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Objective: Choose Your Own Adventure (CYOA) educational activities can be utilized in the classroom to simulate patient cases. The objective of this study was to evaluate changes in pharmacy student knowledge and confidence in hypertension, heart failure, and insulin management skills after completion of CYOA activities., Methods: Three CYOA activities were developed for 3 separate lectures in 2 pharmacy electives on topics of hypertension, heart failure, and insulin management. Two different online platforms were used for the activities. Before and after each activity, instructor-created surveys were administered to students to assess knowledge, confidence, and satisfaction., Results: Overall, 110 potential respondents completed at least 1 of the 3 activities between 2021 and 2023. Average knowledge and confidence improved for each disease-state individually and when combined as a whole. Satisfaction was high (>4.5/5) for all activities and no differences were seen between activity platforms., Conclusion: The CYOA activities can be successfully implemented in Doctor of Pharmacy elective classrooms using a digital platform for a variety of disease states and skills. Knowledge and confidence were improved in each individual topic and overall. Students enjoyed this activity regardless of the platform. Validated surveys and follow-up assessments would be beneficial in the future to determine if knowledge gains are sustainable., Competing Interests: Declaration of Competing Interest The authors have no financial disclosures or conflicts of interest. The authors did receive an internal grant from the University of Texas Faculty Innovation Center to fund the use of advanced features of Typeform., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between food insecurity and achieving glycemic goals among Medicare beneficiaries with type 2 diabetes., Methods: This study analyzed the nationally representative 2019 Medicare Current Beneficiary Survey of 1340 beneficiaries aged ≥65 years with type 2 diabetes. The binary dependent variable was whether beneficiaries' blood glucose was at target (A1C ≤ 7.5% or average fasting blood glucose of ≤140 mg/dL, all/most of the time). Food insecurity, a binary variable, was adapted based on the USDA's food security questions. A survey-weighted multivariable logistic model, adjusted for sociodemographics and comorbidities, was conducted to estimate predictive margins for comparing prevalence of having above-target blood glucose levels across groups., Results: Of study beneficiaries, 20.9% reported not achieving glycemic targets. The predictive marginal prevalence of having higher than target blood glucose levels was significantly greater in females over males (23.8% [95% confidence interval [CI], 20.1-27.4] vs 17.6% [14.3-20.9]); those with less than high school education over those with college education (31.0% [23.6-38.3] vs 18.6% [14.8-22.3]); and those reporting food insecurity over their counterparts (33.4% [24.5-42.3] vs 19.1% [16.6-21.7])., Conclusions: Sociodemographic disparities related to achieving blood glucose goals were observed. Screening for food insecurity and related interventions should be considered for at-risk beneficiaries with diabetes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: No potential conflicts of interest relevant to this article were reported.

