Outpatient and Ambulatory Extended Recovery Robotic Hepatectomy: Multinational Study of 307 Cases.

BACKGROUND: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure. STUDY DESIGN: We audited outpatient (<2 midnights) robotic hepatectomies at six hepatobiliary centers in two nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. ERAS programs were active at all sites, and home digital monitoring was available at one of the institutions. RESULTS: Three hundred and seven outpatient (26 same-day, 281 next-day discharge) robotic hepatectomies were identified (2013-2023). Most were minor hepatectomies (194 single-segments, 90 bi-segmentectomies, 14 three-segments, 8 four-segments). Thirty-nine (13%) were for benign histology, while 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, 208 metastatic disease). Patient characteristics were - median age 60 (18-93), 55% male, and median BMI 26 (14-63). Thirty (10%) had cirrhosis. One-hundred-eighty-seven (61%) had previous abdominal surgery. Median operative time was 163 minutes (30-433), with a median blood loss of 50 cc (10-900). There were no deaths and six complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Re-admission was required in 5 patients (1.6%).Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7/8/4A/2/1), there were 12 positive margins (9%) and two readmissions for abscess. CONCLUSIONS: Outpatient robotic hepatectomies in well-selected cases are safe (0 mortality, 2% complication, 1.6% re-admission), including resections in the superior or posterior portions of the liver that are challenging with non-articulating laparoscopic instruments.

Development and Feasibility Testing of a Decision Aid for Acute Appendicitis.

INTRODUCTION: Patients with acute uncomplicated appendicitis will be increasingly asked to choose between surgery and antibiotic management. We developed a novel decision aid for patients in the emergency department (ED) with acute appendicitis who are facing this choice. We describe the development of the decision aid and an initial feasibility study of its implementation in a busy tertiary care ED. MATERIALS AND METHODS: We conducted a prepost survey analysis comparing patients before and after standardized implementation of the decision aid. Patients were surveyed about their experience making treatment decisions after discharge from the hospital. The primary outcome measure was the total score on the decisional conflict scale (; 0-100; lower scores better). RESULTS: The study included 24 participants (12 in the predecision aid period; 12 in the post period). Only 33% of participants in each group knew antibiotics were a treatment option prior to arriving at the ED. Prior to implementing the use of decision aid, only 75% of patients reported being told antibiotics were a treatment option, while this increased to 100% after implementation of the decision aid. The mean total decisional conflict scalescores were similar in the pre and post periods (mean difference = 0.13, 95% CI: -13 - 13, P > 0.9). CONCLUSIONS: This novel appendicitis decision aid was effectively integrated into clinical practice and helped toinform patients about multiple treatment options. These data support further large-scale testing of the decision aid as part of standardized pathways for the management of patients with acute appendicitis.

Teacher cognition in teaching intercultural communicative competence: A qualitative study on preservice Chinese language teachers in Hong Kong SAR, China.

The purpose of this study is to examine preservice Chinese language teachers' cognition in teaching intercultural communicative competence. In the study we collected data through in-depth interviews with seven preservice teachers in a Master of Education program (Teaching Chinese as a Second Language, TCSL) at a university in Hong Kong SAR, China. The findings indicated that the participants had a relatively positive attitude and inclination toward the development of students' intercultural communicative competence, while their conceptualizations of culture tended to be static and ambiguous. In addition, the participants' objectives in teaching intercultural communicative competence were found to be more attitude-than knowledge- or skill-oriented. The study offers valuable insights that preservice language teachers' cognition plays a crucial role in their future professional development and calls for curricular innovations with intercultural aims in teacher education programs.

Recent Progress in Lyme Disease and Remaining Challenges.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

Age-related changes to macrophages are detrimental to fracture healing in mice.

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age-related diseases. Therefore, we investigated age-related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA-seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up-regulation of M1/pro-inflammatory genes in macrophages from old mice as well as dysregulation of other immune-related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age-matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA-seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age-related changes, and depleting infiltrating macrophages can improve fracture healing in old mice.

A Corpus-Based Study on the Pragmatic Use of the ba Construction in Early Childhood Mandarin Chinese.

