Real-time control of urban drainage systems using neuro-evolution.

With climate change and urbanization, existing urban drainage systems are being stressed beyond their design capacity in many parts of the world. Real-time control (RTC) can improve the performance of these systems and reduce the need for system upgrades. However, developing optimal control policies for RTC is a challenging research area due to computational demands, high uncertainties and system dynamics. This study presents a new RTC method using neuro-evolution for controlling combined sewer overflow (CSO) in urban drainage systems. Neuro-evolution is an approach to neural network research by evolutionary algorithms. Neuro-evolution realizes RTC by training the control policy in advance, thus avoiding the online optimization process in the application period. The simulation results of the benchmark Astlingen network indicate that the trained control policy outperforms the equal filling degree strategy in terms of CSO volume reduction and robustness in the face of tank level uncertainty. The performance analysis of the typical CSO events shows that the control policy mainly makes positive contributions during 'small' CSO events rather than 'large' ones. In particular, the effectiveness of the control policy in 'small' CSO events is more prominent in the initial phase of the events compared with the final phase. This work stands to support a foundation for future studies in the control of urban water systems based on neuro-evolution.

Taurolidine and Heparin as Catheter Lock Solution for Central Venous Catheters in Hemodialysis.

BACKGROUND: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available. CLINICAL TRIALS: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs. THERAPEUTIC ADVANCE: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.

First report of root rot of strawberry caused by Fusarium cugenangense, a member of the F. oxysporum species complex, in Tennessee, USA.

Strawberry (Fragaria × ananassa Duch) in Tennessee is cultivated on plastic mulched beds annually, and production is limited primarily by multiple oomycete and fungal root rot pathogens that result in reduced vigor and black root rot disease symptoms. In early June 2018, plants (cv. Chandler) with reduced shoot vigor and size, and black, necrotic stunted roots were collected from Rhea County, TN. Roots and crowns of 10 plants were cut into 1-3 cm pieces and surface sterilized with 0.6% NaOCl, followed by 70% ethanol for 1 min each, and plated on water agar. White mycelia produced after 3 days were transferred to potato dextrose agar amended with 10 mg/liter rifampicin. After 10 days, fungal colonies were light purple on the surface and dark purple on the colony underside, later developing blue-black pigmentation on the underside. Microconidia on carnation leaf agar were ovoid to ellipsoid, aseptate or septate and 8.0 to 24.2 (13.7) × 3.0 to 4.5 (3.8) µm in size, macroconidia were 3 to 5 septate and falcate to almost straight and 33.7 to 52.8 (44.4) × 4.0 to 5.5 (4.9) µm in size (n=80); both conidia were produced on monophialides. Chlamydospores were globose and subglobose, formed terminally and intercalary on aerial, submerged, and surface mycelium, singly or in pairs and were abundantly produced in sucrose broth and on synthetic nutrient-poor agar (SNA) (diam. 7.6 µm). Morphology was consistent with Fusarium oxysporum (Leslie and Summerell, 2006) and F. cugenangense, a member of the F. oxysporum species complex, as described by Maryani et al. (2019). Fungal mycelia were used for PCR (Phire Plant Direct PCR Master Mix, Thermo Scientific, CA) and the translational elongation factor 1-α (EF1α) region was amplified with primers EF-1/EF-2 (O'Donnell et al., 1998), internal transcribed spacer (ITS) regions amplified with primers ITS1/ITS2 (White et al. 1990), and the RNA polymerase second largest subunit region (RPB2) with primer pairs 5f2/7cr and 7cf/11ar (O'Donnell et al., 2022). PCR products of isolate SC5 were sequenced, and sequences compared to all sequences in the FUSARIOID-ID database using polyphasic identification (Crous et al., 2021) with EF1α (GenBank Accession No. ON703236) and RPB2 (OR472390) sequences. The highest similarity (100%) was with isolates of F. cugenangense, including ex-type isolate InaCC F984 (99.94% similarity) (Maryani et al., 2019). F. cugenangense is closely related to F. callistephi and F. elaeidis, but both species lack chlamydospores, and F. elaeidis has polyphialides (Lombard et al, 2019). To satisfy Koch's postulates, healthy rooted strawberry plants produced in soilless media were transplanted into 4 plastic pots (1.2-liter) containing 5% (w/v) fungal inoculum (grown on barley grain) and mixed into the top 5-cm of peat-based soilless medium. Pots were incubated at 25°C and 50% RH in a growth chamber. Four pots without inoculum served as controls. The trial was repeated. Within 8 weeks, all inoculated plants had low vigor, with necrotic and stunted roots. Root sections of control and inoculated plants were plated, and the pathogen was re-isolated from diseased roots of all inoculated plants only and confirmed as F. cugenangense based on morphology and sequence analysis. To our knowledge, this is the first report of F. cugenangense, or any member of the F. oxysporum species complex, causing root rot of strawberry in Tennessee and could be an important component of the production-limiting black root rot disease complex of strawberry.

