A streamlined multidisciplinary metabolic clinic in psychiatric recovery service: a pilot study.

Background: The metabolic syndrome (MetS) is a collection of risk factors for cardiovascular disease and type-2 diabetes, that includes central obesity, hypertension, hyperglycaemia and dyslipidaemia. An audit indicated inadequate MetS screening in an Australian psychiatric recovery service. Objectives: We aimed to improve MetS screening, identification and intervention by offering streamlined lifestyle education, clinical reviews and discharge planning. This pilot program prioritized holistic, culturally-sensitive, patient-centric, and trauma-informed approaches to enhance metabolic health outcomes. Methods: A Metabolic Clinic was piloted in two psychiatric rehabilitation cottages (n=35), which involved disciplines of dietetics, exercise physiology, diversional therapy, occupational therapy, peer workforce, social work, clinical psychology, pharmacy, nursing and medical. Another cottage (n=15) was assigned as the comparison and received standard care. A 12-week, 3-times-per-week lifestyle and behavioral program, called MetFit, was devised and offered to those identified at screening for the treatment cottages. Outcome measures were feasibility measures, the five metabolic parameters (waist circumference, blood pressure, fasting serum triglycerides, high-density lipoprotein, and glucose), functional measures, and a meal questionnaire. Results: The treatment cottages had qualitative advantages in screening and identifying MetS. Of four enrolled consumers in MetFit, an improvement of triglycerides (p=0.08), squats (p=0.02), and push-ups (p=0.07) was observed. Major challenges of enrolment included an overall lack of acknowledgment of its importance, poor motivation of consumers and resources limitation. Conclusions: The one-stop provision of groups, peer support and inpatient pathway with multidisciplinary team-integration was generally accepted by consumers and the MDT and has iteratively demonstrated the urgent need for consumer-centered physical care and a cultural shift to foster collaboration within a psychiatric service.

Validation par entretien cognitif de l'outil d'évaluation des plaies malignes MWAT-R.

La détresse physique et émotionnelle que peuvent causer au patient et à sa famille les plaies malignes dues à un cancer est souvent négligée. Malheureusement, nous ne disposons pas d'outils de dépistage et d'évaluation fiables et valides pouvant aider à mieux traiter ces plaies. Cette étude a cherché à valider un outil de mesure des résultats rapportés par les patients : le Malignant Wound Assessment Tool - Research (MWAT-R). Pour ce faire, huit patients ont été recrutés et interrogés selon la méthodologie de l'entretien cognitif. La compréhension et l'impression générale des patients vis-à-vis de cet outil ont été analysées. Nous avons constaté que la formulation et les choix de réponse posaient problème aux patients. En général, les participants ont néanmoins trouvé que les questions saisissaient bien les principaux enjeux relatifs aux plaies malignes et tenaient compte du point de vue du patient. Le fait d'établir la validité apparente et de contenu du MWAT-R du point de vue des patients par la technique d'entretien cognitif vient étayer la validité de cet outil.

Validation of the Malignant Wound Assessment Tool - Research (MWAT-R) using cognitive interviewing.

Malignant wounds as a result of cancer are under-recognized for the physical and emotional distress they cause patients and their families. Unfortunately, there is a lack of valid and reliable screening and assessment tools to aid in the management of malignant wounds. This study aims to validate a patient-reported outcome measurement tool, Malignant Wound Assessment Tool - Research (MWAT-R). Eight patients were recruited and interviewed using the cognitive interviewing methodology to validate this tool. Patients' understanding and overall impression of the MWAT-R were explored. Our findings showed that the wording and response options posed challenges for patients in completing the tool. Overall, participants felt that questions captured the key issues related to dealing with a malignant wound and accounted for the patients' perspective. Establishing the content and face validity of the MWAT-R from the patients' perspectives using cognitive interviews has provided further evidence to the validity of this tool.

Geographic clusters in underimmunization and vaccine refusal.

BACKGROUND AND OBJECTIVE: Parental refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in some communities. Such clusters could pose public health risks and barriers to achieving immunization quality benchmarks. Our aims were to (1) describe geographic clusters of underimmunization and vaccine refusal, (2) compare clusters of underimmunization with different vaccines, and (3) evaluate whether vaccine refusal clusters may pose barriers to achieving high immunization rates. METHODS: We analyzed electronic health records among children born between 2000 and 2011 with membership in Kaiser Permanente Northern California. The study population included 154,424 children in 13 counties with continuous membership from birth to 36 months of age. We used spatial scan statistics to identify clusters of underimmunization (having missed 1 or more vaccines by 36 months of age) and vaccine refusal (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes). RESULTS: We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010-2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P < .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them. CONCLUSIONS: Underimmunization and vaccine refusal cluster geographically. Spatial scan statistics may be a useful tool to identify locations with challenges to achieving high immunization rates, which deserve focused intervention.

