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Abstract Background Drought is a major consequence of global heating that has negative impacts on agriculture. Potato is a drought-sensitive crop; tuber growth and dry matter content may both be impacted. Moreover, water deficit can induce physiological disorders such as glassy tubers and internal rust spots. The response of potato plants to drought is complex and can be affected by cultivar type, climatic and soil conditions, and the point at which water stress occurs during growth. The characterization of adaptive responses in plants presents a major phenotyping challenge. There is therefore a demand for the development of non-invasive analytical techniques to improve phenotyping. Results This project aimed to take advantage of innovative approaches in MRI, phenotyping and molecular biology to evaluate the effects of water stress on potato plants during growth. Plants were cultivated in pots under different water conditions. A control group of plants were cultivated under optimal water uptake conditions. Other groups were cultivated under mild and severe water deficiency conditions (40 and 20% of field capacity, respectively) applied at different tuber growth phases (initiation, filling). Water stress was evaluated by monitoring soil water potential. Two fully-equipped imaging cabinets were set up to characterize plant morphology using high definition color cameras (top and side views) and to measure plant stress using RGB cameras. The response of potato plants to water stress depended on the intensity and duration of the stress. Three-dimensional morphological images of the underground organs of potato plants in pots were recorded using a 1.5 T MRI scanner. A significant difference in growth kinetics was observed at the early growth stages between the control and stressed plants. Quantitative PCR analysis was carried out at molecular level on the expression patterns of selected drought-responsive genes. Variations in stress levels were seen to modulate ABA and drought-responsive ABA-dependent and ABA-independent genes. Conclusions This methodology, when applied to the phenotyping of potato under water deficit conditions, provides a quantitative analysis of leaves and tubers properties at microstructural and molecular levels. The approaches thus developed could therefore be effective in the multi-scale characterization of plant response to water stress, from organ development to gene expression.

Advances in gene therapy, especially for brain diseases, have created new imaging demands for noninvasive monitoring of gene expression. While reporter gene imaging using co-expression of fluorescent protein-encoding gene has been widely developed, these conventional methods face significant limitations in longitudinal in vivo applications. Magnetic resonance imaging (MRI), specifically chemical exchange saturation transfer (CEST) MRI, provides a robust noninvasive alternative that offers unlimited depth penetration, reliable spatial resolution, and specificity toward particular molecules. In this study, we explore the potential of CEST-MRI for monitoring gene expression in neurons. We designed a CEST polypeptide reporter expressing 150 arginine residues and evaluated its expression in the living brain after viral vector delivery. A longitudinal study performed at one and 2 months postinjection showed that specific CEST signal was observable. In particular, the CEST contrast exhibited distinct peaks at 0.75 and 1.75 ppm, consistent with the expected hydroxyl and guanidyl protons resonance frequencies. Histological study confirmed the specific neuronal expression of the transgene evidenced by the fluorescence signal from the td-Tomato fluorophore fused to the polypeptide. The ability to image noninvasively a neuron-specific CEST-MRI reporter gene could offer valuable insights for further developments of gene therapy for neurological disorders., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Competing Interests: I declare no competing interests.

