Continuous renal replacement therapy for lithium toxicity: A worthy treatment to avoid intradialytic hypotension and vasopressors.

While intermittent hemodialysis (HD) is the most efficient method of removing lithium in patients with lithium toxicity, continuous renal replacement therapy is an acceptable alternative in the setting of intradialytic hypotension. This form of dialysis can reduce the need for vasopressors during HD, which increases mortality.

Auditory and Visual Hallucinations Associated With Nitrofurantoin Use in an Inpatient Setting: A Case Report.

Nitrofurantoin has been utilized for the prevention and treatment of urinary tract infections (UTIs) since the 1950s, and it has been prescribed with increasing frequency since being recommended as a first-line therapy. The adverse neurological and psychiatric effects of antibiotic medications have been well-established. There is evidence to suggest a direct association between acute psychosis and antibiotic exposures. Nitrofurantoin-induced adverse effects have been reported recurrently; however, to the best of our knowledge, a combination of auditory and visual hallucinations with normal baseline mentation and cognition in an immunocompetent geriatric patient, without previously reported hallucinations, have not been reported in the literature so far. We present a case of an 86-year-old Caucasian female who was admitted with audio and visual hallucinations on the fifth day of starting nitrofurantoin therapy for UTI. During her stay, after ruling out all other probable etiologies, it was determined that the likely pathogenesis of the patient's neuropsychiatric effects was the use of nitrofurantoin.

A multiplexed ion-exchange membrane-based miRNA (MIX·miR) detection platform for rapid diagnosis of myocardial infarction.

Micro RNAs (miRNAs) have shown great potential as rapid and discriminating biomarkers for acute myocardial infarction (AMI) diagnosis. We have developed a multiplexed ion-exchange membrane-based miRNA (MIX·miR) preconcentration/sensing amplification-free platform for quantifying in parallel a panel of miRNAs, including miR-1, miR-208b, and miR-499, from the same plasma samples from: 1) reference subjects with no evident coronary artery disease (NCAD); 2) subjects with stable coronary artery disease (CAD); and 3) subjects experiencing ST-elevation myocardial infarction (STEMI) prior to (STEMI-pre) and following (STEMI-PCI) percutaneous coronary intervention. The picomolar limit of detection from raw plasma and 3-decade dynamic range of MIX·miR permits detection of the miRNA panel in untreated samples from disease patients and its precise standard curve, provided by large 0.1 to 1 V signals and eliminates individual sensor calibration. The use of molecular concentration feature reduces the assay time to less than 30 minutes and increases the detection sensitivity by bringing all targets close to the sensors. miR-1 was low for NCAD patients but more than one order of magnitude above the normal value for all samples from three categories (CAD, STEMI-pre, and STEMI-PCI) of patients with CAD. In fact, miR-1 expression levels of stable CAD, STEMI-pre and STEMI-PCI are each more than 10-fold higher than the previous class, in that order, well above the 95% confidence level of MIX·miR. Its overexpression estimate is significantly higher than the PCR benchmark. This suggests that, in contrast to protein biomarkers of myocardial injury, miR-1 appears to differentiate ischemia from both reperfusion injury and non-AMI CAD patients. The battery-operated MIX·miR can be a portable and low-cost AMI diagnostic device, particularly useful in settings where cardiac catheterization is not readily available to determine the status of coronary reperfusion.

Catastrophic Aortoenteric Fistula Due to an Eroding Bare Metal Duodenal Stent.

Deployment of bare metal duodenal stents for individuals with gastric outlet obstructions (GOOs) is a well-characterized measure to improve the quality of life. However, these interventions are palliative in nature and are associated with known complications. We present an unfortunate case of a previously not well described, albeit not surprising, a complication of stent placement. The individual underwent duodenal stent placement due to obstructive metastatic disease and subsequently presented for gastrointestinal (GI) bleed. It was determined that an aortoduodenal fistula acutely developed and, despite heroic efforts, the patient ultimately expired.

