Spike-Based Neuromorphic Hardware for Dynamic Tactile Perception with a Self-Powered Mechanoreceptor Array.

A self-powered mechanoreceptor array is demonstrated using four mechanoreceptor cells for recognition of dynamic touch gestures. Each cell consists of a triboelectric nanogenerator (TENG) for touch sensing and a bi-stable resistor (biristor) for spike encoding. It produces informative spike signals by sensing a force of an external touch and encoding the force into the number of spikes. An array of the mechanoreceptor cells is utilized to monitor various touch gestures and it successfully generated spike signals corresponding to all the gestures. To validate the practicality of the mechanoreceptor array, a spiking neural network (SNN), highly attractive for power consumption compared to the conventional von Neumann architecture, is used for the identification of touch gestures. The measured spiking signals are reflected as inputs for the SNN simulations. Consequently, touch gestures are classified with a high accuracy rate of 92.5%. The proposed mechanoreceptor array emerges as a promising candidate for a building block of tactile in-sensor computing in the era of the Internet of Things (IoT), due to the low cost and high manufacturability of the TENG. This eliminates the need for a power supply, coupled with the intrinsic high throughput of the Si-based biristor employing complementary metal-oxide-semiconductor (CMOS) technology.

Role of Piezo2 in Schwann Cell Volume Regulation and Its Impact on Neurotrophic Release Regulation.

BACKGROUND/AIMS: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aß-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aß and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. METHODS: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. RESULTS: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. CONCLUSION: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.

Antennal transcriptome analysis reveals sensory receptors potentially associated with host detection in the livestock pest Lucilia cuprina.

BACKGROUND: Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae) is the main causative agent of flystrike of sheep in Australia and New Zealand. Female flies lay eggs in an open wound or natural orifice, and the developing larvae eat the host's tissues, a condition called myiasis. To improve our understanding of host-seeking behavior, we quantified gene expression in male and female antennae based on their behavior. METHODS: A spatial olfactometer was used to evaluate the olfactory response of L. cuprina mated males and gravid females to fresh or rotting beef. Antennal RNA-Seq analysis was used to identify sensory receptors differentially expressed between groups. RESULTS: Lucilia cuprina females were more attracted to rotten compared to fresh beef (> fivefold increase). However, males and some females did not respond to either type of beef. RNA-Seq analysis was performed on antennae dissected from attracted females, non-attracted females and males. Transcripts encoding sensory receptors from 11 gene families were identified above a threshold (≥ 5 transcript per million) including 49 ATP-binding cassette transporters (ABCs), two ammonium transporters (AMTs), 37 odorant receptors (ORs), 16 ionotropic receptors (IRs), 5 gustatory receptors (GRs), 22 odorant-binding proteins (OBPs), 9 CD36-sensory neuron membrane proteins (CD36/SNMPs), 4 chemosensory proteins (CSPs), 4 myeloid lipid-recognition (ML) and Niemann-Pick C2 disease proteins (ML/NPC2), 2 pickpocket receptors (PPKs) and 3 transient receptor potential channels (TRPs). Differential expression analyses identified sex-biased sensory receptors. CONCLUSIONS: We identified sensory receptors that were differentially expressed between the antennae of both sexes and hence may be associated with host detection by female flies. The most promising for future investigations were as follows: an odorant receptor (LcupOR46) which is female-biased in L. cuprina and Cochliomyia hominivorax Coquerel, 1858; an ABC transporter (ABC G23.1) that was the sole sensory receptor upregulated in the antennae of females attracted to rotting beef compared to non-attracted females; a female-biased ammonia transporter (AMT_Rh50), which was previously associated with ammonium detection in Drosophila melanogaster Meigen, 1830. This is the first report suggesting a possible role for ABC transporters in L. cuprina olfaction and potentially in other insects.

Functional Morphology of Leg Mechanosensory Organs in Early Postembryonic Development in the Stick Insect (Sipyloidea chlorotica).

The subgenual organ complex of stick insects has a unique neuroanatomical organisation with two elaborate chordotonal organs, the subgenual organ and the distal organ. These organs are present in all leg pairs and are already developed in newly hatched stick insects. The present study analyses for the first time the morphology of sensory organs in the subgenual organ complex for a membrane connecting the two sensory organs in newly hatched insects (Sipyloidea chlorotica (Audinet-Serville 1838)). The stick insect legs were analysed following hatching by axonal tracing and light microscopy. The subgenual organ complex in first juvenile instars shows the sensory organs and a thin membrane connecting the sensory organs resembling the morphology of adult animals. Rarely was this membrane not detected, where it is assumed as not developed during embryogenesis. The connection appears to influence the shape of the subgenual organ, with one end extending towards the distal organ as under tension. These findings are discussed for the following functional implications: (1) the physiological responses of the subgenual organ complex to mechanical stimuli after hatching, (2) the influence of the membrane on the displacement of the sensory organs, and (3) the connection between the subgenual organ and distal organ as a possible functional coupling.