ENGINEERED NANOBODIES WITH PROGRAMMABLE TARGET ANTIGEN PROTEOLYSIS (PTAP) FUSIONS REGULATE INTRACELLULAR ALPHA-SYNUCLEIN IN VITRO AND IN VIVO.

Alpha-synuclein (αSyn) aggregation and the formation of Lewy pathology (LP) is a foundational pathophysiological phenomenon in synucleinopathies. Delivering therapeutic single-chain and single-domain antibodies that bind pathogenic targets can disrupt intracellular aggregation. The fusion of antibody fragments to a negatively-charged proteasomal targeting motif (PEST) creates bifunctional constructs that enhance both solubility and turnover. With sequence-specific point mutations of PEST sequences that modulate proteasomal degradation efficiency, we report the creation of Programmable Target Antigen Proteolysis (PTAP) technology that can provide graded control over the levels of target antigens. We have previously demonstrated our lead anti-αSyn intrabody, VH14-PEST, is capable of reducing the pathological burden of synucleinopathy in vitro and in vivo. Here, we report a family of fully humanized VH14-PTAP constructs for controllable, therapeutic targeting of intracellular α-Syn. In cells, we demonstrate successful target engagement and efficacy of VH14-hPEST intrabodies, and validate proof-of-principle in human cells using 3D human organoids derived from PD-patient induced pluripotent stem cells (iPSC). In two synuclein-based rat models, PTAP intrabodies attenuated nigral αSyn pathology, preserved nigrostriatal dopaminergic tone, and slowed the propagation of αSyn pathology. These data demonstrate the potency of intracellular αSyn targeting as a method to alleviate pathology and highlight the potential clinical utility of PTAP intrabodies.

Making Waves: Towards data-centric water engineering.

Artificial intelligence (AI) is expected to transform many scientific disciplines, with the potential to significantly accelerate scientific discovery. This perspective calls for the development of data-centric water engineering to tackle water challenges in a changing world. Building on the historical evolution of water engineering from empirical and theoretical paradigms to the current computational paradigm, we argue that a fourth paradigm, i.e., data-centric water engineering, is emerging driven by recent AI advances. Here we define a new framework for data-centric water engineering in which data are transformed into knowledge and insight through a data pipeline powered by AI technologies. It is proposed that data-centric water engineering embraces three principles - data-first, integration and decision making. We envision that the development of data-centric water engineering needs an interdisciplinary research community, a shift in mindset and culture in the academia and water industry, and an ethical and risk framework to guide the development and application of AI. We hope this paper could inspire research and development that will accelerate the paradigm shift towards data-centric water engineering in the water sector and fundamentally transform the planning and management of water infrastructure.

People with painful knee osteoarthritis hold negative implicit attitudes towards activity.

ABSTRACT: Negative attitudes/beliefs surrounding osteoarthritis, pain, and activity contribute to reduced physical activity in people with knee osteoarthritis (KOA). These attitudes/beliefs are assessed using self-report questionnaires, relying on information one is consciously aware of and willing to disclose. Automatic (ie, implicit) assessment of attitudes does not rely on conscious reflection and may identify features unique from self-report. We developed an implicit association test that explored associations between images of a person moving/twisting their knee (activity) or sitting/standing (rest), and perceived threat (safe vs dangerous). We hypothesised that people with KOA would have greater implicit threat-activity associations (vs pain-free and non-knee pain controls), with implicit attitudes only weakly correlating with self-reported measures (pain knowledge, osteoarthritis/pain/activity beliefs, fear of movement). Participants (n = 558) completed an online survey: 223 had painful KOA (n = 157 female, 64.5 ± 8.9 years); 207 were pain free (n = 157 female, 49.3 ± 15.3 years); and 99 had non-KOA lower limb pain (n = 74 female, 47.5 ± 15.04 years). An implicit association between "danger" and "activity" was present in those with and without limb pain (KOA: 0.36, 95% CI 0.28-0.44; pain free: 0.13, 95% CI 0.04-0.22; non-KOA lower limb pain 0.11, 95% CI -0.03 to 0.24) but was significantly greater in the KOA group than in the pain free (P < 0.001) and non-KOA lower limb pain (P = 0.004) groups. Correlations between implicit and self-reported measures were nonsignificant or weak (rho = -0.29 to 0.19, P < 0.001 to P = 0.767). People with painful KOA hold heightened implicit threat-activity associations, capturing information unique to that from self-report questionnaires. Evaluating links between implicit threat-activity associations and real-world behaviour, including physical activity levels, is warranted.

Human mesenchymal stromal cells inhibit Mycobacterium avium replication in clinically relevant models of lung infection.

INTRODUCTION: Novel therapeutic strategies are urgently needed for Mycobacterium avium complex pulmonary disease (MAC-PD). Human mesenchymal stromal cells (MSCs) can directly inhibit MAC growth, but their effect on intracellular bacilli is unknown. We investigated the ability of human MSCs to reduce bacterial replication and inflammation in MAC-infected macrophages and in a murine model of MAC-PD. METHODS: Human monocyte-derived macrophages (MDMs) were infected with M. avium Chester strain and treated with human bone marrow-derived MSCs. Intracellular and extracellular colony-forming units (CFUs) were counted at 72 hours. Six-week-old female balb/c mice were infected by nebulisation of M. avium Chester. Mice were treated with 1×106 intravenous human MSCs or saline control at 21 and 28 days post-infection. Lungs, liver and spleen were harvested 42 days post-infection for bacterial counts. Cytokines were quantified by ELISA. RESULTS: MSCs reduced intracellular bacteria in MDMs over 72 hours (median 35% reduction, p=0.027). MSC treatment increased extracellular concentrations of prostaglandin E2 (PGE2) (median 10.1-fold rise, p=0.002) and reduced tumour necrosis factor-α (median 28% reduction, p=0.025). Blocking MSC PGE2 production by cyclo-oxygenase-2 (COX-2) inhibition with celecoxib abrogated the antimicrobial effect, while this was restored by adding exogenous PGE2. MSC-treated mice had lower pulmonary CFUs (median 18% reduction, p=0.012), but no significant change in spleen or liver CFUs compared with controls. CONCLUSION: MSCs can modulate inflammation and reduce intracellular M. avium growth in human macrophages via COX-2/PGE2 signalling and inhibit pulmonary bacterial replication in a murine model of chronic MAC-PD.

Can Blue-Green Infrastructure enhance resilience in urban drainage systems during failure conditions?

The need to enhance the resilience of urban drainage systems (UDSs) in view of emerging global climate change and urbanisation threats is well recognised. Blue-Green Infrastructure (BGI) provides a suitable strategy for building the resilience of existing UDSs. However, there are limited quantitative studies that provide evidence of their effectiveness for increased uptake in cities. In this research, coupled one-dimensional-two-dimensional (1D-2D) modelling is applied to assess the effectiveness of BGI that include rainwater harvesting systems, infiltration trenches, bioretention cells, and detention ponds using two case study UDSs located in Kampala that experience catastrophic pluvial flooding caused by extreme rainfall. The resulting flooding impacts are quantified considering 'failed' and 'non-failed' UDS initial states, using total flood volume and average flood duration as system performance indicators. The study results suggest that spatially distributed rainwater harvesting systems singularly lead to a reduction in total flood volume and average flood duration of 16-45% and 18-24% in the case study UDSs, respectively. Furthermore, the study results suggest that BGIs are more effective during moderate rainfall (T < 10 years). Based on the study findings, city scale implementation of multifunctional rainwater harvesting systems is recommended as a suitable strategy for enhancing UDSs' resilience.

The effect of green infrastructure on resilience performance in combined sewer systems under climate change.

Climate change is currently reshaping precipitation patterns, intensifying extremes, and altering runoff dynamics. Particularly susceptible to these impacts are combined sewer systems (CSS), which convey both stormwater and wastewater and can lead to combined sewer overflow (CSO) discharges during heavy rainfall. Green infrastructure (GI) can help mitigate these discharges and enhance system resilience under historical conditions; however, the quantification of its effect on resilience in a future climate remains unknown in the literature. This study employs a modified Global Resilience Analysis (GRA) framework for continuous simulation to quantify the impact of climate change on CSS resilience, particularly CSOs. The study assesses the efficacy of GI interventions (green roofs, permeable pavements, and bioretention cells) under diverse future rainfall scenarios based on EURO-CORDEX regional climate models (2085-2099) and three Representative Concentration Pathways (2.6, 4.5, 8.5 W/m2). The findings underscore a general decline in resilience indices across the future rainfall scenarios considered. Notably, the total yearly CSO discharge volume increases by a range of 145 % to 256 % in response to different rainfall scenarios. While GI proves effective in increasing resilience, it falls short of offsetting the impacts of climate change. Among the GI options assessed, green roofs routed to pervious areas exhibit the highest adaptive capacity, ranging from 9 % to 22 % at a system level, followed by permeable pavements with an adaptation capacity between 7 and 13 %. By linking the effects of future rainfall scenarios on CSO performance, this study contributes to understanding GI's potential as a strategic tool for enhancing urban resilience.

Embodiment illusions and eating disorders: snapshot of implications for research and interventions.

In recent years, researchers have increasingly used the embodiment illusion paradigm in subclinical and clinical eating disorder (ED) populations. This has important implications for understanding and ultimately improving bodily misperception. Here, we provide a brief overview of the current 'state of the art' of these implications while highlighting challenges and future directions.

The Effectiveness of Self-supervised Pre-training for Multi-modal Endometriosis Classification*†.

Endometriosis is a debilitating condition affecting 5% to 10% of the women worldwide, where early detection and treatment are the best tools to manage the condition. Early detection can be done via surgery, but multi-modal medical imaging is preferable given the simpler and faster process. However, imaging-based endometriosis diagnosis is challenging as 1) there are few capable clinicians; and 2) it is characterised by small lesions unconfined to a specific location. These two issues challenge the development of endometriosis classifiers as the training datasets tend to be small and contain difficult samples, which leads to overfitting. Hence, it is important to consider generalisation techniques to mitigate this problem, particularly self-supervised pre-training methods that have shown outstanding results in computer vision and natural language processing applications. The main goal of this paper is to study the effectiveness of modern self-supervised pre-training techniques to overcome the two issues mentioned above for the classification of endometriosis from multi-modal imaging data. We also introduce a new masking image modelling self-supervised pre-training method that works with 3D multi-modal medical imaging. Furthermore, to the best of our knowledge, this paper presents the first endometriosis classifier, fine-tuned from the pre-trained model above, which works with multi-modal (i.e., T1 and T2) magnetic resonance imaging (MRI) data. Our results show that self-supervised pre-training improves endometriosis classification by as much as 31%, when compared with classifiers trained from scratch.

Teaching Patients About Pain: The Emergence of Pain Science Education, its Learning Frameworks and Delivery Strategies.

Since it emerged in the early 2000's, intensive education about 'how pain works', widely known as pain neuroscience education or explaining pain, has evolved into a new educational approach, with new content and new strategies. The substantial differences from the original have led the PETAL collaboration to call the current iteration 'Pain Science Education'. This review presents a brief historical context for Pain Science Education, the clinical trials, consumer perspective, and real-world clinical data that have pushed the field to update both content and method. We describe the key role of educational psychology in driving this change, the central role of constructivism, and the constructivist learning frameworks around which Pain Science Education is now planned and delivered. We integrate terminology and concepts from the learning frameworks currently being used across the PETAL collaboration in both research and practice-the Interactive, Constructive, Active, Passive framework, transformative learning theory, and dynamic model of conceptual change. We then discuss strategies that are being used to enhance learning within clinical encounters, which focus on the skill, will, and thrill of learning. Finally, we provide practical examples of these strategies so as to assist the reader to drive their own patient pain education offerings towards more effective learning. PERSPECTIVE: Rapid progress in several fields and research groups has led to the emergence 'Pain Science Education'. This PETAL review describes challenges that have spurred the field forward, the learning frameworks and educational strategies that are addressing those challenges, and some easy wins to implement and mistakes to avoid.

Item development and pre-testing of an Osteoarthritis Conceptualisation Questionnaire to assess knowledge and beliefs in people with knee pain.

Many people with osteoarthritis hold beliefs that physical activity is unhelpful or dangerous for their joints, despite high-level evidence suggesting otherwise. Recent advances in scientific understanding of osteoarthritis have led to new treatments that target an individual's understanding both of their condition and the importance of best-practice management strategies, such as physical activity. Conceptual change has been proposed as an important mechanism by which cognitive interventions, such as pain science education, may reduce pain and improve function. There are currently no specific assessments of osteoarthritis conceptualisation to determine the effectiveness of cognitive interventions in effecting conceptual change in people with knee osteoarthritis. Therefore, we aimed to develop an item bank, as the first phase of developing a questionnaire to assess people's conceptualisations about their knee osteoarthritis and the role of physical activity in managing their osteoarthritis. Using a guideline-informed mixed method design, a panel of experts identified domains relevant to conceptualisation about knee osteoarthritis and physical activity (knowledge, beliefs, understanding) based upon available evidence. The panel created 33 provisional items. Qualitative and quantitative pretesting were used to explore how people with knee osteoarthritis understood the provisional items. Eighteen people with knee osteoarthritis completed cognitive interviews about their comprehension of the wording/grammar of each provisional item. The provisional item bank was field tested with 100 people with knee osteoarthritis. Readability was adequate with a Flesch reading ease score of 57.7. Although 14.7% used the 'Strongly agree' response option, only 3.4% of responses used the 'Strongly disagree' option, suggesting possible response bias. Predictive quality testing identified relevant modifications to the questionnaire instructions. The panel of experts appraised the qualitative data to assess whether and how items should be modified to address the problems identified, resulting in a final item bank of 45 items that can be evaluated for psychometric properties in future research.

Compatibility of Omadacycline With Select Parenteral Products in Simulated Y-site Administration.

PURPOSE: Omadacycline is a broad-spectrum intravenous and oral tetracycline antibiotic approved for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Available information on the compatibility of intravenous omadacycline is limited to sterile water, 0.9% sodium chloride, and 5% dextrose via a dedicated line. The objective of this work was to determine the intravenous compatibility of omadacycline with commonly used intravenous fluids and medications using simulated Y-site administration. METHODS: Omadacycline was prepared at concentrations consistent with a maintenance dose (1 mg/mL) and a loading dose (2 mg/mL) with 0.9% sodium chloride according to the prescribing information. Compatibility via simulated Y-site administration was assessed with selected crystalloids (lactated Ringer's solution, magnesium sulfate, and normal saline with potassium chloride) and intravenous medications (bumetanide, furosemide, heparin, and insulin). Y-site administration was simulated by mixing 5 mL of omadacycline with 5 mL of each parenteral product prepared at standard concentrations for infusion. Compatibility was assessed by using visual, Tyndall beam, microscopy, and spectrophotometry methods at 0, 30, and 60 minutes. FINDINGS: Omadacycline appeared physically compatible with lactated Ringer's solution, magnesium sulfate, normal saline with potassium chloride, bumetanide, heparin, and insulin at standard infusion concentrations. However, although the lower concentrations of omadacycline 1 mg/mL and furosemide 2 mg/mL showed compatibility, higher concentrations of either agent in combination resulted in incompatibility. IMPLICATIONS: Omadacycline appeared physically compatible with all products tested and incompatible with furosemide. Simultaneous administration of omadacycline with tested intravenous medications, except furosemide, is suggested to be safe.

Improved Protocol for Reproducible Human Cortical Organoids Reveals Early Alterations in Metabolism with MAPT Mutations.

Cerebral cortical-enriched organoids derived from human pluripotent stem cells (hPSCs) are valuable models for studying neurodevelopment, disease mechanisms, and therapeutic development. However, recognized limitations include the high variability of organoids across hPSC donor lines and experimental replicates. We report a 96-slitwell method for efficient, scalable, reproducible cortical organoid production. When hPSCs were cultured with controlled-release FGF2 and an SB431542 concentration appropriate for their TGFBR1 / ALK5 expression level, organoid cortical patterning and reproducibility were significantly improved. Well-patterned organoids included 16 neuronal and glial subtypes by single cell RNA sequencing (scRNA-seq), frequent neural progenitor rosettes and robust BCL11B+ and TBR1+ deep layer cortical neurons at 2 months by immunohistochemistry. In contrast, poorly-patterned organoids contain mesendoderm-related cells, identifiable by negative QC markers including COL1A2 . Using this improved protocol, we demonstrate increased sensitivity to study the impact of different MAPT mutations from patients with frontotemporal dementia (FTD), revealing early changes in key metabolic pathways.

Global resilience analysis of combined sewer systems under continuous hydrologic simulation.

Managing and reducing combined sewer overflow (CSO) discharges is crucial for enhancing the resilience of combined sewer systems (CSS). However, the absence of a standardised resilience analysis approach poses challenges in developing effective discharge reduction strategies. To address this, our study presents a top-down method that expands the existing Global Resilience Analysis to quantify resilience performance in CSS. This approach establishes a link between threats (e.g., rainfall) and impacts (e.g., CSOs) through continuous and long-term simulation, accommodating various rainfall patterns, including extreme events. We assess CSO discharge impacts from a resilience perspective by introducing eight new metrics. We conducted a case study in Fehraltorf, Switzerland, analysing the performance of three green infrastructure (GI) types (bioretention cells, green roofs, and permeable pavements) over 38 years. The results demonstrated that GI enhanced all resilience indices, with variations observed in individual CSO performance metrics and their system locations. Notably, in Fehraltorf, green roofs emerged as the most effective GI type for improving resilience, while the downstream outfall displayed the highest resilience enhancement. Overall, our proposed method enables a shift from event-based to continuous simulation analysis, providing a standardised approach for resilience assessment. This approach informs the development of strategies for CSO discharge reduction and the enhancement of CSS resilience.

Neonatal subarachnoid hemorrhage disrupts multiple aspects of cerebellar development.

Over the past decade, survival rates for extremely low gestational age neonates (ELGANs; <28 weeks gestation) has markedly improved. Unfortunately, a significant proportion of ELGANs will suffer from neurodevelopmental dysfunction. Cerebellar hemorrhagic injury (CHI) has been increasingly recognized in the ELGANs population and may contribute to neurologic dysfunction; however, the underlying mechanisms are poorly understood. To address this gap in knowledge, we developed a novel model of early isolated posterior fossa subarachnoid hemorrhage (SAH) in neonatal mice and investigated both acute and long-term effects. Following SAH on postnatal day 6 (P6), we found significant decreased levels of proliferation with the external granular layer (EGL), thinning of the EGL, decreased Purkinje cell (PC) density, and increased Bergmann glial (BG) fiber crossings at P8. At P42, CHI resulted in decreased PC density, decreased molecular layer interneuron (MLI) density, and increased BG fiber crossings. Results from both Rotarod and inverted screen assays did not demonstrate significant effects on motor strength or learning at P35-38. Treatment with the anti-inflammatory drug Ketoprofen did not significantly alter our findings after CHI, suggesting that treatment of neuro-inflammation does not provide significant neuroprotection post CHI. Further studies are required to fully elucidate the mechanisms through which CHI disrupts cerebellar developmental programming in order to develop therapeutic strategies for neuroprotection in ELGANs.

First Report of Strawberry Black Root Rot Caused by Globisporangium sylvaticum in Tennessee, USA.

Globisporangium sylvaticum (syn. Pythium sylvaticum), is an oomycete that causes root rot and damping off of field crops, ornamentals, and vegetables. Several species in Pythiaceae are associated with black root rot of strawberry [(Fragaria × ananassa) Duchesne] (Millner 2006). Mature, stunted 'Chandler' strawberry plants, with reduced shoot vigor and black necrotic roots, were collected from Rhea County (June 2018) and Cumberland County, TN (May 2019). Aboveground symptoms occurred in low incidence (<5% of plants) in the fields. Plant roots were rinsed with tap water, cut into 1 to 3 cm pieces, and surface-disinfested (70% ethanol, 1 min) followed by a sterile water rinse. Root segments were crushed, placed on 20% V8 juice agar, and incubated in the dark at 21°C for 3 days. White fluffy mycelia grew from a majority of roots and coenocytic hyphae with globose hyphal swellings, delimited from hyphae by septa, were observed with microscopy. Hyphae were initially branched, curled, hyaline, and aseptate; however, septations were observed in older cultures. Globose structures (terminal and intercalary) were identified as sporangia [11 to 32 (avg. 22.1) µm diameter] when zoospores were observed (Parikh et al. 2022). Oospores [9 to 21 (avg. 16) µm diameter] were globose, smooth, aplerotic, and thick-walled. Oogonia, with or without one or more inflated antheridia, were observed when isolates were paired in culture, characteristics consistent with descriptions of Campbell and Hendrix (1967), Pratt and Green (1971), van der Plaats-Niterink (1981), and Uzuhashi et al. (2010). Genomic DNA was extracted (Extract-N-Amp™; Sigma-Aldrich, MO) for PCR amplification of internal transcribed spacer (ITS) regions of rDNA with primers ITS1/ITS4 (White et al. 1990); ITS and large subunit rRNA regions with primers UN-up18S42/UN-lo28S22 (Robideau et al. 2011); and cytochrome c oxidase subunit I (COI) mitochondrial DNA with primers OomCoxI-Levup/OomCoxI-Levlo (Robideau et al. 2011). Primers ITS1/ITS4 were used to amplify isolate TN (GenBank Accession MW386310, which had 100% homology with reference isolate MK326528). Primers UN-up18S42/UN-lo28S22 amplified isolates SAP18 and OO1 (Accessions MZ881935 and MZ881936, which had 99.8% homology with HQ665236), and COI primers amplified isolate SAP18 (Accession OK020192, which had 100% homology with GU071816 and KT692835). To satisfy Koch's postulates, inoculum of G. sylvaticum grown on autoclaved wheat seeds was added (5% w/v) to planting mix (1 peat:1 sand, v/v). Young, rooted strawberry plants were planted in 1.2-L pots with infested (n = 6) and control (no pathogen, n = 6) mixes, which was saturated with deionized water. Pots were covered with clear plastic for 48 h to maintain high humidity. Plants were grown in a greenhouse (24°C avg.) for 8 weeks. The disease assay was repeated. All plants in infested mix died, with black, necrotic roots. Plants in the control mix were healthy and well-established. The pathogen was reisolated from roots of all inoculated plants and confirmed to be G. sylvaticum based on morphology and molecular analyses. Root disease of strawberry caused by G. sylvaticum has been reported in the USA (Campbell and Hendrix 1967; Nemec and Sanders 1970; Pratt and Green 1971). This is the first report of G. sylvaticum causing root rot of strawberry in Tennessee. With the loss of methyl bromide, sustainable disease control strategies are needed to provide effective management options for strawberry black root rot.

Neonatal Subarachnoid Hemorrhage Disrupts Multiple Aspects of Cerebellar Development.

Over the past decade, survival rates for extremely low gestational age neonates (ELGANs; <28 weeks gestation) has markedly improved. Unfortunately, a significant proportion of ELGANs will suffer from neurodevelopmental dysfunction. Cerebellar hemorrhagic injury (CHI) has been increasingly recognized in the ELGANs population and may contribute to neurologic dysfunction; however, the underlying mechanisms are poorly understood. To address this gap in knowledge, we developed a novel model of early isolated posterior fossa subarachnoid hemorrhage (SAH) in neonatal mice and investigated both acute and long-term effects. Following SAH on postnatal day 6 (P6), we found significant decreased levels of proliferation with the external granular layer (EGL), thinning of the EGL, decreased Purkinje cell (PC) density, and increased Bergmann glial (BG) fiber crossings at P8. At P42, CHI resulted in decreased PC density, decreased molecular layer interneuron (MLI) density, and increased BG fiber crossings. Results from both Rotarod and inverted screen assays did not demonstrate significant effects on motor strength or learning at P35-38. Treatment with the anti-inflammatory drug Ketoprofen did not significantly alter our findings after CHI, suggesting that treatment of neuro-inflammation does not provide significant neuroprotection post CHI. Further studies are required to fully elucidate the mechanisms through which CHI disrupts cerebellar developmental programming in order to develop therapeutic strategies for neuroprotection in ELGANs.

Somatosensory Impairment and Chronic Pain Following Stroke: An Observational Study.

BACKGROUND: Chronic pain and somatosensory impairment are common following a stroke. It is possible that an interaction exists between pain and somatosensory impairment and that a change in one may influence the other. We therefore investigated the presence of chronic pain and self-reported altered somatosensory ability in individuals with stroke, aiming to determine if chronic pain is more common in stroke survivors with somatosensory impairment than in those without. METHODS: Stroke survivors were invited to complete an online survey that included demographics, details of the stroke, presence of chronic pain, and any perceived changes in body sensations post-stroke. RESULTS: Survivors of stroke (n = 489) completed the survey with 308 indicating that they experienced chronic pain and 368 reporting perceived changes in somatosensory function. Individuals with strokes who reported altered somatosensory ability were more likely to experience chronic pain than those who did not (OR = 1.697; 95% CI 1.585, 2.446). Further, this difference was observed for all categories of sensory function that were surveyed (detection of light touch, body position, discrimination of surfaces and temperature, and haptic object recognition). CONCLUSIONS: The results point to a new characteristic of chronic pain in strokes, regardless of nature or region of the pain experienced, and raises the potential of somatosensory impairment being a rehabilitation target to improve pain-related outcomes for stroke survivors.