Erosive Twiddler's Syndrome: A Severe Case with Externalization of the Pacemaker.

Implantable pacemakers have been the mainstay of therapy for patients with severely decreased left ventricular ejection fractions and recurrent arrhythmias, among other cardiac pathology. Twiddler's syndrome (TS) is an uncommon but potentially life-threatening complication of pacemaker therapy, defined as pacemaker malfunction in the setting of device lead dislodgment due to physical manipulation. Traditionally, there are three distinct TS variants (reeling, ratchet and coiling). This case offers evidence of a unique and new variant of TS, severe recurrent erosive subtype with pacemaker externalization.

Electrochemically Enhanced Drug Delivery Using Polypyrrole Films.

The delivery of drugs in a controllable fashion is a topic of intense research activity in both academia and industry because of its impact in healthcare. Implantable electronic interfaces for the body have great potential for positive economic, health, and societal impacts; however, the implantation of such interfaces results in inflammatory responses due to a mechanical mismatch between the inorganic substrate and soft tissue, and also results in the potential for microbial infection during complex surgical procedures. Here, we report the use of conducting polypyrrole (PPY)-based coatings loaded with clinically relevant drugs (either an anti-inflammatory, dexamethasone phosphate (DMP), or an antibiotic, meropenem (MER)). The films were characterized and were shown to enhance the delivery of the drugs upon the application of an electrochemical stimulus in vitro, by circa (ca.) 10⁻30% relative to the passive release from non-stimulated samples. Interestingly, the loading and release of the drugs was correlated with the physical descriptors of the drugs. In the long term, such materials have the potential for application to the surfaces of medical devices to diminish adverse reactions to their implantation in vivo.

O-Mannosylation and human disease.

Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway.

Mammalian O-mannosylation: unsolved questions of structure/function.

Post-translational modification of polypeptides with glycans increases the diversity of the structures of proteins and imparts increased functional diversity. Here, we review the current literature on a relatively new O-glycosylation pathway, the mammalian O-mannosylation pathway. The importance of O-mannosylation is illustrated by the fact that O-mannose glycan structures play roles in a variety of processes including viral entry into cells, metastasis, cell adhesion, and neuronal development. Furthermore, mutations in the enzymes of this pathway are causal for a variety of congenital muscular dystrophies. Here we highlight the protein substrates, glycan structures, and enzymes involved in O-mannosylation as well as our gaps in understanding structure/function relationships in this biosynthetic pathway.

Intracellular protein glycosylation modulates insulin mediated lifespan in C.elegans.

O-linked-ß-N-acetylglucosamine (O-GlcNAc) modification is a regulatory, nuclear and cytoplasmic post-translational glycosylation of proteins associated with age-related diseases such as Alzheimer's, Parkinson's, and type II diabetes. Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems. InC. elegans, attenuation of the insulin-like signal transduction pathway increases adult lifespan of the nematode. We demonstrate that the O-GlcNAc cycling enzymes OGT and OGA, which add and remove O-GlcNAc respectively, modulate lifespan in C. elegans. Median adult lifespan is increased in an oga-1 deletion strain while median adult life span is decreased upon ogt-1 deletion. The O-GlcNAc-mediated effect on nematode lifespan is dependent on the FoxO transcription factor DAF-16. DAF-16 is a key factor in the insulin-like signal transduction pathway to regulate reproductive development, lifespan, stress tolerance, and dauer formation in C. elegans. Our data indicates that O-GlcNAc cycling selectively influences only a subset of DAF-16 mediated phenotypes, including lifespan and oxidative stress resistance. We performed an affinity purification of O-GlcNAc-modified proteins and observed that a high percentage of these proteins are regulated by insulin signaling and/or impact insulin pathway functional outcomes, suggesting that the O-GlcNAc modification may control downstream effectors to modulate insulin pathway mediated cellular processes.

Smart portable rehabilitation devices.

BACKGROUND: The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s). METHODS: In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device. RESULTS: Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit. CONCLUSION: Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved.