Examining adaptive models of care implemented in hospital ICUs during the COVID-19 pandemic: a qualitative study.

BACKGROUND: The emergence of the COVID-19 pandemic led to an increased demand for hospital beds, which in turn led to unique changes to both the organisation and delivery of patient care, including the adoption of adaptive models of care. Our objective was to understand staff perspectives on adaptive models of care employed in intensive care units (ICUs) during the pandemic. METHODS: We interviewed 77 participants representing direct care staff (registered nurses) and members of the nursing management team (nurse managers, clinical educators and nurse practitioners) from 12 different ICUs. Thematic analysis was used to code and analyse the data. RESULTS: Our findings highlight effective elements of adaptive models of care, including appreciation for redeployed staff, organising aspects of team-based models and ICU culture. Challenges experienced with the pandemic models of care were heightened workload, the influence of experience, the disparity between model and practice and missed care. Finally, debriefing, advanced planning and preparation, the redeployment process and management support and communication were important areas to consider in implementing future adaptive care models. CONCLUSION: The implementation of adaptive models of care in ICUs during the COVID-19 pandemic provided a rapid solution for staffing during the surge in critical care patients. Findings from this study highlight some of the challenges of implementing redeployment as a staffing strategy, including how role clarity and accountability can influence the adoption of care delivery models, lead to workarounds and contribute to adverse patient and nurse outcomes.

Enhancing early parenting in the community: Preliminary results from a learning collaborative approach to scale up Attachment and Biobehavioral Catch-up.

Attachment and Biobehavioral Catch-up (ABC) is a promising home-visiting intervention promoting sensitive caregiving and secure parent-child attachment in families with young children. The goal of this study was to examine a learning collaborative approach to disseminating ABC in a community setting. Training outcomes (e.g., trainee completion, satisfaction, effectiveness of training methods) and intervention outcomes (e.g., parent behavior, parent beliefs, child socioemotional development) were examined. Eighteen practitioners participated in the ABC learning collaborative; 13 completed training. Quantitative and qualitative measures indicated that trainees were satisfied with their experience and valued the unique collaboration opportunities offered by the learning collaborative. In addition, trainees served 67 families in the community, 37 of whom completed all sessions of ABC. The study was conducted in the United States. Racial demographics of the children in the sample included: 56.7% White, 22.4% Black/African-American, 17.9% Bi- or Multi-racial, and 3.0% unknown. Regarding ethnicity, 80.6% were Non-Hispanic/Latino, 10.4% were Hispanic/Latino, and 9.0% were unknown. Caregivers who completed ABC showed more sensitive parenting behavior and reported positive changes in their perceived self-efficacy and their beliefs around infant crying. Children who received ABC showed increased socioemotional functioning. Results demonstrate successful dissemination of ABC in the community using a learning collaborative approach.

El Alcance de Afectividad y Bio-comportamiento (ABC) es una prometedora intervención de visita a casa que promueve el cuidado sensible y una relación progenitor-niño segura en familias con niños pequeños. El propósito de este estudio fue examinar un acercamiento de aprendizaje colaborativo para diseminar el ABC en un escenario comunitario. Se examinaron los resultados de entrenamiento (v.g. que el entrenado completó el proceso, satisfacción, efectividad de los métodos de entrenamiento) y los resultados de intervención (v.g. comportamiento del progenitor, creencias del progenitor, desarrollo socioemocional del niño). Dieciocho profesionales en la práctica participaron en el proceso de aprendizaje colaborativo; 13 completaron el entrenamiento, Las medidas cuantitativas y cualitativas indicaron que quienes se entrenaban estaban satisfechos con su experiencia y valoraron las oportunidades de colaboración que el proceso de aprendizaje colaborativo ofrecía de manera única. Adicionalmente, quienes se entrenaban les sirvieron a 67 familias en la comunidad, 37 de las cuales completaron todas las sesiones del ABC. El estudio se llevó a cabo en los Estados Unidos. Los perfiles demográficos raciales de los niños incluyen: 56.7% de raza blanca, 22.4% de raza negra o Afroamericanos, 17.9% birraciales o multirraciales, con un 3.0% cuya raza se desconoce. En cuanto a la etnicidad, 80.6% no eran hispanos o latinos, 10.4% eran hispanos o latinos, con un 9.0% cuya etnicidad se desconoce. Los cuidadores que completaron el ABC mostraron una conducta de crianza más sensible y reportaron cambios positivos en cuanto a su percepción de auto efectividad y su creencia acerca del llanto del infante. Los niños que recibieron el ABC mostraron un aumento en su funcionamiento socioemocional. Los resultados demuestran una exitosa diseminación del ABC en la comunidad usando un acercamiento de aprendizaje colaborativo.

