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Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography is challenging due to the size and stability constraints of conventional bubble-based agents. Here bicones, truly tiny acoustic contrast agents based on gas vesicles (GVs), a unique class of air-filled protein nanostructures naturally produced in buoyant microbes, are described. It is shown that these sub-80 nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as systemically injectable nanomaterials have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.

Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)-one for use in bacteria and one for use in mammalian cells-identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively. Using these new ARGs, we non-invasively imaged in situ tumor colonization and gene expression in tumor-homing therapeutic bacteria, tracked the progression of tumor gene expression and growth in a mouse model of breast cancer, and performed gene-expression-guided needle biopsies of a genetically mosaic tumor, demonstrating non-invasive access to dynamic biological processes at centimeter depth., (© 2023. The Author(s).)

Localization and tracking of ingestible microdevices in the gastrointestinal (GI) tract is valuable for the diagnosis and treatment of GI disorders. Such systems require a large field-of-view of tracking, high spatiotemporal resolution, wirelessly operated microdevices and a non-obstructive field generator that is safe to use in practical settings. However, the capabilities of current systems remain limited. Here, we report three dimensional (3D) localization and tracking of wireless ingestible microdevices in the GI tract of large animals in real time and with millimetre-scale resolution. This is achieved by generating 3D magnetic field gradients in the GI field-of-view using high-efficiency planar electromagnetic coils that encode each spatial point with a distinct magnetic field magnitude. The field magnitude is measured and transmitted by the miniaturized, low-power and wireless microdevices to decode their location as they travel through the GI tract. This system could be useful for quantitative assessment of the GI transit-time, precision targeting of therapeutic interventions and minimally invasive procedures., Competing Interests: Competing interests S.S., M.G.S. and A.E. have joint US patents (20,210,137,412 and 11,457,835 B2) on the localization and magnetic-field generation concepts. M.G.S. and A.E. are founding members of Tychon Technologies. All the other authors declare no competing interests.

Rapid advances in synthetic biology are driving the development of genetically engineered microbes as therapeutic agents for a multitude of human diseases, including cancer. The immunosuppressive microenvironment of solid tumors, in particular, creates a favorable niche for systemically administered bacteria to engraft and release therapeutic payloads. However, such payloads can be harmful if released outside the tumor in healthy tissues where the bacteria also engraft in smaller numbers. To address this limitation, we engineer therapeutic bacteria to be controlled by focused ultrasound, a form of energy that can be applied noninvasively to specific anatomical sites such as solid tumors. This control is provided by a temperature-actuated genetic state switch that produces lasting therapeutic output in response to briefly applied focused ultrasound hyperthermia. Using a combination of rational design and high-throughput screening we optimize the switching circuits of engineered cells and connect their activity to the release of immune checkpoint inhibitors. In a clinically relevant cancer model, ultrasound-activated therapeutic microbes successfully turn on in situ and induce a marked suppression of tumor growth. This technology provides a critical tool for the spatiotemporal targeting of potent bacterial therapeutics in a variety of biological and clinical scenarios., (© 2022. The Author(s).)

Recent advances in molecular engineering and synthetic biology provide biomolecular and cell-based therapies with a high degree of molecular specificity, but limited spatiotemporal control. Here we show that biomolecules and cells can be engineered to deliver potent mechanical effects at specific locations inside the body through ultrasound-induced inertial cavitation. This capability is enabled by gas vesicles, a unique class of genetically encodable air-filled protein nanostructures. We show that low-frequency ultrasound can convert these biomolecules into micrometre-scale cavitating bubbles, unleashing strong local mechanical effects. This enables engineered gas vesicles to serve as remotely actuated cell-killing and tissue-disrupting agents, and allows genetically engineered cells to lyse, release molecular payloads and produce local mechanical damage on command. We demonstrate the capabilities of biomolecular inertial cavitation in vitro, in cellulo and in vivo, including in a mouse model of tumour-homing probiotic therapy., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Phagocytic clearance and lysosomal processing of pathogens and debris are essential functions of the innate immune system. However, the assessment of these functions in vivo is challenging because most nanoscale contrast agents compatible with noninvasive imaging techniques are made from nonbiodegradable synthetic materials that do not undergo regular lysosomal degradation. To overcome this challenge, we describe the use of an all-protein contrast agent to directly visualize and quantify phagocytic and lysosomal activities in vivo by ultrasound imaging. This contrast agent is based on gas vesicles (GVs), a class of air-filled protein nanostructures naturally expressed by buoyant microbes. Using a combination of ultrasound imaging, pharmacology, immunohistology, and live-cell optical microscopy, we show that after intravenous injection, GVs are cleared from circulation by liver-resident macrophages. Once internalized, the GVs undergo lysosomal degradation, resulting in the elimination of their ultrasound contrast. By noninvasively monitoring the temporal dynamics of GV-generated ultrasound signal in circulation and in the liver and fitting them with a pharmacokinetic model, we can quantify the rates of phagocytosis and lysosomal degradation in living animals. We demonstrate the utility of this method by showing how these rates are perturbed in two models of liver dysfunction: phagocyte deficiency and nonalcoholic fatty liver disease. The combination of proteolytically degradable nanoscale contrast agents and quantitative ultrasound imaging thus enables noninvasive functional imaging of cellular degradative processes.

