Stage of colorectal cancer diagnosis for immigrants: a population-based retrospective cohort study in Ontario, Canada.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer death in Canada. Immigrants in Ontario, Canada's most populous province, are known to have lower rates of CRC screening, but differences in stage of CRC diagnosis are not known. METHODS: We utilized linked administrative databases to compare early (stage I-II) versus late (stage III-IV) stage of CRC diagnosis for immigrants versus long-term residents among patients diagnosed in Ontario between 2012 and 2017 (n = 37,717) and examined the association of immigration-related, sociodemographic, and healthcare-related factors with stage. RESULTS: Almost 45% of those with CRC were diagnosed at a late stage. Immigrants were slightly more likely to be diagnosed at a late stage than their long-term resident counterparts [Adjusted relative risks (ARRs) 1.06 (95% CI 1.02-1.10)], but after adjusting for age and sex, this difference was no longer significant. In fully adjusted models, we observed a higher likelihood of late-stage diagnosis for people with the fewest co-morbidities (ARR 0.86 [95% CI 0.83-0.89]) and those with no visits to primary care (versus a high level of continuity of care) [ARR 1.07 (95% CI 1.03-1.12)]. CONCLUSION: Immigrants were not more likely to have a late-stage CRC diagnosis after adjusting for relevant factors, but access to primary care and healthcare contact was significantly associated with diagnostic stage. IMPACT: Attachment to a primary care provider who provides regular preventive care may play a role in more favorable stage at diagnosis for CRC and thus should be a healthcare system priority.

School food environments associated with adiposity in Canadian children.

BACKGROUND/OBJECTIVES: Targeting obesogenic features of children's environment that are amenable to change represents a promising strategy for health promotion. The school food environment, defined as the services and policies regarding nutrition and the availability of food in the school and surrounding neighborhood, is particularly important given that students travel through the school neighborhood almost daily and that they consume a substantial proportion of their calories at school. SUBJECTS/METHODS: As part of the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) cohort study, we assessed features of school indoor dietary environment and the surrounding school neighborhoods, when children were aged 8-10 years (2005-2008). School principals reported on food practices and policies within the schools. The density of convenience stores and fast-food outlets surrounding the school was computed using a Geographical Information System. Indicators of school neighborhood deprivation were derived from census data. Adiposity outcomes were measured in a clinical setting 2 years later, when participants were aged 10-12 years (2008-2011). We conducted cluster analyses to identify school food environment types. Associations between school types and adiposity were estimated in linear regression models. RESULTS: Cluster analysis identified three school types with distinct food environments. Schools were characterized as: overall healthful (45%); a healthful food environment in the surrounding neighborhood, but an unhealthful indoor food environment (22%); or overall unhealthful (33%). Less healthful schools were located in more deprived neighborhoods and were associated with greater child adiposity. CONCLUSIONS: Despite regulatory efforts to improve school food environments, there is substantial inequity in dietary environments across schools. Ensuring healthful indoor and outdoor food environments across schools should be included in comprehensive efforts to reduce obesity-related health disparities.

Custom-made rotating hinge total knee replacement in a patient with congenital tibial deficiency avoids the need for amputation.

We report a unique case of a patient with type 2 congenital tibial deficiency and disabling knee osteoarthritis in whom a custom-made rotating hinge knee replacement was successfully performed, allowing continued mobilisation with a below-knee prosthesis, thereby avoiding the need for an above-knee amputation. Level of evidence Therapeutic study, Level IV.

Surgical site infection rate is lower in laparoscopic than open colorectal surgery.