Background: One hundred years ago, Albert Calmette developed an avirulent strain of Mycobacterium bovis, but there is no evidence that his BCG strain was more immunogenic than wild-type M. bovis. Geographic variations in BCG efficacy remain ill-understood. We hypothesized that exposure to M. bovis through unpasteurized milk might protect against Mycobacterium tuberculosis and Mycobacterium leprae., Methods: After excluding high-income countries (with universal milk pasteurization) and microstates, an ecological study comprising 113 countries was conducted. National data were obtained from United Nations agencies and international organizations about milk production per capita (1980-1999) as a proxy for exposure to wild-type M. bovis, TB (2000-2019) and leprosy (2005-2019) incidence, HIV prevalence (2000-2019), human development index (2010), global hunger index (2010), neonatal BCG coverage (1980-1999), urbanization (2000) and temperature (1990-2020). Multiple linear regression analyses were performed using log-transformed variables., Results: For TB, the association differed by region. An inverse association with milk production was seen in regions outside, but not within, sub-Saharan Africa, after adjustment for confounders. The incidence of leprosy was inversely associated with milk production when combining all countries, but the association was stronger in sub-Saharan Africa., Conclusions: Exposure to wild-type M. bovis through unpasteurized milk may provide cross-protection against M. tuberculosis and M. leprae and contribute to geographic disparities in BCG efficacy. This needs to be confirmed by individual-level studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants from high-incidence regions who move to low-incidence countries is generally considered an ineffective strategy because only ≈14% of them comply with the multiple steps of the 'cascade of care' and complete treatment. In the Estrie region of Canada, a refugee clinic was opened in 2009. One of its goals is LTBI management., Methods: Key components of this intervention included: close collaboration with community organizations, integration within a comprehensive package of medical care for the whole family, timely delivery following arrival, shorter treatment through preferential use of rifampin, and risk-based selection of patients to be treated. Between 2009-2020, 5131 refugees were evaluated. To determine the efficacy and benefit-cost ratio of this intervention, records of refugees seen in 2010-14 (n = 1906) and 2018-19 (n = 1638) were reviewed. Cases of tuberculosis (TB) among our foreign-born population occurring before (1997-2008) and after (2009-2020) setting up the clinic were identified. All costs associated with TB or LTBI were measured., Results: Out of 441 patients offered LTBI treatment, 374 (85%) were compliant. Adding other losses, overall compliance was 69%. To prevent one case of TB, 95.1 individuals had to be screened and 11.9 treated, at a cost of $16,056. After discounting, each case of TB averted represented $32,631, for a benefit-cost ratio of 2.03. Among nationals of the 20 countries where refugees came from, incidence of TB decreased from 68.2 (1997-2008) to 26.3 per 100,000 person-years (2009-2020). Incidence among foreign-born persons from all other countries not targeted by the intervention did not change., Conclusions: Among refugees settling in our region, 69% completed the LTBI cascade of care, leading to a 61% reduction in TB incidence. This intervention was cost-beneficial. Current defeatism towards LTBI management among immigrants and refugees is misguided. Compliance can be enhanced through simple measures., Competing Interests: The authors have declared that no competing interests exist.

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can be used to study relative changes in glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the gluCEST contrast in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates., Competing Interests: Declaration of Competing Interest The authors do not have financial and non-financial competing interests in relation to the work described., (Copyright © 2022. Published by Elsevier Inc.)

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines became available, it was hypothesized that BCG (Bacillus Calmette-Guérin), which stimulates innate immunity, could provide protection against SARS-CoV-2. Numerous ecological studies, plagued by methodological deficiencies, revealed a country-level association between BCG use and lower COVID-19 incidence and mortality. We aimed to determine whether BCG administered in early life decreased the risk of SARS-CoV-2 infection in adulthood and the severity of COVID-19., Methods: This case-control study was conducted in Quebec, Canada. Cases were patients with a positive SARS-CoV-2 nucleic acid amplification test performed at two hospitals between March-October 2020. Controls were identified among patients with non-COVID-19 samples processed by the same microbiology laboratories during the same period. Enrolment was limited to individuals born in Quebec between 1956 and 1976, whose vaccine status was accessible in a computerized registry of 4.2 million BCG vaccinations., Results: We recruited 920 cases and 2123 controls. Fifty-four percent of cases (n = 424) and 53% of controls (n = 1127) had received BCG during childhood (OR: 1.03; 95% CI: 0.89-1.21), while 12% of cases (n = 114) and 11% of controls (n = 235) had received two or more BCG doses (OR: 1.14; 95% CI: 0.88-1.46). After adjusting for age, sex, material deprivation, recruiting hospital and occupation there was no evidence of protection conferred by BCG against SARS-CoV-2 (AOR: 1.01; 95% CI: 0.84-1.21). Among cases, 77 (8.4%) needed hospitalization and 18 (2.0%) died. The vaccinated were as likely as the unvaccinated to require hospitalization (AOR: 1.01, 95% CI: 0.62-1.67) or to die (AOR: 0.85, 95% CI: 0.32-2.39)., Conclusions: BCG does not provide long-term protection against symptomatic COVID-19 or severe forms of the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988-2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00-1.07), immunosuppression (aOR 4.2, 95% CI 1.5-11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9-14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.

