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We adopt a tripart approach in describing the human-centred challenges with human-swarm interaction. First, the results of large-N laboratory studies will be discussed which found evidence of trust biases (e.g. system-wide trust (SWT)), uncertainties regarding appropriate control strategies and timing, and inaccuracies of perceived swarm reliability. Second, the results of a small-N subject-matter expert study will be discussed, highlighting evidence for component-specific trust (CST) and will highlight concerns from expert operators regarding: understanding appropriate inputs for swarm control, transfer of control, general transparency for swarms including the need for understanding why errors might occur and concerns regarding the effects of command latency. Third, human-centred challenges from the use of swarms in the real world will be discussed. These challenges include lessons learned regarding human-swarm interfaces, the intense challenges of logistics when using swarms in the real world, and otherwise hidden challenges of using swarms for real-world scenarios such as the Defense Advanced Research Project Agency (DARPA) OFFensive Swarm-Enabled Tactics (OFFSET) programme and the use of swarms for monitoring operations for the Air Force Marathon. This article will close with a brief discussion of the opportunity space within human-swarm interaction if the research community is able to close the gap on these human-centred challenges.This article is part of the theme issue 'The road forward with swarm systems'.

Background: Community pharmacists are well placed to identify and vaccinate unimmunized or under-immunized individuals who can put themselves and communities at risk of preventable disease. We designed and tested VaxCheck, a novel life-course vaccine review service that can be used to raise awareness and guide personal vaccination action plans, in community pharmacies in Ontario, Canada., Objective: To understand the experiences of community pharmacists and staff directly involved with providing the VaxCheck service as part of initial testing., Methods: Semi-structured interviews were performed with pharmacy staff from 9 pharmacies who participated in the study. Interviews were conducted at baseline and following each of 3 Plan-Do-Study-Act quality improvement cycles. Activities undertaken to perform VaxCheck were assessed. An inductive thematic analysis was performed to identify dominant themes and subthemes. Activities and descriptive codes were then correlated to the Consolidated Framework for Implementation Research (CFIR)., Results: Twenty-six interviews were conducted. Pharmacy staff described VaxCheck activities as spanning 3 stages: (1) Promotion/offering of VaxCheck, (2) Completing the VaxCheck, and (3) Enacting recommendations and follow-up. VaxCheck activities were compatible with workflow related to delivery of other vaccines and medication reviews. Thematic analysis found 3 considerations guided VaxCheck adoption: (1) Aligning VaxCheck with workflow through flexible integration, (2) Enabling patient-oriented vaccination services, and (3) Contributing to community healthcare provision. Data aligned with all CFIR domains with strengths noted in constructs from the "Innovation characteristics" and "Individuals" domains. Barriers to implementation were identified in "Inner setting," "Outer setting," and "Process" domains, such as pharmacy workflow capacity, patient knowledge about vaccination, availability of vaccine records, and interactions with other healthcare providers., Conclusion: Community pharmacists found VaxCheck to be a valuable, accessible service that was well-received by patients and supported adult vaccination reviews and individualized recommendations. VaxCheck was compatible with pharmacy workflow but needed additional resources for sustainability and promotion with stakeholders., Competing Interests: Disclosure Molly Yang reports board membership with AstraZeneca, Merck, and Pfizer; and speaker’s fees from GSK and Merck. Lisa Dolovich reports funding grants from GSK. Nancy M. Waite reports advisory board participation with Novavax and Sanofi; funding grants from GSK and Merck; and speaker’s fees from Sanofi. Sherilyn K. D. Houle reports advisory board participation with AstraZeneca, GSK, Merck, Novavax, Pfizer, Sanofi, Seqirus, and Valneva; funding grants from GSK, Pfizer, Sanofi, and Valneva; research consulting with Seqirus; and speaker’s fees with Novavax and Valneva. The authors declare no other relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Skydiving is an increasingly popular recreational activity in the United States and worldwide. While it is considered a high-risk sport, the United States Parachute Association reported a fatality of .28 per 100 000 jumps in 2022. Although mortality rates are low, the true rate of survivable injuries is unknown. Injuries requiring hospitalization are not uncommon and may be underreported in the literature. Anticipating these injuries and analyzing short-term outcomes following parachuting accidents would be useful for the development of mitigation strategies and to increase the safety of jumpers., Methods: A retrospective cohort review of 126 consecutive patients presenting to a Level II Trauma Center after skydiving accidents between 2016 and 2023. Patient baseline characteristics, patterns of injury, surgical procedures, and in-hospital outcomes were reviewed., Results: A total of 126 patients were included. One hundred and seventeen patients (93%) presented immediately following the accident, 65 (51.6%) were trauma activations, and 14 (11.1%) patients experienced loss of consciousness. Fractures of the lower extremity occurred in 57 (45%), fractures of the spine 48 (38%), upper extremity 13 (10%), pelvis 11 (9%). Of the spinal injuries, 10 injuries occurred in the cervical spine, 16 thoracic, 22 lumbar, 5 sacral, and 3 coccygeal spine. Eleven patients (9%) suffered multilevel spine injuries. Mean injury severity score was 7 (range 0-75). A third of patients required at least 1 surgical procedure (n = 43, 34%). Median length stay was 2 days (IQR 1, 5). Of patients who survived to our trauma center, there were two mortalities, both due to catastrophic intracranial hemorrhage., Discussion: Although the 30-day mortality rate for patient who presented to our trauma center is low, it can bear significant risks including major injury. The most common injuries were lower extremity and spinal in origin with a third of patients overall requiring at least one operation., 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.

