Behavioral strategies that depend on sensory information are not immutable; rather they can be shaped by the specific sensory context in which animals develop. This behavioral plasticity depends on the remarkable capacity of the brain to reorganize in response to alterations in the sensory environment, particularly when changes in sensory input occur at an early age. To study this phenomenon, we utilize the short-tailed opossum, a marsupial that has been a valuable animal model to study developmental plasticity due to the extremely immature state of its nervous system at birth. Previous studies in opossums have demonstrated that removal of retinal inputs early in development results in profound alterations to cortical connectivity and functional organization of visual and somatosensory cortex; however, behavioral consequences of this plasticity are not well understood. We trained early blind and sighted control opossums to perform a two-alternative forced choice texture discrimination task. Whisker trimming caused an acute deficit in discrimination accuracy for both groups, indicating the use of a primarily whisker-based strategy to guide choices based on tactile cues. Mystacial whiskers were important for performance in both groups; however, genal whiskers only contributed to behavioral performance in early blind animals. Early blind opossums significantly outperformed their sighted counterparts in discrimination accuracy, with discrimination thresholds that were lower by ∼75 μm. Our results support behavioral compensation following early blindness using tactile inputs, especially the whisker system. Summary: Whisker-mediated touch guides texture discrimination in short-tailed opossums. Texture discrimination sensitivity and associated tactile strategies in these marsupials show behavioral plasticity, which is dependent on sensory inputs available during development. The behavioral strategies that animals use to orient themselves and navigate within complex environments are highly dependent on the sensory context in which they live. Over the long time course of evolution, different species exhibit sensory adaptations to the ecological niche they occupy. For example, many subterranean mole rats that dwell in burrow systems, with little to no light, are naturally blind, with microphthalmic eyes and no functional vision . InsteadTo appreciate the extent to which early sensory context can shape tactile-mediated behavior, we experimentally altered the relative weights of different sensory inputs in short-tailed opossums through bilateral enucleation at a very early developmental stage . Enucleation at P4 in opossums is prior to the onset of spontaneous activity in the retina, and before the formation of retinofugal and thalamocortical pathways . PreviouIn their natural habitat, short-tailed opossums are semi-arboreal and crepuscular , preferrShort-tailed opossums have two prominent sets of facial whiskers – the mystacial whiskers (located on the snout) and the genal whiskers (located on the cheek), both of which are involved in tactile exploration through active whisking . As in rIn the current study, we examined the role of the mystacial whiskers and genal whiskers in guiding tactile-based decisions in early blind and sighted opossums, and measured their behavioral discrimination sensitivity to texture cues. To our knowledge, this is the first psychometric investigation of texture discrimination in a marsupial. Moreover, we compare results from sighted animals with those from bilaterally enucleated opossums performing the same task to examine the extent to which developmental history has an impact on texture discrimination sensitivity and the role of facial whiskers in guiding behavior.Monodelphis domestica (Wagner 1842); three males, three females; 4–16 months] obtained from two separate litters. Three of the six animals were bilaterally enucleated at P4 (see below) and were part of a larger study on developmental plasticity of sensory cortex. See Behavioral experiments were performed in six adult short-tailed opossums , but not when the textural difference was maximal  or minimal . Response bias (b) was inversely related to grit size differences and sensitivity, being high for low Δgrit size stimulus combinations (where sensitivity was low) and low for high Δgrit size stimulus combinations (where sensitivity was high). Response bias did not differ significantly between experimental groups when grit size differences were maximal , minimal  or in the intermediate range . Thus, improved texture discrimination performance for smaller textural differences in early blind opossums can be attributed to improved perceptual sensitivity rather than differences in response bias between the two groups.We applied signal detection theory to separate the contributions of sensitivity . Several studies have reported enhanced tactile perception in early blind human subjects , althougThus, whether or not a specific aspect of tactile performance is enhanced in blind individuals could depend on the behavioral strategies that they used to engage with their environment , among o


Tissue regeneration is found in plants and some animal species. The regeneration process is ubiquitous to all multicellular organisms. Regeneration ranges from healing wounded tissue to whole body neoforming (remaking of the new body). In this larger context, regeneration is one facet of two propagation schemes that dominate the evolution of life. Multicellular organisms can propagate asexually or sexually, and regeneration is a form of asexual propagation. The hypothesis presented here claims that the ability to regenerate is determined by the sexual state of the multicellular organisms . The above hypothesis is supported by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to organs or tissues in nonreproductive conditions or by exposure to sex hormones.Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms . The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to organs or tissues in nonreproductive conditions or by exposure to sex hormones. In the past eras, there was a concentration of research efforts of biologists in general and plant scientists in particular to understanding the molecular basis and function of a handful of organisms. These efforts successfully explain the molecular basis and function of many biological phenomena, ranging from cell division in yeast to photosynthesis mechanism in plants to the basis of genetic diseases in humans. However, tissue regeneration in all phyla received much less attention, albeit its therapeutic and agronomic importance. Usually, regeneration was viewed as a curiosity or an agronomic practice only in plant biology, not a purely scientific process, although it has been used in agriculture for at least hundreds and maybe thousands of years. In animals, regeneration was regarded as a rare phenomenon since it was seldom observed or noticed. However, in the last decades, the understanding that tissue regeneration is a widely distributed phenomenon in the animal kingdom and that it is not necessarily connected to embryonic development can contribute to medicine and agriculture alike. Although our world is rich in organismal diversity, some fundamentally common threads are ubiquitous to all multicellular organisms, such as lipid membranes to enclose the active biochemical zones in all cells; Nucleic acids as genetic material to transfer information between generations and to store operational code for cellular and organismal function; and the ability to regenerate wounds and tissues as a survival mechanism against the harsh environment.Regeneration is principally viewed as a unique plant and some animal species process that is performed in response to wounding, but it can be considered in a larger context. In this larger context, regeneration is one facet of a whole reproduction scheme that dominates the evolution of life and is part of the life history theory. There are two main modes of multicellular organism propagation from generation to generation. The first and most common organismal model of multiplication is sexual reproduction. During organismal sexual proliferation, two gametes  of the species must exist, meet and exchange genes. Thus, a new organism arises that contains the genetic heritage of its predecessors.The second and probably evolutionary earlier mode of multicellular organism multiplication is the vegetative or asexual reconstruction of an entire organism, budding or emerging from an older version. Fundamentally asexual propagation can be viewed as the regeneration of a group of cells (multicellular organisms or tissues) to a whole body and not from an embryo. Parthenogenesis (or apomixes) in the context of asexual regeneration is excluded because it is part of an ordered developmental program where cells change to embryos and develop into a whole organism via the embryonic program but without fertilization. Epimorphic regeneration is one facet of asexual propagation that produces a body section such as a limb or a root. Epimorphic regeneration in animals and plants involves forming a blastema in animals and callus in plants that is necessary for proper organ regeneration to occur; in both cases, these are considered undifferentiated cells capable of regenerating neoformed tissues.This mode of multicellular organism multiplication is more commonly known as asexual reproduction. In asexual reproduction, no wounding is necessary to induce the process. Some examples of asexual reproduction not via parthenogenesis are the budding of Hydra , flatworWound repair in multicellular organisms can be viewed as a particular instance of regeneration. For example, liver tissue repair  can be cSeveral types of regeneration are distinguished in plants  and animHydra (phylum Cnidaria) or flatworm (Platyhelminthes) that regenerate half or entire bodies when severed; plants can regenerate roots from severed stems (where roots did not exist before). When the environment of a leaf tissue segment is manipulated with phytohormones [Plants and some animals can regenerate whole bodies such as hormones ,13,14, ohormones , regenerhormones  or even hormones . Plant cRegeneration in all multicellular organisms is the aggregate of developmental processes responding to external and internal cues. Analysis of the different regeneration phases has proven complicated as well as determining each specific phase’s regulation. The regeneration process is usually divided into three phases, competence, induction, and development ,17. The Plant survival depends on the organism’s genomic flexibility; plants can not escape predation or physically move away from harsh environmental conditions. Nevertheless, plants respond to their environment by changing growth habits and phenotypes. Plants and animals differ significantly in their developmental mode and their reactions to damage and the environment. However, both plants and animals can repair wounded tissue and regenerate organs. Plant cell walls prevent cellular mobility within the plant. Thus, plants must