Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Tibial torus and toddler's fractures misdiagnosed as transient synovitis: a case series

<p>Abstract</p> <p>Introduction</p> <p>The high incidence of transient synovitis in early childhood makes it the first suspected pathology in a limping child. Trauma, which has long been regarded as a causative factor for transient synovitis, may be underestimated in a non-cooperative toddler.</p> <p>After excluding most serious conditions, such as septic arthritis, a speculative diagnosis of transient synovitis can be made, and this can easily mask a subtle musculoskeletal injury.</p> <p>Case presentations</p> <p>We report the cases of three Caucasian patients (two boys, aged 20-months- and three-years-old, and one girl, aged two-years-old), with tibial torus and toddler's fractures which were late-diagnosed due to an initial misdiagnosis of transient synovitis of the hip.</p> <p>Conclusion</p> <p>In a non-cooperative child musculoskeletal trauma can be mistaken as a simple causative factor for transient synovitis of the hip and this can easily prevent further investigation for a possible subtle musculoskeletal injury of the lower extremities.</p> <p>Our experience with the presented cases suggests the need to be more vigilant in the differential diagnosis of transient synovitis in young children.</p

Evaluating pharmacological THRomboprophylaxis in Individuals undergoing superficial endoVEnous treatment across NHS and private clinics in the UK: a multi-centre, assessor-blind, randomised controlled trial - THRIVE trial

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.Introduction Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56-70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective. Methods and analysis A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression. Ethics and dissemination Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences. Trial registration number ISRCTN18501431

Genome Majority Vote Improves Gene Predictions

Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps

Grooming Up the Hierarchy: The Exchange of Grooming and Rank-Related Benefits in a New World Primate

Seyfarth's model assumes that female primates derive rank-related benefits from higher-ranking females in exchange for grooming. As a consequence, the model predicts females prefer high-ranking females as grooming partners and compete for the opportunity to groom them. Therefore, allogrooming is expected to be directed up the dominance hierarchy and to occur more often between females with adjacent ranks. Although data from Old World primates generally support the model, studies on the relation between grooming and dominance rank in the New World genus Cebus have found conflicting results, showing considerable variability across groups and species. In this study, we investigated the pattern of grooming in wild tufted capuchin females (Cebus apella nigritus) in Iguazú National Park, Argentina by testing both the assumption (i.e., that females gain rank-related return benefits from grooming) and predictions (i.e., that females direct grooming up the dominance hierarchy and the majority of grooming occurs between females with adjacent ranks) of Seyfarth's model. Study subjects were 9 adult females belonging to a single group. Results showed that grooming was given in return for tolerance during naturally occurring feeding, a benefit that higher-ranking females can more easily grant. Female grooming was directed up the hierarchy and was given more often to partners with similar rank. These findings provide supporting evidence for both the assumption and predictions of Seyfarth's model and represent, more generally, the first evidence of reciprocal behavioural interchanges driven by rank-related benefits in New World female primates

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro

Prostate cancer (PCa) preferentially metastasizes to bone resulting in osteoblastic lesions with underlying osteolytic activities. The mechanisms through which PCa cells promote osteolytic activities and subsequent osteoblastic bone formation remain poorly understood. Parathyroid hormone-related protein (PTHrP), produced by bone cells and PCa, binds to receptors on osteoblasts and stimulates bone formation and resorption. We have previously reported that MCP-1 acts as a paracrine and autocrine factor for PCa progression. However, the role of PTHrP in regulating MCP-1 expression in bone microenvironment, specifically by human bone marrow endothelial cells (HBME) and osteoblasts (hFOB), as well as by PCa cells, has not been studied. Accordingly, we first determined the effect of PTHrP on MCP-1 expression by bone cells and PCa cells. PTHrP induced both MCP-1 protein and mRNA expression by HBME and hFOB cells, but not by PCa LNCaP and PC3 cells. To further determine the mechanisms of PTHrP-induced MCP-1 transcription, analysis of the MCP-1 promoter was performed. MCP-1 promoter activity was induced by PTHrP. Both C/EBPΒ and NF-ΚB binding elements are required for PTHrP-induced MCP-1 transcription. Finally, when a constitutively-active PTH receptor construct was transfected into HBME and hFOB cells, MCP-1 production was increased. The conditioned media collected from these cells induced osteoclast differentiation and PC3 proliferation and invasion in vitro . These inductions were partially inhibited by MCP-1 neutralizing antibody. We conclude that PTHrP-induced MCP-1 production by HBME and hFOB cells promotes osteoclast differentiation in vitro and such induction may play a critical role in PCa development in the bone microenvironment. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56050/1/22704_ftp.pd

Multichannel social signatures and persistent features of ego networks

The structure of egocentric networks reflects the way people balance their need for strong, emotionally intense relationships and a diversity of weaker ties. Egocentric network structure can be quantified with ’social signatures’, which describe how people distribute their communication effort across the members (alters) of their personal networks. Social signatures based on call data have indicated that people mostly communicate with a few close alters; they also have persistent, distinct signatures. To examine if these results hold for other channels of communication, here we compare social signatures built from call and text message data, and develop a way of constructing mixed social signatures using both channels. We observe that all types of signatures display persistent individual differences that remain stable despite the turnover in individual alters. We also show that call, text, and mixed signatures resemble one another both at the population level and at the level of individuals. The consistency of social signatures across individuals for different channels of communication is surprising because the choice of channel appears to be alter-specific with no clear overall pattern, and ego networks constructed from calls and texts overlap only partially in terms of alters. These results demonstrate individuals vary in how they allocate their communication effort across their personal networks and this variation is persistent over time and across different channels of communication

The Winter Worries of Bats : Past and Present Perspectives on Winter Habitat and Management of Cave Hibernating Bats

Winter is a time of fascinating changes in biology for cave-hibernating bats, but it is also a time of vulnerability. Unsurprisingly, assessments of winter habitat for these mammals and how it can be managed have been a focus of many researchers involved with the North American Society for Bat Research over the last 50 years. Over this time, a paradigm shift has occurred in the way scientists think about factors driving selection of winter habitat, especially temperature. To illustrate this change, we review three hypotheses seeking to explain microclimate selection in cavernicolous bats. The first, which we call the “Colder is Better Hypothesis,” posits that bats should select cold microclimates that minimize energy expenditure. The “Hibernation Optimization Hypothesis” suggests that bats should select microclimates that reduce expression of torpor to balance energy conservation against non-energetic costs of hibernation. Finally, the “Thrifty Female Hypothesis” asserts that females should select colder microclimates than males to conserve energy for reproduction. We discuss these hypotheses and the shift from viewing hibernation as a phenomenon driven solely by the need to conserve energy in the context of hibernacula management in North America. We focus on both historical and recent conservation threats, most notably alteration of thermal regimes and the disease white-nose syndrome. We urge against returning to an over-simplified view of winter habitat selection in response to our current conservation challenges.Peer reviewe