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The modelling of scattering data from foams is very challenging due to the complex structure of foams and is therefore often reduced to the fitting of single peak positions or feature mimicking. This article presents a more elaborate model to describe the small-angle neutron scattering (SANS) data from foams. The model takes into account the geometry of the foam bubbles and is based on an incoherent superposition of the reflectivity curves arising from the foam films and the small-angle scattering (SAS) contribution from the plateau borders. The model is capable of describing the complete scattering curve of a foam stabilized by the standard cationic surfactant tetradecyltrimethylammonium bromide (C14TAB) with different water contents, i.e. different drainage states, and provides information on the thickness distribution of liquid films inside the foam. The mean film thickness decreases with decreasing water content because of drainage, from 28 to 22 nm, while the polydispersity increases. These results are in good agreement with the film thicknesses of individual horizontal foam films studied with a thin-film pressure balance. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to describe the B‐mode lung ultrasound (B‐LUS) and contrast‐enhanced ultrasound (CEUS) follow‐up patterns of peripheral pulmonary lesions (PPLs) in patients with confirmed pulmonary embolism (PE). Patients and Methods: Data from 27 patients with a confirmed diagnosis of PE and PPLs over 5 mm from October 2009 to November 2018 were included retrospectively in the study. The inclusion criteria were performance of a baseline CEUS examination, a short‐term B‐LUS and CEUS follow‐up, and a long‐term B‐LUS follow‐up of PPLs. The homogeneity of enhancement of PPLs (homogeneous/inhomogeneous/absent) on CEUS and the presence and size of PPLs on B‐LUS were evaluated. Results: A total of n = 25/27 (92.6%) lesions showed absent or inhomogeneous enhancement during baseline examination or short‐term follow‐up, indicating impaired perfusion. On short‐term CEUS follow‐up, 9/27 cases (33.3%) showed a pattern shift. On B‐LUS long‐term follow‐up, 26/27 lesions (96.3%) were detectable for an average of 10 weeks (range 3–32 weeks). The size of reference lesions was significantly reduced at the time of the final follow‐up examination (P <.05). Conclusion: B‐LUS follow‐up showed that, in patients with confirmed PE, PPLs had a delayed regression. On CEUS follow‐up examination, various perfusion patterns of PPLs were observed, indicating the different ages and the variable reparative processes of pulmonary infarction. In PPLs independent of the underlying signs and symptoms, follow‐up B‐LUS and CEUS examinations may be helpful for a possible retrospective diagnosis of peripheral pulmonary infarction suggestive of PE. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is biologically and behaviorally heterogeneous. Delayed diagnosis of ASD is common and problematic. The complexity of ASD and the low sensitivity of available screening tools are key factors in delayed diagnosis. Identification of biomarkers that reduce complexity through stratification into reliable subpopulations can assist in earlier diagnosis, provide insight into the biology of ASD, and potentially suggest targeted interventions. Quantitative metabolomic analysis was performed on plasma samples from 708 fasting children, aged 18 to 48 months, enrolled in the Children's Autism Metabolome Project (CAMP). The primary goal was to identify alterations in metabolism helpful in stratifying ASD subjects into subpopulations with shared metabolic phenotypes (i.e., metabotypes). Metabotypes associated with ASD were identified in a discovery set of 357 subjects. The reproducibility of the metabotypes was validated in an independent replication set of 351 CAMP subjects. Thirty‐four candidate metabotypes that differentiated subsets of ASD from typically developing participants were identified with sensitivity of at least 5% and specificity greater than 95%. The 34 metabotypes formed six metabolic clusters based on ratios of either lactate or pyruvate, succinate, glycine, ornithine, 4‐hydroxyproline, or α‐ketoglutarate with other metabolites. Optimization of a subset of new and previously defined metabotypes into a screening battery resulted in 53% sensitivity (95% confidence interval [CI], 48%–57%) and 91% specificity (95% CI, 86%–94%). Thus, our metabolomic screening tool detects more than 50% of the autistic participants in the CAMP study. Further development of this metabolomic screening approach may facilitate earlier referral and diagnosis of ASD