repair or regenerate damaged tissue via the neoforming of existing somatic cells and manufacture the new tissue by cell division of the neoformed new cells. Therefore, as compensation, plants evolved a repair mechanism that allows them to survive at extreme wounding or absent reproductive partners. Plants can be reproduced from cuttings of sections of stems, roots, and bulbs, and some are able to create new embryos from somatic cells. While decades of studying plant tissues’ ability to regenerate a complete fertile shoot or root system after induction, the mechanisms by which somatic cells acquire pluripotency and neoform new entire plant organs remain unknown .miR156 levels, a chronologically regulated microRNA in plants, controls shoot regeneration from leaf slices of tobacco plants by steadily increasing SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) mRNA levels [SPL mRNA levels was correlated to a progressive drop in the regeneration of shoots from tobacco and Arabidopsis tissue [SPLs were shown to regulate multiple age-related processes, such as embryonic pattern formation, juvenile-to-adult phase transition, the timing of flowering, and shoot regeneration ability [SPL gene family members and downstream of SPL like FLOWERING LOCUS T (FT) gene the process of juvenile-to-adult phase transition [There are two types of proliferation modes in nature: sexual and asexual, and regeneration is a form of asexual reproduction. Plants can switch from sexual and asexual propagation, especially annual plants such as trees or bushes. Chronological age influences plant rooting ability or shoot regeneration ,19. Zhan ability ,25,26,27ansition .Camellia, Coleus, Vaccinium, Taxus, and broccoli shoots [Reports in past years have shown that the flowering stage reduces rooting, such as Rhododendron, i shoots ,30. Eveni shoots  showed ti shoots . While ti shoots . The aboDouglas fir [Cabralea canjerana (Vell) is a valuable crop tree that flowers between August to October. When 11 clones of Cabralea canjerana were examined for root regeneration of cuttings during the year, 6 out of the 11 clones exhibited reduced root regeneration during the reproductive season [Aphloia theiformis flowering time September–November, Ilex mitis flowering time Sep-Dec, Prunus africana flowering time September–November (Flora of Zimbabwe https://www.zimbabweflora.co.zw/index.php) all the plants’ flower during the cold season in Madagascar. Root regeneration from cuttings segments of stems was dependent on the season when the cutting was obtained. Root regeneration was maximal during the hot season and very low during the flowering season, the cold season [Rooted cuttings from trees vary between species and even individual tree clones within species, cuttings taken from trees at the juvenile stage regenerate roots more efficiently and rapidly than cuttings from trees at the adult stage, e.g., glas fir , radiataglas fir ,35, and glas fir  as exampe season . There we season . The sped season . Stem cud season . Root reFLOWERING LOCUS T (FT) genes or FT-like genes in flowering plants [FT gene family functions as a general growth hormone regulating shoot or root architecture and promoting organ-specific and age-related determinate growth [FT genes show distinctly different expression patterns during development; timing, tissue specificity, and response to photoperiod are varied [Florigen, a mobile plant sexual state determining phytohormone, is encoded by the g plants ,41. FT ge growth . FT genee varied . Controle varied . Florigee varied . The effe varied . This reIn animals, regeneration is primarily attributed to local or migratory stem cells activity. In plants, locating stem cells’ presence during the initial stages of regeneration has been elusive  or shownThe endogenous sex hormone estrogen may enhance bone marrow mesenchymal stem cells vascular endothelial growth factor production. However, not much information exists on testosterone’s effect on stem cell function. Testosterone decreases growth factor production in stem cells, and the removal of testosterone’s deleterious effects via castration proves beneficial in growth factor production . FallopiThe two dominant models in regeneration research in animals are zebrafish, which regenerate caudal fins throughout life, and Axolotl, which can regenerate limbs both as juveniles and adults. Regenerative capacity decays in mammals such as humans and mice as they become chronologically older, but the organisms stop growing shortly after reaching sexual maturity, unlike Axolotl. The highly regenerative amphibian Axolotl reached sexual maturity about one year after hatching but never stopped growing . It has Zebrafish heart regeneration is enhanced by estrogen supplementation and suppressed by the estrogen-antagonist tamoxifen . Brain-dSchmidtea mediterranea regenerates just as well in sexual compared to asexual. However, it takes a couple of days longer . Planarians, as model animals for regeneration studies, are used for experimentation on tissue regeneration. Many factors affect the Planarians’ regeneration capacity, among them; chemicals, temperature, and seasonal factors. Asexual planarian Dugesia ryukyuensis grows sexual organs and undergoes sexual propagation if fed with crushed adults of the oviparous planaria Bdellocephala brunnea [Bdellocephala brunnea. The level of the steroid sex hormone varies seasonally [Girardiatigrina. However, regeneration in Girardiatigrina was reduced significantly by applying testosterone and enhanced by estradiol [Dugesia ryukyuensis worms were fed, Bdellocephala brunnea crushed worms, sexualization changed according to the sexualization of the food animals [Dugesia tigrina in the summer season exceeded the values of those in the winter, autumn, and spring season [Planarian’s asexual propagation is by body splitting or autotomy and subsequent regeneration. Certain planarians will develop hermaphroditic sexual reproductive organs. The sexual planarians are divided into two groups asexual animals that may, under certain conditions, develop sexual reproductive organs; these are acquired sexuality worms and native sexual worms, which will reproduce only via sperm exchange . Sexual  brunnea . Fukushi brunnea  determinasonally . Externastradiol . When Du animals . In the g season .Hydra can be considered immortal clonal animals. Every discrete polyp can propagate by asexual regeneration to form an unlimited number of offspring, similar to the propagation of an orchard from a single tree. Natural autotomy, when the head of the Hydrozoans separates from the foot and lives independently for days and releases sperm, while not mobile and autonomous as a medusa, it can passively perform and distribute its genetic material at the same time the foot regenerates a new head. Hydrozoans’ propagation is very similar to plants as both can reproduce asexually, and both can breed sexually when environmental conditions worsen. There is no evidence of what is the signal that sends Hydrozoan to propagate sexually. However, in the Hydrozoans, the stem cells used for tissue regeneration are also used to build the sexual gonads (testes and ovaries) every time the animal goes into a sexual propagation mode [Hydra oligactis sexual individuals exhibited lower regeneration capacity compared to nonreproductives or asexuals animals [Hydrozoans breed sexually by combining gametes from male and female individual animals when the environmental condition becomes unfavorable (autumn season). Hydrozoans reproduce asexually by budding a new smaller animal during the summer season. When environmental conditions are favorable for growth, budding is the widespread reproduction method. Regeneration is not only the immediate response to injury, but it is an integrated component of the normal Hydrozoans life cycle, taking part in both sexual and asexual propagation . Thus, Hion mode . Hydra o animals .Regeneration is not a mere curiosity nor an evolutionary relic from primitive multicellular organisms but a process necessary for the proper functioning of multicellular organisms. It is not just embryonic events that remain in various tissues of a few kinds of adult organisms.Hydra allows them to escape aging, but the metabolic cost is high. The regenerative capacity can lead to an extended lifespan under asexual proliferation but requires elevated cell proliferation rates.All multicellular organisms possess a certain degree of tissue regeneration ranging from wound repair to whole-body renewal. However, sexual maturation causes a decline in regeneration capacity and rate in all multicellular organisms. Schaible et al.  suggest Plants regeneration process requires metabolic energy input, as exemplified by the fact that plant explants require sugar (sucrose or glucose) in the media and become a sugar sink during regeneration. The cellular competition between cell types somatic or germline idea is not mutually exclusive from the resource allocation theory. Both thoughts explain the observation that tissue regeneration and sexual reproduction are separate during plants’ and animals’ life cycles. The selective forces that work at the level of cells in plants were yet to be investigated. In animals, it is mostly theory due to the lack of a sound model system. It will indeed have to be well-backed by evidence to show that the cellular-level selective forces are more substantial than  whole-body selective forces. I postulate that the ability to regenerate tissue or a whole body in multicellular organisms is thus maybe linked to the preferred mode of proliferation determined by environmental conditions of the organism or tissue. Once the conditions favoring sexual propagation shut down, clonal reproduction and regeneration can preside after diverting maintenance costs from sexual propagation to regeneration and vice versa. As I work on plants, we are now building a models system in tobacco plants to test the allocation of resources during regeneration and sexual reproduction. These tobacco plants will have visual markers  to visualize the movement of sugar and other metabolites during processes such as rooting (regeneration) and reproductive flowering.A distinct negative correlation is observed all over the animal kingdom between regenerative ability, particularly whole body regeneration, and obligate sexuality . Fields While variation in regenerative properties from amputated salamander limb or severed planarian tail or shoot or root regeneration in plants are present in all organisms, the cells that perform the regeneration all have in common the ability to develop into the primary germline cells and to reproduce and neoform the original tissue that is lost. The dissimilarity between all organisms rests in how this pluripotency potential is regulated and limited in the adult organism. One primary regulator is the asexual or sexual stage of the organism, as manifested by the effect of sex hormones on regeneration capacity. Together with other sources of primary regulation such as age and environment, govern the total pluripotential of cells.


Following a pilot, we refined an oral health carepartner intervention for individuals with mild dementia (IMD). In this intervention, we use behavior change techniques (BCTs) to foster changes by carepartners including using new oral-care techniques and developing skills for using cueing and communications approaches to support behavior changes by IMD ; thus, improving plaque and gingival indices. We describe our approach to refining the intervention manual including a) completing the self-paced BCT taxonomy course, b) developing a coding schema, c) coding the original manual for evidence of BCTs, and d) refining the manual to improve use of BCTS in the refined intervention. Our results detail how BCTs can be applied to refine and improve interventions. This research demonstrates the value in using BCTs for interventions to address how carepartners and IMD can collaborate to improve oral hygiene care.


Purpose: To report an unusual presentation with kyrieleis like plaques in a patient with ocular Behcet’s disease.Case presentation: A 28-year-old young male presented with blurring of vision in the left eye, fundus examination revealing focal segmental intra-arterial plaques involving all branches of retinal artery characteristics of kyrieleis-like plaques with no features of retinitis in retinal periphery and mild vitritis. All routine investigations were normal, the patient testing positive for HLA-B51 marker, diagnosed as a case of ocular Bechet’s disease and managed with oral steroids and immunosuppressive agents. Results: The patient had good recovery of vision with substantial resolution of intra-arterial plaques.Conclusion: Ocular Bechet’s disease can present with uncommon features of kyrieleis like plaques. Ophthalmologists need to be vigilant for the presence of such potential ocular manifestations as the likely initial presentation in order to obtain early diagnosis and initiate timely management.  The exact pathogenesis of Kyrieleis plaques is still not known, but it has been suggested that they may represent an immunological response to an infectious agent resulting in the deposition of immune cells within or adjacent to the vessel wall [2]. Kyrieleis plaques were originally described in association with ocular tuberculosis and are most commonly seen in patients of toxoplasmic retinochoroiditis. The similar plaques have also been reported with Rickettsia conorii, Mycobacterium tuberculosis, Syphilis, and Herpes Simplex infections . It has also been hypothesized to result from extravasation of blood lipids into the arterial walls following retinal arterial damage. Wise et al. suggested that these plaques resulted from arteriosclerosis, but few others found them to be a result of the migration of exudates from active choroiditis to periarterial sheaths [4]. These intra-arterial plaques may heal on treatment with corticosteroids or antibiotics depending on aetiology [5]. It results mainly from deposition of immune cells within or adjacent to the vessel wall [6]. It typically presents as bilateral panuveitis with predominant posterior segment manifestations in the form of vitritis, retinitis, vasculitis and papillitis with potentially blinding complications [7]. Kyrieleis like plaques has not been documented as a feature of ocular Behcet’s disease. In the present case, isolated uniocular presentation with kyrieleis like plaques was seen without any significant anterior segment inflammation, which responded considerably to high dose oral steroids and immunomodulator drugs. Behcet’s disease is typically characterized by a triad of oral ulcers, genital ulcers, and ocular lesions [Our case emphasized that Bechet’s disease can present with atypical ocular features like intraarterial plaques. Therefore, the presence of kyrieleis like plaques in an individual with signs of uveitis, should prompt an ophthalmologist for early systemic investigation, to diagnose and treat underlying aetiology with good visual recovery. Conflict of Interest statementThe author(s) declares that they have no potential conflicts of interest.Informed Consent and Human and Animal Rights statementInformed consent has been obtained from all individuals included in this study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the review board of Military Hospital, Kirkee, Pune, India.AcknowledgementsNil.Sources of FundingNone to declare.DisclosuresNone.


As marine aquaculture of macroalgae expands globally, biologists are working to domesticate species of macroalgae by applying these techniques tested in agriculture to wild macroalgae species. Metabolomics has revealed metabolites and pathways that influence agriculturally relevant traits in crops, allowing for informed crop crossing schemes and genomic improvement strategies that would be pivotal to inform selection on macroalgae for domestication. Advances in metagenomics have improved understanding of host–symbiont interactions and the potential for microbial organisms to improve crop outcomes. There is much room in the field of macroalgal biology for further research toward improvement of macroalgae cultivars in aquaculture using metabolomic and metagenomic analyses. To this end, this review discusses the application and necessary expansion of the omics tool kit for macroalgae domestication as we move to enhance seaweed farming worldwide. Aquacul1.1 |Seaweed farming, and its impact on aquaculture, has evolved over hundreds of years . It bega12) and are the only non-fish sources of natural omega-3 long-chain fatty acids  and nuclear magnetic resonance (NMR) on tissues of interest . The speIn an effort to investigate this relationship between metabolic flow and gene expression, metabolomic data sets are often complemented with RNA sequencing and phenotypic data . To modeE. siliculosus, model red alga Chondrus crispus, or the commercial kelp S. japonica, have been characterized with genomic and transcriptomic methods  required for proper growth and development  are recognized to play an essential role in the health and fitness of aquatic plants and algae. As previously reviewed in elopment . To thatelopment . Given telopment . Exploit3 |High-throughput sequencing, such as shotgun metagenomics, is a powerful resource for understanding microbial communities . AdvanceApplication of these methods to macroalgae domestication is a unique opportunity and a powerful tool for research in agriculture and microbiomes because macroalgae is a fast-growing organism and its overall fitness is tightly intertwined with the native microbiome .3.1 |M. pyrifera), a brown macroalgae that thrives in coastal environments and is a promising resource for future domestic biofuel production. Although giant kelp is one of the fastest growing organisms, farms along the US coast would not produce enough harvest to support giant kelp as a viable biofuel feedstock  and zeta (ζ) diversity , small n (sample size)” problem, many multi-locus models are based on regularization/penalized techniques including LASSO (To accomplish GWAS and QTL analysis, the microbial community should be treated as a multi-trait extended phenotype, with groups of community members or functions considered as different traits. For sparse data sets, pairwise distance matrices using beta-diversity can be used as the quantified host phenotype. Several approaches for multi-trait models have been proposed, but analysis can be challenging with correlated traits such as species abundance . One wayng LASSO , elasticng LASSO , Bayesiang LASSO , and adang LASSO . Other mng LASSO .Despite the broad spectrum of multi-trait and multi-locus models in GWAS and trait prediction studies, only a few of them simultaneously incorporate correlated traits and several associated variants . In prinAddressing these challenges is critical to understanding and properly analyzing the impact of the host genome on the recruitment of the native microbiome. Applications described here have not been applied to the seaweed microbiome and should be explored in more detail to have an impact on the aquaculture industry.4 |Advances in modern omics technology, including in sequencing and metabolite profiling, have created powerful tools and analysis pipelines for understanding the metagenome and metabolome of living organisms. Established pipelines from functional genomics research in agriculture are beginning to be applied to seaweed systems but must be expanded to improve the development of seaweed aquaculture. Metabolomic analysis has been used to fine-tune domestication and crop improvement strategies in agriculture by revealing pathways involved in crop nutrition, flavor, and stress response. Applying metabolomics analyses—alongside other functional genomics analyses—more broadly in marine macroalgae toward improvement of cultivars for aquaculture will allow scientists to identify significant pathways for macroalgae domestication more efficiently.The microbiome plays an important role in the overall health of several macroalgal species and it is imperative to further understand microbial communities in the context of host genotypes to ensure the success of the rising macroalgae industry in the United States. Development and understanding of host–microbe associations in aquaculture can lead to microbial inoculations to boost crop yields, and future breeding programs should focus on the compounded benefit of seaweed genotypes and optimized microbial communities. Further investigation of the microbiome and metabolome in seaweeds has the potential to greatly improve current methods of US macroalgae domestication.By treating the metabolome and microbiome as extended phenotypes, pathways for domestication and optimized breeding go beyond the traditional desired physiological traits in crops, such as size and nutrient load. Specifically, functional traits of the microbiome, such as its ability to fix nitrogen or prevent disease, can be exploited to improve overall crop health and fitness. Application of these tools in macroalgae is a unique opportunity because it is a fast-growing organism that heavily relies on an optimal, environment-adapted metabolic profile, and beneficial microbial interactions.With the rise of marine macroalgae in the aquaculture industry, there exists a unique opportunity to utilize modern developed omics tools to domesticate macroalgae species rapidly, including by optimizing their metabolomic and metagenomic profiles . As futu


Medication nonadherence is common among patients with hemodialysis, leading to poorer patient outcomes. Health care professionals have an important role in assessing risk of nonadherence and intervening to support adherence. The aim of this study was to explore physicians’ and nurses’ current medication adherence practices in hemodialysis settings.A generic qualitative design with inductive content analysis and focus group methodology. Focus groups with health care professionals were conducted in four Nephrology Centers, representing three different regions of Denmark. An interview guide was developed in collaboration with 3 patient representatives.Six focus group interviews involving a total of forty-two health care professionals were conducted. Five main categories were identified; Laboratory tests are the “gold standard” for assessing adherence, suggesting that abnormal results motivated investigation of adherence, Varying practices for supporting adherence, alluding to the impact of individual clinician priority and preference on choice of adherence interventions, Unclear allocation of roles and responsibility, specifically referring to uncertainty in the delegation of roles between physicians and nurses, Navigating time and resource limitations, intimating the resources needed to support medication adherence and Suggestions for future strategies.We suggest implementing systematic use of validated patient-reported outcome measures for assessing adherence and deprescribing tools to support adherence, as these instruments might identify the patients who are in most need of support and promote patient adherence to their prescribed medications. The findings also point to a need for interdisciplinary clarification of roles and responsibilities regarding medication adherence, with the aim of building a strong collaborative partnership between professions.The online version contains supplementary material available at 10.1186/s12882-021-02514-8. Medications and chronic dialysis in combination constitute the primary management of patients with end stage kidney disease (ESKD). The medications used for treating concurrent chronic conditions related to ESKD are erythrocyte stimulating agents, iron supplementation, anti-hyperlipidemia, anti-hyperglycemic, anti-hypertensives and agents for derangements in calcium and phosphate metabolism . For patAccording to the World Health Organization (WHO) adherence to medication can be defined as; the degree to which the person’s behavior corresponds with the agreed recommendations from a health care provider . NeverthAccording to WHO, health care professionals (HCPs) can positively impact adherence by systematically assessing risk