Visualizing biomolecular and cellular processes inside intact living organisms is a major goal of chemical biology. However, existing molecular biosensors, based primarily on fluorescent emission, have limited utility in this context due to the scattering of light by tissue. In contrast, ultrasound can easily image deep tissue with high spatiotemporal resolution, but lacks the biosensors needed to connect its contrast to the activity of specific biomolecules such as enzymes. To overcome this limitation, we introduce the first genetically encodable acoustic biosensors-molecules that 'light up' in ultrasound imaging in response to protease activity. These biosensors are based on a unique class of air-filled protein nanostructures called gas vesicles, which we engineered to produce nonlinear ultrasound signals in response to the activity of three different protease enzymes. We demonstrate the ability of these biosensors to be imaged in vitro, inside engineered probiotic bacteria, and in vivo in the mouse gastrointestinal tract.

Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota—such as probiotics, dietary modifications, and fecal microbiota transplantation—offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response. [ABSTRACT FROM AUTHOR]

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal switch with a T7 RNA Polymerase. Due to the orthogonality of the Polymerase, this strategy overcame limitations imposed by the host transcriptional machinery. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40 °C while maintaining leakiness below the detection limit at 37 °C. Furthermore, the thermo-amplifier circuit sustained gene expression beyond the thermal induction duration such that with only 2 h of induction, the bacteria were able to produce pathogen-inhibitory levels of darobactin. This performance was maintained even in physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels. [ABSTRACT FROM AUTHOR]

Besides being responsible for olfaction and air intake, the nose contains abundant vasculature and autonomic nervous system innervations, and it is a cerebrospinal fluid clearance site. Therefore, the nose is an attractive target for functional MRI (fMRI). Yet, nose fMRI has not been possible so far due to signal losses originating from nasal air-tissue interfaces. Here, we demonstrated feasibility of nose fMRI by using novel ultrashort/zero echo time (TE) MRI. Results obtained in the resting-state from 13 healthy participants at 7T and in 5 awake mice at 9.4T revealed a highly reproducible resting-state nose functional network that likely reflects autonomic nervous system activity. Another network observed in humans involves the nose, major brain vessels and CSF spaces, presenting a temporal dynamic that correlates with heart rate and breathing rate. These resting-state nose functional signals should help elucidate peripheral and central nervous system integrations. [ABSTRACT FROM AUTHOR]

Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. [ABSTRACT FROM AUTHOR]

Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans. Our findings indicate that Aqp1 overexpression does not induce ER stress, which is frequently associated with heterologous expression of membrane proteins. Furthermore, we observed that Aqp1 expression had no detrimental effects on native biological activities, such as phagocytosis, immune response, insulin secretion, and tumor cell migration in the analyzed cell lines. These findings should serve to alleviate any lingering safety concerns regarding the utilization of Aqp1 as a genetic reporter and should foster its broader application as a noninvasive reporter for in vivo studies. [ABSTRACT FROM AUTHOR]

Advances in understanding the genetic basis of cancer have driven alternative treatment approaches. Recent findings have demonstrated the potential of bacteria and it’s components to serve as robust theranostic agents for cancer eradication. Compared to traditional cancer therapies like surgery, chemotherapy, radiotherapy, bacteria mediated tumor therapy has exhibited superior cancer suppressing property which is attributed a lot to it’s tumor proliferating and accumulating characteristics. Genetically modified bacteria has reduced inherent toxicity and enhanced specificity towards tumor microenvironment. This anti- tumor activity of bacteria is attributed to its toxins and other active components from the cell membrane, cell wall and spores. Furthermore, bacterial genes can be regulated to express and deliver cytokines, antibodies and cancer therapeutics. Although there is less clinical data available, the pre- clinical research clearly indicates the feasibility and potential of bacteria- mediated cancer therapy. [ABSTRACT FROM AUTHOR]