Background: The objective of this review was to characterize the methods of delivery and assessment of Choose Your Own Adventure (CYOA)-style activities in pharmacy education. A secondary objective was to utilize available data to determine best practices for educators interested in developing similar activities., Methods: A meta-narrative approach according to the guidance of the RAMESES standards was used for this review. A broad literature search was conducted using PubMed and Embase. Studies published on the use of a CYOA-style patient case format in pharmacy education were identified and appraised individually for their relevance., Results: Thirteen studies from the pharmacy education literature were included in the review. Activities were delivered for 25 unique topics, largely in small groups during class via patient simulation or interactive data collection software. Overall, students have a positive perception of CYOA-style activities, with positive results regarding knowledge development and student engagement. The most commonly reported challenge to implementing CYOA-style patient case activities was the up-front time commitment to develop activities., Implications: This review provides a snapshot of the small but expanding body of literature on CYOA-style patient case activities in pharmacy education. CYOA-style activities are recommended for expanded use in pharmacy education as the preponderance of studies that assessed knowledge development showed significant improvement in knowledge after participation in CYOA-style activities. Additionally, students have a positive perception of CYOA-style activities and reported that they were enjoyable, improved their confidence, and helped them learn course material., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anorexia Nervosa is the most deadly mental illness due to the high mortality and relapse rates after reaching remission. The systematic review investigated the effectiveness of two empirically validated interventions (Family-Based Therapy [FBT] and Adolescent-Focused Therapy [AFT]) for an adolescent or young adult living with Anorexia Nervosa to reach partial or full remission and expected weight ratios. Twelve studies published between 1994 and 2015 were evaluated and indicated that FBT resulted in significant weight gain and higher partial and full remission rates than AFT, demonstrating its superiority in treating AN in adolescents and young adult samples, in one instance, at least up to 4 years. Despite FBT and AFT delivery, a significant proportion of participants did not achieve their target weight or full remission, indicating that both treatments may not be effective in all circumstances., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: This study's aim was to compare the time and accuracy of use and participants' satisfaction and preferences with pen devices for the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonists dulaglutide, exenatide XR BCise, and semaglutide., Materials and Methods: In this triple crossover, open-label, simulated injection study, GLP-1 receptor agonist pen devices were compared, with time and accuracy of use and participants' satisfaction and preferences as primary outcomes. Participants had type 2 diabetes and were naive to GLP-1 receptor agonist therapy. Participants watched instructional videos for each device, demonstrated administration, and then provided feedback after each demonstration. Investigators tracked errors and omissions of demonstration steps for accuracy and time. Differences across devices were compared using univariate mixed models, adjusting for multiple comparisons., Results: Of the 60 participants, 50% were male, a majority (65%) were Caucasian, and most (65%) had adequate health literacy. Participants rated the dulaglutide device easier to use than those of exenatide XR BCise or semaglutide ( P <0.001 for each). Participants expressed greater satisfaction with the dulaglutide device compared with those of exenatide XR BCise or semaglutide ( P <0.01 for each). Most participants (75%) preferred the dulaglutide device overall; however, many participants (61%) preferred the size and portability of the semaglutide device. The dulaglutide device took less time to use than the exenatide XR BCise or semaglutide devices (69 vs. 126 and 146 seconds, respectively; P <0.001 for each). Participants were less accurate when using the dulaglutide device., Conclusion: Most participants preferred the dulaglutide device. The dulaglutide device took the least amount of time to demonstrate; however, demonstration accuracy was lower., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© 2023 by the American Diabetes Association.)

Photoionization detectors (PIDs) are lightweight and respond in real time to the concentrations of volatile organic compounds (VOCs), making them suitable for environmental measurements on many platforms. However, the nonselective sensing mechanism of PIDs challenges data interpretation, particularly when exposed to the complex VOC mixtures prevalent in the Earth's atmosphere. Herein, two approaches to this challenge are investigated. In the first, quantum-chemistry calculations are used to estimate photoionization cross sections and ionization potentials of individual species. In the second, machine learning models are trained on these calculated values, as well as empirical PID response factors, and then used for prediction. For both approaches, the resulting information for individual species is used to model the overall PID response to a complex VOC mixture. In complement, laboratory experiments in the Harvard Environmental Chamber are carried out to measure the PID response to the complex molecular mixture produced by α-pinene oxidation under various conditions. The observations show that the measured PID response is 15% to 30% smaller than the PID response modeled by quantum-chemistry calculations of the photoionization cross section for the photo-oxidation experiments and 15% to 20% for the ozonolysis experiments. By comparison, the measured PID response is captured within a 95% confidence interval by the use of machine learning to model the PID response based on the empirical response factor in all experiments. Taken together, the results of this study demonstrate the application of machine learning to augment the performance of a nonselective chemical sensor. The approach can be generalized to other reactive species, oxidants, and reaction mechanisms, thus enhancing the utility and interpretability of PID measurements for studying atmospheric VOCs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The pandemic resulted in increased use of videoconferencing. This study investigated whether Appearance-Related Anxiety, Videoconferencing Appearance-Focused Behaviours, and Weekly Videoconferencing Time contributed to state body dissatisfaction in 191 community Australians. Results indicated moderate to strong positive correlations between the three constructs, a weak negative correlation for weekly video time, although no correlation for total week video time. The three constructs predicted state body dissatisfaction when controlling for age and gender and Appearance Related Anxiety mediated Videoconferencing Appearance-Focused Behaviours and body dissatisfaction. The impact of videoconference communication on body dissatisfaction is discussed.