of non-adherence and intervening to promote adherence .Previous studies of HCPs’ practice for assessing adherence in hemodialysis settings primarily recruited nurses and pharmacists’ –8. The sIn Denmark, physicians and nurses are responsible for assessing adherence in hemodialysis settings. Pharmacists have no role in adherence assessment or support. We therefore wished to gain an deeper insight into physicians and nurses practice for assessing and supporting adherence to medication and their multidisciplinary collaboration in Danish hemodialysis settings.We conducted a generic qualitative multicenter study according to the COREQ guidelines for the conduct and reporting of qualitative research . Please Participants were sampled from four Nephrology Centers, representing all geographical regions of Denmark . Management at each site recruited participants via purposive sampling according to the following inclusion criteria; physicians and nurses with varying levels of experience with adherence assessment practice in dialysis settings. A minimum of > 3 months practice with adherence assessment was required. Eligible participants were contacted via mail or face-to-face. All of the approached participants accepted participation. Two participants dropped out on the day of the interviews due to illness. All participants provided written informed consent prior to interviews. A total of forty-two HCP’s participated in the focus group interviews Table .Table 1To strengthen the patients’ voice in our research process, we invited three patient representatives to participate in the study , 14. We The authors TMN, NS and GK conducted the focus group interviews. All interviewers had solid clinical experience within nephrology, either as a nurse or clinical nurse specialist and/or -educator. TMN and NS had established relationships with some of the participants from site 1 related to previous and present work tasks. Thus, some of the participant in site 1 knew of the project prior to attending the interviews. These participants were selected to participate in the first two pilot interviews. GK had extensive experience within focus group methodology and the moderator role. Accordingly, GK moderated the pilot interviews at site 1. TMN and NS attended the pilot interviews as trainees. After extensive reading and discussion of the moderator’s role within the team, TMN and NS conducted the rest of the interviews taking turns as moderator or observer during the interviews.Two pilot and four focus group interviews were conducted between February and May 2018 resulting in a total of 6 focus groups. The interviews took place in a staff or conference room near the dialysis unit at each participating site. Only the moderator team and the participant were present. Interviews lasted 60–85 min (in average 71 min). Seven of the physicians were residents in nephrology and thirteen were nephrology consultants. Twenty-two nurses participated, of whom fourteen had over 10 years of experience.We initially drafted a semi-structured interview guide based on clinical experience and relevant literature . The patWe applied inductive qualitative content analysis inspired by Elo and Kyngäs . FirstlyWe identified the following main categories through analysis of the transcribed data; Laboratory tests are relied on as the “gold standard” for assessing adherence, Varied practice for supporting adherence with 4 sub-categories, Unclear allocation of roles and responsibility, Navigating time and resource limitations and Suggestions for future strategies. Please see table Participants relied on clinical and paraclinical parameters as the primary, first-line and most valid approach to determining adherence. Both nurses and physicians acknowledged the potential pitfalls of relying solely on these measures, as they could be confounded by drug-drug and drug-food interactions, introducing a risk of misclassification. Taking this into account, both nurses and physicians categorized patients as adherent, when clinical and paraclinical tests were normal, while they suspected non-adherence when tests were abnormal. The latter motivated closer investigation of the patient’s medication adherence and initiation of supportive interventions.We identified 4 main approaches to supporting adherence. The approaches were not mutually exclusive and appeared to be adopted randomly depending on the preferences, experiences, professional background and priorities of the individual HCP.When clinical and paraclinical tests indicated non-adherence, every physician, and to a lesser extent nurses, described how they engaged in investigating why patients were non-adherent. The preferred approach was interviewing with an emphasis on non-judgmental, open-ended questions such as “take me through which medications you take?”, as opposed to close-ended questions such as “have you taken this medication? This approach was adopted to avoid confrontation and forcing the patient on the defensive.Another common approach, especially employed by physicians but also to a small extent by nurses, was collaborative reviewing of the medication list. All physicians and some nurses saw this as an opportunity to educate patients, ensure understanding of the intended effects of the medication and the importance of adherence for achieving these effects. This included informing patients about the indications for medications, correct dosage, and side effects. Some physicians described using the patient’s medication list as a pedagogical tool for aligning medications, doses and timing of medications. Inclusion of personal hand-written comments and underlined text in the medication list aimed to endorse patients’ and relatives understanding and motivation.Most consultants were prone to reduce complex medication regimes as a way of supporting adherence. This was done based on discussions with the individual patient about their priorities with regard to quality of life, experienced side effects and prioritization of prescribed medications. Reaching a compromise between the patient’s need for medications, acknowledgment of the patient’s values and preferences whilst prioritizing medications with the most well-established evidence-based effect was essential. Contrary to this, residents were more comfortable maintaining status quo or prescribing “add-on” medications to manage “irregularities” in clinical tests or experienced side effects. Most residents preferred to leave what they considered the more complex and potentially controversial decision of deprescribing to the consultants.Few nurses considered deprescribing to be a potentially controversial approach, expressing concern that deprescribing might cause patients to lose faith in medicine, thereby indirectly “legalizing” non-adherence.Specifically, at one site some nurses advocated motivational interviewing or elements thereof as a potential door opener specifically to complex patients with longstanding adherence challenges. When supplemented by other strategies such as dose administration aids, smartphone apps prompting patients to take their medications on time, engaging translators in consultations and enlisting the help of family members in maintaining daily medication-taking routines, motivational interviewing was perceived as a very promising intervention.Nurses had varying perceptions of their role and responsibilities in medication adherence practice. Some nurses rarely engaged in conversations with patients about non-adherence, instead they viewed their responsibility as having to pass information about abnormal laboratory tests on to physicians. Other nurses took it upon themselves to investigate reasons for non-adherence, align medications together with the patient, provide up-to-date medication lists and help patients organize their medications, for example using dose administration aids.Physicians were crystal clear about their role in prescribing, reviewing and reconciling medications with patients. They further took it for granted that nurses discussed and followed up on any medication and adherence issues with patients, ideally in relation to dialysis sessions. The nurses described that this was often not the case, however, often because other more urgent issues related to the dialysis took priority.The participants described an environment of care characterized by demands for efficiency combined with resource limitations. Several sites were challenged by a large turn-over of nurses. Others by implementation of new software solutions which was time-consuming and disruptive of otherwise well-established workflows both internally in the hospital and in the transfer of information to the primary care sector. At several sites, medication lists had changed format, making the reviewing process even more time-consuming. Also, recurring status consultations with nurses had been put on hold indefinitely due to implementation, resulting in consultations now taking place during dialysis in rooms with fellow patients. The frequency of physician status consultations had also been reduced in some sites. Physicians argued that they lacked enough time to complete a medication review, elicit patients’ values, experienced side effects and perceived medication barriers during consultations. In light of the complexity of the patients’ medication regimes and the fact that many patients are cognitively impaired by their kidney disease, participants experienced time restraints and resource limitations as a major barrier to comprehensive assessment and support of medication adherence.Both nurses and physicians advocated for systematic and multidisciplinary medication adherence practices Multidisciplinary medication reviews and alignment of medications with patients were also suggested, preferably with the same HCPs attending over time to ensure continuity of care. One site specifically suggested implementing a multidisciplinary adherence team with expertise in aiding and supporting chronically ill vulnerable patients. Participants highlighted the need for social workers to untangle social and economic issues, interpreters for patients with insufficient Danish language proficiency and stronger collaboration with primary care nurses for elderly patients needing assistance in dispensing and administering medication.Our findings suggest that current practices for assessing adherence relied mostly on laboratory tests, while practices for supporting adherence was dependent on the preferences, experience and prioritization of the individual clinician. Thus, a seeming lack of systematic, standardized approaches among physicians and nurses to supporting adherence was suggested. Time and resource constraints were also found to challenge comprehensive alignment of medications and treatment goals with patients. These findings resonate with prior studies and re-confirm the recommendation of more systematic medication adherence practices with active patient involvement in hemodialysis settings –9. Our fLaboratory tests were denoted as what we have metaphorically termed the “gold standard” for adherence assessment with sparse patient involvement if tests were characterized as normal. HCPs were nevertheless aware of the potential pitfalls of relying solely on laboratory tests, as these tests can be contaminated by drug- drug interaction and food intake. Gilad et al. also found that laboratory test had a central role in the assessment of patients’ adherence in their study . Other sDeprescribing incorporating shared decision-making was frequently applied by the consultants. According to Holmes et al. 2018), deprescribing can be defined as “the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes” . In our , deprescThe strengths of our study include a comprehensive qualitative explorative multicenter approach according to the COREQ guidelines and the use of investigator- and data triangulation to enhance credibility and trustworthiness , 35, 36.We took deliberate steps to assess data saturation during the conduct of the study. However, despite attempts to include younger resident physicians, the majority of participants had more than 10 years of experience in nephrology. We can therefore not rule out that aspects of younger clinicians’ perspectives may have been less illuminated. Throughout the conduct of the study, the research team discussed and reflected on their pre-understanding to ascertain the influence on the data collection and analysis , 36.This study sheds light on current medication adherence practices in Danish hemodialysis settings. Laboratory test as comprised the “gold standard” for assessing medication adherence. Medication adherence practices varied and appeared to depend on the priority and preferences of the individual HCP more than on an agreed-upon systematic, multidisciplinary approach. Participants felt challenged by time and resource restraints which compromised comprehensive medication adherence practices. Lack of clarity in professional role perceptions and allocation of interdisciplinary responsibilities for supporting non-adherent patients were additional challenges.Additional file 1.


Down syndrome  and Williams syndrome (WS) are two neurodevelopmental disorders of genetic origin that are accompanied by mild to moderate intellectual disability but exhibit distinct cognitive profiles. In this review we discuss our recent work characterizing the real-world spatial learning and memory abilities of adult individuals with DS and WS. We used several different paradigms in which participants locomote freely and have access to coherent input from all sensory modalities to investigate their fundamental egocentric (body-centered or viewpoint-dependent) and allocentric (world-centered or viewpoint-independent) spatial abilities. We found unequivocal evidence that most individuals with DS exhibit low-resolution egocentric and allocentric spatial learning and memory abilities similar to typically developing (TD) children in the same mental age range. In contrast, most individuals with DS exhibit impaired high-resolution allocentric spatial learning and facilitated response learning as compared to TD children. In comparison, whereas most individuals with WS also exhibit facilitated response learning, their low-resolution allocentric spatial learning and memory abilities are severely impaired as compared to both TD children and individuals with DS. Together with work from other laboratories using real-world or virtual reality paradigms, these findings indicate that in order to navigate in their environment most individuals with DS may use either egocentric route learning that does not integrate individual landmarks, or a low-resolution allocentric spatial representation that encodes the relationships between different locations . In contrast, since most individuals with WS are unable to build or use a low-resolution allocentric or configural representation of the environment they may use visually and verbally encoded landmarks as beacons to learn routes. Finally, we discuss the main neural structures implicated in these different spatial processes and explain how the relative preservation or impairment of specific brain functions may engender the unique cognitive profiles observed in individuals with these neurodevelopmental disorders. Down syndrome  and Williams syndrome (WS) are two neurodevelopmental disorders of genetic origin accompanied by mild to moderate intellectual disability. Despite the fact that individuals with DS and WS have relatively similar IQs , which striatum  and cerestriatum . Interesstriatum , 25, 26 Although prior to our recent studies no previously published study had unequivocally shown the preservation or impairment of either egocentric or allocentric spatial memory capacities in DS or WS, the importance of characterizing basic spatial memory capacities in individuals with intellectual disability are manifold. First, since allocentric spatial representations enable flexible behavior, the ability to create and use such representations is particularly important for developing independence and autonomy. Second, allocentric spatial memory is a fundamental component of episodic memory and thus may serve as a proxy for assessing episodic memory function, especially in individuals with impaired language function. Third, because allocentric spatial memory is one of the hallmark cognitive processes studied in mouse models of DS and WS, clarifying the state of this cognitive process in humans with WS and DS is critical in order to validate rodent models. Fourth, comparing the spatial capacities of individuals with DS and WS can identify cognitive deficits that are syndrome-specific and not just due to general intellectual disability, thus highlighting genes and brain structures that are implicated in these processes. In sum, understanding the relative preservation or impairment of egocentric and allocentric spatial capacities in individuals with these two different genetic syndromes is not only important for helping these individuals and their caregivers to adopt appropriate learning strategies to augment autonomy, but may also provide critical information concerning brain structure-function relationships in both typical and atypical development.When we began our investigations to characterize the allocentric spatial capacities of individuals with DS only one other study had investigated the spatial capacities of this population in a real-world environment. In his unpublished doctoral studies, Mangan studied the response learning, cue learning, and place learning abilities of children with DS and TD children from 16 to 28 months of age . AlthougPrevious studies in our laboratory had shown that from 3.5 years of age TD children can use an allocentric representation to learn and remember with above chance probability the location of three rewarded locations amongst 18 potentially rewarded locations in the open-field paradigm . Since tWe found that individuals with DS performed similarly to TD children when local cues marked the reward locations , confirmThe 10 individuals with DS who performed above chance level exhibited a preference for searching location 5 for their first choice after entering the arena. This finding was revealing because, as is discussed below, in recent years our work and the work of others has provided behavioral and neurological evidence that different spatial competencies, subserved by distinct hippocampal circuits, are necessary for low-resolution “topological” and high-resolution “metric” allocentric spatial coding –35. ConsWe tested the abilities of 27 individuals with DS , 18 individuals with WS , and 19 TD children  to learn and remember the location of one reward amongst four potentially rewarded locations  contribIndividuals with DS exhibit relatively preserved low-resolution allocentric spatial and cognitive mapping abilities . InIndividuals with WS exhibit severely impaired low-resolution allocentric spatial and cognitive mapping abilities . NeOur behavioral findings of impaired homing and allocentric spatial/cognitive mapping abilities in conjunction with facilitated response learning in individuals with WS are consistent with specific dysfunctions in both egocentric processing associated with the dorsal visual stream, as well as allocentric processing associated with the hippocampal formation and directly interconnected brain regions, in particular the retrosplenial cortex. Importantly, the present findings rule out the possibility that spatial impairments in WS arise from the active integration of a corrupted signal from the dorsal visual stream into higher-order regions fundamental for spatial processing that function even in the absence of vision in typically developed individuals. Rather, these findings raise the possibility that integration of corrupted dorsal visual stream information during development permanently and fundamentally changes how spatial information is processed in the hippocampus throughout life in WS.Our studies using real-world laboratory paradigms in which participants locomote freely provide a new and comprehensive perspective on the specific profiles of spatial learning and memory abilities of individuals with DS and WS. As compared to TD children in the same mental age range, the majority of individuals with DS exhibited preserved low-resolution egocentric and allocentric spatial learning and memory abilities, but impaired high-resolution spatial abilities. Interestingly, this spatial memory profile is consistent with neuroanatomical evidence suggesting that hippocampal dysfunction may be linked to abnormalities in the dentate gyrus-CA3 region in DS. In contrast, nearly all individuals with WS exhibited severely impaired low-resolution allocentric spatial learning but facilitated egocentric response learning. This spatial memory profile is consistent with neuroimaging data suggesting impaired processing in the dorsal visual stream and hippocampal dysfunction in WS. Together with work from other laboratories, our findings suggest that in order to navigate in their environment most individuals with DS may use either egocentric route learning that does not integrate many individual landmarks, or low-resolution allocentric spatial representations that encode the relationships between different locations . In contrast, most individuals with WS may use visually and verbally encoded landmarks as beacons to learn routes but they are unable to build or use low-resolution allocentric or configural representations of the environment.PB and PL were responsible for the conception and design of the work, acquisition, analysis and interpretation of the data, and writing of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The study of neuroinflammation provides an exciting opportunity to rapidly understand therapeutically amenable components of many illnesses embedded within the core practices of neurology and psychiatry. In addition to crucial therapeutic benefits, advances in understanding the immune basis of primary autoimmune conditions can present key aetiological and diagnostic insights. Recent advances have led to the growing appreciation for a role of the immune system in the pathogenesis of many other conditions, considered likely to have non-immune primary drivers . These cIn all these, potential immune contributions offer therapeutically tractable approaches. From a biological perspective, a more comprehensive understanding of clinically relevant neuroimmune interactions naturally segues into important basic questions about the anatomy and function of connections between the periphery and the CNS , and theBrain between 2020 and 2021 and use these as a focal point to offer a vision of how anticipated developments in neuroinflammation are likely to impact our understanding of key elements of neurology, and lead to new treatments. In addition, this vision will provide a framework for a series of review articles to stimulate ideas and highlight some of the most exciting areas within this rapidly expanding, clinically relevant and highly translational field.Herein, we highlight eight top neuroinflammation publications in N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis.,in vitro and in animal models.,The autoantibody-mediated diseases of the nervous system provide perhaps the most direct examples to connect an identified pathogenic agent with the corresponding disease process. In these conditions—ranging from myasthenia gravis and neuromyelitis optica to autoimmune encephalitis—autoantibodies target extracellular domains of neuroglial proteins and patients often show highly distinctive, even unique, clinical features. In autoimmune encephalitis, these include faciobrachial dystonic seizures and multiple frequent focal seizure semiologies in patients with leucine-rich glioma-inactivated 1 (LGI1) antibodies,in vivo model systems prior to application of patient NMDAR antibodies.To test this hypothesis at the molecular level, an allosteric modulator of the NMDAR—which crosses the blood–brain barrier—was applied to culture and Indeed, it is possible that in a patient in whom relentless autoantibody production is ongoing, efforts to block end effector autoantibody-mediated mechanisms of brain dysfunction prove fruitless. In contrast, the underlying immunology may present greater therapeutic value. Furthermore, in autoantibody-mediated diseases, working backwards from the soluble autoantibodies to the autoantigen-specific B and T cells and, ultimately, the auto-immunizing events, should provide a far more comprehensive account of disease pathogenesis. Yet, despite the multipronged importance of the immunobiology, few studies have addressed this aspect.Brain isolated a suite of LGI1-specific B cells from patients and retrieved individual LGI1-reactive immunoglobulins to characterize aspects of the disease immunology and neuroscience, in parallel.in vitro and in vivo—with a marked dependence on the targeted epitopes and individual antibody affinities. Hence, the results of this study suggested that the precise nature of the matured autoimmune response could determine its potential pathogenicity.A recent paper in In neurodegenerative diseases, dominant theories concern the necessary and sufficient nature of toxic aggregated proteins as directly pathogenic agents. Removal of these neuroactive species in patients has harnessed a major supremo of immunology: the monoclonal antibody. For example, an amyloid-directed monoclonal antibody effectively removed plaques in humans with Alzheimer’s disease.Brain studied over 100 Down syndrome brain specimens and cultured primary neurons from individuals between 16 gestational weeks and 64 years old.A recent article in Brain paper describing a robust CD8+ T cell infiltration into the substantia nigra pars compacta of Parkinson’s disease brains was a major breakthrough.+ densities in samples with fewer dopaminergic neurons. Perhaps most importantly, these observations were apparent prior to the accumulation of α-synuclein, supporting the author’s bold suggestion that the immune system may ‘initiate and propagate neuronal death and synucleinopathy in Parkinson’s disease’. Together with the identification of antigen-specific T cells and HLA variants in Parkinson’s disease,While attention regarding neuroinflammation in neurodegeneration has centred on innate immune mechanisms, a few reports have provided additional insights by studying the antigen-experienced acquired limb of immunity. Hence, a ,The varied facets of crosstalk between immune and nervous systems are clear when attempting to understand or treat autoimmunity and neoplasia. These carry inherent challenges due to the yin-yang of necessary immunosuppression in inflammatory conditions and obligatory immune stimulation for tumour defence. The latter provokes autoimmunity,,Brain offers a combination of different mechanisms leading to lowered immunity not exclusive to brain tumours, but present in several acute neurological insults and thus possibly specific for the CNS.This double-edged sword of immune mechanisms may not be the only enigma when considering the lack of successes in treating glioblastoma. Recent exciting discoveries suggest neuronal properties of glioblastoma tissue.Despite several decades of research, the field of multiple sclerosis, the most frequent classical autoimmune disorder of the CNS potentially leading to devastating disability in young adults, on the one hand regularly delivers exciting novelties, but on the other still lacks full clarification of the pathology as well as sufficient evidence for successful therapies. Moreover, it is still unclear how the disease is initiated or why grey matter damage patterns—most relevant for disability—seem to differ in different periods of the disease and across brain/spinal cord regions. Unexpected outcomes of treatment trials have revealed that, for example, B cells and cytokines  serve roles other than those originally identified—also pointing to difficulties of ‘true’ translation dogmatically controversial within the community. However, technical advances in immunological and neuroscientific methodologies have led to significant progress and regularly unearth unexpected findings. One recent example is the possibility to detect the extent of neuronal injury outside of the brain, via the assessment of neurofilament light chain (NfL) levels in blood. The value of NfL for clinical progress, namely supporting prognostication and therapy selection, is just one example of stratification, which might benefit both patients and physicians in the near future.After great efforts, the first therapy for primary progressive multiple sclerosis tackling grey matter pathology was achieved by B cell depletion. Bringing different research angles together, a recent experimental study published in this journal demonstrates that novel Bruton tyrosine kinase (BTK) inhibitors, which target B cells, in fact reduce leptomeningeal lymphoid follicles thought to be a feature of progressive multiple sclerosis.Nevertheless, it is surprising how many open questions remain. Given the intensive research and advances in the gut-brain axis, including the influence of nutrition and environment; novel roles for old players, such as astrocytes; and significant developments regarding lymphatics, glymphatics and CNS barriers. Specific points that will need to be clarified include: (i)Why are current therapeutics more effective if they are commenced in the first few years after disease onset?(ii)Why are they less effective in older people?(iii)How can progression be tackled more efficiently than by depleting immune cell populations?(iv)What happens to beneficial roles of the immune system in the CNS upon immunosuppressive or immunomodulatory therapy?(v)Should neural precursor cells still be pursued as a therapeutic option?(vi)Given the disappointment with negative anti-LINGO antibody trials, is remyelination still a possible treatment goal?(vii)Are there unidentified roles of the immune/nervous system crosstalk beyond what is known and what has been indicated by the large genetic map developed by the International MS Genetics Consortium IMSGC?(viii)Which experimental successes—such as the intrathecal mesenchymal cellular approach highlighted in this journalWe have made enormous strides in treating acute stroke, however, the subacute phase where there are cellular infiltrates and inflammation still remains a challenge. Understanding the pathophysiology in humans and appropriate animal models such as non-human primates or other animals that have chronic risk factors similar to patients with stroke could help advance the field by identifying new modes of intervention. Although the potential role of inflammation in mediating atherosclerotic injury and cerebrovascular disease has long been debated, the relationship between the two remains unclear.One way to address this might be to determine the pattern and magnitude of cerebrovascular disease in patients with known inflammatory disorders of the CNS. In a study published in this journal, the authors characterized the brain and systemic vascular pathology in the arterial system in patients with multiple sclerosis at autopsy.Stimulation of innate immune responses is considered detrimental to the brain and have been implicated in the pathophysiology of several, if not most, chronic neuroinflammatory, neuroinfectious and neurodegenerative diseases.et al.By analogy, a study recently published in this journal showed that the gamma subunit of complement component 8 (C8G) inhibits neuroinflammation.There is a close relationship between microbial pathogens and inflammation. The immune system is the major defence against these organisms. A significant immune response can result in clinical manifestations from an inflammatory syndrome such that the organism itself may get masked and hard to detect. This is most apparent in the brain where even small amounts of inflammation can be symptomatic. For these reasons, viruses have long been suspected to be the aetiological agent for many neuroimmune and neurodegenerative diseases but this has been hard to prove. For example, over the years, several viruses have been implicated as the aetiology of multiple sclerosis, including canine distemper virus, Epstein Barr virus, human herpesvirus 6, retroviruses and others but none has been proven as of yet. Similarly, herpes viruses have been implicated in Alzheimer’s disease and retroviruses in amyotrophic lateral sclerosis. These relationships are active areas of investigation and major efforts are underway to determine the role of these agents in the pathophysiology of several neurological diseases.All the same, it is clear that under some circumstances, viral infections can trigger well known autoimmune diseases. For example, herpes simplex virus type 1 encephalitis can result in an autoimmune encephalitis by generation of autoantibodies to neuronal receptors.These virus-triggered immune syndromes or post-viral syndromes have never been more apparent than what we are facing today in the most extraordinary and unprecedented times of the SARS-CoV-2 infection. This virus, similar to other coronaviruses, rarely causes encephalitis yet it can associate with several neuroimmune disorders such as acute disseminated encephalomyelitis, acute necrotizing haemorrhagic encephalopathy, microvascular disease with antiphospholipid syndrome, transverse myelitis, myositis and Miller-Fisher syndrome.Of major concern is that many patients who developed mild symptoms during the initial phase of the pandemic are now complaining of multiple neurological symptoms such as exercise intolerance, dysautonomia, cognitive dysfunction and pain syndromes. The possibility has been raised that these patients may not have cleared the virus due to a lack of a robust immune response in the initial phase resulting in persistent or restricted viral.Brain aims to publish updates and review articles on some of these topics and invites researchers to submit manuscripts that explore relationships between the microbes and human nervous system disease.A prevailing concept is that all microorganisms invade humans from the external environment. However, a large part of the human genome contains relics of prior viral infections that were incorporated over the process of evolution and then, over millions of years, have made multiple copies of themselves within the genome and acquired many mutations along the way. These retroviral elements have acquired important physiological