Homelessness, sex and a tale of two sexually transmitted infections.

The Young People's Health Service (YPHS) is a free, nurse-led Primary Health Care Clinic, in Melbourne, for young people aged 12-24 who are experiencing homelessness. Sexually transmitted infection (STI) screening is routinely offered as part of comprehensive psychosocial assessments. We wanted to determine the number of people positive for Chlamydia trachomatis (Ct) and Mycoplasma genitalium (Mg), amongst this asymptomatic high-risk population. We also wanted to review our screening practice. All asymptomatic sexually active clients seen by YPHS between 2014 and 2016 were offered a first pass urine polymerase chain reaction-based test for Ct and Mg. Urine samples were taken for men and women. Positivity for Ct and Mg out of those tested was determined and association with gender examined. Between 2014-2016, 272 males and 278 females (n = 550) were screened for Ct, and 72 infections were detected (13.1%. Chlamydia positivity did not differ between males (n = 35; 12.9%, 95% confidence interval [CI]: 8.8-16.8) and females (n = 37; 13.3%, 95%CI: 9.3-17.3). Over the same period 273 males and 284 females were screened for Mg (n = 557) and 55 infections were detected (9.9%). A higher proportion of females (n = 35; 12.3%, 95%CI: 8.5-16.1) tested positive compared to males (n = 20; 7.3%, 95%CI: 4.2-10.4), p = 0.048. Our study demonstrates both Ct and Mg are prevalent in the population, Mg being more common in young women than young men. Referral for specialist care for macrolide-resistant Mg increased and the updated Australian STI management guidelines led to a review of practice.

Zinc from foliar-applied nanoparticle fertiliser is translocated to wheat grain: A 65Zn radiolabelled translocation study comparing conventional and novel foliar fertilisers.

Foliar zinc (Zn) fertilisers can be used to supplement or replace soil applications of Zn in situations where soil properties may decrease the plant bioavailability of Zn. However, conventional foliar Zn formulations such as zinc sulfate can cause leaf damage due to the rapid release of high amounts of Zn2+ into leaf tissue which can be locally phytotoxic. Zinc oxide nanoparticles (ZnO-NPs) offer an alternative approach by providing a more sustained release of Zn into leaf tissue, and potentially avoiding the need for multiple applications. We compared the efficacy of ZnO-NPs and microparticles (ZnO-MPs) to that of conventional formulations (ZnCl2 and ZnEDTA) in wheat. This is the first study to use 65Zn radiolabelled formulations and gamma spectrometry to determine the translocation of Zn to the grains and subsequent efficiency of foliar-applied ZnO-NP fertilisers. We found that ZnEDTA was the most efficient fertiliser in terms of the proportion of applied Zn translocated to wheat grain. We also investigated the effect of Zn application rate on fertiliser efficiency. For all forms of Zn, when plants were treated with Zn at 750 mg/L or 75 mg/L, there were no significant differences in the concentration of applied Zn translocated to the grain. This suggests that current Zn application rates could be decreased while still maintaining the nutritional quality of grain. Finally, using photo-stimulated luminescence (PSL) autoradiography and synchrotron-based X-ray fluorescence microscopy (XFM) we showed that the grain distribution of foliar-applied Zn mirrors that of Zn derived from root uptake.

A custom amplicon sequencing approach to detect resistance associated mutations and sequence types in Mycoplasma genitalium.

BACKGROUND: Mycoplasma genitalium resistance to antibiotic treatments is increasing, with very limited treatment alternatives on the horizon. Surveillance via sequencing of multiple M. genitalium loci would allow: monitoring of known antibiotic resistance mutations, associations between resistance/treatment failure and specific mutations, and strain typing for epidemiological purposes. In this study we assessed the performance of a custom amplicon sequencing approach, which negates the cost of library preparation for next generation sequencing. METHODS: Fifty-two M. genitalium positive samples (cervical, vaginal, anal and rectal swabs, and urine) were used. Three regions associated with M. genitalium antibiotic resistance (23S rRNA, parC and gyrA genes) were targeted, in conjunction with a locus used for differentiation of sequence types in the mgpB gene, and findings compared to Sanger sequencing. RESULTS: Amplicon sequencing provided adequate sequence read coverage (>30×) for the majority of samples for 23S rRNA gene (96%) and mgpB (97%), parC (78%) and gyrA (75%). Single nucleotide polymorphisms (SNPs) were characterised in samples for 23S rRNA gene (94%), parC (56%) and gyrA (4%). Unlike Sanger sequencing, mixed mutations could be identified by the amplicon sequencing method, and ratios of mutation types determined. All results, with one exception, were concordant to Sanger sequence results. Sequence diversity in the mgpB region was represented by 15 sequence types, 4 being observed in multiple samples. CONCLUSIONS: We have demonstrated the utility of this custom amplicon sequencing approach for generating highly informative datasets with the capacity to identify and determine ratios of mixed sequences. The use of this customisable amplicon sequencing method enables cost effective, scalable amplicon sequencing of multiple target regions of interest in M. genitalium.

