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Objective: To identify variations among administration and scoring instructions of six upper extremity Fugl-Meyer Assessment (FMA-UE) protocols and to achieve consensus regarding optimal administration procedures., Design: Nominal group consensus technique comprised of iterative independent reviews of protocol content, anonymous voting, and group consensus meetings., Setting: Clinicians working in clinical practice and research settings participated in virtual meetings via Zoom., Participants: Ten experts in stroke rehabilitation and administration of the FMA-UE contributed to the interprofessional consensus group., Interventions: not applicable., Main Outcome Measure: Qualitative reviews of each FMA-UE protocol and rater responses (agree/disagree) regarding variations in general administration instructions (i.e., instructions that could affect the scoring of many individual test items) were discussed and analyzed during a three-phase consensus process. An a priori target of 80% or greater agreement was used to determine group consensus., Results: Consensus was attained for 7/10 general administration instructions. Recommendations from our consensus group summarize "best practice" general instructions for researchers and clinicians. A case example, in which we found up to a 21-point difference between highest and lowest FMA-UE scores, highlights the potential impact of these protocol variations., Conclusions: Variations among FMA-UE administration protocols during stroke rehabilitation studies can lead to discrepancies in the interpretation and translation of research findings across institutions and limit the perceived value and uptake of standardized assessments for evidenced-based practice. Results of this nominal group consensus provide a first step toward developing cohesive FMA-UE recommendations for wider dissemination and review., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Abstract: The COVID-19 pandemic has propelled an unprecedented global implementation of telemedicine and telerehabilitation as well as its integration into the healthcare system. Here, we describe the clinical implementation of the A3E framework for the deployment of telerehabilitation in the inpatient and outpatient rehabilitation continuum by addressing accessibility, adaptability, accountability, and engagement during the COVID-19 pandemic. By using an organized, coordinated, and stratified approach, we increased our telerehabilitation practice from 0 to more than 39,000 visits since the pandemic began. Learning from both the successes and challenges can help address the need to increase access to rehabilitation services even beyond the COVID-19 pandemic., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This article outlines a multidisciplinary approach to implementing a telehealth program in the acute care hospital setting during the coronavirus disease 2019 (COVID-19) pandemic. Telehealth has been used in many practice areas, although it can be a particular challenge to establish in an acute care hospital given the fast-paced environment. However, the COVID-19 pandemic presented a unique situation. In-person treatment interactions became increasingly high risk for both patient and provider, and there was an emerging need to conserve personal protective equipment and limit exposure. In response to these developments, physical therapists, occupational therapists, and speech language pathologists treating an adult population turned to telehealth to supplement in-person treatment. This article outlines the clinical reasoning and practical application to implementing a telehealth program in an acute care hospital and includes regulations, identified successful strategies, barriers, considerations, decision-making algorithms, and discipline-specific interventions., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

In developmental biology, the regulation of stem cell plasticity and differentiation remains an open question. CBP(CREB-binding protein)/p300 is a conserved gene family that functions as a transcriptional co-activator and plays important roles in a wide range of cellular processes, including cell death, the DNA damage response, and tumorigenesis. The acetyl transferase activity of CBPs is particularly important, as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affect gene expression. Many studies have described the conserved functions of CBP/p300 in stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model for the in vivo study of the molecular mechanisms underlying stem cell differentiation during regeneration. However, how this process is regulated genetically and epigenetically is not well-understood yet. We identified 5 distinct Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses revealed that Smed-cbp-2 appears to be essential for stem cell maintenance. On the other hand, the silencing of Smed-cbp-3 resulted in the growth of blastemas that were apparently normal, but remained largely unpigmented and undifferentiated. Smed-cbp-3 silencing also affected the differentiation of several cell lineages including neural, epidermal, digestive, and excretory cell types. Finally, we analysed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their functions in planarian stem cell biology. Our results indicate that planarian cbp genes play key roles in stem cell maintenance and differentiation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There is wide variation in the presence of renal replacement therapy (RRT) registries throughout the world, which is a major obstacle to designing and implementing coordinated strategies for chronic kidney disease care and resource planning. Guatemala does not have a national registry of patients on RRT. We describe the result of a cross-sectional study at a national level on epidemiologic and socioeconomic characteristics of hemodialysis patients in Guatemala: most patients were male (57%), above the age of 20 (90%), unemployed (60%), married or in a civil union (53%), had an elementary school education (47%), and living in the geographical clusters in the south of the country. We also describe a free-access website created with the results of the study. Given that Guatemala is still years away from a complete national registry, this information can be used by interested parties in the meantime to promote rational use of limited resources and to inform data-driven health policies.

