Notes

Ideas associated with evidence-based medicine: via Robert Kochs postulates with a existing EBM idea.
Though children with Down syndrome can learn to read, they may have difficulty developing some component skills, including phonological awareness and word decoding. Given reading's foundation in language, speech-language pathologists (SLPs) should play a central role in supporting access to and providing reading instruction for children with Down syndrome. This article reviews the available research on reading in Down syndrome and offers guidance for SLPs working with this population. We start by reviewing the Down syndrome phenotype, highlighting physical features and cognitive and linguistic patterns of strength and weakness that impact reading development. Next, we define different reading subskills and outline typical reading development, including stages of prereading, learning to read, and transitioning to using reading as a tool for learning. We then use these stages to review what is known about reading in Down syndrome, including relevant intervention work. We also incorporate considerations for clinical practice. In particular, we encourage SLPs to advocate for supporting reading development in children with Down syndrome, to work with families to develop rich home literacy environments, and to work with educators to promote phonological awareness and decoding skills. Lastly, we note limitations in our current knowledge and include a call for more research.Children with Down syndrome (DS) have both strengths and difficulties in speech, language, and social communication. Mental state language-the ability to discuss others' perspectives such as their thoughts, feelings, and intentions-represents a foundational social communicative skill that is delayed in many children with DS, even into the school-age years. The purpose of this article is to review the evidence base on mental state language development in school-age children with DS, focusing in particular on assessment and intervention. We discuss assessment procedures that are both age appropriate and developmentally appropriate for this population. We also present preliminary data highlighting the role of caregivers in supporting mental state language development in school-age children with DS through shared storytelling. We propose that interventions aimed at supporting mental state language development in DS should include a focus on caregiver-child shared storybook reading, even in the school-age years. Therefore, we discuss key considerations for clinicians when teaching caregivers strategies for supporting mental state language and social communication in children with DS.Promoting language abilities, including early word learning, in children with neurogenetic disorders with associated language disorders, such as Down syndrome (DS) and fragile X syndrome (FXS), is a main concern for caregivers and clinicians. For typically developing children, the quality and quantity of maternal language input and maternal gesture use contributes to child word learning, and a similar relation is likely present in DS and FXS. However, few studies have examined the combined effect of maternal language input and maternal gesture use on child word learning. We present a multidimensional approach for coding word-referent transparency in naturally occurring input to children with neurogenetic disorders. We conceptualize high-quality input from a multidimensional perspective, considering features from linguistic, interactive, and conceptual dimensions simultaneously. Using case examples, we highlight how infrequent the moments of word-referent transparency are for three toddlers with DS during play with their mothers. We discuss the implications of this multidimensional framework for children with DS and FXS, including the clinical application of our approach to promote early word learning for these children.This review highlights the ways in which telehealth procedures can be implemented to help bridge the research-to-practice gap in supporting developmental outcomes for youth with fragile X syndrome (FXS). We review how the literature to date has informed potential treatment targets in the areas of speech and language development with a focus on understanding and supporting the dyadic relationship between the child and their biological mother, who is also impacted biologically. Notably, parental responsivity is an area that is strongly related to child language outcomes, both early and into adolescence, and thus, it is an important treatment target for subsequent interventions. To date, several parent-implemented interventions have been done in FXS across a broad age range (2-17-year-olds) all showing support not only that parents are successful in learning responsive strategies but also that there are subsequent impacts to child language development. Moreover, these interventions were successfully implemented at a distance through telehealth procedures including video teleconferencing and shared recordings of parent-child interactions. This review also addresses potential moderators of treatment gains. Implications for scaling such interventions in the future as well as best practices for incorporating telehealth procedures into future research and intervention programs are also discussed.Fragile X syndrome (FXS) is a genetic disorder caused by changes of the FMR1 gene that is passed along among families. A range of developmental processes may be impacted with wide variation in abilities across individuals with FXS. Mothers of children with FXS are often carriers of a "premutation" expansion on the FMR1 gene, which is associated with its own clinical phenotype. These maternal features may increase individual and family vulnerabilities, including increased risk for depression and anxiety disorders and difficulties in social and cognitive ability. These characteristics may worsen with age, and potentially interact with a child's challenging behaviors and with family dynamics. Thus, families of children with FXS may experience unique challenges related to genetic risk, manifested across both children and parents, that should be considered in therapeutic planning to optimize outcomes for children and their families. In this article, we review core features of the FMR1 premutation as expressed in mothers and aspects of the family environment that interface with developmental outcomes of children with FXS. Recommendations for family-centered support services are discussed.SARS-CoV-2 is a novel human pathogenic coronavirus whose predilection for the respiratory tract has given rise to a rapid pandemic spread via airborne particles. Organ-specific susceptibility is substantially determined by the density of cell surface expression of ACE2, which is exploited by viral spike protein as a receptor molecule to mediate adhesion and, thus, to permit internalization of the viral genome into the host cell. Based on an ample data set derived from clinical studies and case reports, evidence suggests that distinct cell populations of the digestive and olfactory-gustatory system are equally equipped with membrane-bound ACE2, rendering them "vulnerable" to SARS-CoV-2. Numerous reports on concomitant gastrointestinal complaints and laboratory abnormalities are thought to reflect a relevant degree of organ dysfunction and underscore the tropism of SARS-CoV-2 for the digestive tract. Organoids are three-dimensional in vitro replicas of organ tissue which, owing to their organotypic complex cellular composition and functional resemblance to primary cells, are particularly appreciated for basic research in the field of infectious diseases. This review specifically addresses the involvement of digestive organs by SARS-CoV-2 and outlines the significant contribution of organoid- and primary-cell culture-based models to gaining a deeper understanding of the underlying pathophysiological processes.
Hepcidin, a liver-derived peptide, regulates the absorption, distribution, and circulation of iron in the body. Tetrazolium Red chemical structure Inflammation or iron overload stimulates hepcidin release, which causes the accumulation of iron in tissues. The inadequate levels of iron in circulation impair erythropoiesis. Inhibition of hepcidin may increase iron in circulation and improve efficient erythropoiesis. Activin-like kinase (ALK) inhibitors decrease hepcidin.