Bacteria, as living agents, have been widely used for microbial therapy due to their inherent ability to colonize different in vivo microenvironments, particularly in the gut and tumor. The interaction with diverse biointerfaces plays a critical role in bacterial colonization, and thereby determine the ultimate efficacy of microbial therapy. Although surface modification of bacteria with exogenous functional motifs can vary their interaction with surroundings, the effects of surface chirality of modified bacteria on mucous adhesion, tumor cell binding, and bacterial competition remain unknown. Here, we describe surface chirality-dependent selective interactions of bacteria to mucins, tumor cells, and pathogens. By coating bacteria with cationic polyethyleneimine modified with different chiral amino acids through electrostatic interaction, we find that bacteria coated with a D-chiral surface structure exhibit greatly increased adhesion to both mucins and tumor cells compared with those of L- and DL-structures. In addition, by adjusting the chirality of the coating, wrapped probiotic bacteria can selectively resist pathogenic bacteria, showing great potential to enhance colonization and positively modulate the gut and tumor microbiota. This work discloses surface chirality-dependent interaction of bacteria with different biointerfaces, showing a potential to tune the colonization and therapeutic effect of living bacterial agents for disease treatment. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess whether articular cartilage changes in an equine model of post‐traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very subtle sharp grooves, could be detected with ex vivo T1 relaxation time mapping utilizing three‐dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T1 relaxation times of the samples (n = 8 + 8 for experimental and n = 12 for contralateral controls) were measured with a variable flip angle 3D multiband‐sweep imaging with Fourier transform sequence. Equilibrium and instantaneous Young's moduli and proteoglycan (PG) content from OD of Safranin‐O‐stained histological sections were measured and utilized as reference parameters for the T1 relaxation times. T1 relaxation time was significantly (p < 0.05) increased in both groove areas, particularly in the blunt grooves, compared with control samples, with the largest changes observed in the superficial half of the cartilage. T1 relaxation times correlated weakly (Rs ≈ 0.33) with equilibrium modulus and PG content (Rs ≈ 0.21). T1 relaxation time in the superficial articular cartilage is sensitive to changes induced by the blunt grooves but not to the much subtler sharp grooves, at the 39‐week timepoint post‐injury. These findings support that T1 relaxation time has potential in detection of mild PTOA, albeit the most subtle changes could not be detected. [ABSTRACT FROM AUTHOR]

New sensors and modulators that interact wirelessly with medical modalities unlock uncharted avenues for in situ brain recording and stimulation. Ongoing miniaturization, material refinement, and sensitization to specific neurophysiological and neurochemical processes are spurring new capabilities that begin to transcend the constraints of traditional bulky and invasive wired probes. Here we survey current state-of-the-art agents across diverse realms of operation and evaluate possibilities depending on size, delivery, specificity and spatiotemporal resolution. We begin by describing implantable and injectable micro- and nano-scale electronic devices operating at or below the radio frequency (RF) regime with simple near field transmission, and continue with more sophisticated devices, nanoparticles and biochemical molecular conjugates acting as dynamic contrast agents in magnetic resonance imaging (MRI), ultrasound (US) transduction and other functional tomographic modalities. We assess the ability of some of these technologies to deliver stimulation and neuromodulation with emerging probes and materials that provide minimally invasive magnetic, electrical, thermal and optogenetic stimulation. These methodologies are transforming the repertoire of readily available technologies paired with compatible imaging systems and hold promise toward broadening the expanse of neurological and neuroscientific diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Autonomous vehicles are continually increasing their presence on public roads. However, before any new autonomous driving software can be approved, it must first undergo a rigorous assessment of driving quality. These quality evaluations typically focus on estimating the frequency of (undesirable) behavioral events. While rate estimation would be straight‐forward with complete data, in the autonomous driving setting this estimation is greatly complicated by the fact that detecting these events within large driving logs is a non‐trivial task that often involves human reviewers. In this article, we outline a streaming partial tiered event review configuration that ensures both high recall and high precision on the events of interest. In addition, the framework allows for valid streaming estimates at any phase of the data collection process, even when labels are incomplete, for which we develop the maximum likelihood estimate and show it is unbiased. Constructing honest and effective confidence intervals (CI) for these rate estimates, particularly for rare safety‐critical events, is a novel and challenging statistical problem due to the complexity of the data likelihood. We develop and compare several CI approximations, including a novel gamma CI method that approximates the exact but intractable distribution with a weighted sum of independent Poisson random variables. There is a clear trade‐off between statistical coverage and interval width across the different CI methods, and the extent of this trade‐off varies depending on the specific application settings (e.g., rare vs. common events). In particular, we argue that our proposed CI method is the best‐suited when estimating the rate of safety‐critical events where guaranteed coverage of the true parameter value is a prerequisite to safely launching a new ADS on public roads. [ABSTRACT FROM AUTHOR]