Retinoic acid (RA) is an important intercellular signaling molecule in vertebrate development, with a well-established role in the regulation of hox genes during hindbrain patterning and in neurogenesis. However, the evolutionary origin of the RA signaling pathway remains elusive. To elucidate the evolution of the RA signaling system, we characterized RA metabolism and signaling in the marine annelid Platynereis dumerilii , a powerful model for evolution, development, and neurobiology. Binding assays and crystal structure analyses show that the annelid retinoic acid receptor (RAR) binds RA and activates transcription just as vertebrate RARs, yet with a different ligand-binding pocket and lower binding affinity, suggesting a permissive rather than instructive role of RA signaling. RAR knockdown and RA treatment of swimming annelid larvae further reveal that the RA signal is locally received in the medial neuroectoderm, where it controls neurogenesis and axon outgrowth, whereas the spatial colinear hox gene expression in the neuroectoderm remains unaffected. These findings suggest that one early role of the new RAR in bilaterian evolution was to control the spatially restricted onset of motor and interneuron differentiation in the developing ventral nerve cord and to indicate that the regulation of hox -controlled anterior-posterior patterning arose only at the base of the chordates, concomitant with a high-affinity RAR needed for the interpretation of a complex RA gradient.

The origin of ancient ligand/receptor couples is often analyzed via reconstruction of ancient receptors and, when ligands are products of metabolic pathways, they are not supposed to evolve. However, because metabolic pathways are inherited by descent with modification, their structure can be compared using cladistic analysis. Using this approach, we studied the evolution of steroid hormones. We show that side-chain cleavage is common to most vertebrate steroids, whereas aromatization was co-opted for estrogen synthesis from a more ancient pathway. The ancestral products of aromatic activity were aromatized steroids with a side chain, which we named "paraestrols." We synthesized paraestrol A and show that it effectively binds and activates the ancestral steroid receptor. Our study opens the way to comparative studies of biologically active small molecules.

Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication-degeneration-complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RARα, RARβ and RARγ. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RARα and RARβ. In contrast, none of the cyclostome receptors studied showed any RARγ-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor-ligand interactions of NRs following WGDs.

The majority of angiosperms are syncarpous- their gynoecium is composed of two or more fused carpels. In Arabidopsis thaliana, this fusion is regulated through the balance of expression between CUP SHAPED COTYLEDON (CUC) genes, which are orthologs of the Petunia hybrida transcription factor NO APICAL MERISTEM (NAM), and their post-transcriptional regulator miR164. Accordingly, the expression of a miR164-insensitive form of A. thaliana CUC2 causes a radical breakdown of carpel fusion. Here, we investigate the role of the NAM/miR164 genetic module in carpel closure in monocarpous plants. We show that the disruption of this module in monocarpous flowers of A. thaliana aux1-22 mutants causes a failure of carpel closure, similar to the failure of carpel fusion observed in the wild-type genetic background. This observation suggested that closely related mechanisms may bring about carpel closure and carpel fusion, at least in A. thaliana. We therefore tested whether these mechanisms were conserved in a eurosid species that is monocarpous in its wild-type form. We observed that expression of MtNAM, the NAM ortholog in the monocarpous eurosid Medicago truncatula, decreases during carpel margin fusion, suggesting a role for the NAM/miR164 module in this process. We transformed M. truncatula with a miR164-resistant form of MtNAM and observed, among other phenotypes, incomplete carpel closure in the resulting transformants. These data confirm the underlying mechanistic similarity between carpel closure and carpel fusion which we observed in A. thaliana. Our observations suggest that the role of the NAM/miR164 module in the fusion of carpel margins has been conserved at least since the most recent common ancestor of the eurosid clade, and open the possibility that a similar mechanism may have been responsible for carpel closure at much earlier stages of angiosperm evolution. We combine our results with studies of early diverging angiosperms to speculate on the role of the NAM/miR164 module in the origin and further evolution of the angiosperm carpel.

