Angiogenic imbalance in maternal and cord blood is associated with neonatal birth weight and head circumference in pregnancies with major fetal congenital heart defect.

OBJECTIVES: To ascertain whether abnormalities in neonatal head circumference and/or body weight are associated with levels of angiogenic/antiangiogenic factors in the maternal and cord blood of pregnancies with a congenital heart defect (CHD) and to assess whether the specific type of CHD influences this association. METHODS: This was a multicenter case-control study of women carrying a fetus with major CHD. Recruitment was carried out between June 2010 and July 2018 at four tertiary care hospitals in Spain. Maternal venous blood was drawn at study inclusion and at delivery. Cord blood samples were obtained at birth when possible. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal and cord blood. Biomarker concentrations in the maternal blood were expressed as multiples of the median (MoM). RESULTS: PlGF, sFlt-1 and sEng levels were measured in the maternal blood in 237 cases with CHD and 260 healthy controls, and in the cord blood in 150 cases and 56 controls. Compared with controls, median PlGF MoM in maternal blood was significantly lower in the CHD group (0.959 vs 1.022; P < 0.0001), while median sFlt-1/PlGF ratio MoM was significantly higher (1.032 vs 0.974; P = 0.0085) and no difference was observed in sEng MoM (0.981 vs 1.011; P = 0.4673). Levels of sFlt-1 and sEng were significantly higher in cord blood obtained from fetuses with CHD compared to controls (mean ± standard error of the mean, 447 ± 51 vs 264 ± 20 pg/mL; P = 0.0470 and 8.30 ± 0.92 vs 5.69 ± 0.34 ng/mL; P = 0.0430, respectively). Concentrations of sFlt-1 and the sFlt-1/PlGF ratio in the maternal blood at study inclusion were associated negatively with birth weight and head circumference in the CHD group. The type of CHD anomaly (valvular, conotruncal or left ventricular outflow tract obstruction) did not appear to alter these findings. CONCLUSIONS: Pregnancies with fetal CHD have an antiangiogenic profile in maternal and cord blood. This imbalance is adversely associated with neonatal head circumference and birth weight. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Distribution of Hg and Se in Muscle and Liver of the Thornback Guitarfish Platyrhinoidis triseriata from the Eastern Pacific Ocean.

Human consumption of the thornback guitarfish (Platyrhinoidis triseriata) is concentrated in coastal populations of the Pacific coast of Mexico as its meat is prized for its high quality. This study analyzes the distribution of mercury and selenium in the muscle and liver of Platyrhinoidis triseriata and the risk to human health associated with its consumption. In order to conduct these estimates, specimens were collected from the Eastern Pacific Ocean in 2015 and 2016 and found mean concentrations (µg g-1 wet weight) of mercury ranging from 0.02 to 0.58 in muscle and 0.10 to 0.31 in liver. Selenium ranged from 0.14 to 1.31 in muscle and from 0.93 to 4.52 in liver. Mercury levels in the muscle of P. triseriata were significantly correlated (positive correlation) with the total length of the specimens. The predominant prey of P. triseriata was the shrimp Pleuroncodes planipes and according to the biomagnification factor, only mercury was biomagnified. The risk to consumers associated with the simultaneous presence of mercury and selenium in the muscle and liver of rays under the selenium health benefit value approach indicated that consumption of P. triseriata from this area is beneficial to human health.

Clinical Approach to Mast Cell Activation Syndrome: A Practical Overview.

The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS.

Bioaccumulation of mercury in Haemulopsis elongatus and Pomadasys macracanthus from the SE Gulf of California: condition indexes and health risk assessment.

