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Underlying inflammation is associated with an increased risk of depression in older adults. In this study, we examined the role of inflammatory biomarkers in antidepressant response in depressed older adults undergoing adjunct Tai Chi Chih (TCC) or Health education interventions.Older adults aged 60 years and above with a diagnosis of major depression were randomized to 12 weeks of TCC versus Health and Wellness Education (HEW) as an adjunct therapy to their stable antidepressant treatment regimen. A panel of 19 cytokine/chemokines was measured at baseline and 12 weeks. Five factors were derived using factor analysis. General linear models were estimated to examine the change in factor scores and the association of these changes on depression remission rates, controlling for age, sex, and body mass index.Of the 170 randomized participants (TCC: n = 85 and HEW: n = 85), 55 TCC and 58 HEW completed the 3-month assessment. The groups did not differ at baseline in any measure. At follow-up, neither the changes in cytokine/chemokines scores nor the depression remission rate differed significantly between TCC and HEW. However, remitters and non-remitters differed significantly in changes in a factor composed of growth-regulated oncogene protein-alpha (GRO-alpha), epidermal growth factor (EGF), and soluble CD40 ligand (sCD40L). GRO-alpha and EGF levels (in both groups) were significantly increased in remitters compared to non-remitters.Changes in certain cytokines/chemokines may accompany improvement in depressive symptoms in older adults. Future studies will need to explore the role of these molecules in remission of late-life depression.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

Purpose The purpose of this study was to gain a holistic view of pro-environmental behavior (PEB) among hospitality and tourism consumers through a systematic review of empirical studies. Based on this comprehensive review, this study demonstrates how the literature has been created and has evolved over time, thereby providing proposals for future research agendas. Design/methodology/approach The preferred reporting items for systematic reviews and meta-analyses method was used as a rigorous searching method to provide an updated picture of the research on the PEBs of consumers in hospitality and tourism contexts. A total of 234 empirical studies from both hospitality and nonhospitality publications were selected for the review. Findings The results reveal a growing interest in PEB in the hospitality and tourism context. Focal points, theories and research designs used to explain PEB among hospitality and tourism consumers were identified. In addition, the findings from the cross-tabulation analyses have provided valuable insights for tourism and hospitality research in this area. Research limitations/implications Based on the research findings, this study makes significant contributions to the literature by providing theoretical and practical implications with detailed directions for future researchers and practitioners. Originality/value This study offers one of the first reviews to comprehensively and systematically analyze the empirical research into PEBs among hospitality and tourism consumers. PEB has received significant attention from researchers, practitioners and those policymakers concerned with the sustainability of environments. The findings of this research provide a comprehensive overview of the literature relating to hospitality and tourism through the identification of gaps that require further investigation. Future suggestions to assist practitioners and policymakers in eliciting PEBs are also discussed.

The competitiveness of tourism products and tourist destinations heavily relies on natural and social resources. At the same time, the tourism industry’s environmental footprint and its contribution to social inequalities are incontestable. A transformation towards more sustainable tourism futures is needed to ensure a positive contribution to fulfilling the UN’s Sustainable Development Goals. Today’s challenges, desirable pathways and solutions are portrayed in this book, which was co-authored by members of the International Competence Network of Tourism Research and Education (ICNT). The different chapters take the reader on a journey around the globe while discussing sustainability along the triple bottom line.

Precompetitive collaborations on new enabling technologies for research and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes projects, often with third-party collaborators, to develop new tools and technologies of mutual interest. Here, we report the results of one of the first ETC projects: the development of a user-friendly population balance model (PBM)-based crystallization simulator software. This project required the development of PBM software with integrated experimental data handling, kinetic parameter regression, interactive process simulation, visualization, and optimization capabilities incorporated in a computationally efficient and robust software platform. Inputs from a team of experienced scientists at 10 ETC member companies helped define a set of software features that guided a team of crystallization modelers to develop software incorporating these features. Communication, continuous testing, and feedback between the ETC and the academic team facilitated the software development. The product of this project, a software tool called CrySiV, an acronym for Crystallization Simulation and Visualization, is reported herein. Currently, CrySiV can be used for cooling, antisolvent, and combined cooling and antisolvent crystallization processes, with primary and secondary nucleation, growth, dissolution, agglomeration, and breakage of crystals. This paper describes the features and the numerical methods of the software and presents two case studies demonstrating its use for parameter estimation. In the first case study, a simulated data set is used to demonstrate the capabilities of the software to find kinetic parameters and its goodness of fit to a known solution. In the second case study, the kinetics of an antisolvent crystallization of indomethacin from a ternary solvent system are estimated, providing a practical example of the tool.

