Multiple Complicated Concurrent Hernias in a Single Patient: A Case Report.

Multiple complicated concurrent hernias with obturator hernia and paraesophageal hernia unusually occur in clinical settings. The obturator hernias belong to a rare pelvic hernia that accounts for a minority of all abdominal hernias. Besides, paraesophageal hernias occur commonly in elderly female patients. Clinical manifestations of these hernias are usually unspecific and the diagnosis is based on computed tomography (CT). In this paper, we presented a case of multiple complicated hernias in an 81-year-old woman. She was admitted to our hospital due to intestinal obstruction that was caused by a simultaneous obturator and paraesophageal hernia. She was successfully treated by laparoscopic hernia repair. Postoperative progression was favorable. She was then discharged from the hospital after four hospital days.

A deep learning approach for projection and body-side classification in musculoskeletal radiographs.

BACKGROUND: The growing prevalence of musculoskeletal diseases increases radiologic workload, highlighting the need for optimized workflow management and automated metadata classification systems. We developed a large-scale, well-characterized dataset of musculoskeletal radiographs and trained deep learning neural networks to classify radiographic projection and body side. METHODS: In this IRB-approved retrospective single-center study, a dataset of musculoskeletal radiographs from 2011 to 2019 was retrieved and manually labeled for one of 45 possible radiographic projections and the depicted body side. Two classification networks were trained for the respective tasks using the Xception architecture with a custom network top and pretrained weights. Performance was evaluated on a hold-out test sample, and gradient-weighted class activation mapping (Grad-CAM) heatmaps were computed to visualize the influential image regions for network predictions. RESULTS: A total of 13,098 studies comprising 23,663 radiographs were included with a patient-level dataset split, resulting in 19,183 training, 2,145 validation, and 2,335 test images. Focusing on paired body regions, training for side detection included 16,319 radiographs (13,284 training, 1,443 validation, and 1,592 test images). The models achieved an overall accuracy of 0.975 for projection and 0.976 for body-side classification on the respective hold-out test sample. Errors were primarily observed in projections with seamless anatomical transitions or non-orthograde adjustment techniques. CONCLUSIONS: The deep learning neural networks demonstrated excellent performance in classifying radiographic projection and body side across a wide range of musculoskeletal radiographs. These networks have the potential to serve as presorting algorithms, optimizing radiologic workflow and enhancing patient care. RELEVANCE STATEMENT: The developed networks excel at classifying musculoskeletal radiographs, providing valuable tools for research data extraction, standardized image sorting, and minimizing misclassifications in artificial intelligence systems, ultimately enhancing radiology workflow efficiency and patient care. KEY POINTS: • A large-scale, well-characterized dataset was developed, covering a broad spectrum of musculoskeletal radiographs. • Deep learning neural networks achieved high accuracy in classifying radiographic projection and body side. • Grad-CAM heatmaps provided insight into network decisions, contributing to their interpretability and trustworthiness. • The trained models can help optimize radiologic workflow and manage large amounts of data.

BAMLET administration via drinking water inhibits intestinal tumor development and promotes long-term health.

Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. ApcMin/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/ß-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone ApcMin/+ mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.

Comparison of Point Accuracy Between Two Widely Used Continuous Glucose Monitoring Systems.

BACKGROUND: Safe and effective self-management of glucose levels requires immediate access to accurate data. We assessed the point accuracy of the Dexcom G7 Continuous Glucose Monitoring System (Dexcom, Inc., San Diego, CA, USA) and FreeStyle Libre 3 (Abbott Diabetes Care, Alameda, CA, USA) sensors in a head-to-head comparison. METHOD: Multicenter, single-arm, prospective, nonsignificant risk evaluation enrolled adults (≥ 18 years) with diagnosed type 1 diabetes (T1D) or type 2 diabetes (T2D). Accuracy was assessed by comparing sensor data to laboratory reference values Yellow Springs Instrument [YSI] and capillary blood glucose values. Outcome measures were differences in mean absolute relative difference (MARD), number and percentage of matched glucose pairs within ±20 mg/dL/±20 of reference values within glucose ranges: < 54, 54 to 69, 70 to 180, 181 to 250, > 250 mg/dL, and combined. RESULTS: Data from 55 adults were included in the analysis. Analysis showed significantly lower MARD with the FreeStyle Libre 3 sensor vs the Dexcom G7 sensor (8.9% vs 13.6%, respectively, P < .0001) with a higher percentage of glucose values within ±20 mg/dL/±20 of reference (91.4% vs 78.6%). The MARD values for both continuous glucose monitoring (CGM) sensors were similar during the first 12 hours; however, the FreeStyle Libre 3 MARD was notably lower than the Dexcom G7 MARD during the next 12 hours (10.0% vs 15.1%, respectively, P < .0001) and throughout the study period. CONCLUSIONS: The FreeStyle Libre 3 sensor was more accurate than the Dexcom G7 sensor in all metrics evaluated throughout the study period. This is the first head-to-head study to our knowledge that compares the flagship products currently in widespread use of the two largest CGM manufacturers.