This article reports on an inquiry that investigated the development of ba constructions in early childhood Mandarin. All cases of ba construction were extracted from the Early Childhood Mandarin Corpus collected from 168 preschoolers aged 2;6, 3;6, 4;6, and 5;6 (year; month; Li and Tse, 2011). Early Childhood Mandarin Corpus, University of Hong Kong. Data analysis indicated that: (1) Mandarin-speaking children produced a repertoire of 11 types of ba construction, and the children in the youngest age group (age 2;6) were able to produce six types of them; (2) children at 4 years old (age 4;6) experienced a critical developmental period of pragmatic use, and at 5 years old (age 5;6) they had attained cognitive and linguistic maturity in understanding the semantic and syntactic features of ba constructions; and (3) there was a significant age effect on the production of three types of ba construction, but no significant association between the children's gender and their production of ba constructions. These findings offer fresh insights into understanding Chinese children's innate capacity to understand the co-occurrence constraints concerning the syntactic, semantic and verb features inherent in ba construction, and their developmental ability to denote telic events by resorting to the appropriate ba sentence patterns.

Plasmon Reflections by Topological Electronic Boundaries in Bilayer Graphene.

Domain walls separating regions of AB and BA interlayer stacking in bilayer graphene have attracted attention as novel examples of structural solitons, topological electronic boundaries, and nanoscale plasmonic scatterers. We show that strong coupling of domain walls to surface plasmons observed in infrared nanoimaging experiments is due to topological chiral modes confined to the walls. The optical transitions among these chiral modes and the band continua enhance the local conductivity, which leads to plasmon reflection by the domain walls. The imaging reveals two kinds of plasmonic standing-wave interference patterns, which we attribute to shear and tensile domain walls. We compute the electronic structure of both wall varieties and show that the tensile wall contains additional confined bands which produce a structure-specific contrast of the local conductivity, in agreement with the experiment. The coupling between the confined modes and the surface plasmon scattering unveiled in this work is expected to be common to other topological electronic boundaries found in van der Waals materials. This coupling provides a qualitatively new pathway toward controlling plasmons in nanostructures.

Using impedance to track fracture healing rates in mice in vivo: A pilot study.

Fracture injuries are highly prevalent worldwide, with treatment of problematic fractures causing a significant burden on the U.S. healthcare system. Physicians typically monitor fracture healing by conducting physical examinations and taking radiographic images. However, nonunions currently take over 6 months to be diagnosed because these techniques are not sensitive enough to adequately assess fracture union. In this study, we display the utility of impedance spectroscopy to track different healing rates in a pilot study of an in vivo mouse tibia fracture model. We have developed small (56 µm) sensors and implanted them in an externally-stabilized fracture for twice-weekly measurement. We found that impedance magnitude increases steadily over time in healing mice but stalls in non-healing mice, and phase angle displays frequency-dependent behavior that also reflects the extent of healing at the fracture site. Our results demonstrate that impedance can track differences in healing rates early on, highlighting the potential of this technique as a method for early detection of fracture nonunion.

New opportunities for fracture healing detection: Impedance spectroscopy measurements correlate to tissue composition in fractures.

Accurate evaluation of fracture healing is important for clinical decisions on when to begin weight-bearing and when early intervention is necessary in cases of fracture nonunion. While the stages of healing involving hematoma, cartilage, trabecular bone, and cortical bone have been well characterized histologically, physicians typically track fracture healing by using subjective physical examinations and radiographic techniques that are only able to detect mineralized stages of bone healing. This exposes the need for a quantitative, reliable technique to monitor fracture healing, and particularly to track healing progression during the early stages of repair. The goal of this study was to validate the use of impedance spectroscopy to monitor fracture healing and perform comprehensive evaluation comparing measurements with histological evidence. Here, we show that impedance spectroscopy not only can distinguish between cadaver tissues involved throughout fracture repair, but also correlates to fracture callus composition over the middle stages of healing in wild-type C57BL/6 mice. Specifically, impedance magnitude has a positive relationship with % trabecular bone and a negative relationship with % cartilage, and the opposite relationships are found when comparing phase angle to these same volume fractions of tissues. With this information, we can quantitatively evaluate how far a fracture has progressed through the healing stages. Our results demonstrate the feasibility of impedance spectroscopy for detection of fracture callus composition and reveals its potential as a method for early detection of bone healing and fracture nonunion. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2620-2629, 2017.

Genome-Wide Transcriptional Start Site Mapping and sRNA Identification in the Pathogen Leptospira interrogans.

