Probing the properties of PTEN specific botulinum toxin type E mutants.

Botulinum neurotoxins (BoNT) are established biopharmaceuticals for neuromuscular and secretory conditions based on their ability to block neurotransmitter release from neurons by proteolyzing specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, a mutant catalytic domain of serotype E (LC/E) exhibiting 16 mutations was reported to cleave the phosphatase and tensin homolog (PTEN). This molecule represents an attractive new target in neurons as several reports support PTEN knockdown as a strategy to stimulate axonal regeneration after injury.

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease.

People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD.

Safe Use of POEM in a Patient With Decompensated Cirrhosis and Severe Achalasia.

Patients with both achalasia and decompensated cirrhosis can often present a therapeutic challenge because portal hypertension has generally been considered a contraindication to definitive therapies for achalasia. This case report depicts a patient who presented with progressive dysphagia, weight loss, and large-volume ascites; was diagnosed with type II achalasia and decompensated cirrhosis without esophageal varices; and underwent peroral endoscopic myotomy after preprocedural transjugular intrahepatic portosystemic shunt placement. Our case highlights the importance of multidisciplinary care and need for definitive therapies for these complex patients at high risk of malnutrition and sarcopenia.

A low-profile electromechanical packaging system for soft-to-flexible bioelectronic interfaces.

Interfacing the human body with the next generation of electronics requires technological advancement in designing and producing bioelectronic circuits. These circuits must integrate electrical functionality while simultaneously addressing limitations in mechanical compliance and dynamics, biocompatibility, and consistent, scalable manufacturing. The combination of mechanically disparate materials ranging from elastomers to inorganic crystalline semiconductors calls for modular designs with reliable and scalable electromechanical connectors.

Initial multicenter experience using a novel articulating through-the-scope traction device for endoscopic submucosal dissection.

A single-operator, articulating, through-the-scope (TTS) traction device was recently developed to facilitate endoscopic submucosal dissection (ESD). Clinical data on the performance of this device are limited. We report an initial multicenter experience with ESD using this articulating TTS traction device.

Integration of hydrogels in microfabrication processes for bioelectronic medicine: Progress and outlook.

Recent research aiming at the development of electroceuticals for the treatment of medical conditions such as degenerative diseases, cardiac arrhythmia and chronic pain, has given rise to microfabricated implanted bioelectronic devices capable of interacting with host biological tissues in synergistic modalities. Owing to their multimodal affinity to biological tissues, hydrogels have emerged as promising interface materials for bioelectronic devices. Here, we review the state-of-the-art and forefront in the techniques used by research groups for the integration of hydrogels into the microfabrication processes of bioelectronic devices, and present the manufacturability challenges to unlock their further clinical deployment.

Epidural electrical stimulation of the cervical dorsal roots restores voluntary upper limb control in paralyzed monkeys.

Regaining arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control has limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury, using spinal cord stimulation.

A modular strategy for next-generation upper-limb sensory-motor neuroprostheses.

Neuroprosthetics is a discipline that aims at restoring lost functions to people affected by a variety of neurological disorders or neurotraumatic lesions. It combines the expertise of computer science and electrical, mechanical, and micro/nanotechnology with cellular, molecular, and systems neuroscience. Rapid breakthroughs in the field during the past decade have brought the hope that neuroprostheses can soon become a clinical reality, in particular-as we will detail in this review-for the restoration of hand functions.

[Monoclonal gammopathies and kidney: a diagnostic challenge without any clues].

Diagnosis of monoclonal gammopathy of renal significance (MGRS) with histopathologic features of proliferative GN with monoclonal immunoglobulin deposits (PGNMID) is a challenge for clinicians because of the absence of laboratory findings suggestive of glomerular involvement in paraproteinemia. Renal biopsy remains the gold standard for diagnosis of PGNMID because it is a monoclonal gammopathy with kidney damage often "without a detectable serum/urine clone". Through this case report, we want to focus on the complexity both in the diagnostic process and in monitoring the renal-hematological response to therapy.

Characterizing and Modeling Smoking Behavior Using Automatic Smoking Event Detection and Mobile Surveys in Naturalistic Environments: Observational Study.

Background: There are 1.1 billion smokers worldwide, and each year, more than 8 million die prematurely because of cigarette smoking. More than half of current smokers make a serious quit every year.

Biomedical Microtechnologies Beyond Scholarly Impact.

