Promising directions for human-robot interactions defined by older adults.

Introduction: Older adults are engaging more and more with voice-based agent and social robot technologies, and roboticists are increasingly designing interactions for these systems with older adults in mind. Older adults are often not included in these design processes, yet there are many opportunities for older adults to collaborate with design teams to design future robot interactions and help guide directions for robot development. Methods: Through a year-long co-design project, we collaborated with 28 older adults to understand the key focus areas that older adults see promise in for older adult-robot interaction in their everyday lives and how they would like these interactions to be designed. This paper describes and explores the robot-interaction guidelines and future directions identified by older adults, specifically investigating the change and trajectory of these guidelines through the course of the co-design process from the initial interview to the design guideline generation session to the final interview. Results were analyzed through an adapted ethnographic decision tree modeling approach to understand older adults' decision making surrounding the various focus areas and guidelines for social robots. Results: Overall, over the course of the co-design process between the beginning and end, older adults developed a better understanding of the robot that translated to them being more certain of their attitudes of how they would like a robot to engage with them in their lives. Older adults were more accepting of transactional functions such as reminders and scheduling and less open to functions that would involve sharing sensitive information and tracking and/or monitoring of them, expressing concerns around surveillance. There was some promise in robot interactions for connecting with others, body signal monitoring, and emotional wellness, though older adults brought up concerns around autonomy, privacy, and naturalness of the interaction with a robot that need to be further explored. Discussion: This work provides guidance for future interaction development for robots that are being designed to interact with older adults and highlights areas that need to be further investigated with older adults to understand how best to design for user concerns.

Practicing Surgeons' Perception of Barriers to Palliative Care Delivery in British Columbia.

BACKGROUND: Utilization of palliative care remains low among surgical patients. We aim to characterize general surgeons' perceptions of barriers to access palliative care in British Columbia (BC). METHODS: Semi-structured interviews were carried out with a total of 11 surgeons in BC. Interviews were transcribed for thematic analysis via interpretive description. Dominant themes were identified and agreed upon between the authors. RESULTS: Several barriers were identified, which include system and institution, communication and surgical workflow barriers. At the system and institutional level, there were difficulties accessing patient information and continuity of care. Themes in the communication included patient misconceptions about palliative care and communication challenges with consulting services. Surgical workflow barriers influenced the overall perceived role of surgeons when caring for patients with palliative care needs. CONCLUSION: Understanding surgeons' perspectives on barriers to palliative care is an important step in changing management. This can aid in the development of strategies that ease access to palliative care.

Acute performance fatigability following continuous vs. intermittent cycling protocols is not proportional to total work done.

Classical training theory postulates that performance fatigability following a training session should be proportional to the total work done (TWD); however, this notion has been questioned. This study investigated indices of performance and perceived fatigability after primary sessions of high-intensity interval (HIIT) and constant-work rate (CWR) cycling, each followed by a cycling time-to-task-failure (TTF) bout. On separate days, 16 participants completed an incremental cycling test, and, in a randomized order, i) a TTF trial at 80% of peak power output (PPO), ii) a HIIT session and iii) a CWR session, both of which were immediately followed by a TTF trial at 80% PPO. Central and peripheral aspects of performance fatigability were measured using interpolated twitch technique, and perceptual measures were assessed prior to and following the HIIT and CWR trials, and again following the TTF trial. Despite TWD being less following HIIT (P=0.029), subsequent TTF trial was an average of 125 s shorter following HIIT vs. CWR (P<0.001), and this was accompanied by greater impairments in voluntary and electrically evoked forces (P<0.001), as well as exacerbated perceptual measures (P<0.001); however, there were no differences in any fatigue measure following the TTF trial (P≥0.149). There were strong correlations between the decline in TTF and indices of peripheral (r=0.70) and perceived fatigability (r≥0.80) measured at the end of HIIT and CWR. These results underscore the dissociation between TWD and performance fatigability and highlight the importance of peripheral components of fatigability in limiting endurance performance during high-intensity cycling exercise.

Performance and perceived fatigability across the intensity spectrum: role of muscle mass during cycling.

