Multi-modal deformation and temperature sensing for context-sensitive machines.

Owing to the remarkable properties of the somatosensory system, human skin compactly perceives myriad forms of physical stimuli with high precision. Machines, conversely, are often equipped with sensory suites constituted of dozens of unique sensors, each made for detecting limited stimuli. Emerging high degree-of-freedom human-robot interfaces and soft robot applications are delimited by the lack of simple, cohesive, and information-dense sensing technologies. Stepping toward biological levels of proprioception, we present a sensing technology capable of decoding omnidirectional bending, compression, stretch, binary changes in temperature, and combinations thereof. This multi-modal deformation and temperature sensor harnesses chromaticity and intensity of light as it travels through patterned elastomer doped with functional dyes. Deformations and temperature shifts augment the light chromaticity and intensity, resulting in a one-to-one mapping between stimulus modes that are sequentially combined and the sensor output. We study the working principle of the sensor via a comprehensive opto-thermo-mechanical assay, and find that the information density provided by a single sensing element permits deciphering rich and diverse human-robot and robot-environmental interactions.

Does enforcing glenohumeral joint stability matter? A new rapid muscle redundancy solver highlights the importance of non-superficial shoulder muscles.

The complexity of the human shoulder girdle enables the large mobility of the upper extremity, but also introduces instability of the glenohumeral (GH) joint. Shoulder movements are generated by coordinating large superficial and deeper stabilizing muscles spanning numerous degrees-of-freedom. How shoulder muscles are coordinated to stabilize the movement of the GH joint remains widely unknown. Musculoskeletal simulations are powerful tools to gain insights into the actions of individual muscles and particularly of those that are difficult to measure. In this study, we analyze how enforcement of GH joint stability in a musculoskeletal model affects the estimates of individual muscle activity during shoulder movements. To estimate both muscle activity and GH stability from recorded shoulder movements, we developed a Rapid Muscle Redundancy (RMR) solver to include constraints on joint reaction forces (JRFs) from a musculoskeletal model. The RMR solver yields muscle activations and joint forces by minimizing the weighted sum of squared-activations, while matching experimental motion. We implemented three new features: first, computed muscle forces include active and passive fiber contributions; second, muscle activation rates are enforced to be physiological, and third, JRFs are efficiently formulated as linear functions of activations. Muscle activity from the RMR solver without GH stability was not different from the computed muscle control (CMC) algorithm and electromyography of superficial muscles. The efficiency of the solver enabled us to test over 3600 trials sampled within the uncertainty of the experimental movements to test the differences in muscle activity with and without GH joint stability enforced. We found that enforcing GH stability significantly increases the estimated activity of the rotator cuff muscles but not of most superficial muscles. Therefore, a comparison of shoulder model muscle activity to EMG measurements of superficial muscles alone is insufficient to validate the activity of rotator cuff muscles estimated from musculoskeletal models.

Significant Advancement in Various Synthetic Strategies and Pharmacotherapy of Piperine Derivatives: A Review.

BACKGROUND: Piperine is a natural compound found in black pepper that has been traditionally used for various therapeutic purposes. In the ayurvedic system of medication there is a lot of evidence which shows that the piperine is widely used for different therapeutic purpose. In recent years, there has been an increasing interest in the pharmacological and therapeutic potential of piperine and its derivatives in modern medicine. In order to increase the bioavailability and therapeutic effectiveness of piperine and its analogs, researchers have been looking at various extraction methods and synthesis approaches. Many studies have been conducted in this area because of the promise of piperine as a natural substitute for synthetic medications. OBJECTIVES: The objective of this review article is to provide an up-to-date analysis of the literature on the synthesis of piperine analogs, including their extraction techniques and various biological activities such as antihypertensive, antidiabetic, insecticidal, antimicrobial, and antibiotic effects. Additionally, the review aims to discuss the potential of piperine in modern medicine, given its traditional use in various medicinal systems such as Ayurveda, Siddha, and Unani. The article also provides a comprehensive analysis of the plant from which piperine is derived. CONCLUSION: This review article provides a thorough examination of piperine and the source plant. The best extraction technique for the extraction of piperine and the synthesis of its analogs with various biological activities, including antihypertensive, antidiabetic, insecticidal, antibacterial, and antibiotic properties, are covered in the article. This review aims to provide an updated analysis of the literature on the synthesis of piperine analogs.