Molecular ionization potentials (IP) and photoionization cross sections (σ) can affect the sensitivity of photoionization detectors (PIDs) and other sensors for gaseous species. This study employs several methods of machine learning (ML) to predict IP and σ values at 10.6 eV (117 nm) for a dataset of 1251 gaseous organic species. The explicitness of the treatment of the species electronic structure progressively increases among the methods. The study compares the ML predictions of the IP and σ values to those obtained by quantum chemical calculations. The ML predictions are comparable in performance to those of the quantum calculations when evaluated against measurements. Pretraining further reduces the mean absolute errors (ε) compared to the measurements. The graph-based attentive fingerprint model was most accurate, for which ε IP = 0.23 ± 0.01 eV and ε σ = 2.8 ± 0.2 Mb compared to measurements and computed cross sections, respectively. The ML predictions for IP correlate well with both the measured IPs ( R 2 = 0.88) and with IPs computed at the level of M06-2X/aug-cc-pVTZ ( R 2 = 0.82). The ML predictions for σ correlated reasonably well with computed cross sections ( R 2 = 0.66). The developed ML methods for IP and σ values, representing the properties of a generalizable set of volatile organic compounds (VOCs) relevant to industrial applications and atmospheric chemistry, can be used to quantitatively describe the species-dependent sensitivity of chemical sensors that use ionizing radiation as part of the sensing mechanism, such as photoionization detectors., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: The purpose of the study was to examine the relationship between satisfaction of Medicare coverage for out-of-pocket costs and problems paying medical bills among Medicare beneficiaries with type 2 diabetes., Methods: The 2019 Medicare Current Beneficiary Survey Public Use File, a nationally representative sample of Medicare beneficiaries aged ≥65 years with type 2 diabetes, was analyzed (n = 2178). A survey-weighted multivariable logit regression model was conducted to examine the association between satisfaction of Medicare coverage for out-of-pocket costs and problems paying medical bills, adjusted for sociodemographics and comorbidities., Results: Among study beneficiaries, 12.6% reported problems paying medical bills. Among those with and without problems paying medical bills, 59.5% and 12.8%, respectively, were dissatisfied with out-of-pocket costs. In the multivariable analysis, beneficiaries who were dissatisfied with out-of-pocket costs were more likely to report problems paying medical bills than those who were satisfied. Younger beneficiaries, beneficiaries with lower incomes, those with functional limitations, and those with multiple comorbidities were more likely to report problems paying medical bills., Conclusions: Despite having health care coverage, more than one-tenth of Medicare beneficiaries with type 2 diabetes reported problems paying medical bills, which raises concerns about delaying or forgoing needed medical care due to unaffordability. Screenings and targeted interventions that identify and reduce financial hardships associated with out-of-pocket costs should be prioritized.

Introduction: Preceptors serve as the gatekeepers between individuals progressing from student pharmacist to independent practitioner. This responsibility is challenging if a student is not progressing as required and is at risk of failure. In this article, we will review the potential consequences and barriers of "failing to fail" a student, share the emotions that come with the decision, and suggest actions that may aid in preceptor decision-making., Commentary: A preceptor's failure to fail a student has a global impact on many parties including the student, their future employer and patients, the preceptor, and the school or college of pharmacy. Despite supportive factors, preceptors may experience an internal struggle about the ripple effect of failing or not failing an experiential student., Implications: Underperformance in the experiential setting is a complex issue that remains largely unseen due to "failure to fail," a concept that should be researched further in the pharmacy setting. Empowering preceptors, particularly newer preceptors, to assess and manage failing students is possible through increased discussion around the topic and focused preceptor development programs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The objective of this educational activity was to evaluate the impact of a virtually simulated Choose Your Own Adventure (CYOA) activity on pharmacy student knowledge and confidence of insulin management., Methods: An online CYOA activity was created using TypeForm, version 2 (TypeForm SL) for a third-year pharmacy school diabetes elective with 16 enrollees over two course offerings. Through use of interactive storytelling, students used critical thinking skills to make decisions in six simulated patient's care including initiation, counseling, conversions, and titration of multiple types of insulin. Instructor-created surveys were administered to students before and after the activity to assess satisfaction, confidence, and knowledge., Results: Ten students (62.5%) completed the activity and both pre- and post-surveys. Average total scores on the five-question insulin knowledge quiz improved significantly from 46% to 68% (P = .02). High satisfaction scores were recorded for each item in the post-survey. Student confidence improved in all aspects related to insulin management (P < .001). No differences in knowledge, confidence, or satisfaction were found between students who completed the activity in an in-person vs. virtual classroom., Conclusions: CYOA activities can be successfully implemented in an in-person and virtual pharmacy classroom using a digital platform. Students viewed the CYOA activity as an enjoyable, low-stakes learning tool to increase confidence in their decision making. This small study did find knowledge improvements, but further research is needed to fully establish the validity of the knowledge assessments and ensure knowledge gains are sustainable., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Volatile organic compounds (VOCs) emitted from forests are important chemical components that affect ecosystem functioning, atmospheric chemistry, and regional climate. Temperature differences between a forest and an adjacent river can induce winds that influence VOC fate and transport. Quantitative observations and scientific understanding, however, remain lacking. Herein, daytime VOC datasets were collected from the surface up to 500 m over the "Rio Negro" river in Amazonia. During time periods of river winds, isoprene, α-pinene, and β-pinene concentrations increased by 50, 60, and 80% over the river, respectively. The concentrations at 500 m were up to 80% greater compared to those at 100 m because of the transport path of river winds. By comparison, the concentration of methacrolein, a VOC oxidation product, did not depend on river winds or height. The differing observations for primary emissions and oxidation products can be explained by the coupling of timescales among emission, reaction, and transport. This behavior was captured in large-eddy simulations with a coupled chemistry model. The observed and simulated roles of river winds in VOC fate and transport highlight the need for improved representation of these processes in regional models of air quality and chemistry-climate coupling.

