Agenesis of inferior vena cava in pregnancy: A case report and narrative review.

Agenesis of inferior vena cava (AIVC) is an extremely rare congenital abnormality. In AIVC, venous flow from the lower extremities enter superior vena cava mainly through the azygous and hemiazygous system, forming anastomotic collateral vessels. A global increase in intra-abdominal pressure by the gravid uterus may further stress the collateral system, increase venous stasis and decrease venous return. We present the management of a 37-year old pregnant woman with AIVC who underwent caesarean section with norepinephrine infusion and general anaesthesia. She presented with shortness of breath when seated, episodes of dizziness while walking or sitting upright with subsequent tachycardia. Cardiac status was monitored using an arterial pulse contour CO monitor. We did not observe large fluctuations in CO, SV, MAP during induction and intubation as well as during delivery. We believe that administration of an infusion of norepinephrine from induction to anaesthesia through caesarean section contributed to this result. Sympathetic activation caused venoconstriction, which significantly increased venous return and maintained haemodynamic stability.

Seizure outcome after epilepsy surgery in tuberous sclerosis complex: Results and analysis of predictors from a multicenter study.

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.

Permeation kinetics of active drugs through lanolin-based artificial membranes.

Skin-penetration studies play an essential role in the selection of drugs for dermal or transdermal application. In vivo experiments in humans are not always possible for ethical, practical, or economic reasons, especially in the first part of the drug development. It is necessary to develop alternative methods using accessible and reproducible surrogates for in vivo human skin. The in vitro methodologies using biological membranes (human and animal skin) are recognized and well accepted as an alternative but present high inter- and intra-individual variability. Therefore, the formation of synthetic membranes has been studied to obtain skin- mimicking models for permeation studies. The aim of this work is to create lanolin-based artificial membranes that can mimic the absorption through the skin of compounds applied topically. A series of synthetic membranes using two different types of lanolin (water-extracted (WE) and solvent-extracted (SE)) were prepared. Next, the in vitro release test of three drugs (diclofenac sodium, ibuprofen and lidocaine) was performed on artificial membranes and on porcine skin placed on Franz cells. The percentage of release, flux, permeability coefficient, lag time, area under the curve, maximal concentration and time were determined for each compound in the different types of membrane. The results showed that lanolin membranes presented a strong diminution of permeability compared to most artificial membranes, leading to a very similar permeability to that of skin. The SE and WE membranes showed a diminution of transepidermal water loss and permeability of compounds compared with membranes alone. The results from WE membranes were similar to those found for the skin. The lanolin membranes were not capable of perfectly mimicking permeation through the skin, but they did have the same rank order of drug penetration as the skin. It may be deduced from these tests that these systems provide more reliable results for compounds with low to medium lipophilicity. The results demonstrated that new lanolin-based artificial membranes have the potential to be exploited as screening models for determining the permeability of a compound destined to be topically delivered.

Ultra-High-Field Targeted Imaging of Focal Cortical Dysplasia: The Intracortical Black Line Sign in Type IIb.

BACKGROUND AND PURPOSE: Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. MATERIALS AND METHODS: Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. RESULTS: We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). CONCLUSIONS: The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.

Modelling for the inheritance of multiple births and fertility in endangered equids: Determining risk factors and genetic parameters in donkeys (Equus asinus).

Multiple births or twinning in equids are dangerous, undesirable situations that compromise the life of the dam and resulting offspring. However, embryo vitrification and freezing techniques take advantage of individuals whose multiple ovulations allow flushing more fertilised embryos from the oviduct to be collected, increasing the productivity and profitability of reproductive techniques. Embryo preservation is especially important in highly endangered populations such as certain donkey (Equus asinus) breeds; for which conventional reproductive techniques have previously been deemed inefficient. For instance, becoming an effective alternative to artificial insemination with frozen semen to preserve the individuals' genetic material. The objective of this study was to examine the historical foaling records of Andalusian donkeys to estimate prevalence, risk factors, phenotypic and genetic parameters for multiple births, assessing the cumulative foal number born per animal, maximum foal number per birth and multiple birth number per animal. We designed a Bayesian General Animal Mixed Model with single records considering the 'fixed' effects of birth year, birth season, birth month, sex, farm, location, and husbandry system. Age was considered and included as a linear and quadratic covariate. Gibbs sampling reported heritability estimates ranging from 0.18 ±â€¯0.101 to 0.24 ±â€¯0.078. Genetic and phenotypic correlations ranged from 0.496 ±â€¯0.298 to 0.846 ±â€¯0.152 and 0.206 ±â€¯0.063 to 0.607 ±â€¯0.054, respectively. Predicted breeding values obtained enable the potential selection against/for these traits, offering a new perspective for donkey breeding and conservation.