Since invasive bladder cancer (BC) is one of the most lethal urological malignant tumors worldwide, understanding the molecular mechanisms that trigger the migration, invasion, and metastasis of BC has great significance in reducing the mortality of this disease. Although RelA/p65, a member of the NF-kappa B transcription factor family, has been reported to be upregulated in human BCs, its regulation of BC motility and mechanisms have not been explored yet.NF-κBp65 expression was evaluated in N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced high invasive BCs by immunohistochemistry staining and in human BC cell lines demonstrated by Western Blot. The effects of NF-κBp65 knockdown on BC cell migration and invasion, as well as its regulated RhoGDIα and FBW7, were also evaluated in T24T cells by using loss- and gain-function approaches. Moreover, the interaction of FBW7 with RhoGDIα was determined with immunoprecipitation assay, while critical role of ubiquitination of RhoGDIα by FBW7 was also demonstrated in the studies.p65 protein was remarkably upregulated in the BBN-induced high invasive BCs and in human BC cell lines. We also observed that p65 overexpression promoted BC cell migration by inhibiting RhoGDIα expression. The regulatory effect of p65 on RhoGDIα expression is mediated by its upregulation of FBW7, which specifically interacted with RhoGDIα and promoted RhoGDIα ubiquitination and degradation. Mechanistic studies revealed that p65 stabilizing the E3 ligase FBW7 protein was mediated by its attenuating pten mRNA transcription.We demonstrate that p65 overexpression inhibits pten mRNA transcription, which stabilizes the protein expression of ubiquitin E3 ligase FBW7, in turn increasing the ubiquitination and degradation of RhoGDIα protein and finally promoting human BC migration. The novel identification of p65/PTEN/FBW7/RhoGDIα axis provides a significant insight into understanding the nature of BC migration, further offering a new theoretical support for cancer therapy.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Chinese international students constitute the largest international student market in New Zealand, and this market seems set to increase in the future. This study investigated Mainland Chinese inte...

Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of “1” and were included in the ADH upstaging risk calculator. A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery—of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more “high-risk” lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.

A breast cancer synoptic operative report was developed using a modified Delphi process METHODS: Data from the British Columbia Cancer Breast Cancer Outcomes Unit (BCOU) was used to analyze the association between the completion of a synoptic operative report and reporting of operative details and The American Society of Breast Surgeons quality indicators.3662 patients had surgery for breast cancer by 185 surgeons. 2281 reports were narrative and 1007 synoptic. Requested surgical details were more commonly reported with synoptic reports for both posterior (96 vs 58%, p 0.0001) and anterior margins (96 vs 5%, p 0.0001). This was true for high and low volume surgeons. Quality Indicators were higher in those cases with an associated synoptic report for high and low volume surgeons.Communication of operative details is improved with synoptic reporting. Investment in platforms to facilitate synoptic reporting could improve patient care through improved multidisciplinary communication.

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. Soft electronic patches worn on the skin of infants or children in intensive-care units have a wide range of capabilities in aiding critical care, including monitoring of hemodynamic parameters, cardiac activity, movement and crying.

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.

Driver monitoring, whether accompanying vehicle automation or not, appears poised for wide deployment in the near future. Driver monitoring is itself a form of automation (often needed in response to having automated other aspects of driving). Yet research to date on driver monitoring has yet to grapple with human-automation interaction issues with driver monitoring. Automation research has indicated that accurate mental models of driver monitoring will be important. In this study, a descriptive survey of car owners examined perceived capabilities of generic driver monitoring systems (DMS) to detect 30 different potentially distracting behaviors or adverse mental states. Additional open-ended questions queried drivers about beliefs regarding how DMS work and how they might be defeated. Exploratory factor analysis revealed that perceived capabilities factored into four categories, including beliefs that driver monitoring systems can detect: (1) console and control interactions; (2) smartphone interactions; (3) gaze position and in-cabin movement; and (4) adverse mental states. Although research and industry analysis have suggested that camera-based gaze monitoring will be the path forward, a considerable minority of drivers appear to believe that console interactions will be monitored. Further, car owners in this study generally were skeptical about the ability DMS to detect adverse mental states, which may be in misalignment with the capabilities of systems that will be available in the near future. For future research, questions remain about the potential implications of false alarms (real and perceived) in driver monitoring, as well as the role of experience and initial training/instruction for deployed systems.

