Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor eIF-4A1

Control of translation initiation was recognised as a critical checkpoint for cell proliferation and tumorigenesis. In human melanoma cells, we have previously reported consistent overexpression of translation initiation factor eIF-4A1. Here, we investigated by transfection of antisense constructs its significance for the control of melanoma cell growth. The tetracycline-inducible expression system was established in melanoma cells, and three fragments of the 5′-, central-, and 3′-portion of the eIF-4A1 cDNA were subcloned in antisense and in sense orientation after a tetracycline inducible promoter. Significant proliferation decrease was obtained after transient transfection and induction of antisense RNA directed against the 5′- and the central portion (up to 10%), whereas, no effects were seen after induction of the 3′-fragment and the sense controls. Cell clones stably transfected with the central antisense fragment revealed after doxycycline induction reduced expression of endogeneous eIF-4A1 mRNA correlated with decreased proliferation rates (up to 6%). These data demonstrate the applicability of antisense strategies against translation factors in melanoma cells. Translation initiation factor eIF-4A1 contributes to the control of melanoma cell proliferation and may be taken into consideration when scheduling new therapeutic approaches targeting the translational control

Progress towards early detection services for infants with hearing loss in developing countries

BACKGROUND: Early detection of infants with permanent hearing loss through infant hearing screening is recognised and routinely offered as a vital component of early childhood care in developed countries. This article investigates the initiatives and progress towards early detection of infants with hearing loss in developing countries against the backdrop of the dearth of epidemiological data from this region. METHODS: A cross-sectional, descriptive study based on responses to a structured questionnaire eliciting information on the nature and scope of early hearing detection services; strategies for financing services; parental and professional attitudes towards screening; and the performance of screening programmes. Responses were complemented with relevant data from the internet and PubMed/Medline. RESULTS: Pilot projects using objective screening tests are on-going in a growing number of countries. Screening services are provided at public/private hospitals and/or community health centres and at no charge only in a few countries. Attitudes amongst parents and health care workers are typically positive towards such programmes. Screening efficiency, as measured by referral rate at discharge, was generally found to be lower than desired but several programmes achieved other international benchmarks. Coverage is generally above 90% but poor follow-up rates remain a challenge in some countries. The mean age of diagnosis is usually less than six months, even for community-based programmes. CONCLUSION: Lack of adequate resources by many governments may limit rapid nationwide introduction of services for early hearing detection and intervention, but may not deter such services altogether. Parents may be required to pay for services in some settings in line with the existing practice where healthcare services are predominantly financed by out-of-pocket spending rather than public funding. However, governments and their international development partners need to complement current voluntary initiatives through systematic scaling-up of public awareness and requisite manpower development towards sustainable service capacities at all levels of healthcare delivery

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The feasibility and acceptability of training volunteer mealtime assistants to help older acute hospital inpatients: the Southampton Mealtime Assistance Study.

AIMS AND OBJECTIVES: To determine the feasibility and acceptability of using trained volunteers as mealtime assistants for older hospital inpatients. BACKGROUND: Poor nutrition among hospitalised older patients is common in many countries and associated with poor outcomes. Competing time pressures on nursing staff may make it difficult to prioritise mealtime assistance especially on wards where many patients need help. DESIGN: Mixed methods evaluation of the introduction of trained volunteer mealtime assistants on an acute female medicine for older people ward in a teaching hospital in England. METHODS: A training programme was developed for volunteers who assisted female inpatients aged 70 years and over on weekday lunchtimes. The feasibility of using volunteers was determined by the proportion recruited, trained, and their activity and retention over one year. The acceptability of the training and of the volunteers' role was obtained through interviews and focus groups with 12 volunteers, nine patients and 17 nursing staff. RESULTS: Fifty-nine potential volunteers were identified: 38 attended a training session, of whom 29 delivered mealtime assistance, including feeding, to 3911 (76%) ward patients during the year (mean duration of assistance 5·5 months). The volunteers were positive about the practical aspects of training and ongoing support provided. They were highly valued by patients and ward staff and have continued to volunteer. CONCLUSIONS: Volunteers can be recruited and trained to help acutely unwell older female inpatients at mealtimes, including feeding. This assistance is sustainable and is valued. RELEVANCE TO CLINICAL PRACTICE: This paper describes a successful method for recruitment, training and retention of volunteer mealtime assistants. It includes a profile of those volunteers who provided the most assistance, details of the training programme and role of the volunteers and could be replicated by nursing staff in other healthcare units

Triggering dieback in an invasive plant: endophyte diversity and pathogenicity

Dieback causes a progressive reduction in plant population health, resulting in the death of plant parts and often plant death. It is prevalent in many invasive woody weeds in Australia and has been suggested as a potential mechanism for biocontrol of these species. Parkinsonia aculeata one such invasive tree in northern Australia. It has naturalised across a wide range of climatic zones and some populations have been heavily reduced by dieback occurrence. The cause(s) of dieback in parkinsonia remain elusive, although fungal endophytes have been previously implicated. In this study, we characterised the culturable fungal endophyte community of healthy and dieback-affected parkinsonia using culture-based techniques, and identified cultured isolates via amplicon sequencing of the internal transcribed spacer (ITS) of the rDNA operon. Eight isolates, identified as pathogens, were selected for a 10-week pathogenicity trial, including water stress treatments, on parkinsonia seedlings. We isolated a taxonomically diverse fungal community from parkinsonia, representing 54 unique species from 25 families. Communities were similar across healthy and dieback-affected plants, but differed by plant tissue. Of the eight putative pathogenic isolates tested in the pathogenicity trial, inoculation with Lasiodiplodia pseudotheobromae, Botryosphaeria dothidea and Pestalotiopsis mangiferae resulted in the largest lesions, but systemic infection or dieback-like symptoms were not observed in any treatment despite plant stress being induced by drought or inundation. We concluded that inoculation of parkinsonia with the tested putative fungal pathogens is unlikely to result in dieback, which has implications for future work in biocontrol of parkinsonia