Tubular aggregate myopathy causing progressive fatiguable weakness.

Tubular aggregate myopathies comprise a rare group of disorders with characteristic pathological findings and heterogeneous phenotypes, including myasthenic syndrome. We describe a patient with tubular aggregate myopathy who presented with fatiguable weakness improving with pyridostigmine, respiratory involvement and possible cardiac manifestations. We highlight the utility of muscle biopsy in atypical myasthenic syndrome.

3D Motion Analysis for the Assessment of Dynamic Coupling in Transtibial Prosthetics: A Proof of Concept.

Assessment of coupling between transtibial sockets and users is historically based on clinicians' observations and experience, but can be inaccurate and unreliable. Therefore, we present a proof of concept, for five out of six possible degrees of freedom coupling metric system for a socket, using motion analysis calibrated on a 3D printed limb substitute. The method is compatible with any socket suspension method and does not require prior modifications to the socket. Calibration trials were used to locate the axis of rotation of the knee joint referenced against a marker cluster on the thigh; this allowed for the identification of the limb during test trials despite the entire residuum being obscured from view by the socket. The error in the technique was found to be within 0.7 mm in displacement and 0.7 degrees in rotation, based on the control data. Dynamic testing showed the Inter Quartile Range (IQR) of inter time step variance was <0.5 mm/deg for all metrics. The method can form a basis for objective socket evaluation, improve clinical practice and the quality of life for amputees.

Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats.

Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation (RAD) may play beneficial roles in attenuating oxidative stress and sympathetic activity in hypertension. This study investigated the impact of selective RAD on hypertension and vascular remodeling. Nine-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to selective renal afferent denervation (RAD) with 33 mM of capsaicin for 15 min. Treatment with the vehicle of capsaicin was used as a control. The selective denervation was confirmed by the reduced calcitonin gene-related peptide expression and the undamaged renal sympathetic nerve activity response to the stimulation of adipose white tissue. Selective RAD reduced plasma norepinephrine levels, improved heart rate variability (HRV) and attenuated hypertension in SHR.It reduced NADPH oxidase (NOX) expression and activity, and superoxide production in the hypothalamic paraventricular nucleus (PVN), aorta and mesenteric artery of SHR. Moreover, the selective RAD attenuated the vascular remodeling of the aorta and mesenteric artery of SHR. These results indicate that selective removal of renal afferents attenuates sympathetic activity, oxidative stress, vascular remodeling and hypertension in SHR. The attenuated superoxide signaling in the PVN is involved in the attenuation of sympathetic activity in SHR, and the reduced sympathetic activity at least partially contributes to the attenuation of vascular oxidative stress and remodeling in the arteries of hypertensive rats.

The Use of Smartphone Photogrammetry to Digitise Transtibial Sockets: Optimisation of Method and Quantitative Evaluation of Suitability.

The fit of a lower limb prosthetic socket is critical for user comfort and the quality of life of lower limb amputees. Sockets are conventionally produced using hand-crafted patient-based casting techniques. Modern digital techniques offer a host of advantages to the process and ultimately lead to improving the lives of amputees. However, commercially available scanning equipment required is often expensive and proprietary. Smartphone photogrammetry could offer a low cost alternative, but there is no widely accepted imaging technique for prosthetic socket digitisation. Therefore, this paper aims to determine an optimal imaging technique for whole socket photogrammetry and evaluate the resultant scan measurement accuracy. A 3D printed transtibial socket was produced to create digital and physical twins, as reference models. The printed socket was photographed from 360 positions and simplified genetic algorithms were used to design a series of experiments, whereby a collection of photos were processed using Autodesk ReCap. The most fit technique was used to assess accuracy. The accuracy of the socket wall volume, surface area and height were 61.63%, 99.61% and 99.90%, respectively, when compared to the digital reference model. The scanned model had a wall thickness ranging from 2.075 mm at the top to 7.758 mm towards the base of the socket, compared to a consistent thickness of 2.025 mm in the control model. The technique selected did not show sufficient accuracy for clinical application due to the degradation of accuracy nearer to the base of the socket interior. However, using an internal wall thickness estimation, scans may be of sufficient accuracy for clinical use; assuming a uniform wall thickness.

Electrical impedance guides electrode array in cochlear implantation using machine learning and robotic feeder.