The impact of sample storage on molecular-based detection of Mycoplasma genitalium.

AIMS: Mycoplasma genitalium causes a common, sexually transmitted bacterial infection. This study assessed the detection of M. genitalium in stored urine samples to understand the impact of sample storage on M. genitalium detection. METHODS: Aliquots of M. genitalium-positive urine (n = 20 patients) were stored at either room temperature (22°C) or 4°C, without a preservative. At weekly intervals, samples were tested using the commercial test ResistancePlus MG® (SpeeDx® , Australia). We report the analysis at 1 week, an acceptable collection-to-test turnaround time, with further analysis over 5 weeks to illustrate degradation trends. RESULTS: After storing at 4°C, the proportion of specimens that remained positive for M. genitalium was 100% after 1 week and 95% after 4 weeks. Storage at 22°C led to more rapid decline in detection in the first 4 weeks, with 95% detected after 1 week and 85% at 2 weeks onwards. At 5 weeks, samples stored at both temperatures had an 85% M. genitalium detection rate, with increase in crossing points (Cq) of 0·72 (95% confidence interval (CI) 0·01-1·43; P-trend = 0·027) at 4°C, and 1·75 ((95% CI 0·79-2·71), P-trend <0·001) at 22°C. CONCLUSIONS: Urine samples stored without preservative, and unfrozen, retained high M. genitalium detection levels over the short term (up to 5 weeks). To minimize degradation, storing at 4°C is recommended. SIGNIFICANCE AND IMPACT OF THE STUDY: There is little known about the stability of clinical samples for M. genitalium detection. This study found that a high proportion (85-100%) of samples are still suitable for M. genitalium detection after storage for up to 5 weeks.

Invasive Methicillin-Resistant Staphylococcus aureus USA500 Strains from the U.S. Emerging Infections Program Constitute Three Geographically Distinct Lineages.

USA500 isolates are clonal complex 8 (CC8) Staphylococcus aureus strains closely related to the prominent community- and hospital-associated USA300 group. Despite being relatively understudied, USA500 strains cause a significant burden of disease and are the third most common methicillin-resistant S. aureus (MRSA) strains identified in the U.S. Emerging Infections Program (EIP) invasive S. aureus surveillance. To better understand the genetic relationships of the strains, we sequenced the genomes of 539 USA500 MRSA isolates from sterile site infections collected through the EIP between 2005 and 2013 in the United States. USA500 isolates fell into three major clades principally separated by their distribution across different U.S. regions. Clade C1 strains, found principally in the Northeast, were associated with multiple IS256 insertion elements in their genomes and higher levels of antibiotic resistance. C2 was associated with Southern states, and E1 was associated with Western states. C1 and C2 strains all shared a frameshift in the gene encoding AdsA surface-attached surface protein. We propose that the term "USA500" should be used for CC8 strains sharing a recent common ancestor with the C1, C2, and E1 strains but not in the USA300 group.IMPORTANCE In this work, we have removed some of the confusion surrounding the use of the name "USA500," placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.

Diphenylcyclopropenone for the treatment of cutaneous in-transit melanoma metastases - results of a prospective, non-randomized, single-centre study.

