Hemispheric functional segregation facilitates target detection during sustained visuospatial attention

Visuospatial attention is strongly lateralized, with the right hemisphere commonly exhibiting stronger activation and connectivity patterns than the left hemisphere during attentive processes. However, whether such asymmetry influences inter‐hemispheric information transfer and behavioral performance is not known. Here we used a region of interest (ROI) and network‐based approach to determine steady‐state fMRI functional connectivity (FC) in the whole cerebral cortex during a leftward/rightward covert visuospatial attention task. We found that the global FC topology between either ROIs or networks was independent on the attended side. The side of attention significantly modulated FC strength between brain networks, with leftward attention primarily involving the connections of the right visual network with dorsal and ventral attention networks in both the left and right hemisphere. High hemispheric functional segregation significantly correlated with faster target detection response times (i.e., better performance). Our findings suggest that the dominance of the right hemisphere in visuospatial attention is associated with an hemispheric functional segregation that is beneficial for behavioral performance.     

Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01302-y.     

Postbiotics and Kidney Disease

Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation.     

Co-Occurrence of Hypoglycin A and Hypoglycin B in Sycamore and Box Elder Maple Proved by LC-MS/MS and LC-HR-MS

Hypoglycin A (HGA) and methylenecyclpropylglycine (MCPrG) are formed by some maple trees (Acer species) and have been associated with incidences of atypical myopathy among horses in pastures. In this work, a simple and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method without derivatization was developed for the quantification of HGA and MCPrG in maple samples and validated according to EU guidelines. The LOQ presented here for HGA (16.4 µg/kg) is considerably lower than the lowest published LOQ (500 µg/kg). This method confirms that sycamore and box elder maple contain considerable amounts of HGA and MCPrG. In addition, the presence of the dipeptides hypoglycin B and γ-glutamyl-MCPrG in these two maple species is shown using high-resolution MS. This is the first report on the presence of these dipeptides in maple since 1973. The presence of HGB and γ-glutamyl-MCPrG could change the way we understand animal intoxication following the ingestion of maple.     

Programmatic adaptations to acute malnutrition screening and treatment during the COVID‐19 pandemic

The COVID‐19 pandemic presented numerous challenges to acute malnutrition screening and treatment. To enable continued case identification and service delivery while minimising transmission risks, many organisations and governments implemented adaptations to community‐based management of acute malnutrition (CMAM) programmes for children under 5. These included: Family mid‐upper arm circumference (MUAC); modified admission and discharge criteria; modified dosage of therapeutic foods; and reduced frequency of follow‐up visits. This paper presents qualitative findings from a larger mixed methods study to document practitioners'' operational experiences and lessons learned from these adaptations. Findings reflect insights from 37 interviews representing 15 organisations in 17 countries, conducted between July 2020 and January 2021. Overall, interviewees indicated that adaptations were mostly well‐accepted by staff, caregivers and communities. Family MUAC filled screening gaps linked to COVID‐19 disruptions; however, challenges included long‐term accuracy of caregiver measurements; implementing an intervention that could increase demand for inconsistent services; and limited guidance to monitor programme quality and impact. Modified admission and discharge criteria and modified dosage streamlined logistics and implementation with positive impacts on staff workload and caregiver understanding of the programme. Reduced frequency of visits enabled social distancing by minimising crowding at facilities and lessened caregivers'' need to travel. Concerns remained about how adaptations impacted children''s identification for and progress through treatment and programme outcomes. Most respondents anticipated reverting to standard protocols once transmission risks were mitigated. Further evidence, including multi‐year programmatic data analysis and rigorous research, is needed in diverse contexts to understand adaptations'' impacts, including how to ensure equity and mitigate unintended consequences.     

Cell chirality exhibition of brain microvascular endothelial cells is dependent on micropattern width

Left-right asymmetry is a conserved property in nature and observed in the human body, a property known as cell chirality. Cell chirality is often studied using micropatterned in vitro models. However, micropattern geometry and size often varies across different studies, making it challenging to compare results. Here, we utilized micropatterned RGD-peptide lines on hyaluronic acid hydrogels to investigate the effect of the micropattern width on the exhibited cell chirality bias of brain microvascular endothelial cells. Overall, this cell type exhibited a negative chirality bias on micropatterned lines ranging from 10 μm to 400 μm in width, where the negative bias was most pronounced on the 100 μm wide lines. We also observed that this exhibited chirality bias varied across the line width. This work serves as a guide to determine optimal micropattern width for further investigations on cell chirality bias and its prominence in e.g., disease states or upon exposure to toxic substances.

Brain endothelial microvascular cell chirality is dependent on micropattern width and spatial localization. Finding the optimal micropattern width and including only the centre cells in the analysis for chirality-based experiments might improve further experimental results.     

Folic acid functionalization for targeting self-assembled paclitaxel-based nanoparticles

Hetero-nanoparticles self-assembled from a conjugate bearing folic acid as the targeting agent, and another bearing paclitaxel as the active agent are reported. Hetero-nanoparticles containing varying percentages of folic acid conjugates are characterised, and their biological activity is determined.

Self-assembled hetero-nanoparticles are obtained by mixing paclitaxel and folic acid conjugates.     

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province,Italy, December 2019 to January 2020

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.