The countryside or the city: Which environment is better for the honeybee?

For a number of years, the decline of honeybee (Apis mellifera) in North America and Europe has been the subject of much debate. Among the many factors proposed by hundreds of studies to explain this phenomenon is the hypothesis that agricultural activities using pesticides contribute to the weakness of bee colonies. Moreover, while urban beekeeping is presently booming in several cities, we do not know if this environment is more beneficial for bees than the typical, rural area. In the summer of 2018, we sampled honeybees (foragers and larvae) in rural (Laurentians) and urban (city of Montreal) areas and compared them using the following biomarkers: carotenoids, retinoids, α-tocopherol, metallothionein-like proteins (MTLPs), lipid peroxidation, triglycerides, acetylcholinesterase activity (AChE) and proteins. Pesticides, pharmaceuticals and personal care products (PPCPs) and metals were also quantified in honeybees' tissues. Our result revealed that, globally, urban foragers had higher levels of insecticides and PPCPs and that metals were in greater concentrations in urban larvae. Compared to rural foragers, urban foragers had higher concentrations of MTLPs, triglycerides, protein and AChE activity. The multifactorial analysis confirmed that insecticides, some metals and PPCPs were the most influential components in the contaminant‒biomarker relationships for both foragers and larvae.

Risk factors for Clostridioides difficile infection in hospitalized patients and associated mortality in Japan: a multi-centre prospective cohort study.

BACKGROUND: Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood. AIM: This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan. METHODS: Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated. FINDINGS: In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection >18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis. CONCLUSION: Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation.

Keratinocyte replicative senescence has an important role in time-dependent changes of the epidermis, a tissue with high turnover. Senescence encompasses growth arrest during which cells remain metabolically active but acquire a typical enlarged, vacuolar and flattened morphology. It is also accompanied by the expression of endogenous senescence-associated-ß-galactosidase and specific gene expression profiles. MicroRNAs levels have been shown to be modulated during keratinocytes senescence, playing key roles in inhibiting proliferation and in the acquisition of senescent markers. Here, we identify miR-191 as an anti-proliferative and replicative senescence-associated miRNA in primary human keratinocytes. Its overexpression is sufficient per se to induce senescence, as evaluated by induction of several senescence-associated markers. We show that SATB1 and CDK6 3'UTRs are two miR-191 direct targets involved in this pathway. Cdk6 and Satb1 protein levels decrease during keratinocytes replicative senescence and their silencing by siRNA is able to induce a G1 block in cell cycle, accompanied by an increase in senescence-associated markers.

Delivering cervical cancer prevention services in low-resource settings.

The goals of any cervical cancer prevention program should be threefold: to achieve high coverage of the population at risk, to screen women with an accurate test as part of high-quality services, and to ensure that women with positive test results are properly managed. This article focuses on the experiences of the Alliance for Cervical Cancer Prevention (ACCP) in delivery of screening and treatment services as part of cervical cancer prevention projects in Africa, Latin America, and Asia. Research and experience show that cervical cancer can be prevented when strategies and services are well planned and well managed and when attention is paid to program monitoring and evaluation. Coordination of program components, reduction of the number of visits, improvement of service quality, and flexibility in how services are delivered are all essential features of an effective service.

Random effects survival models gave a better understanding of heterogeneity in individual patient data meta-analyses.

BACKGROUND AND OBJECTIVE: Individual patient data meta-analysis consists in combining data from all available trials dealing with a therapeutic problem in order to increase the power of statistical analyses. A key issue when analyzing these pooled data sets is intertrial heterogeneity. In survival data, heterogeneity manifests itself either by differing treatment effects between the included trials or by a baseline hazard that differs between studies. One way to investigate and accommodate this heterogeneity is to use models that include random effects. METHODS: We apply this class of models to the Meta-Analysis of Chemotherapy in Head and Neck Cancers, in which strong heterogeneity is exhibited. This meta-analysis pooled 63 trials involving 10,741 patients. RESULTS: We show that such modeling permits a better understanding of heterogeneity in the MACH-NC data, both from a frequentist and from a Bayesian point of view. In particular, the modeling suggests the presence of two outlying sets of trials whose baseline risk could explain the apparent efficacy or inefficacy of some treatment protocols. CONCLUSION: We conclude that this family of random-effects models is a useful tool for exploring heterogeneity in meta-analyses of time-to-event data, and that its features can be applied to a very wide range of studies.