Healthcare students' knowledge, attitudes, and perspectives toward artificial intelligence in the southern Vietnam.

The application of new technologies in medical education still lags behind the extraordinary advances of AI. This study examined the understanding, attitudes, and perspectives of Vietnamese medical students toward AI and its consequences, as well as their knowledge of existing AI operations in Vietnam. A cross-sectional online survey was administered to 1142 students enrolled in undergraduate medicine and pharmacy programs. Most of the participants had no understanding of AI in healthcare (1053 or 92.2 %). The majority believed that AI would benefit their careers (890 or 77.9 %) and that such innovation will be used to oversee public health and epidemic prevention on their behalf (882 or 77.2 %). The proportion of students with satisfactory knowledge significantly differed depending on gender (P < 0.001), major (P = 0.003), experience (P < 0.001), and income (P = 0.011). The percentage of respondents with positive attitudes significantly differed by year level (P = 0.008) and income (P = 0.003), and the proportion with favorable perspectives regarding AI varied considerably by age (P = 0.046) and major (P < 0.001). Most of the participants wanted to integrate AI into radiology and digital imaging training (P = 0.283), while the fifth-year students wished to learn about AI in medical genetics and genomics (P < 0.001, 4.0 ± 0.8). The male students had 1.898 times more adequate knowledge of AI than their female counterparts, and those who had attended webinars/lectures/courses on AI in healthcare had 4.864 times more adequate knowledge than those having no such experiences. The majority believed that the barrier to implementing AI in healthcare is the lack of financial resources (83.54 %) and appropriate training (81.00 %). Participants saw AI as a "partner" rather than a "competitor", but the majority of low knowledge was recorded. Future research should take into account the way to integrate AI into medical training programs for healthcare students.

Pelvic arteriovenous malformation mimicking benign prostatic hyperplasia: A case report.

Pelvic arteriovenous malformation is a rare vascular abnormality, espescially in male patients, and is difficult to treat because of its nature supplied by multiple arterial feeders. We report a 70-year-old male patient admitted due to symptoms of benign prostatic hyperplasia. Ultrasound was performed initially, and no other abnormalities were found other than an enlarged prostate. CT scan later demonstrated a pelvic arteriovenous malformation adjacent to the prostate, with multiple arterial feeders from the right internal iliac artery. Angiography confirmed the diagnosis, and transaterial embolization was successfully done. The symptoms disappeared several days later, and the patient remained asymptompmatic during follow-up.

FAS and SREBP-1c Inhibition via AMPK Activation in HepG2 Cells by Biovip, Tox-off, and Traphanoside GO1 from Glinus oppositifolius.

Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.

Performance of ChatGPT, human radiologists, and context-aware ChatGPT in identifying AO codes from radiology reports.

While radiologists can describe a fracture's morphology and complexity with ease, the translation into classification systems such as the Arbeitsgemeinschaft Osteosynthesefragen (AO) Fracture and Dislocation Classification Compendium is more challenging. We tested the performance of generic chatbots and chatbots aware of specific knowledge of the AO classification provided by a vector-index and compared it to human readers. In the 100 radiological reports we created based on random AO codes, chatbots provided AO codes significantly faster than humans (mean 3.2 s per case vs. 50 s per case, p < .001) though not reaching human performance (max. chatbot performance of 86% correct full AO codes vs. 95% in human readers). In general, chatbots based on GPT 4 outperformed the ones based on GPT 3.5-Turbo. Further, we found that providing specific knowledge substantially enhances the chatbot's performance and consistency as the context-aware chatbot based on GPT 4 provided 71% consistent correct full AO codes for the compared to the 2% consistent correct full AO codes for the generic ChatGPT 4. This provides evidence, that refining and providing specific context to ChatGPT will be the next essential step in harnessing its power.

