Association between paediatric eye injuries, later academic success and social performance.

Aim: To investigate an association between eye injury and later academic and social performance. Materials: A retrospective longitudinal study of taking measurements multiple times was conducted including all severe eye injuries admitted during 2011-2017 at the main regional clinic to investigate changes in academic success and social inclusion before and after an injury. Parents/caregivers were surveyed asking questions on academic performance, and community/social involvement. In 2023 data on employment status were obtained. Kappa (ĸ) and non-parametric Wilcox-on signed-rank test for multiple comparisons were used. For association of employment status and post-injury visual acuity Fisher score was tested. Results: The total sample for assessing social inclusion and academic success was 36 and 25 children, respectively. In the following academic year ĸ agreements decreased from 0.88 (p<0.001) comparing pre-injury with a one-year post to 0.5106 (p<.0001) in the second year and 0.4750 (p=0.003) in the third, suggesting a deteriorating trend. A comparison of academic success before injury to two and three years after injury showed the trend significantly worsening with time (p=0.005, and 0.003, respectively). No association between an eye injury and social inclusion, as well as between employment and final visual acuity was noticed. Conclusion: Our findings suggest no association between social inclusion, employment, and eye trauma, while in later years academic success may be more impacted by the eye injury. Due to eye injury unpredictability in childhood age, both an informed and supportive climate environment at home and school is essential to minimize deleterious responses to eye trauma.

Size- and Shape-Dependent Interactions of Lipid-Coated Silver Nanoparticles: An Improved Mechanistic Understanding through Model Cell Membranes and In Vivo Toxicity.

The widespread use of silver nanoparticles (AgNPs) in various applications and industries has brought to light the need for understanding the complex relationship between the physicochemical properties (shape, size, charge, and surface chemistry) of AgNPs that affect their ability to enter cells and cause toxicity. To evaluate their toxicological outcomes, this study systematically analyzed a series of homogeneous hybrid lipid-coated AgNPs spanning sizes from 5 to 100 nm with diverse shapes (spheres, triangles, and cubes). The hybrid lipid membrane comprises hydrogenated phosphatidylcholine (HPC), sodium oleate (SOA), and hexanethiol (HT), which shield the AgNP surface from surface oxidation and toxic Ag+ ion release to minimize its contribution to toxicity. To reduce any significant effects by surface chemistry, the HPC, SOA, and HT membrane composition ratio was kept constant, and the AgNPs were assessed using embryonic zebrafish (Danio rerio). While a direct comparison cannot be drawn due to the lack of complementary sizes below 40 nm for triangular plates and cubes due to synthetic challenges, significant mortality was observed for spherical AgNPs (AgNSs) of 5, 20, 40, and 60 nm at 120 h postfertilization at concentrations ≥6 mg Ag/L. In contrast, the 10, 80, and 100 nm AgNSs, 40, 70, and 100 nm triangular plate AgNPs (AgNPLs), and 55, 75, and 100 nm cubic AgNPs (AgNCs) showed no significant mortality at 5 days postfertilization following exposure to AgNPs at concentrations up to 12 mg Ag/L. With constant surface chemistry on the AgNPs, size is the dominant factor driving toxicological responses, with smaller nanoparticles (5 to 60 nm) being the most toxic. Larger AgNSs, AgNCs, and AgNPLs from 75 to 100 nm do not show any evidence of toxicity. However, when closely examining sizes between 40 and 60 nm for AgNSs, AgNCs, and AgNPLs, there is evidence that discriminates shape as a driver of toxicity since sublethal responses generally were observed to follow a pattern, suggesting toxicity is most significant for AgNSs followed by AgNPLs and then AgNCs, which is the least toxic. Sum frequency generation vibrational spectroscopy showed that irrespective of size or shape, all hybrid lipid-coated AgNPs interact with membrane surfaces and "snorkel" between phases into the lipid monolayer with minimal energetic cost. These findings decisively demonstrate that not only smaller AgNPs but also the shape of the AgNPs influences their biological compatibility.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Temporal Changes in the Surface Chemistry and Topography of Reactive Ion Plasma-Treated Poly(vinyl alcohol) Alter Endothelialization Potential.