Non-equilibrium compression achieving high sensitivity and linearity for iontronic pressure sensors.

Flexible pressure sensors with high sensitivity and linearity are highly desirable for robot sensing and human physiological signal detection. However, the current strategies for stabilizing axial microstructures (e.g., micro-pyramids) are mainly susceptible to structural stiffening during compression, thereby limiting the realization of high sensitivity and linearity. Here, we report a bending-induced non-equilibrium compression process that effectively enhances the compressibility of microstructures, thereby crucially improving the efficiency of interfacial area growth of electric double layer (EDL). Based on this principle, we fabricate an iontronic flexible pressure sensor with vertical graphene (VG) array electrodes. Ultra-high sensitivity (185.09 kPa-1) and linearity (R2 = 0.9999) are realized over a wide pressure range (0.49 Pa-66.67 kPa). It also exhibits remarkable mechanical stability during compression and bending. The sensor is successfully employed in a robotic gripping task to recognize the targets of different materials and shapes based on a multilayer perception (MLP) neural network. It opens the door to realizing haptic sensing capabilities for robotic hands and prosthetic limbs.

Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Bio-Inspired Sensory Receptors for Artificial-Intelligence Perception.

In the era of artificial intelligence (AI), there is a growing interest in replicating human sensory perception. Selective and sensitive bio-inspired sensory receptors with synaptic plasticity have recently gained significant attention in developing energy-efficient AI perception. Various bio-inspired sensory receptors and their applications in AI perception are reviewed here. The critical challenges for the future development of bio-inspired sensory receptors are outlined, emphasizing the need for innovative solutions to overcome hurdles in sensor design, integration, and scalability. AI perception can revolutionize various fields, including human-machine interaction, autonomous systems, medical diagnostics, environmental monitoring, industrial optimization, and assistive technologies. As advancements in bio-inspired sensing continue to accelerate, the promise of creating more intelligent and adaptive AI systems becomes increasingly attainable, marking a significant step forward in the evolution of human-like sensory perception.

Utilizing a High-Performance Piezoelectric Nanocomposite as a Self-Activating Component in Piezotronic Artificial Mechanoreceptors.

Challenges such as poor dispersion and insufficient polarization of BaTiO3 (BTO) nanoparticles (NPs) within poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) composites have hindered their piezoelectricity, limiting their uses in pressure sensors, nanogenerators, and artificial sensory synapses. Here, we introduce a high-performance piezoelectric nanocomposite material consisting of P(VDF-TrFE)/modified-BTO (mBTO) NPs for use as a self-activating component in a piezotronic artificial mechanoreceptor. To generate high-performance piezoelectric nanocomposite materials, the surface of BTO is hydroxylated, followed by the covalent attachment of (3-aminopropyl)triethoxysilane to improve the dispersibility of mBTO NPs within the P(VDF-TrFE) matrix. We also aim to enhance the crystallization degree of P(VDF-TrFE), the efficiency characteristics of mBTO, and the poling efficiency, even when incorporating small amounts of mBTO NPs. The piezoelectric potential mechanically induced from the P(VDF-TrFE)/mBTO NPs nanocomposite was three times greater than that from P(VDF-TrFE) and twice as high as that from the P(VDF-TrFE)/BTO NPs nanocomposite. The piezoelectric potential generated by mechanical stimuli on the piezoelectric nanocomposite was utilized to activate the synaptic ionogel-gated field-effect transistor for the development of self-powered piezotronics artificial mechanoreceptors on a polyimide substrate. The device successfully emulated fast-adapting (FA) functions found in biological FA mechanoreceptors. This approach has great potential for applications to future intelligent tactile perception technology.

Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice.

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aß fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.

Sensory cells in tunicates: insights into mechanoreceptor evolution.