Background: The use of an escape room in education helps promote communication, teamwork, and leadership amongst interprofessional learners in a unique and engaging manner; however, it is unknown if this method can change clinical knowledge related to the opioid crisis and interprofessional attitudes. Our objective was to evaluate the use of an interprofessional escape room activity to increase clinical knowledge related to the opioid crisis and to change attitudes toward interprofessional collaboration., Interprofessional Education Activity: The session was developed as part of an interprofessional program at University of Colorado Anschutz Medical Campus. In this educational escape room activity, teams of interprofessional students solved six puzzles to gain knowledge of the opioid crisis. Knowledge gains were assessed using a pretest and posttest, while changes in interprofessional attitudes were assessed using the Student Perceptions of Interprofessional Clinical Education-Revised (SPICE-R) instrument., Discussion: Of the 88 total participants, 70 students from six different health professions completed both the pretest and posttest and were included in the analysis. Knowledge of the opioid crisis improved, particularly in identifying signs of opioid overdose. Overall, SPICE-R ratings increased, which was driven by improvement in understanding professional roles and responsibilities., Implications: The use of an interprofessional escape room as an educational method was effective in increasing some aspects of opioid crisis related knowledge and enhancing attitudes toward interprofessional collaboration. The educational model is applicable to various topics and interprofessional groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Organisms depend on visual, auditory, and olfactory cues to signal the presence of danger that could impact survival and reproduction. Drosophila melanogaster emits an olfactory alarm signal, termed the Drosophila stress odorant (dSO), in response to mechanical agitation or electric shock. While it has been shown that conspecifics avoid areas previously occupied by stressed individuals, the contextual underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that while D. melanogaster, D. simulans, and D. suzukii, have different dSO profiles, its avoidance was not species-specific. Thus, dSO should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra- and inter-specific cues differed between Drosophila species and possible reasons for these differences are discussed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Machine learning (ML) and deep learning (DL) can successfully predict high prevalence events in very large databases (big data), but the value of this methodology for risk prediction in smaller cohorts with uncommon diseases and infrequent events is uncertain. The clinical course of spontaneous coronary artery dissection (SCAD) is variable, and no reliable methods are available to predict mortality. Based on the hypothesis that machine learning (ML) and deep learning (DL) techniques could enhance the identification of patients at risk, we applied a deep neural network to information available in electronic health records (EHR) to predict in-hospital mortality in patients with SCAD. We extracted patient data from the EHR of an extensive urban health system and applied several ML and DL models using candidate clinical variables potentially associated with mortality. We partitioned the data into training and evaluation sets with cross-validation. We estimated model performance based on the area under the receiver-operator characteristics curve (AUC) and balanced accuracy. As sensitivity analyses, we examined results limited to cases with complete clinical information available. We identified 375 SCAD patients of which mortality during the index hospitalization was 11.5%. The best-performing DL algorithm identified in-hospital mortality with AUC 0.98 (95% CI 0.97-0.99), compared to other ML models (P < 0.0001). For prediction of mortality using ML models in patients with SCAD, the AUC ranged from 0.50 with the random forest method (95% CI 0.41-0.58) to 0.95 with the AdaBoost model (95% CI 0.93-0.96), with intermediate performance using logistic regression, decision tree, support vector machine, K-nearest neighbors, and extreme gradient boosting methods. A deep neural network model was associated with higher predictive accuracy and discriminative power than logistic regression or ML models for identification of patients with ACS due to SCAD prone to early mortality.

