Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.

Aims-To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. Methods-Review of community care, outpatient attendances, and readmissions in the first two years after birth. Patients: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. Results-The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. Conclusion-RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

BackgroundSignificant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.Method and Findings Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values.ResultsOf 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg/day), lamotrigine (600mg/day) and topical capsaicin (0.075% q.d.s.).ConclusionsEvidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.

In this study HIV-related lung cancer occurred more frequently in the post-HAART era, when compared with the HIV-negative population. Unfortunately, the outcome of these patients remains poor despite HAART.

SummaryStudy participants with HIV-associated sensory polyneuropathy (HIV-SN) had higher plasma triglyceride concentrations, depression, anxiety, catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN.

Thirty-two female students participated in a single-session experiment during which they carried out two 8-min trials of high-intensity exercise and two 8-min trials of low-intensity exercise. One high- and one low-exercise trial were accompanied by music; the other two trials were accompanied by metronome. Mood was assessed with a modification of the Profile of Mood States before and immediately after each trial. The purpose of the experiment was disguised to reduce the influence of subject expectations on mood responses. Participants were divided into fit and unfit groups based on heart rate responses during high-exercise trials. Overall, high-intensity exercise led to increases in tension/anxiety and fatigue, whereas positive mood changes (vigor and exhilaration) were seen following low-intensity exercise only. No group differences in mood responses were observed. Explanations of these results are considered in light of other literature concerning the acute effects of exercise on mood.

The palliative care needs of patients with cancer are understood and managed well by specialist palliative care services. Patients dying of non-cancer diseases are rarely offered these services. A literature review was conducted to determine the physical and psychosocial problems of patients dying from non-cancer diseases. Studies were identified using a systematic keyword search of six electronic databases. Fourteen studies were identified and assessed according to rigour of design. Findings suggest that some patients dying of non-cancer have needs comparable with those dying of cancer. Low response rates, subject bias, and measurement bias mean that findings should be viewed with caution. More prospective, rigorously designed research is necessary to identify which patients with non-cancer diagnoses may benefit from specialist palliative care.