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation. [ABSTRACT FROM AUTHOR]

Perception of peripersonal space (PPS) and interpersonal distance (IPD) has been shown to be modified by external factors such as perceived danger, the use of tools, and social factors. Especially in times of social distancing in the context of the COVID-19 pandemic, it is vital to study factors that modify PPS and IPD. The present work addresses the question of whether wearing a face mask as a protection tool and social interaction impact the perception of IPD. We tested estimated IPD in pictures at three distances: 50 cm, 90 cm, and 150 cm in both social interaction (shaking hands) and without interaction and when the two people in the pictures wore a face mask or not. Data from 60 subjects were analyzed in a linear mixed model (on both difference in distance estimation to the depicted distance and in absolute distance estimation) and in a 3 (distance: 50, 90, 150) × 2 (interaction: no interaction, shake hands), × 2 face mask (no mask, mask) rmANOVA on distance estimation difference. All analyses showed that at a distance of 50 and 90 cm, participants generally underestimated the IPD while at an IPD of 150 cm, participants overestimated the distance. This could be grounded in perceived danger and avoidance behavior at closer distances, while the wider distance between persons was not perceived as dangerous. Our findings at an IPD of 90 cm show that social interaction has the largest effect at the border of our PPS, while the face mask did not affect social interaction at either distance. In addition, the ANOVA results indicate that when no social interaction was displayed, participants felt less unsafe when depicted persons wore a face mask at distances of 90 and 150 cm. This shows that participants are on the one hand aware of the given safety measures and internalized them; on the other hand, that refraining from physical social interaction helps to get close to other persons. [ABSTRACT FROM AUTHOR]

To compare alveolar bone height and width measurements from zero-echo-time MRI (ZTE-MRI) and cone beam CT (CBCT), in human specimens. Twenty posterior edentulous sites in human cadaver specimens were imaged with CBCT and ZTE-MRI. Bone height and width at 1, 3, 5, 7 and 9 mm from the top of the alveolar ridge was measured by two trained observers in cross-sections of a site where an implant was to be planned. Twenty percent of the sample was measured in duplicate to assess method error and intra-observer reproducibility (ICC). The differences between CBCT and ZTE-MRI measurements were compared (t-test). Inter- and intra-observer reproducibility was >0.90. The method error (average between observers) for bone height was 0.45 mm and 0.39 mm, and for bone width (average) was 0.52 mm and 0.80 mm (CBCT and ZTE-MRI, respectively). The majority of the bone measurement differences were statistically insignificant, except bone width measurements at 5 mm (p ≤.05 for both observers). Mean measurement differences were not larger than the method error. ZTE-MRI is not significantly different from CBCT when comparing measurements of alveolar bone height and width. [ABSTRACT FROM AUTHOR]

Peripersonal space is the space surrounding our body, where multisensory integration of stimuli and action execution take place. The size of peripersonal space is flexible and subject to change by various personal and situational factors. The dynamic representation of our peripersonal space modulates our spatial behaviors towards other individuals. During the COVID-19 pandemic, this spatial behavior was modified by two further factors: social distancing and wearing a face mask. Evidence from offline and online studies on the impact of a face mask on pro-social behavior is mixed. In an attempt to clarify the role of face masks as pro-social or anti-social signals, 235 observers participated in the present online study. They watched pictures of two models standing at three different distances from each other (50, 90 and 150 cm), who were either wearing a face mask or not and were either interacting by initiating a hand shake or just standing still. The observers' task was to classify the model by gender. Our results show that observers react fastest, and therefore show least avoidance, for the shortest distances (50 and 90 cm) but only when models wear a face mask and do not interact. Thus, our results document both pro- and anti-social consequences of face masks as a result of the complex interplay between social distancing and interactive behavior. Practical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