Mercury (Hg) was measured in the muscle, liver, and gonads of Haemulopsis elongatus and Pomadasys macracanthus from Mazatlán (SE Gulf of California) to determine the relationships of the hepatosomatic index (HSI) and gonadosomatic index (GSI) of fish with Hg concentrations in the corresponding tissues. Health risk to consumers was assessed by using the hazard quotient (HQ), considering the average rate of fish consumption in Mexico and Hg concentration in the edible tissue. In H. elongatus, the highest Hg levels were measured in the liver (3.748 µg g-1); in P. macracanthus, the highest Hg concentration was quantified in the muscle (0.574 µg g-1). In P. macracanthus, the HSI was negatively correlated with Hg concentration in the liver; in H. elongatus, there was also a negative relationship between Hg levels in gonads and the GSI. Mean HQ values in Haemulopsis elongatus (0.005) and Pomadasys macracanthus (0.002) were below the value (HQ ≥ 1) of concern. The significant reduction of HSI and GSI with Hg increase in the liver and gonads may suggest that Hg bioaccumulation in these fish shows adverse physiological effects. Though HQ values in both species were below the unit, i.e., the consumption of the muscle from this species does not represent a health risk, it is necessary to carry out surveys of fish consumption rates in coastal areas of Mexico to do a more precise health risk assessment associated to Hg intake.

High SNP diversity in the non-toxic indigenous Jatropha curcas germplasm widens the potential of this upcoming major biofuel crop species.

BACKGROUND AND AIMS: Jatropha curcas (jatropha) is an oil crop cultivated in (sub)tropical regions around the world, and holds great promise as a renewable energy source. However, efforts to fully commercialize jatropha are currently hampered by the lack of genetic diversity in the extant breeding germplasm, and by the toxicity of its seeds meaning that its seed cake cannot be used as a protein source in animal feed, among other constraints. In Mexico, the species' native range, there are jatropha plants whose seeds are used to prepare traditional meals. This non-toxic jatropha 'type' is considered to harbour low genetic variation due to a presumed domestication bottleneck and therefore to be of limited breeding value; yet, very little is known regarding its origin and genetic diversity. METHODS: Using genotyping-by-sequencing (GBS), we extensively genotyped both indigenous toxic and non-toxic jatropha collected along roads and home gardens throughout southern Mexico. KEY RESULTS: Single nucleotide polymorphism diversity in non-toxic jatropha is relatively high, particularly in northern Veracruz state, the probable origin of this germplasm. Genetic differences between toxic and non-toxic indigenous genotypes are overall quite small. A a genome-wide association study supported a genomic region (on LG 8, scaffold NW_012130064), probably involved in the suppression of seed toxicity. CONCLUSIONS: Conservation actions are urgently needed to preserve this non-toxic indigenous, relatively wild germplasm, having potential as a fuel feedstock, animal feed and food source among other uses. More generally, this work demonstrates the value of conservation genomic research on the indigenous gene pool of economically important plant species.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

Brain angiogenic gene expression in fetuses with congenital heart disease.

OBJECTIVE: To assess potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue of euploid fetuses with congenital heart disease (CHD) vs those without. METHODS: Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses that had undergone termination of pregnancy. Expression profiles of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and of genes associated with chronic hypoxia were determined by real-time polymerase chain reaction in tissue from the frontal cortex and the basal ganglia of the fetuses. RESULTS: Expression of sFlt-1 was 48% higher in the frontal cortex (P = 0.0431) and 72% higher in the basal ganglia (P = 0.0369) of CHD fetuses compared with controls. The expression of VEGF-A was 60% higher (P = 0.0432) and that of hypoxia-inducible factor 2-alpha was 98% higher (P = 0.0456) in the basal ganglia of CHD fetuses compared with controls. No significant differences were observed between the two groups in the expression of PlGF and hypoxia-inducible factor 1-alpha. CONCLUSION: An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue of fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Lettuce Allergy Is a Lipid Transfer Syndrome-Related Food Allergy With a High Risk of Severe Reactions.

BACKGROUND AND OBJECTIVE: Lipid transfer protein (LTP) sensitization is the most common cause of food allergy in the Mediterranean area, with peach allergy acting as the primary sensitizer in most cases. Lettuce has been described as a common offending food in patients with LTP syndrome. The aim of the study was to investigate the frequency and clinical expression of LTP syndrome in a sample of lettuceallergic patients. METHODS: We determined specific IgE to Pru p 3 and lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms elicited by other LTP-containing plant-derived foods and the presence of cofactors were assessed. RESULTS: The clinical symptoms of lettuce allergy were frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the patients had allergic reactions to other plant foods. Cofactors were involved in the clinical reactions of 13 of the 30 patients. Sensitization to pollens was found in 90% of patients. CONCLUSIONS: Lettuce allergy is found not as an isolated condition but in the context of LTP syndrome and it is characterized by severe reactions and frequent cofactor association.