Caffeine delivery in porcine skin: a confocal Raman study.

Confocal Raman microscopy is a novel optical method for studies of pro-drug and drug delivery. This method is a promising technique that enables non-destructive measurement of the permeation profile through skin layers. Peaks of compounds are usually normalised to skin peaks (amino-acid and amide I) for semi-quantitative evaluation. The present study seeks to optimise a methodology for complete quantitative measurement of the amount of an active compound at different depths. Caffeine was used as a tracer to evaluate compound's skin penetration using confocal Raman microscopy. A semi-quantitative depth profile of caffeine was obtained with normalisation of the Raman intensities. These ratios of Raman intensities were correlated with the caffeine concentration using an external calibration curve. The calibration curve was carried out with porcine skin incubated in different concentrations of caffeine; afterwards, each skin sample was analysed by confocal Raman microscopy and HPLC to determine the relation between the Raman signal intensity and the caffeine concentration per skin mass and to create a depth profile. These correlation curves allow the full quantification of the caffeine in skin from Raman intensity ratios at different depths.

Aneuploidy identification in pre-B acute lymphoblastic leukemia patients at diagnosis by Multiplex Ligation-dependent Probe Amplification (MLPA).

Three-quarters of the patients with acute lymphoblastic leukemia (ALL), show numerical or structural chromosomal alterations, which are important factors in leukemogenesis. The use of Multiplex Ligation-dependent Probes Amplification (MLPA) has been mainly limited for searching copy number alterations of genes, suggesting that MLPA could detect numerical alterations in cancer. However, the use of MLPA in pediatrics to analyze subtelomeric sequences for aneuploidy detection has not been considered in previous studies. The aim of this study was to identify aneuploidy for the first time using MLPA and correlate the results with karyotype and DNA-index (DI), from preB ALL patients. Forty-two bone marrow samples were analyzed by cytogenetics and flow cytometry to determine the DI. The chromosomal gains and/or losses were detected by the SALSA MLPA P036 Subtelomere Mix 1 probemix®. The chromosomal number matched in 36 out of 42 samples between MLPA and karyotype (R2=0.7829, p=3.7×10-10), 18/42 between MLPA and DI (R2=0.1556, p=0.023), and 20/42 between karyotype and DI (R2=0.1509, p=0.015). MLPA results correlated with karyotype and DI. The use of MLPA led us to identify a gained marker chromosome. Our results indicate that MLPA could be a useful and fast alternative tool for aneuploidy identification in pediatric leukemia.

A model to infer the demographic structure evolution of endangered donkey populations.

Stemming from The Worldwide Donkey Breeds Project, an initiative aiming at connecting international researchers and entities working with the donkey species, molecularly tested pedigree analyses were carried out to study the genetic diversity, structure and historical evolution of the Andalusian donkey breed since the 1980s to infer a model to study the situation of international endangered donkey breeds under the remarkably frequent unknown genetical background status behind them. Demographic and genetic variability parameters were evaluated using ENDOG (v4.8). Pedigree completeness and generation length were quantified for the four gametic pathways. Despite mean inbreeding was low, highly inbred animals were present in the pedigree. Average coancestry, relatedness, and non-random mating degree trends were computed. The effective population size based on individual inbreeding rate was about half when based on individual coancestry rate. Nei's distances and equivalent subpopulations number indicated differentiated farms in a highly structured population. Although genetic diversity loss since the founder generations could be considered small, intraherd breeding policies and the excessive contribution of few ancestors to the gene pool could lead to narrower pedigree bottlenecks. Long average generation intervals could be considered when reducing inbreeding. Wright's fixation statistics indicated slight inbreeding between farms. Pedigree shallowness suggested applying new breeding strategies to reliably estimate descriptive parameters and control the negative effects of inbreeding, which could indeed, mean the key to preserve such valuable animal resources avoiding the extinction they potentially head towards, making the present model become an international referent when assessing endangered donkey populations.

A novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family.

Classic Galactosemia (OMIM 230400) is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. This disease caused by the inability to metabolize galactose is potentially life-threatening but its pathophysiology has not been clearly defined. GALT gene presents high allelic heterogeneity and around 336 variations have been identified. Here, we report the case of a patient with Classic Galactosemia who was detected during a neonatal screening in Ecuador. Molecular study revealed a mutation in GALT gene intron 1, c.82+3A>G in homozygous condition, this mutation has not been previously reported. This gene variation was not found in any of the 119 healthy Ecuadorian individuals used as control. Furthermore, the mutation was the only alteration detected in the propositus's GALT after sequencing all exons and introns of this gene. In silico modeling predicted that the mutation was pathogenic.

Skin permeation and antioxidant efficacy of topically applied resveratrol.

The permeation of resveratrol was assessed by in vitro and in vivo experiments 24 h after topical administration. The in vitro profile of resveratrol was assessed by Raman spectroscopy. Human skin permeation was analysed in vivo by the tape stripping method with the progressive removal of the stratum corneum layers using adhesive tape strips. Moreover, the free radical scavenging activity of resveratrol after its topical application was determined using the DPPH assay. The Raman spectra indicated that the topically applied resveratrol penetrates deep into the skin. The results showed high amounts of resveratrol in the different stratum corneum layers close to the surface and a constant lower amount in the upper layers of the viable epidermis. The concentration of resveratrol present in the outermost stratum corneum layers was obtained by tape stripping after in vivo application. The results demonstrated that resveratrol mainly remained in the human stratum corneum layers. After topical application, resveratrol maintained its antiradical activity. The antioxidant efficacy of the compound was higher in the inner layers of the stratum corneum. As these results have demonstrated, topically applied resveratrol reinforces the antioxidant system of the stratum corneum and provides an efficient means of increasing the tissue levels of antioxidants in the human epidermis.

Bowel function and quality of life after local excision or total mesorectal excision following chemoradiotherapy for rectal cancer.

BACKGROUND: Local excision for rectal cancer is expected to offer a better functional outcome than conventional surgery. The aim of the present study was to compare quality of life and bowel function in patients with rectal cancer who underwent either local excision or conventional surgery after chemoradiotherapy. METHODS: This was a retrospective multicentre study. Patients who underwent local excision were compared with those who had mesorectal excision. Quality of life and bowel function were investigated using validated questionnaires (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29 and Memorial Sloan-Kettering Cancer Center Bowel Function Instrument) at a median follow-up of 49 (range 13-95) months. Further analysis was undertaken of data from patients who underwent local excision alone compared with those requiring subsequent radical surgery. Statistical significance was set at P < 0·010. RESULTS: The mean constipation score was significantly better in the local excision group than in the mesorectal excision group (3·8 (95 per cent c.i. 0·3 to 7·2) versus 19·8 (12·1 to 27·4); P < 0·001). Compared with patients who underwent mesorectal excision, those who had local excision had less sensation of incomplete emptying (mean score 3·7 (3·4 to 4·0) versus 2·8 (2·5 to 3·1); P < 0·001) and second bowel movements within 15 min (mean score 3·6 (3·3 to 3·9) versus 3·0 (2·7 to 3·3); P = 0·006). Patients who underwent local excision alone scored better than those who had mesorectal excision, particularly for bowel function, who, in turn, scored better than patients requiring subsequent radical surgery following local excision. CONCLUSION: Patients who underwent local excision had a better quality of life and bowel function than those who underwent mesorectal excision.

Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid.

In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-ε-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non-invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME-GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC.

The influence of hair lipids in ethnic hair properties.