Background: There is a shortage of primary care medical providers, particularly in rural communities and communities of racial and ethnic minority groups. Clinical pharmacists can help fill gaps in care among these vulnerable populations., Objective: To identify characteristics of ambulatory care pharmacists that pursue and maintain employment within underserved areas., Methods: An original survey was distributed nationwide to ambulatory care clinical pharmacists in underserved settings. Respondent characteristics were analyzed using descriptive statistics., Results: Of the 111 completed surveys, a majority of respondents were White, non-Hispanic, female, with English as their only spoken language. A majority of pharmacists completed a clinical experience or specialized training focused on underserved care prior to their position. The top three motivators for pharmacists accepting their clinical position as well as staying at their job were passion for caring for underserved populations, the presence of a faculty appointment, or the freedom and flexibility of advanced clinical roles., Conclusions: With a large majority of our respondents identifying as White and unilingual, there remains a large opportunity to increase diversity in the clinical pharmacy ambulatory care workforce caring for underserved populations. There is an observed correlation between early experiential or specialized training in underserved care and pharmacists pursuing employment in these areas. Thus, one potential long-term strategy to diversify and grow the ambulatory care clinical pharmacist workforce in underserved settings is for clinical practice sites to partner with colleges of pharmacy to recruit and maintain quality individuals who can meet the needs of diverse patient populations as well as expand student and resident training opportunities in underserved settings., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest., (Copyright: © The Authors.)

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.

Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It is also becoming increasingly important in industrial and medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular delivery from 1911 until the present. These methods achieve rapid, direct, and universal delivery of almost any cargo molecule or material that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo types-small molecules, proteins/peptides, nucleic acids, synthetic nanomaterials, and large cargo. The review then presents a broad comparison of delivery strategies followed by an analysis of membrane disruption mechanisms and the biology of the cell response. We cover mechanical, electrical, thermal, optical, and chemical strategies of membrane disruption with a particular emphasis on their applications and challenges to implementation. Throughout, we highlight specific mechanisms of membrane disruption and suggest areas in need of further experimentation. We hope the concepts discussed in our review inspire scientists and engineers with further ideas to improve intracellular delivery.

To divide, most animal cells drastically change shape and round up against extracellular confinement. Mitotic cells facilitate this process by generating intracellular pressure, which the contractile actomyosin cortex directs into shape. Here, we introduce a genome-scale microcantilever- and RNAi-based approach to phenotype the contribution of > 1000 genes to the rounding of single mitotic cells against confinement. Our screen analyzes the rounding force, pressure and volume of mitotic cells and localizes selected proteins. We identify 49 genes relevant for mitotic rounding, a large portion of which have not previously been linked to mitosis or cell mechanics. Among these, depleting the endoplasmic reticulum-localized protein FAM134A impairs mitotic progression by affecting metaphase plate alignment and pressure generation by delocalizing cortical myosin II. Furthermore, silencing the DJ-1 gene uncovers a link between mitochondria-associated Parkinson's disease and mitotic pressure. We conclude that mechanical phenotyping is a powerful approach to study the mechanisms governing cell shape.

The deployment of molecular to microscale carriers for intracellular delivery has tremendous potential for biology and medicine, especially for in vivo therapies. The field remains limited, however, by a poor understanding of how carriers gain access to the cell interior. In this review, we provide an overview of the different types of carriers, their speculated modes of entry, putative pathways of vesicular transport, and sites of endosomal escape. We compare this alongside pertinent examples from the cell biology of how viruses, bacteria, and their effectors enter cells and escape endosomal confinement. We anticipate insights into the mechanisms of cellular entry and endosomal escape will benefit future research efforts on effective carrier-mediated intracellular delivery. WIREs Nanomed Nanobiotechnol 2016, 8:465-478. doi: 10.1002/wnan.1377 For further resources related to this article, please visit the WIREs website., (© 2015 Wiley Periodicals, Inc.)