and, ultimately, more targeted treatments. Lay Summary Analysis of a selected set of metabolites in blood samples from children with autism and typically developing children identified reproducible differences in the metabolism of about half of the children with autism. Testing for these differences in blood samples can be used to help screen children as young as 18 months for risk of autism that, in turn, can facilitate earlier diagnoses. In addition, differences may lead to biological insights that produce more precise treatment options. We are exploring other blood‐based molecules to determine if still a higher percentage of children with autism can be detected using this strategy. Autism Res 2020, 13: 1270–1285. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background: The VATER/VACTERL association refers to the nonrandom co‐occurrence of at least three of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). Patients presenting with two CFs have been termed VATER/VACTERL‐like phenotypes. Methods: We surveyed the exome for recessive disease variants in three affected sib‐pairs. Sib‐pair 971 consisted of two brothers with ARM and additional hydronephrosis in one brother. Sib‐pair 1098 consisted of two sisters with ARM. In family 1346, the daughter presented with ARM and additional hypoplasia of both small fingers and ankyloses. Her brother presented with unilateral isolated radial hypoplasia. Sib‐pairs 971 and 1346 resembled a VATER/VACTERL‐like phenotype. Results: We detected a novel maternally inherited missense variant (c.1340G > T) and a rare paternally inherited deletion of the trans‐allele in HSPA6 in both siblings of family 1346. HSPA6 belongs to the heat shock protein (HSP) 70 family. Re‐sequencing of HSPA6 in 167 patients with VATER/VACTERL and VATER/VACTERL‐like phenotypes did not reveal any additional bi‐allelic variants. Conclusions: Until now, only TNF‐receptor associated protein 1 (TRAP1) had been reported as an autosomal recessive disease‐gene for the VATER/VACTERL association. TRAP1 belongs to the heat shock protein 90 family (HSP90). Both Hsp70 and Hsp90 genes have been shown to be important embryonic drivers in the formation of mouse embryonic forelimb tissue. Our results suggest HSPA6 as a new candidate gene in VATER/VACTERL‐like phenotypes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate genetic effects in the formation of congenital lower urinary tract obstruction (LUTO) comprising posterior urethral valves (PUV), urethral atresia, and urethras with variable degrees of stenosis. Methods: A classic twin study was performed by assessing LUTO twin pairs from the literature. Furthermore, data regarding 3 previously unreported twin pairs with PUV from University of Bonn, Essen and Wrocławs own in‐house databases were added. Both pair‐ and probandwise concordance rates were calculated and compared for monozygotic (MZ) and dizygotic (DZ) twin pairs. Results: The pairwise concordance rates for all LUTO were 53% (95% confidence interval [CI] 32%–73%) and 17% (95% CI 3%–56%) for MZ and DZ twin pairs, respectively (P = .180). The probandwise concordance rates were 69% (95% CI 51%–83%) and 29% (CI 95% 8%–64%) for MZ and DZ twin pairs respectively (P = .084). The MZ/DZ ratios of the pair‐ and probandwise concordance rates were 3.1 and 2.4, respectively. Conclusion: The present study did not show significant differences in comparisons of concordance rates of MZ and DZ twin pairs, probably due to the small number of twin pairs reported. However, the more than 2‐fold higher pair‐ and probandwise concordance rates for MZ versus DZ twin pairs are very suggestive of a contribution of genetic factors to the development of LUTO. [ABSTRACT FROM AUTHOR]

Abstract: Dynamic regulation of the interactions between specific molecules on functional surfaces and biomolecules, for example, proteins or cells, is critical for biosensor and biomedical devices. Herein, we present a spiropyran (SP)‐based light‐responsive surface coating, hPG (hyperbranched polyglycerol)‐SP, to control the adsorption of proteins and adhesion of cells. In the normal state, the SP groups on the coating surface were in hydrophobic ring‐closed form, which promotes the nonspecific protein adsorption and cell adhesion. Under UV irradiation, the grafted SP groups were dynamically isomerized into hydrophilic/zwitterionic merocyanine. Both hydrophilicity and zwitterions support the formation of a hydrated layer and hence the resulting hPG‐MC coatings highly resist protein adsorption and cell adhesion. Moreover, the presented hPG also provided a robust bioinert background to suppress the nonspecific protein adsorption and cells adhesion. Therefore, this functionalized coating exhibited a good photoregulated antifouling behavior. Moreover, the detachment of adsorbed proteins and adhered cells from the coating surface was also realized. [ABSTRACT FROM AUTHOR]

Background: Syndromic brain malformations comprise a large group of anomalies with a birth prevalence of about 1 in 1,000 live births. Their etiological factors remain largely unknown. To identify causative mutations, we used whole‐exome sequencing (WES) in aborted fetuses and children with syndromic brain malformations in which chromosomal microarray analysis was previously unremarkable. Methods: WES analysis was applied in eight case‐parent trios, six aborted fetuses, and two children. Results: WES identified a novel de novo mutation (p.Gly268Arg) in ACTB (Baraitser‐Winter syndrome‐1), a homozygous stop mutation (p.R2442*) in ASPM (primary microcephaly type 5), and a novel hemizygous X‐chromosomal mutation (p.I250V) in SLC9A6 (X‐linked syndromic mentaly retardation, Christianson type). Furthermore, WES identified a de novo mutation (p.Arg1093Gln) in BAZ1A. This mutation was previously reported in only one allele in 121.362 alleles tested (dbSNP build 147). BAZ1A has been associated with neurodevelopmental impairment and dysregulation of several pathways including vitamin D metabolism. Here, serum vitamin‐D (25‐(OH)D) levels were insufficient and gene expression comparison between the child and her parents identified 27 differentially expressed genes. Of note, 10 out of these 27 genes are associated to cytoskeleton, integrin and synaptic related pathways, pinpointing to the relevance of BAZ1A in neural development. In situ hybridization in mouse embryos between E10.5 and E13.5 detected Baz1a expression in the central and peripheral nervous system. Conclusion: In syndromic brain malformations, WES is likely to identify causative mutations when chromosomal microarray analysis is unremarkable. Our findings suggest BAZ1A as a possible new candidate gene. [ABSTRACT FROM AUTHOR]

Liddle syndrome (LS) is a familial disease characterized by early onset hypertension (HT). Although regarded as rare, its incidence may be greater than expected because the classical findings of hypokalemic metabolic alkalosis with suppressed renin and aldosterone levels are not consistently present. Herein, we present the case of an adolescent boy and maternal relatives who were followed up with misdiagnosis of essential HT for a long duration. Clinical diagnosis of LS was confirmed on genetic analysis. Despite carrying the same mutation, the index patient and the family members manifested heterogeneous phenotypes of the disease including age at presentation, degree of HT, presence of hypokalemia and renal/cardiac complications. LS should be considered in the differential diagnosis of HT in children with a strong family history of HT resistant to conventional treatment; and genetic screening should be performed in these circumstances. [ABSTRACT FROM AUTHOR]

BACKGROUND For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS Here, we used array-based molecular karyotyping to search for causative CNVs in 33 fetuses of terminated pregnancies with prenatally detected brain malformations and additional extracerebral anomalies. RESULTS In 11 fetuses, we identified 15 CNVs (0.08 Mb to 29.59 Mb), comprising four duplications and eleven deletions. All larger CNVs (> 5 Mb) had also been detected by prenatal conventional karyotyping. None of these CNVs was present in our 1307 healthy in-house controls (frequency < 0.0008). Among these CNVs, we prioritized six chromosomal regions (1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, 18q21.1) due to their previous association with human brain malformations or owing to the presence of a single gene expressed in human brain. Prioritized genes within these regions were UBTD2, SKA1, SVIP, and, most convincingly, GPR52. However, re-sequencing of GPR52 in 100 samples from fetuses with brain malformations or patients with intellectual disability and brain malformations revealed no disease-causing mutation. CONCLUSION Our study suggests chromosomal regions 1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, and 18q21.1 to be involved in human brain development. Within three of these regions, we suggest UBTD2, GPR52, and SKA1 as possible candidate genes. Because the overall detection rate of array-based molecular karyotyping was slightly higher (23%) than that of conventional prenatal karyotyping (20%), we suggest it's use for prenatal diagnostic testing in fetuses with nonisolated brain malformations. Birth Defects Research (Part A) 106:16-26, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Anorectal malformations (ARM) have a prevalence of around 1 in 2500 live births. In around 50% of patients, the malformation is isolated, while in the remainder it arises within the context of complex genetic abnormalities or a defined genetic syndrome. Recent studies have implicated rare copy number variations (CNVs) in both isolated and nonisolated ARM, and identified plausible candidate genes. Methods: In the present study, array-based molecular karyotyping was performed to identify causative CNVs in 32 sporadic ARM patients with comorbid abnormalities of the central nervous system (CNS). This phenotype was selected to enrich for rare CNVs, since previous research has implicated rare CNVs in both CNS abnormalities and ARM. Results: In five patients, a probable disease-causing CNV was identified (del6q14.3q16.3, del14q32.2, del17q12q21.2, and two patients with del22q11.21). In three of these patients, the CNVs were de novo. For the remaining two patients, no parental DNA was available. Deletions at 22q11.21 and 6q14.3 have been associated with both CNS abnormalities and ARM. In contrast, deletions at 14q32.2 have only been described in patients with CNS abnormalities, and the del17q12q21.2 is a novel CNV. Expression studies in mice suggest that NEUROD2 and RARA, which reside within the newly identified del17q12q21.2 region, are candidate genes for the formation of microcephaly and ARM. Conclusion: The present data suggest that CNVs are a frequent cause of the ARM with CNS abnormalities phenotype, and that array-analysis is indicated in such patients. Birth Defects Research (Part A) 103:235-242, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A rapid and universal approach for multifunctional material coatings was developed based on a mussel-inspired dendritic polymer. This new kind of polymer mimics not only the functional groups of mussel foot proteins (mfps) but also their molecular weight and molecular structure. The large number of catechol and amine groups set the basis for heteromultivalent anchoring and crosslinking. The molecular weight reaches 10 kDa, which is similar to the most adhesive mussel foot protein mfp-5. Also, the dendritic structure exposes its functional groups on the surface like the folded proteins. As a result, a very stable coating can be prepared on virtually any type of material surface within 10 min by a simple dip-coating method, which is as fast as the formation of mussel byssal threads in nature. [ABSTRACT FROM AUTHOR]

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Background: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. Methods: A case-control study was conducted among 371 nonsyndromic ARM cases and 714 population-based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital-Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. Results: No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8-1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. Conclusion: This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene-environment interaction. Birth Defects Research (Part A) 100:483-492, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND Bladder-exstrophy-epispadias complex (BEEC) is a severe congenital anomaly that represents a spectrum of urological abnormalities where parts or all of the distal urinary tract fail to close during development. Multiple lines of evidence strongly suggested p63 as a plausible candidate gene. We conducted a candidate gene association study to further investigate the role of p63 in human BEEC. METHODS We conducted a family-based association study of p63 using 154 Caucasian patients with nonsyndromic BEEC and their unaffected parents. High throughput single nucleotide polymorphism (SNP) genotyping was carried out using Illumina's Golden Gate Assay for 109 selected tagging SNPs localized within p63 with a minor allele frequency > 0.01. Individual and haplotype SNP transmission disequilibrium tests were conducted using Plink and Haploview, respectively. We also examined parent-of-origin effects using paternal asymmetry tests implemented in FAMHAP (http://famhap.meb.uni-bonn.de/index.html). RESULTS Nominally significant associations were identified between BEEC and six SNPs (rs17447782, rs1913720, rs6790167, rs9865857, rs1543969, rs4687100), and four haplotype blocks including or near these significant SNPs. Analysis of parent-of-origin effects showed significant results for seven SNPs (rs4118375, rs12696596, rs6779677, rs13091309, rs7642420, rs1913721, and rs1399774). None of these results remained significant after multiple testing correction. CONCLUSION The altered transmission of p63 variants in nonsyndromic BEEC patients may be suggestive of its involvement in the disease etiology. Further and large multi-institutional collaborative studies are required to elucidate the role of p63 in nonsyndromic BEEC. Birth Defects Research (Part A), 97:759-763, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND The exstrophy-epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC. METHODS Array-based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high-penetrance mutations involving small sequence changes. RESULTS A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ. CONCLUSIONS The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples. 19p13.12, microduplication, bladder exstrophy-epispadias complex, array-based molecular karyotyping, in situ hybridization analysis, copy number variations, WIZ Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The term 'luteal phase deficiency' was first coined more than 60 years ago, and, since then, it has been suggested as a clinical entity per se and an aetiological factor for subfertility, implantation failure and recurrent miscarriage. Despite the existing recommendations for rational work-up in subfertility, luteal phase evaluation and progesterone therapy alone is still common in daily practice. This review comprises results from a Pubmed literature search with the terms 'luteal phase' and 'subfertility', focussing on clinical situations not primarily related to assisted reproduction techniques. Additional data from the experimental studies published in the past 10 years on follicular maturation, oocyte developmental competence and the ovulatory cascade are integrated into the clinical continuum of dysfunctional ovulation, menstrual cycle irregularity and impaired corpus luteum function. As reliable diagnostic tools for adequate luteal function are missing, the presence of clinical symptoms such as cycle irregularity or premenstrual spotting is indicative and should initiate early follicular phase diagnostic work-up. New evidence on the interdependence of oocyte and follicular maturation and resulting developmental competence of the embryo further support the use of ovarian stimulation as the first-line therapeutic option in different subsets of patients with subfertility including luteal phase deficiency. [ABSTRACT FROM AUTHOR]

BACKGROUND Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA. METHODS A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA. RESULTS The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs ( p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs ( p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively. CONCLUSION The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE Exstrophy of the bladder (EB) is part of the bladder-exstrophy-epispadias complex (BEEC). Because familial occurrence of BEEC is rare, exogenous factors are thought to play a major role in the etiology of most BEEC cases. We aimed to investigate a possible genetic basis of BEEC in a consanguineous kindred of Moroccan origin with three members showing the same phenotypic expression of BEEC. PATIENTS AND METHODS The three affected males (two cousins and their maternal uncle) all presenting with nonsyndromic classic EB, were born in Morocco or The Netherlands. One Moroccan patient had an open bladder surface for 22 years due to late surgical reconstruction, avoided upright posture and developed severe lumbar scoliosis. Because three maternally related males from a consanguineous family living in different environments are affected, a genetic basis for EB is likely in this family. To screen for chromosomal aberrations and micro-aberrations in the two patients who were still alive, conventional karyotyping and array-based comparative genomic hybridization (array-CGH) were used on DNA-microarrays with a genome-wide average resolution of <0.5 Mb. RESULTS Chromosome banding revealed normal karyotypes. By array-CGH, one of 8000 clones was aberrant in both affected cousins. This clone from 1p21.1 contained the AMY1B, AMY2B, AMY2A genes coding for salivary and pancreatic amylases. CONCLUSION The aberration detected by array-CGH in both affected cousins is a known copy-number variant and most likely unrelated to the EB-phenotype. Nevertheless, in this family the nonsyndromic EB could be a monogenic disorder inherited in an autosomal-recessive or X-linked fashion. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are suggested to be important neurosteroids. We investigated steroid sulfatase (STS) in human temporal lobe biopsies in the context of possible cerebral DHEA(S) de novo biosynthesis. Formation of DHEA(S) in mature human brain tissue has not yet been studied. 17α-Hydroxylase/C17-20-lyase and hydroxysteroid sulfotransferase catalyze the formation of DHEA from pregnenolone and the subsequent sulfoconjugation, respectively. Neither their mRNA nor activity were detected, indicating that DHEA(S) are not produced within the human temporal lobe. Conversely, strong activity and mRNA expression of DHEAS desulfating STS was found, twice as high in cerebral neocortex than in subcortical white matter. Cerebral STS resembled the characteristics of the known placental enzyme. Immunohistochemistry revealed STS in adult cortical neurons as well as in fetal and adult Cajal-Retzius cells. Organic anion transporting proteins OATP-A, -B, -D, and -E showed high mRNA expression levels with distinct patterns in cerebral neocortex and subcortical white matter. Although it is not clear whether they are expressed at the blood–brain barrier and facilitate an influx rather than an efflux, they might well be involved in the transport of steroid sulfates from the blood. Therefore, we hypothesize that DHEAS and/or other sulfated 3β-hydroxysteroids might enter the human temporal lobe from the circulation where they would be readily converted via neuronal STS activity. [ABSTRACT FROM AUTHOR]

Five apple juices were produced on a pilot scale by crushing the fruit, treating the mash with pectolytic enzymes, pressing, extracting water from the pomace, pasteurization, treatment of the juice with enzymes, combined gelatin/silica sol fining and final ultrafiltration. The temperature of the mash treatment was either ambient or one of 30, 40, 50 or 60 °C, in order to test whether this led to different compositional changes in the corresponding juices. The main emphasis was put on detection of D-galacturonic acid as the indicator substance for the extent of the enzymatic treatment. In the pasteurized raw juices after pressing we found values from 226 to 398 mg L -1 . A distinct increase of the galacturonic acid levels could be observed during the clarification steps. Enzymatic juice treatment raised the concentrations to 580–720 mg L -1 . After ultrafiltration, final values of 790–1100 mg L -1 were measured. Generally, the highest values were found in the 50 °C sample, which is the optimum temperature for pectinase activity. This was also true for the colloid concentrations and polyphenols. The influence of the temperature of the enzymatic mash treatment on other characteristic juice parameters like total titratable acidity, density, sugar, and minerals concentrations was low. [ABSTRACT FROM AUTHOR]

Background. A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n =77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n =62) or vaginal progesterone only (group III, n =70). Method. All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was ≥ 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n =83) or progesterone only (group V, n =121). For vaginal progesterone Utrogest® was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). Results. Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p <0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. Conclusion. Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient. [ABSTRACT FROM AUTHOR]

Subject: Luteal phase support has been shown in the past to be an essential part of ovarian stimulation protocols, especially the long protocol. It could be shown that hCG is as effective as is progesterone for luteal phase support but hCG is accompanied by a higher rate of complications.Methods: Progesterone can be administered in several routes. The oral, intramuscular (i.m.) and vaginal routes have been chosen frequently in the past. The oral route is ineffective, since progesterone has a low oral bioavailability (<10%), and a high rate of metabolites, which may result in side effects such as somnolence etc. Intramuscular administration provides very high serum levels of progesterone and this route is effective with regard to pregnancy rates. Injection of progesterone, however, is painful and cannot be done by the patient herself. The vaginal route is also effective, progesterone can be administered by the patient herself and progesterone is delivered directly to the uterus, where high levels are achieved (first uterine pass effect).Results: Several studies could show, in the past, that the vaginal administration of progesterone is effective also with regard to the downregulation of uterine contractions. Crinone 8% Vaginal Gel is especially designed for vaginal use with a special applicator and has to be administered once daily in the morning. It adheres to the vaginal epithelium, and leakage of the gel is substantially reduced as compared to other drugs like capsules or suppositories.Conclusions: Since progesterone is as effective as hCG for luteal phase support but provides a higher safety with regard to ovarian hyperstimulation syndromes, and vaginal progesterone is as effective as intramuscular progesterone, vaginal progesterone should be the standard choice for luteal phase support. Crinone 8% seems to be the most comfortable way of vaginal administration of progesterone for luteal phase support in IVF cycles. [ABSTRACT FROM AUTHOR]

Hypotrichosis is a rare form of progressive hair loss characterized by sparse and occasionally woolly hair that is curly and breaks easily. Disease-causing mutations in LIPH, LPAR6 and KRT74 have recently been identified. We describe a four-generation pedigree from Turkey following an autosomal recessive pattern, in which the four affected members had hypotrichosis and woolly hair. By sequencing LPAR6 and the use of SNP arrays, we revealed a homozygous loss of the entire LPAR6 gene in the affected individuals. We hypothesize that the 12-kb deletion resulted from illegitimate recombination secondary to slip-replication. The orientation of three Alu repeats around LPAR6 may have provoked the formation of a 'triple-barrel' structure during replication, thereby allowing strand slipping. This first report of complete LPAR6 loss expands the spectrum of known LPAR6 mutations and suggests a novel mechanism for this gene and for the formation of DNA rearrangements in general. [ABSTRACT FROM AUTHOR]

Anorectal malformations (ARMs) comprise a broad spectrum of conditions ranging from mild anal anomalies to complex cloacal malformations. In 40-50% of cases, ARM occurs within the context of defined genetic syndromes or complex multiple congenital anomalies, such as VATER/VACTERL (vertebral defects [V], ARMs [A], cardiac defects [C], tracheoesophageal fistula with or without esophageal atresia [TE], renal malformations [R], and limb defects [L]) association. Here, we report the identification of deletions at chromosome 13q using single nucleotide polymorphism-based array analysis in two patients with mild ARM as part of VATER/VACTERL and VATER/VACTERL-like associations. Both deletions overlap the previously defined critical region for ARM. Heterozygous Efnb2 murine knockout models presenting with mild ARM suggest EFNB2 as an excellent candidate gene in this region. Our patients showed a mild ARM phenotype, closely resembling that of the mouse. We performed a comprehensive mutation analysis of the EFNB2 gene in 331 patients with isolated ARM, or ARM as part of VATER/VACTERL or VATER/VACTERL-like associations. However, we did not identify any disease-causing mutations. Given the convincing argument for EFNB2 as a candidate gene for ARM, analyses of larger samples and screening of functionally relevant non-coding regions of EFNB2 are warranted. In conclusion, our report underlines the association of chromosome 13q deletions with ARM, suggesting that routine molecular diagnostic workup should include the search for these deletions. Despite the negative results of our mutation screening, we still consider EFNB2 an excellent candidate gene for contributing to the development of ARM in humans., (© 2013 Wiley Periodicals, Inc.)

We report on a father and daughter with hand-foot-genital syndrome (HFGS) with typical skeletal and genitourinary anomalies due to a 14-residue polyalanine expansion in HOXA13. This is the largest (32 residues) polyalanine tract so far described for any polyalanine mutant protein. Polyalanine expansion results in protein misfolding, cytoplasmic aggregation and degradation; however, HOXA13 polyalanine expansions appear to act as loss of function mutations in contrast to gain of function for HOXD13 polyalanine expansions. To address this paradox we examined the cellular consequences of polyalanine expansions on HOXA13 protein using COS cell transfection and immunocytochemistry. HOXA13 polyalanine expansion proteins form cytoplasmic aggregates, and distribution between cytoplasmic aggregates or the nucleus is polyalanine tract size-dependent. Geldanamycin, an Hsp90 inhibitor, reduces the steady-state abundance of all polyalanine-expanded proteins in transfected cells. We also found that wild-type HOXA13 or HOXD13 proteins are sequestered in HOXA13 polyalanine expansion cytoplasmic aggregates. Thus, the difference between HOXA13 polyalanine expansion loss-of-function and HOXD13 polyalanine expansion dominant-negative effect is not the ability to aggregate wild-type group 13 paralogs but perhaps to variation in activities associated with refolding, aggregation or degradation of the proteins., ((c) 2007 Wiley-Liss, Inc.)