When small words foretell academic success: the case of college admissions essays.

The smallest and most commonly used words in English are pronouns, articles, and other function words. Almost invisible to the reader or writer, function words can reveal ways people think and approach topics. A computerized text analysis of over 50,000 college admissions essays from more than 25,000 entering students found a coherent dimension of language use based on eight standard function word categories. The dimension, which reflected the degree students used categorical versus dynamic language, was analyzed to track college grades over students' four years of college. Higher grades were associated with greater article and preposition use, indicating categorical language (i.e., references to complexly organized objects and concepts). Lower grades were associated with greater use of auxiliary verbs, pronouns, adverbs, conjunctions, and negations, indicating more dynamic language (i.e., personal narratives). The links between the categorical-dynamic index (CDI) and academic performance hint at the cognitive styles rewarded by higher education institutions.

MEMS-based shear characterization of soft hydrated samples.

We have designed, fabricated, calibrated and tested actuators for shear characterization to assess microscale shear properties of soft substrates. Here we demonstrate characterization of dry silicone and hydrated polyethelyne glycol. Microscale tools, including atomic force microscopes and nanoindenters, often have limited functionality in hydrated environments. While electrostatic comb-drive actuators are particularly susceptible to moisture damage, through chemical vapor deposition of hexamethyldisiloxane, we increase the hydrophobicity of our electrostatic devices to a water contact angle 90 ± 3°. With this technique we determine the effective shear stiffness of both dry and hydrated samples for a range of soft substrates. Using computational and analytical models, we compare our empirically determined effective shear stiffness with existing characterization methods, rheology and nanoindentation, for samples with shear moduli ranging from 5-320 kPa. This work introduces a new approach for microscale assessment of synthetic materials that can be used on biological materials for basic and applied biomaterials research.

In verbis, vinum? Relating themes in an open-ended writing task to alcohol behaviors.

Alcohol's function as a regulator of emotions has long been denoted in figures of speech, most famously 'in vino, veritas' (in wine, truth). In contrast, we ask whether an individual's self-reported alcohol consumption and related attitudes can be correlated with the words they use to write about alcohol. Participants completed an open-ended essay as part of a survey on alcohol attitudes and behaviors. We used a computerized technique, the Meaning Extraction Method, to summarize the responses into thematic tropes, and correlated these with quantitative measurements of demographics, attitudes and behaviors. Participants were recruited using a random population postal survey in the UK (n=1001). Principal components analysis identified regular co-occurring words, to locate themes in the responses. Seven themes were identified that corresponded to both negative and positive aspects of alcohol consumption ranging from concern for the influence of alcohol on others (e.g., children and family) to participants' own enjoyment of alcohol (e.g., social drinking). Small but significant correlations suggested a relationship between the essay responses and individual consumption patterns and attitudes.

Protein-engineered injectable hydrogel to improve retention of transplanted adipose-derived stem cells.

Improved retention of transplanted stem cells is achieved through minimally invasive delivery in MITCH, a mixing-induced two-component hydrogel that was engineered to possess shear-thinning and self-healing thixotropic properties. MITCH, an ideal injectable cell-delivery vehicle, supports 3D stem-cell culture, resulting in high cell viability and physiologically relevant cell morphology.

Spontaneous cardiomyocyte differentiation of mouse embryoid bodies regulated by hydrogel crosslink density.

Cellular therapies have great potential to provide alternative treatment options for those suffering from heart disease. In order to optimize cell delivery for therapeutic efficacy, a greater understanding of parameters that impact stem cell differentiation, survival, growth, and development are needed. In this study, we examine the role of hydrogel crosslink density on spontaneous cardiomyocyte (CM) differentiation of murine embryoid bodies (EBs). CM differentiation was accelerated in hydrogels of low crosslink density, where 100% of the hydrogels were positive for CM differentiation compared to only 53% in the high crosslink density group after 8 days of culture. DNA microarray data suggests that enhanced CM differentiation in the low crosslink density hydrogels was not tissue specific but rather a result of favoured EB development and cell proliferation. Additionally, enhanced EB growth and differentiation in low crosslink density hydrogels was independent of RGD ligand density and not a consequence of enhanced diffusion. We also demonstrate that matrix metalloproteinase activity is required for spontaneous CM differentiation in 3D hydrogels. Low hydrogel crosslink density regulates spontaneous EB differentiation by promoting EB growth and development. Elucidating the effects of microenvironmental cues on cell differentiation can aid in the optimization of stem cell-based therapies for tissue regeneration.