Background and Objectives: This study aims to develop and evaluate NeuNN, a system based on convolutional neural networks (CNN) and generative adversarial networks (GAN) for the automatic identification of normal neutrophils and those containing several types of inclusions or showing hypogranulation., Methods: From peripheral blood smears, a set of 5605 digital images was obtained with neutrophils belonging to seven categories: Normal neutrophils (NEU), Hypogranulated (HYP) or containing cryoglobulins (CRY), Döhle bodies (DB), Howell-Jolly body-like inclusions (HJBLI), Green-blue inclusions of death (GBI) and phagocytosed bacteria (BAC). The dataset utilized in this study has been made publicly available. The class of GBI was augmented using synthetic images generated by GAN. The NeuNN classification model is based on an EfficientNet-B7 architecture trained from scratch., Results: NeuNN achieved an overall performance of 94.3% accuracy on the test data set. Performance metrics, including sensitivity, specificity, precision, F1-Score, Jaccard index, and Matthews correlation coefficient indicated overall values of 94%, 99.1%, 94.3%, 94.3%, 89.6%, and 93.6%, respectively., Conclusions: The proposed approach, combining data augmentation and classification techniques, allows for automated identification of morphological findings in neutrophils, such us inclusions or hypogranulation. The system can be used as a support tool for clinical pathologists to detect these specific abnormalities with clinical relevance., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Combining knowledge of clinical pathologists and deep learning models is a growing trend in morphological analysis of cells circulating in blood to add objectivity, accuracy, and speed in diagnosing hematological and non-hematological diseases. However, the variability in staining protocols across different laboratories can affect the color of images and performance of automatic recognition models. The objective of this work is to develop, train and evaluate a new system for the normalization of color staining of peripheral blood cell images, so that it transforms images from different centers to map the color staining of a reference center (RC) while preserving the structural morphological features., Methods: The system has two modules, GAN1 and GAN2. GAN1 uses the PIX2PIX technique to fade original color images to an adaptive gray, while GAN2 transforms them into RGB normalized images. Both GANs have a similar structure, where the generator is a U-NET convolutional neural network with ResNet and the discriminator is a classifier with ResNet34 structure. Digitally stained images were evaluated using GAN metrics and histograms to assess the ability to modify color without altering cell morphology. The system was also evaluated as a pre-processing tool before cells undergo a classification process. For this purpose, a CNN classifier was designed for three classes: abnormal lymphocytes, blasts and reactive lymphocytes., Results: Training of all GANs and the classifier was performed using RC images, while evaluations were conducted using images from four other centers. Classification tests were performed before and after applying the stain normalization system. The overall accuracy reached a similar value around 96% in both cases for the RC images, indicating the neutrality of the normalization model for the reference images. On the contrary, it was a significant improvement in the classification performance when applying the stain normalization to the other centers. Reactive lymphocytes were the most sensitive to stain normalization, with true positive rates (TPR) increasing from 46.3% - 66% for the original images to 81.2% - 97.2% after digital staining. Abnormal lymphocytes TPR ranged from 31.9% - 95.7% with original images to 83% - 100% with digitally stained images. Blast class showed TPR ranges of 90.3% - 94.4% and 94.4% - 100%, for original and stained images, respectively., Conclusions: The proposed GAN-based normalization staining approach improves the performance of classifiers with multicenter data sets by generating digitally stained images with a quality similar to the original images and adaptability to a reference staining standard. The system requires low computation cost and can help improve the performance of automatic recognition models in clinical settings., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

This work aimed to assess the effects of the coadministration of pentoxifylline (PTX) on the pharmacokinetic profile of florfenicol (FFC) after intramuscular administration in rabbits. Ten New Zealand white rabbits, 1 year of age and 3.9 ± 0.1 kg body weight, were assigned according to a randomized block design to Group 1 (FFC): treated with 30 mg/kg of FFC intramuscularly, and Group 2 (PTX + FFC) treated with an oral dose of 30 mg/kg PTX 45 min before the intramuscular injection of 30 mg/kg FFC. Blood samples were collected before and at different times between 0.5 and 12.0 h after drug administration. FFC plasma concentrations were determined by high-performance liquid chromatography. Results showed that IM injection of the long-acting formulation of FFC in rabbits resulted in a slow increase in mean plasma concentrations reaching a C max of 3.09 ± 0.52 ug/mL at 2.8 ± 0.45 h (T max ) after drug administration. While coadministration of PTX and FFC decreased the time to achieve the maximal concentration by modifying the absorption of FFC without changes in the other pharmacokinetic parameters., (© 2023 John Wiley & Sons Ltd.)

In vivo studies in dentistry require a high level of precision, since they involve the experimentation with a living organism, and further comprehensive histological analysis to validate the initial hypothesis. However, the process to obtained the histological slides to be studied is often wrongly minimized. In order to obtain high quality histological sections, which may be able to react favorably to more complex immunological techniques, it is necessary to preserve or "fix" the tissues of interest in an optimal manner. Intracardiac perfusion fixation has been described as a technique that offers superior results to other tissue fixation methods, allowing not only adequate sample stability, but also a deep cleansing and hardening of the tissues to allow further manipulation. Through a variation of the technique, it is possible to occlude the main arterial supply of the abdominal region to maintain direct perfusion of the fixator in the region of interest, such as the maxillofacial and thoracic region., Competing Interests: Conflicto de intereses: Los autores no reportaron ningún conflicto de intereses