A Context-based Chatbot Surpasses Trained Radiologists and Generic ChatGPT in Following the ACR Appropriateness Guidelines.

Background Radiological imaging guidelines are crucial for accurate diagnosis and optimal patient care as they result in standardized decisions and thus reduce inappropriate imaging studies. Purpose In the present study, we investigated the potential to support clinical decision-making using an interactive chatbot designed to provide personalized imaging recommendations from American College of Radiology (ACR) appropriateness criteria documents using semantic similarity processing. Methods We utilized 209 ACR appropriateness criteria documents as specialized knowledge base and employed LlamaIndex, a framework that allows to connect large language models with external data, and the ChatGPT 3.5-Turbo to create an appropriateness criteria contexted chatbot (accGPT). Fifty clinical case files were used to compare the accGPT's performance against general radiologists at varying experience levels and to generic ChatGPT 3.5 and 4.0. Results All chatbots reached at least human performance level. For the 50 case files, the accGPT performed best in providing correct recommendations that were "usually appropriate" according to the ACR criteria and also did provide the highest proportion of consistently correct answers in comparison with generic chatbots and radiologists. Further, the chatbots provided substantial time and cost savings, with an average decision time of 5 minutes and a cost of 0.19 € for all cases, compared to 50 minutes and 29.99 € for radiologists (both p < 0.01). Conclusion ChatGPT-based algorithms have the potential to substantially improve the decision-making for clinical imaging studies in accordance with ACR guidelines. Specifically, a context-based algorithm performed superior to its generic counterpart, demonstrating the value of tailoring AI solutions to specific healthcare applications.

Advanced Soft Robotic System for In Situ 3D Bioprinting and Endoscopic Surgery.

Three-dimensional (3D) bioprinting technology offers great potential in the treatment of tissue and organ damage. Conventional approaches generally rely on a large form factor desktop bioprinter to create in vitro 3D living constructs before introducing them into the patient's body, which poses several drawbacks such as surface mismatches, structure damage, and high contamination along with tissue injury due to transport and large open-field surgery. In situ bioprinting inside a living body is a potentially transformational solution as the body serves as an excellent bioreactor. This work introduces a multifunctional and flexible in situ 3D bioprinter (F3DB), which features a high degree of freedom soft printing head integrated into a flexible robotic arm to deliver multilayered biomaterials to internal organs/tissues. The device has a master-slave architecture and is operated by a kinematic inversion model and learning-based controllers. The 3D printing capabilities with different patterns, surfaces, and on a colon phantom are also tested with different composite hydrogels and biomaterials. The F3DB capability to perform endoscopic surgery is further demonstrated with fresh porcine tissue. The new system is expected to bridge a gap in the field of in situ bioprinting and support the future development of advanced endoscopic surgical robots.

The heterogeneity of public preferences for the first healthcare visit: A discrete choice experiment in the context of Vietnam.

Primary healthcare is critical in addressing the main health problems of communities. In Vietnam, the increasing healthcare demands cause major challenges, especially overcrowding. This study identified public preferences regarding the selection of healthcare facilities for first visit. A discrete choice online survey was generated from five attributes including visit duration, travel time, personal connection with medical staff, doctors' experience, and health insurance. A Dz -efficient design constructed 36 choice sets, divided into three blocks of 12 choice sets. Each block formed one version of the questionnaire, which was randomly distributed to the participants. Heterogeneity in participant preferences was analysed by a latent class model with socio demographic characteristics and experiences of the last visit. 822 participants valued doctors' experience for both minor and severe symptoms. Preference heterogeneity for minor symptoms was quick service provision, highly experienced doctors, and payment through health insurance for the first (44.18%), second (32.17%), and third classes (23.66%), respectively. Regarding severe symptoms, they favoured all five attributes, quick health service, and reduced travel time for the first, second, and third classes, respectively (heterogeneities of 58.16%, 27.79%, and 14.05%, respectively). Predictions of choice from the worst to optimal healthcare facility scenario were 8.91%-61.91% and 10.16%-69.83% for minor and severe symptoms, respectively. Knowledge regarding public preference heterogeneity supports policymakers increase public acceptance in choosing primary healthcare facilities. Visit duration and doctors' experience should be considered a priority in decision making.

