Postoperative complications of colorectal cancer.

Colorectal cancer is the third most common cancer, and surgery is the most common treatment. Several surgical options are available, but each is associated with a range of potential complications. The timely and efficient identification of these complications is vital for effective clinical management of these patients in order to minimise their morbidity and mortality. This review aims to describe the range of commonly performed surgical treatments for colorectal surgery. In addition, frequent post-surgical complications are explored with investigative options explained and illustrated.

Characterization of the mid-coronal plane method for measurement of radiographic change in knee joint space width across different levels of image parallax.

OBJECTIVE: Radiographic measurement of the change in knee joint space width (ΔJSW) is often affected by image parallax, which causes an apparent exaggeration of JSW due to projectional differences. This issue with parallax (quantified by intermargin distance) can in part be addressed with a novel mid-coronal plane (MCP) measurement method. The objectives of the study were to determine 1) accuracy and 2) reproducibility of the MCP method, and 3) compare the MCP method to that used in the Osteoarthritis Initiative (OAI) for different categories of parallax. METHODS: Posteroanterior radiographs (n = 70) with known JSW were digitally reconstructed from CT images of cadaver knees and used to determine the accuracy of ΔJSW using the MCP method for parallax categories of None, Mild/Moderate, and Severe. Reproducibility was determined from pairs of clinical radiographs selected from the OAI (n = 170). The MCP method was also compared to the OAI methodology. Both reproducibility and agreement were characterized by Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: The MCP method was accurate to 0.11 mm in cases with no parallax, and 0.18 mm across all categories of parallax for medial and lateral compartments. Reproducibility of the MCP method was graded "excellent" (ICC 0.98, 95% CI [0.98, 0.99]). The MCP results agreed very well with the OAI (ICC 0.92, 95% CI [0.89, 0.94]), with mean absolute differences between methods increasing with increasing parallax. CONCLUSION: The MCP method is an accurate, reproducible alternative to the OAI method for multi-center clinical trials where subject and X-ray beam positioning may be variable.

Hemizygosity for the gene encoding glycoprotein Ibß is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome.

Essentials How thrombocytopenia relates to bleeding in 22q11 deletion syndrome (22q11DS) is not clear. Bleeding severity, platelet count and volume, and GPIBB were examined in patients with 22q11DS. Macrothrombocytopenia and bleeding typified imperfectly overlapping subsets of 22q11DS patients. GPIBB hemizygosity does not cause macrothrombocytopenia or bleeding in patients with 22q11DS. SUMMARY: Background and objectives Macrothrombocytopenia and bleeding are frequently associated with 22q11 deletion syndrome (22q11DS). GPIBB, which encodes the glycoprotein (GP) Ibß subunit of GPIb-IX-V, is commonly deleted in patients with 22q11DS. Absence of functional GPIb-IX-V causes Bernard-Soulier syndrome, which is a severe bleeding disorder characterized by macrothrombocytopenia. Patients with 22q11DS are often obligate hemizygotes for GPIBB, and those with only a pathogenically disrupted copy of GPIBB present with Bernard-Soulier syndrome. The objective of this study was to determine how GPIBB hemizygosity and sequence variation relate to macrothrombocytopenia and bleeding in patients with 22q11DS who do not have Bernard-Soulier syndrome. Patients/methods We thoroughly characterized bleeding severity, mean platelet volume, platelet count and GPIBB copy number and sequence in patients with 22q11DS. Results and conclusions Macrothrombocytopenia and mild bleeding were observed in incompletely overlapping subsets of patients, and GPIBB copy number and sequence variation did not correlate with either macrothrombocytopenia or bleeding in patients with 22q11DS. These findings indicate that GPIBB hemizygosity does not result in either macrothrombocytopenia or bleeding in these patients. Alternative genetic causes of macrothrombocytopenia, potential causes of acquired thrombocytopenia and bleeding and ways in which platelet size, platelet count and GPIBB sequence information can be used to aid in the diagnosis and management of patients with 22q11DS are discussed.

"There is not a safe space where they can find themselves to be free": (Un)safe spaces and the promotion of queer visibilities among township males who have sex with males (MSM) in Cape Town, South Africa.