OBJECTIVE: Few studies have investigated whether surgical site infection (SSI) incidence differs between laparoscopic colorectal surgery (LCS) and open colorectal surgery (OCS). This study investigated the SSI incidence using the validated UK SSI Surveillance Service (SSISS) criteria for diagnosing wound infections. METHOD: Prospective data collection recorded patients' demographics, operative details, antibiotic use, wound evaluation and microbiological wound culture results, for consecutive patients undergoing elective resectional LCS and OCS. Postdischarge surveillance consisted of patient questionnaires sent out at 30 days and the primary care communication. RESULTS: A total of 122 patients underwent colorectal resections over 1 year (LCS 43; OCS 79). Patients' demographics and operative case-mix were similar for both groups, including body mass index (BMI), diabetic and smoking status. Operative duration was longer in the LCS group compared with OCS group (P = 0.012, Mann-Whitney U-test), but hospital stay was shorter for LCS (P = 0.0001, Mann-Whitney U-test). The SSI rate was significantly lower in the LCS than OCS group (7%vs 25% respectively; P = 0.015, two-tailed Fisher's exact test). BMI > 30 and operation length > 4 h influenced the risk of SSI formation (P < 0.05, chi-squared test). One LCS patient required conversion to a limited laparotomy. CONCLUSIONS: Surgical site infection incidence is significantly lower following LCS when compared with OCS. Confounding factors in this study include patient selection for LCS and nonrandomization.

HPV sampling options for cervical cancer screening: preferences of urban-dwelling Canadians in a changing paradigm.

Introduction: Of women in Canada diagnosed with invasive cervical cancer, 50% have not been screened according to guidelines. Interventions involving self-collected samples for human papillomavirus (hpv) screening could be an avenue to increase uptake. To guide the development of cervical cancer screening interventions, we assessed ■ preferred sample collection options,■ sampling preferences according to previous screening behaviours, and■ preference for self-sampling among women not screened according to guidelines, as a function of their reasons for not being screened. Methods: Data were collected in an online survey (Montreal, Quebec; 2016) and included information from female participants between the ages of 21 and 65 years who had not undergone hysterectomy and who had provided answers to survey questions about screening history, screening interval, and screening preferences (n = 526, weighted n = 574,392). Results: In weighted analyses, 68% of all women surveyed and 82% of women not recently screened preferred screening by self-sampling. Among women born outside of Canada, the United States, or Europe, preference ranged from 47% to 60%. Nearly all women (95%-100%) who reported fear or embarrassment, dislike of undergoing a Pap test, or lack of time or geography-related availability of screening as one of their reasons for not being screened stated a preference for undergoing screening by self-sampling. Conclusions: The results demonstrate a strong preference for self-sampling among never-screened and not-recently-screened women, and provides initial evidence for policymakers and researchers to address how best to integrate self-sampling hpv screening into both organized and opportunistic screening contexts.

Limb contouring after massive weight loss: functional rather than aesthetic improvement.

BACKGROUND: After massive weight loss, both upper and lower limbs show a similar deformity which consists of redundancy and ptosis of the cutaneous mantle. Many disturbances are associated with this abnormality, which can be treated surgically. A retrospective review of limb-contouring procedures after massive weight loss is presented. METHODS: Thigh lift and arm lift procedures are described. All surgeries of upper and lower limbs contouring performed between 2003 and 2006 are reviewed with regard to quantity of tissue removed, comorbidities, complications and patients' satisfaction, which was surveyed through a questionnaire exploring functional and esthetic results (maximum score 3). RESULTS: Among 48 bilateral limb-contouring procedures, medial thigh lifts were 35 (73%) and brachioplasties were 13 (27%). Mean age was 46 and average body mass index variation was 20 kg/m(2). The most frequent comorbidity was gallstones (28%). In 46% of the whole group of patients, there was no complication to mention. The most frequent complication was acute anaemia in both procedures (43% in thigh lift and 54% in arm lift). Mean quantity of adipose-dermoid tissue removed was 766 g in thigh lift and 463 g in arm lift. In case of surgery combined with liposuction, the average aspirated volume was 1,933 ml (thighs) and 1,117 ml (arms). Patients' satisfaction was 2.7 for thighs and 2.6 for arms, as average. CONCLUSION: The rate of complications in limb contouring after weight loss is higher than the analogue esthetic procedures. Nevertheless, due to the rehabilitative significance of limb surgery after weight loss, this step is to be included as fundamental in obese patients' surgical therapy.

Area-level income disparities in colorectal screening in Canada: evidence to inform future surveillance.