Synthetic small-diameter vascular grafts (<6 mm) are used in the treatment of cardiovascular diseases, including coronary artery disease, but fail much more readily than similar grafts made from autologous vascular tissue. A promising approach to improve the patency rates of synthetic vascular grafts is to promote the adhesion of endothelial cells to the luminal surface of the graft. In this study, we characterized the surface chemical and topographic changes imparted on poly(vinyl alcohol) (PVA), an emerging hydrogel vascular graft material, after exposure to various reactive ion plasma (RIP) surface treatments, how these changes dissipate after storage in a sealed environment at standard temperature and pressure, and the effect of these changes on the adhesion of endothelial colony-forming cells (ECFCs). We showed that RIP treatments including O2, N2, or Ar at two radiofrequency powers, 50 and 100 W, improved ECFC adhesion compared to untreated PVA and to different degrees for each RIP treatment, but that the topographic and chemical changes responsible for the increased cell affinity dissipate in samples treated and allowed to age for 230 days. We characterized the effect of aging on RIP-treated PVA using an assay to quantify ECFCs on RIP-treated PVA 48 h after seeding, atomic force microscopy to probe surface topography, scanning electron microscopy to visualize surface modifications, and X-ray photoelectron spectroscopy to investigate surface chemistry. Our results show that after treatment at higher RF powers, the surface exhibits increased roughness and greater levels of charged nitrogen species across all precursor gases and that these surface modifications are beneficial for the attachment of ECFCs. This study is important for our understanding of the stability of surface modifications used to promote the adhesion of vascular cells such as ECFCs.

Quality control applications for recovering an inbred colony of Bagrada hilaris (Hemiptera: Pentatomidae).

The invasive stink bug, Bagrada hilaris (Burmeister), recently became established in the southwestern United States and has become a major pest of broccoli and other cole crops. Due to concerns about its possible establishment in Florida, a colony of this pest was maintained in quarantine to conduct research on its environmental requirements. The colony was reared reliably with approximately 300 adults per generation but began to decline in generation 16. Due to unknown causes, only about 73 females were recovered to mate and oviposit during the final 46 days. However, a corresponding decrease in the number of mated pairs did not reduce the yield of eggs, nymphs, and adults per day, but the females were maintained for fewer than the normal 160 days per generation. Therefore, quality control procedures were implemented to increase the number of days the colony produced adults in subsequent generations. The goal of producing approximately 400 adults per generation was accomplished during 104, 160, and 156 days, respectively, in generations 17, 18, and 19. The purpose of this research was to develop quality control procedures for rearing B. hilaris, use the procedures to restore a colony in quarantine, and describe how quality control can be used to maintain small colonies of insects. Implementing quality control procedures when a colony is established can help to prevent its decline.

Comparative Thermodynamic and Structural Analysis of Polyfluorinated Dodecylphosphonic Acid Adsorption to Distilled and River Water Interfaces.

As concerns rise about the health risks posed by per- and polyfluoroalkyl substances (PFAS) in the environment, there is a need to understand how these pollutants accumulate at environmental interfaces. Untangling the details of molecular adsorption, particularly when there are potential interactions with other molecules in environmental systems, can obscure the ability to focus on a particular contaminant with molecular specificity. Often adsorption studies of environmental interfaces require a reductionist approach, where laboratory experiments may not be fully tractable to environmental systems. In this work, we study polyfluorinated dodecylphosphonic acid (F21-DDPA) at the aqueous surfaces of distilled water (the most reduced "environmental" surface) and river water to explore the use of vibrational sum-frequency (VSF) spectroscopy as an experimental probe of fluorinated contaminants at natural environmental surfaces. We demonstrate how VSF spectroscopy offers advantages over nonspecific surface tension measurements when measuring PFAS adsorption isotherms at river water surfaces. VSF spectra of the C-F stretching region selectively probe the presence of F21-DDPA and can be used to extract meaningful structural insights and calculate surface concentrations, even at the complex river water surface. This study highlights the potential for VSF spectroscopy to be developed as a probe of fluorinated contaminants at natural environmental interfaces.

