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The integration of flexible sensors into human-machine interfaces (HMIs) is in increasing demand for intuitive and effective manipulation. Traditional glove-based HMIs, constrained by nonconformal rigid structures or the need for bulky batteries, face limitations in continuous operation. Addressing this, we introduce yarn-based bend sensors in our smart glove, which are wirelessly powered and harvest energy from a fully textile 5.8 GHz WiFi-band antenna receiver. These sensors exhibit a gauge factor (GF) of 5.60 for strains ranging from 0 to 10%. They show a consistent performance regardless of the straining frequency when being stretched and released at frequencies between 0.1 and 0.7 Hz. This reliability ensures that the sensor output is solely dependent on the yarn's elongation. Accurately detecting finger-bending movements from 0° to 90° in a virtual environment, the sensors enable enhanced degrees of freedom for human finger interaction. When integrated with advanced machine-learning techniques, the system achieves a classification accuracy of 98.75% for object recognition, demonstrating its potential for precise and accurate HMI. Unlike conventional near-field energy transfer methods that rely on magnetic flux and are limited by power loss over distance, our fully textile design effectively harvests microwave energy, showing no voltage deterioration up to 1 m away. This minimalist microwave-powered smart glove represents a significant advancement, offering a viable and practical solution for developing intuitive and reliable HMIs.

Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 μm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitro and in vivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation in vivo. This in vivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation., Competing Interests: Declaration of interests A Singapore patent application no.10202303337R has been filed on November 24, 2023 for this work. C.R.E. and J.C.I.B. are employees of Altos Labs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Soft robots have received much attention due to their impressive capabilities including high flexibility and inherent safety features for humans or unstructured environments compared with hard-bodied robots. Soft actuators are the crucial components of soft robotic systems. Soft robots require dexterous soft actuators to provide the desired deformation for different soft robotic applications. Most of the existing soft actuators have only one or two deformation modes. In this article, a new soft pneumatic actuator (SPA) is proposed taking inspiration from Kirigami. Kirigami-inspired cuts are applied to the actuator design, which enables the SPA to be equipped with multiple deformation modes. The proposed Kirigami-inspired soft pneumatic actuator (KiriSPA) is capable of producing bending motion, stretching motion, contraction motion, combined motion of bending and stretching, and combined motion of bending and contraction. The KiriSPA can be directly manufactured using 3D printers based on the fused deposition modeling technology. Finite element method is used to analyze and predict the deformation modes of the KiriSPA. We also investigated the step response, creep, hysteresis, actuation speed, stroke, workspace, stiffness, power density, and blocked force of the KiriSPA. Moreover, we demonstrated that KiriSPAs can be combined to expand the capabilities of various soft robotic systems including the soft robotic gripper for delicate object manipulation, the soft planar robotic manipulator for picking objects in the confined environment, the quadrupedal soft crawling robot, and the soft robot with the flipping locomotion.

Post-surgical scarring is a known cause of trabeculectomy failure. The aim of this study was to investigate the effectiveness of ranibizumab as an adjuvant anti-scarring agent in experimental trabeculectomy. Forty New Zealand white rabbits were randomised into four eye treatment groups: groups A (control), B (ranibizumab 0.5 mg/mL), C (mitomycin C [MMC] 0.4 mg/mL), and D (ranibizumab 0.5 mg/mL and MMC 0.4 mg/mL). Modified trabeculectomy was performed. Clinical parameters were assessed on post-operative days 1, 2, 3, 7, 14, and 21. Twenty rabbits were euthanised on day 7, and the other twenty were euthanised on day 21. Eye tissue samples were obtained from the rabbits and stained with haematoxylin and eosin (H&E). All treatment groups showed a significant difference in IOP reduction compared with group A ( p < 0.05). Groups C and D showed a significant difference in bleb status on days 7 ( p = 0.001) and 21 ( p = 0.002) relative to group A. H&E staining showed significantly low fibrotic activity ( p < 0.001) in group C on both days and inflammatory cell grade in group B on day 7 ( p < 0.001). The grade for new vessel formation was significantly low in groups B and D on day 7 ( p < 0.001) and in group D on day 21 ( p = 0.007). Ranibizumab plays a role in reducing scarring, and a single application of the ranibizumab-MMC combination showed a moderate wound-modulating effect in the early post-operative phase.

Access to healthcare is a Social Determinant of Health that is associated with public health outcomes and barriers to access disproportionately affect African American adults. This study used a health and financial literacy approach to qualitatively assess how African American adults access healthcare and potential barriers faced (n = 20). Results indicated a wide range of experiences generally split between positive and negative experiences in access to healthcare. Specific themes that emerged included scheduling issues and appointment availability, expense of care, lack of transparency in insurance coverage, the need for more primary care clinics and enhanced community outreach and education on how to access healthcare. This research identifies a need for increased education surrounding health insurance coverage and an identified need for more local physicians or ease of scheduling. All participants in this study stated they were covered by health insurance of some form. Future research should examine these issues in the context of socioeconomic and insurance status.

Forceps, clamps, and haemostats are essential surgical tools required for all surgical interventions. While they are widely used to grasp, hold, and manipulate soft tissue, their metallic rigid structure may cause tissue damage due to the potential risk of applying excessive gripping forces. Soft pneumatic surgical grippers fabricated by silicone elastomeric materials with low Young's modulus may offer a promising solution to minimize this unintentional damage due to their inherent excellent compliance and compressibility. The goal of this work is to evaluate and compare the grip-induced nerve damage caused by the soft pneumatic elastomeric gripper and conventional haemostats during surgical manipulation. Twenty-four Wistar rats (male, seven weeks) are subjected to sciatic nerve compression (right hind limb) using the soft pneumatic elastomer gripper and haemostats. A histopathological analysis is conducted at different time-points (Day 0, Day 3, Day 7 and Day 13) after the nerve compression to examine the morphological tissue changes between the rats in the 'soft gripper' group and the 'haemostats' group. A free walking analysis is also performed to examine the walking function of the rats after recovery from different time points. Comparing the rigid haemostats and soft gripper groups, there is a visible difference in the degree of axonal vacuolar degeneration between the groups, which could suggest the presence of substantial nerve damage in the 'haemostats' group. The rats in the haemostats group exhibited reduced right hind paw pressure and paw size after the nerve compression. It shows that the rats tend not to exert more force on the affected right hind limb in the haemostats group compared to the soft gripper group. In addition, the stance duration was reduced in the injured right hind limb compared to the normal left hind limb in the haemostats group. These observations show that the soft pneumatic surgical gripper made of silicone elastomeric materials might reduce the severity of grip-induced damage by providing a safe compliant grip compared to the conventional haemostats. The soft pneumatic elastomer gripper could complement the current surgical gripping tool in delicate tissue manipulation.

This paper contributes to a new design of the three-dimensional printable robotic ball joints capable of creating the controllable stiffness linkage between two robot links through pneumatic actuation. The variable stiffness ball joint consists of a soft pneumatic elastomer actuator, a support platform, an inner ball and a socket. The ball joint structure, including the inner ball and the socket, is three-dimensionally printed using polyamide-12 (PA12) by selective laser sintering (SLS) technology as an integral mechanism without the requirement of assembly. The SLS technology can make the ball joint have the advantages of low weight, simple structure, easy to miniaturize and good MRI compatibility. The support platform is designed as a friction-based braking component to increase the stiffness of the ball joint while withstanding the external loads. The soft pneumatic elastomer actuator is responsible for providing the pushing force for the support platform, thereby modulating the frictional force between the inner ball, the socket and the support platform. The most remarkable feature of the proposed variable stiffness design is that the ball joint has 'zero' stiffness when no pressurized air is supplied. In the natural state, the inner ball can be freely rotated and twist inside the socket. The proposed ball joint can be quickly stiffened to lock the current position and orientation of the inner ball relative to the socket when the pressurized air is supplied to the soft pneumatic elastomer actuator. The relationship between the stiffness of the ball joint and the input air pressure is investigated in both rotating and twisting directions. The finite element analysis is conducted to optimize the design of the support platform. The stiffness tests are conducted, demonstrating that a significant stiffness enhancement, up to approximately 508.11 N·mm reaction torque in the rotational direction and 571.93 N·mm reaction torque in the twisting direction at the pressure of 400 kPa, can be obtained. Multiple ball joints can be easily assembled to form a variable stiffness structure, in which each ball joint has a relative position and an independent stiffness. Additionally, the degrees of freedom (DOF) of the ball joint can be readily restricted to build the single-DOF or two-DOFs variable stiffness joints for different robotic applications.