The recent tremendous advances in medical technology at the level of academic research have set high expectations for the clinical outcomes they promise to deliver. To the demise of patient hopes, however, the more disruptive and invasive a new technology is, the bigger the gap is separating the conceptualization of a medical device and its adoption into healthcare systems. When technology breakthroughs are reported in the biomedical scientific literature, news focus typically lies on medical implications rather than engineering progress, as the former are of higher appeal to a general readership.

Chronic recording of cortical activity underlying vocalization in awake minipigs.

Background: Investigating brain dynamics underlying vocal production in animals is a powerful way to inform on the neural bases of human speech. In particular, brain networks underlying vocal production in non-human primates show striking similarities with the human speech production network. However, despite increasing findings also in birds and more recently in rodents, the extent to which the primate vocal cortical network model generalizes to other non-primate mammals remains unclear.

Extended Barrier Lifetime of Partially Cracked Organic/Inorganic Multilayers for Compliant Implantable Electronics.

Flexible and soft bioelectronics display conflicting demands on miniaturization, compliance, and reliability. Here, the authors investigate the design and performance of thin encapsulation multilayers against hermeticity and mechanical integrity. Partially cracked organic/inorganic multilayer coatings are demonstrated to display surprisingly year-long hermetic lifetime under demanding mechanical and environmental loading.

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams.

Dimensional scaling of thin-film stimulation electrode systems in translational research.

Electrical stimulation of biological tissue is an established technique in research and clinical practice that uses implanted electrodes to deliver electrical pulses for a variety of therapies. Significant research currently explores new electrode system technologies and stimulation protocols in preclinical models, aiming at both improving the electrode performance and confirming therapeutic efficacy. Assessing the scalability of newly proposed electrode technology and their use for tissue stimulation remains, however, an open question.

Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival, impairs neurological recovery, increases the risk of cardiovascular disease, and reduces quality of life. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury, and restored walking after paralysis.

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear.

Correction to: Functional and clinical significance of ROR1 in lung adenocarcinoma.

An amendment to this paper has been published and can be accessed via the original article.

Guidelines to Study and Develop Soft Electrode Systems for Neural Stimulation.

Electrical stimulation of nervous structures is a widely used experimental and clinical method to probe neural circuits, perform diagnostics, or treat neurological disorders. The recent introduction of soft materials to design electrodes that conform to and mimic neural tissue led to neural interfaces with improved functionality and biointegration. The shift from stiff to soft electrode materials requires adaptation of the models and characterization methods to understand and predict electrode performance.

Reveal Temporal Patterns of Smoking Behavior in Real Life Using Data Acquired through Automatic Tracking Systems.

Accurately monitoring and modeling smoking behavior in real life settings is critical for designing and delivering appropriate smoking-cessation interventions through mHealth applications. In this paper, we inspect smoking patterns based on data collected from 52 volunteers during a 4-week period of their everyday lives. These data are acquired by an automatic data acquisition system comprising an electric lighter, two wearable sensors and one mobile phone, which together can automatically track smoking events, collect concurrent context and physiology, and trigger pop-up questionnaires.

Relationship Between Chronic Stress and Heart Rate Over Time Modulated by Gender in a Cohort of Office Workers: Cross-Sectional Study Using Wearable Technologies.

Background: Chronic stress is increasing in prevalence and is associated with several physical and mental disorders. Although it is proven that acute stress changes physiology, much less is known about the relationship between physiology and long-term stress. Continuous measurement of vital signs in daily life and chronic stress detection algorithms could serve this purpose.

Structured nanoscale metallic glass fibres with extreme aspect ratios.

Micro- and nanoscale metallic glasses offer exciting opportunities for both fundamental research and applications in healthcare, micro-engineering, optics and electronics. The scientific and technological challenges associated with the fabrication and utilization of nanoscale metallic glasses, however, remain unresolved. Here, we present a simple and scalable approach for the fabrication of metallic glass fibres with nanoscale architectures based on their thermal co-drawing within a polymer matrix with matched rheological properties.

Soft, Implantable Bioelectronic Interfaces for Translational Research.

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab-based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e-dura.

Skin immunity and its dysregulation in atopic dermatitis, hidradenitis suppurativa and vitiligo.

While the epidermis is the frontline defense against infections and indeed, it is a peripheral lymphoid organ, the same immunological mechanisms may initiate and sustain pathological conditions. Indeed, a deregulated action against exogenous pathogens could activate a T cell response in atopic dermatitis, hidradenitis suppurativa and vitiligo. Atopic dermatitis (AD) is a chronic inflammatory skin condition with a complex pathophysiology.