BioBits™ Bright: A fluorescent synthetic biology education kit.

Synthetic biology offers opportunities for experiential educational activities at the intersection of the life sciences, engineering, and design. However, implementation of hands-on biology activities in classrooms is challenging because of the need for specialized equipment and expertise to grow living cells. We present BioBits™ Bright, a shelf-stable, just-add-water synthetic biology education kit with easy visual outputs enabled by expression of fluorescent proteins in freeze-dried, cell-free reactions. We introduce activities and supporting curricula for teaching the central dogma, tunable protein expression, and design-build-test cycles and report data generated by K-12 teachers and students. We also develop inexpensive incubators and imagers, resulting in a comprehensive kit costing

A Review of the Available Guidance Regarding Management of Medical Emergencies in Primary Dental Care.

This article provides an overview of the recent changes in guidance relating to the management of medical emergencies in primary dental care in the UK. The guidance relating to automated external defibrillators is also presented. The expectations of our regulatory bodies are discussed, as are the requirements for continued professional development. The potential shortcomings of the changes to the guidance are also discussed, as well as proposed solutions, such as the development of algorithms to use in a dental practice setting. Clinical relevance: All dental practitioners should be able to deal with medical emergencies in their practice.

Lead optimization of 4,4-biaryl piperidine amides as γ-secretase inhibitors.

Alzheimer's disease is a major unmet medical need with pathology characterized by extracellular proteinaceous plaques comprised primarily of ß-amyloid. γ-Secretase is a critical enzyme in the cellular pathway responsible for the formation of a range of ß-amyloid peptides; one of which, Aß42, is believed to be responsible for the neuropathological features of the disease. Herein, we report 4,4 disubstituted piperidine γ-secretase inhibitors that were optimized for in vitro cellular potency and pharmacokinetic properties in vivo. Key agents were further characterized for their ability to lower cerebral Aß42 production in an APP-YAC mouse model. This structural series generally suffered from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled the discovery of γ-secretase inhibitors capable of lowering cerebral Aß42 production in mice.

Amygdala volume in late-life depression: relationship with age of onset.

OBJECTIVES: Depression is common in the elderly population. Although numerous neuroimaging studies have examined depressed elders, there is limited research examining how amygdala volume may be related to depression. DESIGN: A cross-sectional examination of amygdala volume comparing elders with and without a diagnosis of major depressive disorder, and between depressed subjects with early and later initial depression onset. SETTING: An academic medical center. PARTICIPANTS: Ninety-one elderly patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression (54 early-onset depressed and 37 late-onset depressed) and 31 elderly subjects without any psychiatric diagnoses. MEASUREMENTS: Amygdala and cerebral volumes were measured using reliable manual tracing methods. RESULTS: In models controlling for age, sex, and cerebral volume, there was a significant difference between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] = 16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares mean group analyses, both early- and late-onset depressed subjects exhibited smaller bilateral amygdala volumes than did the nondepressed cohort (all comparisons p < 0.0001), but the two depressed cohorts did not exhibit a statistically significant difference. LIMITATIONS: Limitations include missing antidepressant treatment data, recall bias, inability to establish a causal relationship between amygdala size and depression given the cross-sectional nature of the design. CONCLUSIONS: Depression in later life is associated with smaller amygdala volumes, regardless of age of initial onset of depression.

A prospective 1-year study of changes in neuropsychological functioning after implantable cardioverter-defibrillator surgery.

BACKGROUND: The testing of the implantable cardioverter-defibrillator (ICD), through the induction of repeated episodes of ventricular fibrillation, has been associated with disturbances in cerebral activity and increased levels of cytoplasmic enzymes. However, the neuropsychological outcomes of cerebral changes and their quality-of-life implications are unknown. METHODS AND RESULTS: Fifty-two ICD recipients completed standardized validated neuropsychological tests 1 to 3 days before ICD surgery and then 6 weeks, 6 months, and 12 months after surgery. They also completed psychometric tests measuring anxiety, depression, and quality of life. Between 31% and 39% of patients showed a significant neuropsychological impairment from their baseline function 6 weeks, 6 months, and 12 months after surgery. Ten percent of patients had late-onset deficits at 12 months only. Frequent areas of impairment were auditory and visual memory and attention. Neuropsychological impairment was not related to mood or quality of life at follow-up, although anxiety and depression predicted reduced quality of life. CONCLUSIONS: ICD implantation is associated with neuropsychological impairment that dissipates for the majority of recipients after 12 months. Short-term memory function and attention are particularly vulnerable to changes in oxygen during ICD testing. Although anxiety and depression are prevalent, there is little evidence for the direct impact of mood on cognition, and deficits appear not to be associated with reduced quality of life. These results provide evidence for longitudinal outcomes of ICD surgery and have implications for patient rehabilitation and adjustment.