Henoch-Schönlein purpura with antecedent allergic diseases in a 4-year-old child: a case report.

Henoch-Schönlein purpura (HSP)/immunoglobulin A vasculitis is an acute immunoglobulin-mediated vascular disorder compromising a triad of non-blanchable purpuric rashes, colicky abdominal pain and haematuria. Incidence ranging for large populations has been most common vasculitis among children with a mean age of 6years. Disease presentation ranges from small petechial rash to the most severe form of renal involvement so early diagnosis is important. Case presentation: Here the authors present a 4-year-old girl with antecedent allergic history associated HSP. She presented with non-blanchable purpuric rashes, abdominal pain with bilateral ankle swelling. She had been treated for atopic dermatitis and acute urticaria without angioedema and acute tonsillitis. The potential association of HSP and these condition should be kept in mind in order not to miss the impediment complications of HSP. Clinical discussion: HSP usually presents with rash, abdominal pain and vomiting, joint pain especially involving knees and ankles, subcutaneous oedema but in severe cases there could be renal involvement leading to nephritis, neurological manifestation involving neuropathies, altered mental status and many others. Conclusion: This case highlights the rarity of disease, presentation, association with allergic diseases and availability of treatment modality.

Sensorless force and displacement estimation in soft actuators.

Sensing forms an integral part of soft matter based robots due to their compliance, dependence on loading conditions, and virtually infinite degrees of freedom. Previous studies have developed several extrinsic sensors and embedded them into soft actuators for displacement and force estimation. What has not been investigated is whether soft robots themselves possess intrinsic sensing capabilities, especially in the case of pneumatically powered soft robots. Such an approach, that exploits the inherent properties of a system toward sensing is called sensorless estimation. Here, we introduce sensorless estimation for the first time in pneumatically powered soft actuators. Specifically, we show that the intrinsic properties of pressure and volume can be used to estimate the output force and displacement of soft actuators. On testing this approach with a bending actuator, we observed errors under 10% and 15% for force and displacement estimation respectively, with randomized and previously unseen test conditions. We also show that combining this approach with a conventional embedded sensor improves estimation accuracy due to sensing redundancy. By modelling soft actuators additionally as sensors, this work presents a new, readily implementable sensing modality that helps us better understand the highly complex behaviour of soft matter based robots.

Stage migration as a surrogate of survival in hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUND AIMS: Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE. APPROACH: We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019. The primary outcome was overall survival from the date of the first TACE treatment, and the primary exposure of interest was Barcelona Clinic Liver Cancer stage migration to a more advanced stage within 6 months of TACE. Survival analysis was completed using Kaplan-Meier and multiple Cox proportional hazard models adjusted by the site. RESULTS: Of 651 eligible patients (51.9% Barcelona Clinic Liver Cancer stage A and 39.6% stage B), 129 (19.6%) patients experienced stage migration within 6 months of TACE. Those with stage migration had larger tumors (5.6 vs. 4.2 cm, p < 0.01) and higher AFP levels (median 92 vs. 15 ng/mL, p < 0.01). In multivariate analysis, stage migration was significantly associated with worse survival (HR: 2.82, 95% CI: 2.66-2.98), with a median survival of 8.7 and 15.9 months in those with and without stage migration. Other predictors of worse survival included the White race, higher AFP levels, a higher number of tumors, and a larger maximum HCC diameter. CONCLUSION: Stage migration is associated with increased mortality after TACE in patients with HCC and could serve as a surrogate end point in clinical trials evaluating locoregional therapies such as TACE.

Clinical Outcomes of Patients With Suspicious (LI-RADS 4) Liver Observations.

Hepatocellular cancer (HCC) surveillance is associated with increased curative treatment and improved survival, underscoring its importance in patients with cirrhosis.1 Surveillance is 1 step in a larger HCC screening continuum, and those with abnormal screening results must undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) classifies liver observations in at-risk patients based on risk of malignancy and HCC, with LR-5 observations having a positive predictive value exceeding 95% for HCC. However, indeterminate liver nodules (ie, LR-3 or LR-4) are commonly observed in clinical practice, associated with heterogenous HCC risk, and have large variations in practice management.3,4 We previously reported the natural history of LR-3 observations in a multicenter cohort of patients with cirrhosis, demonstrating a high annual incidence for HCC development of 8.4 cases per 100 person-years;5 however, the natural history of LR-4 observations remains uncertain. Herein, we aimed to characterize clinical outcomes in patients with LR-4 observations in a multicenter cohort.