The role of muscle mass in modulating performance and perceived fatigability across the entire intensity spectrum during cycling remains unexplored. We hypothesized that at task failure (Tlim), muscle contractile function would decline more following single- (SL) versus double-leg (DL) cycling within severe and extreme intensities, but not moderate and heavy intensities. After DL and SL ramp-incremental tests, on separate days, 11 recreationally active males (V̇o2max: 49.5 ± 7.7 mL·kg-1·min-1) completed SL and DL cycling until Tlim within each intensity domain. Power output for SL trials was set at 60% of the corresponding DL trial. Before and immediately after Tlim, participants performed an isometric maximal voluntary contraction (MVC) coupled with one superimposed and three resting femoral nerve stimulations [100 Hz; 10 Hz; single twitch (Qtw)] to measure performance fatigability. Perceived fatigue, leg pain, dyspnea, and effort were collected during trials. Tlim within each intensity domain was not different between SL and DL (all P > 0.05). MVC declined more for SL versus DL following heavy- (-42 ± 16% vs. -30 ± 18%; P = 0.011) and severe-intensity cycling (-41 ± 12% vs. -31 ± 15%; P = 0.036). Similarly, peak Qtw force declined more for SL following heavy- (-31 ± 12% vs. -22 ± 10%; P = 0.007) and severe-intensity cycling (-49 ± 13% vs. -40 ± 7%; P = 0.048). Except for heavy intensity, voluntary activation reductions were similar between modes. Similarly, except for dyspnea, which was lower for SL versus DL across all domains, ratings of fatigue, pain, and effort were similar at Tlim between exercise modes. Thus, the amount of muscle mass modulates the extent of contractile function impairment in an intensity-dependent manner.NEW & NOTEWORTHY We investigated the modulatory role of muscle mass on performance and perceived fatigability across the entire intensity spectrum. Despite similar time-to-task failure, single-leg cycling resulted in greater impairments in muscle contractile function within the heavy- and severe-intensity domains, but not the moderate- and extreme-intensity domains. Perceived fatigue, pain, and effort were similar between cycling modes. This indicates that the modulatory role of muscle mass on the extent of performance fatigability is intensity domain-dependent.

Immunophenotyping, Part I: Instrument Calibration and Reagent Qualification for Immunophenotyping Analysis of Human Peripheral Blood Mononuclear Cell Cultures.

Nanoparticles are increasingly used in biomedical applications to influence the way the immune system reacts to tumors and infectious disease-causing agents. Nanoparticles not-intended for immunomodulation can also influence immune responses by affecting immune cell subsets' viability and/or activity. While immunophenotyping is commonly used to assess the effects of drugs and nanoparticles on immune cell subsets, no standardized approach exists due to the breadth of available cell models and instrumentation. In this chapter, we describe a protocol for flow cytometer calibration and reagent qualification prior to its use in the immunophenotyping experiment. The strategies described herein can be adapted to other instruments. The subsequent chapter-immunophenotyping part II (Chap. 25 )-provides detailed instructions for applying this methodology to analyze nanoparticle effects on subsets of immune cells present in peripheral blood.

Immunophenotyping, Part II: Analysis of Nanoparticle Effects on the Composition and Activation Status of Human Peripheral Blood Mononuclear Cells.

The use of nanoparticles as drug delivery carriers requires analysis of their safety, which among other tests, includes immunotoxicity. Nanoparticles are also increasingly used for applications intended to specifically activate, inhibit, or modify the immune system's responses to improve the treatment of inflammatory and autoimmune disorders, cancer immunotherapy, and vaccines targeting cancer cells and viral and bacterial pathogens. In addition to the safety, the analysis of nanoparticles intended for immune system targeting includes mechanistic immunology investigations. Immunophenotyping provides researchers with a tool to assess the immune cell viability and activation status. These results provide mechanistic insights into nanoparticle efficacy and toxicity and therefore are of interest to the biomedical nanotechnology field. However, no standardized approaches exist due to the breadth of methods and instruments available for this analysis. This chapter provides detailed instructions for applying this methodology to analyze nanoparticle effects on subsets of immune cells present in peripheral blood. While this experimental strategy is specific to the NovoCyte 3005 flow cytometer, it can be adapted to other instruments. Instructions for instrument setup, calibration, and antibody qualification are described in this book's Chapter 24 , Immunophenotyping, part I.