In this work, we have investigated an ALK inhibitor LDN193189 for its efficacy in iron homeostasis. The effect of LDN193189 treatment was assessed in C57BL6/J mice, in which hepcidin was induced by either ferrous sulfate or lipopolysaccharide (LPS) injection.

After two hours of treatment, ferrous sulfate increased serum and liver iron, serum hepcidin, and liver hepcidin expression. On the other hand, LPS reduced serum iron in a dose-related manner after six hours of treatment. LDN193189 treatment increased serum iron, decreased spleen and liver iron, decreased serum hepcidin and liver hepcidin expression in ferrous sulfate-treated mice, and increased serum iron in LPS-induced hypoferremia. We observed that ferrous sulfate caused a significantly higher increase in liver iron, serum hepcidin, and liver hepcidin than turpentine oil or LPS in mice. Iron dextran (intraperitoneal or intravenous) increased serum iron, but LDN193189 did not show hyperferremia with iron dextran stimulus.

Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.
Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.The aim of this study was to examine the effects of chronological age on acceleration and deceleration match performance in professional soccer players. A total of 5317 individual match observations were collected on 420 professional players competing in the Spanish LaLiga during the 2018-2019 season, using a multiple-camera computerised tracking system (TRACAB; ChyronHego, Melville, NY, USA). Players were classified using a k-means cluster analysis into four different age groups 17-23 years, 24-27 years, 28-30 years, and 31-38 years. Linear mixed models were adjusted to compare the players' match performance according to their age group and playing position (central defenders, external defenders, central midfielders, external midfielders, and forwards). The results showed that players aged between 31-38 years performed a significantly less total number of accelerations (ES=0.30-0.48) and decelerations (ES=0.29-0.49) in comparison with younger players. These age-related physical performance declines were more pronounced among central defenders, central midfielders, and forwards. However, no significant effects were obtained for players' maximum acceleration and deceleration capacities. The current findings provide useful information for coaches and strength and conditioning specialists to better understand the effects of age on players' physical performance and to develop age-tailored training programs.
Fracture detection by artificial intelligence and especially Deep Convolutional Neural Networks (DCNN) is a topic of growing interest in current orthopaedic and radiological research. As learning a DCNN usually needs a large amount of training data, mostly frequent fractures as well as conventional X-ray are used. Therefore, less common fractures like acetabular fractures (AF) are underrepresented in the literature. The aim of this pilot study was to establish a DCNN for detection of AF using computer tomography (CT) scans.

Patients with an acetabular fracture were identified from the monocentric consecutive pelvic injury registry at the BG Trauma Center XXX from 01/2003 - 12/2019. All patients with unilateral AF and CT scans available in DICOM-format were included for further processing. All datasets were automatically anonymised and digitally post-processed. Extraction of the relevant region of interests was performed and the technique of data augmentation (DA) was implemented to artificially increase the number of training samples.
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