The First World War (1914-1918) was the first truly industrial conflict in human history. Never before had rifle fire and artillery barrage been employed on a global scale. It was a conflict that over 4 years would leave over 750,000 British troops dead with a further 1.6 million injured, the majority with orthopaedic injuries. Against this backdrop, the skills of the orthopaedic surgeon were brought to the fore. Many of those techniques and systems form the foundation of modern orthopaedic trauma management. On the centenary of 'the War to end all Wars', we review the significant advances in wound management, fracture treatment, nerve injury and rehabilitation that were developed during that conflict., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Little is known about how mitotic cells round against epithelial confinement. Here, we engineer micropillar arrays that subject cells to lateral mechanical confinement similar to that experienced in epithelia. If generating sufficient force to deform the pillars, rounding epithelial (MDCK) cells can create space to divide. However, if mitotic cells cannot create sufficient space, their rounding force, which is generated by actomyosin contraction and hydrostatic pressure, pushes the cell out of confinement. After conducting mitosis in an unperturbed manner, both daughter cells return to the confinement of the pillars. Cells that cannot round against nor escape confinement cannot orient their mitotic spindles and more likely undergo apoptosis. The results highlight how spatially constrained epithelial cells prepare for mitosis: either they are strong enough to round up or they must escape. The ability to escape from confinement and reintegrate after mitosis appears to be a basic property of epithelial cells.

Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease., (© 2014. Published by The Company of Biologists Ltd.)

A series of Ni-based electrocatalysts, [Ni(7P(Ph)2N(C6H4X))2](BF4)2, featuring seven-membered cyclic diphosphine ligands incorporating a single amine base, 1-para-X-phenyl-3,6-triphenyl-1-aza-3,6-diphosphacycloheptane (7P(Ph)2N(C6H4X), where X = OMe, Me, Br, Cl, or CF3), have been synthesized and characterized. X-ray diffraction studies have established that the [Ni(7P(Ph)2N(C6H4X))2](2+) complexes have a square planar geometry, with bonds to four phosphorus atoms of the two bidentate diphosphine ligands. Each of the complexes is an efficient electrocatalyst for hydrogen production at the potential of the Ni(II/I) couple, with turnover frequencies ranging from 2400 to 27,000 s(-1) with [(DMF)H](+) in acetonitrile. Addition of water (up to 1.0 M) accelerates the catalysis, giving turnover frequencies ranging from 4100 to 96,000 s(-1). Computational studies carried out on the [Ni(7P(Ph)2N(C6H4X))2](2+) family indicate the catalytic rates reach a maximum when the electron-donating character of X results in the pKa of the Ni(I) protonated pendant amine matching that of the acid used for proton delivery. Additionally, the fast catalytic rates for hydrogen production by the [Ni(7P(Ph)2N(C6H4X))2](2+) family relative to the analogous [Ni(P(Ph)2N(C6H4X)2)2](2+) family are attributed to preferred formation of endo protonated isomers with respect to the metal center in the former, which is essential to attain suitable proximity to the reduced metal center to generate H2. The results of this work highlight the importance of precise pKa matching with the acid for proton delivery to obtain optimal rates of catalysis.