Assessment of Health-Related Quality of Life in Patients with Chronic Heart Failure: A Cross-Sectional Study in Vietnam.

Introduction Heart failure is currently a global health issue, imposing a burden on disease prevalence and mortality rates for patients, while simultaneously impacting the quality of life for affected individuals. Data on assessing the health-related quality of life (HRQoL) of patients with chronic heart failure in developing countries, including Vietnam, is still limited. This study was conducted with the aim of describing the quality of life of patients with chronic heart failure in Vietnam. Methods This cross-sectional investigation enrolled 140 chronic heart failure outpatients, utilizing a convenience sample at Hai Duong Province Hospital, Vietnam, spanning from December 2021 to April 2022. Essential patient variables encompassing age, gender, and heart failure duration were gathered. Surveying of patients took place at the outpatient clinic during chronic heart failure follow-up visits using the 36-Item Short Form Health Survey (SF-36) questionnaire. The SF-36 comprises eight dimensions: (1) Physical functioning, (2) Role limitations due to physical health, (3) Bodily pain, (4) General health perceptions, (5) Vitality, (6) Social role functioning, (7) Role limitations due to emotional health, and (8) Mental health. Component analysis of the SF-36 revealed two distinct concepts: a physical component summary (PCS) reflecting the physical aspect and a mental component summary (MCS) reflecting the mental aspect. Results The research involved 140 participants diagnosed with chronic heart failure, having a median age of 59 years (interquartile range (IQR): 52-63). Among them, 61.4% were male, and 50% exhibited reduced left ventricular ejection fraction (LVEF) (≤ 40%). The role limitations due to the physical health domain indicated the lowest score, registering a median value of 0 (IQR 0-25). Domains with median scores below the 25-point threshold encompassed role limitations due to physical health (0 points). Those with scores ranging from 25 to 49 points constituted general health perceptions (25 points), role limitations due to emotional health (33.3 points), vitality (45 points), and mental health (48 points). Bodily pain and social role functioning achieved median scores at a moderate level (50-74 points), scoring 62 and 62.5 points, respectively. The overall HRQoL score on the SF-36 scale was 45.2 (IQR: 32.1-58.7) points. Median scores for the PCS and MCS were 44.3 (IQR: 30.5-52) and 47.0 (IQR: 32.6-65.4), respectively. No statistically significant differences in PCS and MCS scores were observed when subgroup analysis was performed based on variables like age, gender, or LVEF. However, in the vitality domain, female patients exhibited a significantly lower median score than male patients (p-value = 0.046). In the physical functioning domain, individuals aged ≥ 60 had lower median scores than those aged < 60 years (p = 0.022). Additionally, the group with LVEF ≤ 40% had lower median scores compared to the group with LVEF > 40% (p = 0.038) in role limitations due to emotional health domain. Conclusion In Vietnam, the HRQoL in the outpatient population with chronic heart failure was notably low when assessed using the SF-36 questionnaire. Large-scale, multicenter studies are needed to provide stronger, more conclusive evidence.

Glucose-Dependent Insulin Secretion from ß Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide.

Type 1 diabetes results from the loss of pancreatic ß cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost ß cells with stem cell-derived ß cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise ß cell function within implants. We know that native ß cell function is enhanced by cell-cell and cell-extracellular matrix interactions within the islets of Langerhans. Reproducing these interactions in 2D, such as culture on matrix proteins, does enhance insulin secretion. However, the impact of matrix proteins on the 3D organoids that would be in implants has not been widely studied. Here, we use native ß cells that are dispersed from islets and reaggregated into small spheroids. We show these ß cell spheroids have enhanced glucose-dependent insulin secretion when embedded into softer alginate hydrogels conjugated with RGD peptide (a common motif in extracellular matrix proteins). Embedding into alginate-RGD causes activation of integrin responses and repositioning of liprin, a protein that controls insulin secretion. We conclude that insulin secretion from ß cell spheroids can be enhanced through manipulation of the surrounding environment.

The effect of vaccination beliefs regarding vaccination benefits and COVID-19 fear on the number of vaccination injections.