Background: We carried out a case-control study that examined whether receipt of the inactivated influenza vaccine during the 2019-2020 season impacted on the risk of coronavirus disease 2019 (COVID-19), as there was a concern that the vaccine could be detrimental through viral interference., Methods: A total of 920 cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (diagnosed between March and October 2020) and 2,123 uninfected controls were recruited from those who were born in Québec between 1956 and 1976 and who had received diagnostic services at two hospitals (Montréal and Sherbrooke, Québec). After obtaining consent, a questionnaire was administered by phone. Data were analyzed by logistic regression., Results: Among healthcare workers, inactivated influenza vaccine received during the previous influenza season was not associated with increased COVID-19 risk (AOR: 0.99, 95% CI: 0.69-1.41). Among participants who were not healthcare workers, influenza vaccination was associated with lower odds of COVID-19 (AOR: 0.73, 95% CI 0.56-0.96)., Conclusion: We found no evidence that seasonal influenza vaccine increased the risk of developing COVID-19., Competing Interests: Competing interests: None.

Background: Drought is a major consequence of global heating that has negative impacts on agriculture. Potato is a drought-sensitive crop; tuber growth and dry matter content may both be impacted. Moreover, water deficit can induce physiological disorders such as glassy tubers and internal rust spots. The response of potato plants to drought is complex and can be affected by cultivar type, climatic and soil conditions, and the point at which water stress occurs during growth. The characterization of adaptive responses in plants presents a major phenotyping challenge. There is therefore a demand for the development of non-invasive analytical techniques to improve phenotyping., Results: This project aimed to take advantage of innovative approaches in MRI, phenotyping and molecular biology to evaluate the effects of water stress on potato plants during growth. Plants were cultivated in pots under different water conditions. A control group of plants were cultivated under optimal water uptake conditions. Other groups were cultivated under mild and severe water deficiency conditions (40 and 20% of field capacity, respectively) applied at different tuber growth phases (initiation, filling). Water stress was evaluated by monitoring soil water potential. Two fully-equipped imaging cabinets were set up to characterize plant morphology using high definition color cameras (top and side views) and to measure plant stress using RGB cameras. The response of potato plants to water stress depended on the intensity and duration of the stress. Three-dimensional morphological images of the underground organs of potato plants in pots were recorded using a 1.5 T MRI scanner. A significant difference in growth kinetics was observed at the early growth stages between the control and stressed plants. Quantitative PCR analysis was carried out at molecular level on the expression patterns of selected drought-responsive genes. Variations in stress levels were seen to modulate ABA and drought-responsive ABA-dependent and ABA-independent genes., Conclusions: This methodology, when applied to the phenotyping of potato under water deficit conditions, provides a quantitative analysis of leaves and tubers properties at microstructural and molecular levels. The approaches thus developed could therefore be effective in the multi-scale characterization of plant response to water stress, from organ development to gene expression., (© 2021. The Author(s).)

Competing Interests: Intérêts concurrents: Aucun intérêt concurrent n’a été déclaré.

Identification of relevant biomarkers is fundamental to understand biological processes of neurodegenerative diseases and to evaluate therapeutic efficacy. Atrophy of brain structures has been proposed as a biomarker, but it provides little information about biochemical events related to the disease. Here, we propose to identify early and relevant biomarkers by combining biological specificity provided by 1 H-MRS and high spatial resolution offered by gluCEST imaging. For this, two different genetic mouse models of Huntington's disease (HD)-the Ki140CAG model, characterized by a slow progression of the disease, and the R6/1 model, which mimics the juvenile form of HD-were used. Animals were scanned at 11.7 T using a protocol combining 1 H-MRS and gluCEST imaging. We measured a significant decrease in levels of N-acetyl-aspartate, a metabolite mainly located in the neuronal compartment, in HD animals, and the decrease seemed to be correlated with disease severity. In addition, variations of tNAA levels were correlated with striatal volumes in both models. Significant variations of glutamate levels were also observed in Ki140CAG but not in R6/1 mice. Thanks to its high resolution, gluCEST provided complementary insights, and we highlighted alterations in small brain regions such as the corpus callosum in Ki140CAG mice, whereas the glutamate level was unchanged in the whole brain of R6/1 mice. In this study, we showed that 1 H-MRS can provide key information about biological processes occurring in vivo but was limited by the spatial resolution. On the other hand, gluCEST may finely point to alterations in unexpected brain regions, but it can also be blind to disease processes when glutamate levels are preserved. This highlights in a practical context the complementarity of the two methods to study animal models of neurodegenerative diseases and to identify relevant biomarkers., (© 2020 John Wiley & Sons, Ltd.)

