Immediate-early protein of equid herpesvirus type 1 as a target for cytotoxic T-lymphocytes in the Thoroughbred horse.

Cytotoxic T-lymphocytes (CTLs) are associated with protective immunity against disease caused by equid herpesvirus type 1 (EHV-1). However, the EHV-1 target proteins for CTLs are poorly defined. This limits the development of vaccine candidates designed to stimulate strong CTL immunity. Here, classical CTL assays using lymphocytes from horses of three defined MHC class I types that experienced natural infection with EHV-1 and a modified vaccinia virus construct containing an EHV-1 gene encoding the immediate-early (IE) protein are reported. Horses homozygous for the equine leukocyte antigen (ELA)-A2 haplotype, but not the ELA-A5 haplotype, produced MHC-restricted CTL responses against the IE protein. Previously, horses homozygous for the ELA-A3 haplotype also mounted CTL responses against the IE protein. Both haplotypes are common in major horse breeds, including the Thoroughbred. Thus, the IE protein is an attractive candidate molecule for future studies of T-cell immunity to EHV-1 in the horse.

Walk-in telemental health clinics improve access and efficiency: a 2-year follow-up analysis.

INTRODUCTION: Telemedicine has demonstrated potential to improve access and quality of mental health services in underserved areas. Use of telemedicine to deliver health services may enable a range of synergistic innovations in care practices, but such innovations will require rigorous evaluation. MATERIALS AND METHODS: We evaluated a telemental health program designed to increase access by eliminating clinician travel time in a multisite rural community mental health center. The program included both traditionally scheduled and "open scheduled" clinics provided via telemedicine. An initial 13-month evaluation showed better access, quality, and sustainability compared with similar services delivered using traditional methods available elsewhere within the organization. A 24-month follow-up analysis was undertaken to determine if initial findings remained consistent. RESULTS: Telemedicine clinics continued to show remarkably consistent advantages in both access and quality compared with traditional services. Cost-efficiency gains were also robust, maintaining a 20-percentage-point advantage in conversion of scheduled time to billable time over traditional clinics. Much of this advantage was attributable to the 20% of clinic volume that was open-scheduled or "walk-in" in nature. CONCLUSIONS: This study confirms earlier findings that telemedicine technology can support synergistic innovations in service format (such as "open scheduling") and maintain measurable advantages in access and quality along with cost-efficiencies past the initial implementation period.

Receptor protein tyrosine phosphatases are novel components of a polycystin complex.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of PKD1 and PKD2 that encode polycystin-1 and polycystin-2. Polycystin-1 is tyrosine phosphorylated and modulates multiple signaling pathways including AP-1, and the identity of the phosphatases regulating polycystin-1 are previously uncharacterized. Here we identify members of the LAR protein tyrosine phosphatase (RPTP) superfamily as members of the polycystin-1complex mediated through extra- and intracellular interactions. The first extracellular PKD1 domain of polycystin-1 interacts with the first Ig domain of RPTPσ, while the polycystin-1 C-terminus of polycystin-1 interacts with the regulatory D2 phosphatase domain of RPTPγ. Additional homo- and heterotypic interactions between RPTPs recruit RPTPδ. The multimeric polycystin protein complex is found localised in cilia. RPTPσ and RPTPδ are also part of a polycystin-1/E-cadherin complex known to be important for early events in adherens junction stabilisation. The interaction between polycystin-1 and RPTPγ is disrupted in ADPKD cells, while RPTPσ and RPTPδ remain closely associated with E-cadherin, largely in an intracellular location. The polycystin-1 C-terminus is an in vitro substrate of RPTPγ, which dephosphorylates the c-Src phosphorylated Y4237 residue and activates AP1-mediated transcription. The data identify RPTPs as novel interacting partners of the polycystins both in cilia and at adhesion complexes and demonstrate RPTPγ phosphatase activity is central to the molecular mechanisms governing polycystin-dependent signaling. This article is part of a Special Issue entitled: Polycystic Kidney Disease.

Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo.

The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous studies have demonstrated that M33 is important for MCMV dissemination to or replication within the salivary glands. In this study, we probed N- and C-terminal regions of M33 as well as known 7TMR signature motifs in transmembrane (TM) II and TM III to determine the impact on cell surface expression, constitutive signaling, and in vivo phenotype. The region between amino acids R(340) and A(353) of the C terminus was found to be important for CREB- and NFAT-mediated signaling, although not essential for phosphatidylinositol turnover. Tagging or truncation of the N terminus of M33 resulted in loss of cell surface expression. Within TM II, an F79D mutation abolished constitutive signaling, demonstrating a role, as in other cellular and viral 7TMR, of TM II in receptor activation. In TM III, the arginine (but not the asparagine) residue of the NRY motif (the counterpart of the common DRY motif in cellular 7TMR) was found to be essential for constitutive signaling. Selected mutations incorporated into recombinant MCMV showed that disruption of constitutive signaling for a viral 7TMR homologue resulted in a reduced capacity to disseminate to or replicate in the salivary glands. In addition, HCMV UL33 was found to partially compensate for the lack of M33 in vivo, suggesting conserved biological roles of the UL33 gene family.

Adequacy of consent in patients with distal radius fractures.

Health professionals have a legal and ethical obligation to obtain a valid consent before any procedure. The aim of this study was to assess the adequacy of consent for treatment of distal radius fractures. It also outlines potential improvements that could be made. A study of patients undergoing treatment for distal radius fracture was undertaken. We analysed the risks and complications recorded on the consent form. The common recorded risks were infection (95.6%), vascular injuries (77.8%), nerve injuries (66.7%) and stiffness (42.2%); 31.1% of the consent forms had abbreviations. Junior doctors who consented the patients performed 6.7% of the procedures. The poor documentation of risks or complications indicates that patients are not given appropriate information to ensure that the consent is valid. Proper documentation and refining of consent forms is mandatory to ensure that all major risks are understood by patients. This could go a long way in preventing litigation.

Dislocation of the fibular head in an unusual sports injury: a case report.

INTRODUCTION: One of the primary functions of the proximal tibiofibular joint is slight rotation to accommodate rotational stress at the ankle. Proximal tibiofibular joint dislocation is a rare injury and accounts for less than 1% of all knee injuries. This dislocation has been reported in patients who had been engaged in football, ballet dancing, equestrian jumping, parachuting and snowboarding. CASE PRESENTATION: A 20-year-old man was injured whilst playing football. He felt a pop in the right knee and was subsequently unable to bear weight on it. The range of movement in his knee joint was limited. Anterior-posterior and lateral X-rays of the knee revealed anterolateral dislocation of the proximal tibiofibular joint. Comparison views confirmed the anterolateral dislocation. He had a failed manipulation under anaesthesia and the joint needed an open reduction in which the fibular head was levered back into place. Operative findings revealed a horizontal type of joint. CONCLUSION: An exceedingly rare dislocation of a horizontal type of proximal tibiofibular joint was presented following a football injury. This dislocation was irreducible by a closed method.