Nuclear receptors are transcription factors that regulate networks of target genes in response to small molecules. There is a strong bias in our knowledge of these receptors because they were mainly characterized in classical model organisms, mostly vertebrates. Therefore, the evolutionary origins of specific ligand-receptor couples still remain elusive. Here we present the identification and characterization of a retinoic acid receptor (RAR) from the mollusk Nucella lapillus (NlRAR). We show that this receptor specifically binds to DNA response elements organized in direct repeats as a heterodimer with retinoid X receptor. Surprisingly, we also find that NlRAR does not bind all-trans retinoic acid or any other retinoid we tested. Furthermore, NlRAR is unable to activate the transcription of reporter genes in response to stimulation by retinoids and to recruit coactivators in the presence of these compounds. Three-dimensional modeling of the ligand-binding domain of NlRAR reveals an overall structure that is similar to vertebrate RARs. However, in the ligand-binding pocket (LBP) of the mollusk receptor, the alteration of several residues interacting with the ligand has apparently led to an overall decrease in the strength of the interaction with the ligand. Accordingly, mutations of NlRAR at key positions within the LBP generate receptors that are responsive to retinoids. Altogether our data suggest that, in mollusks, RAR has lost its affinity for all-trans retinoic acid, highlighting the evolutionary plasticity of its LBP. When put in an evolutionary context, our results reveal new structural and functional features of nuclear receptors validated by millions of years of evolution that were impossible to reveal in model organisms.

Retinoic acid (RA) is a vitamin A-derived morphogen controlling important developmental processes in vertebrates, and more generally in chordates, including axial patterning and tissue formation and differentiation. In the embryo, endogenous RA levels are controlled by RA synthesizing and degrading enzymes and the RA signal is transduced by two retinoid receptors: the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). Both RAR and RXR are members of the nuclear receptor superfamily of ligand-activated transcription factors and mainly act as heterodimers to activate the transcription of target genes in the presence of their ligand, all-trans RA. This signaling pathway was long thought to be a chordate innovation, however, recent findings of gene homologs involved in RA signaling in the genomes of a wide variety of non-chordate animals, including ambulacrarians (sea urchins and acorn worms) and lophotrochozoans (annelids and mollusks), challenged this traditional view and suggested that the RA signaling pathway might have a more ancient evolutionary origin than previously thought. In this chapter, we discuss the evolutionary history of the RA signaling pathway, and more particularly of the RARs, which might have experienced independent gene losses and duplications in different animal lineages. In sum, the available data reveal novel insights into the origin of the RA signaling pathway as well as into the evolutionary history of the RARs.

Extensive research carried out over the last 100 years has established that the fat-soluble organic compound vitamin A plays crucial roles in early development, organogenesis, cell proliferation, differentiation and apoptosis as well as in tissue homeostasis. Given its importance during development, the delivery of vitamin A to the embryo is very tightly regulated with perturbations leading to severe malformations. This review discusses the roles of vitamin A during human development and the molecular mechanisms controlling its biological effects, hence bridging the gap between human development and molecular genetic work carried out in animal models. Vitamin A delivery during pregnancy and its developmental teratology in humans are thus discussed alongside work on model organisms, such as chicken or mice, revealing the molecular layout and functions of vitamin A metabolism and signaling. We conclude that, during development, vitamin A-derived signals are very tightly controlled in time and space and that this complex regulation is achieved by elaborate autoregulatory loops and by sophisticated interactions with other signaling cascades., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To present a procedure for opiate detoxication in primary care and to assess results., Design: A retrospective analysis of medical records., Setting: The Valle-Inclán urban Health Centre, Ourense., Patients: The first 58 heroin addicts treated under the standard procedure for detoxication at our centre., Interventions: The method of detoxication based on administering decreasing doses of dextropropoxyphene (Deprancol), accompanied by anxiolytic and hypnotic drugs. The patient attended the clinic, and accompanied by a responsible family member. The treatment ended with naloxone induction., Measurements and Results: We analysed the social, demographic, toxicological and treatment data, always in relation to the result (positive or negative). 85% of patients were male, with average age 27 and average time of consumption > 4 years, with a daily average of 250 mg per day of heroin (125-1,000 mg). 50% were working or studying, 67% lived in their family of origin. The treatment led to a positive result in 79.3% of cases. The only factors which seemed to be associated with this were: age under 30, staying in their original family and the existence of family support for the patient., Conclusions: The procedure developed by our team was effective and would be more so with better choice of patients. It opens up further perspectives for tackling drug dependency from primary care.