Papillomavirus infection in rural women in southern India.

To investigate the prevalence of, and the risk factors for, cervical infection with 44 types of human papillomavirus (HPV) in a rural area in the Dindigul District, Tamil Nadu, India, we interviewed and obtained cervical cell samples from 1891 married women aged 16-59 years. HPV prevalence was 16.9% overall and 14.0% among women without cervical abnormalities, or 17.7 and 15.2%, respectively, age-standardised to the world standard population. In all, 21.9% of infections involved more than one HPV type. High-risk HPV types predominated, particularly HPV 16 (22.5% of women infected), followed by HPV 56, HPV 31, HPV 33 and HPV 18. Unlike most populations studied in developed countries, HPV prevalence was constant across the age groups. HPV positivity was inversely associated with education level (odds ratio (OR) among women with high school vs no education=0.6) and positively associated with widowhood and divorce (OR=1.7), nulligravidity (OR=2.3), and condom use (OR=2.6). It is unclear how much low clearance of, or frequent reinfection with HPV accounted for the study prevalence of infection in different age groups.

Accuracy of conventional cytology: results from a multicentre screening study in India.

OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in five cross-sectional studies. Three thresholds were used to define test positivity: atypical squamous cells of uncertain significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for final disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically confirmed HSIL. RESULTS: The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A significantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. CONCLUSION: The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and specificity.

Micromixers to produce cosmetic emulsions.

In the cosmetics industry, emulsions play a key-role in active solubilization and texture/efficacy optimization. However, depending on their physico-chemical properties, the active ingredients are often more stable in a single phase: for example, Vitamin A is more stable in an oily phase than in a water phase. We have developed a special mixing device which produces an emulsion in the body of the pump, immediately before application on the skin. The mixing unit consists of two silicon chips. Each chip has several Y-shaped microchannels and intersections etched on its upper surface. When the two etched surfaces are bonded together, they produce series of interconnecting micromixing elements which permit the repeat mixing of the two phases, thus producing an extremely homogenous emulsion. These micromixers require carefully designed formulae in which the physico-chemical properties of each raw material are essential to obtain a spontaneous emulsion. This device has been incorporated into a spray pack and optimized to deliver the spontaneous emulsion when finger pressure is applied.

Experimental determination of a procedure for casting a solid coloured emulsion.

The aim of this study was to determine the experimental procedure for casting a solid water/oil (W/O) emulsion foundation. This process will enable us to preserve the organoleptic qualities of the foundation (hardness, surface appearance and cosmetic sensation) as well as maintaining the percentage of water contained in the formula. Two different industrial parameters were studied: * Influence of the temperature used to cast the bulk in the mould. * Influence of the type of cooling used for the mould, once full. For each trial, the hardness and the melting point were measured. The optimum results for this process were as follows: * Casting temperature: 65 degrees C. * Cooling temperature: 4 degrees C.

HIV-1 epidemic trends in rural south-west Uganda over a 10-year period.

The objective of this study was to examine the epidemic trends of HIV-1 infection in a rural population cohort in Uganda followed for 10 years. The methods used were to assess incidence and prevalence trends in adults in this longitudinal cohort study. The results showed that incidence of infection has fallen significantly in all adults, and separately in males, females, young adults and older adults over the course of the study period. There was also a reduction in prevalence, especially in young men and women. There was some evidence of a cohort effect in women. The conclusions are that this study provides the first evidence of a falling incidence in a rural general population in Africa. This was an observational cohort exposed to national health education messages, giving hope that similar campaigns elsewhere in Africa could be used effectively in efforts to control the HIV epidemic.

Generalizability of population-based studies on AIDS: a comparison of newly and continuously surveyed villages in rural southwest Uganda.

