The relations between maternal language input and language development for children with Williams syndrome.

For typically developing (TD) children, maternal language input (MLI) is an important contributor to early language development. Until now, possible relations between MLI and language development for children with Williams syndrome (WS), a genetic neurodevelopmental disorder associated with language delay and intellectual disability, have not been addressed. The aim of the present study was two-fold: to examine concurrent relations between MLI and child language abilities at 24 months and to determine if individual differences in MLI and children’s lexical and cognitive abilities at 24 months make significant unique contributions to the variance in child language abilities at 48 months for children with WS. Participants included 34 mother-child dyads. Lexical diversity (number of different words; NDW) and grammatical complexity (mean length of utterance in morphemes; MLUm) measures of MLI were assessed during a 30-minute naturalistic play session at 24 months of age. For the child, standardized assessments of language and cognitive ability, as well as lexical (NDW) and grammatical (MLUm) ability measures from the play session were collected at 24 and 48 months of age. Mothers also completed a parent-report measure of child lexical and grammatical abilities at both ages. Concurrent relations between MLI and child measures of language and cognitive development were significant for maternal NDW but not for maternal MLUm. Regression analyses indicated that maternal NDW contributed significant unique variance to child receptive language at 48 months, even after taking into account child 24-month expressive vocabulary and 24-month nonverbal reasoning ability. Maternal MLUm accounted for significant unique variance in child receptive language and child MLUm at 48 months, even after accounting for the contributions of child 24-month expressive vocabulary and nonverbal reasoning ability. Implications of these findings are discussed

Investigation of Avaren-Fc\u27s therapeutic potential against ovarian cancer.

This thesis describes the investigation of Avaren-Fc (AvFc), a novel lectin-based therapeutic fusion protein consisting of the recombinant Avaren lectin and the Fc region of human IgG1, against ovarian cancer. AvFc possesses selectivity toward tumor associated N-linked high-mannose-type glycans. The present study demonstrates AvFc’s in vitro activity against OVCA cell lines via antibody-dependent cell-mediated cytotoxicity and its ability to extend the survival of mice challenged with murine ID8 OVCA cells after repeated systemic administration. Furthermore, AvFc treatment in this model was found to increase the presence of peritoneal leukocytes, suggesting a shift toward an improved antitumor immune response. Another key finding of the current work was AvFc’s preferential binding to primary human OVCA tumor tissue over healthy adjacent tissue. Overall, these results emphasize AvFc’s therapeutic potential by effectively leveraging OVCA-associated high-mannose glycans as a target to induce cancer cell elimination

Avaren-Fc, a Novel Immunotherapeutic, Recruits NK Cells in B16F10 Melanoma Tumor Tissue

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro. Furthermore, flow cytometry analysis revealed that AvFc treatment exhibited a trend towards increased NK cell infiltration within the B16F10 flank tumor tissue of C57bl/c mice. The objective of the current study is to assess the B16F10 tumor microenvironment by immunohistochemistry, quantifying NK cells and an associated NK cell activation signal in AvFc-treated B16F10 tumor tissue compared to untreated tissue. Based on our previous flow cytometry analysis data, we hypothesized that AvFc-treated tissue may have an elevated NK cell count, indicative of AvFc-mediated recruitment of NK cells. The study utilized fluorescent immunohistochemistry, which probed for NK cells (NK1.1) and NK cell activation (CD107a). The results demonstrated a significant increase in the number of NK-1.1+ cells (p = 0.0056, Wilcoxon Rank Sum Test) and CD107a+ signal (p = 0.0009, Wilcoxon Rank Sum Test) in AvFc-treated tissue when compared to untreated tissue. Colocalization of NK-1.1 and CD107a was also deemed significant in AvFc-treated tissue (p = 0.0032, Wilcoxon Rank Sum Test), thus supporting the presence and associated activation of NK cells in the tumor microenvironment. These results warrant further analysis to elucidate the underlying mechanism by which AvFc recruits additional NK cells to the tumor tissue. Overall, the results from this study corroborate that AvFc’s anti-cancer activity is mediated via NK cell activation and support its development as a potential immunotherapeutic for melanoma treatment

Evaluation of Intraoperative Volumetric Assessment of Breast Volume Using 3D Handheld Stereo Photogrammetric Device.