With the in-depth understanding of the anti-cancer immunity, immunotherapy has become a promising cancer treatment after surgery, radiotherapy, and chemotherapy. As natural immunogenicity substances, some bacteria can preferentially colonize and proliferate inside tumor tissues to interact with the host and exert anti-tumor effect. However, further research is hampered by the infection-associated toxicity and their unpredictable behaviors in vivo. Due to modern advances in genetic engineering, synthetic biology, and material science, modifying bacteria to minimize the toxicity and constructing a bacteria-based immunotherapy platform has become a hotspot in recent research. This review will cover the inherent advantages of unedited bacteria, highlight how bacteria can be engineered to provide greater tumor-targeting properties, enhanced immune-modulation effect, and improved safety. Successful applications of engineered bacteria in cancer immunotherapy or as part of the combination therapy are discussed as well as the bacteria based immunotherapy in different cancer types. In the end, we highlight the future directions and potential opportunities of this emerging field. [ABSTRACT FROM AUTHOR]

The pandemic of COVID-19 led to restrictions in all kinds of music activities. Airborne transmission of SARS-CoV-2 requires risk assessment of wind instrument playing in various situations. Previous studies focused on short-range transmission, whereas long-range transmission risk has not been assessed. The latter requires knowledge of aerosol emission rates from wind instrument playing. We measured aerosol concentrations in a hermetically closed chamber of 20 m3 in an operating theatre as resulting from 20 min standardized wind instrument playing (19 flute, 11 oboe, 1 clarinet, 1 trumpet players). We calculated aerosol emission rates showing uniform distribution for both instrument groups. Aerosol emission from wind instrument playing ranged from 11 ± 288 particles/second (P/s) up to 2535 ± 195 P/s, expectation value ± uncertainty standard deviation. The analysis of aerosol particle size distributions shows that 70–80% of emitted particles had a size of 0.25–0.8 µm and thus are alveolar. Masking the bell with a surgical mask did not reduce aerosol emission. Aerosol emission rates were higher from wind instrument playing than from speaking or breathing. Differences between instrumental groups could not be found but high interindividual variance, as expressed by uniform distribution of aerosol emission rates. Our findings indicate that aerosol emission depends on physiological factors and playing techniques rather than on the type of instrument, in contrast to some previous studies. Based on our results, we present transmission risk calculations for long-range transmission of COVID-19 for three typical woodwind playing situations. [ABSTRACT FROM AUTHOR]

Background: Equal-tailed confidence intervals that maintain nominal coverage (0.95 or greater probability that a 95% confidence interval covers the true value) are useful in interval-based statistical reliability standards, because they remain conservative. For age-adjusted death rates, while the Fay–Feuer gamma method remains the gold standard, modifications have been proposed to streamline implementation and/or obtain more efficient intervals (shorter intervals that retain nominal coverage). Methods: This paper evaluates three such modifications for use in interval-based statistical reliability standards, the Anderson–Rosenberg, Tiwari, and Fay–Kim intervals, when data are sparse and sample size-based standards alone are overly coarse. Initial simulations were anchored around small populations (P = 2400 or 1200), the median crude all-cause US mortality rate in 2010–2019 (833.8 per 100,000), and the corresponding age-specific probabilities of death. To allow for greater variation in the age-adjustment weights and age-specific probabilities, a second set of simulations draws those at random, while holding the mean number of deaths at 20 or 10. Finally, county-level mortality data by race/ethnicity from four causes are selected to capture even greater variation: all causes, external causes, congenital malformations, and Alzheimer disease. Results: The three modifications had comparable performance when the number of deaths was large relative to the denominator and the age distribution was as in the standard population. However, for sparse county-level data by race/ethnicity for rarer causes of death, and for which the age distribution differed sharply from the standard population, coverage probability in all but the Fay–Feuer method sometimes fell below 0.95. More efficient intervals than the Fay–Feuer interval were identified under specific circumstances. When the coefficient of variation of the age-adjustment weights was below 0.5, the Anderson–Rosenberg and Tiwari intervals appeared to be more efficient, whereas when it was above 0.5, the Fay–Kim interval appeared to be more efficient. Conclusions: As national and international agencies reassess prevailing data presentation standards to release age-adjusted estimates for smaller areas or population subgroups than previously presented, the Fay–Feuer interval can be used to develop interval-based statistical reliability standards with appropriate thresholds that are generally applicable. For data that meet certain statistical conditions, more efficient intervals could be considered. [ABSTRACT FROM AUTHOR]