L'attachement et le rattrapage bio-comportemental (en anglais Attachment and Biobehavioral Catch-up, soit ABC) est une intervention prometteuse de visite à domicile promouvant des soins sensibles et un attachement parent-enfant sécure chez les familles avec de jeunes enfants. Le but de cette étude est d'examiner une approche collaborative d'apprentissage à la dissémination de l'ABC dans le contexte d'une communauté. Les résultats de la formation (par exemple le fait de terminer le stage, la satisfaction, l'efficacité des méthodes de formation) et les résultats de l'intervention (par exemple le comportement du parent, les croyances parentales, le développement socio-émotionnel de l'enfant) ont été examinés. Dix-huit praticiens ont participé à la collaboration d'apprentissage ABC; 13 ont terminé la formation. Les mesures quantitatives and qualitatives ont indiqué que les stagiaires étaient satisfaits de leur expérience et avaient apprécié la chance d'une collaboration unique offerte par la collaboration d'apprentissage. De plus les stagiaires ont aidé 67 familles dans la communauté, 37 d'entre elles ayant terminé toutes les séances de l'ABC. L'étude a été faite aux Etats-Unis d'Amérique. Les données démographiques raciales des enfants dans l'échantillon ont inclus: 56,7% blancs, 22,4% noirs américains, 17,9% métisses ou multi-ethniques, et 3,0% de race inconnue. Concernant l'ethnicité, 80,6% était Non-Hispaniques/Non-Latinos, 10,4% étaient Hispaniques/Latinos et 9,0% étaient d'une ethnicité inconnue. Les personnes prenant soin des enfants qui ont complété l'ABC ont fait preuve d'un comportement de parentage plus sensible et fait état de changements positifs dans leur auto-efficacité perçue et leurs croyances concernant les pleurs des bébés. Les enfants ayant reçu l'ABC ont démontré un fonctionnement socio-émotionnel plus élevé. Les résultats démontrent une dissémination réussie de l'ABC dans une communauté en utilisant une approche collaborative d'apprentissage.

Chemically Induced Extracellular Ice Nucleation Reduces Intracellular Ice Formation Enabling 2D and 3D Cellular Cryopreservation.

3D cell assemblies such as spheroids reproduce the in vivo state more accurately than traditional 2D cell monolayers and are emerging as tools to reduce or replace animal testing. Current cryopreservation methods are not optimized for complex cell models, hence they are not easily banked and not as widely used as 2D models. Here we use soluble ice nucleating polysaccharides to nucleate extracellular ice and dramatically improve spheroid cryopreservation outcomes. This protects the cells beyond using DMSO alone, and with the major advantage that the nucleators function extracellularly and hence do not need to permeate the 3D cell models. Critical comparison of suspension, 2D and 3D cryopreservation outcomes demonstrated that warm-temperature ice nucleation reduces the formation of (fatal) intracellular ice, and in the case of 2/3D models this reduces propagation of ice between adjacent cells. This demonstrates that extracellular chemical nucleators could revolutionize the banking and deployment of advanced cell models.

Synthesis of Poly(2-(methylsulfinyl)ethyl methacrylate) via Oxidation of Poly(2-(methylthio)ethyl methacrylate): Evaluation of the Sulfoxide Side Chain on Cryopreservation.

Conventional cryopreservation solutions rely on the addition of organic solvents such as DMSO or glycerol, but these do not give full recovery for all cell types, and innovative cryoprotectants may address damage pathways which these solvents do not protect against. Macromolecular cryoprotectants are emerging, but there is a need to understand their structure-property relationships and mechanisms of action. Here we synthesized and investigated the cryoprotective behavior of sulfoxide (i.e., "DMSO-like") side-chain polymers, which have been reported to be cryoprotective using poly(ethylene glycol)-based polymers. We also wanted to determine if the polarized sulfoxide bond (S+O- character) introduces cryoprotective effects, as this has been seen for mixed-charge cryoprotective polyampholytes, whose mechanism of action is not yet understood. Poly(2-(methylsulfinyl)ethyl methacrylate) was synthesized by RAFT polymerization of 2-(methylthio)ethyl methacrylate and subsequent oxidation to sulfoxide. A corresponding N-oxide polymer was also prepared and characterized: (poly(2-(dimethylamineoxide)ethyl methacrylate). Ice recrystallization inhibition assays and differential scanning calorimetry analysis show that the sulfoxide side chains do not modulate the frozen components during cryopreservation. In cytotoxicity assays, it was found that long-term (24 h) exposure of the polymers was not tolerated by cells, but shorter (30 min) incubation times, which are relevant for cryopreservation, were tolerated. It was also observed that overoxidation to the sulfone significantly increased the cytotoxicity, and hence, these materials require a precision oxidation step to be deployed. In suspension cell cryopreservation investigations, the polysulfoxides did not increase cell recovery 24 h post-thaw. These results show that unlike hydrophilic backboned polysulfides, which can aid cryopreservation, the installation of the sulfoxide group onto a polymer does not necessarily bring cryoprotective properties, highlighting the challenges of developing and discovering macromolecular cryoprotectants.

Chemical approaches to cryopreservation.

Cryopreservation of cells and biologics underpins all biomedical research from routine sample storage to emerging cell-based therapies, as well as ensuring cell banks provide authenticated, stable and consistent cell products. This field began with the discovery and wide adoption of glycerol and dimethyl sulfoxide as cryoprotectants over 60 years ago, but these tools do not work for all cells and are not ideal for all workflows. In this Review, we highlight and critically review the approaches to discover, and apply, new chemical tools for cryopreservation. We summarize the key (and complex) damage pathways during cellular cryopreservation and how each can be addressed. Bio-inspired approaches, such as those based on extremophiles, are also discussed. We describe both small-molecule-based and macromolecular-based strategies, including ice binders, ice nucleators, ice nucleation inhibitors and emerging materials whose exact mechanism has yet to be understood. Finally, looking towards the future of the field, the application of bottom-up molecular modelling, library-based discovery approaches and materials science tools, which are set to transform cryopreservation strategies, are also included.

Pollen derived macromolecules serve as a new class of ice-nucleating cryoprotectants.

Cryopreservation of biological material is vital for existing and emerging biomedical and biotechnological research and related applications, but there remain significant challenges. Cryopreservation of cells in sub-milliliter volumes is difficult because they tend to deeply supercool, favoring lethal intracellular ice formation. Some tree pollens are known to produce polysaccharides capable of nucleating ice at warm sub-zero temperatures. Here we demonstrated that aqueous extractions from European hornbeam pollen (pollen washing water, PWW) increased ice nucleation temperatures in 96-well plates from ≈ - 13 °C to ≈ - 7 °C. Application of PWW to the cryopreservation of immortalized T-cells in 96-well plates resulted in an increase of post-thaw metabolic activity from 63.9% (95% CI [58.5 to 69.2%]) to 97.4% (95% CI [86.5 to 108.2%]) of unfrozen control. When applied to cryopreservation of immortalized lung carcinoma monolayers, PWW dramatically increased post-thaw metabolic activity, from 1.6% (95% CI [- 6.6 to 9.79%]) to 55.0% (95% CI [41.6 to 68.4%]). In contrast to other ice nucleating agents, PWW is soluble, sterile and has low cytotoxicity meaning it can be readily incorporated into existing cryopreservation procedures. As such, it can be regarded as a unique class of cryoprotectant which acts by inducing ice nucleation at warm temperatures.

Candida albicans oscillating UME6 expression during intestinal colonization primes systemic Th17 protective immunity.

Systemic immunity is stringently regulated by commensal intestinal microbes, including the pathobiont Candida albicans. This fungus utilizes various transcriptional and morphological programs for host adaptation, but how this heterogeneity affects immunogenicity remains uncertain. We show that UME6, a transcriptional regulator of filamentation, is essential for intestinal C. albicans-primed systemic Th17 immunity. UME6 deletion and constitutive overexpression strains are non-immunogenic during commensal colonization, whereas immunogenicity is restored by C. albicans undergoing oscillating UME6 expression linked with ß-glucan and mannan production. In turn, intestinal reconstitution with these fungal cell wall components restores protective Th17 immunity to mice colonized with UME6-locked variants. These fungal cell wall ligands and commensal C. albicans stimulate Th17 immunity through multiple host pattern recognition receptors, including Toll-like receptor 2 (TLR2), TLR4, Dectin-1, and Dectin-2, which work synergistically for colonization-induced protection. Thus, dynamic gene expression fluctuations by C. albicans during symbiotic colonization are essential for priming host immunity against disseminated infection.

What about trauma? Accounting for trauma exposure and symptoms in the risk of suicide among adolescents who have been adopted.

BACKGROUND: Research suggests that individuals who have been adopted are at increased risk for suicidal behaviors, but this research does not account for the role of trauma. OBJECTIVES: The study provided rates of trauma exposure among individuals who were adopted with child welfare involvement. The study also examined risk of suicidal ideation (SI) and behaviors (SB) based on adoption status, first as bivariate associations and then in context of trauma exposure and symptoms. PARTICIPANTS AND SETTING: Participants in the LONGSCAN study were recruited at multiple US sites based on various risk factors for maltreatment. The current study included only those individuals with adequate information at key timepoints (n = 894), 106 (11.9%) of whom were adopted. METHODS: Measures were collected at multiple timepoints, including caregiver-report, self-report, and review of child welfare records. Data were analyzed through logistic regression and descriptive statistics. RESULTS: High rates of potentially traumatic experiences were found among individuals who were adopted (over 93%). The bivariate logistic regression replicated previous findings that adolescents who were adopted had increased likelihood of endorsing SI (OR 2.14, 95% CI 1.27-3.60, p = .004) and SB (OR 2.40, 95% CI 1.24-4.63, p = .009) compared to non-adopted peers. However, when polytrauma and traumatic stress symptoms were added to the model, adoption was no longer a significant predictor for SI (OR 1.35, 95% CI 0.70-2.60, p = .369) or SB (OR 1.46, 95% CI 0.68-3.13, p = .332). CONCLUSIONS: Although much remains to be explored about the association between adoption and risk for suicidal thoughts and behaviors, the current study indicates that traumatic stress plays a critical role.

Chemical approaches to cryopreservation.

Cryopreservation of cells and biologics underpins all biomedical research from routine sample storage to emerging cell-based therapies, as well as ensuring cell banks provide authenticated, stable and consistent cell products. This field began with the discovery and wide adoption of glycerol and dimethyl sulfoxide as cryoprotectants over 60 years ago, but these tools do not work for all cells and are not ideal for all workflows. In this Review, we highlight and critically review the approaches to discover, and apply, new chemical tools for cryopreservation. We summarize the key (and complex) damage pathways during cellular cryopreservation and how each can be addressed. Bio-inspired approaches, such as those based on extremophiles, are also discussed. We describe both small-molecule-based and macromolecular-based strategies, including ice binders, ice nucleators, ice nucleation inhibitors and emerging materials whose exact mechanism has yet to be understood. Finally, looking towards the future of the field, the application of bottom-up molecular modelling, library-based discovery approaches and materials science tools, which are set to transform cryopreservation strategies, are also included.

Delivering an efficient and effective support group for patients with implantable cardioverter-defibrillators (ICDs): patient perspectives of key concerns and predictors of inclination to attend.

BACKGROUND: A subset of patients experience psychological distress following insertion of an implantable cardioverter-defibrillator (ICD) and ICD support groups are recommended, however access to these groups is limited. This study aimed: to gauge a better understanding of patients' key ICD-related concerns; to determine patient interest in a support group and topics deemed helpful to address in a support group; and to examine factors which affect patient inclination to attend. METHODS: One hundred and thirty nine patients completed the ICD Patient Concerns Questionnaire - Brief (ICDC-B) and a semi-structured survey. Non-parametric tests were used to examine associations and differences in the quantitative data. Qualitative data were analysed using thematic analysis. RESULTS: 42% of respondents said they would attend a support group and inclination to attend was associated with higher ICD concerns and a shorter time since implant. Topics considered important to address in a group were information about heart conditions and devices, the impact of an ICD on daily life and coping with fear of shocks. CONCLUSION: We concluded that there is interest in further support amongst many patients and that ICD support groups may be delivered efficiently by targeting patients who have higher levels of ICD concerns and within the first few years after implant.

Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants.

OBJECTIVE: The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. MATERIAL AND METHODS: Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. RESULTS: Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. CONCLUSION: Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, 'gold standard' water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. CLINICAL TRIAL: This trial was registered at ClinicalTrials.gov as NCT03191045.

Feasibility Study of a New Magnetic Resonance Imaging Mini-capsule Device to Measure Whole Gut Transit Time in Paediatric Constipation.

OBJECTIVE: In England, 27,500 children are referred annually to hospital with constipation. An objective measure of whole gut transit time (WGTT) could aid management. The current standard WGTT assessment, the x-ray radiopaque marker (ROM) test, gives poor definition of colonic anatomy and the radiation dose required is undesirable in children. Our objective was to develop an alternative magnetic resonance imaging (MRI) WGTT measure to the x-ray ROM test and to demonstrate its initial feasibility in paediatric constipation. METHODS: With the Nottingham Young Person's Advisory Group we developed a small (8 × 4 mm), inert polypropylene capsule shell filled with MRI-visible fat emulsion. The capsule can be imaged using MRI fat and water in-phase and out-of-phase imaging. Sixteen patients with constipation and 19 healthy participants aged 7 to 18 years old were recruited. Following a common ROM protocol, the participants swallowed 24 mini-capsules each day for 3 days and were imaged on days 4 and 7 using MRI. The number of successful studies (feasibility) and WGTT were assessed. Participants' EuroQoL Visual Analogue Scale were also collected and compared between the day before the taking the first set of mini-capsules to the day after the last MRI study day. RESULTS: The mini-capsules were imaged successfully in the colon of all participants. The WGTT was 78 ±â€Š35 hours (mean ±â€Šstandard deviation) for patients, and 36 ±â€Š16 hours, P < 0.0001 for healthy controls. Carrying out the procedures did not change the EuroQoL Visual Analogue Scale scores before and after the procedures. CONCLUSIONS: Magnetic Resonance Imaging in Paediatric Constipation was a first-in-child feasibility study of a new medical device to measure WGTT in paediatric constipation using MRI. The study showed that the new method is feasible and is well tolerated.

Low DMSO Cryopreservation of Stem Cells Enabled by Macromolecular Cryoprotectants.

Mesenchymal stromal (stem) cells have potential in regenerative medicine and modulating the immune system. To deliver any cell-based therapy to the patient, it must be cryopreserved, most commonly in DMSO, which impacts cell function and causes clinical side effects. Here we report the use of a synthetically scalable polyampholyte to rescue the cryopreservation of mesenchymal stromal cells in low [DMSO] cryopreservation. Flow cytometry showed retention of key markers of multipotency comparable to 10% (v/v) DMSO, and the cells could be differentiated, showing this polymer material can be used to improve, or replace, current cryopreservation strategies.

Post-Thaw Culture and Measurement of Total Cell Recovery Is Crucial in the Evaluation of New Macromolecular Cryoprotectants.

The storage and transport of cells is a fundamental technology which underpins cell biology, biomaterials research, and emerging cell-based therapies. Inspired by antifreeze and ice-binding proteins in extremophiles, macromolecular (polymer) cryoprotectants are emerging as exciting biomaterials to enable the reduction and/or replacement of conventional cryoprotective agents such as DMSO. Here, we critically study post-thaw cellular outcomes upon addition of macromolecular cryoprotectants to provide unambiguous evidence that post-thaw culturing time and a mixture of assays are essential to claim a positive outcome. In particular, we observe that only measuring the viability of recovered cells gives false positives, even with non-cryoprotective polymers. Several systems gave apparently high viability but very low total cell recovery, which could be reported as a success but in practical applications would not be useful. Post-thaw culture time is also shown to be crucial to enable apoptosis to set in. Using this approach we demonstrate that polyampholytes (a rapidly emerging class of cryoprotectants) improve post-thaw outcomes across both measures, compared to poly(ethylene glycol), which can give false positives when only viability and short post-thaw time scales are considered. This work will help guide the discovery of new macromolecular cryoprotectants and ensure materials which only give positive results under limited outcomes can be quickly identified and removed.

Combinatorial Biomaterials Discovery Strategy to Identify New Macromolecular Cryoprotectants.

Cryoprotective agents (CPAs) are typically solvents or small molecules, but there is a need for innovative CPAs to reduce toxicity and increase cell yield, for the banking and transport of cells. Here we use a photochemical high-throughput discovery platform to identify macromolecular cryoprotectants, as rational design approaches are currently limited by the lack of structure-property relationships. Using liquid handling systems, 120 unique polyampholytes were synthesized using photopolymerization with RAFT agents. Cryopreservation screening identified "hit" polymers and nonlinear trends between composition and function, highlighting the requirement for screening, with polymer aggregation being a key factor. The most active polymers reduced the volume of dimethyl sulfoxide (DMSO) required to cryopreserve a nucleated cell line, demonstrating the potential of this approach to identify materials for cell storage and transport.

Polyampholytes as Emerging Macromolecular Cryoprotectants.

Cellular cryopreservation is a platform technology which underpins cell biology, biochemistry, biomaterials, diagnostics, and the cold chain for emerging cell-based therapies. This technique relies on effective methods for banking and shipping to avoid the need for continuous cell culture. The most common method to achieve cryopreservation is to use large volumes of organic solvent cryoprotective agents which can promote either a vitreous (ice free) phase or dehydrate and protect the cells. These methods are very successful but are not perfect: not all cell types can be cryopreserved and recovered, and the cells do not always retain their phenotype and function post-thaw. This Perspective will introduce polyampholytes as emerging macromolecular cryoprotective agents and demonstrate they have the potential to impact a range of fields from cell-based therapies to basic cell biology and may be able to improve, or replace, current solvent-based cryoprotective agents. Polyampholytes have been shown to be remarkable (mammalian cell) cryopreservation enhancers, but their mechanism of action is unclear, which may include membrane protection, solvent replacement, or a yet unknown protective mechanism, but it seems the modulation of ice growth (recrystallization) may only play a minor role in their function, unlike other macromolecular cryoprotectants. This Perspective will discuss their synthesis and summarize the state-of-the-art, including hypotheses of how they function, to introduce this exciting area of biomacromolecular science.

Dimeric benzoboroxoles for targeted activity against Mycobacterium tuberculosis.

Dimeric benzoboroxoles that are covalently linked by a short scaffold enhance selective anti-tubercular activity. These multimeric benzoboroxole compounds are capable of engaging the specific extracellular Mycobacterium tuberculosis glycans, do not lead to the evolution of resistance and bypass the need to cross the impermeable mycobacterial cell envelope barrier.

Synthetically Scalable Poly(ampholyte) Which Dramatically Enhances Cellular Cryopreservation.

The storage and transport of frozen cells underpin the emerging/existing cell-based therapies and are used in every biomedical research lab globally. The current gold-standard cryoprotectant dimethyl sulfoxide (DMSO) does not give quantitative cell recovery in suspension or in two-dimensional (2D) or three-dimensional (3D) cell models, and the solvent and cell debris must be removed prior to application/transfusion. There is a real need to improve this 50-year-old method to underpin emerging regenerative and cell-based therapies. Here, we introduce a potent and synthetically scalable polymeric cryopreservation enhancer which is easily obtained in a single step from a low cost and biocompatible precursor, poly(methyl vinyl ether-alt-maleic anhydride). This poly(ampholyte) enables post-thaw recoveries of up to 88% for a 2D cell monolayer model compared to just 24% using conventional DMSO cryopreservation. The poly(ampholyte) also enables reduction of [DMSO] from 10 wt % to just 2.5 wt % in suspension cryopreservation, which can reduce the negative side effects and speed up post-thaw processing. After thawing, the cells have reduced membrane damage and faster growth rates compared to those without the polymer. The polymer appears to function by a unique extracellular mechanism by stabilization of the cell membrane, rather than by modulation of ice formation and growth. This new macromolecular cryoprotectant will find applications across basic and translational biomedical science and may improve the cold chain for cell-based therapies.

A pilot study of visceral fat and its association with adipokines, stool calprotectin and symptoms in patients with diverticulosis.

BACKGROUND: Complications of diverticular disease are increasingly common, possibly linked to increasing obesity. Visceral fat could contribute to the development of symptomatic diverticular disease through its pro-inflammatory effects. OBJECTIVE: The study had 2 aims. A) to develop a semi-automated algorithm to measure abdominal adipose tissue from 2-echo magnetic resonance imaging (MRI) data; B) to use this to determine if visceral fat was associated with bowel symptoms and inflammatory markers in patients with symptomatic and asymptomatic diverticular disease. DESIGN: An observational study measuring visceral fat using MRI together with serum adiponectin, leptin, stool calprotectin and patient-reported somatisation and bowel habit. SETTING: Medical and imaging research centres of a university hospital. PARTICIPANTS: MRI scans were performed on 55 patients after an overnight fast measuring abdominal subcutaneous and visceral adipose tissue volumes together with small bowel water content (SBWC). Blood and stool samples were collected and patients kept a 2 week stool diary and completed a somatisation questionnaire. MAIN OUTCOME MEASURES: Difference in the volume of visceral fat between symptomatic and asymptomatic patients. RESULTS: There were no significant differences in visceral (p = 0.98) or subcutaneous adipose (p = 0.60) tissue between symptomatic and asymptomatic patients. However measured fat volumes were associated with serum adipokines. Adiponectin showed an inverse correlation with visceral adipose tissue (VAT) (Spearman ρ = -0.5, p = 0.0003), which correlated negatively with SBWC (ρ = -0.3, p = 0.05). Leptin correlated positively with subcutaneous adipose tissue (ρ = 0.8, p < 0.0001). Overweight patients (BMI > 25 kgm-2) showed a moderate correlation between calprotectin and VAT (ρ = 0.3, p = 0.05). Somatization scores were significantly higher in symptomatic patients (p < 0.0003). CONCLUSIONS: Increasing visceral fat is associated with lower serum adiponectin and increased faecal calprotectin suggesting a pro-inflammatory effect which may predispose to the development of complications of diverticulosis.

Promoting trauma-informed parenting of children in out-of-home care: An effectiveness study of the resource parent curriculum.

The Resource Parent Curriculum (RPC) is a workshop designed to promote trauma-informed parenting among foster, adoptive, and kinship caregivers (i.e., resource parents). The ultimate goal of RPC is to improve placement stability and promote healing from traumatic stress in children who have been placed in out-of-home care. The current study examined data from multiple RPC implementation sites throughout the United States. This study used a pre- versus postworkshop design to assess resource parents' (n = 314) improvement on trauma-informed parenting, perceived self-efficacy for parenting a child who experienced trauma, tolerance of child misbehavior, and whether parent characteristics moderated the impact of RPC on these outcomes. A repeated measures multivariate analysis of variance (MANOVA) demonstrated improvement from pre- to postworkshop on trauma-informed parenting F(1, 259) = 11.96, p = .001, η2 = .044; parenting self-efficacy F(1, 259) = 17.41, p = .000, η2 = .063; and tolerance of child misbehavior F(1, 259) = 3.94, p = .048, η2 = .015, regardless of parent characteristics (e.g., age, gender race/ethnicity, and resource parent type). The results of the current study support prior work showing the effectiveness of RPC in improving resource parents' trauma-informed knowledge and attitudes and further demonstrates the effectiveness of RPC with a diverse range of resource parents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).