Total mercury in muscles and liver of Mugil spp. from three coastal lagoons of NW Mexico: concentrations and risk assessment.

Total mercury (Hg) concentrations were determined by atomic absorption spectrophotometry in muscles and liver of composite samples of Mugil cephalus and M. curema collected during November 2013 and in January, April, and July 2014 from the coastal lagoons Altata-Ensenada del Pabellón (AEP), Ceuta (CEU), and Teacapán-Agua Brava (TAG) of Sinaloa State. The mean Hg contents and information on local consumption were used to assess the possible risk caused by fish ingestion. Mean total mercury levels in the muscles ranged from 0.11 to 0.39 µg/g, while the range for liver was 0.12-3.91 µg/g. The mean Hg content of the liver was significantly (p < 0.001) higher than that of the muscles only in samples collected from AEP. Although total Hg levels in the muscles were lower than the official permissible limit, the HQ values for methyl mercury calculated for the younger age classes of one fishing community were >1, indicating a possible risk for some fishing communities of the Mexican Pacific coast.

Mercury in the Blue Marlin (Makaira nigricans) from the Southern Gulf of California: Tissue Distribution and Inter-Annual Variation (2005-2012).

With the aim of knowing annual variations of Hg concentrations in muscle and liver of blue marlin (Makaira nigricans) from the southern Gulf of California, fish were collected between 2005 and 2012 in three areas. In general, Hg levels were more elevated in liver than in muscle. Variations of Hg concentrations in muscle and liver among the studied years were not significant. Hg levels in muscle and liver increased significantly with length and weight of fish. In comparison to other studies, Hg levels in muscle and liver were lower. With respect to maximum permissible limits (1.0 µg g-1 wet weight) of Hg in Mexico, the average concentration (1.91 µg g-1 wet weight) in the edible portion (muscle) of blue marlin was over the legal limit; this issue is worth research efforts in relation to the rate of ingestion of this species and the co-occurrence of selenium in the edible portion.

Mercury and selenium concentrations in marine shrimps of NW Mexico: health risk assessment.

We determined total Hg and Se contents of hepatopancreas, exoskeleton, and muscle, and the Se:Hg molar ratios in the muscle of shrimps Farfantepenaeus californiensis and Litopenaeus stylirostris caught in NE Pacific Mexican waters. Total Hg mean values in muscle, hepatopancreas, and exoskeleton were 0.31 ± 0.26, 0.28 ± 0.29, and 0.24 ± 0.06 µg g-1, and 0.46 ± 0.46, 0.41 ± .034, and 0.24 ± 0.06 µg g-1 for F. californiensis and L. stylirostris, respectively. In all tissues, the mean concentrations of Se tended to be close to one order of magnitude higher than the respective Hg values. In F. californiensis, the hepatopancreas of the larger commercial size had significantly (p < 0.05) higher Hg content than smaller sizes, but correlations size-Hg concentration calculated for each tissue of either species were not significant. The Hg content of the muscle of all commercial sizes of both species was lower than the permissible limit and their Se:Hg ratios in all sizes were higher than 1, indicating low risk for human consumption.

Mercury Concentrations in Pacific Angel Sharks (Squatina californica) and Prey Fishes from Southern Gulf of California, Mexico.

Concentrations of mercury (Hg) were quantified in muscle tissues of the Pacific angel shark, Squatina californica sampled from Southern Gulf of California, Mexico, considering total length, sex, diet and the dietary risk assessment. High Hg levels are typically associated with carnivorous fishes, however S. californica showed low Hg concentrations (<1.0 µg g(-1)) in muscle (0.24 ± 0.27 µg g(-1) wet weight; n = 94). No effect of sex, total length and weight on Hg concentrations were observed in the shark (p > 0.05). Hg concentrations were highest in the darkedge mishipman: Porichthys analis (0.14 ± 0.08 µg g(-1)) and red-eye round herring Etrumeus teres (0.13 ± 0.05 µg g(-1)) relative to other prey species, which could suggest that Hg concentrations in S. californica were influenced by these species. Given the relatively low concentration of Hg across age-classes and sex, consumption of S. californica's muscle tissue poses limited risk to humans.