Perioperative management of adults with traumatic brain injury.

Despite advances in management strategy, traumatic brain injury remains strongly associated with neurological impairment and mortality. Management of traumatic brain injury requires careful and targeted management of the physiological consequences which extend beyond the scope of the primary impact to the cranium. Here, we present a review of the principles of its acute management in adults. We outline the procedure which patients are assessed and the critical physiological variables which must be monitored to prevent further neurological damage. We describe current interventional strategies from the context of the underlying physiological mechanisms and recent clinical data and identify persisting challenges in traumatic brain injury management and potential avenues of future progress.

Longitudinal map of transcriptome changes in the Lyme pathogen Borrelia burgdorferi during tick-borne transmission.

Borrelia burgdorferi (Bb), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a tick bloodmeal, Bb alters its gene expression to prepare for vertebrate infection; however, the full range of transcriptional changes that occur over several days inside of the tick are technically challenging to capture. We developed an experimental approach to enrich Bb cells to longitudinally define their global transcriptomic landscape inside nymphal Ixodes scapularis ticks during a transmitting bloodmeal. We identified 192 Bb genes that substantially change expression over the course of the bloodmeal from 1 to 4 days after host attachment. The majority of upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 outer surface lipoproteins embedded in the unusual protein-rich coat of Bb. As these proteins may facilitate Bb interactions with the host, we utilized mass spectrometry to identify candidate tick proteins that physically associate with Bb. The Bb enrichment methodology along with the ex vivo Bb transcriptomes and candidate tick interacting proteins presented here provide a resource to facilitate investigations into key determinants of Bb priming and transmission during the tick stage of its unique transmission cycle.

Persistent Contralateral Pain Compromises Exercise Tolerance but Does not Alter Corticomotor Responses During Repeated, Submaximal Isometric Knee Extensions to Task Failure.

Muscle pain is an important determinant of exercise tolerance, but its relationship with neurophysiological responses during a submaximal exercise trial is unclear. The purpose of this study was to determine the effect of persistent contralateral pain on neurophysiological function and perceptual responses during ipsilateral isometric knee extensions to task failure. Ten participants performed a single-leg repeated submaximal isometric knee extensions with (PAIN) or without (CTRL) constant pain induced by intermittent blood flow occlusion combined with evoked muscle contraction applied to the contralateral, resting leg. Transcranial magnetic stimulation (TMS) applied over the motor cortex was used to assess corticospinal excitability (quantified as motor evoked potentials), corticospinal inhibition (quantified as silent period duration), and short interval intracortical inhibition. Maximal voluntary contractions (MVCs), coupled with femoral nerve stimulation to the exercising leg, were performed every 12 submaximal contractions to assess neuromuscular function. Perceived leg pain and effort were also assessed throughout the exercise. The experimental pain shortened the time to task failure compared to CTRL (P = 0.019). Although time effects were present, no differences appeared between conditions for MVC force, voluntary activation, or potentiated twitch force across both tasks (all P > 0.05). Additionally, no differences between CTRL and PAIN were demonstrated for any TMS-derived measures assessing corticospinal responses. Exercising leg pain was higher in CTRL (P = 0.018), as was perceived exertion (P = 0.030). Overall, when using a persistent, submaximal experimental pain intervention, it appears that although muscle pain compromises exercise tolerance, this phenomenon occurs independently of potential alterations in corticomotor mechanisms.

Multicolor flow cytometry-based immunophenotyping for preclinical characterization of nanotechnology-based formulations: an insight into structure activity relationship and nanoparticle biocompatibility profiles.