Hydrogel crosslinking density regulates temporal contractility of human embryonic stem cell-derived cardiomyocytes in 3D cultures.

Systematically tunable in vitro platforms are invaluable in gaining insight to stem cell-microenvironment interactions in three-dimensional cultures. Utilizing recombinant protein technology, we independently tune hydrogel properties to systematically isolate the effects of matrix crosslinking density on cardiomyocyte differentiation, maturation, and function. We show that contracting human embryonic stem cell-derived cardiomyocytes (hESC-CMs) remain viable within four engineered elastin-like hydrogels of varying crosslinking densities with elastic moduli ranging from 0.45 to 2.4 kPa. Cardiomyocyte phenotype and function was maintained within hESC embryoid bodies for up to 2 weeks. Interestingly, increased crosslinking density was shown to transiently suspend spontaneous contractility. While encapsulated cells began spontaneous contractions at day 1 in hydrogels of the lowest crosslinking density, onset of contraction was increasingly delayed at higher crosslinking densities up to 6 days. However, once spontaneous contraction was restored, the rate of contraction was similar within all materials (71 ± 8 beats/min). Additionally, all groups successfully responded to electrical pacing at both 1 and 2 Hz. This study demonstrates that encapsulated hESC-CMs respond to 3D matrix crosslinking density within elastin-like hydrogels and stresses the importance of investigating temporal cellular responses in 3D cultures.

Tetrakis(hydroxymethyl) phosphonium chloride as a covalent cross-linking agent for cell encapsulation within protein-based hydrogels.

Native tissues provide cells with complex, three-dimensional (3D) environments comprised of hydrated networks of extracellular matrix proteins and sugars. By mimicking the dimensionality of native tissue while deconstructing the effects of environmental parameters, protein-based hydrogels serve as attractive, in vitro platforms to investigate cell-matrix interactions. For cell encapsulation, the process of hydrogel formation through physical or covalent cross-linking must be mild and cell compatible. While many chemical cross-linkers are commercially available for hydrogel formation, only a subset are cytocompatible; therefore, the identification of new and reliable cytocompatible cross-linkers allows for greater flexibility of hydrogel design for cell encapsulation applications. Here, we introduce tetrakis(hydroxymethyl) phosphonium chloride (THPC) as an inexpensive, amine-reactive, aqueous cross-linker for 3D cell encapsulation in protein-based hydrogels. We characterize the THPC-amine reaction by demonstrating THPC's ability to react with primary and secondary amines of various amino acids. In addition, we demonstrate the utility of THPC to tune hydrogel gelation time (6.7±0.2 to 27±1.2 min) and mechanical properties (storage moduli ∼250 Pa to ∼2200 Pa) with a recombinant elastin-like protein. Lastly, we show cytocompatibility of THPC for cell encapsulation with two cell types, embryonic stem cells and neuronal cells, where cells exhibited the ability to differentiate and grow in elastin-like protein hydrogels. The primary goal of this communication is to report the identification and utility of tetrakis(hydroxymethyl) phosphonium chloride (THPC) as an inexpensive but widely applicable cross-linker for protein-based materials.

Experimental manipulations of perspective taking and perspective switching in expressive writing.

Previous studies suggest that those who naturally vary their pronoun use over the course of expressive writing subsequently report the greatest improvements in physical and mental health. To explore possible perspective taking or perspective switching effects, two studies manipulated writing perspectives about emotional events from either a first-person, second-person, or third-person perspective. In Study 1, 55 students were randomly assigned to one of the three writing perspectives and were asked to write from the same perspective for three 5-minute writing sessions. In Study 2, 129 students wrote for three 5-minute sessions, one from each perspective in a counterbalanced order. The results showed that writing from a first-person perspective conferred more perceived benefits and was associated with using more cognitive mechanism words, whether engaged in perspective taking or perspective switching.

