Deletions of the esterase D locus from a survey of 200 retinoblastoma patients

Summary Esterase D levels from 200 retinoblastoma patients have been measured in an attempt to identify individuals carrying deletions of chromosome region 13q14. In this series 75% had bilateral tumours and 23% were familial. Of nine patients identified as having low esterase D levels, five had not previously been diagnosed as deletion carriers. These observations demonstrate the benefit of screening retinoblastoma populations for esterase D deficiency.     

The use of low doses of dopamine in intensive care medicine

The dopamine alpha- and beta-adrenoceptor dose-response curves are investigated in four patients who are exempt from cardiovascular disease. A dose-related increase in CO, HR and SV is observed with infusion rates of up to 3 micrograms kg-1 min-1. With concentrations greater than 10 micrograms kg-1 min-1, both BP and SVR increase. Low-dose dopamine infusion less than 3 micrograms kg-1 min-1 is investigated in ten other patients. With this infusion rate, a selective renal vasodilation is induced without peripheral or cardiac beta-adrenoceptor activation. Dopamine is responsible for an increase in diuresis FENa, GFR and RBF. These properties are indicated in renal failure, and when haemodynamic support is required in cardiac failure, if an infusion rate of up to 10 micrograms kg-1 min-1 is able to reverse cardiac insufficiency.     

Creatine and creatinine quantification in olympic athletes: dried blood spot analysis pilot study

Capillary dried blood spot (DBS) samples facilitate field-based collection without venipuncture. This pilot study aims to evaluate the viability of creatine (Cr) and creatinine (Crt) quantification using fresh capillary serum (Cr_S/Crt_S) and DBS samples (Cr_DBS/Crt_DBS), using Flow Injection Analysis Mass Spectrometry (FIA – MS). Nine Olympic Athletes provided a capillary blood sample to assess Cr_S/Crt_S and Cr_DBS/Crt_DBS quantified by FIA – MS. No difference between Crt_S (mean ± SD: 813.6 ± 102.4 μmol/L) and Crt_DBS (812.4 ± 108.1 μmol/L) was observed with acceptable variance [SEM 88.7; CV 10.7%; ICC 0.57 (CI 95% 0.06 – 0.84)] and agreement [very strong (Spearman: r = 0.77; p < 0.01) or strong (Pearson: r = 0.56; p = 0.04); Bland Altman: lower (-193) and upper (+196) limits of agreement]. Cr_S (mean ± SD: 691.8 ± 165.2 μmol/L) was significantly different to Cr_DBS (2911 ± 571.4 μmol/L) with unacceptable variance [SEM 171.6; CV 27%; ICC 0.002 (CI 95% -0.02 – 0.07)] and ‘weak’ agreement [Spearman: r = 0.21, p = 0.47 and Pearson: r = 0.06, p = 0.84; Bland Altman lower (-3367) and upper (-1072) limits of agreement]. Crt quantification is viable using both Crt_S and Crt_DBS (but not for Cr and Cr_S/Cr_DBS), with the DBS tissue handling technique offering several methodological and practice facing advantages. Future work should expand upon the sample size, explore sport/discipline relevant analytes across a full competitive season, including key training, recovery and performance blocks of their periodized performance plan.     

The Gram-positive side of plant–microbe interactions

Plant growth and development are significantly influenced by the presence and activity of microorganisms. To date, the best-studied plant-interacting microbes are Gram-negative bacteria, but many representatives of both the high and low G+C Gram-positives have excellent biocontrol, plant growth-promoting and bioremediation activities. Moreover, actinorhizal symbioses largely contribute to the global biological nitrogen fixation and many Gram-positive bacteria promote other types of symbioses in tripartite interactions. Finally, several prominent and devastating phytopathogens are Gram-positive. We summarize the present knowledge of the beneficial and detrimental interactions of Gram-positive bacteria with plants to underline the importance of this particular group of bacteria.     

On Circuit Functionality in Boolean Networks

It has been proved, for several classes of continuous and discrete dynamical systems, that the presence of a positive (resp. negative) circuit in the interaction graph of a system is a necessary condition for the presence of multiple stable states (resp. a cyclic attractor). A positive (resp. negative) circuit is said to be functional when it “generates” several stable states (resp. a cyclic attractor). However, there are no definite mathematical frameworks translating the underlying meaning of “generates.” Focusing on Boolean networks, we recall and propose some definitions concerning the notion of functionality along with associated mathematical results.     

Poly(D,L-lactide-co-glycolide acid) nanoparticles for DNA delivery: waiving preparation complexity and increasing efficiency

When designing a nonviral gene delivery system based on polymeric nanoparticles (NPs), it is important to keep in mind obstacles associated with future clinical applications. Simplifying the procedure of NPs production and taking toxicity into account are the most important issues that need to be addressed. Toxicity concerns in clinical trials may be raised when using additives such as cationic polymers/lipids, buffering reagents, and proteins. Therefore, the aim of this study was to simplify the formulation of poly (lactide-co-glycolide) acid NPs by shortening steps such as sonication time and by avoiding the use of additives while preserving its efficiency. NPs (300 nm) were formulated using a modified w/o/w technique with DNA entrapment efficiency of 80%. Once achieving such NPs, formulation parameters such as DNA loading, release kinetics, DNA integrity and bioactivity, uptake by cells, and toxicity were addressed. The NPs were readily taken by several cell lines and were localized mostly in their endo-lysosomal compartments. The NPs did not affect cells viability. Most importantly, transfection studies in COS-7 and Cf2th cells resulted with a 250-fold protein expression levels when compared with the control. These expression levels are higher than ones achieved with more complicated NPs systems, demonstrating the efficiency of our simplified NPs for gene delivery.     

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial

BackgroundWomen with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.Methods and findingsIn this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m²) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (−6.6 ± 5.4% versus −0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.ConclusionsA preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02432209","term_id":"NCT02432209"}}NCT02432209.

Richard Legro and colleagues investigate the impact of a preconception weight loss intervention on healthy live birth rates in women with obesity and unexplained infertility.