Introduction: Immunophenotyping, which is the identification of immune cell subsets based on antigen expression, is an integral technique used to determine changes of cell composition and activation in various disease states or as a response to different stimuli. As nanoparticles are increasingly utilized for diagnostic and therapeutic applications, it is important to develop methodology that allows for the evaluation of their immunological impact. Therefore, the development of techniques such as immunophenotyping are desirable. Currently, the most common technique used to perform immunophenotyping is multicolor flow cytometry. Methods: We developed two distinct multicolor flow cytometry immunophenotyping panels which allow for the evaluation of the effects of nanoparticles on the composition and activation status of treated human peripheral blood mononuclear cells. These two panels assess the presence of various lymphoid and myeloid-derived cell populations as well as aspects of their activation statuses-including proliferation, adhesion, co-stimulation/presentation, and early activation-after treatment with controls or nanoparticles. To conduct assay performance qualification and determine the applicability of this method to preclinical characterization of nanoparticles, we used clinical-grade nanoformulations (AmBisome, Doxil and Feraheme) and research-grade PAMAM dendrimers of different sizes (G3, G4 and G5) and surface functionalities (amine-, carboxy- and hydroxy-). Results and Discussion: We found that formulations possessing intrinsic fluorescent properties (e.g., Doxil and AmBisome) interfere with accurate immunophenotyping; such interference may be partially overcome by dilution. In the absence of interference (e.g., in the case of dendrimers), nanoparticle size and surface functionalities determine their effects on the cells with large amine-terminated dendrimers being the most reactive.

Intermittent blood flow occlusion modulates neuromuscular, perceptual, and cardiorespiratory determinants of exercise tolerance during cycling.

PURPOSE: Constant blood flow occlusion (BFO) superimposed on aerobic exercise can impair muscle function and exercise tolerance; however, no study has investigated the effect of intermittent BFO on the associated responses. Fourteen participants (n = 7 females) were recruited to compare neuromuscular, perceptual, and cardiorespiratory responses to shorter (5:15s, occlusion-to-release) and longer (10:30s) BFO applied during cycling to task failure. METHODS: In randomized order, participants cycled to task failure (task failure 1) at 70% of peak power output with (i) shorter BFO, (ii) longer BFO, and (iii) no BFO (Control). Upon task failure in the BFO conditions, BFO was removed, and participants continued cycling until a second task failure (task failure 2). Maximum voluntary isometric knee contractions (MVC) and femoral nerve stimuli were performed along with perceptual measures at baseline, task failure 1, and task failure 2. Cardiorespiratory measures were recorded continuously across the exercises. RESULTS: Task failure 1 was longer in Control than 5:15s and 10:30s (P < 0.001), with no differences between the BFO conditions. At task failure 1, 10:30s elicited a greater decline in twitch force compared to 5:15s and Control (P < 0.001). At task failure 2, twitch force remained lower in 10:30s than Control (P = 0.002). Low-frequency fatigue developed to a greater extent in 10:30s compared to Control and 5:15s (P < 0.047). Dyspnea and Fatigue were greater for Control than 5:15s and 10:30s at the end of task failure 1 (P < 0.002). CONCLUSION: Exercise tolerance during BFO is primarily dictated by the decline in muscle contractility and accelerated development of effort and pain.

Preoperative planning to preserve glenoid subchondral bone in anatomical total shoulder replacement.

Background: Glenoid loosening remains a concern in anatomical total shoulder replacement. Preoperative planning software allows optimization of the component positioning, but the target orientation remains unclear due to conflicting optimization priorities. Commonly, the component is aligned to the prescribed version and inclination that reflect the population's average anatomy. The freehand technique attempts to secure strong fixation by aiming to preserve the subchondral bone. This study compared the state of the subchondral plate after reaming and compared the results of these two techniques. Methods: Two groups of shoulder computed tomography scans were assessed, 34 normal and 34 osteoarthritic. Preoperative planning software was used to place the glenoid component in prescribed adjusted angles, with neutral (0o,0o), retroverted (-10o,0o) and inclined alignment (0o,10o). The computed tomography Hounsfield values at the virtually reamed surface were assessed to determine the percentage of the intended component-bone interface consisting of cortical bone, here termed "cortical bone seating". This was then compared to positioning the component using a freehand technique. Results: The freehand technique improved cortical bone seating in the osteoarthritic group with a mean (standard deviation) of 53.3% (14.3), while neutral alignment resulted in 36.7% (10.8), retroversion 40.4% (13.1), and inclination 39.3% (13.5), P < .001. A similar trend was observed in the normal group. Conclusions: The freehand method resulted in significantly improved cortical bone seating compared to the prescribed adjusted angles. These findings question the use of a one-size-fits-all-orientation and suggest that applying a technique that aims for maximum cortical fixation (freehand) may reduce the risk of aseptic loosening.