Background: Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the anti-inflammatory and immunomodulatory properties of pentoxifylline (PTX) as an adjuvant to enhance the efficacy of antibiotics, the anti-inflammatory effects of the interaction FFC/PTX over the E. coli Lipopolysaccharide (LPS)-induced acute inflammatory response was evaluated in rabbits., Methods: Twenty-five clinically healthy New Zealand rabbits (3.8 ± 0.2 kg body weight: bw), were distributed into five experimental groups. Group 1 (control): treated with 1 mL/4 kg bw of 0.9% saline solution (SS) intravenously (IV). Group 2 (LPS): treated with an IV dose of 5 µg/kg of LPS. Group 3 (pentoxifylline (PTX) + LPS): treated with an oral dose of 30 mg/kg PTX, followed by an IV dose of 5 µg/kg of LPS 45 min after PTX. Group 4 (Florfenicol (FFC) + LPS): treated with an IM dose of 20 mg/kg of FFC, followed by an IV dose of 5 µg/kg of LPS 45 min after FFC administration. Group 5 (PTX + FFC + LPS): treated with an oral dose of 30 mg/kg of PTX, followed by an IM dose of 20 mg/kg of FFC, and, 45 min after an IV dose of 5 µg/kg of LPS was administered. The anti-inflammatory response was evaluated through changes in plasma levels of interleukins (TNF-α, IL-1β and IL-6), C-reactive protein (CRP), and body temperature., Results: It has been shown that each drug produced a partial inhibition over the LPS-induced increase in TNF-α, IL-1β, and CRP. When both drugs were co-administered, a synergistic inhibitory effect on the IL-1β and CRP plasma concentrations was observed, associated with a synergic antipyretic effect. However, the co-administration of PTX/FFC failed to modify the LPS-induced increase in the TNF-α plasma concentrations., Conclusions: We concluded that the combination of FFC and PTX in our LPS sepsis models demonstrates immunomodulatory effects. An apparent synergistic effect was observed for the IL-1β inhibition, which peaks at three hours and then decreases. At the same time, each drug alone was superior in reducing TNF-α levels, while the combination was inferior. However, the peak of TNF-α in this sepsis model was at 12 h. Therefore, in rabbits plasma IL-1β and TNF-α could be regulated independently, thus, further research is needed to explore the effects of this combination over a more prolonged period.

The Sphaeralcea angustifolia plant is used as an anti-inflammatory and gastrointestinal protector in Mexican traditional medicine. The immunomodulatory and anti-inflammatory effects have been attributed to scopoletin ( 1 ), tomentin ( 2 ), and sphaeralcic acid ( 3 ) isolated from cells in suspension cultures and identified in the aerial tissues of the wild plant. The hairy roots from S. angustifolia established by infecting internodes with Agrobacterium rhizogenes were explored to produce active compounds based on biosynthetic stability and their capacity to produce new compounds. Chemical analysis was resumed after 3 years in these transformed roots, SaTRN12.2 (line 1) produced scopoletin (0.0022 mg g -1 ) and sphaeralcic acid (0.22 mg g -1 ); instead, the SaTRN7.1 (line 2) only produced sphaeralcic acid (3.07 mg g -1 ). The sphaeralcic acid content was 85-fold higher than that reported for the cells in the suspension cultivated into flakes, and it was similar when the cells in suspension were cultivated in a stirring tank under nitrate restriction. Moreover, both hairy root lines produced stigmasterol ( 4 ) and β-sitosterol ( 5 ), as well as two new naphthoic derivates: iso-sphaeralcic acid ( 6 ) and 8-methyl-iso-sphaeralcic acid ( 7 ), which turned out to be isomers of sphaeralcic acid ( 3 ) and have not been reported. The dichloromethane-methanol extract from SaTRN7.1 hairy root line had a gastroprotective effect on an ulcer model in mice induced with ethanol.