Objective: To investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon., Design: We tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies., Results: Overall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15-49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work)., Conclusion: We found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anosmia and dysgeusia have been reported as potential symptoms of coronavirus disease 2019. This study aimed to confirm whether anosmia and dysgeusia are specific symptoms among those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We conducted an age-matched case-control study in the Eastern Townships region of Quebec between Mar. 10 and Mar. 23, 2020. We included adults (age ≥ 18 yr) who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction. Cases were matched (1:1) according to 5-year age groups with control patents selected randomly from among all patients who tested negative for SARS-CoV-2 during the same period. Demographic and laboratory information was collected from medical records. Clinical symptoms and comorbidities associated with anosmia and dysgeusia were obtained by telephone interview with a standardized questionnaire., Results: Among 2883 people tested for SARS-CoV-2, we identified 134 positive cases (70 women [52.2%] and 64 men [47.8%]; median age 57.1 [interquartile range 41.2-64.5] yr). The symptoms independently associated with SARS-CoV-2 positivity in conditional logistic regression were anosmia or dysgeusia or both (adjusted odds ratio [OR] 62.9, 95% confidence interval [CI] 11.0-359.7), presence of myalgia (adjusted OR 7.6, 95% CI 1.9-29.9), blurred vision (adjusted OR 0.1, 95% CI 0.0-0.8) and chest pain (adjusted OR 0.1, 95% CI 0.0-0.6)., Interpretation: We found a strong association between olfactory and gustatory symptoms and SARS-CoV-2 positivity. These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative., Competing Interests: Competing interests: None declared., (© 2020 Joule Inc. or its licensors.)

Background: Several clinical prediction rules (CPRs) for complications and mortality of Clostridioides difficile infection (CDI) have been developed but only a few have gone through external validation, and none is widely recommended in clinical practice., Methods: CPRs were identified through a systematic review. We included studies that predicted severe or complicated CDI (cCDI) and mortality, reported at least an internal validation step, and for which data were available with minimal modifications. Data from a multicenter prospective cohort of 1380 adults with confirmed CDI were used for external validation. In this cohort, cCDI occurred in 8% of the patients and 30-day all-cause mortality occurred in 12%. The performance of each tool was assessed using individual outcomes, with the same cut-offs and standard parameters., Results: Seven CPRs were assessed. Three predictive scores for cCDI showed low sensitivity (25-61%) and positive predictive value (PPV; 9-31%), but moderate specificity (54-90%) and negative predictive value (NPV; 82-95%). One model [using age, white blood cell count (WBC), narcotic use, antacids use, and creatinine ratio > 1.5× the normal level as covariates] showed a probability of 25% of cCDI at the optimal cut-off point with 36% sensitivity and 84% specificity. Two scores for mortality had low sensitivity (4-55%) and PPV (25-31%), and moderate specificity (71-78%) and NPV (87-92%). One predictive model for 30-day all-cause mortality [Charlson comorbidity index, WBC, blood urea nitrogen (BUN), diagnosis in ICU, and delirium] showed an AUC-ROC of 0.74. All other CPRs showed lower AUC values (0.63-0.69). Errors in calibration ranged from 12%- 27%., Conclusions: Included CPRs showed moderate performance for clinical use in a large validation cohort with a majority of patients infected with ribotype 027 strains and a low rate of cCDI and mortality. These data show that better CPRs need to be developed and validated., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: L.V. has served on advisory boards for Merus, Merck, Abbott, and Wyeth, and has received compensation to conduct clinical trials involving antibacterials from Wyeth, Pfizer, Optimer, Cubist, Merck and Actelion. A.E.S. served on Merck Advisory Boards and received honoraria for speaking on behalf of Merck Canada Inc. All other authors have no competing interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no restrictions on sharing of data and/or materials.

