mRNA levels during the protozoea substage Z1, which could be explained by the endogenous-exogenous feeding transition in white shrimp. In conclusion, Z1 substage shows a high molecular plasticity for metabolism which becomes the preferential developmental window for future programming experiments in L. vannamei.Statement of relevanceOur study aimed at characterizing for the first time the ontogenesis of expressions of genes involved in intermediary metabolism (nutrient metabolism). This approach determined developmental windows with high molecular plasticity (Z1 and PL stages). These data will support future studies in nutritional programming for the whiteleg shrimp by determining the timing for early stimulu