Background and Objectives: Visual analysis of cell morphology has an important role in the diagnosis of hematological diseases. Morphological cell recognition is a challenge that requires experience and in-depth review by clinical pathologists. Within the new trend of introducing computer-aided diagnostic tools in laboratory medicine, models based on deep learning are being developed for the automatic identification of different types of cells in peripheral blood. In general, well-annotated large image sets are needed to train the models to reach a desired classification performance. This is especially relevant when it comes to discerning between cell images in which morphological differences are subtle and when it comes to low prevalent diseases with the consequent difficulty in collecting cell images. The objective of this work is to develop, train and validate SyntheticCellGAN (SCG), a new system for the automatic generation of artificial images of white blood cells, maintaining morphological characteristics very close to real cells found in practice in clinical laboratories., Methods: SCG is designed with two sequential generative adversarial networks. First, a Wasserstein structure is used to transform random noise vectors into low resolution images of basic mononuclear cells. Second, the concept of image-to-image translation is used to build specific models that transform the basic images into high-resolution final images with the realistic morphology of each cell type target: 1) the five groups of normal leukocytes (lymphocytes, monocytes, eosinophils, neutrophils and basophils); 2) atypical promyelocytes and hairy cells, which are two relevant cell types of complex morphology with low abundance in blood smears., Results: The images of the SCG system are evaluated with four experimental tests. In the first test we evaluated the generated images with quantitative metrics for GANs. In the second test, morphological verification of the artificial images is performed by expert clinical pathologists with 100% accuracy. In the third test, two classifiers based on convolutional neural networks (CNN) previously trained with images of real cells are used. Two sets of artificial images of the SCG system are classified with an accuracy of 95.36% and 94%, respectively. In the fourth test, three CNN classifiers are trained with artificial images of the SCG system. Real cells are identified with an accuracy ranging from 87.7% to 100%., Conclusions: The SCG system has proven effective in creating images of all normal leukocytes and two low-prevalence cell classes associated with diseases such as acute promyelocyte leukemia and hairy cell leukemia. Once trained, the system requires low computational cost and can help augment high-quality image datasets to improve automatic recognition model training for clinical laboratory practice., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The role of osteopontin (OPN) following severe injury remains to be elucidated, especially its relationship with type I collagen (encoded by the Col1a1 gene) secretion by newly-differentiated odontoblast-like cells (OBLCs). In this study, we examined the role of OPN in the process of reparative dentin formation with a focus on reinnervation and revascularization after tooth replantation in Opn knockout (KO) and wild-type (WT) mice., Methods: Maxillary first molars of 2- and 3-week-old- Opn KO and WT mice ( Opn KO 2W, Opn KO 3W, WT 2W, and WT 3W groups) were replanted, followed by fixation 3-56 days after operation. Following micro-computed tomography analysis, the decalcified samples were processed for immunohistochemistry for Ki67, Nestin, PGP 9.5, and CD31 and in situ hybridization for Col1a1 ., Results: An intense inflammatory reaction occurred to disrupt pulpal healing in the replanted teeth of the Opn KO 3W group, whereas dental pulp achieved healing in the Opn KO 2W and WT groups. The tertiary dentin in the Opn KO 3W group was significantly decreased in area compared with the Opn KO 2W and WT groups, with a significantly low percentage of Nestin-positive, newly-differentiated OBLCs during postoperative days 7-14. In the Opn KO 3W group, the blood vessels were significantly decreased in area and pulp healing was disturbed with a failure of pulpal revascularization and reinnervation., Conclusions: OPN is necessary for proper reinnervation and revascularization to deposit reparative dentin following severe injury within the dental pulp of erupted teeth with advanced root development., Competing Interests: The authors declare no conflicts of interest related to this study., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Laboratory medicine plays a fundamental role in the detection, diagnosis and management of COVID-19 infection. Recent observations of the morphology of cells circulating in blood found the presence of particular reactive lymphocytes (COVID-19 RL) in some of the infected patients and demonstrated that it was an indicator of a better prognosis of the disease. Visual morphological analysis is time consuming, requires smear review by expert clinical pathologists, and is prone to subjectivity. This paper presents a convolutional neural network system designed for automatic recognition of COVID-19 RL. It is based on the Xception71 structure and is trained using images of blood cells from real infected patients. An experimental study is carried out with a group of 92 individuals. The input for the system is a set of images selected by the clinical pathologist from the blood smear of a patient. The output is the prediction whether the patient belongs to the group associated with better prognosis of the disease. A threshold is obtained for the classification system to predict that the smear belongs to this group. With this threshold, the experimental test shows excellent performance metrics: 98.3% sensitivity and precision, 97.1% specificity, and 97.8% accuracy. The system does not require costly calculations and can potentially be integrated into clinical practice to assist clinical pathologists in a more objective smear review for early prognosis.