BACKGROUND: Current treatments for in-transit melanoma (ITM) metastases are frequently invasive and do not improve overall survival. Recently, there has been increasing investigation into the use of topical agents. Diphenylcyclopropenone or diphencyprone (DPCP) is a novel, topical therapy that has been reported to have immune-sensitizing properties useful in the treatment of ITM. OBJECTIVE: To assess the clinical outcomes of patients treated within a prospective, non-randomized, non-comparative study using DPCP for cutaneous ITM metastases. METHODS: A review was conducted assessing the outcomes of 58 patients prospectively treated using DPCP. Patients had satellite or in-transit disease (stage IIIB+), with all lesion morphology types included. The patients were treated through a single, specialized clinic with regular outpatient follow-up. DPCP was topically applied as an aqueous cream in 0.005-1% concentrations once to twice per week for up to 24-48 h of duration. To assess variables associated with response, a per-protocol statistical analysis was performed. RESULTS: Fifty-four patients were treated who satisfied eligibility criteria for analysis. The overall response rates were as follows: complete response 22%, partial response 39%, stable disease 24% and progressive disease 15%. The mean time to complete response was 10.5 months, mean duration (disease-free interval) 12.3 months and recurrence rate in complete responders 41%. Lesion morphology was predictive of clinical benefit with a higher response in epidermotropic disease (P < 0.05). CONCLUSIONS: DPCP provided a well-tolerated, convenient and efficacious treatment for cutaneous ITM metastases. Identifying patterns of response may assist treatment selection and improve patient-rated outcomes.

Influence of feeding strategy and diet for reproductive rabbit does on intake, performances, and health of young and females before and after weaning.

This study aimed to determine the influences of feeding strategy and diet for reproductive females on feed intake, BW, reproductive performances, and milk composition and their effects on kit performances from birth (d 0) to 70 d of age (d 70). A total of 133 does followed for 3 reproductive cycles and their offspring, 2,322 kits from 236 litters, were divided into 3 experimental groups that differed only by the diet offered to the doe. Three experimental diets were used: a reproduction (Repro) diet (11.01 MJ DE/kg, 24.0 g lipids/kg, 161 g starch/kg, and 343 g/kg NDF), a lactation (Lact) diet (11.88 MJ DE/kg, 49.0 g lipids/kg, 161 g starch/kg, and 302 g/kg NDF), and a fattening (Fatt) diet (9.73 MJ DE/kg, 23.0 g lipids/kg, 70 g starch/kg, and 415 g/kg NDF). In group RR, does received feed Repro throughout the study (d 0 to 42 of each cycle). In group RF, does received diet Repro from d 0 to 25 and d 35 to 42 and diet Fatt from d 25 to 35. In group LR, does received diet Lact from d 0 to 25 and diet Repro from d 25 to 42. Kits in all groups received diet F from d 18 to 70, where intake was restricted from d 35 to 63. Doe BW was similar throughout the study (4,495 g; > 0.05). Doe feed intake differed only from weaning to the subsequent kindling (+7.8% in group RF; = 0.042). Reproductive performances were similar, except for litter weight at birth (+3.6% in group LR; = 0.029). From d 0 to 25, a negative energy balance was observed in does yet most markedly in group LR (-8.61 MJ vs. -3.15 and -2.39 for groups RF and RR, respectively; < 0.01). Milk intake per kit was greater in group LR than in the other 2 groups at 17 d (+14.5%; < 0.001) and 23 d (+14.9%; < 0.05). Kit BW was highest in group LR at 18 and 25 d (+10.1% and +8.2%, respectively; < 0.01), but no difference was observed at 35 or 70 d ( > 0.05). Feed intake per kit from d 18 to 25 was greater in groups RR and RF than in group LR (+26%; < 0.001) and greater in group RF than in group LR from d 25 to 35 (+8%; < 0.05). Feed intake, when fed ad libitum (63 to 70 d), was similar in all groups ( = 0.292). Kit mortality before weaning was similar in all groups (8.1%; > 0.05) but was lowest in group RF after weaning compared to groups RR and LR (1.7 vs. 4.8 and 5.8%, respectively; < 0.001). Our results suggest that stimulating milk production through the incorporation of fat at the beginning of lactation offers few benefits for females and had a negative effect on early solid feed intake, which could explain animal health after weaning.

Risk factors associated with incident sexually transmitted infections in HIV-positive patients in the Australian HIV Observational Database: a prospective cohort study.

OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.

A systematic review of non-surgical treatments for lentigo maligna.

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow-up durations of 1-96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow-up durations of 2-49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow-up durations of 8-78 months. in each of the treatment series the I(2) value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta-analysis of included data were inappropriate. For non-surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non-invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long-term efficacy and overall utility of these treatments.

Duration of syphilis symptoms at presentations in men who have sex with men in Australia: are current public health campaigns effective?

The rapid rise in syphilis cases has prompted a number of public health campaigns to assist men who have sex with men (MSM) recognize and present early with symptoms. This study aimed to investigate the temporal trend of the duration of self-report symptoms and titre of rapid plasma reagin (RPR) in MSM with infectious syphilis. Seven hundred and sixty-one syphilis cases in MSM diagnosed at the Melbourne Sexual Health Centre (MSHC) from 2007-2013 were reviewed. Median duration of symptoms and RPR titres in each year were calculated. The median durations of symptoms with primary and secondary syphilis were 9 [interquartile range (IQR) 6-14] days and 14 (IQR 7-30) days, respectively. The overall median titre of RPR in secondary syphilis (median 128, IQR 64-256) was higher than in primary syphilis (median 4, IQR 1-32) and in early latent syphilis (median 32, IQR 4-64). The median duration of symptoms for primary syphilis, secondary syphilis and titre of RPR level did not change over time. Public health campaigns were not associated with a significant shorter time from onset of symptoms to treatment. Alternative strategies such as more frequent testing of MSM should be promoted to control the syphilis epidemic in Australia.

Draft Genome Sequence of the Pandoraea apista LMG 16407 Type Strain.

Pandoraea species, in particular Pandoraea apista, are opportunistic, multidrug-resistant pathogens in persons with cystic fibrosis (CF). To aid in understanding the role of P. apista in CF lung disease, we used Illumina MiSeq and nanopore MinION technology to sequence the whole genome of the P. apista LMG 16407(T).

Ratio of anogenital warts between different anatomical sites in homosexual and heterosexual individuals in Australia, 2002-2013: implications for susceptibility of different anatomical sites to genital warts.

There is little known regarding the transmissibility of human papillomavirus (HPV) between different sites in men who have sex with men (MSM) and heterosexual individuals. We conducted a retrospective analysis investigating all new patients attending the Melbourne Sexual Health Centre in Australia between 2002 and 2013. We describe the prevalence and ratio of the first episode of anogenital warts in MSM and heterosexual males and females. The proportion of new MSM clients with anal and penile warts was 4·0% (362/8978) and 1·6% (141/8978), respectively; which gave an anal-to-penile wart ratio of 1:2·6. About 13·7% (1656/12112) of heterosexual males had penile warts and 10·0% (1121/11166) of females had vulval warts, which yielded a penile-to-vulval wart ratio of 1:0·7. Penile-anal transmission has a higher ratio than penile-vulval transmission, suggesting that the anal epithelium may be more susceptible to HPV infection than the vulval epithelium in females; these ratios are important in modelling the control of HPV in MSM.

Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: We describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/µL. METHODS: In a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores < -1 in at least two of six cognitive domains. RESULTS: A total of 608 participants had a median age of 34 years; 11% were women and 15% were black; the median time since HIV diagnosis was 0.9 years; the median CD4 cell count was 633 cells/µL; 19.9% had mild NCI. Better NP was independently associated with younger age, being white, higher body mass index (0.10 per 10 kg/m(2) higher), and higher haematocrit percentage (0.19 per 10% higher). Worse NP was associated with longer time since HIV diagnosis (-0.17 per 10 years), diabetes (-0.29) and higher Framingham risk score (-0.15 per 10 points higher). QNPZ-8 scores differed significantly between geographical locations, with the lowest scores in Brazil and Argentina/Chile. CONCLUSIONS: This is the largest study of NP in ART-naïve HIV-positive adults with CD4 counts > 500 cells/µL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

Routine CD4 cell count monitoring seldom contributes to clinical decision-making on antiretroviral therapy in virologically suppressed HIV-infected patients.