Cochlear Implant provides an electronic substitute for hearing to severely or profoundly deaf patients. However, postoperative hearing outcomes significantly depend on the proper placement of electrode array (EA) into scala tympani (ST) during cochlear implant surgery. Due to limited intra-operative methods to access array placement, the objective of the current study was to evaluate the relationship between EA complex impedance and different insertion trajectories in a plastic ST model. A prototype system was designed to measure bipolar complex impedance (magnitude and phase) and its resistive and reactive components of electrodes. A 3-DoF actuation system was used as an insertion feeder. 137 insertions were performed from 3 different directions at a speed of 0.08 mm/s. Complex impedance data of 8 electrode pairs were sequentially recorded in each experiment. Machine learning algorithms were employed to classify both the full and partial insertion lengths. Support Vector Machine (SVM) gave the highest 97.1% accuracy for full insertion. When a real-time prediction was tested, Shallow Neural Network (SNN) model performed better than other algorithms using partial insertion data. The highest accuracy was found at 86.1% when 4 time samples and 2 apical electrode pairs were used. Direction prediction using partial data has the potential of online control of the insertion feeder for better EA placement. Accessing the position of the electrode array during the insertion has the potential to optimize its intraoperative placement that will result in improved hearing outcomes.

Mock circulatory loops used for testing cardiac assist devices: A review of computational and experimental models.

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD's performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.

A Capacitive Cochlear Implant Electrode Array Sensing System to Discriminate Fold-Over Pattern.

Purpose During insertion of the cochlear implant electrode array, the tip of the array may fold back on itself and can cause serious complications to patients. This article presents a sensing system for cochlear implantation in a cochlear model. The electrode array fold-over behaviors can be detected by analyzing capacitive information from the array tip. Method Depending on the angle of the array tip against the cochlear inner wall when it enters the cochlear model, different insertion patterns of the electrode array could occur, including smooth insertion, buckling, and fold-over. The insertion force simulating the haptic feedback for surgeons and bipolar capacitance signals during the insertion progress were collected and compared. The Pearson correlation coefficient (PCC) was applied to the collected capacitive signals to discriminate the fold-over pattern. Results Forty-six electrode array insertions were conducted and the deviation of the measured insertion force varies between a range of 20% and 30%. The capacitance values from electrode pair (1, 2) were recorded for analyzing. A threshold for the PCC is set to be 0.94 that can successfully discriminate the fold over insertions from the other two types of insertions, with a success rate of 97.83%. Conclusions Capacitive measurement is an effective method for the detection of faulty insertions and the maximization of the outcome of cochlear implantation. The proposed capacitive sensing system can be used in other tissue implants in vessels, spinal cord, or heart.

A Novel Capacitive Cochlear Implant Electrode Array Sensing System to Discriminate Failure Patterns.

OBJECTIVES: The research is to propose a sensing system to ensure the electrode array being correctly placed inside the cochlea. Instead of applying extra sensors to the array, the capacitive information from multiple points of the array is gathered and analyzed to determine the state and behavior of the electrode array. METHODS: The sensing system measures electrode bipolar capacitances between multiple pairs of electrodes during the insertion. The principal component analysis (PCA) method is then applied to analysis the recorded data to discriminate insertion patterns. RESULTS: In total, 384 capacitance profiles from electrode pair (1, 2), and electrode pair (15, 16) were analyzed and compared. In an account of both the electrode pairs, the threshold distance was examined to be d = 1.99 at the average comparison type. The experiment results showed the success rate is over 80% to identify buckling during the insertion on a 2D cochlear model. CONCLUSION: This early-stage investigation shows great potential compared with the current practice, which does not provide any feedback to surgeons. The system demonstrates the feasibility of a sensing method for auto-reoccupation electrodes behavior, and it will help surgeons to avoid misplacement of the electrode array inside the cochlea.

Host fibrinogen drives antimicrobial function in Staphylococcus aureus peritonitis through bacterial-mediated prothrombin activation.

The blood-clotting protein fibrinogen has been implicated in host defense following Staphylococcus aureus infection, but precise mechanisms of host protection and pathogen clearance remain undefined. Peritonitis caused by staphylococci species is a complication for patients with cirrhosis, indwelling catheters, or undergoing peritoneal dialysis. Here, we sought to characterize possible mechanisms of fibrin(ogen)-mediated antimicrobial responses. Wild-type (WT) (Fib+) mice rapidly cleared S. aureus following intraperitoneal infection with elimination of ∼99% of an initial inoculum within 15 min. In contrast, fibrinogen-deficient (Fib-) mice failed to clear the microbe. The genotype-dependent disparity in early clearance resulted in a significant difference in host mortality whereby Fib+ mice uniformly survived whereas Fib- mice exhibited high mortality rates within 24 h. Fibrin(ogen)-mediated bacterial clearance was dependent on (pro)thrombin procoagulant function, supporting a suspected role for fibrin polymerization in this mechanism. Unexpectedly, the primary host initiator of coagulation, tissue factor, was found to be dispensable for this antimicrobial activity. Rather, the bacteria-derived prothrombin activator vWbp was identified as the source of the thrombin-generating potential underlying fibrin(ogen)-dependent bacterial clearance. Mice failed to eliminate S. aureus deficient in vWbp, but clearance of these same microbes in WT mice was restored if active thrombin was administered to the peritoneal cavity. These studies establish that the thrombin/fibrinogen axis is fundamental to host antimicrobial defense, offer a possible explanation for the clinical observation that coagulase-negative staphylococci are a highly prominent infectious agent in peritonitis, and suggest caution against anticoagulants in individuals susceptible to peritoneal infections.