Aims: Atypical lymphocytes circulating in blood have been reported in COVID-19 patients. This study aims to (1) analyse if patients with reactive lymphocytes (COVID-19 RL) show clinical or biological characteristics related to outcome; (2) develop an automatic system to recognise them in an objective way and (3) study their immunophenotype., Methods: Clinical and laboratory findings in 36 COVID-19 patients were compared between those showing COVID-19 RL in blood (18) and those without (18). Blood samples were analysed in Advia2120i and stained with May Grünwald-Giemsa. Digital images were acquired in CellaVisionDM96. Convolutional neural networks (CNNs) were used to accurately recognise COVID-19 RL. Immunophenotypic study was performed throughflow cytometry., Results: Neutrophils, D-dimer, procalcitonin, glomerular filtration rate and total protein values were higher in patients without COVID-19 RL (p<0.05) and four of these patients died. Haemoglobin and lymphocyte counts were higher (p<0.02) and no patients died in the group showing COVID-19 RL. COVID-19 RL showed a distinct deep blue cytoplasm with nucleus mostly in eccentric position. Through two sequential CNNs, they were automatically distinguished from normal lymphocytes and classical RL with sensitivity, specificity and overall accuracy values of 90.5%, 99.4% and 98.7%, respectively. Immunophenotypic analysis revealed COVID-19 RL are mostly activated effector memory CD4 and CD8 T cells., Conclusion: We found that COVID-19 RL are related to a better evolution and prognosis. They can be detected by morphology in the smear review, being the computerised approach proposed useful to enhance a more objective recognition. Their presence suggests an abundant production of virus-specific T cells , thus explaining the better outcome of patients showing these cells circulating in blood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized "The Cancer Genome Atlas" (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic of effector T helper cell (T h ) subsets by ELISA using plasma from each AA and CA participant. Results: Colon tumors from AA patients showed significant fold-change increase in gene expression when compared to CA for FOXP3 (6.22 vs. 3.22), IL1B (103 vs. 11.4) and IL8 (220 vs. 28.9) ( p < 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and the immunotherapy targets PDL1 ( CD274 ) and CTLA4 ( p < 0.05). TCGA data validated our observed higher gene expression of GZMB and PDL1 in CA patients when compared to AA. Notably, our observations on immune cell populations show that AA tumors have significantly higher number of exhausted CD8+ cells ( p < 0.01), mast cells ( p < 0.02) and increased T regulatory cells when compared to CA. AA colon cancer patients differed from CA in cytokine production patterns in plasma (i.e., reduced IL-12). Conclusions: Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches., (Copyright © 2020 Paredes, Zabaleta, Garai, Ji, Imtiaz, Spagnardi, Alvarado, Li, Akadri, Barrera, Munoz-Sagastibelza, Gupta, Alshal, Agaronov, Talus, Wang, Carethers, Williams and Martello.)

Background and study aims  Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods  Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results  A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions  This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Background and Objectives: Ventral hernia repair is one of the most commonly performed general surgery procedures, and minimally invasive approaches are increasingly preferred. The physiologic repair offered by the preperitoneal approach is favorable, with reduced complications, but it remains a technical challenge. The robotic platform allows for enhanced instrument flexibility and ease of operation. We conducted a retrospective review of our experience with robotic transabdominal preperitoneal repair (rTAPP) versus robotic intraperitoneal onlay mesh (rIPOM) at a tertiary care hospital in an urban setting., Methods: We reviewed the records of patients undergoing minimally invasive ventral hernia repair from March 2014 through March 2017. Demographics, complication rates, and operative time were compared by t test and Chi square test, as applicable., Results: Sixty-three patients met the criteria for inclusion in the study. Of those, 27 underwent ventral hernia repair with rIPOM and 36 with rTAPP, with no major intraoperative complications. There were no significant differences in demographics between the 2 groups in age, BMI, and sex. The difference in mean operative time was not significant (rIPOM 167.26 [SD 51.76] minutes vs rTAPP 158.84 minutes [SD 61.5]; P = .57), whereas mean console time was significantly different (rIPOM 70.88 minutes [SD 32.88] vs rTAPP 90.26 [SD 31.17]; P = .018). Postoperative complications occurred only with rIPOM and included urinary retention, seroma, and fever., Conclusions: rTAPP is a promising alternative to rIPOM, with reduced complications without adding significant operative time, and may allow for reduced costs.

