A genetically humanized mouse model for hepatitis C virus infection

Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo

Sleep in care homes

Sleep problems in older adults are common and disturbance in sleep is associated with increased mortality. These problems are more pronounced in the care home population because of institutional factors and a high prevalence of frailty and comorbidity. This article reviews the randomized controlled trials undertaken to address sleep problems in care homes. These suggest that standalone therapies – oral melatonin and light therapy – have no effect on sleep but that combination treatments – physical exercise plus sleep hygiene, physical exercise plus sleep hygiene plus light and melatonin plus light – may have positive effects. These effects are more marked for daytime arousal than nocturnal sleep. Practical considerations for care homes are how to maximise light exposure, incorporate exercise into daily routines and minimize night-time disruption for residents. Trials undertaken so far are compromised by small sample size and inappropriate randomization strategies and further research is therefore required

Reduced intensity conditioning haematopoietic stem cell transplantation with mesenchymal stromal cells infusion for the treatment of metachromatic leukodystrophy: a case report.

We report the case of a 23-year-old woman who presented with an adult form of metachromatic leukodystrophy (MLD) evolving over one year with a progressive neurological deterioration. A non-myeloablative matched related haematopoietic stem cell transplantation (HSCT) with concomitant mesenchymal stromal cells (MSCs) infusion was performed. Engraftment occurred rapidly with no significant toxicity or side effects following the MSC infusion. At a follow up of 40 months, the patient had a stabilisation of all neurological manifestations of her disease. This case report suggests the feasibility and the potential efficacy of reduced intensity conditioning (RIC) allogeneic HSCT combined with MSC infusion for patients with the adult form of MLD.Case ReportsJournal Articleinfo:eu-repo/semantics/publishe

Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study.

Mesenchymal stromal cells (MSCs) are important in the support of hematopoiesis. In this pilot study, we evaluated the safety and efficiency of donor-expanded MSC infusion after allogeneic hematopoietic stem cell transplantation (HSCT) in six patients with poor hematopoietic recovery. MSCs were infused without HSC and without conditioning at a dose of 1 x 10(6)/kg weight. Two patients displayed rapid hematopoietic recovery (days 12 and 21), and four patients showed no response. The two patients who showed hematopoietic recovery were in first complete remission (CR1) compared to the other heavily pretreated patients. There were no toxic side effects linked to MSC infusion. One patient developed cytomegalovirus (CMV) reactivation 12 days following the MSC infusion and died from CMV disease. We found that infusion of MSCs without HSC co-infusion can restore medullary function in some patients with poor hematopoietic recovery. Our data suggest that patients with a less damaged stroma could benefit from this approach.Journal Articleinfo:eu-repo/semantics/publishe

A shared care approach to the management of erectile dysfunction in the community

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of underlying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Botulinum toxin for dysphagia due to cricopharyngeal dysfunction

Botulinum injection in the cricopharyngeal muscle has not yet been described thoroughly. In reviewing the literature, only 24 cases were found in which botulinum injection was used to treat cricopharyngeal dysfunction. We want to add another four cases and discuss specific indications and necessary pre-treatment examinations. Depending on the patient's history and the clinical findings, botulinum injection may be performed. Manometry and videofluoroscopy are not mandatory. The type of functional pathology defines whether botulinum toxin will be a definite treatment or a temporary relief.SCOPUS: ar.jinfo:eu-repo/semantics/publishe