Background: Participation in colorectal screening remains low even in countries with universal health coverage. Area-level determinants of low screening participation in Canada remain poorly understood. Methods: We assessed the association between area-level income and two indicators of colorectal screening (having never been screened, having not been screened recently) by linking census-derived local area-level income data with self-reported screening data from urban-dwelling respondents to the Canadian Community Health Survey (50-75 years of age, cycles 2005 and 2007, n = 18,362) who reported no known risk factors for colorectal cancer. Generalized estimating equation Poisson models estimated the prevalence ratios and differences for having never been screened and having not been screened recently, adjusting for individual-level income, education, marital status, having a regular physician, age, and sex. Results: About 53% of the study population had never been screened. Among individuals who had ever been screened, 35% had been screened recently. Adjusting for covariates, lower area-level income was associated with having never been screened [covariate-adjusted prevalence ratios: 1.24 for quartile 1; 95% confidence limits (cl): 1.16, 1.34; 1.25 for quartile 2; 95% cl: 1.15, 1.33; 1.15 for quartile 3; 95% cl: 1.08, 1.23]. Among individuals who had been screened in their lifetime, area-level income was not associated with having not been screened recently. Conclusions: Lower area-level income is associated with having never been screened for colorectal cancer even after adjusting for individual socioeconomic factors. Those findings highlight the potential importance of socioeconomic contexts for colorectal screening initiation and merit attention in both future research and surveillance efforts.

Visual Outcomes Following Intravitreal Ranibizumab for Diabetic Macular Edema in a Pro Re Nata Protocol from Baseline: A Real-World Experience.

PURPOSE: To investigate long-term outcomes of pro re nata (PRN) treatment protocol of ranibizumab for diabetic macular edema (DME) adopted from the first month of therapy without 3 loading doses. DESIGN: Retrospective interventional study. METHODS: We analyzed 180 eyes of 144 patients treated with ranibizumab for DME with a minimum follow-up of 1 year during December 2013 to December 2017. Data of all patients with treatment-naive center-involving DME who received at least 1 intravitreal injection of ranibizumab during the study period were drawn from a locally adapted electronic form for DME. The primary outcome measure was change in best-corrected visual acuity (BCVA) from baseline at 1-year follow-up, with intergroup comparisons in BCVA between eyes receiving 1, 2, and 3 injections in the first 3 months of treatment. RESULTS: The mean baseline BCVA was 0.47 ± 0.30 logMAR, which improved to 0.38 ± 0.3 logMAR (P = 0.003) at 3 months and stabilized at 0.35 ± 0.27 logMAR at 1 year (P = 0.46 vs BCVA at 3 months) and 0.34 ± 0.26 logMAR at 2 years of follow-up (P = 0.44 vs BCVA at 3 months). At 3 months, 24 eyes (13%) underwent 1 intravitreal injection, 52 eyes (29%) had 2 injections, and the majority (n = 104 eyes, 58%) had 3 injections on a monthly basis. During the first year, the group that received only 1 injection in the first 3 months also required fewer injections and fewer follow-up visits compared with those receiving 2 or 3 injections in the first 3 months. CONCLUSIONS: One-third of eyes with DME responded well to PRN treatment strategy from the first month without 3 loading doses of ranibizumab. Baseline visual acuity is the best predictor of vision at 1 and 2 years of follow-up.

Unemployment as a risk factor for AIDS and death for HIV-infected patients in the era of highly active antiretroviral therapy.

OBJECTIVES: To assess the association between social situation and disease progression among patients diagnosed with HIV infection since the advent of highly active antiretroviral therapy (HAART), taking late testing into account. METHODS: Prospective cohort study of adults diagnosed with HIV since 1996 in six large HIV reference centres in France. Associations between social situation and death, disease progression and treatment initiation were assessed using Cox regression model. Analysis was restricted to 5302 patients (77.9% of the sample) for whom the status at HIV diagnosis (late or not late) was known. RESULTS: 134 people (2.5%) died and 400 presented with a new AIDS defining event (7.5%). In multivariate analysis, probabilities of death (HR 3.75, 95% CI 2.11 to 6.66) and disease progression (HR 1.59, 95% CI 1.17 to 2.15) were higher for non-working patients and for late testers (HR 9.18, 95% CI 4.32 to 19.48 for death) and lower for treated patients (HR 0.18, 95% CI 0.08 to 0.41 for death and HR 0.29, 95% CI 0.20 to 0.42 for disease progression). The probability of receiving antiretroviral treatment was not associated with employment status but was higher for late testers, for those living in a stable relationship and lower for those diagnosed after 2000. CONCLUSION: Among patients diagnosed for HIV infection in the HAART era, poor social situation is an independent risk factor of mortality and morbidity, and is not explained by delayed access to diagnosis or treatment.