Leptospira are emerging zoonotic pathogens transmitted from animals to humans typically through contaminated environmental sources of water and soil. Regulatory pathways of pathogenic Leptospira spp. underlying the adaptive response to different hosts and environmental conditions remains elusive. In this study, we provide the first global Transcriptional Start Site (TSS) map of a Leptospira species. RNA was obtained from the pathogen Leptospira interrogans grown at 30°C (optimal in vitro temperature) and 37°C (host temperature) and selectively enriched for 5' ends of native transcripts. A total of 2865 and 2866 primary TSS (pTSS) were predicted in the genome of L. interrogans at 30 and 37°C, respectively. The majority of the pTSSs were located between 0 and 10 nucleotides from the translational start site, suggesting that leaderless transcripts are a common feature of the leptospiral translational landscape. Comparative differential RNA-sequencing (dRNA-seq) analysis revealed conservation of most pTSS at 30 and 37°C. Promoter prediction algorithms allow the identification of the binding sites of the alternative sigma factor sigma 54. However, other motifs were not identified indicating that Leptospira consensus promoter sequences are inherently different from the Escherichia coli model. RNA sequencing also identified 277 and 226 putative small regulatory RNAs (sRNAs) at 30 and 37°C, respectively, including eight validated sRNAs by Northern blots. These results provide the first global view of TSS and the repertoire of sRNAs in L. interrogans. These data will establish a foundation for future experimental work on gene regulation under various environmental conditions including those in the host.

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes.

Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ). Hypertrophic chondrocytes in the TZ activate expression of the pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], and conditional knock-out of Sox2 during fracture healing results in reduction of the fracture callus and a delay in conversion of cartilage to bone. The signal(s) triggering expression of the pluripotency genes are unknown, but we demonstrate that endothelial cell conditioned medium upregulates these genes in ex vivo fracture cultures, supporting histological evidence that transdifferentiation occurs adjacent to the vasculature. Elucidating the cellular and molecular mechanisms underlying fracture repair is important for understanding why some fractures fail to heal and for developing novel therapeutic interventions.

Fracture healing in osteoporotic bone.

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models.

A high-density microelectrode-tissue-microelectrode sandwich platform for application of retinal circuit study.

BACKGROUND: Microelectrode array (MEA) devices are frequently used in neural circuit studies, especially in retinal prosthesis. For a high throughput stimulation and recording paradigm, it is desirable to obtain the responses of multiple surface RGCs initiated from the electrical signals delivered to multiple photoreceptor cells. This can be achieved by an high density MEA-tissue-MEA (MTM) sandwich configuration. However, the retina is one of the most metabolically active tissues, consumes oxygen as rapidly as the brain. The major concern of the MTM configuration is the supply of oxygen. METHODS: We aimed to develop a high density MTM sandwich platform which consists of stacks of a stimulation MEA, retinal tissue and a recording MEA. Retina is a metabolically active tissue and the firing rate is very sensitive to oxygen level. We designed, simulated and microfabricated porous high density MEAs and an adjustable perfusion system that electrical signals can be delivered to and recorded from the clipped retinal tissue. RESULTS: The porous high-density MEAs linked with stimulation or recording devices within a perfusion system were manufactured and the MTM platform was assembled with a retina slice inside. The firing rate remained constant between 25 and 55 min before dramatically declined, indicating that within certain period of time (e.g. 30 min after habituation), the retina condition was kept by sufficient oxygen supply via the perfusion holes in the MEAs provided by the double perfusion system. CONCLUSIONS: MTM sandwich structure is an efficient platform to study the retinal neural circuit. The material and arrangement of high density microelectrodes with porous design make this MEA appropriate for sub-retina prosthesis. Finding ways to prolong the recording time and reduce the signal-to-noise ratio are important to improve our MTM prototype.

The pathological role and prognostic impact of miR-181 in acute myeloid leukemia.

In addition to genetic abnormalities, such as chromosomal translocations and somatic mutations that have been widely acknowledged in the leukemogenesis of acute myeloid leukemia (AML), epigenetic modifications also play a vital role in this process. MicroRNA (miRNA) regulation is emerging as a new layer of epigenetic regulation besides DNA methylation and histone modifications. Among the miRNAs first identified to be specifically expressed in hematopoietic cells, the miR-181 family has been implicated in regulating the differentiation of B cells, T cells, and natural killer cells during normal hematopoiesis, and has been linked tightly to the pathogenesis and prognosis of AML. Accumulating evidence indicates that miR-181 acts as a tumor suppressor in the pathogenesis of AML and exhibits a significant impact on the survival of patients with AML. Herein, we review the role of miR-181 as a diagnostic marker and prognostic predictor in AML, and discuss the potential use of miR-181 as a therapeutic target for AML.

Role of muscle stem cells during skeletal regeneration.

Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7(-/-) mice and satellite cell ablation in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications.

The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis.

The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/ß-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further supports the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis.

Experimental Evidence for Dark Excitons in Monolayer WSe_{2}.