functions in early embryonic development but are epigenetically silenced in adults. Reactivation of these viral elements have been described in various cancers and have recently been associated with neuroinflammatory and neurodegenerative diseases.Despite rapidly emerging insights into the mutual interaction of the immune and the nervous systems, in particular within the CNS, several rarer disorders, like sarcoidosis and cerebral vasculitis, remain ‘under-researched’ areas, often without sufficient mechanistic and investigational precision. The same is currently true for post-infectious disorders including so-called ‘long COVID syndrome’.Brain we are keen to publish methodologically sound clinical trials that offer insights into disease pathogenesis.An area of key interest, and with potential for major public health benefits, surrounds the contributions of autoimmunity and inflammation in primary psychiatric conditions. Within these disorders, the emerging concepts of immune-dependent brain homeostasis or resilience may exert major influences.Brain in the recent past focused on neuroinflammation. We invite authors to submit manuscripts in related areas that study human populations or experimental models and further our knowledge of these complex and emerging neuroimmune interactions.Neuroinflammation is a rapidly evolving field with the realization that inflammatory cascades play an important role in the pathogenesis of several neurological diseases. However, the inflammatory response is complex and the cell types and signalling pathways involved may be disease-specific. Further, neuroinflammation can be both protective and detrimental to the host. Hence, a thorough understanding of these mechanisms and an open approach to both basic experimental and human study strategies is critical for development of optimal therapeutic strategies. We have highlighted several manuscripts published by


Scientific Reports 10.1038/s41598-020-78996-7, published online 14 December 2020Correction to: The original version of this Article previously published contained lower resolution images for Figures 1 and 5.In addition, the last paragraph of the Discussion section was a duplication of information contained in the second last paragraph and has now been removed.The original last paragraph is provided below.47, and could be used to transport DNA into its internal compartments for subsequent LAMP amplification and BART detection. Similarly nanopore DNA sequencing approaches have been applied in droplet interface bilayers51,52 and could be combined with preceding in situ LAMP amplification within the droplet itself. DNA expression through in vitro transcription and translation (IVTT) has been demonstrated in similar droplet interface bilayers systems, along with the ability to incorporate subsequently expressed protein channels in their lipid bilayers44,45,46, in combination this would enable multistep compartmentalised functionality akin to biological cells. In this regard, the multicompartment nature of the eDIB constructs may allow for multiple assays to take place within a single eDIB, for example. Or for more complex chemical processing to occur via the transport of molecular species through pores or channels within the lipid bilayers of the droplet network to link otherwise segregated reaction chemistries. Furthermore, low copy DNA sequence specific triggers may be harnessed with LAMP, to generate and amplify coupled biochemical responses energised via the associated avalanched generation of pyrophosphate from the LAMP reaction which is subsequently converted to ATP. This is exemplified here in the form of light emitting artificial cells, with the temporal growth and subsequent inhibition of light emission determined by DNA concentration. In addition to application in soft-matter diagnostic devices for DNA detection, this approach could be harnessed as a generic reporting mechanism in smart artificial cells, or coupled to other ATP dependent biochemistries as a means for artificial cell energisation.”“These experiments provide a proof-of-concept for DNA to be amplified and detected within the droplets of an eDIB artificial cells. This represents a foundation for the use of eDIBs as stable, storable, self-contained analytical devices to detect specific DNA sequences in liquid samples. Membrane protein channels have been shown to be able to insert in the lipid bilayers of eDIBsThe original Article has been corrected.


Recent research has indicated a seemingly increased propensity for both falls and accelerated bone loss in people living with HIV (PLWH). Physiotherapists play a crucial role in optimising function and quality of life of PLWH through prevention of falls and reducing the harm that results.This study aimed to explore physiotherapists’ awareness of falls risk and accelerated bone demineralisation in PLWH and their perceptions of current falls prevention strategies in the care of PLWH in selected regions of sub-Saharan Africa.An exploratory descriptive qualitative research method was employed to explore physiotherapists’ perceptions and experiences regarding bone health and falls in PLWH. In-depth semi-structured telephonic interviews were used to collect data from 21 physiotherapists working in primary HIV care. Transcribed interview data were coded in Atlas.ti.8® and analysed using inductive thematic analysis.The primary study revealed a lack of awareness by physiotherapists of falls risk and bone demineralisation in PLWH. As such, physiotherapists did not link falls or fractures to HIV or antiretroviral therapy (ART) when they did observe such events during their general patient assessments. However, in retrospect, some physiotherapists were able to recognise risk factors linked to falls in those with HIV. Current services for falls prevention, as perceived by the physiotherapists, were sub-optimal.Physiotherapists may need to be more aware of the potential risk of falls and bone demineralisation in PLWH and routinely assess for these phenomena in both older and younger PLWH.The online version contains supplementary material available at 10.1186/s12913-021-06343-1. Falls among people living with HIV (PLWH) is an emerging concern. The first study was published recently, in 2012 . As affoThe scope of physiotherapy practice in the rehabilitation of PLWH in the ART era is progressively being understood by physiotherapists in LMICs , 6. RandA knowledge gap exists regarding physiotherapists’ awareness of falls and bone demineralisation in PLWH or falls prevention practices for this population, especially in sub-Saharan Africa where the greatest burden of HIV exists . StudiesAn exploratory descriptive qualitative study was used since little is known about this topic. Ethical approval was obtained from the Health Research Ethics Committee of Stellenbosch University (S18/07/137) and permission to conduct the study granted from the health professions or research regulatory bodies in all four countries. Written informed consent was obtained from all participants prior to the interviews. This paper reports on a subset of interview data collected regarding physiotherapists’ awareness of fall risk and accelerated bone loss in PLWH. The other interview data has been used to report on health care system challenges affecting falls prevention in PLWH and has been reported in another paper . The repAll investigators were physiotherapists and had experience in qualitative research.We purposively sampled physiotherapists who had at least two years’ experience in the primary care of PLWH and were currently working in public primary care facilities in the urban districts of the capital cities of four sub-Saharan African countries . Physiotherapists were excluded if they were not currently registered with their respective physiotherapy boards/councils and if they did not provide written consent. Randomised lists of primary health care (PHC) facilities from each selected district were created using the automated function in Microsoft Excel. Following these lists, the randomly selected PHC facilities were telephoned to identify physiotherapists who met the inclusion criteria. Participant information booklets and consent forms, in which the nature and purpose of the study was fully explained, were electronically mailed to willing participants. Participants who returned their signed consent forms were further contacted to arrange for an interview within a month’s timeframe.According to recommended sample size for phenomenological studies , it was Telephonic in-depth interviews took place between December 2018 and July 2019 at pre-appointed times that would not interrupt the participants’ clinical practice. All interviews were conducted by the primary investigator (PI) although a second interviewer (KB or QL) was present to ensure consistency and coherence. An interview guide , frailty, muscle wasting, dizziness, ART non-adherence and comorbidities such as depression, tuberculosis, cerebral meningitis, stroke, hypertension, Kaposi Sarcoma and peripheral neuropathy. Two physiotherapists were aware of the negative impact of falls on the lives of PLWH, mentioning consequences such as fear of falling and fall-related fragility fractures.‘Some of my patients have presented with just general complaints after starting ARV’s maybe, they are feeling tired, they are feeling weak and also like general joint pain or body pains as well … I can’t say that it has been on their bones no.’ Participant 8, South Africa.‘I don’t have enough understanding on that aspect. I only know that ART can have an effect on the nerves … On the nerves, yes, I know, but on the bones, I am not so much sure.’ Participant 11, Zambia.Some felt that it would require a bit of research to compare the differences in BMD of PLWH and seronegative patients. All the facilities did not have dual energy x-ray absorptiometry (DXA), considered the gold standard for BMD measurement. Most used normal x-rays as their main diagnostic tool for osteoporosis with limited use of computer topography due to its high cost.Most physiotherapists were not aware of the effect of HIV infection or ARVs on increased risk of bone demineralisation in PLWH. They were aware of other side effects of ART such as lethargy, paraesthesia and myalgia but not accelerated bone loss.n = 3) supported the fact that ART or HIV infection itself can have a negative impact on BMD, having observed osteoporotic bones on X-rays of PLWH. A few cases of pathological fractures in PLWH were also reported. Some participants attributed bone loss in PLWH to effects of prolonged bed rest rather than effects of ART or HIV infection itself.A minority of the participants  was the most mentioned outcome measure used for assessment of balance, which the physiotherapists carried out as part of their generic assessment without specifically assessing for falls.Lack of rehabilitation-specific generic falls assessment tools in their facilities to guide them in their provision of care to any patient, let alone tools specific to PLWH, emerged as one of the hindrances to fall prevention practice. It was left to individuals’ discretion to decide which tool to use for assessment of falls in PLWH.‘From what I recall we would be the end point … ’ Participant 17, Zimbabwe.‘Inasmuch as I know people refer these patients to me so that I prevent the falls. I get referrals and then I address the issue. I don’t refer to anyone else cause they would have been passed onto me.’ Participant 20, Zimbabwe.Some physiotherapists were aware of the need to involve other health care professionals in their management of falls risk. Health care professionals mentioned included dieticians, ophthalmologists, psychologists, social workers, and occupational therapists. However, two participants did not see the relevance of referring to other health care professionals once the patient had been referred to them.This is the first study to explore the awareness by physiotherapists working in primary care facilities in sub-Saharan Africa of falls risk and bone demineralisation in PLWH and current fall prevention practice. The physiotherapists lacked adequate awareness of falls risk and bone demineralisation among PLWH. They did not necessarily link falls or fragility fractures to HIV or ART and deemed fall prevention services to be sub-optimal. The findings from this study have several implications for physiotherapy practice.The study results demonstrate a need for physiotherapists to be more anticipatory of the risk of falls and bone demineralisation when assessing PLWH. Most physiotherapists were not aware and therefore did not consider falls when assessing PLWH. The main reasons PLWH were referred to physiotherapy were linked to comorbidities such as tuberculosis, cerebral toxoplasmosis, Kaposi sarcoma and polyneuropathies that resulted in pain, altered function, and reduced QoL. The physiotherapists would often prioritise the pain, motor deficits and respiratory dysfunctions. The risk of falls and related fractures were often assessed as a safety precaution before mobilising patients with obvious balance and co-ordination problems. No comparable studies were identified on awareness of falls in PLWH and physiotherapists (85%) seem to be more aware of falls in other at-risk populations, such as stroke survivors  and geriMost participants’ responses were inclined towards hospitalised PLWH post-fall, while information about community-dwelling PLWH mostly emerged after probing. By considering physiotherapists working in primary care settings for inclusion in this study, it was expected that most responses would concern primary falls prevention among community-dwelling PLWH. This finding could mean that less falls occur in community-dwelling PLWH compared to hospitalised PLWH. On the other hand, community-dwelling persons may have experienced more falls than hospitalised persons  . HoweverThe need for physiotherapists to be wary of falls in PLWH is further augmented by the finding that physicians rarely referred patients specifically for falls management, but rather for mobility. Chou et al.  reportedAlthough some participants were aware of the risk factors for falls in PLWH, most did not use standardised screening tools or outcome measures to identify and assess PLWH at risk of falls. A few participants used the BBS as an outcome measure in balance assessments. Physiotherapists’ inconsistent use of screening tools for falls has been documented. For example, although 56.9% of the physiotherapists in one Belgian survey  acknowleWith regards to screening for BMD loss, most participants were not able to access Dual-energy X-ray absorptiometry (DXA), a tool most predictive in identifying patients at high fall risk because of BMD loss . The phyA few differences were noted between the countries and health care settings that may have influenced the perspectives of the physiotherapists about the risk of bone demineralisation and falls in PLWH. Botswana and South Africa, both upper-middle income countries, had a few physiotherapists (less than a third) who were aware of falls in hospitalised PLWH. These were mostly from facilities that had gone through the hospital accreditation process which may have reinforced fall prevention as part of patient safety . AnotherBy considering physiotherapists working in urban districts of the selected cities, the results of this study may not be generalised to physiotherapists working in rural primary HIV care settings where different health system structures and patients with different socio-demographic profiles may exist. Also, our sample may have been biased towards a more knowledgeable sample since some participants declined participation in the study because they felt they had insufficient knowledge about the subject.Further research is needed to establish the magnitude of certain problems highlighted in our study by quantification of data. For example, a quantitative survey would determine what proportion of physiotherapists lack awareness of falls and bone demineralisation in PLWH and therefore whether there is a need to employ interventions to raise an awareness among physiotherapists.Word clouds  may not have been the most accurate way to display the current falls prevention strategies as they conflate the number of participants who used a word and the number of times all participants used a word . HoweverFindings from this study indicate that physiotherapists in sub-Saharan Africa are not aware of the potential risk of falls and bone demineralisation in PLWH, and thus do not routinely assess for these phenomena in both older and younger PLWH. Meanwhile, more research is evidently needed regarding falls in PLWH and the effects of BMD loss on falls in PLWH, especially in sub-Saharan Africa. This evidence may form the basis for revision of undergraduate rehabilitation curricula and continuous professional education needed to improve awareness and delivery of care among physiotherapists and other health professionals involved in primary HIV care. Evidence-based practice will ultimately result in improved health care outcomes and quality of care for PLWH.Additional file 1.


With the advancement of cancer treatment and minimally invasive surgery, the indications for surgery for metastatic spinal tumors are expanding. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by calcification and ossification of ligaments and entheses. In Japan, the prevalence of DISH is increasing with its superaging society. The purpose of this article is to report a case of applying a novel screw technique for pathological fracture in a patient with DISH and spinal metastasis. An 80-year-old man with spinal metastasis presented with acute onset of severe back pain, and investigations revealed a fracture of a metastatic lesion in T10–T12 in the range of DISH. We performed posterior fixation with a percutaneous pedicle screw system using a penetrating endplate technique. The patient's back pain improved, and he was able to mobilize with minimal assistance and survived for 8 months with a good quality of life. Spinal fracture accompanied by DISH sometimes occurs with severe instability because of injury across 3-column injury and its long lever arm. Spinal instability neoplastic score indicates instability of pathological fractures of spinal metastases but needs to be evaluated carefully when DISH is present. The prevalence of DISH is increasing in the elderly, and penetrating endplate screws can be an effective option in posterior fusion surgery for patients with DISH and spinal metastases. Surgical treatment of spinal metastases is largely palliative. The aim of palliative surgery in such cases is to improve pain control and reduce or eliminate neurological deficits, thus improving the patient's quality of life . With thDiffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by calcification and ossification of ligaments and entheses . ResnickRecently, several studies reported the efficacy of a transdiscal screw technique with its strong fixing force for some instances of lumbar degenerative disease –15. DISHWe have applied a transdiscal “penetrating endplate screw (PES) technique” to fix thoracolumbar DISH-related fractures in patients with spinal metastasis.An 80-year-old man had a history of cervical OPLL surgery and multiple lumbar degenerative disease surgeries. He had been diagnosed with renal cell carcinoma (RCC) and underwent surgery to excise the tumor 12 years ago. He received radiation therapy and bone-modifying drug therapy 5 years later for thoracic spine metastasis, lung metastasis, and lymph node metastasis . The patHere, we have applied a transdiscal screw to fix a thoracolumbar DISH-related fracture in a patient with spinal metastasis. In recent years, rapid progress has been made in the treatment of malignant tumors, and with the development of anticancer drugs, widespread use of tumor-targeted therapy, and the advent of molecular-targeted drugs, patients with cancers who were previously expected to have a prognosis of only a few months once metastasis to the spine was confirmed can now be expected to survive for years , 2. TherPatients with DISH-related vertebral fractures are at risk of developing delayed paralysis due to their immobilized spinal column and significant fracture site instability with long lever arms –24. SurgAdditionally, patients with DISH tend to be of advanced age with multiple comorbidities, indicating a high rate of complications and perioperative mortality –23. RigiIn this case, the patient's SINS was 12: intermediate instability. However, the patient had DISH in his thoracolumbar spine, so the instability was considered to have been higher than indicated by the SINS. Spinal fracture accompanied by DISH sometimes occurs with severe instability because of injury across 3 columns and its long lever arm. In general, SINS indicates instability of pathological fractures of spinal metastases. However, we need to be careful to evaluate the patients with fractures when DISH is present in the patient's spine because its instability is higher than fracture patients without DISH.In summary, we experienced thoracolumbar pathological fracture in an elderly patient. Minimally invasive and strong fixation was thought to be desirable. We applied penetrating endplate screws using a percutaneous system and were able to eliminate back pain effectively, using minimally invasive surgery.