Chest wall and hemidiaphragm reconstruction with Gore-Tex mesh and omolateral latissimus dorsi flap. A case report.

There are various method of reconstruction when chest wall resection is performed for the treatment of tumors of the chest wall. In this case a chest wall resection and reconstruction was performed using an omolateral latissimus dorsi flap, together with Gore-Tex mesh. A 42-year-old woman was diagnosed as having a huge low grade chondrosarcoma and underwent surgical resection which interested the anterior chest wall from the level of the IV to X rib and the right hemidiaphragm. Gore-Tex mesh was fixed to the residual chest wall and an ipsilateral pedicled latissimus dorsi muscle flap was placed on the alloplastic mesh. The patient was discharged from the hospital 17 days postoperatively. The postoperative course was uneventful and the wound was fine.

Lenz microphthalmic syndrome in an Indian patient.

A case of Lenz microphthalmia syndrome in a seven-month-old male child having features of unilateral anophthalmia, microcephaly, external ear and finger abnormalities, hydrocele and hypospadias is being reported. The unilateral involvement and anophthalmia is rare in Lenz syndrome. The manifestation of hydrocele in association with this syndrome has not been seen in earlier cases. This is the first documented case from India.

Evidence for the extracellular reduction of alpha-lipoic acid by Leishmania donovani promastigotes: a transplasma membrane redox system.

Leishmania donovani cells, capable of reducing certain electron acceptors with redox potentials at pH 7.0 down to -290 mV, outside the plasma membrane, can reduce the oxidised form of alpha-lipoic acid. alpha-Lipoic acid has been used as natural electron acceptor probe for studying the mechanism of transplasma membrane electron transport. Transmembrane alpha-lipoic acid reduction by Leishmania was not inhibited by mitochondrial inhibitors as azide, cyanide, rotenone or antimycin A, but responded to hemin, modifiers of sulphhydryl groups and inhibitor of glycolysis. The protonophores carbonyl cyanide chlorophenylhydrazone and 2,4-dinitrophenol showed inhibition of alpha-lipoic acid reduction. This transmembrane redox system differs from that of mammalian cells in respect to its sensitivity of UV irradiation and stimulation by diphenylamine. Thus a naphthoquinone coenzyme appears to be involved in alpha-lipoic acid reduction by Leishmania cells.

Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats.

The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the U.S. Congress to declare it a controlled substance, although conclusive evidence of its anabolic/androgenic activity is lacking. We determined whether THG affects myogenic differentiation and androgen receptor (AR)-mediated signaling, whether it binds to AR, and whether it has androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats. THG bound to AR with an affinity similar to that of dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR expression, induced AR nuclear translocation, dose dependently increased the area of myosin heavy chain type II-positive myotubes, and up-regulated myogenic determination and myosin heavy chain type II protein expression. The interaction between AR and the A ring of THG was similar to that between AR and the A ring of dihydrotestosterone, but the C17 and C18 substituents in THG had a unique stabilizing interaction with AR. THG administration prevented the castration-induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of fat-free mass in orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for rapid screening of anabolic/androgenic agents.

Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite.

A regulated protein turnover machinery in the cell is essential for effective cellular homeostasis; any interference with this system induces cellular stress and alters the normal functioning of proteins important for cell survival. In this study, we show that persistent cellular stress and organelle dysfunction because of disruption of cellular homeostasis in human malaria parasite Plasmodium falciparum, leads to apoptosis-like cell death. Quantitative global proteomic analysis of the stressed parasites before onset of cell death, showed upregulation of a number of proteins involved in cellular homeostasis; protein network analyses identified upregulated metabolic pathways that may be associated with stress tolerance and pro-survival mechanism. However, persistent stress on parasites cause structural abnormalities in endoplasmic reticulum and mitochondria, subsequently a cascade of reactions are initiated in parasites including rise in cytosolic calcium levels, loss of mitochondrial membrane potential and activation of VAD-FMK-binding proteases. We further show that activation of VAD-FMK-binding proteases in the parasites leads to degradation of phylogenetically conserved protein, TSN (Tudor staphylococcal nuclease), a known target of metacaspases, as well as degradation of other components of spliceosomal complex. Loss of spliceosomal machinery impairs the mRNA splicing, leading to accumulation of unprocessed RNAs in the parasite and thus dysregulate vital cellular functions, which in turn leads to execution of apoptosis-like cell death. Our results establish one of the possible mechanisms of instigation of cell death by organelle stress in Plasmodium.

