The effects of summarization and factual retrieval practice on text comprehension and text retention in elementary education.

When reading a text in school, the goal is both text comprehension and text retention. We examined the effects of the learning strategies summarization and factual retrieval practice on third- and fourth-grade pupils' text comprehension and retention of factual knowledge from a text, using restudy as a control condition. The experiment was conducted in an authentic classroom setting, with teachers executing the experiment using original course materials. In 2016, 57 regular third- and fourth-grade pupils (M = 9.04 years old) read three different texts, and each applied three different learning strategies (summarization, retrieval practice and restudy, which were counterbalanced across texts) in subsequent practice sessions. After a 2-week delay, a final test was administered. The learning strategy summarization had a larger positive effect on text comprehension than factual retrieval practice, but had a similar effect compared to restudy. The learning strategy factual retrieval practice had a larger positive effect on text retention than both summarization and restudy. Implications for educational practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Search for a genetic cause in children with unilateral isolated microtia and congenital aural atresia.

PURPOSE: Microtia describes a spectrum of auricular malformations ranging from mild dysplasia to anotia. A vast majority of microtia patients demonstrate congenital aural atresia (CAA). Isolated microtia has a right ear predominance (58-61%) and is more common in the male sex. Isolated microtia is a multifactorial condition involving genetic and environmental causes. The aim of this study is to describe the phenotype of children with unilateral isolated microtia and CAA, and to search for a common genetic cause trough DNA analysis. METHODS: Phenotyping included a complete clinical examination. Description on the degree of auricular malformation (Weerda classification-Weerda 1988), assessment for hemifacial microsomia and age-appropriate audiometric testing were documented. Computerized tomography of the temporal bone with 3-D rendering provided a histopathological classification (HEAR classification-Declau et al. 1999). Genetic testing was carried out by single nucleotide polymorphism (SNP) microarray. RESULTS: Complete data are available for 44 children (50% was younger than 33 days at presentation; 59.1% boys; 72.7% right ear). Type III microtia was present in 28 patients. Type 2b CAA existed in 32 patients. All patients had a normal hearing at the non-affected side. Genome wide deletion duplication analysis using microarray did not reveal any pathological copy number variant (CNV) that could explain the phenotype. CONCLUSIONS: Type III microtia (peanut-shell type) in combination with a type 2b CAA was the most common phenotype, present in 23 of 44 (52.3%) patients with isolated unilateral microtia. No abnormalities could be found by copy number variant (CNV) analysis. Whole exome sequencing in a larger sample with a similar phenotype may represent a future diagnostic approach.

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms.

Mutations in DAXX/ATRX, MEN1 and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel. Novel amplicon-based algorithms were used to identify both single nucleotide variants (SNVs) and insertion-deletions (indels) present in >10% of reads (high abundance) and in <10% of reads (low abundance). Found variants were validated by Sanger sequencing. Sequencing resulted in 416,711,794 reads with an average target base coverage of 2663 ± 1476. Across all samples, 32 high-abundance somatic, 3 germline and 30 low-abundance mutations were withheld after filtering and validation. Overall, 92% of high-abundance and 84% of low-abundance mutations were predicted to be protein damaging. Frequently, mutated genes were MEN1, DAXX, ATRX, TSC2, PI3K/Akt/mTOR and MAPK-ERK pathway-related genes. Additionally, recurrent alterations on the same genomic position, so-called hotspot mutations, were found in DAXX, PTCH2 and CYFIP2. This first ultra-deep sequencing study highlighted genetic intra-tumor heterogeneity in pNEN, by the presence of low-abundance mutations. The importance of the ATRX/DAXX pathway was confirmed by the first-ever pNEN-specific protein-damaging hotspot mutation in DAXX. In this study, both novel genes, including the pro-apoptotic CYFIP2 gene and hedgehog signaling PTCH2, and novel pathways, such as the MAPK-ERK pathway, were implicated in pNEN.