Males who have sex with males (MSM) are prioritised in the global fight against HIV/AIDS, as a key affected population to receive HIV prevention, treatment, and HIV-related care and support (WHO, 2016). There is, however, limited empirical research conducted on how to engage communities of South African MSM in clinical HIV prevention research programs. The development of LGBTIQ safe spaces may potentially be a viable option to promote community-based engagement by bridging the divides between HIV-prevention researchers, marginalised queer populations, and other HIV-prevention stakeholders located in heteronormative spaces (Molyneux et al., 2016). We conducted ten in-depth, qualitative interviews with MSM safe space members who have been involved in HIV prevention research programs. Data were analysed using a thematic analytic strategy (Braun and Clarke, 2006). Our results indicate that the "safe spaces" currently operational in Cape Town are not stable spaces nor are they always safe, but they form part of a broader and much more long-term political and geographical strategy of inclusion and emancipation.

The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In-Situ Measurements in the Tropical Lower Stratosphere.

Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that may be intentionally enhanced in the future to offset greenhouse gases (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in maintaining background SAs has been debated for decades without in-situ measurements of SO2 at the tropical tropopause to inform this issue. Here we clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements to evaluate climate models and satellite retrievals. We then use the observed tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across the tropical tropopause. These analyses show that the tropopause background SO2 is about 5 times smaller than reported by the average satellite observations that have been used recently to test atmospheric models. This shifts the view of SO2 as a dominant source of SAs to a near-negligible one, possibly revealing a significant gap in the SA budget.

The use of a negative pressure wound management system in perineal wound closure after extralevator abdominoperineal excision (ELAPE) for low rectal cancer.

BACKGROUND: Perineal wound healing is a significant challenge after extralevator abdominoperineal excision (ELAPE) due to a high rate of wound breakdown. Negative pressure therapy has proven benefits in open wounds, and recently a negative pressure system has been developed for use on closed wounds at high risk of breakdown, such as apronectomy and hysterectomy. The aim of the present study was to determine whether negative pressure therapy applied to closed perineal wounds after ELAPE improved wound healing and compare outcomes to the published literature and outcomes from a historical cohort of patients who had undergone 'standard' abdominoperineal resection (APR) and primary closure of the perineal wounds. METHODS: Prospective data on consecutive patients having ELAPE in the period from November 2012 to April 2015 were collected. The pelvic floor defect was reconstructed with biologic mesh. The adipose tissue layer was closed with vicryl sutures, a suction drain was left in the deep layer, the subcuticular layer and skin were closed, and the negative pressure system was applied. Any wound breakdown within the first 30 days postoperatively was recorded. RESULTS: Of the 32 consecutive ELAPE patients whose perineal wounds were closed within 30 days with the use of the negative pressure system, there was 1 patient with major perineal wound breakdown and 2 patients with a 1 cm superficial wound defect, which needed no further treatment. In the remaining 29 (90 %) patients, the perineal wounds healed fully without complications. Twenty-five patients underwent standard APR in 2010-2011 with primary closure of their perineal wounds. Ten out of 25(40 %) of patients who had undergone standard APR and primary closure of perineal wounds had major wound complications (p = 0.01). CONCLUSIONS: Our results suggest that after ELAPE the application of a negative pressure system to the perineal wound closed with biologic mesh may reduce perineal wound complications and may reduce the need for major perineal reconstruction.

Delayed laparoscopic mesh infection presenting as an abdominal mass.

A 56-year-old man presented with a delayed mesh infection 8 years following an elective laparoscopic totally extraperitoneal (TEP) bilateral hernia repair. Sterile pus was drained percutaneously as a temporising measure prior to removal of the right-hand mesh; the left-sided mesh was adherent to the femoral vessels and minimally contaminated. Delayed mesh infection is a rare occurrence. This case is the fourth example and the longest following initial operation. Removal of the infected mesh is advocated.

Porous and strong three-dimensional carbon nanotube coated ceramic scaffolds for tissue engineering.

Biomaterials research is investigating increasingly complex materials capable of mirroring the highly organized biochemical and architectural environments of the body. Accordingly, tissue scaffolds with nanoscale properties that mirror the fibrous proteins present in tissue are being developed. Such materials can benefit from the inherent dimensional similarities and nanocomposite nature of the cellular environment, altering nanoscale dimensional and biochemical properties to mimic the regulatory characteristics of natural cellular environments. One nanomaterial which demonstrates potential across a diverse range of biomaterial applications is carbon nanotubes (CNTs). Building on previous reports, a method to coat CNTs throughout 3D porous structures is developed. Through modifications to typical chemical vapour deposition (CVD), a high-quality uniform coating of carbon nanotubes (CNTs) is demonstrated over ß-tricalcium phosphate/hydroxyapatite (or TCP/HA), which is in clinical use; and the high-mechanical-strength multicomponent ceramic Ca2ZnSi2O7-ZnAl2O4, (or Sr-HT-Gah). The resulting materials address deficiencies of previously reported CNT biomaterials by simultaneously presenting properties of high porosity, biocompatibility and a mechanical stability. Together, this unique combination of properties makes these scaffolds versatile materials for tissue engineering in load bearing applications.