Risk of Hepatocellular Carcinoma in Patients With Indeterminate (LI-RADS 3) Liver Observations.

Early hepatocellular cancer (HCC) detection is associated with curative treatment and improved survival.1 The American Association for the Study of Liver Diseases recommends semiannual ultrasound and α-fetoprotein (AFP) in patients with cirrhosis, and those with abnormal results should undergo diagnostic multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) was devised to standardize reporting of liver observations in at-risk individuals, ranging from LR-1 ("definitely benign") to LR-5 ("definitely HCC''), with indeterminate observations classified as LR-3 ("intermediate probability of malignancy").3 A study among 999 cirrhosis patients found that indeterminate liver observations are common, being reported on diagnostic CT or MRI in 98 (38.3%) of 256 patients with abnormal ultrasound results.4 Prior studies have reported a wide range in HCC risk, from 4% to 31%, for LR-3 observations, so there is insufficient evidence to recommend a standardized strategy for monitoring LR-3 observations.5,6.

Quality changes in fish sausages supplemented with pangas protein isolates as affected by frozen storage and casing material.

Influence of pangas protein isolates (10PI) and casing material on frozen storage (-18 °C) characteristics of pangas mince sausages was studied for a period of three months along with control sausages (CO). The expressible fluid content of sausage emulsion increased as storage progressed to 3 months, reaching 31.32 and 17.57 g 100 g-1 for control and 10% PI emulsions, respectively. Water holding capacity and cooking yield values showed a gradual and significant (p < 0.05) reduction with progress in the storage time. The G' and G″ values decreased during storage, indicating the change in protein structure and gelling ability. Sausages packed in LDPE casings had higher oxidation and bacterial counts than sausages packed in cellulose casings. Irrespective of the casing material and protein isolates, the sensory scores varied non-significantly in all the sausages during the initial storage phase. After three months, sausages from COCL and 10PICL were still acceptable with sensory scores of 5.6 and 5.8, respectively, indicating better quality of sausages stuffed into cellulose casings than LDPE casings. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05222-1.

Haptigami: A Fingertip Haptic Interface With Vibrotactile and 3-DoF Cutaneous Force Feedback.

Wearable fingertip haptic devices aim todeliver somatosensory feedback for applications such as virtual reality, rehabilitation, and enhancing hardware/physical control interfaces. However, providing various kinds of feedback requires several Degrees of Freedom (DoF) and high mechanical complexity which are mechanically difficult to achieve at the mesoscale. Using compliant low-profile transmissions embedded in an origami structure and PCBmotors as actuators, we designed and fabricated a novel 3-DoF fingertip haptic device, called Haptigami. This under-actuated system, measuring 36 x 25 x 26 mm and weighing 13 g, can render vibrotactile and cutaneous force feedback. We tested our device by creating a novel experimental protocol and robotic platform allowing quantitative characterization of mechanical performance. The current prototype of Haptigami produces 678 mN in compression, and 400 mN and 150 mN in shear for the Y and X directions, respectively. By virtue of its unique origami-inspired design, Haptigami brings a new direction for future designs of lightweight and compact wearable robots.

Insight into the Isolation, Synthesis, and Structure-Activity Relationship of Piperine Derivatives for the Development of New Compounds: Recent Updates.

Currently, black pepper commands the leading position among all the spices as a spice of great commercial importance in all the world trade and finds its way into the dietary habits of millions of people worldwide. Black pepper is biologically known as Piper nigrum and contains piperine as the main active chemical constituent. This paper highlights various general methods for extracting piperine from the crude drug such as maceration extraction, hydrotropic extraction, accelerated solvent extraction, thin-layer chromatography, and extraction with ethanol & dichloromethane Ionic fluid-based ultrasonic-assisted extraction, etc. In this review, piperine and its analogs exhibit numerous pharmacological activities and synthetic schemes of insecticidal activity, anti-cancer activity, anti-inflammatory activity, anti-diabetic activity, anti-hyperlipidemic activity, antifungal activity, narcotic activity, etc. and its structure-activity relationship. The biochemistry of piperine has also been summarized in the presented article. This very exhaustive review details the complete information about piperine, its derivatives, and further processing. Furthermore, the current study summarises recent research that has linked piperine to its use as a treatment for a variety of ailments.