Objectives: Rates of infection following transrectal ultrasound-guided prostate biopsy (TRUSPB) are increasing. The aim of this study was to evaluate the effectiveness of fosfomycin tromethamine (FMT) prophylaxis in preventing post-TRUSPB infectious complications., Methods: This nested case-control study included patients undergoing TRUSPB in a Canadian tertiary-care hospital who developed post-TRUSPB bacteraemia or urinary tract infection. Four prophylaxis periods were defined: (i) ciprofloxacin, low-resistance period (CIPRO-LOW), 2002-2009; (ii) ciprofloxacin, high-resistance period (CIPRO-HIGH), 2010-October 2013; (iii) oral FMT, one dose (FOSFO1), December 2013-September 2015; and (iv) oral FMT, two doses (FOSFO2), November 2015-June 2016. Incidence rates of the infection were calculated., Results: TRUSPB (n=9391) resulted in 138 cases of urinary sepsis (58% with bacteraemia). The incidence rates were 1.8% (CIPRO-HIGH), 3.5% (FOSFO1; P=0.004 vs. CIPRO-HIGH) and 2.7% (FOSFO2; P=0.19 vs. CIPRO-HIGH). Although Escherichia coli remained the predominant pathogen with fosfomycin-based regimens, the proportion of infections caused by Klebsiella spp. was higher (20/66; 30.3%) than with ciprofloxacin-based regimens (2/77; 2.6%; P<0.0001)., Conclusion: Independent risk factors for infection were the prophylactic regimen administered, presence of urological co-morbidities and diabetes. FMT was therefore not an effective alternative to ciprofloxacin for preventing post-TRUSPB urinary sepsis. These results highlight the need for novel antibacterial prophylaxis approaches., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could be associated with unfavorable outcomes. We applied high-resolution multilocus variable-number tandem-repeat analysis (MLVA) to characterize C. difficile R027 isolates collected from confirmed CDI patients recruited across 10 Canadian hospitals from 2005 to 2008. PCR ribotyping was performed first to select R027 isolates that were then analyzed by MLVA ( n  = 450). Complicated CDI (cCDI) was defined by the occurrence of any of admission to an intensive care unit, colonic perforation, toxic megacolon, colectomy, and if CDI was the cause or contributed to death within 30 days after enrollment. Three major MLVA clusters were identified, MC-1, MC-3, and MC-10. MC-1 and MC-3 were exclusive to Quebec centers, while MC-10 was found only in Ontario. Fewer cases infected with MC-1 developed cCDI (4%) than those infected with MC-3 and MC-10 (15% and 16%, respectively), but a statistically significant difference was not reached. Our data did not identify a clear association between subpopulations of R027 and different clinical outcomes; however, the data confirmed the utility of MLVA's higher discrimination potential to better characterize CDI populations in an epidemiological analysis. For a patient with CDI, the progression toward an unfavorable outcome is a complex process that probably includes several interrelated strain and host characteristics., (Copyright © 2019 American Society for Microbiology.)

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate., (© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.)

Objectives: To examine secular changes in the incidence of invasive beta-hemolytic streptococcal infections, and to assess the efficacy of immunoglobulins and clindamycin as adjunctive therapies in the management of Streptococcus pyogenes infections., Methods: Retrospective cohort study of all cases of invasive group A (GAS), B (GBS), C or G (GCGS) streptococcal infections managed in a Canadian tertiary center from 1996-2016. Population incidence was measured for diabetics and non-diabetics. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated by logistic regression., Results: 741 cases were identified (GAS: 249; GBS: 304; GCGS: 188). While the incidence of invasive GAS infections fluctuated with no clear trend, incidence of invasive GBS and GCGS increased over time and were 8.4 and 6.3 times higher in diabetics. Mortality of invasive GAS infections decreased from 16% (6/37) in 1996-2001 to 4% (4/97) in 2011-15. Among patients with GAS infections, clindamycin administered concomitantly with a beta-lactam within 24 hours of admission decreased mortality (AOR: 0.04, 95%CI: 0.003-0.55, P = 0.02. Immunoglobulins had no such effect (AOR: 1.66, 95%CI: 0.16-17.36, P = 0.67). The protective effect of clindamycin was similar in patients with pneumonia/empyema compared to all others., Conclusion: Incidence of GBS and GCGS infections increased due to an expansion of the high-risk population (elderly diabetics), but also rose in non-diabetics. No such secular change was seen for invasive GAS infections. The decrease in mortality in patients with invasive GAS infections presumably reflects better case-management. Adjunctive clindamycin reduced mortality in invasive GAS infections; immunoglobulins did not, but power was limited. The highest mortality was seen in patients with GAS pneumonia/empyema, for whom clindamycin was protective but underused., Competing Interests: The authors have declared that no competing interests exist.