Background: The Malaysian public healthcare system is tax funded, with healthcare costs highly subsidized by the Government. The current health financing is not sustainable to cover all the healthcare resources. Introducing a national health insurance (NHI), a prepayment method, would protect the population from financial hardship by reducing out-of-pocket payment, minimizing the barrier to accessing health and achieving equitable healthcare. Studies on the willingness to pay (WTP) for NHI are available in different contexts; however, little was found in Malaysia. In addition, factors affecting the WTP for NHI have been less researched in the Malaysian context., Objective: This study investigates the WTP for NHI and factors influencing it in Melaka, Malaysia., Method: Using the contingent valuation method, the researchers distributed a pre-tested self-administered questionnaire to 489 respondents in three leading public hospitals from 1 to 9 November 2019. Multi-stage sampling forms the selection of respondents. Respondents were presented with a hypothetical scenario on NHI and asked whether they would be willing to pay for NHI. Chi-square was used to examine the association between categorical independent variables and WTP for NHI, and binary logistic regression was applied to determine the variables with the most predictive effect towards WTP for NHI., Results: Out of 462 usable responses, 344 respondents (74.5%) were willing to pay for NHI. The majority (51.3%) of the respondents were willing to pay 15 Malaysian Ringgit (3.70 US dollars) or more for the NHI scheme. Chi-square analysis revealed that age, marital status, education level, employment status, chronic diseases, and perception towards NHI were significantly associated with WTP for NHI. Binary regression analysis found that marital status and perception towards NHI have the most predictive effect on respondents' WTP for NHI., Conclusion: This study revealed that the majority of the respondents are willing to pay for NHI if implemented in Malaysia. The findings lay a foundation for implementing a future NHI framework in Malaysia and reference future health financing research., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Studies have acknowledged that social media enables students to connect with and learn from experts from different ties available in the students' personal learning environment (PLE). The inclusion of experts in formal learning activities through social media such as in scaffolding problem-solving activities helps students see the practicality of experts' thinking in solving real-world problems. However, studies that evaluate experts' problem-solving styles and how these influence the experts' thinking process in delivering the know-how to students on social media based on the ties that the students have with the experts in social media are scarce in the extant literature. The study aimed to explore the problem-solving styles that the experts portrayed on Facebook based on their ties with the students.  Methods: This study employed a simultaneous within-subject experimental design which was conducted in three closed Facebook groups with 12 final year management students, six business experts, and one instructor as the participants. The experts were invited by the students from the weak and strong ties in their PLE. Hinging on the Theory of Fluid and Crystallised intelligence and the Strength of Weak Ties Theory, this study employed thematic analysis using the ATLAS.ti qualitative data analysis software to map the experts' comments on Facebook. Results:  The use of strong ties in combination with weak ties balances out the negative aspects of the business experts' problem-solving styles.  All the experts used both fluid and crystallised intelligence in scaffolding the students' learning; however, the degree of its usage correlated with the working experience of the experts. Conclusion: The use of weak or strong ties benefited the students as it expedited their problem-solving tasks since the experts have unique expertise to offer depending on the degree of their working experiences and the proximity of the students' relationship with the experts., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Abdullah AH et al.)

The compliant nature of soft fingers allows for safe and dexterous manipulation of objects by humans in an unstructured environment. A soft prosthetic finger design with tactile sensing capabilities for texture discrimination and subsequent sensory stimulation has the potential to create a more natural experience for an amputee. In this work, a pneumatically actuated soft biomimetic finger is integrated with a textile neuromorphic tactile sensor array for a texture discrimination task. The tactile sensor outputs were converted into neuromorphic spike trains, which emulate the firing pattern of biological mechanoreceptors. Spike-based features from each taxel compressed the information and were then used as inputs for the support vector machine classifier to differentiate the textures. Our soft biomimetic finger with neuromorphic encoding was able to achieve an average overall classification accuracy of 99.57% over 16 independent parameters when tested on 13 standardized textured surfaces. The 16 parameters were the combination of 4 angles of flexion of the soft finger and 4 speeds of palpation. To aid in the perception of more natural objects and their manipulation, subjects were provided with transcutaneous electrical nerve stimulation to convey a subset of four textures with varied textural information. Three able-bodied subjects successfully distinguished two or three textures with the applied stimuli. This work paves the way for a more human-like prosthesis through a soft biomimetic finger with texture discrimination capabilities using neuromorphic techniques that provide sensory feedback; furthermore, texture feedback has the potential to enhance user experience when interacting with their surroundings.