Comparison of Echocardiographic Variables in Patients With Severe Aortic Stenosis and Preserved Ejection Fraction Grouped by Flow and Gradient.

The pathophysiology of severe aortic stenosis (AS) is complex with vascular, valvular, and myocardial components. To better define this process, we compared echocardiographic and clinical variables in patients with severe AS and preserved EF according to flow and gradient. We retrospectively studied the clinical and echocardiographic data of 287 patients (mean age 76 ± 11 years, 57% men) from 2012 to 2017 with severe AS (indexed aortic valve area <0.6 cm2/m2) and preserved ejection fraction (>50%). Patients were divided into 4 groups based on flow (stroke volume index < or ≥35 ml/m2) and mean aortic pressure gradient (< or ≥40 mm Hg): normal flow, high gradient (NFHG), normal flow, low gradient (NFLG), low flow, high gradient (LFHG) and low flow, low gradient (LFLG). Among patients with severe AS, 23% had NFHG, 44% had NFLG, 10% had LFHG, and 23% had LFLG. Only diabetes was marginally significantly different among the clinical variables. Aortic valve area index was largest in NFLG and smallest in LFHG (p < 0.001 for pairwise comparisons). Valvuloarterial impedance was highest in LFHG (p < 0.01 for pairwise comparisons). Systemic arterial compliance was lower and systemic vascular resistance was higher in low flow compared with normal flow groups. In conclusion, LFHG had the smallest valve area index along with markers of increased vascular resistance combined with high gradients, which suggests a unique pathophysiology in this group of severe AS patients with preserved EF.

CMOS-Inspired Complementary Fluidic Circuits for Soft Robots.

The latest efforts in digital fluidic circuits' research aim at being electronics-free, light-weight, and compliant controllers for soft robots; however, challenges arise to adjust the fluidic circuit's digital logic operations. Currently there is no other way to modulate the amplitude or frequency but to structurally redesign the entire fluidic circuitry. This is mainly because there is currently no method to create an analog circuit-like behavior in the digital fluidic circuits using conventional digitized fluidic gates. In this work, a new approach is presented to designing a circuit with digitized fluidic gates that is comparable to an analog circuit capable of actively tuning the circuit's fluidic characteristics, such as pressure gain, amplitude of output, and time response. For the first time, a pressure-controlled oscillator is modeled, designed, and prototyped that not only controls the fluidic oscillation, but also modulates its frequency using only a single, quasi-static pressure input. It can also demonstrate the circuit's performance for the control of a soft robotic system by actively modulating the motion of a soft earthworm robot up to twice of crawling speeds. This work has distinct contributions to designing and building intelligent pneumatic controllers toward truly comprehensive soft robotic systems.

1,3,4-Oxadiazoles as Potential Pharmacophore for Cytotoxic Potentiality: A Comprehensive Review.

Cancer is a kind of human cell degenerative disease that has affected many people for several years. Cancer is caused due to the abnormal growth of cells in every particular part of the body. The 1,3,4-oxadiazole ring is found to be a binding moiety that has anticancer potential. Various works on the 1,3,4-oxadiazole moiety showing anticancer activity have been reported. The present analysis summarizes general synthetic methods for 1,3,4 oxadiazole. Different receptors on which these drug acts are discussed. This review also presents pharmacophore models for topoisomerase-I, histone deacetylase, and epidermal growth factor enzymes.

DentalVibe reduces pain during the administration of local anesthetic injection in comparison to 2% lignocaine gel: results from a clinical study.