Humans typically create and maintain social bonds through interactions that occur at close social distances. The interpersonal distance of at least 1 m recommended as a relevant measure for COVID-19 contagion containment requires a significant change in everyday behavior. In a web-based experimental study conducted during the first pandemic wave (mid-April 2020), we asked 242 participants to regulate their preferred distance towards confederates who did or did not wear protective masks and gloves and whose COVID-19 test results were positive, negative, or unknown. Information concerning dispositional factors (perceived vulnerability to disease, moral attitudes, and prosocial tendencies) and situational factors (perceived severity of the situation in the country, frequency of physical and virtual social contacts, and attitudes toward quarantine) that may modulate compliance with safety prescriptions was also acquired. A Bayesian analysis approach was adopted. Individual differences did not modulate interpersonal distance. We found strong evidence in favor of a reduction of interpersonal distance towards individuals wearing protective equipment and who tested negative to COVID-19. Importantly, shorter interpersonal distances were maintained towards confederates wearing protective gear, even when their COVID-19 test result was unknown or positive. This protective equipment-related regulation of interpersonal distance may reflect an underestimation of perceived vulnerability to infection; this perception must be discouraged when pursuing individual and collective health-safety measures. [ABSTRACT FROM AUTHOR]

Aims : The potential benefits of workplace physical activity (PA) interventions are in improving both health and important workplace outcomes. Despite the differences in PA level between physically strenuous and inactive work, the literature reporting the effectiveness of the interventions does not usually differentiate physically active and inactive jobs. The aim of the current study was therefore to collect and synthesise research evidence on workplace PA interventions to promote work ability specifically among workers in physically strenuous jobs by means of a scoping review. Methods : The databases Medline, Cochrane Central and Scopus were used to identify interventions to promote work ability by increasing PA among workers in physically strenuous jobs. An iterative method was used to obtain an overview of the study elements and to extract details on the study design, sample, intervention, outcomes and effectiveness. Results : A total of 47 studies evaluating eight categories of interventions were found. Out of these, 18 reported significant effects on work ability. Positive results came from a range of different interventions, including aerobic exercise, strength training, combined aerobic exercise and strength training, stretching, yoga, consultation and tailored physical exercise programmes. Conclusions : Few interventions were effective in promoting work ability by increasing PA among workers in physically strenuous jobs. In particular, trials based on the demands of work, multimodal interventions and applying wearable technology are needed. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) studies in animal models provide invaluable information regarding normal and abnormal brain function, especially when combined with complementary stimulation and recording techniques. The echo planar imaging (EPI) pulse sequence is the most common choice for fMRI investigations, but it has several shortcomings. EPI is one of the loudest sequences and very prone to movement and susceptibility-induced artefacts, making it suboptimal for awake imaging. Additionally, the fast gradient-switching of EPI induces disrupting currents in simultaneous electrophysiological recordings. Therefore, we investigated whether the unique features of Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) overcome these issues at a high 9.4 T magnetic field, making it a potential alternative to EPI. MB-SWIFT had 32-dB and 20-dB lower peak and average sound pressure levels, respectively, than EPI with typical fMRI parameters. Body movements had little to no effect on MB-SWIFT images or functional connectivity analyses, whereas they severely affected EPI data. The minimal gradient steps of MB-SWIFT induced significantly lower currents in simultaneous electrophysiological recordings than EPI, and there were no electrode-induced distortions in MB-SWIFT images. An independent component analysis of the awake rat functional connectivity data obtained with MB-SWIFT resulted in near whole-brain level functional parcellation, and simultaneous electrophysiological and fMRI measurements in isoflurane-anesthetized rats indicated that MB-SWIFT signal is tightly linked to neuronal resting-state activity. Therefore, we conclude that the MB-SWIFT sequence is a robust preclinical brain mapping tool that can overcome many of the drawbacks of conventional EPI fMRI at high magnetic fields. • MB-SWIFT is significantly quieter than EPI, and insensitive to body movement. • Almost whole-brain functional parcellation was achieved in awake rats with MB-SWIFT. • EEG and MB-SWIFT fMRI signals had excellent correlation in anesthetized rats. • Gradient artefacts in EEG-fMRI recordings were only minimal during MB-SWIFT. • MB-SWIFT is a robust fMRI method that can overcome many of the drawbacks of EPI. [ABSTRACT FROM AUTHOR]

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Purpose: The management of small (≤5 mm) rectal neuroendocrine neoplasms (r-NENs), incidentally removed during colonoscopy, still remains under debate. Methods: All consecutive patients affected by r-NENs from January 2013 to December 2017 were studied. The inclusion criteria were: (1) patients having an incidental pathological diagnosis of very small (≤5 mm) polypoid r-NENs; (2) patients treated with a standard polypectomy as first-line therapy and (3) patients treated by endoscopic submucosal dissection (ESD) as salvage therapy. The primary endpoint was to identify the factors related to residual disease after a standard polypectomy. The secondary endpoint was to calculate the accuracy of endoscopic ultrasound (EUS), grading and size in predicting residual disease. Results: Starting from a prospective database of 123 consecutive patients affected by r-NENs, only 31 met the inclusion criteria. A final pathological examination of an ESD specimen showed residual disease in 7 out of 31 patients (22.6%). A multivariate analysis showed that the size of the polyps was the only independent factor related to residual disease with an odds ratio of 8.7 ± 7.5 (P = 0.013) for each millimetre. The accuracy of EUS, grading and tumour size (3.1 mm cut-off point) and area under the curves were 0.661 ± 0.111, 0.631 ± 0.109 and 0.821 ± 0.109, respectively. Conclusions: When the r-NEN polyp was larger than 3 mm, ESD was indicated. Unlike the size of the tumour, grading and EUS features did not accurately predict residual disease. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to look at the practices and perspectives of residential aged care facility (RACF) care staff regarding the provision of oral health care in RACFs.Background: Emphasis has been placed on the provision of adequate oral health care in RACFs through the Better Oral Health in Residential Aged Care programme. Endorsed by the Australian government, this programme provided oral health education and training for aged care staff. However, recent evidence suggests that nearly five years after the implementation of this programme, the provision of oral care in RACFs in NSW remains inadequate.Materials and Methods: This project utilised an exploratory qualitative design which involved a focus group with 12 RACF care staff. Participants were asked to discuss the current oral health practices in their facility, and their perceived barriers to providing oral health care.Results: The key findings demonstrated current oral health practices and challenges among care staff. Most care staff had received oral health training and demonstrated positive attitudes towards providing dental care. However, some participants identified that ongoing and regular training was necessary to inform practice and raise awareness among residents. Organisational constraints and access to dental services also limited provision of dental care while a lack of standardised guidelines created confusion in defining their role as oral healthcare providers in the RACF.Conclusion: This study highlighted the need for research and strategies that focus on capacity building care staff in oral health care and improving access of aged care residents to dental services. [ABSTRACT FROM AUTHOR]

Copyright of Ornitologia Colombiana is the property of Asociacion Colombiana de Ornitologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose To use contrast based on longitudinal relaxation times (T1) or rates (R1) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs. Methods Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naïve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues. Results Signal enhancement from positive T1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R1 and volumetric SAR in hyperthermia therapy was observed. Conclusion The linear dependence between R1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702-712, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

The article discusses the potential benefits of vitrification for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. It examines the use of inductive heating of magnetic nanoparticles in improving tissue cryopreservation and determined physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues.

To investigate the effect of a preventive strength training program on cardiovascular, metabolic and muscular strains during welding. Welders are one of the occupation groups which typically have to work in extended forced postures which are known to be an important reason for musculoskeletal disorders. Subjects (exercise group) accomplished a 12-week strength training program, while another group served as controls (control group). Pre and post training examinations included the measurements of the one repetition maximum and an experimental welding test. Local muscle activities were analysed by surface electromyography. Furthermore, heart rate, blood pressure, lactate and rating of perceived exertion were examined. In the exercise group, strength training lead to a significant increase of one repetition maximum in all examined muscles (p <.05). During the experimental welding test muscle activities of trunk and shoulder muscles and arm muscles were significantly reduced in the exercise group after intervention (p <.05). While no changes of neither cardiovascular nor metabolic parameters were found, subjects of the exercise group rated a significantly decreased rate of perceived exertion welding (p <.05). Effects of strength training can be translated in an improved working ergonomics and tolerance against the exposure to high physical demands at work. [ABSTRACT FROM AUTHOR]