Transition metal dichalcogenides in the class MX_{2} (M=Mo, W; X=S, Se) have been identified as direct-gap semiconductors in the monolayer limit. Here, we examine light emission of monolayer WSe_{2} using temperature-dependent photoluminescence and time-resolved photoluminescence spectroscopy. We present experimental evidence for the existence of an optically forbidden dark state of the band-gap exciton that lies tens of meV below the optically bright state. The presence of the dark state is manifest in the strong quenching of light emission observed at reduced temperatures. The experimental findings are consistent with theoretical predictions of spin-polarized conduction and valence bands at the K point of the Brillouin zone, with the minimum gap occurring between bands of opposite electron spin.

Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy.

Duchenne muscular dystrophy (DMD) patients exhibit skeletal muscle weakness with continuous cycles of muscle fiber degeneration/regeneration, chronic inflammation, low bone mineral density, and increased risks of fracture. Fragility fractures and associated complications are considered as a consequence of the osteoporotic condition in these patients. Here, we aimed to establish the relationship between muscular dystrophy and fracture healing by assessing bone regeneration in mdx mice, a model of DMD with absence of osteoporosis. Our results illustrate that muscle defects in mdx mice impact the process of bone regeneration at various levels. In mdx fracture calluses, both cartilage and bone deposition were delayed followed by a delay in cartilage and bone remodeling. Vascularization of mdx fracture calluses was also decreased during the early stages of repair. Dystrophic muscles are known to contain elevated numbers of macrophages contributing to muscle degeneration. Accordingly, we observed increased macrophage recruitment in the mdx fracture calluses and abnormal macrophage accumulation throughout the process of bone regeneration. These changes in the inflammatory environment subsequently had an impact on the recruitment of osteoclasts and the remodeling phase of repair. Further damage to the mdx muscles, using a novel model of muscle trauma, amplified both the chronic inflammatory response and the delay in bone regeneration. In addition, PLX3397 treatment of mdx mice, a cFMS (colony stimulating factor receptor 1) inhibitor in monocytes, partially rescued the bone repair defect through increasing cartilage deposition and decreasing the number of macrophages. In conclusion, chronic inflammation in mdx mice contributes to the fracture healing delay and is associated with a decrease in angiogenesis and a transient delay in osteoclast recruitment. By revealing the role of dystrophic muscle in regulating the inflammatory response during bone repair, our results emphasize the implication of muscle in the normal bone repair process and may lead to improved treatment of fragility fractures in DMD patients.

MMP9 regulates the cellular response to inflammation after skeletal injury.

Like other tissue injuries, bone fracture triggers an inflammatory response, which plays an important role in skeletal repair. Inflammation is believed to have both positive and negative effects on bone repair, but the underlying cellular mechanisms are not well understood. To assess the role of inflammation on skeletal cell differentiation, we used mouse models of fracture repair that stimulate either intramembranous or endochondral ossification. In the first model, fractures are rigidly stabilized leading to direct bone formation, while in the second model, fracture instability causes cartilage and bone formation. We compared the inflammatory response in these two mechanical environments and found changes in the expression patterns of inflammatory genes and in the recruitment of inflammatory cells and osteoclasts. These results suggested that the inflammatory response could influence skeletal cell differentiation after fracture. We then exploited matrix metalloproteinase 9 (MMP9) that is expressed in inflammatory cells and osteoclasts, and which we previously showed is a potential regulator of cell fate decisions during fracture repair. Mmp9(-/-) mice heal stabilized fractures via endochondral ossification, while wild type mice heal via intramembranous ossification. In parallel, we observed increases in macrophages and T cells in the callus of Mmp9(-/-) compared to wild type mice. To assess the link between the profile of inflammatory cells and skeletal cell fate functionally, we transplanted Mmp9(-/-) mice with wild type bone marrow, to reconstitute a wild type hematopoietic lineage in interaction with the Mmp9(-/-) stroma and periosteum. Following transplantation, Mmp9(-/-) mice healed stabilized fractures via intramembranous ossification and exhibited a normal profile of inflammatory cells. Moreover, Mmp9(-/-) periosteal grafts healed via intramembranous ossification in wild type hosts, but healed via endochondral ossification in Mmp9(-/-) hosts. We observed that macrophages accumulated at the periosteal surface in Mmp9(-/-) mice, suggesting that cell differentiation in the periosteum is influenced by factors such as BMP2 that are produced locally by inflammatory cells. Taken together, these results show that MMP9 mediates indirect effects on skeletal cell differentiation by regulating the inflammatory response and the distribution of inflammatory cells, leading to the local regulation of periosteal cell differentiation.