Noise Exposure on Human Cochlea During Cochleostomy Formation Using Conventional and a Hand Guided Robotic Drill.

OBJECTIVE: To investigate the disturbance induced in the cochlea during cochleostomy using conventional drill and a hand guided robotic drill. STUDY DESIGN: The study is based on experimental measurements using the Laser Doppler Vibrometer during the drilling processes converted to Sound Pressure Levels (SPL) for comparison. SETTING: The study is based on experimental results of three sets of cochleostomies on human cadaver heads. MAIN OUTCOME MEASURE(S): Robotic drilling, in comparison to the conventional drilling method, creates a consistently lower level of disturbance in cochlea across the hearing frequency range. RESULTS: Robotic drilling, in comparison to the conventional drilling method, creates a consistently lower level of disturbance in cochlea across the hearing frequency range. CONCLUSIONS: It is reasonable to conclude that robotic drilling has a lower possibility of creating acoustic trauma in cochlea that endangers the residual hearing of patients.

A review of implantable pulsatile blood pumps: Engineering perspectives.

It has been reported that long-term use of continuous-flow mechanical circulatory support devices (CF-MCSDs) may induce complications associated with diminished pulsatility. Pulsatile-flow mechanical circulatory support devices (PF-MCSDs) have the potential of overcoming these shortcomings with the advance of technology. In order to promote in-depth understanding of PF-MCSD technology and thus encourage future mechanical circulatory support device innovations, engineering perspectives of PF-MCSD systems, including mechanical designs, drive mechanisms, working principles, and implantation strategies, are reviewed in this article. Some emerging designs of PF-MCSDs are introduced, and possible elements for next-generation PF-MCSDs are identified.

Online sample clean-up and enrichment of proteins from salty media with dynamic double gradients on a paper fluidic channel.

Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10-300 mg‧L-1 (R2 = 0.99) with a limit of detection (LOD) of 4.9 mg‧L-1. Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (ɑ = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples.

Novel field amplification for sensitive colorimetric detection of microalbuminuria on a paper-based analytical device.

Field-amplified stacking (FAS) is a commonly used method for enhancing the sensitivity of charged species from low conductive media in capillary electrophoresis. FAS also showed significant sensitivity enhancement effect on a uniform paper fluidic channel by proper design of the electrolyte. In this paper, a novel method of introducing electric field gradient is proposed by geometry design of a 2D paper fluidic channel, and field amplification effect was successfully demonstrated with reduced requirement on the sample's conductivity. Sensitive colorimetric detection of microalbuminuria (MAU) from urine samples was demonstrated by mobile phone camera. Experimental results showed that, with active electric field motivation, up to 93.5% of the loaded protein probe could be effectively transferred and stacked into a narrow band on the newly designed paper fluidic channel. A limit of detection (LOD) of 6.5 mg‧L-1 HSA was achieved with a dynamic range of 10-300 mg‧L-1 (linear in the range of 10-100 mg‧L-1, R2 = 0.991). Combined with selective staining of albumin with bromophenol blue (BPB), the established method was applied to the detection of MAU from clinical urine samples, and consistent results with that of the clinical method were obtained. With this paper-based analytical device (PAD), MAU from highly conductive urine samples can be directly loaded and detected without any pretreatment. This method provides a way to develop highly sensitive point-of-care test (POCT) for rapid screening of some diseases.

Imaging of pediatric neurovascular emergencies.

Pediatric strokes are rare but critical diagnoses to make in the emergency setting. They are associated with a set of pathologies that are not frequently encountered in the adult population. Some of these diseases have variable clinical presentations and imaging appearance depending on the age of onset and severity of the underlying pathologies. This article reviews the differential diagnoses and noninvasive imaging evaluation of pediatric cerebral ischemic and hemorrhagic diseases.

A hand-guided robotic drill for cochleostomy on human cadavers.

BACKGROUND: An arm supported robotic drill has been recently demonstrated for preparing cochleostomies in a pilot research clinical trial. In this paper, a hand-guided robotic drill is presented and tested on human cadaver trials. METHODS: The innovative smart tactile approach can automatically detect drilling mediums and decided when to stop drilling to prevent penetrating the endosteum. The smart sensing scheme has been implemented in a concept of a hand guided robotic drill. RESULTS: Experiments were carried out on two adult cadaveric human bodies for verifying the drilling process and successfully finished cochleostomy on three cochlea. The advantage over a system supported by a mechanical arm includes the flexibility in adjusting the trajectory to initiate cutting without slipping. Using the same concept as a conventional drilling device, the user will also be benefit from the lower setup time and cost, and lower training overhead. CONCLUSION: The hand-guided robotic drill was recently developed for testing on human cadavers. The robotic drill successfully prepared cochleostomies in all three cases.

Mechatronic feasibility of minimally invasive, atraumatic cochleostomy.

Robotic assistance in the context of lateral skull base surgery, particularly during cochlear implantation procedures, has been the subject of considerable research over the last decade. The use of robotics during these procedures has the potential to provide significant benefits to the patient by reducing invasiveness when gaining access to the cochlea, as well as reducing intracochlear trauma when performing a cochleostomy. Presented herein is preliminary work on the combination of two robotic systems for reducing invasiveness and trauma in cochlear implantation procedures. A robotic system for minimally invasive inner ear access was combined with a smart drilling tool for robust and safe cochleostomy; evaluation was completed on a single human cadaver specimen. Access to the middle ear was successfully achieved through the facial recess without damage to surrounding anatomical structures; cochleostomy was completed at the planned position with the endosteum remaining intact after drilling as confirmed by microscope evaluation.

Feasibility study of a hand guided robotic drill for cochleostomy.

The concept of a hand guided robotic drill has been inspired by an automated, arm supported robotic drill recently applied in clinical practice to produce cochleostomies without penetrating the endosteum ready for inserting cochlear electrodes. The smart tactile sensing scheme within the drill enables precise control of the state of interaction between tissues and tools in real-time. This paper reports development studies of the hand guided robotic drill where the same consistent outcomes, augmentation of surgeon control and skill, and similar reduction of induced disturbances on the hearing organ are achieved. The device operates with differing presentation of tissues resulting from variation in anatomy and demonstrates the ability to control or avoid penetration of tissue layers as required and to respond to intended rather than involuntary motion of the surgeon operator. The advantage of hand guided over an arm supported system is that it offers flexibility in adjusting the drilling trajectory. This can be important to initiate cutting on a hard convex tissue surface without slipping and then to proceed on the desired trajectory after cutting has commenced. The results for trials on phantoms show that drill unit compliance is an important factor in the design.

Role of p53 in preadipocyte differentiation.

Insulin resistance, diabetes and many kinds of cancers are common in overweight and obese individuals. The tumor suppressor p53 is important in securing genetic stability, but its role in the regulation of metabolic processes and cell differentiation remains unclear. We have investigated the role of p53 in adipocyte differentiation. Using 3T3-L1 cells, a mouse embryonic fibroblast preadipocyte model and DIO rat model, p53 expression and function during adipocyte differentiation were investigated. p53 expression increased on the second and fourth day of adipocyte differentiation and decreased thereafter. Its overexpression in 3T3-L1 preadipocytes markedly reduced adipogenesis and marker gene expression. p53 activity was weakened in DIO rat abdominal adipose tissue because of an decreased expression of its activated phosphorylated form. In contrast, p53 knockout enhanced adipogenesis and the expression of marker genes, but significantly reduced insulin-stimulated Akt phosphorylation. These results indicate that p53 partly suppresses preadipocyte differentiation and adipogenesis by regulating adipocyte gene expression and Akt signaling.

Comparison on intracochlear disturbances between drilling a manual and robotic cochleostomy.

During cochlear implantation, hearing preservation is a concern. Minimizing disturbances to the cochlea and protection of the underlying endosteal membrane during the formation of a cochleostomy are considered important factors. The robotic micro-drill system tested in this article is the first example of an autonomous surgical drill successfully producing a cochleostomy, which keeps the underlying endosteal membrane intact. This study compares induced disturbances within the cochlea during formation of cochleostomy using the robotic micro-drill with that of conventional manual drilling. The disturbance of the endosteal membrane is measured using a Microscope Scanning Vibrometer at a third window, produced in the cochlea. Results show that the highest velocity amplitude measured was associated with manual drilling technique. The robotic micro-drill technique produced only about 1% of the peak velocity amplitude seen in manual drilling and exhibited much more uniform behaviour, while keeping the underlying membrane intact. The technique applied when using the robotic drill could be a major step in reducing the trauma to the cochlea, by reducing disturbance levels.