The Coronavirus disease pandemic of 2019 is a vast worldwide public health hazard, impacting people of all ages and socioeconomic statuses. Vaccination is one of the most effective methods of controlling a pandemic like COVID-19. This study aims to investigate the relationship between the number of vaccination injections and fear of COVID-19 and test whether beliefs benefit from vaccination COVID-19 mediate the effect of fear of COVID-19 on the number of vaccination injections. A total of 649 Vietnamese adults were enrolled online to finish answering, including scales The Health Belief Model (HBM) and The Fear of COVID-19 (FCV-19S), consisting of 340 (52.4%) males and 309 (47.6%) females. The data were analyzed using variance, regression, and a simple mediation model. The total score of COVID-19 fear was M = 22.26, SD = 5.49. Vietnamese fear of COVID-19 was at a medium level. Our results suggest that 18- to 20-year-olds are more fearful of COVID-19 than others. People who received the first dosage exhibited a greater fear of COVID-19 than those who received the second dose and were not inoculated. Additionally, the beliefs benefit of vaccination COVID-19 has a role in the relationship between the number of vaccination injections and fear of COVID-19. During the pandemic, adults in Vietnam are more afraid of COVID-19 than during prior outbreaks. Besides, the Vietnamese populace demonstrated a considerable demand for and high acceptability of the COVID-19 vaccine. The current study indicates that psychological counselors and therapists should counsel clients on the value of vaccination and address the fear of COVID-19 as public understanding of the benefits of vaccines increases. To further clarify the effect of this issue on the correlation between fear of COVID-19 and the number of vaccinations, the results of this study indicate that the existing vaccine communication factor for COVID-19 vaccination should be modified to increase confidence in the benefits of immunization.

Apply MIKE 11 model to study impacts of climate change on water resources and develop adaptation plan in the Mekong Delta, Vietnam: a case of Can Tho city.

Can Tho city in the Mekong Delta is in the top ten areas affected by climate change. Therefore, assessing climate change impacts, social and economic activities require proposed solutions to respond to climate change. This study aims to (i) apply the MIKE 11 model (Hydrodynamic module and Advection-Dispersion module) to simulate the impacts of climate change scenarios on water resources in Can Tho city; (ii) calculate water balance in Can Tho city; and (iii) suggest climate change adaptation plan for sustainable social-economic activities of the city. The results show that when the rainfall changes due to climate change, the flow rate tends to decrease at high tide and increase at low tide. When the sea level rises due to climate change, the flow rate tends to increase at high tide and decrease at low tide. For 2030, the flow will decrease up to 15.6% and 14.3% at the low tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The flow will increase up to 63.5% and 58.9% at the high tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The water demand evaluation shows that the water resource reserve in Can Tho city meets water demands in current and future scenarios under climate change. While rainwater and groundwater can provide enough water in the rainy season, the city has to use surface water during the dry season due to a lack of rainwater. Of these, agriculture contributes the most water demands (85%). Eight adaptation measures to climate change for Can Tho city are developed from 2021 to 2050.

An XGBoost-Based Fitted Q Iteration for Finding the Optimal STI Strategies for HIV Patients.

The computational algorithm proposed in this article is an important step toward the development of computational tools that could help guide clinicians to personalize the management of human immunodeficiency virus (HIV) infection. In this article, an XGBoost-based fitted Q iteration algorithm is proposed for finding the optimal structured treatment interruption (STI) strategies for HIV patients. Using the XGBoost-based fitted Q iteration algorithm, we can obtain acceptable and optimal STI strategies with fewer training data, when compared with the extra-tree-based fitted Q iteration algorithm, deep Q-networks (DQNs), and proximal policy optimization (PPO) algorithm. In addition, the XGBoost-based fitted Q iteration algorithm is computationally more efficient than the extra-tree-based fitted Q iteration algorithm.

Emergence of mobile tigecycline resistance gene tet(X4)-harbouring Shewanella xiamenensis in a water environment.