Multimodal Intervention Assessing the Appropriateness of Acid Suppression Therapy is Associated With Reduced Prescriptions at the Time of Discharge for Hospitalized Inpatients.

Background: Acid suppression therapy (AST), including proton pump inhibitors and histamine 2 receptor antagonists, are an overused class of medications. When used inappropriately, AST leads to polypharmacy, increased healthcare costs, and possible negative health consequences. Objective: To assess whether an intervention including prescriber education combined with a pharmacist-driven protocol was effective in reducing the percentage of patients who were discharged with inappropriate AST. Methods: This was a prospective pre-post study of adult patients who were prescribed AST before or during their admission to an internal medicine teaching service. All internal medicine resident physicians received education on appropriate AST prescribing. During the 4-week intervention period, dedicated pharmacists assessed the appropriateness of AST and made recommendations regarding deprescribing if no appropriate indication was identified. Results: During the study period, there were 14 166 admissions during which patients were prescribed AST. Out of the 1143 admissions during the intervention period, appropriateness of AST was assessed by a pharmacist for 163 patients. AST was determined to be inappropriate for 52.8% (n = 86) of patients and discontinuation or de-escalate of therapy occurred in 79.1% (n = 68) of these cases. The percentage of patients discharged on AST decreased from 42.5% before the intervention to 39.9% after the intervention (P = .007). Conclusion: This study suggests that a multimodal deprescribing intervention reduced prescriptions for AST without an appropriate indication at the time of discharge. To increase the efficiency of the pharmacist assessment several workflow improvements were identified. Further study is necessary to understand the long-term outcomes of this intervention.

Factors associated with recurrent appendicitis after nonoperative management.

BACKGROUND: The objective of this study is to identify predictors for recurrent appendicitis in patients with appendicitis previously treated nonoperatively. METHODS: This is a prospective cohort study of all adult patients with appendicitis treated at a tertiary care hospital. Patient demographics, radiographic information, management, and clinical outcomes were recorded. The primary outcome was recurrent appendicitis within 6 months after discharge from the index admission. Given the competing risk of interval appendectomy, a time-to-event competing-risk analysis was performed. RESULTS: Of the 699 patients presenting with appendicitis, 74 were treated nonoperatively (35 [47%] were women; median [IQR] age, 48 [33,64] years), and 21 patients (29%) had recurrent appendicitis. On univariate and multivariate analysis, presence of an appendicolith on imaging was the only factor associated with a higher risk of recurrent appendicitis (p = 0.02). CONCLUSIONS: The presence of appendicolith was associated with an increased risk of developing recurrent appendicitis within 6 months.

Photosynthesis re-wired on the pico-second timescale.

Photosystems II and I (PSII, PSI) are the reaction centre-containing complexes driving the light reactions of photosynthesis; PSII performs light-driven water oxidation and PSI further photo-energizes harvested electrons. The impressive efficiencies of the photosystems have motivated extensive biological, artificial and biohybrid approaches to 're-wire' photosynthesis for higher biomass-conversion efficiencies and new reaction pathways, such as H2 evolution or CO2 fixation1,2. Previous approaches focused on charge extraction at terminal electron acceptors of the photosystems3. Electron extraction at earlier steps, perhaps immediately from photoexcited reaction centres, would enable greater thermodynamic gains; however, this was believed impossible with reaction centres buried at least 4 nm within the photosystems4,5. Here, we demonstrate, using in vivo ultrafast transient absorption (TA) spectroscopy, extraction of electrons directly from photoexcited PSI and PSII at early points (several picoseconds post-photo-excitation) with live cyanobacterial cells or isolated photosystems, and exogenous electron mediators such as 2,6-dichloro-1,4-benzoquinone (DCBQ) and methyl viologen. We postulate that these mediators oxidize peripheral chlorophyll pigments participating in highly delocalized charge-transfer states after initial photo-excitation. Our results challenge previous models that the photoexcited reaction centres are insulated within the photosystem protein scaffold, opening new avenues to study and re-wire photosynthesis for biotechnologies and semi-artificial photosynthesis.