Role of Extracellular Vesicles in the Propagation of Lung Fibrosis in Systemic Sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) has the highest mortality rate among the rheumatic diseases, with lung fibrosis leading as the cause of death. A characteristic of severe SSc-related lung fibrosis is its progressive nature. Although most research has focused on the pathology of the fibrosis, the mechanism mediating the fibrotic spread remains unclear. We hypothesized that extracellular vesicle (EV) communication drives the propagation of SSc lung fibrosis. METHODS: EVs were isolated from normal (NL) or SSc-derived human lungs and primary lung fibroblasts (pLFs). EVs were also isolated from human fibrotic lungs and pLFs induced experimentally with transforming growth factor-ß (TGFß). Fibrotic potency of EVs was assessed using functional assays in vitro and in vivo. Transmission electron microscopy, nanoparticle tracking analysis, real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunofluorescence were used to analyze EVs, their cargo, extracellular matrix (ECM) fractions, and conditioned media. RESULTS: SSc lungs and pLFs released significantly more EVs than NL lungs, and their EVs showed increased fibrotic content and activity. TGFß-stimulated NL lung cores and pLFs increased packaging of fibrotic proteins, including fibronectin, collagens, and TGFß, into released EVs. The EVs induced a fibrotic phenotype in recipient pLFs and in vivo in mouse lungs. Furthermore, EVs interacted with and contributed to the ECM. Finally, suppressing EV release in vivo reduced severity of murine lung fibrosis. CONCLUSIONS: Our findings highlight EV communication as a novel mechanism for propagation of SSc lung fibrosis. Identifying therapies that reduce EV release, activity, and/or fibrotic cargo in SSc patient lungs may be a viable therapeutic strategy to improve fibrosis.

A comparison of the quadhelix and the nickel-titanium palatal expander in the treatment of narrow maxillary arches: A prospective clinical study.

OBJECTIVES: The study aimed to compare the effects of quadhelix and nickel-titanium (NiTi) expander appliances on lower facial height, to quantify, and evaluate dentoalveolar and orthopedic changes in transverse plane, respectively, to estimate the difference in changes between these two appliances. MATERIALS AND METHODS: Twenty patients, ten for the quadhelix and NiTi expander in the two-appliance group, respectively, participated in this study. A total of 8 readings, 1 for clinical facial height, 2 for model analysis, and 5 for posteroanterior cephalometric analysis were recorded. The statistical tests used were, Student's unpaired and paired t-tests. RESULTS: Both appliances individually, produced statistically highly significant (p < 0.01) expansion every month in both premolar and molar areas with more uniform expansion for quadhelix and less expansion in NiTi palatal expander in the premolar region initially. The skeletal to dental change ratio showed that there was more dental change than skeletal with no inter-appliance differences statistically while assessing the PA cephalometric readings. CONCLUSIONS: This study infers that both appliances are equally efficacious maxillary expanders, which are primarily dentoalveolar and not skeletal (p < 0.05).

The Molecular Mechanisms of Systemic Sclerosis-Associated Lung Fibrosis.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has the highest mortality rate among the rheumatic diseases. One of the hallmarks of SSc is fibrosis, which may develop systemically, affecting the skin and virtually any visceral organ in the body. Fibrosis of the lungs leads to interstitial lung disease (ILD), which is currently the leading cause of death in SSc. The identification of effective treatments to stop or reverse lung fibrosis has been the main challenge in reducing SSc mortality and improving patient outcomes and quality of life. Thus, understanding the molecular mechanisms, altered pathways, and their potential interactions in SSc lung fibrosis is key to developing potential therapies. In this review, we discuss the diverse molecular mechanisms involved in SSc-related lung fibrosis to provide insights into the altered homeostasis state inherent to this fatal disease complication.

Bioactive Synthetic Polymer-Based Polyelectrolyte LbL Coating Assembly on Surface Treated AZ31-Mg Alloys.

Polyelectrolyte layer-by-layer (LbL) films on pretreated Mg containing 3 wt.% Al and 1 wt.% Zn (MgAZ31) alloy surfaces were prepared under physiological conditions offering improved bioresponse and corrosive protection. Pretreatments of the model MgAZ31 substrate surfaces were performed by alkaline and fluoride coating methods. The anti-corrosion and cytocompatibility behavior of pretreated substrates were evaluated. The LbL film assembly consisted of an initial layer of polyethyleneimine (PEI), followed by alternate layers of poly (lactic-co-glycolic acid) (PLGA) and poly (allylamine hydrochloride) (PAH), which self-arrange via electrostatic interactions on the pretreated MgAZ31 alloy substrate surface. The physicochemical characterization, surface morphologies, and microstructures of the LbL films were investigated using Fourier-transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The in vitro stability studies related to the LbL coatings confirmed that the surface treatments are imperative to achieve the lasting stability of PLGA/PAH layers. Electrochemical impedance spectroscopy measurements demonstrated that pretreated and LbL multilayered coated substrates enhanced the corrosion resistance of the bare MgAZ31 alloy. Cytocompatibility studies using human mesenchymal stem cells seeded directly over the substrates showed that the pretreated and LbL-generated surfaces were more cytocompatible, displaying reduced cytotoxicity than the bare MgAZ31. The release of bovine serum albumin protein from the LbL films was also studied. The initial data presented cooperatively demonstrate the promise of creating LbL layers on Mg-related bioresorbable scaffolds to obtain improved surface bio-related activity.

Orientation of the Dysferlin C2A Domain is Responsive to the Composition of Lipid Membranes.

Dysferlin is a 230 kD protein that plays a critical function in the active resealing of micron-sized injuries to the muscle sarcolemma by recruiting vesicles to patch the injured site via vesicle fusion. Muscular dystrophy is observed in humans when mutations disrupt this repair process or dysferlin is absent. While lipid binding by dysferlin's C2A domain (dysC2A) is considered fundamental to the membrane resealing process, the molecular mechanism of this interaction is not fully understood. By applying nonlinear surface-specific vibrational spectroscopy, we have successfully demonstrated that dysferlin's N-terminal C2A domain (dysC2A) alters its binding orientation in response to a membrane's lipid composition. These experiments reveal that dysC2A utilizes a generic electrostatic binding interaction to bind to most anionic lipid surfaces, inserting its calcium binding loops into the lipid surface while orienting its ß-sheets 30-40° from surface normal. However, at lipid surfaces, where PI(4,5)P2 is present, dysC2A tilts its ß-sheets more than 60° from surface normal to expose a polybasic face, while it binds to the PI(4,5)P2 surface. Both lipid binding mechanisms are shown to occur alongside dysC2A-induced lipid clustering. These different binding mechanisms suggest that dysC2A could provide a molecular cue to the larger dysferlin protein as to signal whether it is bound to the sarcolemma or another lipid surface.

Sex-Specific Alterations in Inflammatory MicroRNAs in Mouse Brain and Bone Marrow CD11b+ Cells Following Traumatic Brain Injury.

Sex is a key biological variable in traumatic brain injury (TBI) and plays a significant role in neuroinflammatory responses. However, the molecular mechanisms contributing to this sexually dimorphic neuroinflammatory response remain elusive. Here we describe a significant and previously unreported tissue enrichment and sex-specific alteration of a set of inflammatory microRNAs (miRNAs) in CD11b+ cells of brain and bone marrow isolated from naïve mice as well as mice subjected to TBI. Our data from naïve mice demonstrated that expression levels of miR-146a-5p and miR-150-5p were relatively higher in brain CD11b+ cells, and that miR-155-5p and miR-223-3p were highly enriched in bone marrow CD11b+ cells. Furthermore, while miR-150-5p and miR-155-5p levels were higher in male brain CD11b+ cells, no significant sexual difference was observed for miR-146a-5p and miR-223-3p. However, TBI resulted in sex-specific differential responses of these miRNAs in brain CD11b+ cells. Specifically, miR-223-3p levels in brain CD11b+ cells were markedly elevated in both sexes in response to TBI at 3 and 24 h, with levels in females being significantly higher than males at 24 h. We then focused on analyzing several miR-223-3p targets and inflammation-related marker genes following injury. Corresponding to the greater elevation of miR-223-3p in females, the miR-223-3p targets, TRAF6 and FBXW7 were significantly reduced in females compared to males. Interestingly, anti-inflammatory genes ARG1 and IL4 were higher in females after TBI than in males. These observations suggest miR-223-3p and other inflammatory responsive miRNAs may play a key role in sex-specific neuroinflammatory response following TBI.

Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis.

OBJECTIVES: Lung fibrosis is the leading cause of death in SSc, with no cure currently available. Antifibrotic Endostatin (ES) production does not reach therapeutic levels in SSc patients, suggesting a deficit in its release from Collagen XVIII by the main cleavage enzyme, Cathepsin L (CTSL). Thus, elucidating a potential deficit in CTSL expression and activity unravels an underlying molecular cause for SSc-driven lung fibrosis. METHODS: Fibrosis was induced experimentally using TGF-ß in vitro, in primary human lung fibroblasts (pLFs), and ex vivo, in human lung tissues. ES and CTSL expression was quantified using ELISA, RT-qPCR, immunoblotting or immunofluorescence. Recombinant NC1-FLAG peptide was used to assess CTSL cleavage activity. CTSL expression was also compared between SSc vs normal (NL)-derived pLFs and lung tissues. RESULTS: ES levels were significantly reduced in media conditioned by TGF-ß-induced pLFs. TGF-ß-stimulated pLFs significantly reduced expression and secretion of CTSL into the extracellular matrix (ECM). CTSL was also sequestered in its inactive form into extracellular vesicles, further reducing its availability in the ECM. Media conditioned by TGF-ß-induced pLFs showed reduced cleavage of NC1-Flag and reduced release of the antifibrotic ES fragment. SSc-derived pLFs and lung tissues expressed significantly lower levels of CTSL compared with NL. CONCLUSIONS: Our findings identify CTSL as a protein protective against lung fibrosis via its activation of antifibrotic ES, and whose expression in SSc pLFs and lung tissues is suppressed. Identifying strategies to boost CTSL endogenous levels in SSc patients could serve as a viable therapeutic strategy.

Prevalence of Incidental Extraspinal Findings on MR Imaging of the Lumbar Spine in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Low back pain is common worldwide. MR imaging may identify extraspinal findings that are not related to the proposed clinical question. The prevalence of extraspinal incidental findings and their clinical significance has not been well-established. PURPOSE: This review aimed to evaluate the prevalence of extraspinal findings on MR imaging of the lumbar spine in adults and the prevalence of clinically significant incidental findings. DATA SOURCES: A systematic search of MEDLINE and EMBASE was performed, including studies published before June 14, 2023. STUDY SELECTION: Studies presenting a prevalence of extraspinal findings in patients 16 years of age or older were included. DATA ANALYSIS: A random effects meta-analysis was used to generate composite prevalence measures of extraspinal findings, patients with extraspinal findings, and clinically significant findings. DATA SYNTHESIS: Sixteen studies were included in this meta-analysis, with a total of 19,593 patients and 6,006 extraspinal incidental findings. The overall prevalence of extraspinal findings was 19.9% (95% CI, 11.1%-30.7%). Overall, 26.7% of patients had an extraspinal finding identified (95% CI, 14.8%-40.6%). The most common subgroup of extraspinal findings was genitourinary findings in males (27.1%; 95% CI, 25.6%-28.8%). Data from 8 studies demonstrated the prevalence of clinically significant findings at 5.4% (95% CI, 3.2%-8.1%). LIMITATIONS: Retrospective populations with small numbers of participants in clinically relevant subgroups may result in heterogeneity and imprecision within composite outcome measures. CONCLUSIONS: Extraspinal findings are common, detected in more than one-quarter of patients. Five percent of findings are clinically significant and may require further action.

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.

SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-11 polyprotein, whose mature products include cofactors of the viral replicase, and identified the order of cleavages. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and x-ray scattering yielded a nsp7-11 structural ensemble, demonstrating shared secondary structural elements with individual nsps. The pattern of cross-links and HDX footprint of the C145A Mpro and nsp7-11 complex demonstrate preferential binding of the enzyme active site to the polyprotein junction sites and additional transient contacts to help orient the enzyme on its substrate for cleavage. Last, proteolysis assays were used to characterize the effect of inhibitors/binders on Mpro processing/inhibition using the nsp7-11 polyprotein as substrate.

Shape-dependent gold nanoparticle interactions with a model cell membrane.

Customizable gold nanoparticle platforms are motivating innovations in drug discovery with massive therapeutic potential due to their biocompatibility, stability, and imaging capabilities. Further development requires the understanding of how discrete differences in shape, charge, or surface chemistry affect the drug delivery process of the nanoparticle. The nanoparticle shape can have a significant impact on nanoparticle function as this can, for example, drastically change the surface area available for modifications, such as surface ligand density. In order to investigate the effects of nanoparticle shape on the structure of cell membranes, we directly probed nanoparticle-lipid interactions with an interface sensitive technique termed sum frequency generation (SFG) vibrational spectroscopy. Both gold nanostars and gold nanospheres with positively charged ligands were allowed to interact with a model cell membrane and changes in the membrane structure were directly observed by specific SFG vibrational modes related to molecular bonds within the lipids. The SFG results demonstrate that the +Au nanostars both penetrated and impacted the ordering of the lipids that made up the membrane, while very little structural changes to the model membrane were observed by SFG for the +Au nanospheres interacting with the model membrane. This suggests that the +Au nanostars, compared to the +Au nanospheres, are more disruptive to a cell membrane. Our findings indicate the importance of shape in nanomaterial design and provide strong evidence that shape does play a role in defining nanomaterial-biological interactions.

Low Baseline Expression of Fibrotic Genes in an Ex Vivo Human Skin Model is a Potential Indicator of Excessive Skin Scarring.

One of the challenges plastic surgeons face is the unpredictability of postoperative scarring. The variability of wound healing and subsequent scar formation across patients makes it virtually impossible to predict if a patient's surgery will result in excessive fibrosis and scarring, possibly amounting to keloids or hypertrophic scars. There is a need to find predictive molecular indicators of patients or skin location with high risk of excessive scarring. We hypothesized that baseline expression levels of fibrotic genes in the skin can serve as a potential indicator of excessive scarring. Methods: An ex vivo model of skin fibrosis was used with abdominal and breast skin tissue from 45 patients undergoing breast reduction and/or abdominoplasty. Fibrosis was induced in skin explants in organ culture with transforming growth factor-ß (TFGß). Fibrotic gene response was assessed via quantitative real-time polymerase chain reaction and correlated with skin location, age, and baseline levels of fibrotic genes. Results: The increase in TFGß-induced fibronectin1 (FN1) gene expression in skin explants was significantly higher than for Collagen 1A1, alpha smooth muscle actin, and connective tissue growth factor. Also, FN1 expression positively correlated with donor age. Moreover, lower expression of the fibrotic genes FN1, Collagen 1A1, and alpha smooth muscle actin correlated with a more pronounced fibrotic response, represented by higher induction levels of these genes. Conclusions: Skin sites exhibit different baseline levels of profibrotic genes. Further, low baseline expression levels of fibrotic genes FN1, Collagen 1A1, and alpha smooth muscle actin, in donor skin may indicate a potential for excessive scarring of the skin.

Functional recovery outcomes following acute stroke is associated with abundance of gut microbiota related to inflammation, butyrate and secondary bile acid.

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and play a role in stroke rehabilitation. However, the microbial species alterations associated with stroke and their correlation with functional outcome measures following acute stroke remain unknown. Here we measure post-stroke gut dysbiosis and how it correlates with gut permeability and cognitive functions in 12 stroke participants, 18 controls with risk factors for stroke, and 12 controls without risk factors. Stool samples were used to measure the microbiome with whole genome shotgun sequencing and leaky gut markers. We genotyped APOE status and measured diet composition and motor, cognitive, and emotional status using NIH Toolbox. We used linear regression methods to identify gut microbial associations with cognitive and emotional assessments. We did not find significance differences between the two control groups. In contrast, the bacteria populations of the Stroke group were statistically dissimilar from the control groups. Relative abundance analysis revealed notable decreases in butyrate-producing microbial taxa, secondary bile acid-producing taxa, and equol-producing taxa. The Stroke group had higher levels of the leaky gut marker alpha-1-antitrypsin in the stool than either of the groups and several taxa including Roseburia species (a butyrate producer) were negatively correlated with alpha-1-antitrypsin. Stroke participants scored lower on memory testing than those in the two control groups. Stroke participants with more Roseburia performed better on the picture vocabulary task; more Bacteroides uniformis (a butyrate producer) and less Escherichia coli (a pro-inflammatory species) reported higher levels of self-efficacy. Intakes of fiber, fruit and vegetable were lower, but sweetened beverages were higher, in the Stroke group compared with controls. Vegetable consumption was correlated with many bacterial changes among the participants, but only the species Clostridium bolteae, a pro-inflammatory species, was significantly associated with stroke. Our findings indicate that stroke is associated with a higher abundance of proinflammatory species and a lower abundance of butyrate producers and secondary bile acid producers. These altered microbial communities are associated with poorer functional performances. Future studies targeting the gut microbiome should be developed to elucidate whether its manipulation could optimize rehabilitation and boost recovery.