BACKGROUND: This study was designed to compare the efficacy of DentalVibe against 2% lidocaine gel in reducing pain during the administration of local anesthetic injection in the adult population. METHODS: This was a split-mouth open-label, randomized, controlled clinical study conducted in the Department of Oral and Maxillofacial Surgery of a dental institute. Fifty patients who were scheduled for bilateral dental extractions requiring an inferior alveolar nerve block were enrolled in the study. Site A (n = 50) was coated with 2% lidocaine gel followed by a local anesthetic injection, and DentalVibe with local anesthetic injection was used for Site B (n = 50). The primary outcome was pain, which was recorded immediately after the administration of anesthetic injection using the Visual Analogue Scale [VAS 0 - 10]. RESULTS: The VAS pain scores ranged from 4 to 10 for site A and 0 to 6 for site B. Comparison between the two sites showed a statistically significant difference [Mann-Whitney U test value = 51.50, P < 0.001] favoring site B. CONCLUSION: This study showed that DentalVibe reduces pain during injection of local anesthesia compared to topical anesthetic gel.

Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis.

INTRODUCTION: Little is known about the use of compounded steroids for eosinophilic esophagitis (EoE). METHODS: We conducted a telephone survey of all compounding pharmacies in Michigan and queried about practices and costs of compounded budesonide for EoE. RESULTS: Of 68 Michigan pharmacies, 93% responded, and 20 (29%) offer compounded budesonide suspension for EoE. Formulations, dose, and instructions for use varied across pharmacies. The mean cost for a 30-day supply was $74.50. DISCUSSION: Although few compounding pharmacies offer budesonide suspension and there are substantial variations in formulations, this may be a significantly more affordable treatment option for many.

Pneumatic Supply System Parameter Optimization for Soft Actuators.

Soft actuators using pressurized air are being widely used due to their inherent compliance, conformability, and customizability. These actuators are powered and controlled by pneumatic supply systems (PSSs) consisting of components such as compressors, valves, tubing, and reservoirs. Regardless of the choice of actuator, the PSS critically affects overall performance of soft robots because it governs the soft actuator pressure dynamics, and thereby, the general dynamic behavior. While selecting and controlling PSS components for meeting desired soft actuator performance, specifications such as PSS mass, volume, and duration of operation must also be considered. Currently, there is no comprehensive study on PSS optimization for meeting dynamic performance and PSS specifications, due to limited understanding of soft actuator pressure dynamics, large solution space for PSSs, and variability in soft actuators. By considering critical parameters of PSS and soft actuators, we introduce and demonstrate PSS parameter optimization. We propose a normalized model for soft actuator pressure dynamics and quantify the relationship between PSS parameters, soft actuator design parameters, and dynamic performance metrics of rise time, fall time, and actuation frequency. After experimental validation, we applied these results and optimally select and control PSS components to meet desired soft actuator performance for a soft exosuit, while minimizing mass of selected components. The measured pressure response with this prototype agrees well with simulations, with root mean square errors <5.2%. This work is a step toward furthering the scope of soft robotics, as it enables PSS modeling and optimization, for meeting the desired soft actuator performance while also addressing PSS specifications.

Painless injections-a possibility with low level laser therapy.

BACKGROUND: Dental procedures commonly involve the injection of local anesthetic agents, which causes apprehension in patients. The objective of dental practice is to provide painless treatment to the patient. The purpose of this study was to evaluate the effect of Low Level Laser Therapy (LLLT) in reducing the pain due to local anesthetic injection. MATERIALS AND METHODS: A prospective, split-mouth study was conducted on 25 patients. In Condition A, LLLT was administered followed by the administration of a standard local anesthetic agent. Patients' perception of pain with use of LLLT was assessed based on a Visual Analogue Scale (VAS). In Condition B, LLLT was directed to the mucosa but not activated, followed by the administration of local anesthesia. VAS was used to assess the pain level without the use of LLLT. RESULTS: Comparison between Condition A and Condition B was done. A P value < 0.001 was considered significant, indicating a definite statistical difference between the two conditions. CONCLUSION: In our study, we observed that LLLT reduced pain during injection of local anesthesia. Further multi-centric studies with a larger sample size and various modifications in the study design are required.

Mechanochemical actuators of embryonic epithelial contractility.

Spatiotemporal regulation of cell contractility coordinates cell shape change to construct tissue architecture and ultimately directs the morphology and function of the organism. Here we show that contractility responses to spatially and temporally controlled chemical stimuli depend much more strongly on intercellular mechanical connections than on biochemical cues in both stimulated tissues and adjacent cells. We investigate how the cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation. The stimulation-response circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells. These findings may enable one to create a biological actuator that actively drives morphogenesis.