We report a case series of young adults who were admitted to hospital with seizures after regular kratom beverage consumption. This study aimed to determine kratom consumption habits and seizure characteristics and to explore whether chronic kratom ingestion without concomitant drug abuse leads to recurrent seizure or epilepsy. All patients underwent blood investigations, a brain computed tomography (CT) scan, electroencephalography, and urine testing for mitragynine and drug toxicology. Eleven participants who had a positive urine mitragynine test were included in the study. The longest duration of kratom consumption was 84 months: - most drank more than eight times per month (>200 mL/drink). Seizure developed within 10 minutes or up to 72 hours post-ingestion. Seizure occurred one to three times per year in most cases. Four patients had a focal to bilateral tonic-clonic seizure whereas the remaining participants had a generalized tonic-clonic seizure. Four patients mixed kratom with diphenhydramine syrup, and one patient took methamphetamine. Two patients had positive urine results for recreational drugs (opioid and amphetamine). This study provided indirect evidence that chronic kratom use with or without concomitant drug abuse can cause recurrent seizures in susceptible individuals, which may progress to epilepsy or require antiepileptic medication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This paper introduces the development of an anthropomorphic soft robotic hand integrated with multiple flexible force sensors in the fingers. By leveraging on the integrated force sensing mechanism, grip state estimation networks have been developed. The robotic hand was tasked to hold the given object on the table for 1.5 s and lift it up within 1 s. The object manipulation experiment of grasping and lifting the given objects were conducted with various pneumatic pressure (50, 80, and 120 kPa). Learning networks were developed to estimate occurrence of object instability and slippage due to acceleration of the robot or insufficient grasp strength. Hence the grip state estimation network can potentially feedback object stability status to the pneumatic control system. This would allow the pneumatic system to use suitable pneumatic pressure to efficiently handle different objects, i.e., lower pneumatic pressure (50 kPa) for lightweight objects which do not require high grasping strength. The learning process of the soft hand is made challenging by curating a diverse selection of daily objects, some of which displays dynamic change in shape upon grasping. To address the cost of collecting extensive training datasets, we adopted one-shot learning (OSL) technique with a long short-term memory (LSTM) recurrent neural network. OSL aims to allow the networks to learn based on limited training data. It also promotes the scalability of the network to accommodate more grasping objects in the future. Three types of LSTM-based networks have been developed and their performance has been evaluated in this study. Among the three LSTM networks, triplet network achieved overall stability estimation accuracy at 89.96%, followed by LSTM network with 88.00% and Siamese LSTM network with 85.16%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khin, Low, Ang and Yeow.)

Monoethylhexyl phthalate (MEHP) is one of the main active metabolites of the plasticizer di(2-ethylhexyl) phthalate. It has been known that MEHP has an impact on lipolysis; however, its mechanism on the cellular lipid metabolism remains largely unclear. Here, we first utilized global lipid profiling to fully characterize the lipid synthesis and degradation pathways upon MEHP treatment on hepatic cells. Meanwhile, we further identified the possible MEHP-targeted proteins in living cells using the cellular thermal shift assay (CETSA) method. The lipidomics results showed that there was a significant accumulation of fatty acids and other lipids in the cell. The CETSA identified 18 proteins and fatty acid β-oxidation inhibition pathways that were significantly perturbed. MEHP's binding with selected proteins HADH and HSD17B10 was further evaluated using molecule docking, and results showed that MEHP has higher affinities as compared to endogenous substrates, which was further experimentally confirmed in the surface plasma resonance interaction assay. In summary, we found a novel mechanism for MEHP-induced lipid accumulation, which was probably due to its inhibitive effects on the enzymes in fatty acid β-oxidation. This mechanism substantiates the public concerns on the high exposure level to plasticizers and their possible role as an obesogen.

Emerging soft exoskeletons pose urgent needs for high-performance strain sensors with tunable linear working windows to achieve a high-precision control loop. Still, the state-of-the-art strain sensors require further advances to simultaneously satisfy multiple sensing parameters, including high sensitivity, reliable linearity, and tunable strain ranges. Besides, a wireless sensing system is highly desired to enable facile monitoring of soft exoskeleton in real time, but is rarely investigated. Herein, wireless Ti 3 C 2 T x MXene strain sensing systems were fabricated by developing hierarchical morphologies on piezoresistive layers and incorporating regulatory resistors into circuit designs as well as integrating the sensing circuit with near-field communication (NFC) technology. The wireless MXene sensor system can simultaneously achieve an ultrahigh sensitivity (gauge factor ≥ 14,000) and reliable linearity ( R 2 ≈ 0.99) within multiple user-designated high-strain working windows (130% to ≥900%). Additionally, the wireless sensing system can collectively monitor the multisegment exoskeleton actuations through a single database channel, largely reducing the data processing loading. We finally integrate the wireless, battery-free MXene e-skin with various soft exoskeletons to monitor the complex actuations that assist hand/leg rehabilitation.

For the first time, a flexible and deformable liquid dielectric resonator antenna (LDRA) is proposed for air pressure sensing. The proposed LDRA can be made very compact as it has employed liquidized organic dielectric with high dielectric constant (~ 33) with low loss tangent (~ 0.05). Here, a soft elastomer container has been fabricated using soft-lithography method for holding the liquid, and an air cavity is tactfully embedded into the central part of a cylindrical DRA to form an annular structure that can be used for sensing air pressure. It will be shown that the inclusion of the air cavity is essential for making the antenna structure sensitive to pressure changes. Simulations and experiments have been conducted to verify the functionalities of the proposed organic LDRA as microwave radiator and as air pressure sensor. It has been proven to have higher antenna gain than the water LDRA in the frequency range of 1.8-2.8 GHz, while achieving a good air pressure sensitivity of 270 MHz/bar.

Human pluripotent stem cell-derived kidney organoids recapitulate developmental processes and tissue architecture, but intrinsic limitations, such as lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, producing a correlative level of vascular endothelial growth factor A (VEGFA) to define a resident vascular network. Single-cell RNA sequencing identifies a subset of nephron progenitor cells as a potential source of renal vasculature. These kidney organoids undergo further structural and functional maturation upon implantation. Using this kidney organoid platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD), the cystic phenotype of which can be effectively prevented by gene correction or drug treatment. Our studies provide new avenues for studying human kidney development, modeling disease pathogenesis, and performing patient-specific drug validation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Soft robotic fingers have shown great potential for use in prostheses due to their inherent compliant, light, and dexterous nature. Recent advancements in sensor technology for soft robotic systems showcase their ability to perceive and respond to static cues. However, most of the soft fingers for use in prosthetic applications are not equipped with sensors which have the ability to perceive texture like humans can. In this work, we present a dexterous, soft, biomimetic solution which is capable of discrimination of textures. We fabricated a soft finger with two individually controllable degrees of freedom with a tactile sensor embedded at the fingertip. The output of the tac- tile sensor, as texture plates were palpated, was converted into spikes, mimicking the behavior of a biological mechanoreceptor. We explored the spatial properties of the textures captured in the form of spiking patterns by generating spatial event plots and analyzing the similarity between spike trains generated for each texture. Unique features representative of the different textures were then extracted from the spikes and input to a classifier. The textures were successfully classified with an accuracy of 94% when palpating at a rate of 42 mm/s. This work demonstrates the potential of providing amputees with a soft finger with sensing capabilities, which could potentially help discriminate between different objects and surfaces during activities of daily living (ADL) through palpation.

This paper presents fabric-based soft robotic modules with primitive morphologies, which are analogous to basic geometrical polygons-trilateral and quadrilateral. The two modules are the inflatable beam (IB) and fabric-based rotary actuator (FRA). The FRA module is designed with origami-inspired V-shaped pleats, which creates a trilateral outline. Upon pressurization, the pleats unfold, which enables propagation of angular displacement of the FRA module. This allows the FRA module to be implemented as a mobility unit in the larger assembly of pneumatic structures. In the following, we examine various ways by which FRA modules can be connected to IB modules. We studied how different ranges of motion can be achieved by varying the design of the rotary joint of the assemblies. Using a state transition-based position control system, movement of the assembled modules could be controlled by regulating the pneumatic pressurization of the FRA module at the joint. These basic modules allow us to build different types of pneumatic structures. In this paper, using IB and FRA modules of various dimensions, we constructed a soft robotic limb with an end effector, which can be attached to wheelchairs to provide assistive grasping functions for users with disabilities.

Forceps are essential tools for digital nerve manipulation during digital nerve repair surgery. However, surgeons have to operate forceps with extreme caution to prevent detrimental post-operative complications caused by over-gripping force. Their intrinsically safe characteristics have led to the increasing adoption of soft robotics in various biomedical applications. In this paper, a miniaturized hybrid soft surgical gripper is proposed for safe nerve manipulation in digital nerve repair surgery. This new surgical gripper includes a soft inflatable actuator and a gripper shell with a hook-shaped structure. The ability to achieve a compliant grip and safe interaction with digital nerves is provided by the inflated soft pneumatic actuator, while the rigid hook retractor still allows surgeons to scoop up the nerve from its surrounding tissues during surgery. The performance of the proposed surgical gripper was evaluated by the contact/pulling force sensing experiments and deformation measurement experiments. In the cadaver experiments, this new surgical gripper was able to complete the required nerve manipulation within the limited working space. The average deformation of the digital nerve with an average diameter of 1.45 mm gripped by the proposed surgical gripper is less than 0.22 mm. The average deformity is less than 15% of its original diameter.