OBJECTIVES: Tigecycline resistance mediated by the mobile tigecycline-inactivating enzyme gene tet(X) in Gram-negative bacteria is an emerging concern for global public health. However, limited information is available on the distribution of tet(X) in the natural environment. In this study, we investigated the presence of tet(X) in environmental Gram-negative bacteria. METHODS: A carbapenem- and tigecycline-resistant Shewanella xiamenensis isolate (NUITM-VS1) was obtained from an urban drainage in Hanoi, Vietnam, in March 2021. Whole-genome sequencing analysis was performed by long- and short-read sequencing, resulting in a complete genome sequence. Antimicrobial resistance genes (ARGs) in the genome were detected based on the custom ARG database, including all known tigecycline resistance genes. RESULTS: Shewanella xiamenensis isolate NUITM-VS1 harboured the tet(X4) gene and the blaOXA-48 carbapenemase gene on the chromosome. tet(X4) was flanked by IS91 family transposase genes, suggesting that the acquisition of tet(X4) was mediated by this mobile gene element (MGE), whereas no MGE was found surrounding blaOXA-48, consistent with previous findings that blaOXA-48-like ß-lactamase genes are species-specific intrinsic ARGs in Shewanella spp. CONCLUSION: To the best of our knowledge, this is the first report of a tet(X4)-harbouring Shewanella sp. isolate. Our results provide genetic evidence of the complexity of the dynamics of clinically important ARGs among bacteria in the water environment.

Propagating Error through Traveling-Wave Ion Mobility Calibration.

Native mass spectrometry (MS) is used to elucidate the stoichiometry of protein complexes and quantify binding interactions by maintaining native-like, noncovalent interactions in the gas phase. However, ionization forces proteins into specific conformations, losing the solution-phase dynamics associated with solvated protein structures. Comparison of gas-phase structures to those in solution, or to other gas-phase ion populations, has many biological implications. For one, analyzing the variety of conformations that are maintained in the gas-phase can provide insight into a protein's solution-phase energy landscape. The gas-phase conformations of proteins and complexes can be investigated using ion mobility (IM) spectrometry. Specifically, drift tube (DT)-IM utilizes uniform electric fields to propel a population of gas-phase ions through a region containing a neutral gas. By measuring the mobility (K) of gas-phase ions, users are able to calculate an average momentum transfer cross section (DTCCS), which provides structural information on the ion. Conversely, in traveling-wave ion mobility spectrometry (TWIMS), TWCCS values cannot be derived directly from an ion's mobility but must be determined following calibration. Though the required calibration adds uncertainty, it is common to report only an average and standard deviation of the calculated TWCCS, accounting for uncertainty associated with replicate measurements, which is a fraction of the overall uncertainty. Herein, we calibrate a TWIMS instrument and derive TWCCSN2 and TWCCSN2→He values for four proteins: cytochrome c, ubiquitin, apo-myoglobin, and holo-myoglobin. We show that compared to reporting only the standard deviation of TWCCS, propagating error through the calibration results in a significant increase in the number of calculated TWCCS values that agree within experimental error with literature values (DTCCS). Incorporating this additional uncertainty provides a more thorough assessment of a protein ion's gas-phase conformations, enabling the structures sampled by native IM-MS to be compared against other reported structures, both experimental and computational.

In Situ Coatings of Silver Nanoparticles for Biofilm Treatment in Implant-Retention Surgeries: Antimicrobial Activities in Monoculture and Coculture.

Bacterial biofilms are indicated in most medical device-associated infections. Treating these biofilms is challenging yet critically important for applications such as in device-retention surgeries, which can have reinfection rates of up to 80%. This in vitro study centered around our new method of treating biofilm and preventing reinfection. Ionic silver (Ag, in the form of silver nitrate) combined with dopamine and a biofilm-lysing enzyme (α-amylase) were applied to model 4-day-old Staphylococcus aureus biofilms on titanium substrates to degrade the extracellular matrix of the biofilm and kill the biofilm bacteria. In this process, the oxidative self-polymerization of dopamine converted Ag ions into Ag nanoparticles that, together with the resultant self-adhering polydopamine (PDA), formed coatings that strongly bound to the treated substrates. Surprisingly, although these Ag/PDA coatings significantly reduced S. aureus growth in standard bacterial monoculture, they showed much lower antimicrobial activity in coculture of the bacteria and osteoblastic MC3T3-E1 cells in which the bacteria were also found attached to the osteoblasts. This S. aureus- osteoblast interaction was also linked to bacterial survival against gentamicin treatment observed in coculture. Our study thus provided clear evidence suggesting that bacteria's interactions with tissue cells surrounding implants may significantly contribute to their resistance to antimicrobial treatment.

Towards engineering heart tissues from bioprinted cardiac spheroids.

Currentin vivoandin vitromodels fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advancedin vitromodels of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long termin vitrotesting. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.