Background: The aim of this study was to investigate a novel resident education model that turns the traditional surgical hierarchy upside down, termed a "reverse" peer-assisted learning curriculum., Methods: Thirty surgical topics were randomized between medical students and chief residents on each clinical team, with 1 topic being presented briefly during morning rounds. An exam evaluating junior residents' knowledge of these topics was administered before and after 1 month of presentations. A questionnaire was distributed to evaluate the junior residents' perceptions of this teaching model., Results: Thirty-four residents participated. There was a significant improvement in the mean examination score (54 vs 74, P < .05). No significant difference was noted in the mean score differentials of topics presented by either the medical students or the chief resident (21 vs 18, P = .22). More than 80% of the residents responded positively about the effectiveness of this exercise and agreed that they would like to see this model used on other services., Conclusions: This study confirms the hypothesis that medical students can teach surgical topics to junior residents at least as effectively as their chief residents., (Published by Elsevier Inc.)

In rodents, the barrel cortex is a specialized area within the somatosensory cortex that processes signals from the mystacial whiskers. We investigated the normal development of myelination in the barrel cortex of mice, as well as the effects of sensory deprivation on this pattern. Deprivation was achieved by trimming the whiskers on one side of the face every other day from birth. In control mice, myelin was not present until postnatal day 14 and did not show prominence until postnatal day 30; adult levels of myelination were reached by the end of the second postnatal month. Unbiased stereology was used to estimate axon density in the interbarrel septal region and barrel walls as well as the barrel centers. Myelin was significantly more concentrated in the interbarrel septa/barrel walls than in the barrel centers in both control and sensory-deprived conditions. Sensory deprivation did not impact the onset of myelination but resulted in a significant decrease in myelinated axons in the barrel region and decreased the amount of myelin ensheathing each axon. Visualization of the oligodendrocyte nuclear marker Olig2 revealed a similar pattern of myelin as seen using histochemistry, but with no significant changes in Olig2+ nuclei following sensory deprivation. Consistent with the anatomical results showing less myelination, local field potentials revealed slower rise times following trimming. Our results suggest that myelination develops relatively late and can be influenced by sensory experience., (Copyright © 2012 Wiley Periodicals, Inc.)

The opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised individuals, including individuals with the heritable disease cystic fibrosis. Like the carbon sources metabolized by many disease-causing bacteria, the carbon sources metabolized by P. aeruginosa at the host infection site are unknown. We recently reported that l-alanine is a preferred carbon source for P. aeruginosa and that two genes potentially involved in alanine catabolism (dadA and dadX) are induced during in vivo growth in the rat peritoneum and during in vitro growth in sputum (mucus) collected from the lungs of individuals with cystic fibrosis. The goals of this study were to characterize factors required for alanine catabolism in P. aeruginosa and to assess the importance of these factors for in vivo growth. Our results reveal that dadA and dadX are arranged in an operon and are required for catabolism of l-alanine. The dad operon is inducible by l-alanine, d-alanine, and l-valine, and induction is dependent on the transcriptional regulator Lrp. Finally, we show that a mutant unable to catabolize dl-alanine displays decreased competitiveness in a rat lung model of infection.

In contrast to adult colonic intussusception in which malignancy is the dominant cause, small bowel intussusceptions are mostly benign. Although surgery is the accepted standard treatment, its necessity in small bowel intussusceptions identified by CT scan is unknown. Twenty-three patients from 2005 to 2008 (16 males; median age, 44 years) with acute abdominal pain and CT-proven small bowel intussusception were studied. Factors associated with the necessity for surgery were determined. Among 11 patients who were managed operatively, surgery was deemed unnecessary in two patients based on negative explorations. Follow up in 10 of 12 patients managed nonoperatively was not associated with any recurrence of intussusception or malignancy (median follow up, 14 months). The only predictor of the need for surgery was CT evidence of small bowel obstruction and/or a radiologically identified lead point, which was present in 7 of 9 (78%) patients having a necessary operation and absent in 12 of 14 (86%) with no indication for surgery (P = 0.008). All small bowel intussusceptions found on CT scan in patients with acute abdominal pain do not require operative management. CT findings of small bowel obstruction and/or presence of a lead point are indications for surgery.