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Colorectal cancer with peritoneal metastases is currently treated by cytoreductive surgery and locoregional chemotherapeutics. This standard treatment is associated with high morbidity, mortality, and recurrence rate. To augment the existing therapy, we developed a liposome-based delivery system containing 1,2-stearoyl-3-trimethylammonium-propane chloride (DSTAP), a cationic lipid, to localize a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity (PerC) for enhancing the immune response against cancer that had spread to the PerC. The liposomes delivered by intraperitoneal injection increased peritoneal retention of R848 by 14-fold while retarding its systemic absorption, leading to a 5-fold decreased peak plasma concentration compared to free R848 in mice. Within the PerC, the DSTAP-liposomes were found in ~40% of the dendritic cells by flow cytometry. DSTAP-R848 significantly upregulated interferon α (IFN-α) in the peritoneal fluid by 2-fold compared to free R848, without increasing the systemic level. Combined with oxaliplatin, a cytotoxic agent inducing immunogenic cell death, DSTAP-R848 effectively inhibited the progression of CT26 murine colorectal tumor in the PerC, while the combination with free R848 only showed a mild effect. Moreover, the combination of oxaliplatin and DSTAP-R848 significantly increased infiltration of CD8+ T cells in the PerC compared to oxaliplatin combined with free R848, indicating enhanced immune response against the tumor. The results suggest that DSTAP-R848 exhibits potential in augmenting existing therapies for treating colorectal cancer with peritoneal metastases via immune activation.

Although immune checkpoint inhibitors (ICIs) have significantly improved the oncological outcomes, about one-third of patients affected by clear cell renal cell carcinoma (ccRCC) still experience recurrence. Current prognostic algorithms, such as the Leibovich score (LS), rely on morphological features manually assessed by pathologists and are therefore subject to bias. Moreover, these tools do not consider the heterogeneous molecular milieu present in the Tumour Microenvironment (TME), which may have prognostic value. We systematically developed a semi-automated method to investigate 62 markers and their combinations in 150 primary ccRCCs using Multiplex Immunofluorescence (mIF), NanoString GeoMx ® Digital Spatial Profiling (DSP) and Artificial Intelligence (AI)-assisted image analysis in order to find novel prognostic signatures and investigate their spatial relationship. We found that coexpression of cancer stem cell (CSC) and epithelial-to-mesenchymal transition (EMT) markers such as OCT4 and ZEB1 are indicative of poor outcome. OCT4 and the immune markers CD8, CD34, and CD163 significantly stratified patients at intermediate LS. Furthermore, augmenting the LS with OCT4 and CD34 improved patient stratification by outcome. Our results support the hypothesis that combining molecular markers has prognostic value and can be integrated with morphological features to improve risk stratification and personalised therapy. To conclude, GeoMx ® DSP and AI image analysis are complementary tools providing high multiplexing capability required to investigate the TME of ccRCC, while reducing observer bias.

Background: Multidisciplinary simulation has been shown to improve teamwork in the obstetrical literature by providing a safe, but realistic, environment for participants to learn. However, the impact of team members' personality traits on how the team performs during an obstetrical emergency has not been studied in medicine., Objective: Our objective was to evaluate teamwork and communication of simulation participants in association with personality traits within a multidisciplinary obstetrical simulation program., Study Design: This was a prospective observational study of postpartum hemorrhage simulations involving participants from Obstetrics, Nursing, Midwifery, and Anesthesia. Before simulation, individual personality testing was performed on participants using the Big Five Inventory. Each team was scored using the Clinical Teamwork Scale after simulation. Communication and teamwork scores were evaluated for association, and personality traits were analyzed for association with teamwork and communication. For each personality trait, an interaction model was tested for 3 of the team scores: teamwork, communication, and situational awareness. Analysis of variance with 2 level interactions was used in this effort., Results: From July 2018 to June 2019, 22 obstetrical simulations were performed with a total of 270 staff. Overall, teamwork was significantly associated with communication for each team. When examining individual personality scores, neuroticism was negatively associated with teamwork when coupled with communication. That is, increased neuroticism was significantly associated with increased communication that was detrimental to the overall teamwork. Other personality traits were not significantly associated with teamwork and communication (P=.03)., Conclusion: In a multidisciplinary simulation, communication was positively associated with teamwork, and specific personality traits negatively affected team performance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective and Impact Statement . Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases. Introduction . Traditional thermal sensors allow measurements at surfaces or at near-surface regions of the skin or of certain body cavities. Evaluations at depth require implanted devices connected to external readout electronics via physical interfaces that lead to risks for infection and movement constraints for the patient. Also, surgical extraction procedures after a period of need can introduce additional risks and costs. Methods . Here, we report a wireless, bioresorbable class of temperature sensor that exploits multilayer photonic cavities, for continuous optical measurements of regional, deep-tissue microenvironments over a timeframe of interest followed by complete clearance via natural body processes. Results . The designs decouple the influence of detection angle from temperature on the reflection spectra, to enable high accuracy in sensing, as supported by in vitro experiments and optical simulations. Studies with devices implanted into subcutaneous tissues of both awake, freely moving and asleep animal models illustrate the applicability of this technology for in vivo measurements. Conclusion . The results demonstrate the use of bioresorbable materials in advanced photonic structures with unique capabilities in tracking of thermal signatures of tissue microenvironments, with potential relevance to human healthcare., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Wubin Bai et al.)

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care.

Telomere shortening has been shown to contribute to the pathogenesis of atherosclerosis directly or through influencing cardiovascular risk factors. We examined telomere length (TL) and change in ankle-brachial index (ABI) over 5 years in a Chinese population aged 65 years and older living in the community. Telomere length was determined using the quantitative polymerase chain reaction (PCR) method in 976 men and 1030 women. Ankle-brachial index was measured using Doppler ultrasound. Analysis of covariance was used to examine the relationship between quartiles of TL and baseline ABI values as well as percentage change in ABI, adjusting for confounders. Women had longer TL and lower ABI values compared with men, and there was a significant trend for an inverse association between TL and percentage decline in ABI after adjustment for confounders. No significant association was observed in men. The findings support the association between TL and markers of atherosclerosis in older women but not men.

Vitamin K-dependent carboxylation activity measured with pentapeptide substrate (Phe-Leu-Glu-Glu-Leu) gradually decreases upon in vivo injection of vitamin K to vitamin K-deficient rats. A decrease in pentapeptide carboxylation can also be observed by the in vitro addition of antibodies against prothrombin and other vitamin K-dependent proteins to the soluble system derived from vitamin K-deficient rat liver microsomes. In both cases, adding back in vitro partially decarboxylated vitamin K-dependent proteins or purified hepatic prothrombin precursor restores the level of pentapeptide carboxylation. After warfarin treatment, a 3-fold increase in carboxylation results, which can be abolished by giving cycloheximide along with the warfarin. However, the resulting decreased activity is restored by the in vitro addition of partially decarboxylated vitamin K-dependent proteins. These data are consistent with the hypothesis that (after warfarin treatment) increased peptide carboxylation is primarily due to activation of the system by precursor proteins, rather than synthesis of an increased amount of enzyme.