Carryover negligibility and relevance in bioequivalence studies.

The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non-existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focuses on average bioequivalence studies based on 2 × 2 crossover designs and on the main problem associated with carryover: type I error inflation. We propose an equivalence testing approach to these questions and suggest reasonable negligibility or relevance limits for carryover. Finally, we illustrate this approach on some real datasets.

Effects of Ultrasonic Disintegrates from Epimastigote Biomass of Trypanosoma cruzi Albarrada Strain (Mexico) on the Development of L5178Y Solid Malignant Transplanted Tumors in Male BALB/c Mice.

We studied in vivo antitumor effect of epimastigote form detritus of Trypanosoma cruzi, Mexican Albarrada strain, on L5178Y malignant tumor in BALB/c mice. The antitumor effect of ultrasonic detritus of the parasite was confirmed by shrinkage of the tumor and changed size of its symplastic necroses.

Enhancement of second harmonic signal in nanofabricated cones.

Geometrical effects in optical nanostructures on nanoscale can lead to interesting phenomena such as inhibition of spontaneous emission,1,2 high-reflecting omnidirectional mirrors, structures that exhibit low-loss-waveguiding,3 and light confinement.4,5 Here, we demonstrate a similar concept of exploiting the geometrical effects on nanoscale through precisely fabricating lithium niobate (LiNbO3) nanocones arrays devices. We show a strong second harmonic generation (SHG) enhancement, shape and arrangement dependent, up to 4 times bigger than the bulk one. These devices allow below diffraction limited observation, being perfect platforms for single molecule fluorescence microscopy6 or single cell endoscopy.7 Nanocones create a confined illumination volume, devoid from blinking and bleaching, which can excite molecules in nanocones proximity. Illumination volume can be increased by combining the SH enhancement effect with plasmon resonances, excited thanks to a gold plasmonic shell deposited around the nanostructures. This results in a local further enhancement of the SH signal up to 20 times. The global SH enhancement can be rationally designed and tuned through the means of simulations.

First case of synophthalmia and albinism in the Pacific angel shark Squatina californica.

The first record in Mexican waters of albinism and synophthalmia (partial cyclopia) in the Pacific angel shark, Squatina californica is presented. Albinism is not lethal, but synophthalmia may cause the death of the individual immediately after birth.

Mercury levels in myliobatid stingrays (Batoidea) from the Gulf of California: tissue distribution and health risk assessment.

With the aim of knowing Hg distribution in selected tissues of myliobatid stingrays and assessing health risk to Mexican population, Hg concentration was determined in the muscle and liver of four ray species. Total Hg levels were determined by cold vapor atomic absorption spectrophotometry. With respect to the muscle, devil rays (Mobula spp.) showed lower Hg levels (<0.22 µg g(-1)) than Rhinoptera steindachneri (0.37 ± 0.25 µg g(-1) wet weight). In the case of the liver, the highest Hg concentration was found in Mobula japanica (0.22 ± 0.01 µg g(-1)). Hg levels in the muscle and liver varied according to the species; in some case, the liver accumulated more Hg than the muscle and the opposite pattern in other cases. R. steindachneri showed a significant difference between both tissues. No significant differences of Hg levels between males and females and between juveniles and adult specimens of R. steindachneri were found. Positive correlation between Hg concentrations and disc width and total weight was not significant for R. steindachneri (Rs < 0.36, p > 0.05). Batoids showed Hg values below the Mexican (NOM-027-SSA1-1993) limits (1.0 µg g(-1)) in fishes for human consumption. The species with the highest potential of Hg transfer to human population is R. steindachneri; however, an adult (70 kg) could consume approximately 943 g per week without representing a health risk. Nevertheless, further and continuous monitoring is needed since batoids support an important fishery in Mexican waters, being a food resource and income to coastal communities.