Over the last few decades, significant efforts have concentrated on mitigating biofouling in reverse osmosis (RO) systems, with a focus on non-toxic and sustainable strategies. Here, we explored the potential of applying quorum quenching (QQ) bacteria to control biofouling in a laboratory-scale RO system. For these experiments, Pantoea stewartii was used as a model biofilm forming organism because it was previously shown to be a relevant wastewater isolate that also forms biofilms in a quorum sensing (QS) dependent fashion. A recombinant Escherichia coli strain, which can produce a QQ enzyme, was first tested in batch biofilm assays and significantly reduced biofilm formation by P. stewartii. Subsequently, RO membranes were fouled with P. stewartii and the QQ bacterium was introduced into the RO system using two different strategies, direct injection and immobilization within a cartridge microfilter. When the QQ bacterial cells were directly injected into the system, N-acylhomoserine lactone signals were degraded, resulting in the reduction of biofouling. Similarly, the QQ bacteria controlled biofouling when immobilized within a microfilter placed downstream of the RO module to remove QS signals circulating in the system. These results demonstrate the proof-of-principle that QQ can be applied to control biofouling of RO membranes and may be applicable for use in full-scale plants., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer., Methods and Materials: Between 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3., Results: The median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm 3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity., Conclusions: Despite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Post-transcriptional gene silencing holds great promise in discovery research for addressing intricate biological questions and as therapeutics. While various gene silencing approaches, such as siRNA and CRISPR-Cas9 techniques, are available, these cannot be effectively applied to "hard-to-transfect" primary T-lymphocytes. The locked nucleic acid-conjugated chimeric antisense oligonucleotide, called "GapmeR", is an emerging new class of gene silencing molecule. Here, we show that GapmeR internalizes into human primary T-cells through macropinocytosis. Internalized GapmeR molecules can associate with SNX5-positive macropinosomes in T-cells, as detected by super-resolution microscopy. Utilizing the intrinsic self-internalizing capability of GapmeR, we demonstrate significant and specific depletion (>70%) of the expression of 5 different endogenous proteins with varying molecular weights (18 kDa Stathmin, 80 kDa PKCε, 180 kDa CD11a, 220 kDa Talin1 and 450 kDa CG-NAP/AKAP450) in human primary and cultured T-cells. Further functional analysis confirms CG-NAP and Stathmin as regulators of T-cell motility. Thus, in addition to screening, identifying or verifying critical roles of various proteins in T-cell functioning, this study provides novel opportunities to silence individual or multiple genes in a subset of purified human primary T-cells that would be exploited as future therapeutics.

Soft compliant gripping is essential in delicate surgical manipulation for minimizing the risk of tissue grip damage caused by high stress concentrations at the point of contact. It can be achieved by complementing traditional rigid grippers with soft robotic pneumatic gripper devices. This manuscript describes a rod-based approach that combined both 3D-printing and a modified soft lithography technique to fabricate the soft pneumatic gripper. In brief, the pneumatic featureless mold with chamber component is 3D-printed and the rods were used to create the pneumatic channels that connect to the chamber. This protocol eliminates the risk of channels occluding during the sealing process and the need for external air source or related control circuit. The soft gripper consists of a chamber filled with air, and one or more gripper arms with a pneumatic channel in each arm connected to the chamber. The pneumatic channel is positioned close to the outer wall to create different stiffness in the gripper arm. Upon compression of the chamber which generates pressure on the pneumatic channel, the gripper arm will bend inward to form a close grip posture because the outer wall area is more compliant. The soft gripper can be inserted into a 3D-printed handling tool with two different control modes for chamber compression: manual gripper mode with a movable piston, and robotic gripper mode with a linear actuator. The double-arm gripper with two actuatable arms was able to pick up objects of sizes up to 2 mm and yet generate lower compressive forces as compared to elastomer-coated and non-coated rigid grippers. The feasibility of having other designs, such as single-arm or hook gripper, was also demonstrated, which further highlighted the customizability of the soft gripper device, and it's potential to be used in delicate surgical manipulation to reduce the risk of tissue grip damage.

In this study, we report that the integrin LFA-1 cross-linking with its ligand ICAM-1 in human PBMCs or CD4(+) T cells promotes Th1 polarization by upregulating IFN-γ secretion and T-bet expression. LFA-1 stimulation in PBMCs, CD4(+) T cells, or the T cell line HuT78 activates the Notch pathway by nuclear translocation of cleaved Notch1 intracellular domain (NICD) and upregulation of target molecules Hey1 and Hes1. Blocking LFA-1 by a neutralizing Ab or specific inhibition of Notch1 by a γ-secretase inhibitor substantially inhibits LFA-1/ICAM-1-mediated activation of Notch signaling. We further demonstrate that the Notch pathway activation is dependent on LFA-1/ICAM-1-induced inactivation of glycogen synthase kinase 3β (GSK3β), which is mediated via Akt and ERK. Furthermore, in silico analysis in combination with coimmunoprecipitation assays show an interaction between NICD and GSK3β. Thus, there exists a molecular cross-talk between LFA-1 and Notch1 through the Akt/ERK-GSK3β signaling axis that ultimately enhances T cell differentiation toward Th1. Although clinical use of LFA-1 antagonists is limited by toxicity related to immunosuppression, these findings support the concept that Notch inhibitors could be attractive for prevention or treatment of Th1-related immunologic disorders and have implications at the level of local inflammatory responses., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Mesenchymal stem cells (MSCs) have drawn much attention amongst stem cell researchers in the past few decades. The ability of the MSC to differentiate into cells of mesodermal and non-mesodermal origins has made them an attractive approach for cell-based therapy and regenerative medicine. The MSCs have immunosuppressive activities that may have considerable therapeutic values in autoimmune diseases. However, despite the many beneficial effects reported, there is a growing body of evidence, which suggests that MSCs could be a culprit of enhanced tumour growth, metastasis and drug resistance in leukaemia, via some modulatory effects. Many controversies regarding the interactions between MSCs and leukaemia still exist. Furthermore, the role of MSCs in leukemogenesis and its progression remain largely unknown. Hence it is important to understand how the MSCs modulate leukaemia before these cells could be safely used in the treatment of leukaemia patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Biofouling remains a key challenge for membrane-based water treatment systems. This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. The potential of PROLI NONOate to control RO membrane biofouling was also examined. Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: The growing ageing population and high prevalence of knee osteoarthritis (OA) in athletes across nations have created a strong demand for improved non-invasive therapeutic alternatives for knee OA. The aim of this study is to investigate the effect of the variable stiffness shoe (VSS), a new non-invasive therapeutic approach, on external knee adduction moment (EKAM) in various dynamic exercises. EKAM is believed to have positive correlation with the progression and development of knee OA., Methods: Thirty young participants (16 male and 14 female; age 22.6 ± 1.9 years) from National University of Singapore were enrolled in this study. The tested activities were walking, running, drop-landing, and lateral hopping. All the dynamic exercises were recorded simultaneously by the 8-camera VICON Motion Systems (Oxford Metric, UK) with a sampling rate of 100 Hz., Results: The results showed that the EKAM was reduced in all the dynamic exercises with the use of VSS. The VSS produced significant reductions in the peak EKAM during walking (4.97%, p = 0.039), running (11.15%, p = 0.011), drop-landing (11.18%, p = 0.038) and lateral hopping (17.34%, p = 0.023) as compared to the control shoe., Conclusions: The reduction of EKAM with the use of VSS in various dynamic exercises demonstrates its potential in delaying the onset and the progression of knee OA in early stage of knee OA patients.

Anterior cruciate ligament (ACL) injuries are highly prevalent during sporting activities. These injuries often are associated with maneuvers involving landing or sudden change in direction, which are thought to "destabilize" the knee joint and cause ACL rupture. ACL injuries can affect one's mobility and quality of life because of abnormal locomotion and consequent knee pain. This review presents key findings from prior biomechanics studies that aimed to understand ACL injury mechanisms. These studies, ranging from motion analyses and in vitro impact tests to knee finite element simulations and multibody dynamics musculoskeletal simulations, have collectively revealed the multifactorial nature of ACL injury mechanisms. Therefore, the second part of this review addresses the strong need to develop prophylactic strategies that can attenuate the factors involved in ACL injury mechanisms, such that the knee joint can be protected from ACL injuries. Previous studies have emphasized strategies such as knee bracing and strength training of important muscle groups. Although these strategies were intended to mitigate ACL injury-causing factors, their clinical outcomes remain controversial. Given the rapid progress of technologies in this area, however, the current state of uncertainty will gradually lead to prospective biomechanics research that can adopt a multifactorial approach toward protecting the ACL from injury.

Background: Epidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. This review was originally published in 2006 and was updated in 2011., Objectives: To assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 11) via Ovid; Ovid MEDLINE (from inception to week 1 November 2010); and EMBASE (from inception to week 1, November 2010). The original search was performed in 2004. We assessed non-English language reports and contacted researchers in the field. We did not seek unpublished data., Selection Criteria: We included all randomized and quasi-randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adult patients who underwent elective open abdominal aortic surgery., Data Collection and Analysis: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data., Main Results: We included 15 trials that involved 1297 patients (633 patients received epidural analgesia and 664 received systemic opioid analgesia) in this review. This included one trial we found in our updated search and one trial from our original review that had been awaiting translation. The epidural analgesia group showed significantly lower visual analogue scale scores for pain on movement (up to postoperative day three) regardless of the site of the epidural catheter and epidural formulation. The postoperative duration of tracheal intubation and mechanical ventilation was significantly shorter, by about 48%, in the epidural analgesia group. The overall event rates of myocardial infarction, acute respiratory failure (defined as an extended need for mechanical ventilation), gastrointestinal complications, and renal complications were significantly lower in the epidural analgesia group., Authors' Conclusions: Epidural analgesia provides better pain relief (especially during movement) in the period up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly half. The occurrence of prolonged postoperative mechanical ventilation, myocardial infarction, gastric complications and renal complications was reduced by epidural analgesia. However, current evidence does not confirm the beneficial effect of epidural analgesia on postoperative mortality and other types of complications.

Chloroquine (CQ) and mefloquine (MQ) are no longer potent antimalarial drugs due to the emergence of resistant Plasmodium falciparum. Combination therapy has become the standard for many regimes in overcoming drug resistance. Roxithromycin (ROM), a known p-glycoprotein inhibitor, is reported to have antimalarial activity and it is hoped it will potentiate the effects of both CQ/MQ and reverse CQ/MQ-resistance. We assayed the effects of CQ and MQ individually and in combination with ROM on synchronized P. falciparum (Dd2 strain) cultures. The IC(50) values of CQ and MQ were 60.0+/-5.0 and 16.0+/-3.0 ng/ml; these were decreased substantially when combined with ROM. Isobolograms indicate that CQ-ROM combinations were relatively more synergistic (mean FICI 0.70) than MQ-ROM (mean FICI 0.85) with their synergistic effect at par with CQ-verapamil (VRP) (mean FICI 0.64) and MQ-VRP (mean FICI 0.60) combinations. We conclude that ROM potentiates the CQ/MQ response on multidrug-resistant P. falciparum.

Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations.

Background: Epidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear., Objectives: To assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery., Search Strategy: We searched the Cochrane Central Register of Controlled Trials via OVID (CENTRAL) (The Cochrane Library, Issue 3, 2004); OVID MEDLINE (1966 to July 2004); and EMBASE (1980 to June 2004). We assessed non-English language reports and contacted researchers in the field. We did not seek unpublished data., Selection Criteria: We included all randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adult patients who underwent elective open abdominal aortic surgery., Data Collection and Analysis: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data., Main Results: Thirteen studies involving 1224 patients met our inclusion criteria; 597 patients received epidural analgesia and 627 received systemic opioid analgesia. The epidural analgesia group showed significantly lower visual analogue scale for pain on movement (up to postoperative day three), regardless of the site of epidural catheter and epidural formulation. Postoperative duration of tracheal intubation and mechanical ventilation was significantly shorter by about 20% in the epidural analgesia group. The overall incidence of cardiovascular complication; myocardial infarction; acute respiratory failure (defined as an extended need for mechanical ventilation); gastrointestinal complication; and renal insufficiency was significantly lower in the epidural analgesia group, especially in trials that used thoracic epidural analgesia., Authors' Conclusions: Epidural analgesia provides better pain relief (especially during movement) for up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly 20%. The occurrence of prolonged postoperative mechanical ventilation, overall cardiac complication, myocardial infarction, gastric complication and renal complication was also reduced by epidural analgesia, especially thoracic. However, current evidence does not confirm the beneficial effect of epidural analgesia on postoperative mortality and other types of complications.

Introduction: The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS., Materials and Methods: From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997., Results: Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study., Conclusions: The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Genome-wide scans have implicated several susceptibility loci, but linkage of 19p13 (IBD6) to Crohn's disease (CD) has not been fully replicated. We report a replication study of IBD6 in a UK Caucasian population. Two hundred eighty-four affected sibling pairs from 234 families were used for the linkage study. Linkage between IBD6 linkage and CD was replicated (LOD score = 1.59). Two candidate genes (DDXL and ICAM-1) within the IBD6 locus were examined in a case/control study with a total of 228 CD and 243 ulcerative colitis (UC) patients and 407 healthy controls. No association to either UC or CD was found in three novel intronic single nucleotide polymorphisms (SNPs) in DDXL. For ICAM-1, a significant association was found between K469 homozygosity and CD overall (39.9% vs 29.4%; Pc = 0.0096) and between E469 and fistulating disease (21.8% vs 10.0%, Pc = 0.030). In the UC group, limited disease extent was associated with homozygosity of the G241 allele (82.7% vs 64.7%, Pc = 0.0040). These data support linkage for CD at 19p13 and suggest that the amino acid polymorphisms in ICAM-1 may be associated with IBD.

Background: The management of epidural analgesia is controversial. Many intensive care unit (ICU) patients may benefit from this form of analgesia but have one or more contraindications to its use. Sepsis, coagulopathy, insertion in a sedated, ventilated patient, and lack of consent are common problems in ICU patients. Little has been published to help guide practice in this area. I wished to establish the current practice of the management of epidural analgesia in general ICUs in England when relative or absolute contraindications occur, in order to determine the current standard of care for placement and use of epidural analgesia in ICU patients., Methods: A postal questionnaire survey of the management of epidural analgesia in critically ill patients was sent to the named clinical director of all (216) general ICUs in England., Results: Responses were received from 159 (75%) units: 89% of responding units use epidural analgesia but only 51(32%) have a written policy covering its use. Anesthetists or intensivists with an anesthetic background sited all epidural catheters; 68% of units would not site an epidural in a patient with positive blood cultures; but only 52% considered culture negative sepsis (systemic signs of sepsis with no organism isolated) to be a contraindication. Neither lack of consent nor the need for anticoagulation after the catheter had been sited were considered contraindications to inserting an epidural catheter by the majority of respondents. Although 71% of the units would remove an epidural catheter if a patient developed positive blood cultures after it had been sited, the majority of the ICUs did not consider culture negative sepsis and the need for anticoagulation contraindications to maintain a previously sited epidural., Conclusions: Practice varied considerably with little consensus. Although all the respondents use epidural analgesia in critically ill patients, the indications and contraindications to epidural analgesia remain controversial, and further research is required to help define the role of epidural analgesia in this high-risk group.