Tunicates, the sister group of vertebrates, offer a unique perspective for evolutionary developmental studies (Evo-Devo) due to their simple anatomical organization. Moreover, the separation of tunicates from vertebrates predated the vertebrate-specific genome duplications. As adults, they include both sessile and pelagic species, with very limited mobility requirements related mainly to water filtration. In sessile species, larvae exhibit simple swimming behaviors that are required for the selection of a suitable substrate on which to metamorphose. Despite their apparent simplicity, tunicates display a variety of mechanoreceptor structures involving both primary and secondary sensory cells (i.e., coronal sensory cells). This review encapsulates two decades of research on tunicate mechanoreception focusing on the coronal organ's sensory cells as prime candidates for understanding the evolution of vertebrate hair cells of the inner ear and the lateral line organ. The review spans anatomical, cellular and molecular levels emphasizing both similarity and differences between tunicate and vertebrate mechanoreception strategies. The evolutionary significance of mechanoreception is discussed within the broader context of Evo-Devo studies, shedding light on the intricate pathways that have shaped the sensory system in chordates.

The interplay between biochemical mediators and mechanotransduction in chondrocytes: Unravelling the differential responses in primary knee osteoarthritis.

In primary or idiopathic osteoarthritis (OA), it is unclear which factors trigger the shift of articular chondrocyte activity from pro-anabolic to pro-catabolic. In fact, there is a controversy about the aetiology of primary OA, either mechanical or inflammatory. Chondrocytes are mechanosensitive cells, that integrate mechanical stimuli into cellular responses in a process known as mechanotransduction. Mechanotransduction occurs thanks to the activation of mechanosensors, a set of specialized proteins that convert physical cues into intracellular signalling cascades. Moderate levels of mechanical loads maintain normal tissue function and have anti-inflammatory effects. In contrast, mechanical over- or under-loading might lead to cartilage destruction and increased expression of pro-inflammatory cytokines. Simultaneously, mechanotransduction processes can regulate and be regulated by pro- and anti-inflammatory soluble mediators, both local (cells of the same joint, i.e., the chondrocytes themselves, infiltrating macrophages, fibroblasts or osteoclasts) and systemic (from other tissues, e.g., adipokines). Thus, the complex process of mechanotransduction might be altered in OA, so that cartilage-preserving chondrocytes adopt a different sensitivity to mechanical signals, and mechanic stimuli positively transduced in the healthy cartilage may become deleterious under OA conditions. This review aims to provide an overview of how the biochemical exposome of chondrocytes can alter important mechanotransduction processes in these cells. Four principal mechanosensors, i.e., integrins, Ca2+ channels, primary cilium and Wnt signalling (canonical and non-canonical) were targeted. For each of these mechanosensors, a brief summary of the response to mechanical loads under healthy or OA conditions is followed by a concise overview of published works that focus on the further regulation of the mechanotransduction pathways by biochemical factors. In conclusion, this paper discusses and explores how biological mediators influence the differential behaviour of chondrocytes under mechanical loads in healthy and primary OA.

Identification of candidate genes associated with host-seeking behavior in the parasitoid wasp Diachasmimorpha longicaudata.

BACKGROUND: Diachasmimorpha longicaudata is a hymenopteran fruit fly endoparasitoid. Females of this species find their hosts for oviposition by using complex sensorial mechanisms in response to physical and chemical stimuli associated with the host and host habitat. Ecological and behavioral aspects related to host-seeking behavior for oviposition have been extensively studied in D. longicaudata, including the identification of volatile organic compounds acting as attractants to females. In this sense, molecular mechanisms of chemoreception have been explored in this species, including a preliminary characterization of odorant-binding proteins (OBPs), chemosensory proteins (CSPs) and odorant receptors (ORs), among other proteins. Functional assays on OBP and CSP have been conducted as a first approach to identify molecular mechanisms associated with the female host-seeking behavior for oviposition. The aims of the present study were to identify the D. longicaudata sensory gene repertoire expressed in the antenna of sexually mature and mated individuals of both sexes, and subsequently, characterize transcripts differentially expressed in the antennae of females to identify candidate genes associated with the female host-seeking behavior for oviposition. RESULTS: A total of 33,745 predicted protein-coding sequences were obtained from a de novo antennal transcriptome assembly. Ten sensory-related gene families were annotated as follows: 222 ORs, 44 ionotropic receptors (IRs), 25 gustatory receptors (GRs), 9 CSPs, 13 OBPs, 2 ammonium transporters (AMTs), 8 pickpocket (PPKs) receptors, 16 transient receptor potential (TRP) channels, 12 CD36/SNMPs and 3 Niemann-Pick type C2 like proteins (NPC2-like). The differential expression analysis revealed 237 and 151 transcripts up- and downregulated, respectively, between the female and male antennae. Ninety-seven differentially expressed transcripts corresponded to sensory-related genes including 88 transcripts being upregulated (87 ORs and one TRP) and nine downregulated (six ORs, two CSPs and one OBP) in females compared to males. CONCLUSIONS: The sensory gene repertoire of D. longicaudata was similar to that of other taxonomically related parasitoid wasps. We identified a high number of ORs upregulated in the female antenna. These results may indicate that this gene family has a central role in the chemoreception of sexually mature females during the search for hosts and host habitats for reproductive purposes.