The reduction in glutamate release is predictive of cognitive and emotional alterations that are corrected by the positive modulator of AMPA receptors S 47445 in perinatal stressed rats.

S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the perinatal stress (PRS) rat model, known to have a high predictive validity with monoaminergic antidepressants. The effects of a chronic treatment (i.p.) with S 47445 were investigated on risk-taking, motivational and cognitive behavior. S 47445 (1 and 10 mg/kg) increased the exploration of the elevated-plus maze and light/dark box as well as the time spent grooming in the splash test, and improved social memory in PRS rats. Also, the effects of S 47445 were examined on the synaptic neurotransmission. The reduced depolarization-evoked glutamate release induced by PRS was corrected with S 47445 (10 mg/kg). Remarkably, the reduction in glutamate release induced by PRS and corrected by S 47445 chronic treatment was correlated with all the behavioral changes. S 47445 at 10 mg/kg also normalized the lower levels of synaptic vesicle-associated proteins in ventral hippocampus in PRS rats. Finally, S 47445 reversed the decrease of mGlu5 receptors, GR and OXTR induced by PRS. Collectively, in an animal model of stress-related disorders, S 47445 corrected the imbalance between excitatory and inhibitory neurotransmission by regulating glutamate-evoked release that is predictive of PRS behavioral alterations, and also normalized the reduction of trafficking of synaptic vesicles induced by PRS. These results support the interest of glutamatergic-based therapeutic strategies to alleviate stress-related disorders.

Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.

BACKGROUND: Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. MATERIALS AND METHODS: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided. RESULTS: Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125). CONCLUSION: The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted. TRIAL REGISTRATION (CLINICALTRIALS.GOV): PRIME (NCT00364013), PEAK (NCT00819780).

Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration.

In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells.

Cardiovascular disease prevention.

Cardiovascular diseases remain the first killer in the Western countries. Equivalent contributions of prevention initiatives, pharmaceutical developments and technological improvements have led to an important success in the reduction of mortality related to cardiovascular diseases in some of the countries of the Western world. However, increase in life expectance, incomplete adherence to guidelines, difficulties in convincing governments and the population to support and adhere to prevention measures make that the burden of cardiovascular diseases is still extremely high. This review gives a restricted summary of the most important prevention guidelines supported by the European Society of Cardiology. It also illustrates the still very incomplete adherence to these guidelines in the different European countries as published in the EUROASPIRE surveys.

[Epidermolysis bullosa simplex congenital antenatal discovery and contribution of 3D ultrasound]. / Épidermolyse bulleuse simplex congénitale de découverte anténatale et apport de l'échographie 3D.

Epidermolysis bullosa (EB) comprises a heterogeneous group of genodermatoses whose prognosis is variable. The diagnosis is suggested by prenatal ultrasound at signs, especially for junctional EB with pyloric atresia. The authors report a case of antenatal image limited skin undermining highlighted by the ultrasound three-dimensional (3D) in connection with a diagnosis of a congenital epidermolysis simplex confirmed postnatal period.

Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome.

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.

Potentiometric sensors doped with biomolecules as a new approach to small molecule/biomolecule binding kinetics analysis.

The most successful binding kinetics analysis systems at this moment include surface plasmon resonance (SPR), quartz microcrystal balance (QMB) and surface acoustic wave (SAW). Although these are powerful methods, they generally are complex, expensive and require the use of monolayers. Here, we report on potentiometric sensors as an inexpensive and simple alternative to do binding kinetics analysis between small molecules in solution and biomolecules (covalently) attached in a biopolymer sensor coating layer. As an example, dopamine and an anti-dopamine aptamer were used as the small molecule and the biomolecule respectively. Binding between both follows a Langmuir adsorption type model and creates a surface potential. The system operates in Flow Injection Analysis mode (FIA). Besides being an interesting new binding kinetics tool, the approach allows systematic design of potentiometric biosensors (in the present study a dopamine sensor), and gives new insights into the functioning of ion-selective electrodes (ISE's).