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy.

BACKGROUND: The potentially lethal zoonosis alveolar echinococcosis (AE) is caused by the metacestode larval stage of the tapeworm Echinococcus multilocularis. Current AE treatment options are limited and rely on surgery as well as on chemotherapy involving benzimidazoles (BZ). BZ treatment, however, is mostly parasitostatic only, must be given for prolonged time periods, and is associated with adverse side effects. Novel treatment options are thus urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: By applying a broad range of kinase inhibitors to E. multilocularis stem cell cultures we identified the proto-oncogene PIM kinase as a promising target for anti-AE chemotherapy. The gene encoding the respective E. multilocularis ortholog, EmPim, was characterized and in situ hybridization assays indicated its expression in parasite stem cells. By yeast two-hybrid assays we demonstrate interaction of EmPim with E. multilocularis CDC25, indicating an involvement of EmPim in parasite cell cycle regulation. Small molecule compounds SGI-1776 and CX-6258, originally found to effectively inhibit human PIM kinases, exhibited detrimental effects on in vitro cultured parasite metacestode vesicles and prevented the formation of mature vesicles from parasite stem cell cultures. To improve compound specificity for EmPim, we applied a high throughput in silico modelling approach, leading to the identification of compound Z196138710. When applied to in vitro cultured metacestode vesicles and parasite cell cultures, Z196138710 proved equally detrimental as SGI-1776 and CX-6258 but displayed significantly reduced toxicity towards human HEK293T and HepG2 cells. CONCLUSIONS/SIGNIFICANCE: Repurposing of kinase inhibitors initially designed to affect mammalian kinases for helminth disease treatment is often hampered by adverse side effects of respective compounds on human cells. Here we demonstrate the utility of high throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. We propose EmPim as a promising target for respective approaches towards AE treatment.

Neuromuscular and perceptual mechanisms of fatigue accompanying task failure in response to moderate-, heavy-, severe-, and extreme-intensity cycling.

A comprehensive characterization of neuromuscular and perceptual mechanisms of fatigue at task failure following exercise across the entire intensity spectrum is lacking. This study evaluated the extent of peripheral and central fatigue, and corresponding perceptual attributes, at task failure following cycling within the moderate-(MOD), heavy-(HVY), severe-(SVR), and extreme-(EXT) intensity domains. After a ramp-incremental test, 11 young males performed four constant-power output trials to the limit of tolerance (Tlim) at 4 distinct domain-specific workloads. These trials were preceded and followed by 5-s knee-extension maximal voluntary contractions (MVCs) and femoral nerve electrical stimuli to quantify peripheral and central fatigue. In addition, perceptual measures including ratings of global fatigue, legs pain, dyspnea, and perceived effort (RPE) were also collected. At Tlim, reductions in MVC were independent of intensity (P > 0.05). However, peripheral fatigue was greater following EXT and SVR and progressively, but distinctively, lower following HVY and MOD (P < 0.05). Central fatigue was similar after SVR, HVY, and MOD, but absent after EXT (P < 0.05). At Tlim, subjective ratings of global fatigue were progressively higher with lower exercise intensities, whereas ratings of legs pain and dyspnea were progressively higher with higher exercise intensities. On the other hand, RPE was maximal following HVY, SVR, and EXT, but not MOD. The findings demonstrate that at Tlim, the extent of peripheral fatigue is highly domain-specific, whereas the extent of central fatigue is not. Sensations such as fatigue, pain, and dyspnea may integrate with mechanisms of sense of effort to determine task failure in a manner specific to each intensity domain.NEW & NOTEWORTHY Together with other physiological responses, the neuromuscular fatigue mechanisms, and related perceptual responses, accompanying task failure are suggested to be dependent on the intensity domain within which exercise is sustained. Here, we show that peripheral fatigue demonstrates a high domain specificity, whereas such specificity is absent for central fatigue. Sensations of fatigue, pain, and breathlessness demonstrated intensity domain specificity and might have contributed to reaching maximal levels of RPE and, thus, task failure.