The importance of foot posture when recording lower leg electromyography when walking in non-textured and textured foot orthoses.

Foot posture describes the anatomical variance in an individual's overall foot shape, an important consideration in the provision of foot orthoses. Current orthoses designs could be optimized by considering the topographical organization of cutaneous mechanoreceptors. Currently, the effect of foot orthoses designs to enhance skin stimulation across different anatomical foot posture remains unknown. Thus, the purpose of this study was to investigate how foot posture variance modulates lower leg muscle activity when walking in non-textured orthoses and in textured orthoses which facilitates cutaneous mechanoreceptors under five different regions of the foot sole. Fifty-one (51) healthy young adults were subdivided by the Foot Posture Index and completed level walking trials wearing non-textured and textured foot orthoses. Surface and fine-wire electromyography (EMG) recorded muscle activity in 8 lower leg muscles. Statistically significant interactions were observed in each muscle's average EMG across textured location and Foot Posture Index score. For example, in pes cavus compared to pes planus feet, texture under the calcaneus generated greater aEMG of the tibialis anterior (44.9 mV ± 22.7 mV to 30.9 mV ± 11.4 mV) medial gastrocnemius (26.1 mV ± 16.7 mV to 17.5 mV ± 6.0 mV), and tibialis posterior (84.4 mV ± 77.1 mV to 64.4 mV ± 44.5 mV) muscles. This study demonstrates that lower leg muscle activity is modulated across the foot posture spectrum wearing non-textured and textured foot orthoses. Furthermore, in the development of new orthoses designs, specifically with texture, foot posture remains an important consideration when clinicians interpret EMG results and academics are designing new experimental protocols.

Distribution of nerve endings in human thumb interphalangeal joint.

This study aims to quantitatively analyze the distribution of encapsulated nerve endings in the human thumb interphalangeal (IP) joint capsule. There are three types of nerve endings. Type-I nerve endings (Ruffini-like ending) sense pressure changes, Type II (Pacini-like ending) nerve endings contribute to the kinesthetic sense, and Type III (Golgi-like ending) nerve ending provides proprioceptive information. We dissected five right thumbs IP joints from freshly frozen cadavers (5 men). The mean age of the cadavers at the time of death was 63.4 years (55-73). Sections were stained with the hematoxylin-eosin and antiprotein gene product 9.5 (PGP9.5) to identify encapsulated nerve endings. Transverse sections were cut and divided into volar, dorsal, and then into two equal parts, proximal and distal. The density of encapsulated nerve endings compared to volar versus dorsal and proximal versus distal regions was examined. This study showed that type 1 nerve endings were more common in the distal parts of the IP joint (p < 0.05). Also, type 3 nerve endings were observed in the thumb IP joint. There was no difference between regions in type II and type III nerve endings. The current study demonstrates that the distribution of encapsulated nerve endings in the IP joint is different from the PIP and DIP joints. Moreover, further studies are required to understand the thumb's physiology.

Mechanosensory encoding in ex vivo muscle-nerve preparations.

Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo studies, stretch-evoked firing for confirmed MS afferents in the ex vivo preparation was markedly reduced in firing rate and deficient in encoding dynamic features of muscle stretch. These deficiencies precluded conventional means of discriminating type Ia and II afferents. Muscle afferents, including confirmed Ib afferents were often indistinguishable based on their similar firing responses to the same physiologically relevant stretch paradigms. These observations raise uncertainty about conclusions drawn from earlier ex vivo studies that either attribute findings to specific afferent types or suggest an absence of treatment effects on dynamic firing. However, we found that replacing the recording solution with bicarbonate buffer resulted in afferent firing rates and profiles more like those seen in vivo. Improving representation of the distinctive sensory encoding properties in ex vivo muscle-nerve preparations will promote accuracy in assigning molecular markers and mechanisms to heterogeneous types of muscle mechanosensory neurons.

An adeno-associated viral labeling approach to visualize the meso- and microanatomy of mechanosensory afferents and autonomic innervation of the rat urinary bladder.

