A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen. Methods: CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m−2) weekly for six cycles followed by CRT (40 mg m−2 of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT. Results: Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%). Conclusion: A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%)

Readmission and overstay after day case nasal surgery

BACKGROUND: A readmission is classified as a patient necessitating readmission to hospital due to a post-operative complication following discharge. An overstay however, is classified as a patient having to stay longer than the planned duration in hospital (not having been discharged in the interim) due to a post-operative complication. This study aims to investigate patient-related factors that predispose to readmission or overstay and thus make recommendations to decrease the likelihood of readmission or overstay. METHOD: In this retrospective study 312 'day-case nasal procedures', were selected from a total cohort of 4274 ENT patients over a 17-month period. This sub-group was investigated for a range of demographic factors including, age, gender and ethnicity with regards to their relationship to readmission rates and overstay frequency and duration. RESULTS: The rates were 2.88% and 9.62% for readmission and overstay respectively. The total number of days spent in hospital as a result of readmission was 27. Epistaxis was the leading cause for readmission/overstay (28.9%) followed by high levels of post-operative pain preventing them from being discharged (23.7%). All procedures in this study had readmission rates that were below those recommended in the guidelines set by the Royal College of Surgeons of England. Women overstayed significantly longer (t = 1.65, p < 0.05) than men. CONCLUSIONS: Suitable candidates for day-case ENT surgery highlighted by this study include healthy individuals between the ages of 20 and 60. Operating in the morning would increase the immediate post-operative recovery time, which may reduce the numbers of patients who complain of high levels of pain at the time of discharge. Procedures such as septorhinoplasty being performed routinely in the ambulatory setting require additional research into more effective methods of pain control. Standards need to be improved so that the causes of overstay and readmission are clearly identifiable in patient records

Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Mycoplasma hominis brain abscess following uterus curettage: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Mycoplasma hominis </it>is mostly known for causing urogenital infections. However, it has rarely been described as an agent of brain abscess.</p> <p>Case presentation</p> <p>We describe a case of <it>M. hominis </it>brain abscess in a 41-year-old Caucasian woman following uterus curettage. The diagnosis was obtained by 16S rDNA amplification, cloning and sequencing from the abscess pus, and confirmed by a specifically designed real-time polymerase chain reaction assay.</p> <p>Conclusions</p> <p>Findings from our patient's case suggest that <it>M. hominis </it>should be considered as a potential agent of brain abscess, especially following uterine manipulation.</p

Does home neighbourhood supportiveness influence the location more than volume of adolescent's physical activity? An observational study using Global Positioning Systems

Background: Environmental characteristics of home neighbourhoods are hypothesised to be associated with residents’ physical activity levels, yet many studies report only weak or equivocal associations. We theorise that this may be because neighbourhood characteristics influence the location of activity more than the volume. Using a sample of UK adolescents, we examine the role of home neighbourhood supportiveness for physical activity, both in terms of volume of activity undertaken and a measure of proximity to home at which activity takes place. Methods: Data were analysed from 967 adolescents living in and around the city of Bristol, UK. Each participant wore an accelerometer and a GPS device for seven days during school term time. These data were integrated into a Geographical Information System containing information on the participants’ home neighbourhoods and measures of environmental supportiveness. We then identified the amount of out-of-school activity of different intensities that adolescents undertook inside their home neighbourhood and examined how this related to home neighbourhood supportiveness. Results: We found that living in a less supportive neighbourhood did not negatively impact the volume of physical activity that adolescents undertook. Indeed these participants recorded similar amounts of activity (e.g. 20.5 mins per day of moderate activity at weekends) as those in more supportive neighbourhoods (18.6 mins per day). However, the amount of activity adolescents undertook inside their home neighbourhood did differ according to supportiveness; those living in less supportive locations had lower odds of recording activity inside their home neighbourhood. This was observed across all intensities of activity including sedentary, light, moderate, and vigorous. Conclusions: Our findings suggest that the supportiveness of the neighbourhood around home may have a greater influence on the location of physical activity than the volume undertaken. This finding is at odds with the premise of the socio-ecological models of physical activity that have driven this research field for the last two decades, and has implications for future research, as by simply measuring volumes of activity we may be underestimating the impact of the environment on physical activity behaviours

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Effect of valdecoxib pretreatment on pain and secondary hyperalgesia: a randomized controlled trial in healthy volunteers [ISRCTN05282752, NCT00260325]

BACKGROUND: Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization – induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers. METHODS: The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped. RESULTS: The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation. CONCLUSION: We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers

The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa strains with mutation in other flagellar genes, as well as mucoid, nonmotile isolates from cystic fibrosis patients, were also permeabilized by SP-A. Provision of the wild-type fliC gene restored the resistance to SP-A-mediated membrane permeabilization in the fliC-deficient bacteria. In addition, non-mucoid, motile revertants of CF isolates reacquired resistance to SP-A-mediated membrane permeability. Resistance to SP-A was dependent on the presence of an intact flagellar structure, and independent of flagellar-dependent motility. We provide evidence that flagellar-deficient mutants harbor inadequate amounts of LPS required to resist membrane permeabilization by SP-A and cellular lysis by detergent targeting bacterial outer membranes. Thus, the flagellum of P. aeruginosa plays an indirect but important role resisting SP-A-mediated clearance and membrane permeabilization