BACKGROUND: Population-based studies are thought to provide generalizable epidemiological data on the human immunodeficiency virus type 1 (HIV-1) epidemic. However, longitudinal studies are susceptible to bias from added attention caused by study activities. We compare HIV-1 prevalence in previously and newly surveyed villages in rural southwest Uganda. METHODS: The study population resided in 25 neighbouring villages, of which 15 have been surveyed for 10 years. Respondents (>/=13 years) provided socio-demographic and sexual behaviour data and a blood sample for HIV-1 serology in private after informed consent. We tested the independent effect of residency: (1) original versus new villages; (2) proximity to main road; and (3) proximity to trading centre on HIV-1 serostatus of respondents using multivariate logistic regression. RESULTS: There were 8,990 adults censused, 68.3% were from the original villages, 48.2% were males and 6111 (68.0%) were interviewed and had definite HIV-1 serostatus. The HIV-1 prevalence was 6.1% overall, 5.7% in the new, and 6.4% in the original villages (P = 0.25). Residency in the new or original villages did not independently predict HIV-1 serostatus of respondents (P = 0.46). Independent predictors of HIV-1 serostatus were education (primary or higher, odds ratio [OR] = 1.7 and 1.4, respectively), being separated or widowed OR = 4.2, reported previous use of a condom OR = 1.8, or reported genital ulceration OR = 3.3, and age group 25-34 and 35-44 years OR = 5.8 and OR = 4.8 (all P

Diarrhea, CD4 counts and enteric infections in a community-based cohort of HIV-infected adults in Uganda.

OBJECTIVES: To examine relationships between diarrhoea, CD4 cell counts and stool pathogens in a community-based cohort of HIV-infected adults in Uganda. PATIENTS AND METHODS: Stool specimens, obtained between October 1995 and December 1997, were linked to patients' symptoms and laboratory results. The relationship between CD4 counts and symptoms was tested using the Wilcoxon rank-sum test and those between organisms and diarrhoea using first a univariate Mantel-Haenszel analysis and then a logistic regression model adjusted for CD4 count and multiple organisms. RESULTS: 1,213 HIV-infected individuals (70% women, median CD4 cell count at enrollment 215 cells/microl) were followed for 1,224 person years of observation (pyo). 484 stool samples were examined, 357 from patients with diarrhoea. The rate of diarrhoea was 661 episodes per 1,000 pyo. CD4 counts were significantly lower in individuals with diarrhoea than those without (P < 0.001, Wilcoxon rank-sum test). Forty-nine percent of diarrhoeal stools and 39% of stools from asymptomatic patients contained enteric pathogens. The most frequent isolates were helminths (29.5% of all stools), followed by bacteria (19.2%) and then protozoa (8.9%). Rates of isolation of diarrhoea-associated pathogens were 29% from diarrhoeal stools and 17% from asymptomatic stools (P = 0.01, chi(2) test). The association between diarrhoea and infection with bacteria or protozoa was weak and there was no association with helminths. Cryptosporidium parvum infection alone was associated with low CD4 counts. CONCLUSIONS: Diarrhoea was common and most strongly associated with low CD4 counts. Bacteria were frequently found, even in stools from asymptomatic individuals. Over two-thirds of diarrhoeal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhoea in this population.

Declining HIV-1 incidence and associated prevalence over 10 years in a rural population in south-west Uganda: a cohort study.

BACKGROUND: In Uganda, there have been encouraging reports of reductions in HIV-1 prevalence but not in incidence, which is the most reliable measure of epidemic trends. We describe HIV-1 incidence and prevalence trends in a rural population-based cohort between 1989 and 1999. METHODS: We surveyed the adult population of 15 neighbouring villages for HIV-1 infection using annual censuses, questionnaires, and serological surveys. We report crude annual incidence rates by calendar year and prevalence by survey round. FINDINGS: 6566 HIV-1 seronegative adults were bled two or more times between January, 1990, and December, 1999, contributing 31984 person years at risk (PYAR) and 190 seroconversions. HIV-1 incidence fell from 8.0 to 5.2 per 1000 PYAR between 1990 and 1999 (p=0.002, chi(2) for trend). Significant sex-specific and age-group-specific reductions in incidence were evident. Incidence was 37% lower for 1995-99 than for 1990-94 (p=0.002, t-test). On average, 4642 adult residents had a definite HIV-1 serostatus at each yearly survey round. HIV-1 prevalence fell significantly between the first and tenth annual survey rounds (p=0.03, chi(2) for trend), especially among men aged 20-24 years (6.5% to 2.2%) and 25-29 years (15.2% to 10.9%) and women aged 13-19 years (2.8% to 0.9%) and 20-24 years (19.3% to 10.1%) (all p<0.001, chi(2) for trend). INTERPRETATION: Our findings of a significant drop in adult HIV-1 incidence in rural Ugandans give hope to AIDS control programmes elsewhere in sub-Saharan Africa where rates of HIV-1 infection remain high.