Postmortem findings in a case of variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulfate.

BACKGROUND: A small number of patients with variant Creutzfeldt-Jakob disease (vCJD) have been treated with intraventicular pentosan polysulfate (iPPS) and extended survival has been reported in some cases. To date, there have been no reports on the findings of postmortem examination of the brain in treated patients and the reasons for the extended survival are uncertain. We report on the neuropathological findings in a case of vCJD treated with PPS. METHODS: Data on survival in vCJD is available from information held at the National CJD Research and Surveillance Unit and includes the duration of illness in 176 cases of vCJD, five of which were treated with iPPS. One of these individuals, who received iPPS for 8 years and lived for 105 months, underwent postmortem examination, including neuropathological examination of the brain. RESULTS: The mean survival in vCJD is 17 months, with 40 months the maximum survival in patients not treated with PPS. In the 5 patients treated with PPS survival was 16 months, 45 months, 84 months, 105 months and 114 months. The patient who survived 105 months underwent postmortem examination which confirmed the diagnosis of vCJD and showed severe, but typical, changes, including neuronal loss, astrocytic gliosis and extensive prion protein (PrP) deposition in the brain. The patient was also given PPS for a short period by peripheral infusion and there was limited PrP immunostaining in lymphoreticular tissues such as spleen and appendix. CONCLUSIONS: Treatment with iPPS did not reduce the overall neuropathological changes in the brain. The reduced peripheral immunostaining for PrP may reflect atrophy of these tissues in relation to chronic illness rather than a treatment effect. The reason for the long survival in patients treated with iPPS is unclear, but a treatment effect on the disease process cannot be excluded.

Use of conjoint analysis to assess HIV vaccine acceptability: feasibility of an innovation in the assessment of consumer health-care preferences.

Engaging consumers in prospectively shaping strategies for dissemination of health-care innovations may help to ensure acceptability. We examined the feasibility of using conjoint analysis to assess future HIV vaccine acceptability among three diverse communities: a multiethnic sample in Los Angeles, CA, USA (n = 143); a Thai resident sample in Los Angeles (three groups; n = 27) and an Aboriginal peoples sample in Toronto (n = 13). Efficacy had the greatest impact on acceptability for all three groups, followed by cross-clade protection, side-effects and duration of protection in the Los Angeles sample; side-effects and duration of protection in the Thai-Los Angeles sample; and number of doses and duration of protection in the Aboriginal peoples-Toronto sample. Conjoint analysis provided insights into universal and population-specific preferences among diverse end users of future HIV vaccines, with implications for evidence-informed targeting of dissemination efforts to optimize vaccine uptake.

HIV vaccine acceptability and culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada.

This study explored HIV vaccine acceptability and strategies for culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada, among those at highest HIV risk. We conducted four focus groups (n=23) with Aboriginal male (1) and female (1) service users, peer educators (1) and service providers (1) in Ontario, Canada. Transcripts were analysed with narrative thematic techniques from grounded theory, using NVivo. Participants' mean age was 37 years; about half (52%) were female, half (48%) Two-spirit or lesbian, gay or bisexual (LGB)-identified, 48% had a high-school education or less and 57% were unemployed. Vaccine uptake was motivated by community survival; however, negative HIV vaccine perceptions, historically based mistrust of government and healthcare institutions, perceived conflict between western and traditional medicine, sexual prejudice and AIDS stigma within and outside of Aboriginal communities, and vaccine cost may present formidable obstacles to HIV vaccine acceptability. Culturally appropriate processes of engagement emerged on individual levels (i.e., respect for self-determination, explanations in Native languages, use of modelling and traditional healing concepts) and community levels (i.e., leadership by Aboriginal HIV advocates and political representatives, identification of gatekeepers, and procuring Elders' endorsements). Building on cultural strengths and acknowledging the history and context of mistrust and social exclusion are fundamental to effective HIV vaccine dissemination.

"Once Bitten, Twice Shy": participant perspectives in the aftermath of an early HIV vaccine trial termination.

The Step Study phase IIb HIV-1 vaccine trial was terminated early due to futility; subsequent analyses revealed increased susceptibility to HIV infection among a subset of test vaccine recipients. We conducted a mixed methods investigation, including a brief, self-administered baseline questionnaire and in-depth, semi-structured, 1-h interviews after unblinding, to explore experiences and perspectives among trial participants and key informants. Interviews were digitally recorded, transcribed, and analyzed using NVivo and thematic techniques. Forty-eight trial participants (46 gay/bisexual men) completed baseline surveys; 15 (14 gay/bisexual men) engaged in post-trial interviews. Participants indicated surprise and disappointment about the early trial termination and unexpected risks. Some articulated understanding the uncertainties of clinical trials, steadfast support and willingness to participate in the future; others reported greater risks than they deemed acceptable and unlikelihood of volunteering again. A few indicated mistrust of trial sponsors and ethics. Participants' most profound criticism was not about unexpected results, but perceived delays in unblinding and gaps in post-trial dissemination of information. Future HIV vaccine trials may benefit from increased emphasis on: (1) communication mechanisms among participants, investigators and trial sponsors, and (2) post-trial dissemination of information and psychosocial support.

PECAM-1 functions as a negative regulator of laminin-induced platelet activation.

SUMMARY BACKGROUND: Interaction of resting platelets with exposed components of the subendothelial matrix is an important early activating event that takes place at sites of vascular injury. Platelet responses to collagen are mediated by integrin alpha(2)beta(1) and the glycoprotein (GP)VI-Fc receptor (FcR) gamma-chain complex, whereas platelet activation by laminin is mediated by the related integrin, alpha(6)beta(1), and similarly requires signaling through GPVI-FcR gamma-chain. OBJECTIVE: Because the cell adhesion and signaling receptor PECAM-1 has previously been shown to dampen collagen-induced platelet activation, we sought to determine whether PECAM-1 might similarly regulate platelet activation by laminin. METHODS/RESULTS: We found that PECAM-1 became tyrosine phosphorylated on its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs following adhesion of either human or murine platelets to immobilized laminin. Whereas the presence or absence of PECAM-1 had no effect on either the rate or extent of platelet adhesion or spreading on laminin, PECAM-1 inhibited laminin-induced phosphorylation of GPVI-FcR gamma-chain immunoreceptor tyrosine-based activation motifs (ITAMs) and activation of its downstream effector, Syk kinase, and suppressed granule secretion. CONCLUSIONS: Taken together, these data are consistent with previous findings in platelets and other blood and vascular cells that PECAM-1 functions by modulating ITAM-mediated signaling pathways that amplify cellular activation.

Correlates of paid sex among men who have sex with men in Chennai, India.

OBJECTIVES: To assess correlates of paid sex among men who have sex with men (MSM) in Chennai, India. METHODS: A randomised survey was conducted among 200 MSM recruited from public sex environments using time-space sampling. The association of predictors with paid sex was assessed with chi(2) tests and multiple logistic regression. RESULTS: Participants' mean age was 28.5 years (SD 8.7). Most (71.5%) were kothis; 60% had less than high school education and two-thirds had a monthly income less than 2000 Indian rupees. More than one-third (35.0%) reported daily/weekly harassment; 40.5% reported forced sex in the past year. The prevalence of paid sex was 59.5% (95% CI 52.7% to 66.3%). Univariate analyses indicated that paid sex was associated with kothi identity (chi(2) = 14.46; p<0.01), less than high school education (chi(2) = 4.79; p<0.05), harassment (chi(2) = 11.75; p<0.01) and forced sex (chi(2) = 3.98; p<0.05). Adjusted analyses revealed that paid sex was associated with kothi identity (adjusted odds ratio (AOR) 2.62, 95% CI 1.34 to 5.10) and harassment (AOR 2.34, 95% CI 1.16 to 4.72). MSM who engaged in paid sex (versus no paid sex) had a mean of 31 partners in the past month (versus 4, t = 6.17, p<0.001) and 71.2% used condoms consistently (versus 46.4%, chi(2) = 18.34; p<0.01). Overall, 32.5% were never tested for HIV. CONCLUSIONS: Epidemic rates of harassment and sexual violence against MSM who engage in paid sex, predominantly kothis, suggest that interventions should target structural factors placing these men at increased risk of HIV/sexually transmitted infections and other health-compromising conditions. The effectiveness of individual-level, knowledge-based and condom-focused preventive interventions may be constrained in the context of poverty, low education, harassment and sexual violence.

Evaluation of cotton rats as a model for severe acute respiratory syndrome.

Experimental studies were conducted to evaluate two species of cotton rats, Sigmodon hispidus and Sigmodon fulviventer, as a model for severe acute respiratory syndrome (SARS). Blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after SARS coronavirus (CoV) infection for determining the growth curve of virus, if any, by the standard infectivity assay in Vero E6 cells. In addition, sections of the lung, liver, spleen, and kidney were taken and used for histology analysis. All animals were observed daily for signs of illness, and in some experiments, animals were weighed on the day when they were sacrificed. The results indicated that the cotton rat species, S. hispidus and S. fulviventer, were not a useful model for either SARS-CoV infection or disease. This observation was supported by the absence of any signs of illness, the failure to consistently demonstrate virus in the blood and tissues, and the absent of any notable histopathology. However, infected animals were capable of producing neutralizing antibodies against SARS-CoV, suggesting the seroconversion did occur. Further studies are warranted to consider other animal species in efforts to find better animal models for the evaluation of SARS-CoV vaccines and antiviral drugs.

On the electrodeposition of titanium in ionic liquids.

The ability to electrodeposit titanium at low temperatures would be an important breakthrough for making corrosion resistant layers on a variety of technically important materials. Ionic liquids have often been considered as suitable solvents for the electrodeposition of titanium. In the present paper we have extensively investigated whether titanium can be electrodeposited from its halides (TiCl(4), TiF(4), TiI(4)) in different ionic liquids, namely1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIm]Tf(2)N), 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl-sulfonyl)amide ([BMP]Tf(2)N), and trihexyltetradecyl-phosphonium bis(trifluoromethylsulfonyl)amide ([P(14,6,6,6)]Tf(2)N). Cyclic voltammetry and EQCM measurements show that, instead of elemental Ti, only non-stoichiometric halides are formed, for example with average stoichiometries of TiCl(0.2), TiCl(0.5) and TiCl(1.1). In situ STM measurements show that-in the best case-an ultrathin layer of Ti or TiCl(x) with thickness below 1 nm can be obtained. In addition, results from both electrochemical and chemical reduction experiments of TiCl(4) in a number of these ionic liquids support the formation of insoluble titanium cation-chloride complex species often involving the solvent. Solubility studies suggest that TiCl(3) and, particularly, TiCl(2) have very limited solubility in these Tf(2)N based ionic liquids. Therefore it does not appear possible to reduce Ti(4+) completely to the metal in the presence of chloride. Successful deposition processing for titanium in ionic liquids will require different maybe tailor-made titanium precursors that avoid these problems.

Determinants of sexual risk behavior among men who have sex with men accessing public sex environments in Chennai, India.

We conducted structured interviews with 200 men who have sex with men (MSM) recruited using time-space sampling from public sex environments (PSEs) in Chennai, India. Predictors of sexual risk behavior were assessed with chi2 tests and multiple logistic regression. One-third reported unprotected receptive anal sex (URAS) last time and 36% inconsistent condom use in the past month. URAS was associated with younger age, less than high school education, low income, and low HIV transmission knowledge (adjusted odds ratio [AOR] = 2.1, 2.5, 3.7 and 2.5, respectively). Inconsistent condom use was associated with less than high school education (AOR = 3.2) and low HIV transmission knowledge (AOR = 3.5). Multilevel HIV prevention strategies tailored for low socioeconomic kothis and other MSM in PSEs in Chennai should include peer interventions to increase knowledge of HIV transmission risks and sexually transmitted infections (STIs), and structural interventions to expand economic and educational opportunities, and accessible STI testing and treatment.

Human platelets circulating in mice: applications for interrogating platelet function and survival, the efficacy of antiplatelet therapeutics, and the molecular basis of platelet immunological disorders.

Herein we describe a novel animal model for examining the survival and function of human platelets following their circulation in non-obese diabetic/severe combined immunodeficient mice. Resting human platelets in platelet-rich plasma are introduced into the retro-orbital plexus, where they are absorbed with high efficiency and circulate for up to 2 days, comprising 10-20% of total circulating platelets. During this period of time, the human platelets can be exposed to a number of biochemical and immunochemical reagents, including novel antithrombotic compounds, or human antiplatelet antibodies that have been implicated in platelet destruction, activation or clearance. Platelets can also be subjected to a variety of storage conditions before infusion, and their relative survival and function following storage and circulation compared. The ability to evaluate in living mice the in vivo function and survival of circulating human platelets may prove valuable for determining mechanisms of antibody-mediated platelet passivation, and aid in the development of novel antiplatelet therapeutics.