Protein-engineered biomaterials: nanoscale mimics of the extracellular matrix.

BACKGROUND: Traditional materials used as in vitro cell culture substrates are rigid and flat surfaces that lack the exquisite nano- and micro-scale features of the in vivo extracellular environment. While these surfaces can be coated with harvested extracellular matrix (ECM) proteins to partially recapitulate the bio-instructive nature of the ECM, these harvested proteins often exhibit large batch-to-batch variability and can be difficult to customize for specific biological studies. In contrast, recombinant protein technology can be utilized to synthesize families of 3 dimensional protein-engineered biomaterials that are cyto-compatible, reproducible, and fully customizable. SCOPE OF REVIEW: Here we describe a modular design strategy to synthesize protein-engineered biomaterials that fuse together multiple repeats of nanoscale peptide design motifs into full-length engineered ECM mimics. MAJOR CONCLUSIONS: Due to the molecular-level precision of recombinant protein synthesis, these biomaterials can be tailored to include a variety of bio-instructional ligands at specified densities, to exhibit mechanical properties that match those of native tissue, and to include proteolytic target sites that enable cell-triggered scaffold remodeling. Furthermore, these biomaterials can be processed into forms that are injectable for minimally-invasive delivery or spatially patterned to enable the release of multiple drugs with distinct release kinetics. GENERAL SIGNIFICANCE: Given the reproducibility and flexibility of these protein-engineered biomaterials, they are ideal substrates for reductionist biological studies of cell-matrix interactions, for in vitro models of physiological processes, and for bio-instructive scaffolds in regenerative medicine therapies. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

Identification of osteoconductive and biodegradable polymers from a combinatorial polymer library.

Combinatorial polymer syntheses are now being utilized to create libraries of materials with potential utility for a wide variety of biomedical applications. We recently developed a library of photopolymerizable and biodegradable poly(beta-amino ester)s (PBAEs) that possess a range of tunable properties. In this study, the PBAE library was assessed for candidate materials that met design criteria (e.g., physical properties such as degradation and mechanical strength and in vitro cell viability and osteoconductive behavior) for scaffolding in mineralized tissue repair. The most promising candidate, A6, was then processed into three-dimensional porous scaffolds and implanted subcutaneously and only presented a mild inflammatory response. The scaffolds were then implanted intramuscularly and into a critical-sized cranial defect either alone or loaded with bone morphogenetic protein-2 (BMP-2). The samples in both locations displayed mineralized tissue formation in the presence of BMP-2, as evident through radiographs, micro-computed tomography, and histology, whereas samples without BMP-2 showed minimal or no mineralized tissue. These results illustrate a process to identify a candidate scaffolding material from a combinatorial polymer library, and specifically for the identification of an osteoconductive scaffold with osteoinductive properties via the inclusion of a growth factor.

Inpatient treatment to online aftercare: e-mailing themes as a function of therapeutic outcomes.

The authors applied the meaning extraction method (MEM) to 4,241 e-mails written by 297 participants of an email-based aftercare program following inpatient psychotherapy. Principal-components analysis of the most frequently used nouns in the e-mails yielded nine components: life decisions and coping, relationship conflict, psychological and physical symptoms, family of origin, social and leisure activities, present family and household, treatment, exercise and diet, and work. Relative to men, women focused more on symptoms, exercise and diet, and family of origin, but less on work. Older participants were more likely to e-mail about their present family. Younger participants were more likely to e-mail about their family of origin and exercise and diet. Patients who showed no therapeutic gains during their prior treatment wrote more about symptoms than patients who had improved. The potentials and limitations of the MEM for the analysis of therapy corpora are discussed.

Tuning hydrogel properties for applications in tissue engineering.

Biomaterial design is an important component towards tissue engineering applications. There are many parameters that may be adjusted including physical properties (i.e., degradation and mechanics) and chemical properties (e.g., adhesion and cellular interactions). These design components may dictate the success or failure of a tissue engineering approach. Our group is particularly interested in the use of swollen hydrogels as cell carriers. One material that is used to fabricate hydrogels is hyaluronic acid (HA), which is found in many tissues in the body. Here, we show the control over hydrogel degradation, both in the bulk and locally to cells to control both the distribution of extracellular matrix by cells and whether or not a cell spreads in the hydrogels. These signals are important in the final structure and mechanical properties of engineered tissues, and potentially the differentiation of encapsulated stem cells.