Involvement of tryptophan residues of lysozyme in its binding with cytosine arabinoside.

Cytosine-1-beta-D-arabinofuronaside, an antileukemic drug and hen egg white lysozyme (E.C. 3.2.1.17) form a 1:1 complex with Ka 1.2 X 10(4) M-1 at low drug concentrations. However, association was cooperative in nature at high concentrations with values of Ka = 1.8 X 10(4) M-1 and N = 2. Involvement of tryptophan in the drug protein complex was evident from fluorescence quenching and from the association of the drug with free tryptophan with a Ka = 1.5 X 10(4) M-1. Modification of tryptophan 108 reduced the binding by 89% suggesting a major role for this residue in the binding process. Oxidation of tryptophan 62 and acetylation of lysine residues also decreased the affinity of the drug to the protein by 55 and 66% respectively. Binding improved with increase in temperature and positive values for change in enthalpy and entropy were obtained. Ara-C inhibited lysozyme activity noncompetitively.

FT-IR and near-infrared FT-Raman studies of the secondary structure of insulinotropin in the solid state: alpha-helix to beta-sheet conversion induced by phenol and/or by high shear force.

Insulinotropin (glucagon-like peptide I) is a peptide containing 31 amino acid residues. It stimulates the secretion of the hormone insulin. The solubility of this peptide is highly dependent on its environment and the treatment that it has undergone. For instance, synthetic insulinotropin is highly soluble in neutral phosphate-buffered saline (1 mg/mL). However, the application of shear force by stirring renders it extremely insoluble (1 micrograms/mL). This property may be explained in terms of a change in peptide secondary structure with no alteration in primary structure. In order to understand this phenomenon, FT-IR and near-IR FT-Raman were employed to examine four samples prepared under different experimental conditions. It was found that solubility decreases as the alpha-helix is converted to an antiparallel beta-sheet structure.

The effects of clofazimine, niclosamide & amphotericin B, on electron transport of Leishmania donovani promastigotes.

BACKGROUND & OBJECTIVES: The study was undertaken to explore the locus of interaction of clofazimine and niclosamide which showed substantial growth inhibition property in Leishmania donovani promastigotes. METHODS: The uptake of final electron acceptor oxygen and 2,6-dichlorophenolindophenol (DCPIP) reduction in the electron transport chain were measured by constant volume Warburg respirometer and monitoring absorbance at 600 nm, respectively. Irreversibility of O2 uptake inhibition by clofazimine and niclosamide was determined by dilution of cell suspension followed by centrifugation. RESULTS: Clofazimine and niclosamide showed their minimum inhibitory concentration (MIC) at 33 and 150 micrograms/ml, respectively. Oxygen uptake inhibition by clofazimine and niclosamide was not reversed by removal of the drug by centrifugation. Rotenone, a potent inhibitor of mammalian electron transport chain showed no inhibition on the electron transport chain of L. donovani promastigotes. Cyanide at 1 mM concentration showed partial inhibition in L. donovani promastigotes. Oxygen uptake and DCPIP reduction by L. donovani promastigotes were highly sensitive to sulphhydryl group inhibitors. Strong inhibition of oxygen uptake (80-100%) by L. donovani promastigotes was achieved by clofazimine, niclosamide and amphotericin B. Amphotericin B failed to inhibit DCPIP reduction by L. donovani promastigotes, whereas DCPIP reduction was inhibited by clofazimine and niclosamide, respectively. INTERPRETATION & CONCLUSION: DCPIP reduction was mediated by transplasma membrane electron transport as evidenced by its inhibition with membrane impermeable quinone 1,2-naphthoquinone-4-sulphonic acid (NQSA). Transplasma membrane electron transport requires b-cytochromes and sulphhydryl groups for its function and was inhibited by clofazimine and niclosamide.