Radio-frequency tissue ablation of the liver: effects of vascular occlusion on lesion diameter and biliary and portal damages in a pig model.

The aim of this study was to assess the effect of vascular occlusion on radio-frequency (RF) lesion size and on potential associated biliary and portal lesions. Radio-frequency lesions using a 1-cm exposed-tip cooled electrode were created in pig liver. Liver perfusion was modified by arterial embolization (n=2), left portal clamping (n=2), and both (n=2). Two pigs were used as controls. Two weeks after, control portography was performed, animals were killed, and ex-vivo cholangiography was carried out. Pathological studies evaluated the lesion surface and associated portal and biliary damages. A mathematical regression model showed that portal occlusion increased by 43 mm2 (+40%) the surface of RF lesions, arterial occlusion by 135 mm2 (+126%), and associated occlusion by 466 mm2 (+435%). Biliary stenoses were found in 4 cases (two arterial occlusions, one portal occlusion, and one associated occlusion). One case of partial portal vein thrombosis was found in one case of portal occlusion and resolved at 2 weeks. Ischemic damages adjacent to RF lesions were found in cases of combined occlusions. The reduction of liver perfusion increases significantly the size of RF lesions but is associated with a risk of biliary, portal, or parenchymal complications.

[Statistical analysis of a prognostic study]. / L'analyse statistique d'une etude pronostique.

Prognostic studies aim to stress and quantify the effect of some individual characteristics on the evolution of an illness. Statistically speaking, most of the time, a prognostic study relying on a censored endpoint can be summarized in building a Cox model. Even though they are often encountered in clinical research or in epidemiology, prognostic studies are rarely reliable and there is no real consensus on the way to perform them. The aim of this article is to give some directions regarding the analysis of such studies. For illustration purpose, this paper relies on commented results from a study in oncology.

Absence of a recognizable seroconversion illness in Africans infected with HIV-1.

It is difficult to assess the proportion of individuals who experience an acute seroconversion illness after infection with HIV-1. We found that five out of 27 recent HIV-1 seroconverters (18.5%) in a population-based cohort in rural Uganda and four out of 22 HIV-negative controls (18.2%) reported a flu-like illness. More symptoms were reported by seroconverters, but the duration of illness was similar in both groups. We found no association between symptoms and infection with HIV-1 subtype A or D.

Genital ulceration in rural Uganda: sexual activity, treatment-seeking behavior, and the implications for HIV control.

BACKGROUND: Genital ulcer disease (GUD) is documented as a significant risk factor for HIV acquisition. Its prompt recognition and effective treatment are important components of HIV control in sub-Saharan Africa. GOALS: To determine the rate and risk factors for GUD, and to describe sexual and treatment-seeking behavior. STUDY DESIGN: A longitudinal follow-up study of 525 individuals, both those infected with HIV and those uninfected, was conducted in a population-based, clinical cohort over 9 years. RESULTS: The rate of GUD in this population was 16/100 person years, and 30% of the participants reported an episode during the follow-up period. The rates were almost four times higher in participants infected with HIV than in those who were HIV-negative. Half of the participants with a regular sexual partner reported engaging in sex while symptomatic, and only 16% informed their partner. Treatment was sought for only 12% of the genital ulcer disease episodes, despite open access to doctors at a free clinic. A self-diagnosis of genital herpes did not affect treatment-seeking or sexual behavior. CONCLUSIONS: Genital ulcer disease is very common in this rural population, especially among those infected with HIV. Few seek treatment, and many continue sexual activity despite symptoms without informing their partners. The implications of these findings for HIV control are a cause for concern.

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.