Use of potentiometric detection in (ultra) high performance liquid chromatography and modelling with adsorption/desorption binding kinetics.

Observation of a potentiometric sensor's response behaviour after injection in flow injection analysis at different concentrations allowed studying "on" and "off" kinetics of the analyte's adsorption/diffusion behaviour. The alkaloid metergoline was mostly used as an example. k(on) and k(off) rate constant values were measured, and the association constant K(ass), and ΔG values of the analyte-surface interaction were calculated with an adsorption-based model which proved to be fully applicable. k(on) increased by decreasing the sensor dimensions, while koff was unaffected by miniaturization. Increasing acetonitrile concentrations in the running buffer increased k(off), while k(on) was unaffected. The experimentally determined ΔG values of the analyte-surface interaction showed a linear relation to the response of the sensor, in mV. This knowledge was applied to optimize the potentiometric detection of plant alkaloids in (U)HPLC. Sub-micromolar detection limits were obtained with the potentiometric detector/(U)HPLC combination. This is the first time that the response rates and the response itself can be modelled accurately for coated wire potentiometric sensors, and it is the first application of a potentiometric detector in UPLC.

Genetic diagnostics of early childhood hearing loss: better testing with next-generation DNA sequencing.

Hearing loss is the most common sensory disorder in children, with an incidence of 1 in 500 newborns. Most cases are caused by mutations in a single gene. However, DNA diagnostics for hearing loss are challenging, since it is an extremely heterogeneous trait. Although more than 47 causative genes have been identified for the nonsyndromic forms of hearing loss alone, diagnostic application of the scientific progress has lagged behind. The reason for this is the cost: screening all the known causative genes for hearing loss in one patient with the current golden standard for DNA diagnostics, Sanger sequencing, would be extremely expensive. Consequently, current routine DNA diagnostic testing for hearing loss is restricted to one or two of the most common causative genes, and the responsible gene is identified in only 10-20% of cases. Several recent reports have shown that "next-generation DNA sequencing techniques" have the potential to provide a novel testing platform that could test all known genes in a sensitive, specific and cost-efficient manner. It is to be expected that these new tests will greatly improve DNA diagnostics in the coming years.

Use of potentiometric sensors to study (bio)molecular interactions.

Potentiometric sensors were used to study molecular interactions in liquid environments with sensorgram methodology. This is demonstrated with a lipophilic rubber-based and a collagen-based hydrogel sensor coating. The investigated molecules were promazine and tartaric acid, respectively. The sensors were placed in a hydrodynamic wall-jet system for the recording of sensorgrams. Millivolt sensor responses were first converted to a signal, expressing the concentration of adsorbed organic ions. Using a linearization method, a pseudo-first order-kinetic model of adsorption was shown to fit the experimental results perfectly. K(assoc), k(on), and k(off) values were calculated. The technique can be used over 4 decades of concentration, and it is very sensitive to low-MW compounds as well as to multiply charged large biomolecules. This study is the first to demonstrate the application of potentiometric sensors as an alternative and complement to surface plasmon resonance methods.

Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution.

The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all.

Inherited mitochondrial variants are not a major cause of age-related hearing impairment in the European population.

Mitochondrial DNA (mtDNA) mutations have been implicated in various age-related diseases. To further clarify the role of mtDNA variants in age-related hearing impairment (ARHI), we determined the DNA sequence of the entire mitochondrial genome of 400 individuals using the Affymetrix Human Mitochondrial Resequencing Array. These were the 200 worst hearing and the 200 best hearing from a collection of 947 Belgian samples. We performed association tests with individual mitochondrial variants, comparison of the mutation load, and association with European haplogroups and their interaction with environmental risk factors. We also tested the influence of rare variants on ARHI. None of these tests showed any association with ARHI.