Synthetic biology and bioelectrochemical tools for electrogenetic system engineering.

Synthetic biology research and its industrial applications rely on deterministic spatiotemporal control of gene expression. Recently, electrochemical control of gene expression has been demonstrated in electrogenetic systems (redox-responsive promoters used alongside redox inducers and electrodes), allowing for the direct integration of electronics with biological processes. However, the use of electrogenetic systems is limited by poor activity, tunability, and standardization. In this work, we developed a strong, unidirectional, redox-responsive promoter before deriving a mutant promoter library with a spectrum of strengths. We constructed genetic circuits with these parts and demonstrated their activation by multiple classes of redox molecules. Last, we demonstrated electrochemical activation of gene expression under aerobic conditions using a novel, modular bioelectrochemical device. These genetic and electrochemical tools facilitate the design and improve the performance of electrogenetic systems. Furthermore, the genetic design strategies used can be applied to other redox-responsive promoters to further expand the available tools for electrogenetics.

Xanthogranulomatous cholangitis mimicking cholangiocarcinoma: Case report and review of literature.

INTRODUCTION: Xanthogranulomatous cholangitis is an extremely rare diagnosis and is believed to be an extension of xanthogranulomatous cholecystitis, a benign inflammatory process characterized by lipid-laden foamy macrophages (called "xanthoma cells") occurring in a background of chronic inflammation consisting of lymphocytes, plasma cells, and eosinophils. Here, we report a case of xanthogranulomatous cholangitis mimicking cholangiocarcinoma. CASE PRESENTATION: A 72 year old male with history of recurrent cholangitis had preoperative workup highly suggestive of intrahepatic cholangiocarcinoma. He underwent right hepatectomy and portal lymphadenectomy, with pathology showing xanthogranulomatous cholangitis, with no evidence of malignancy. Interestingly, the patient did not have xanthogranulomatous cholecystitis. DISCUSSION: We reviewed the current literature on xanthogranulomatous cholangitis, and identified only 14 previously reported cases. In our case series, there were six female and eight male patients. Among the 14 patients, 11 presented to the hospital with jaundice. Twelve patients had preoperative workup concerning for malignancy. The diagnosis of xanthogranulomatous cholangitis was confirmed through pathology in 13 patients, and through endoscopic ultrasound biopsy in one patient. In our review, seven patients had associated xanthogranulomatous cholecystitis, three patients had an isolated case of xanthogranulomatous cholangitis, and four patients had unknown status. Our patient is the fourth case of isolated xanthogranulomatous cholangitis without xanthogranulomatous cholecystitis. CONCLUSION: Xanthogranulomatous cholangitis is a very rare phenomenon that can lead to benign strictures of the bile ducts, especially in the setting of recurrent cholangitis. It can mimic malignancies, such as cholangiocarcinoma, and should be considered in the differential diagnosis.

3D-printed hierarchical pillar array electrodes for high-performance semi-artificial photosynthesis.

The rewiring of photosynthetic biomachineries to electrodes is a forward-looking semi-artificial route for sustainable bio-electricity and fuel generation. Currently, it is unclear how the electrode and biomaterial interface can be designed to meet the complex requirements for high biophotoelectrochemical performance. Here we developed an aerosol jet printing method for generating hierarchical electrode structures using indium tin oxide nanoparticles. We printed libraries of micropillar array electrodes varying in height and submicrometre surface features, and studied the energy/electron transfer processes across the bio-electrode interfaces. When wired to the cyanobacterium Synechocystis sp. PCC 6803, micropillar array electrodes with microbranches exhibited favourable biocatalyst loading, light utilization and electron flux output, ultimately almost doubling the photocurrent of state-of-the-art porous structures of the same height. When the micropillars' heights were increased to 600 µm, milestone mediated photocurrent densities of 245 µA cm-2 (the closest thus far to theoretical predictions) and external quantum efficiencies of up to 29% could be reached. This study demonstrates how bio-energy from photosynthesis could be more efficiently harnessed in the future and provide new tools for three-dimensional electrode design.