The combination of atomic force microscopy (AFM) and optical microscopy has gained popularity for mechanical analysis of living cells. In particular, recent AFM-based assays featuring tipless cantilevers and whole-cell deformation have yielded insights into cellular function, structure, and dynamics. However, in these assays the standard ≈10° tilt of the cantilever prevents uniaxial loading, which complicates assessment of cellular geometry and can cause cell sliding or loss of loosely adherent cells. Here, we describe an approach to modify tipless cantilevers with wedges and, thereby, achieve proper parallel plate mechanics. We provide guidance on material selection, the wedge production process, property and geometry assessment, and the calibration of wedged cantilevers. Furthermore, we demonstrate their ability to simplify the assessment of cell shape, prevent lateral displacement of round cells during compression, and improve the assessment of cell mechanical properties., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The electrocatalytic reduction of protons to H(2) by [Ni((P(Ph)(2)N(C6H4-hex))(2)(2)]((BF(4))(2) (where P(Ph)(2)N(C6H4-hex)(2) = 1,5-di(4-n-hexylphenyl)-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane) in the highly acidic ionic liquid dibutylformamidium bis(trifluoromethanesulfonyl)amide shows a strong dependence on added water. A turnover frequency of 43,000-53,000 s(-1) has been measured for hydrogen production at 25 °C when the mole fraction of water (χ(H(2)O)) is 0.72. The same catalyst in acetonitrile with added dimethylformamidium trifluoromethanesulfonate and water has a turnover frequency of 720 s(-1). Thus, the use of an ionic liquid/aqueous solution enhances the observed catalytic rate by more than a factor of 50, compared to a similar acid in a traditional organic solvent. Complexes [Ni((P(Ph)(2)N(C6H4X))(2)(2)]((BF(4))(2) (X = H, OMe,CH(2)P(O)(OEt)(2), Br) are also catalysts in the ionic liquid/water mixture, and the observed catalytic rates correlate with the hydrophobicity of X.

To understand the role of physical forces at a cellular level, it is necessary to track mechanical properties during cellular processes. Here we present a protocol that uses flat atomic force microscopy (AFM) cantilevers clamped at constant height, and light microscopy to measure the resistance force, mechanical stress and volume of globular animal cells under compression. We describe the AFM and cantilever setup, live cell culture in the AFM, how to ensure stability of AFM measurements during medium perfusion, integration of optical microscopy to measure parameters such as volume and track intracellular dynamics, and interpretation of the physical parameters measured. Although we use this protocol on trypsinized interphase and mitotic HeLa cells, it can also be applied to other cells with a relatively globular shape, especially animal cells in a low-adhesive environment. After a short setup phase, the protocol can be used to investigate approximately one cell per hour.

A series of [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes containing the cyclic diphosphine ligands [P(R)(2)N(Ph)(2) = 1,5-diaza-3,7-diphosphacyclooctane; R = benzyl (Bn), n-butyl (n-Bu), 2-phenylethyl (PE), 2,4,4-trimethylpentyl (TP), and cyclohexyl (Cy)] have been synthesized and characterized. X-ray diffraction studies reveal that the cations of [Ni(P(Bn)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) and [Ni(P(n-Bu)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) have distorted trigonal bipyramidal geometries. The Ni(0) complex [Ni(P(Bn)(2)N(Ph)(2))(2)] was also synthesized and characterized by X-ray diffraction studies and shown to have a distorted tetrahedral structure. These complexes, with the exception of [Ni(P(Cy)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2), all exhibit reversible electron transfer processes for both the Ni(II/I) and Ni(I/0) couples and are electrocatalysts for the production of H(2) in acidic acetonitrile solutions. The heterolytic cleavage of H(2) by [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes in the presence of p-anisidine or p-bromoaniline was used to determine the hydride donor abilities of the corresponding [HNi(P(R)(2)N(Ph)(2))(2)](BF(4)) complexes. However, for the catalysts with the most bulky R groups, the turnover frequencies do not parallel the driving force for elimination of H(2), suggesting that steric interactions between the alkyl substituents on phosphorus and the nitrogen atom of the pendant amines play an important role in determining the overall catalytic rate., (© 2011 American Chemical Society)

Reduction of acids to molecular hydrogen as a means of storing energy is catalyzed by platinum, but its low abundance and high cost are problematic. Precisely controlled delivery of protons is critical in hydrogenase enzymes in nature that catalyze hydrogen (H(2)) production using earth-abundant metals (iron and nickel). Here, we report that a synthetic nickel complex, [Ni(P(Ph)(2)N(Ph))(2)](BF(4))(2), (P(Ph)(2)N(Ph) = 1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane), catalyzes the production of H(2) using protonated dimethylformamide as the proton source, with turnover frequencies of 33,000 per second (s(-1)) in dry acetonitrile and 106,000 s(-1) in the presence of 1.2 M of water, at a potential of -1.13 volt (versus the ferrocenium/ferrocene couple). The mechanistic implications of these remarkably fast catalysts point to a key role of pendant amines that function as proton relays.