Methods for assessing three-dimensional (3D) breast volume are becoming increasingly popular in breast surgery. However, the precision of intraoperative volumetric assessment is still unclear. Until now, only non-validated scanning systems have been used for intraoperative volumetric analyses. This study aimed to assess the feasibility, handling, and accuracy of a commercially available, validated, and portable device for intraoperative 3D volumetric evaluation. All patients who underwent breast surgery from 2020 to 2022 were identified from our institutional database. Intraoperative 3D volumetric assessments of 103 patients were included in this study. Standardized 3D volumetric measurements were obtained 3 months postoperatively to compare the intraoperatively generated volumetric assessment. All of the study participants were women with a mean age of 48.3 ± 14.7 years (range: 20-89). The mean time for intraoperative volumetric assessment was 8.7 ± 2.6 min. The postoperative 3D volumetric assessment, with a mean volume of 507.11 ± 206.29 cc, showed no significant difference from the intraoperative volumetric measurements of 504.24 ± 276.61 cc (p = 0.68). The mean absolute volume difference between the intraoperative simulations and postoperative results was 27.1 cc. Intraoperative 3D volumetric assessment using the VECTRA H2 imaging system seems to be a feasible, reliable, and accurate method for measuring breast volume. Based on this finding, we plan to investigate whether volumetric objective evaluations will help to improve breast symmetry in the future

CDHR1 mutations in retinal dystrophies

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders. In one family, homozygosity mapping with subsequent candidate gene analysis was performed. Stringent filtering for rare and potentially disease causing variants following a model of autosomal recessive inheritance led to the identification of eleven different CDHR1 variants in nine index cases. All variants were novel at the time of their identification. In silico analyses confirmed their pathogenic potential. Minigene assays were performed for two non-canonical splice site variants and revealed missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of retinal dystrophy. Our study further expands the mutational spectrum of this gene and the associated clinical presentation

A deep scattering layer under the North Pole pack ice

The 3.3 million km marine ecosystem around the North Pole, defined as the Central Arctic Ocean (CAO), is a blind spot on the map of the world\u27s fish stocks. The CAO essentially comprises the permanently ice-covered deep basins and ridges outside the continental shelves, and is only accessible by ice-breakers. Traditional trawling for assessing fish stocks is impossible under the thick pack ice, and coherent hydroacoustic surveys are unachievable due to ice-breaking noise. Consequently, nothing is known about the existence of any pelagic fish stocks in the CAO, although juveniles of Boreogadus saida richly occur at the surface associated with the sea ice and ice-associated Arctogadus glacialis has been reported as well. We here present a first indication of a possible mesopelagic fish stock in the CAO. We had the opportunity to analyse a geophysical hydroacoustic data set with 13 time windows of usable acoustic data over a transect from 84.4 \ub0N in the Nansen Basin, across the North Pole (90.0 \ub0N), to 82.4 \ub0N in the Canada Basin. We discovered a deep scattering layer (DSL), suggesting the presence of zooplankton and fish, at 300–600 m of depth in the Atlantic water layer of the CAO. Maximum possible fish abundance and biomass was very low; values of ca. 2,000 individuals km and ca. 50 kg km were calculated for the DSL in the North-Pole area according to a model assuming that all acoustic backscatter represents 15-cm long B. saida and/or A. glacialis. The true abundance and biomass of fish is even lower than this, but cannot be quantified from this dataset due to possible backscatter originating from pneumatophores of physonect siphonophores that are known to occur in the area. Further studies on the DSL of the CAO should include sampling and identification of the backscattering organisms. From our study we can conclude that if the central Arctic DSL contains fish, their biomass is currently too low for any sustainable fishery

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding

Study protocol of the Bergen brain-gut-microbiota-axis study: A prospective case-report characterization and dietary intervention study to evaluate the effects of microbiota alterations on cognition and anatomical and functional brain connectivity in patients with irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS. Methods: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection. Discussion: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown.publishedVersio