OBJECTIVES: In Australia, CD4 cell count is monitored approximately every 6 months in HIV-infected patients during antiretroviral therapy (ART). The aim of this study was to determine if routine CD4 monitoring contributed to decisions on changes to ART, and to estimate how reduced CD4 monitoring could contribute to cost savings in Australia. METHODS: We conducted a retrospective cohort analysis investigating all HIV-infected patients who attended the Melbourne Sexual Health Centre (MSHC) in Australia from 1 April 2011 to 1 October 2013. We reviewed the electronic medical records of all patients who changed or stopped antiretroviral regimens during this time period to determine whether CD4 cell count could have contributed to this clinical decision. RESULTS: Among 1004 patients with HIV infection on ART, none [95% confidence interval (CI) 0-2.3%] of the 162 clinical decisions to change or stop treatment were influenced by CD4 cell counts. Reducing the current biannual CD4 monitoring strategy to annually could potentially save ∼AU$ 1.5 million (US$ 1.4 million) each year in Australia [i.e. ∼AU$ 74 700 (US$ 67 700) could be saved per 1000 HIV-infected patients during ART]. CONCLUSIONS: Routine CD4 monitoring in HIV-infected patients during ART could be reduced from biannually to annually, as it rarely influences clinical decisions in patients' management. Not only could this avoid patients being unnecessarily anxious about normal fluctuations in their CD4 counts but it would also result in cost savings.

The significance of low-level viraemia in diverse settings: analysis of the Treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD).

OBJECTIVES: The aim of the study was to assess the significance of low-level viraemia (LLV) and the timing of treatment change in low/middle-income country (L/MIC) compared with high-income country (HIC) settings. METHODS: Patients with virological control following commencement of combination antiretroviral therapy (cART) were included in the study. LLV was defined as undetectable viral load (<50 HIV-1 RNA copies/mL) followed by confirmed detectable viral load < 1000 copies/mL. Virological failure was defined as viral load > 1000 copies/mL. Kaplan-Meier plots of time to virological failure by prior LLV and income category were generated. Regimen changes in the setting of LLV were compared between sites. Sensitivity analysis of rates of LLV and virological failure by person-years and number of tests was conducted for differing definitions of LLV and virological failure. RESULTS: A total of 1748 patients from HICs and 823 patients from L/MICs were included in the study. One hundred and ninety-six (11.2%) HIC participants and 36 (4.4%) L/MIC participants experienced at least one episode of LLV. Of the patients who underwent regimen switch in HIC settings, the majority changed from a nucleoside reverse transcriptase inhibitor (NRTI)/protease inhibitor (PI) regimen to an NRTI/nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen (26.8%). Very few switches were made in L/MIC settings. Rates of LLV were significantly higher for HICs compared with L/MICs per 1000 person-years (28.6 and 9.9 per 1000 person-years, respectively), but not in terms of the number of tests (9.4 and 7.2 per 1000 tests, respectively). Rates of virological failure per test were significantly higher for L/MICs compared with HICs (30.7 vs. 19.6 per 1000 tests, respectively; P < 0.001). LLV was a significant predictor of virological failure at 2 years in L/MICs [0.25; 95% confidence interval (CI) 0.11-0.50; P = 0.043] but not in HICs (0.13; 95% CI 0.08-0.22; P = 0.523). CONCLUSIONS: LLV is weakly predictive of virological failure at 2 years in L/MICs but not in HICs. This suggests that interventions targeted at subjects with LLV in L/MICs would help to improve treatment outcomes.

What are 30-day postoperative outcomes following splenic flexure mobilization during anterior resection?

BACKGROUND: The aim of this study was to determine whether mobilization of the splenic flexure during anterior resection is associated with an increased number of complications. METHODS: This is a retrospective cohort analysis of all non-emergent anterior resections with anastomosis (open and laparoscopic) between January 2005 and December 2009 from the American College of Surgeons National Surgical Quality Improvement Program. Infectious, renal, and pulmonary adverse events as well as operative times were analyzed for cases with splenic flexure mobilization as compared to no mobilization. We then constructed multivariate models to identify risk factors for postsurgical adverse events. RESULTS: During the 5-year study period, 6,324 (57 %) open resections and 4,788 (43 %) laparoscopic resections were performed. Mobilization of the splenic flexure was associated with an increase in operating room time (204 vs 172 min, p < 0.0001). Although anastomotic leaks were not recorded, there was no difference in organ space infections (3.9 vs 3.7 %, p = 0.7) or return to operating room events between the two groups. However, patients who underwent splenic flexure mobilization had significantly more superficial surgical site infections (10.6 vs 8.4 %, p < 0.0002). Multivariate analysis accounting for laparoscopic or open surgery and standard preoperative and intraoperative variables demonstrated a persistent increase in superficial surgical site infections for patients with splenic flexure mobilization. CONCLUSIONS: Operating room times are longer and superficial surgical site infections are more common when the splenic flexure is mobilized. The absolute indications for splenic flexure mobilization should be addressed in further research.

Size of anal squamous cell carcinomas at diagnosis: a retrospective case series.

Anal squamous cell carcinoma is more common in HIV-positive homosexual men than in the general population and prognosis worsens with increasing tumour size. To identify opportunities for earlier diagnosis, we aimed to determine size and visibility of anal squamous cell carcinoma at diagnosis. We conducted a retrospective review of medical records between 1992 and 2010 from one hospital radiotherapy centre, a major centre for HIV care, in Melbourne, Australia. Of 128 cases of anal squamous cell carcinoma, 24 (19%) were in HIV-positive men. At diagnosis, half (52%) of the tumours were externally visible and mean estimated tumour size was 36 mm (29 mm in HIV-positive and 38 mm in HIV-negative patients; p = 0.04) and 114/121 (94%) tumours were 1 cm or larger. The most frequent symptoms were bleeding (43%) and pain (36%) and mean duration of symptoms was 22 weeks. This suggests most anal squamous cell carcinoma were visible or palpable for some time before diagnosis, meaning that screening high-risk groups by anal inspection and palpation is plausible.

Acceptability of digital anal cancer screening examinations in HIV-positive homosexual men.

OBJECTIVES: Anal cancer is more common in HIV-positive homosexual men than in HIV-negative homosexual men and the general population. Earlier diagnosis leads to improved prognosis. We aimed to determine if regular anal inspection and digital examination of asymptomatic homosexual men attending for routine HIV care were acceptable and to record the rate of referral for diagnosis of potentially malignant anal lesions. METHODS: We offered anal examinations to consecutive homosexual men with HIV infection aged ≥ 35 years during their routine HIV clinic visits, aiming to complete three examinations over a 12-month period. Acceptability questionnaires were completed at baseline and after each examination and doctors recorded examination findings and all resulting interventions. Hospital referral outcomes were collected and interventions were costed using the Australian Medical Benefits Schedule. RESULTS: Of 142 men who were offered enrolment in the study, 102 [72%; 95% confidence interval (CI) 64-79%] participated. Following the initial anal examinations, four men were referred to surgeons. Cancer was excluded in three men (3%; 95% CI 1-8%) and one was diagnosed with anal squamous cell carcinoma (SCC). Three men had anoscopy performed at the time and two were referred for colonoscopy. Ninety-eight per cent (95% CI 93-100%) of respondents said that they would probably have the examination next time. The intervention was estimated to cost approximately Australian $16 per examination. CONCLUSIONS: Regular anal digital examinations are an acceptable and inexpensive addition to the routine care of homosexual men with HIV infection.

Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma.

Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neurooncology. Our previous studies have shown that proliferation of GNPs is regulated by Sonic hedgehog (Shh), and that aberrant activation of the Shh pathway can lead to medulloblastoma. Moreover, we have demonstrated that Shh-dependent proliferation of GNPs and medulloblastoma cells can be blocked by basic fibroblast growth factor (bFGF). But while the mitogenic effects of Shh signaling have been confirmed in vivo, the inhibitory effects of bFGF have primarily been studied in culture. Here, we demonstrate that mice lacking FGF signaling in GNPs exhibit no discernable changes in GNP proliferation or differentiation. In contrast, activation of FGF signaling has a potent effect on tumor growth: treatment of medulloblastoma cells with bFGF prevents them from forming tumors following transplantation, and inoculation of tumor-bearing mice with bFGF markedly inhibits tumor growth in vivo. These results suggest that activators of FGF signaling may be useful for targeting medulloblastoma and other Shh-dependent tumors.