Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model.

Mutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson's disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN and PINK1, mutated in autosomal recessive PD, regulate the preferential autophagic clearance of dysfunctional mitochondria ("mitophagy") by inducing ubiquitylation of mitochondrial proteins, a process counteracted by deubiquitylation via USP30.

A high Q piezoelectric resonator as a portable VLF transmitter.

Very low frequency communication systems (3 kHz-30 kHz) enable applications not feasible at higher frequencies. However, the highest radiation efficiency antennas require size at the scale of the wavelength (here, >1 km), making portable transmitters extremely challenging. Facilitating transmitters at the 10 cm scale, we demonstrate an ultra-low loss lithium niobate piezoelectric electric dipole driven at acoustic resonance that radiates with greater than 300x higher efficiency compared to the previous state of the art at a comparable electrical size.

The discovery and optimization of benzimidazoles as selective Na1.8 blockers for the treatment of pain.

The voltage gated sodium channel Na1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole Na1.

Does overstuffing of the patellofemoral joint in total knee arthroplasty have a significant effect on postoperative outcomes?

Background: There is ongoing debate in the literature as to whether or not patellofemoral joint overstuffing has a clinically significant effect on postoperative outcomes following total knee arthroplasty (TKA). This study investigates the effect of patellofemoral joint overstuffing on patient-reported outcomes using novel methods of radiographic measurement.

Methods: The study population consisted of a prospective cohort of 266 patients receiving a Triathlon® (Stryker, Kalamazoo, MI, USA) TKA between 2006 and 2009.

Does the femoral offset affect replacements? The results from a National Joint Registry.

Background: Femoral component offset influences the torque forces exerted on a femoral stem and may therefore adversely affect femoral component survival. This study investigated the influence of femoral component offset on revision rates for primary total hip replacements (THR) registered on the New Zealand Joint Registry (NZJR).

Methods: There were 106,139 primary THRs registered, resulting in 4960 revisions for any cause.

The Use of Routine Postoperative Microscopy and Culture Screening Following Elective Hip and Knee Arthroplasty: An Unnecessary Cost With No Effect on Clinical Management?

Background: The use of microscopy and culture screening to detect pathogenic microorganisms followed by a decolonization protocol is a widely performed practice prior to elective hip and knee arthroplasty. In our center, the routine care of hip and knee arthroplasty also involves postoperative screening including direct culture of the surgical site. The aim of this study was to assess the frequency of pathogen detection following these tests and to determine whether routine postoperative screening, with particular reference to postoperative surgical site culture, led to any change in clinical management of these patients.

Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors.

This review examines the small molecules described over the past decade as inhibitors of any of the approximately 100 human deubiquitinating enzymes (DUBs). Structures from patent publications as well as from the primary literature are included. Inhibitors of two viral DUBs are also described since these proteases share structural similarity with one of the human DUB sub-families.

The long-term outcome of the Gschwend-Scheier-Bähler III elbow replacement.

Background: The Gschwend-Scheier-Bähler III (GSBIII) is a semiconstrained, sloppy-hinge total elbow replacement. We report the long-term functional and radiological outcome of a cohort of patients more than 10 years after surgery.

Methods: All GSBIII prostheses implanted from September 1996 to June 2004 were identified from our surgical database.

Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain.

Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Nav1.

A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability.

Background And Purpose: NaV 1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain. Here, we describe the effects of PF-01247324, a new generation, selective, orally bioavailable Nav 1.

Complications after revision surgery of malreduced ankle fractures.

Ankle fractures are common orthopedic injuries requiring reduction and cast immobilization or fixation. Fractures fixed in a malreduced (misaligned) position can require revision surgery. However, because this has been a relatively rare occurrence, little is known about the complications that can occur after such surgery.

Deubiquitylating enzymes and DNA damage response pathways.

Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention.

Functional and oncological outcome following marginal excision of well-differentiated forearm liposarcoma with nerve involvement.

Purpose: Liposarcoma is one of the most common soft tissue sarcomas in adults. It is often low-grade and can occasionally involve neurovascular structures. We present the functional and oncological outcome resulting from planned marginal excision of a series of forearm low-grade liposarcomas with nerve involvement.

Avulsion of the perforating branch of the peroneal artery secondary to an ankle sprain: a cause of acute compartment syndrome in the leg.

In this report, we describe the case of an adult male who developed an acute compartment syndrome localized to the anterior compartment of the leg following an ankle sprain. Compartment syndrome in association with ankle sprain is unusual, and has been previously described in association with avulsion of the perforating peroneal artery. Because of the potential for severe morbidity, we feel that it is important to make foot and ankle surgeons aware of this unusual injury.

Modulation of the partition coefficient between octanol and buffer at pH 7.4 and pKa to achieve the optimum balance of blood clearance and volume of distribution for a series of tetrahydropyran histamine type 3 receptor antagonists.

The relationship between rat pharmacokinetics and physicochemical parameters [the partition coefficient between octanol and buffer at pH 7.4 (log D((7.4))) and pK(a)] was studied for a series of tetrahydropyran compounds.

Subtype-specific actions of beta-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (alpha7, alpha4beta2, alpha3beta4) expressed in Xenopus laevis oocytes.

Two-electrode voltage-clamp electrophysiology has been used to study the actions of two amyloid peptides (Abeta(1-42), Abeta(1-40)) on alpha7, alpha4beta2 and alpha3beta4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes. The application of Abeta(1-42) or Abeta(1-40) (1 pM-100 nM) for 5 s does not directly activate expressed human alpha7, alpha4beta2 or alpha3beta4 nicotinic AChRs.Abeta(1-42) and Abeta(1-40) are antagonists of alpha7 nicotinic AChRs.