The urinary bladder is supplied by a rich network of sensory and autonomic axons, commonly visualized by immunolabeling for neural markers. This approach demonstrates overall network patterning but is less suited to understanding the structure of individual motor and sensory terminals within these complex plexuses. There is a further limitation visualizing the lightly myelinated (A-delta) class of sensory axons that provides the primary mechanosensory drive for initiation of voiding. Whereas most unmyelinated sensory axons can be revealed by immunolabeling for specific neuropeptides, to date no unique neural marker has been identified to immunohistochemically label myelinated visceral afferents. We aimed to establish a non-surgical method to visualize and map myelinated afferents in the bladder in rats. We found that in rats, the adeno-associated virus (AAV), AAV-PHP.S, which shows a high tropism for the peripheral nervous system, primarily transduced myelinated dorsal root ganglion neurons, enabling us to identify the structure and regional distribution of myelinated (mechanosensory) axon endings within the muscle and lamina propria of the bladder. We further identified the projection of myelinated afferents within the pelvic nerve and lumbosacral spinal cord. A minority of noradrenergic and cholinergic neurons in pelvic ganglia were transduced, enabling visualization and regional mapping of both autonomic and sensory axon endings within the bladder. Our study identified a sparse labeling approach for investigating myelinated sensory and autonomic axon endings within the bladder and provides new insights into the nerve-bladder interface.

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering.

Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

Colon Conundrum: A Fascinating Case Report Unraveling the Enigmatic Tactoid Bodies.

Tactile corpuscle-like bodies (TCLBs) are specialized mechanoreceptors found in the dermal papilla of glabrous skin. They are normally not found in the gastrointestinal (GI) mucosa. There has been an increase in incidental detection in the GI mucosa due to the widespread use of colonoscopy procedures. However, TCLB's clinical implications in the GI tract remain unknown. We present a case of a 74-year-old man who was noted to have TCLBs in the rectosigmoid mucosa following resection for iatrogenic perforation. The TCLBs were spindle-shaped, positive for S-100, and negative for CD68. We review the literature on TCLBs in the GI tract and discuss their potential function in the GI mucosa.

Wrist proprioception-An update on scientific insights and clinical implications in rehabilitation of the wrist.

The field of wrist proprioception, as it relates to rehabilitation and surgery, has gone through a period of intense growth in the past decade. From being primarily focused on the function of the joint and ligaments in patients with wrist trauma or after wrist surgery, the understanding is now that of a greater complexity in treating not just the wrist but the hand and arm as a whole. Proprioception is derived from the Latin words "proprius" - belonging to (oneself) and "-ception" to sense. In other words, how to sense ourselves. To have a complete sense of self, multiple sensory afferents originating from joints, ligaments, muscles, tendons, nerves, skin, vision, and hearing work together to orchestrate a balanced integration of sensorimotor functions, with the true goal to perceive and adapt to the physical world around us. In this update on wrist proprioception, we review current developments in the understanding of proprioception, with an implication for our everyday work as hand therapists and hand surgeons. Each contributing sense-joint, ligaments, muscles, skin, and brain-will be reviewed, and the clinical relevance will be discussed. An updated wrist rehabilitation protocol is proposed where the therapist is guided to rehabilitate a patient after wrist trauma and/or surgery in 4 stages: (1) basic hand and wrist rehabilitation with a focus on reducing edema, pain, and scar formation; (2) proprioception awareness to improve the sense of joint motion and position; (3) conscious neuromuscular rehabilitation where isometric exercises of muscles that are beneficial for a particular injury are promoted, whereas others that are potentially harmful are avoided; and (4) unconscious neuromuscular rehabilitation with training of the reflex and joint protective senses.

Is There a Difference in the Distribution of Mechanoreceptors among the Three Sections of the Anterior Talofibular Ligament?

BACKGROUND: We investigated whether the distribution of mechanoreceptors in three sections of the anterior talofibular ligament (ATFL) differed. METHODS: The ATFL was obtained from 29 ankles of 21 fresh-frozen cadavers and divided into fibular attachment, mid-ligament, and talar attachment parts. Histologically, mechanoreceptors were classified as Ruffini (type I), Vater-Pacini (type II), Golgi-Mazzoni (type III), and free nerve ending corpuscles (type IV); the presence of these mechanoreceptors was compared among the three ATFL sections. RESULTS: Type I mechanoreceptors were significantly more numerous than the other receptor types. Comparing the three sections of the ATFL, the number of type I mechanoreceptors differed significantly between the mid-ligament and fibular attachment (p = 0.006), while the number of type III mechanoreceptors differed significantly between the talar and fibular attachments (p = 0.005) and between the mid-ligament and talar attachment (p = 0.011). CONCLUSIONS: The four types of mechanoreceptors were distributed differently among the three sections of the ATFL. Type I mechanoreceptors were more numerous in all sections compared to the other receptors.