The NAD(+) salvage pathway modulates cancer cell viability via p73.

The involvement of the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway in cancer cell survival is poorly understood. Here we show that the NAD(+) salvage pathway modulates cancer cell survival through the rarely mutated tumour suppressor p73. Our data show that pharmacological inhibition or knockdown of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD(+) salvage pathway, enhances autophagy and decreases survival of cancer cells in a p53-independent manner. Such NAMPT inhibition stabilizes p73 independently of p53 through increased acetylation and decreased ubiquitination, resulting in enhanced autophagy and cell death. These effects of NAMPT inhibition can be effectively reversed using nicotinamide mononucleotide (NMN), the enzymatic product of NAMPT. Similarly, knockdown of p73 also decreases NAMPT inhibition-induced autophagy and cell death, whereas overexpression of p73 alone enhances these effects. We show that the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) harbour significantly higher levels of NAMPT and lower levels of p73 than does the normal cell line (MCF-10A), and that NAMPT inhibition is cytotoxic exclusively to the cancer cells. Furthermore, data from 176 breast cancer patients demonstrate that higher levels of NAMPT and lower levels of p73 correlate with poorer patient survival, and that high-grade tumours have significantly higher NAMPT/p73 mRNA ratios. Therefore, the inverse relationship between NAMPT and p73 demonstrable in vitro is also reflected from the clinical data. Taken together, our studies reveal a new NAMPT-p73 nexus that likely has important implications for cancer diagnosis, prognosis and treatment.

National survey of the management of eye emergencies in the accident and emergency departments by senior house officers: 10 years on--has anything changed?

OBJECTIVE: To assess changes in basic ophthalmic training of accident and emergency (A&E) senior house officers (SHOs) in the last 10 years, their own perceived level of confidence and the availability of appropriate equipment in their departments. METHODS: A standardised structured questionnaire from a telephone survey carried out in 1993 was used. One SHO from each A&E department listed in the British Association of Emergency Medicine directory of 2003 was chosen at random and interviewed. RESULTS: 168 A&E departments were contacted and 133 SHOs were successfully interviewed (response rate 79.2%). The number of A&E departments with a slit lamp increased by 25.7% from 1993, and slit lamp training increased by 21%. There was no significant change in the prevalence of training in the management of eye emergencies (74.0% in 1993 vs 77.4% in 2003) and the proportion of SHOs who felt confident in dealing with these cases was unchanged. CONCLUSIONS: A&E departments are better equipped with slit lamps 10 years on, and staff are being trained to use them. This has unfortunately not improved the confidence levels in dealing with eye emergencies, reflecting the lack of adequate basic ophthalmic training for A&E SHOs. Recent changes in postgraduate medical training could provide a platform to bring about the changes required.

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision however still requires additional refractive power usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which includes the Eyes and Vision Group Trials Register) on The Cochrane Library (2006, Issue 3), MEDLINE (1966 to July 2006), EMBASE (1980 to July 2006), NRR (2006, Issue 3) and PUBMED searched on 25 July 2006, limit: 90 days (entry date). We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal intraocular lenses for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Data were collected and trial quality was assessed. Where possible, statistical summary measures were calculated otherwise data were tabulated. MAIN RESULTS: Ten trials were identified, and a further three are pending review. There was significant variability between the trials in which outcomes were reported. Unaided distance acuity was similar in multifocal and monofocal IOLs (standardised mean difference (SMD) 0.03, 95% Confidence Interval (CI) -0.13 to 0.19). There was no statistical difference between multifocal IOLs and monofocals with respect to the proportion of participants achieving 6/6 best corrected visual acuity (Peto odds ratio (OR) 1.05, 95% CI 0.67 to 1.63). Unaided near vision was improved with the multifocal IOLs. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs (OR for spectacle dependence 0.17, 95% CI 0.12 to 0.24). Adverse effects included reduced contrast sensitivity and the subjective experience of haloes around lights. AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients. Motivation to achieve spectacle independence is likely to be the deciding factor.

Neuralgic amyotrophy: A rare cause of bilateral diaphragmatic paralysis.

Neuralgic amyotrophy, also known as brachial neuritis, is a well described clinical entity. Diaphragmatic dysfunction, as a result of phrenic nerve root involvement (cervical roots 3 to 5), is an uncommon, but increasingly recognized association. The case of a previously healthy 61-year-old woman who, after a prodrome of neck and shoulder discomfort, presented with severe orthopnea is described. Pulmonary function and electrophysiological studies led to a diagnosis of bilateral diaphragmatic paralysis. The patient's clinical course and the exclusion of other nerve entrapment syndromes and neurological disorders strongly favoured the diagnosis of neuralgic amyotrophy.

A preliminary investigation of high-school counseling resources on the Cape Peninsula.

In South Africa, counseling and guidance services remain marginalized. The aim of this study was to determine the structure and function of the counseling facilities in high schools on the Cape Peninsula. The first telephone survey comprising 68 representatively and randomly selected schools revealed that 26% of schools had no guidance department, and the mean full-time guidance teacher-pupil ratio was 1:897. The second survey involving 33 randomly selected full-time and part-time guidance teachers from the first sample showed that they could assign on average 14.4 minutes of counselling per pupil in one school year. Analysis of the full-time guidance teachers (N = 22) time allocation revealed that 23% of time was allocated to counseling, 32% to guidance, and 45% to formal teaching and administration. These results suggest that the allocation of personnel and time to counselling are deficient. An implication is that adolescents with psychological problems go undetected and therefore untreated.