Predictive constitutive equations that connect easy-to-measure transport properties (e.g., viscosity and conductivity) with system performance variables (e.g., power consumption and efficiency) are needed to design advanced thermal and electrical systems. In this work, we explore the use of fluorescent particle-streak analysis to directly measure the local velocity field of a pressure-driven flow, introducing a new Python package (FSVPy) to perform the analysis. Fluorescent streak velocimetry combines high-speed imaging with highly fluorescent particles to produce images that contain fluorescent streaks, whose length and intensity can be related to the local flow velocity. By capturing images throughout the sample volume, the three-dimensional velocity field can be quantified and reconstructed. We demonstrate this technique by characterizing the channel flow profiles of several non-Newtonian fluids: micellar Cetylpyridinium Chloride solution, Carbopol 940, and Polyethylene Glycol. We then explore more complex flows, where significant acceleration is created due to microscale features encountered within the flow. We demonstrate the ability of FSVPy to process streaks of various shapes and use the variable intensity along the streak to extract position-specific velocity measurements from individual images. Thus, we demonstrate that FSVPy is a flexible tool that can be used to extract local velocimetry measurements from a wide variety of fluids and flow conditions.

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.

In recent years, routine excision of papillary neoplasms (PN) of the breast has been questioned and controversy exists over when excision is necessary. The aim of this study was to evaluate the upstage rate to malignancy of core needle biopsy (CNB) diagnosed PNs from multiple diagnostic centers in our area and to identify factors predictive of malignancy. Patients presenting to our surgical center between 2013 and 2017 for excision of CNB PN were evaluated. The primary endpoint was upstage to malignancy. The association of age, diagnostic center where CNB performed, type of CNB, palpability, discharge, clinical exam size, imaging size, family history of breast cancer, and presence of atypia, as risk factors for upstaging to cancer were also evaluated. Of the 317 PN cases, 83 upstaged to malignancy following surgical excision. 77% of patients with CNB of Atypical PN upstaged, 39% of PN with concurrent atypical ductal hyperplasia, and 0% of PN with concurrent atypical lobular hyperplasia/flat epithelial atypia. Of the 206 non-atypical PNs on CNB, 3.4% upstaged to malignancy, but further review demonstrated a 1% upstage rate when atypia excluded. Factors found to be associated with malignancy included: older patient age, larger size, and presence of atypia. We recommend excision of PN with atypia, concurrent cancerous lesion, or radiologic–pathologic non-concordance, and serial imaging follow up may be considered for image detected PN, less than 1 cm, with no atypia.

Crystallization, often as the final isolation and purification step in drug substance manufacturing, has substantial impact on downstream efficiency and final drug product quality. It is a critical but challenging step in developing end-to-end continuous manufacturing, which has been identified as an emerging technology in the pharmaceutical manufacturing sector by the U.S. Food and Drug Administration (FDA). A traditional stirred tank crystallizer (STC) operated as a mixed-suspension-mixed-product-removal (MSMPR) system is a popular choice for continuous crystallization for its utilization of existing knowledge and equipment. However, there are disadvantages associated with agitational systems like the STC, such as poor local mixing and high shear rate. A commercial dynamic baffle crystallizer (DBC) was studied here as an alternative unit operation. The DBC in this study consists of a jacketed glass vessel with dynamic ‘donut’ shaped baffles to provide oscillatory mixing to improve heat and mass transfer while exerting less shear. Our goal is to compare continuous operation performances in the DBC with the STC as MSMPR systems. First, residence time distribution (RTD) studies of both systems were performed considering single phase (liquid only) and two-phase (solid-liquid) operation. The RTD gives good insights into the mixing dynamics without computationally heavy fluid dynamic simulations. Continuous cooling crystallization of paracetamol was performed in the DBC and the STC. The DBC showed good potential to be used as an MSMPR system producing more uniform RTDs as well as higher quality crystallization products compared to a traditional STC.

PHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1a translation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5'untranslated region (UTR) of Phlpp1 mRNA. Further studies indicate that the attenuation of Mir6981 expression is due to macroautophagy/autophagy-mediated degradation of Mir6981 in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1 is upregulated by CDKN1B at the level of transcription via enhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981 suppresses PHLPP1 translation by binding directly to its mRNA 5'-UTR, rather than classical binding to the 3'-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1. Abbreviations: ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco's modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde -3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3'-UTR; 3'-untranslated region; 5'-UTR: 5'-untranslated region.

Significance Monitoring vital signs for laboring women and their fetuses is foundational to the delivery of obstetrical care; however, monitoring platforms for pregnancy have undergone little innovation over the last several decades with many low-income settings lacking basic access. We report a new time-synchronized, flexible, and wireless sensor system applicable across the entire continuum of antepartum and postpartum care that provides continuous, comprehensive, and noninvasive monitoring (heart rate, respiratory rate, and pulse oxygenation) compatible with a wide range of mobile devices. This system offers advanced features such as continuous blood pressure, uterine electrohysterography, and automated body position classification. We further demonstrate the performance of this new system among pregnant individuals (n = 576) in both high-resource settings and low-resource care settings., Vital signs monitoring is a fundamental component of ensuring the health and safety of women and newborns during pregnancy, labor, and childbirth. This monitoring is often the first step in early detection of pregnancy abnormalities, providing an opportunity for prompt, effective intervention to prevent maternal and neonatal morbidity and mortality. Contemporary pregnancy monitoring systems require numerous devices wired to large base units; at least five separate devices with distinct user interfaces are commonly used to detect uterine contractility, maternal blood oxygenation, temperature, heart rate, blood pressure, and fetal heart rate. Current monitoring technologies are expensive and complex with implementation challenges in low-resource settings where maternal morbidity and mortality is the greatest. We present an integrated monitoring platform leveraging advanced flexible electronics, wireless connectivity, and compatibility with a wide range of low-cost mobile devices. Three flexible, soft, and low-profile sensors offer comprehensive vital signs monitoring for both women and fetuses with time-synchronized operation, including advanced parameters such as continuous cuffless blood pressure, electrohysterography-derived uterine monitoring, and automated body position classification. Successful field trials of pregnant women between 25 and 41 wk of gestation in both high-resource settings (n = 91) and low-resource settings (n = 485) demonstrate the system’s performance, usability, and safety.

Robust literature supports the positive effects of kangaroo mother care (KMC) on infant physiologic stability and parent-infant bonding in the Neonatal Intensive Care Unit (NICU). Comparatively little is known about kangaroo father care (KFC) in the NICU, and KFC implementation has been limited. Our pilot feasibility study objective was to examine KFC effects on premature infants and fathers as compared to KMC. Parents of preterm NICU infants independently completed a 90-min Kangaroo Care (KC) session on consecutive days. Infant heart rate variability (HRV) and apnea/periodicity measures were compared (pre-KC to KC; KFC to KMC). Additionally, we assessed the feasibility of administering three psychosocial questionnaires to fathers and mothers in the NICU and after discharge. Ten preterm infants completed 20 KC sessions (334/7 -374/7 weeks post-menstrual age). Results demonstrated similar infant physiologic responses between KMC and KFC, including significant differences in measures of HRV (p

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

BACKGROUND One of the arguments against early intervention for micrognathia in Pierre Robin sequence is the concept that the growth of the mandible will eventually "catch up." Long-term growth of the mandible and occlusal relationships of conservatively managed Pierre Robin sequence patients remain unknown. In this study, the authors evaluated the orthognathic surgery requirements for Pierre Robin sequence patients at skeletal maturity. METHODS Orthognathic surgical requirements of conservatively managed Pierre Robin sequence and isolated cleft patients (aged ≥13 years) at two institutions were reviewed and analyzed using t test, chi-square test, and Fisher's exact test. Values of p < 0.05 were considered statistically significant. RESULTS Of the Pierre Robin sequence patients (n = 64; mean age ± SD, 17.9 ± 2.9 years), 65.6 percent were syndromic (primarily Stickler and velocardiofacial syndrome), 96.9 percent had a cleft palate, and 39.1 percent required orthognathic surgery at skeletal maturity. Nonsyndromic and syndromic Pierre Robin sequence patients demonstrated no differences in occlusal relationships or mandibular surgery frequency. The majority of Pierre Robin sequence patients requiring mandibular advancement had a class II occlusion. Comparison of Pierre Robin sequence patients to isolated cleft palate patients (n = 17) revealed a comparable frequency of orthognathic surgery between the two; however, Pierre Robin sequence patients did require mandibular advancement surgery at a greater frequency than cleft palate patients (p = 0.006). CONCLUSIONS The present study found that 39.1 percent of conservatively managed Pierre Robin sequence patients required orthognathic surgery at skeletal maturity, of which the vast majority required mandibular advancement for class II malocclusion. These data suggest that mandibular micrognathia in conservatively managed Pierre Robin sequence patients may not resolve over time and may require surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, II.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery., Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.

Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions of increased pressure and temperature as limb volume changes during daily activities. Conventional pressure transducers and temperature sensors cannot provide comfortable, irritation-free measurements because of their relatively rigid construction and requirements for wired interfaces to external data acquisition hardware. Here, we introduce a millimeter-scale pressure sensor that adopts a soft, three-dimensional design that integrates into a thin, flexible battery-free, wireless platform with a built-in temperature sensor to allow operation in a noninvasive, imperceptible fashion directly at the skin-prosthesis interface. The sensor system mounts on the surface of the skin of the residual limb, in single or multiple locations of interest. A wireless reader module attached to the outside of the prosthetic socket wirelessly provides power to the sensor and wirelessly receives data from it, for continuous long-range transmission to a standard consumer electronic device such as a smartphone or tablet computer. Characterization of both the sensor and the system, together with theoretical analysis of the key responses, illustrates linear, accurate responses and the ability to address the entire range of relevant pressures and to capture skin temperature accurately, both in a continuous mode. Clinical application in two prosthesis users demonstrates the functionality and feasibility of this soft, wireless system.

PHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1a translation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5ʹuntranslated region (UTR) of Phlpp1 mRNA. Further studies indicate that the attenuation of Mir6981 expression is due to macroautophagy/autophagy-mediated degradation of Mir6981 in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1 is upregulated by CDKN1B at the level of transcription via enhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981 suppresses PHLPP1 translation by binding directly to its mRNA 5ʹ-UTR, rather than classical binding to the 3ʹ-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1. Abbreviations: ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco’s modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde −3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3ʹ-UTR; 3ʹ-untranslated region; 5ʹ-UTR: 5ʹ-untranslated region.

We are amidst a digital transformation in our cities. Both private and public sectors are eager to deploy emerging technologies to improve efficiency of processes, infrastructure systems, and quality of life. At the same time, distribution of resources and implementation of new technologies has historically and presently been unequal, typically leaving socially vulnerable populations behind while wealthier and more politically empowered communities advance. Client WSP asks “how can we develop a framework for implementing tech-enabled infrastructure (TEI) to address social equity issues? Can we create a roadmap that empowers municipalities and communities to recognize the benefits of TEI in their own neighborhoods and implement in a way that prioritizes social equity?” The Capstone “Curb Value Capture: Tech Enabled Infrastructure on Sidewalks for Community Equity Goals” applies an equity lens to TEI to fill the existing gap between smart cities and equitable cities practices. Through analyzing three precedents, the COSMOS¹ testbed in Harlem, Sidewalk Toronto in Quayside, small cell in San Francisco, the Capstone developed a set of recommendations for implementing TEI including how to build the relationships, innovate the processes and bridge the capacities. ¹COSMOS stands for Cloud Enhanced Open Software Defined Mobile Wireless Testbed for City-Scale Deployment

Psoriasis in an inflammatory skin disorder associated with systemic inflammation. This systematic review summarizes the epidemiology, histology, and function of the gastrointestinal (GI) system in patients with psoriasis. Although psoriasis patients are at higher risk for developing inflammatory bowel disease and celiac disease, estimates of their prevalence have varied and it is unclear whether psoriasis patients without GI symptoms may harbor subclinical inflammation. In a meta-analysis, the pooled prevalence of Crohn disease, ulcerative colitis (UC), and celiac disease among patients with psoriasis was 0.4, 0.5, and 2%, respectively. The pooled prevalence of psoriasis among patients with Crohn disease was 9.5% and among patients with UC was 6.6%. A significant proportion of psoriasis patients harbor lymphocytic infiltrates in the small and large intestine; 40–50% of the psoriasis patients demonstrate abnormal intestinal absorption based on fecal fat, D-xylose, and lactose tolerance tests. These results suggest that the inflammatory state of psoriasis may in some patients extend to the GI tract.