The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells.

The potential of mesenchymal stem cells (MSCs) as a viable cell source for cartilage repair hinges on the development of engineered scaffolds that support adequate cartilage tissue formation. Evolving networks (hydrogels with mesh sizes that change over time due to crosslink degradation) may provide the control needed to enhance overall tissue formation when compared to static scaffolds. In this study, MSCs were photoencapsulated in combinations of hydrolytically and enzymatically degradable hyaluronic acid (HA) hydrogels to investigate the tunability of these hydrogels and the influence of network evolution on neocartilage formation. In MSC-laden HA hydrogels, compressive mechanical properties increased when degradation complemented extracellular matrix deposition and decreased when degradation was too rapid. In addition, dynamic hydrogels that started at a higher wt% and decreased to a lower wt% were not equivalent to static hydrogels that started at the higher or lower wt%. Specifically, evolving 2 wt% hydrogels (2 wt% degrading to 1 wt%) expressed up-regulation of type II collagen and aggrecan, and exhibited increased glycosaminoglycan content over non-evolving 2 and 1 wt% hydrogels. Likewise, mechanical properties and size maintenance were superior in the dynamic system compared to the static 2 wt% and 1 wt% hydrogels, respectively. Thus, hydrogels with dynamic properties may improve engineered tissues and help translate tissue engineering technology to clinical application.

Influence of three-dimensional hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells whose plasticity and self-renewal capacity have generated significant interest for applications in tissue engineering. The objective of this study was to investigate MSC chondrogenesis in photo-cross-linked hyaluronic acid (HA) hydrogels. Because HA is a native component of cartilage, and MSCs may interact with HA via cell surface receptors, these hydrogels could influence stem cell differentiation. In vitro and in vivo cultures of MSC-laden HA hydrogels permitted chondrogenesis, measured by the early gene expression and production of cartilage-specific matrix proteins. For in vivo culture, MSCs were encapsulated with and without transforming growth factor beta-3 (TGF-beta3) or pre-cultured for 2 weeks in chondrogenic medium before implantation. Up-regulation of type II collagen, aggrecan, and sox 9 was observed for all groups over MSCs at the time of encapsulation, and the addition of TGF-beta3 further enhanced the expression of these genes. To assess the influence of scaffold chemistry on chondrogenesis, HA hydrogels were compared with relatively inert poly(ethylene glycol) (PEG) hydrogels and showed enhanced expression of cartilage-specific markers. Differences between HA and PEG hydrogels in vivo were most noticeable for MSCs and polymer alone, indicating that hydrogel chemistry influences the commitment of MSCs to undergo chondrogenesis (e.g., approximately 43-fold up-regulation of type II collagen of MSCs in HA over PEG hydrogels). Although this study investigated only early markers of tissue regeneration, these results emphasize the importance of material cues in MSC differentiation microenvironments, potentially through interactions between scaffold materials and cell surface receptors.

Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels.

Degenerative disease and damage to articular cartilage represents a growing concern in the aging population. New strategies for engineering cartilage have employed mesenchymal stem cells (MSCs) as a cell source. However, recent work has suggested that chondrocytes (CHs) produce extracellular matrix (ECM) with superior mechanical properties than MSCs do. Because MSC-biomaterial interactions are important for both initial cell viability and subsequent chondrogenesis, we compared the growth of MSC- and CH-based constructs in three distinct hydrogels-agarose (AG), photocrosslinkable hyaluronic acid (HA), and self-assembling peptide (Puramatrix, Pu). Bovine CHs and MSCs were isolated from the same group of donors and seeded in AG, Pu, and HA at 20 million cells/mL. Constructs were cultured for 8 weeks with biweekly analysis of construct physical properties, viability, ECM content, and mechanical properties. Correlation analysis was performed to determine quantitative relationships between formed matrix and mechanical properties for each cell type in each hydrogel. Results demonstrate that functional chondrogenesis, as evidenced by increasing mechanical properties, occurred in each MSC-seeded hydrogel. Interestingly, while CH-seeded constructs were strongly dependent on the 3D environment in which they were encapsulated, similar growth profiles were observed in each MSC-laden hydrogel. In every case, MSC-laden constructs possessed mechanical properties significantly lower than those of CH-seeded AG constructs. This finding suggests that methods for inducing MSC chondrogenesis have yet to be optimized to produce cells whose functional matrix-forming potential matches that of native CHs.