Atomic force microscopy (AFM) is a force sensing nanoscopic tool that can be used to undertake a multiscale approach to understand the mechanisms that underlie cell shape change, ranging from the cellular to molecular scale. In this review paper, we discuss the use of AFM to characterize the dramatic shape changes of mitotic cells. AFM-based mechanical assays can be applied to measure the considerable rounding force and hydrostatic pressure generated by mitotic cells. A complementary AFM technique, single-molecule force spectroscopy, is able to quantify the interactions and mechanisms that functionally regulate individual proteins. Future developments of these nanomechanical methods, together with advances in light microscopy imaging and cell biological and genetic tools, should provide further insight into the biochemical, cellular and mechanical processes that govern mitosis and other cell shape change phenomena., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A series of mononuclear nickel(II) bis(diphosphine) complexes [Ni(P(Ph)(2)N(C6H4X)(2))(2)](BF(4))(2) (P(Ph)(2)N(C6H4X)(2) = 1,5-di(para-X-phenyl)-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane; X = OMe, Me, CH(2)P(O)(OEt)(2), Br, and CF(3)) have been synthesized and characterized. X-ray diffraction studies reveal that [Ni(P(Ph)(2)N(C6H4Me)(2))(2)](BF(4))(2) and [Ni(P(Ph)(2)N(C6H4OMe)(2))(2)](BF(4))(2) are tetracoordinate with distorted square planar geometries. The Ni(II/I) and Ni(I/0) redox couples of each complex are electrochemically reversible in acetonitrile with potentials that are increasingly cathodic as the electron-donating character of X is increased. Each of these complexes is an efficient electrocatalyst for hydrogen production at the potential of the Ni(II/I) couple. The catalytic rates generally increase as the electron-donating character of X is decreased, and this electronic effect results in the favorable but unusual situation of obtaining higher catalytic rates as overpotentials are decreased. Catalytic studies using acids with a range of pK(a) values reveal that turnover frequencies do not correlate with substrate acid pK(a) values but are highly dependent on the acid structure, with this effect being related to substrate size. Addition of water is shown to dramatically increase catalytic rates for all catalysts. With [Ni(P(Ph)(2)N(C6H4CH2P(O)(OEt)2)(2))(2)](BF(4))(2) using [(DMF)H](+)OTf(-) as the acid and with added water, a turnover frequency of 1850 s(-1) was obtained.

During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.

Introduction: British military forces remain heavily committed on combat operations overseas. UK military operations in Afghanistan (Operation HERRICK) are currently supported by a surgical facility at Camp Bastion, in Helmand Province, in the south of the country. There have been no large published series of surgical workload on Operation HERRICK. The aim of this study is to evaluate this information in order to determine the appropriate skill set for the modern military surgical team., Method: A retrospective analysis of operating theatre records between 1st May 2006 and 1st May 2008 was performed. Data was collated on a monthly basis and included patient demographics, operation type and time of operation., Results: During the study period 1668 cases required 2210 procedures. Thirty-two per cent were coalition forces (ISAF), 27% were Afghan security forces (ANSF) and 39% were civilians. Paediatric casualties accounted for 14.7% of all cases. Ninety-three per cent of cases were secondary to battle injury and of these 51.3% were emergencies. The breakdown of procedures, by specialty, was 66% (1463) orthopaedic, 21% (465) general surgery, 6% (139) head and neck, 5% (104) burns surgery and a further 4% (50) non-battle, non-emergency procedures. There was an almost twofold increase in surgical workload in the second year (1103 cases) compared to the first year of the deployment (565 cases, p<0.05)., Discussion: Surgical workload over the study period has clearly increased markedly since the initial deployment of ISAF forces to Helmand Province. A 6-week deployment to Helmand Province currently provides an equivalent exposure to penetrating trauma as 3 years trauma experience in the UK NHS. The spectrum of injuries seen and the requisite skill set that the military surgeon must possess is outside that usually employed within the NHS. A number of different strategies; including the deployment of trainee specialist registrars to combat hospitals, more focused pre-deployment military surgery training courses, and wet-laboratory work are proposed to prepare for future generations of surgeons operating in conflict environments., ((c) 2009 Elsevier Ltd. All rights reserved.)