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.

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.

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.

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.

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.

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.

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.

Characterizing exogenous mRNA delivery, trafficking, cytoplasmic release and RNA-protein correlations at the level of single cells.

The use of synthetic messenger ribonucleic acid (mRNA) to express specific proteins is a highly promising therapeutic and vaccine approach that avoids many safety issues associated with viral or DNA-based systems. However, in order to optimize mRNA designs and delivery, technology advancements are required to study fundamental mechanisms of mRNA uptake and localization at the single-cell and tissue level. Here, we present a single RNA sensitive fluorescent labeling method which allows us to label and visualize synthetic mRNA without significantly affecting function. This approach enabled single cell characterization of mRNA uptake and release kinetics from endocytic compartments, the measurement of mRNA/protein correlations, and motivated the investigation of mRNA induced cellular stress, all important mechanisms influencing protein production. In addition, we demonstrated this approach can facilitate near-infrared imaging of mRNA localization in vivo and in ex-vivo tissue sections, which will facilitate mRNA trafficking studies in pre-clinical models. Overall, we demonstrate the ability to study fundamental mechanisms necessary to optimize delivery and therapeutic strategies, in order to design the next generation of novel mRNA therapeutics and vaccines.

The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls.

Psyllium is a widely used treatment for constipation. It traps water in the intestine increasing stool water, easing defaecation and altering the colonic environment. We aimed to assess the impact of psyllium on faecal microbiota, whose key role in gut physiology is being increasingly recognised. We performed two randomised, placebo-controlled, double-blinded trials comparing 7 days of psyllium with a placebo (maltodextrin) in 8 healthy volunteers and 16 constipated patients respectively. We measured the patients' gastrointestnal (GI) transit, faecal water content, short-chain fatty acid (SCFA) and the stool microbiota composition. While psyllium supplement had a small but significant effect on the microbial composition of healthy adults (increasing Veillonella and decreasing Subdoligranulum), in constipated subjects there were greater effects on the microbial composition (increased Lachnospira, Faecalibacterium, Phascolarctobacterium, Veillonella and Sutterella and decreased uncultured Coriobacteria and Christensenella) and alterations in the levels of acetate and propionate. We found several taxa to be associated with altered GI transit, SCFAs and faecal water content in these patients. Significant increases in three genera known to produce butyrate, Lachnospira, Roseburia and Faecalibacterium, correlated with increased faecal water. In summary, psyllium supplementation increased stool water and this was associated with significant changes in microbiota, most marked in constipated patients.

Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS) via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small- and large-bowel contents after oral challenge. METHODS: We performed a 3-period, cross-over study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/wk) and reported bloating. In parallel, we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500-mL drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects' responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary end point was whether participants had a clinically important symptom response during the 300 minutes after consumption of the drink. RESULTS: More patients with IBS reached the predefined symptom threshold after intake of inulin (13 of 29) or fructose (11 of 29) than glucose (6 of 29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small-bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared with glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P < .05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach the symptom threshold. CONCLUSIONS: Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses after intake of fructose or inulin; patients reported symptoms more frequently after inulin than controls. In patients with a response to inulin, symptoms related to levels of intraluminal gas, but peak gas levels did not differ significantly between responders, nonresponders, or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT01776853.

Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans.

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment.

Effects of Bolus and Continuous Nasogastric Feeding on Gastric Emptying, Small Bowel Water Content, Superior Mesenteric Artery Blood Flow, and Plasma Hormone Concentrations in Healthy Adults: A Randomized Crossover Study.

OBJECTIVE: We aimed to demonstrate the effect of continuous or bolus nasogastric feeding on gastric emptying, small bowel water content, and splanchnic blood flow measured by magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal hormone secretion. BACKGROUND: Nasogastric/nasoenteral tube feeding is often complicated by diarrhea but the contribution of feeding strategy to the etiology is unclear. METHODS: Twelve healthy adult male participants who underwent nasogastric intubation before a baseline MRI scan, received 400  mL of Resource Energy (Nestle) as a bolus over 5 minutes or continuously over 4  hours via pump in this randomized crossover study. Changes in gastric volume, small bowel water content, and superior mesenteric artery blood flow and velocity were measured over 4  hours using MRI and blood glucose and plasma concentrations of insulin, peptide YY, and ghrelin were assayed every 30 minutes. RESULTS: Bolus nasogastric feeding led to significant elevations in gastric volume (P < 0.0001), superior mesenteric artery blood flow (P < 0.0001), and velocity (P = 0.0011) compared with continuous feeding. Both types of feeding reduced small bowel water content, although there was an increase in small bowel water content with bolus feeding after 90 minutes (P < 0.0068). Similarly, both types of feeding led to a fall in plasma ghrelin concentration although this fall was greater with bolus feeding (P < 0.0001). Bolus feeding also led to an increase in concentrations of insulin (P = 0.0024) and peptide YY (P < 0.0001), not seen with continuous feeding. CONCLUSION: Continuous nasogastric feeding does not increase small bowel water content, thus fluid flux within the small bowel is not a major contributor to the etiology of tube feeding-related diarrhea.

Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies.

IMPORTANCE: Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care. OBJECTIVE: To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies. DESIGN, SETTING, AND PARTICIPANTS: Case series identified from 125,426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation. EXPOSURES: NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y). MAIN OUTCOMES AND MEASURES: Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort. RESULTS: From a cohort of 125,426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident. CONCLUSIONS AND RELEVANCE: In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.

Differential effects of FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) on small and large intestinal contents in healthy subjects shown by MRI.

OBJECTIVES: The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. METHODS: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan. RESULTS: Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0-5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11-132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17-106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121-12,300) p.p.m./min relative to fructose alone (P<0.01, n=13). CONCLUSIONS: Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.

Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state.

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

Comparison of uptake and predictors of adherence in primary and secondary prevention of cardiovascular disease in a community-based cardiovascular prevention programme (MyAction Westminster).

BACKGROUND: Despite the benefits of cardiac rehabilitation, uptake and adherence remain suboptimal. With the advent of NHS Health Checks, primary prevention programmes have also been advocated, but little is known about uptake and adherence rates. This study examined rates and predictors of adherence amongst patients with cardiovascular disease (CVD) and those at high multifactorial risk (HRI) attending an innovative programme integrating primary and secondary prevention. METHODS: Comparison of rates of uptake and adherence and also predictors of adherence between 401 CVD patients and 483 HRI. The outcome was the number of sessions attended and predictor variables included clinical and psychosocial variables. Differences between groups were examined using t-tests and non-parametric tests. Multivariable regression analyses examined predictors of adherence. RESULTS: Uptake to the assessment (CVD: 97%, HRI: 88%) and the programme (CVD: 78%, HRI: 74%) were high for both groups. An average of 8/12 was attended in both groups. Beliefs about treatment predicted adherence for both groups (P < 0.01). The alcohol causal belief also predicted poorer adherence amongst CVD patients (P < 0.02). Older age also predicted better adherence amongst HRI (P < 0.001). CONCLUSIONS: Rates of uptake and adherence were high for both HRI and CVD patients. Further research is needed to examine whether interventions targeting predictor variables further improve adherence.

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.

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.

Hospital on a page: standardizing data presentation to drive quality improvement.

Over the past five years, the Credit Valley Hospital (CVH) invested time and financial and human resources into performance measurement systems. In doing so, CVH launched a number of data tools including electronic scorecards and dashboards. However, the processes and accountability structures associated with the tools struggled to gain credibility with clinical and administrative leadership as the performance measurement system was primarily driven by the technology rather than a sound information strategy. Although a corporate-level scorecard was regularly updated, program-related scorecards and other measurement tools were only populated when programs reported to the board, at the time of accreditation or as a result of regulatory requirements. In addition, information contained in data reports was often presented in a manner that did not engage clinical and corporate decision-makers in the key issues of quality, access and sustainability. Following the release of its new strategic plan in 2009, CVH renewed its performance measurement framework and the methods by which it presented data so that the organization's strategic plan could be implemented and measured from the boardroom to the bedside. Long, complex spreadsheets were transformed into strategically designed, easy-to-understand, easy-to-access reports released in a standardized method in terms of format, media, content and timing. The following article describes the method CVH adopted to communicate the organization's performance and the role it played in enhancing the culture of quality and patient safety within the hospital.

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.