Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles

Spermatozoa selection at high magnification before intracytoplasmic sperm injection seems to be positively associated with pregnancy rates after day 3 embryo transfers. The aim was to demonstrate an association between the presence of vacuoles in sperm nuclei and the competence of embryos to develop to day 5. Grading of spermatozoa at x 6000-x 12,500 magnification: grade I, no vacuoles; grade II, or=1 large vacuole; grade IV, large vacuoles with other abnormalities. The outcome of embryo development in a group of 25 patients after sibling oocyte injection with the four different grades of spermatozoa showed no significant difference in embryo quality up to day 3. However, the occurrence of blastocyst formation was 56.3 and 61.4% with grade I and II spermatozoa respectively, compared with 5.1% with grade III and 0% with grade IV respectively (P < 0.001). Spermatozoa selection at high magnification using Nomarski interference contrast is useful to identify more precisely the size and the number of nuclear vacuoles that greatly exert a negative effect on embryo development to the blastocyst stage. These observations confirm previous studies pointing to possible 'early and late paternal effects', both of which may have an impact on early embryonic development.     

Investigation of Electrical Transitions in the First Steps of Spark Plasma Sintering: Effects of Pre-Oxidation and Mechanical Loading within Copper Granular Media

Spark Plasma Sintering (SPS) has become a conventional and promising sintering method for powder consolidation. This study aims to well understand the mechanisms of densification encountered during SPS treatments, especially in the early stages of sintering. The direct current (DC) electrical behavior of copper granular medium is characterized. Their properties are correlated with their microstructural evolutions through post-mortem scanning electron microscope (SEM) observations to allow a thorough understanding of the involved Branly effect that is suspected to occur in SPS. The electrical response is studied by modifying the initial thickness of the oxide layer on particles surfaces and applying various mechanical loads on the granular medium. Without load and at low current, the measured quasi-reversible behavior is connected to the formation of spots at the microcontacts between the particles. By increasing the current, the Branly transition from an insulating to a conductive state suddenly occurs. The insulating oxide layer is destroyed, and micro-bridges are created. The application of a mechanical pressure strongly modifies the DC Branly effect. Increasing low stress leads to a strong decrease in the breakdown field. For high-applied pressure, successive drops in the electric field are detected during the electrical transition. These successive drops are induced by microcracking of the insulating oxide layer.     

Anemia and blood transfusion in critically ill patients

Context  Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined. Objectives  To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Design  Prospective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study. Setting and Patients  The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Main Outcome Measures  Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. Results  The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P<.001) and total volume drawn (r = 0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; ² = 50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; ² = 88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P = .02); the Kaplan-Meier log-rank test confirmed this difference. Conclusions  This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.      

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues.Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints.However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin.