Small for gestational age as an independent risk factor for long-term pediatric gastrointestinal morbidity of the offspring*

Objective: The concept of neonatal programming has begun to emerge as an important component of adult health. Scarce data exist regarding perinatal risk factors for long-term gastrointestinal (GI) morbidity of the offspring. We aimed to evaluate the association between birthweight (BW) at term and long-term pediatric GI morbidity.

Study design: A population-based cohort analysis was performed, comparing the risk of long-term GI morbidity (up to the age of 18 years) in children delivered at term according to their BW. The study included all term deliveries occurring between 1991 and 2014 at a single regional tertiary medical center. Multiple gestations and fetuses with congenital malformations were excluded. BW was subdivided into: small for gestational age (small for gestational age (SGA) – BW?≤?5th centile), appropriate for gestational age (AGA ?5th centile?Results: During the study period, 225,600 term singleton deliveries met the inclusion criteria. Of them, 4.6% (n?=?10,415) were SGA and 4.3% (n?=?9796) were LGA. During the 18-years follow-up period, 11,791 (5.2%) children were hospitalized with GI morbidity. Hospitalizations were significantly more common in the SGA group, as compared with the AGA and LGA groups (6.6 versus 5.2 versus 4.5%, respectively, p?p?p?Conclusions: SGA offspring are at an increased and independent risk for long-term pediatric GI morbidity.     

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source

PurposeThe aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.MethodsWe performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.ResultsThere were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).ConclusionsThe use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.     

Scaling of morphogen gradients by an expansion-repression integral feedback control

Despite substantial size variations, proportions of the developing body plan are maintained with a remarkable precision. Little is known about the mechanisms that ensure this adaptation (scaling) of pattern with size. Most models of patterning by morphogen gradients do not support scaling. In contrast, we show that scaling arises naturally in a general feedback topology, in which the range of the morphogen gradient increases with the abundance of some diffusible molecule, whose production, in turn, is repressed by morphogen signaling. We term this mechanism “expansion–repression” and show that it can function within a wide range of biological scenarios. The expansion-repression scaling mechanism is analogous to an integral-feedback controller, a key concept in engineering that is likely to be instrumental also in maintaining biological homeostasis.     

Functional properties of human embryonic stem cell-derived cardiomyocytes: intracellular Ca2+ handling and the role of sarcoplasmic reticulum in the contraction

Since cardiac transplantation is limited by the small availability of donor organs, regeneration of the diseased myocardium by cell transplantation is an attractive therapeutic modality. To determine the compatibility of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) (7 to 55 days old) with the myocardium, we investigated their functional properties regarding intracellular Ca2+ handling and the role of the sarcoplasmic reticulum in the contraction. The functional properties of hESC-CMs were investigated by recording simultaneously [Ca2+]i transients and contractions. Additionally, we performed Western blot analysis of the Ca2+-handling proteins SERCA2, calsequestrin, phospholamban, and Na+/Ca2+ exchanger (NCX). Our major findings are, first, that hESC-CMs displayed temporally related [Ca2+]i transients and contractions, negative force-frequency relations, and lack of post-rest potentiation. Second, ryanodine, thapsigargin, and caffeine did not affect the [Ca2+]i transient and contraction, indicating that at this developmental stage, contraction depends on transsarcolemmal Ca2+ influx rather than on sarcoplasmic reticulum Ca2+ release. Third, in agreement with the notion that a voltage-dependent Ca2+ current is present in hESC-CMs and contributes to the mechanical function, verapamil completely blocked contraction. Fourth, whereas hESC-CMs expressed SERCA2 and NCX at levels comparable to those of the adult porcine myocardium, calsequestrin and phospholamban were not expressed. Our study shows for the first time that functional properties related to intracellular Ca2+ handling of hESC-CMs differ markedly from the adult myocardium, probably due to immature sarcoplasmic reticulum capacity.     

Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety-related personality trait: TPQ harm avoidance.

The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.     

Long-Term (over 10 Years) Retrospective Follow-up of Laparoscopic Adjustable Gastric Banding

Background

Laparoscopic adjustable gastric banding (LAGB) placements have progressively decreased in recent years. This is related to poor long-term weight loss outcomes and necessity for revision or removal of these bands. Long-term outcome results following LAGB are limited. The aim of our study was to determine the long-term outcome after LAGB at our institution.

Objectives

The aim of our study was to determine the long-term outcome after LAGB at our institution.

Setting

The setting of this is Academic Center, Israel.

Methods

Patients who underwent LAGB between 1999 and 2004 were reviewed. Patient comorbidities and weight loss parameters were collected preoperatively and at defined postoperative periods. Improvement in weight loss was defined as percent excess weight lost, and improvement in comorbidities was defined based on standardized reporting definitions.

Results

In total, 74 (80%) patients who underwent LAGB met inclusion criteria. The mean age at LAGB placement was 50.5 ± 9.6 years, and the mean body mass index (BMI) was 45.5 ± 4.8 kg/m². Preoperative comorbidities were diabetes mellitus (13.5%), hypertension (32%), hyperlipidemia (12.1%), obstructive sleep apnea (5.4%), joints disease (10.8%), mood disorders (5.4%), and gastro-esophageal reflux disease (GERD) symptoms (8.1%). The mean follow-up was 162.96 ± 13.9 months; 44 patients (59.4%) had their band removed, and 22 (30%) had another bariatric surgery. The follow-up BMI was 35.7 ± 6.9 (p < 0.001), and the % total weight loss was 21.0 ± 0.13. There was no improvement in any of the comorbidities. GERD symptoms worsened at long-term follow-up (p < 0.001). Undergoing another bariatric procedure was associated with a higher weight loss (OR 12.8; CI 95% 1.62–23.9; p = 0.02).

Conclusion

LAGB required removal in the majority of our patients and showed poor resolution of comorbidities with worsening of GERD-related symptoms. Patients who go on to have another bariatric procedure have more durable weight loss outcomes.

     

Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study

OBJECTIVE: Velocardiofacial syndrome, caused by a deletion on chromosome 22q11.2, is often accompanied by cognitive, behavioral, and psychiatric impairments. Specifically, velocardiofacial syndrome has been proposed as a disease model for a genetically mediated subtype of schizophrenia. Velocardiofacial syndrome is also known to affect brain structure. The most prominent structural findings in velocardiofacial syndrome are reduced white matter volumes. However, the structure of white matter and extent of specific regional involvement in this syndrome have never been investigated. The current study used diffusion tensor imaging to investigate white matter structure in children and young adults with velocardiofacial syndrome. METHOD: Nineteen participants with velocardiofacial syndrome and 19 age- and gender-matched comparison subjects underwent diffusion-weighted magnetic resonance imaging scans. Whole brain voxel-by-voxel analyses were conducted to investigate white matter fractional anisotropy differences between the groups. RESULTS: Relative to the comparison group, the velocardiofacial syndrome group had reduced white matter anisotropy in the frontal, parietal, and temporal regions as well as in tracts connecting the frontal and temporal lobes. CONCLUSIONS: This study demonstrates that alterations of white matter tract structure occur in velocardiofacial syndrome. Reduced white matter anisotropy was observed in individuals with velocardiofacial syndrome in areas previously implicated in the neurocognitive phenotype of velocardiofacial syndrome. The finding of aberrant parietal white matter tracts as well as aberrant frontotemporal connectivity in velocardiofacial syndrome and in previous schizophrenia studies may be associated with increased vulnerability for development of psychotic symptoms.     

When is gender accessed? A study of paraphasias in Hebrew anomia

This study explored access to grammatical gender during naming in Hebrew. Studies of anomia and tip-of-the-tongue states (TOT) found that speakers of various languages (Italian, Spanish, German, Dutch) have information about the grammatical gender of words they fail to retrieve. In Hebrew, on the other hand, a TOT study found that Hebrew speakers could not provide gender information. To test access to gender in single words in Hebrew we used an implicit measure--the analysis of paraphasias of anomic patients with respect to whether or not they preserved the grammatical gender of the target word. The rationale behind this measure was that when a paraphasia is created, it generally conforms to the partial knowledge the speaker has on the target word. If speakers have gender knowledge when they fail to name, they should produce paraphasias that match their partial information, and thus match the gender of the target. Such gender preservation in paraphasias was found in German for individuals with anomia, and in Arabic, French and German for slips of the tongue. Participants were 22 Hebrew-speaking aphasic patients with phonological, semantic or conceptual anomia, who produced 532 paraphasias. None of the participants showed gender preservation in their paraphasias. Even phonological anomics, who have access to semantic information, did not preserve grammatical gender in a single-word naming task. We suggest that this difference between Hebrew and previously studied languages relates to the fact that in Hebrew bare nouns are allowed, and therefore gender is not accessed in single-word naming, whereas in languages in which a noun should be produced as a full NP (with a determiner or case-marking for example) gender has to be accessed even in single-word tasks. We propose a hypothesis according to which gender is accessed if and only if the noun is incorporated into a syntactic tree (or a chunk of a tree) that includes an agreement phrase.