Pre-ICD illness beliefs affect postimplant perceptions of control and patient quality of life.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is a device used in the treatment of ventricular arrhythmias and the prevention of sudden cardiac death. However, the ICD has been associated with negative psychological outcomes such as anxiety, depression, panic, and poor quality of life (QoL). Recent studies suggest that the preimplantation psychology of patients, combined with their postimplantation perceptions about their cardiac condition, are greater contributory factors than their medical status to a poor outcome. METHOD: Our study employed an interview-based qualitative grounded theory methodology to explore whether medical history hetereogeneity and illness beliefs impact on the QoL of 13 ICD patients. RESULTS: Perceived control emerged as the core category related to QoL with three subsystem themes related to control: (1) illness beliefs, attributions, and appraisals; (2) coping resources and strategies; and (3) the social world. Patients at risk for the poorest adaptation were younger (<45), unemployed, and with an acute onset cardiac history. These patients interpreted their illness as severe, utilized emotion-focused coping (e.g., avoidance of situations), and believed themselves to be socially excluded. Adjusted patients used proactive problem-focused coping (e.g., normalizing) and minimized consequences of the device. CONCLUSIONS: The data developed a theoretical model of QoL, which identified perceived control, illness beliefs, and coping impacting on adjustment. From our study, we have a wider understanding of the combination psychological issues relevant to ICD patients and are able to treat those at risk with interventions to promote adjustment in the context of a society that values health and well-being.

Analysis of calvarial bone defects in rats using microcomputed tomography: potential for a novel composite material and a new quantitative measurement.

Reconstruction of craniomaxillofacial defects is a challenge for surgeons and has psychological and functional burdens for patients. Undoubtedly, there is a need for improved biomaterials and techniques for craniomaxillofacial reconstruction. We assessed the potential regeneration of bone using three modifications of a novel composite and explored the validity of a new measurement using microcomputed tomography (micro-CT). We placed three different composite samples in calvarial defects in rats and analysed healing with micro-CT. The results showed that polycaprolactone (PCL) with phosphate glass fibre is promising for non-load bearing applications in the craniomaxillofacial region. Also, the new micro-CT measurement of the temporal characterisation of the mineralisation of bone (TCBM) has the potential to evolve into a reliable predictor of bony healing and its quality.

Patients with diabetes speak: exploring the implications of patients' perspectives for their diabetes appointments.

Type 2 diabetes puts patients at risk for serious health consequences that they can prevent or delay by achieving glycemic control. However, glycemic control depends largely on self-management. Consequently, determining what physicians might do in medical appointments to improve patients' self-management is of utmost concern. Patients were asked to discuss, in focus groups, their illness experience and their goals for regularly scheduled appointments. Six interrelated themes emerged from the analysis of transcripts: complications and comorbidities, time, control, information, family influences, and the physician-patient encounter. These themes and their implications for diabetes appointments were explored, specifically considering how physicians might use information about patients' perspectives to improve patients' self-management and thereby their glycemic control.

Biomimetic self-assembling peptides as injectable scaffolds for hard tissue engineering.

The production of bone-, dentine- and enamel-like biomaterials for the engineering of mineralized (hard) tissues is a high-priority in regenerative medicine and dentistry. An emerging treatment approach involves the use of short biomimetic peptides that self-assemble to form micrometer-long nanofibrils with well defined surface chemistry and periodicity that display specific arrays of functional groups capable of mineral nucleation. The fibrils also give rise to dynamically stable 3D scaffold gels for the potential control of crystal disposition and growth. Peptides can also be injected in their monomeric fluid state, with subsequent self-assembly and gelation in situ triggered by physiological conditions. In this way, they can infiltrate and self-assemble within irregular or microscopic cavities, for restorative treatment of bone defects, dentinal hypersensitivity or dental decay. Cell adhesion and proliferation is also supported by these scaffolds, offering further advantages for applications in hard tissue engineering. These self-assembling matrices also provide well defined model systems that can contribute greatly to the elucidation of the biological mechanisms of protein-mediated biomineralization.

Studies of liquid-phase complexes in acetonitrile/water solutions by attenuated total reflection infrared spectroscopy with acetaldehyde as a model solute.

Chemometric methods combined with infrared (IR) spectroscopy, using attenuated total reflectance (ATR) sampling, are employed here to characterize the stoichiometry of complexes of solvent molecules in the liquid phase. The spectral information provides insight into the liquid microstructure present in liquid chromatographic mobile phases. This information should make it easier to understand and predict the effects of changes in mobile phase composition on the results of chromatographic separations. In this paper, mobile phases consisting of 0 mol % to 100 mol % acetonitrile in water were studied, with the addition of acetaldehyde as a model solute at concentrations ranging from 3 to 8 mol %. Using three-way multivariate curve resolution by the alternating least squares method (MCR-ALS) it was possible to resolve eight unique spectra: four mobile phase components, and four unique spectra of acetaldehyde solvated in different environments. The directions of the shifts of the important acetaldehyde infrared bands show good correlation with those predicted by gas-phase ab initio calculations of small solvated clusters.

Physeal dysplasia with slipped capital femoral epiphysis in a cat.

A 14-month-old, intact male cat presented with acute onset, severe right hind limb lameness. Pelvic radiographs, excision of the femoral head, and histopathologic examination resulted in a diagnosis of physeal dysplasia with slipped capital femoral epiphysis. The cat rapidly regained use of the affected limb.