OBJECTIVE: Biochemical studies have mainly focused on the composition of hair. African hair exhibited lower moisturization and less radial swelling when flushing with water compared with Asian or Caucasian hair, and they assumed a possible lipid differentiation among human populations. This study consists in the lipid characterization of different ethnic hairs (Caucasian, Asian and African hairs) and the influence of these lipids in different hair properties such as humidity and mechanical properties. Evaluation of water sorption and desorption of the different ethnic hairs and with and without lipids is also studied mainly to determine permeation changes of the keratin fibres. METHODS: Extractions of exogenous and endogenous lipids with different organic solvents were performed; lipid analysis and its quantification using thin-layer chromatography coupled to an automated flame ionization detector (TLC/FID) were performed. Absorption and desorption curves were obtained in a thermogravimetric balance equipped with a controlled humidity chamber, the Q5000SA Sorption Analyzer (TA Instruments, New Castle, IL, U.S.A.). Also, mechanical properties (breaking stress and breaking elongation) were analysed using a computer programmable dynamometer (Instron 5500R). RESULTS: Lipid extraction showed the highest amount of total lipids for the African hair which may come from external sebaceous lipids compared with Asian or Caucasian hair. Caucasian fibres were found to be the most hydrated fibre, and a decrease in moisture was found in the extracted fibres, again, which is more important for the Caucasian hair. A superior lineal mass was found for the Asian fibres which supported their higher strength. The results obtained from the analysis of the mechanical properties of delipidized fibres indicate a surprising increase in the strength of African and Caucasian fibres. Perhaps this increase in strength could be related to the humidity decrease in lipid-extracted hair fibres. Results of water uptake and desorption indicate that Asian and Caucasian hairs present the lower diffusion coefficients compared with the African ones. At least for the African fibre, an extraction of its lipids that mainly account for apolar lipids ameliorates the fibre structure, decreasing its permeability to water and increasing its tensile strength. CONCLUSION: The ethnic hairs were assessed related to their lipid composition, and some differences between them were found in terms of water uptake and mechanical properties.

Genetic parameters of traits associated with the growth curve in Segureña sheep.

This paper studies the genetic importance of growth curve parameters and their relevance as selection criteria in breeding programmes of Segureño sheep. Logistic and Verhulst growth functions were chosen for their best fit to BW/age in this breed; the first showed the best general fit and the second the best individual fit. Live weights of 41 330 individuals from the historical archives of the National Association of Segureña Sheep Breeders were used in the analysis. The progeny of 1464 rams and 27 048 ewes were used to study the genetic and phenotypic parameters of growth curve parameters and derived traits. Reproductive management in the population consists in controlled natural mating inside every herd, with a minimum of 15% of the females fertilized by artificial insemination with fresh semen; with the purpose being the herd genetic connections, all herd genealogies are screened with DNA markers. Estimates of growth curve parameters from birth to 80 days were obtained for each individual and each function by the non-linear regression procedure using IBM SPSS statistics (version 21) with the Levenberg-Marquart estimation method. (Co)variance components and genetic parameters were estimated by using the REML/Animal model methodology. The heritability of mature weight was estimated as 0.41±0.042 and 0.38±0.021 with the logistic and Verhulst models, respectively, and the heritability of other parameters ranged from 0.41 to 0.62 and 0.37 to 0.61, with the models, respectively. A negative genetic correlation between mature weight and rate of maturing was found.

Characterization of commercial and biological growth curves in the Segureña sheep breed.

Non-linear models were analysed to describe both the biological and commercial growth curves of the Segureña sheep, one of the most important Spanish breeds. We evaluated Brody, von Bertalanffy, Verhulst, logistic and Gompertz models, using historical data from the National Association of Segureña Sheep Breeders (ANCOS). These records were collected between 2000 and 2013, from a total of 129 610 weight observations ranging from birth to adulthood. The aim of this research was to establish the mathematical behaviour of body development throughout this breed's commercial life (birth to slaughter) and biological life (birth to adulthood); comparison between both slopes gives important information regarding the best time for slaughter, informs dietary advice according to animals' needs, permits economical predictions of productions and, by using the curve parameters as selection criteria, enables improvements in growth characteristics of the breed. Models were fitted according to the non-linear regression procedure of statistical package SPSS version19. Model parameters were estimated using the Levenberg-Marquardt algorithm. Candidate models were compared using the determinative coefficient, mean square error, number of iterations, Akaike information coefficient and biological coherence of the estimated parameters. The von Bertalanffy and logistic models were found to be best suited to the biological and commercial growth curves, respectively, for both sexes. The Brody equation was found to be unsuitable for studying the commercial growth curve. Differences between the parameters in both sexes indicate a strong impact of sexual dimorphism on growth. This can emphasize the value of the highest growth rate for females, indicating that they reach maturity earlier.

The concept of temporal 'plus' epilepsy.

The concept of temporal 'plus' epilepsy (T+E) is not new, and a number of observations made by means of intracerebral electrodes have illustrated the complexity of neuronal circuits that involve the temporal lobe. The term T+E was used to unify and better individualize these specific forms of multilobar epilepsies, which are characterized by electroclinical features primarily suggestive of temporal lobe epilepsy, MRI findings that are either unremarkable or show signs of hippocampal sclerosis, and intracranial recordings which demonstrate that seizures arise from a complex epileptogenic network including a combination of brain regions located within the temporal lobe and over closed neighbouring structures such as the orbitofrontal cortex, the insulo-opercular region, and the temporo-parieto-occipital junction. We will review here how the term of T+E has emerged, what it means, and which practical consideration it raises.

Ultra-high-field MR imaging in polymicrogyria and epilepsy.

BACKGROUND AND PURPOSE: Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified. MATERIALS AND METHODS: Ten adult patients with polymicrogyria previously diagnosed by using 3T MR imaging underwent additional imaging at 7T. We assessed polymicrogyria according to topographic pattern, extent, symmetry, and morphology. Additional imaging sequences at 7T included 3D T2* susceptibility-weighted angiography and 2D tissue border enhancement FSE inversion recovery. Minimum intensity projections were used to assess the potential of the susceptibility-weighted angiography sequence for depiction of cerebral veins. RESULTS: At 7T, we observed perisylvian polymicrogyria that was bilateral in 6 patients, unilateral in 3, and diffuse in 1. Four of the 6 bilateral abnormalities had been considered unilateral at 3T. While 3T imaging revealed 2 morphologic categories (coarse, delicate), 7T susceptibility-weighted angiography images disclosed a uniform ribbonlike pattern. Susceptibility-weighted angiography revealed numerous dilated superficial veins in all polymicrogyric areas. Tissue border enhancement imaging depicted a hypointense line corresponding to the gray-white interface, providing a high definition of the borders and, thereby, improving detection of the polymicrogyric cortex. CONCLUSIONS: 7T imaging reveals more anatomic details of polymicrogyria compared with 3T conventional sequences, with potential implications for diagnosis, genetic studies, and surgical treatment of associated epilepsy. Abnormalities of cortical veins may suggest a role for vascular dysgenesis in pathogenesis.

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including the AKT3 gene.

Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1-q44 chromosomal region, encompassing the AKT3 gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub-cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K/AKT/mTOR pathway. These findings indicate that AKT3 upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to AKT3 upregulation may be related to the embryonic stage when the post-zygotic gene alteration occurs.

In vivo and in vitro evaluation of topical formulations containing physiological lipid mixture for replacement of skin barrier function.

AIM: The aim of the study was to describe a new in vivo and in vitro approach of the efficacy evaluation of cosmetic emollients to better understand the link between the formulation and the activity of cosmetic products. METHODS: Two long term in vivo studies were carried out on nine healthy Caucasian volunteers mean age 40±12 years to evaluate the protecting and repairing effects of the two different barrier repair cosmetic formulations. The application of the formulations was repeated once a day during 7 days and biophysical parameters (TEWL and Skin Hydration) were measured before and after Sodium laureth sulphate exposure The in vitro study was carried out by freeze substitution transmission electron microscopy (FSTEM) on stratum corneum samples obtained by sections of fresh skin from young pigs, depleted with a solvent mixture and treated with the two products RESULTS: The in vivo results demonstrated that daily product application provided a reinforcement of the skin barrier with protecting and repairing effects from chemical injuries the extent of which was dependent on the formulation features (product A>product B) The role of the technical form on the lipid availability was confirmed by the in vitro evaluation tests. CONCLUSION: The results point out that a daily application of physiological lipid mixture containing emulsion can protect healthy skin and promote the reparing effect on unpaired barrier skin, reducing TEWL and maintaining hydration of the stratum corneum. The efficacy degree is higher when the cosmetic form promotes the availability of active ingredients increasing the product performance.

Enantiomeric analysis of limonene and carvone by direct introduction of aromatic plants into multidimensional gas chromatography.

Analysis of chiral compounds in complex mixtures is achieved by multidimensional gas chromatography using heptakis-(2,3,6-tri-O-methyl)-ß-cyclodextrin stationary phase as the main column of the system to separate specific selected cuts containing components unresolved in the first dimension. The proposed procedure allows rapid analysis of both solid and liquid matrices by direct introduction, into the programmed temperature vaporizer (PTV) of a gas chromatograph, of either the plant material or the essential oil, respectively. A comparison between enantiomeric excesses data obtained, from plant leaves (or plant seeds) and the corresponding essential oils, by direct injection (i.e., without sample pretreatment or concentration step) into the multidimensional system is also included. Reported data demonstrate that no racemization occurs during analysis as identical enantiomeric excesses are obtained in both cases for specific chiral compounds.