Myofibrillar myopathy caused by a mutation in the motor domain of mouse MyHC IIb

Ariel is a mouse mutant that suffers from skeletal muscle myofibrillar degeneration due to the rapid accumulation of large intracellular protein aggregates. This fulminant disease is caused by an ENU-induced recessive mutation resulting in an L342Q change within the motor domain of the skeletal muscle myosin protein MYH4 (MyHC IIb). Although normal at birth, homozygous mice develop hindlimb paralysis from Day 13, consistent with the timing of the switch from developmental to adult myosin isoforms in mice. The mutated myosin (MYH4(L342Q)) is an aggregate-prone protein. Notwithstanding the speed of the process, biochemical analysis of purified aggregates showed the presence of proteins typically found in human myofibrillar myopathies, suggesting that the genesis of ariel aggregates follows a pathogenic pathway shared with other conformational protein diseases of skeletal muscle. In contrast, heterozygous mice are overtly and histologically indistinguishable from control mice. MYH4(L342Q) is present in muscles from heterozygous mice at only 7% of the levels of the wild-type protein, resulting in a small but significant increase in force production in isolated single fibres and indicating that elimination of the mutant protein in heterozygotes prevents the pathological changes observed in homozygotes. Recapitulation of the L342Q change in the functional equivalent of mouse MYH4 in human muscles, MYH1, results in a more aggregate-prone protein.     

The role of sexually transmitted infections in the evolution of the South African HIV epidemic

Objectives To assess the extent to which sexually transmitted infections (STIs) have contributed to the spread of HIV in South Africa and to estimate the extent to which improvements in STI treatment have reduced HIV incidence. Methods A mathematical model was used to simulate interactions between HIV and six other STIs (genital herpes, syphilis, chancroid, gonorrhoea, chlamydial infection and trichomoniasis) as well as bacterial vaginosis and vaginal candidiasis. The effects of STIs on HIV transmission probabilities were assumed to be consistent with meta‐analytic reviews of observational studies, and the model was fitted to South African HIV prevalence data. Results The proportion of new HIV infections in adults that were attributable to curable STIs reduced from 39% (uncertainty range: 24–50%) in 1990 to 14% (8–18%) in 2010, while the proportion of new infections attributable to genital herpes increased. Syndromic management programmes are estimated to have reduced adult HIV incidence by 6.6% (3.3–10.3%) between 1994 and 2004, by which time syndromic management coverage was 52%. Had syndromic management been introduced in 1986, with immediate achievement of 100% coverage and a doubling of the rate of health seeking, HIV incidence would have reduced by 64% (36–82%) over the next decade, but had the same intervention been delayed until 2004, HIV incidence would have reduced by only 5.5% (2.8–9.0%). Conclusions Sexually transmitted infections have contributed significantly to the spread of HIV in South Africa, but STI control efforts have had limited impact on HIV incidence because of their late introduction and suboptimal coverage.     

Evaluation of a Commercial PCR Kit for Diagnosis of Cytomegalovirus Infection of the Central Nervous System

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.     

Supporting older people following out of hours discharge from the Emergency Department: An integrative review of the literature

Background

For many older people the emergency department (ED) is an important but sometimes difficult step in their healthcare journey. They often attend the ED with co and multi morbidities. Discharge home at evenings and weekends when post-discharge support services are limited can result in a delay or failure to follow through on their discharge plan leading to adverse health outcomes and in some cases, readmission to ED.

Objective

The aim of this integrative review was to identify and appraise the support available to older people following discharge from the ED out of hours (OOH).

Methods

For this review, out of hours referred to those times after 17.30 until 08.00 a.m. on Mondays to Fridays, all hours on weekends and public holidays. Whittemore and Knafl's (Journal of Advanced Nursing, 2005;52:546), framework was used to guide all stages of the review process. Articles were retrieved following a rigorous search of published works using various databases, the grey literature and hand search of the reference lists of the studies included.

Results

In total 31 articles were included in the review. These comprised systematic reviews, randomised control studies, cohort studies and surveys. Main themes identified included processes that enable support, support provision by health and social care professionals and telephone follow-up. Results identified a significant dearth of out of hours discharge research and a strong recommendation for more concise and thorough research in this important area of care transition.

Conclusion

Older person discharge home from the ED presents an associated risk as previous research has identified frequent readmission and periods of ill health and dependency. Out of hours discharge can be even more problematic when it may be difficult to arrange support services and ensure continuity of care. Further work in this area is required, taking cognisance of the findings and recommendations identified in this review.     

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.