Cameroon is thought to have one of the highest prevalences of hepatitis C virus (HCV) infection in the world (4.9% among adults). A marked cohort effect exists in several communities where ≈50% of the elderly are infected. Better assessment of HCV distribution is needed for planning treatment programmes. We tested for HCV antibodies 14 150 capillary blood samples collected during the 2011 Demographic and Health Survey, whose participants were representative of the Cameroonian population aged 15-49 (both genders) and 50-59 years (men only). Historical data on exposure to medical care were collected and factors associated with HCV assessed through logistic regression and geospatial analyses. To estimate prevalence in all persons aged ≥15 years, we used data from the survey for the 15-59 years fraction and modelled a cohort effect for older individuals. The nationwide HCV prevalence was 0.81% for the 15-49 years group, and 2.51% for all individuals aged ≥15 years. Only 0.2% of individuals aged 15-19 were seropositive. Among participants aged 15-44 years, HCV was associated with age, rural residence and, for males, with ritual circumcision. For those aged 45-59 years, HCV was associated with age and access to medical care in the late 1950s. Prevalence of HCV seropositivity in Cameroon is half of previous estimates. Nationwide surveys are essential to rationalize resources allocation. The high prevalence among older cohorts, a colonial legacy, has had little spillover into younger cohorts. HCV-free generations might be attainable in countries not plagued with intravenous drug abuse., (© 2018 John Wiley & Sons Ltd.)

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea), cognitive deficits and psychiatric disturbances. The most striking neuropathological change in HD is the early atrophy of the striatum. While the disease progresses, other brain structures also degenerate, including the cerebral cortex. Changes are also seen outside the brain, in particular weight loss/cachexia despite high dietary intake. The disease is caused by an abnormal expansion of a CAG repeat in the gene encoding the huntingtin protein (Htt). This mutation leads to the expression of a poly-glutamine stretch that changes the biological functions of mutant Htt (mHtt). The mechanisms underlying neurodegeneration in HD are not totally elucidated. Here, we discuss recent results obtained in patients, animal and cellular models suggesting that early disturbance in energy metabolism at least in part associated with mitochondrial defects may play a central role, even though all data are not congruent, possibly because most findings were obtained in cell culture systems or using biochemical analyses of post mortem tissues from rodent models. Thus, we put a particular focus on brain imaging studies that could identify biomarkers of energy defects in vivo and would be of prime interest in preclinical and clinical trials testing the efficacy of new therapies targeting energy metabolism in HD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Patients with Clostridium difficile infection (CDI) who are re-exposed to antibiotics have a high likelihood of recurrence. We aimed to determine whether oral vancomycin as secondary prophylaxis reduces the risk of recurrence in patients recently diagnosed with CDI who undergo subsequent antibiotic exposure (CDI-AE)., Methods: We conducted a retrospective cohort study of patients diagnosed with CDI (initial episode or recurrence) between 2003 and 2011 in two tertiary care centers in Quebec, Canada and who received antibiotics not targeted against CDI within 90 days after their CDI diagnosis. Risk factors for subsequent recurrence after this exposure to antibiotics were assessed through Cox regression analyses., Results: We included 551 episodes of CDI-AE (379 initial episodes, 172 recurrences). Recurrence occurred after exposure to antibiotics in 181 episodes (32.9%). Recurrence was more likely in older patients (for each additional year of age: adjusted hazard ratio (AHR), 1.01; 95% confidence interval (CI), 1.00-1.03; P=0.02) and among cases where the CDI-AE episode was itself a first (AHR, 3.59; 95% CI, 2.52-5.13; P<0.0001) or a second recurrence (AHR, 4.88; 95% CI, 3.38-7.06; P<0.0001). Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose CDI-AE itself was a recurrence (AHR, 0.47; 95% CI, 0.32-0.69; P<0.0001) but not in those whose CDI-AE was an initial episode (AHR, 0.91; 95% CI, 0.57-1.45; P=0.68)., Conclusions: Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive and psychiatric symptoms. Atrophy of the striatum has been proposed for several years as a biomarker to assess disease progression in HD gene carriers. However, it does not provide any information about the biological mechanisms linked to HD pathogenesis. Changes in brain metabolites have been also consistently seen in HD patients and animal models using Magnetic Resonance Spectroscopy (MRS), but metabolite measurements are generally limited to a single voxel. In this study, we used Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) in order to map glutamate distribution in the brain of a knock-in mouse model (Ki140CAG) with a precise anatomical resolution. We demonstrated that both heterozygous and homozygous mice with pathological CAG repeat expansion in gene encoding huntingtin exhibited an atrophy of the striatum and a significant alteration of their metabolic profile in the striatum as compared to wild type littermate controls. The striatal decrease was then confirmed by gluCEST imaging. Surprisingly, CEST imaging also revealed that the corpus callosum was the most affected structure in both genotype groups, suggesting that this structure could be highly vulnerable in HD. We evaluated for the first time gluCEST imaging as a potential biomarker of HD and demonstrated its potential for characterizing metabolic defects in neurodegenerative diseases in specific regions., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The human immunodeficiency virus type 1 (HIV-1) pandemic was ignited in Léopoldville (now known as Kinshasa), in the former Belgian Congo. Factors that jump-started its early expansion remain unclear. Nonlethal hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV-1) can be used to investigate past iatrogenic transmission., Methods: We undertook a cross-sectional study of elderly inhabitants of Kinshasa, with serological assays, amplification, and sequencing. Risk factors were assessed through logistic regression. Phylogenetic methods reconstructed the genetic history of HCV., Results: A total of 217 of 839 participants (25.9%) were HCV seropositive; 26 (3.1%) were HTLV-1-seropositive. Amplification products were obtained from 118 HCV-seropositive participants; subtypes 4k (in 47 participants) and 4r (in 38) were most common. Independent risk factors for HCV subtype 4r seropositivity were intramuscular tuberculosis therapy, intravenous injections at hospital A, intravenous injections before 1960, and injections at a colonial-era venereology clinic. Intravenous injections at hospital B and antimalarials were associated with HCV subtype 4k seropositivity. Risk factors for HTLV-1 seropositivity included intravenous injections at hospitals C or D and transfusions. Evolutionary analysis of viral sequences revealed independent exponential amplification of HCV subtypes 4r and 4k from the 1950s onward., Conclusions: Iatrogenic transmission of HCV and HTLV-1 occurred in mid-20th century Kinshasa, at the same time and place HIV-1 emerged. Iatrogenic routes may have contributed to the early establishment of the pandemic., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI., Methods: This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode., Results: We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences., Conclusions: This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Introduction: The overall aim of this project is to help develop knowledge about primary care delivery models likely to improve the accessibility, quality and efficiency of care. Operationally, this objective will be achieved through supporting and evaluating 8 primary care team pilot sites that rely on an expanded nursing role within a more intensive team-based, interdisciplinary setting., Methods and Analysis: The first research component is aimed at supporting the development and implementation of the pilot projects, and is divided into 2 parts. The first part is a logical analysis based on interpreting available scientific data to understand the causal processes by which the objectives of the intervention being studied may be achieved. The second part is a developmental evaluation to support teams in the field in a participatory manner and thereby learn from experience. Operationally, the developmental evaluation phase mainly involves semistructured interviews. The second component of the project design focuses on evaluating pilot project results and assessing their costs. This component is in turn made up of 2 parts. Part 1 is a pre-and-post survey of patients receiving the intervention care to analyse their care experience. In part 2, each patient enrolled in part 1 (around 4000 patients) will be matched with 2 patients followed within a traditional primary care model, so that a comparative analysis of the accessibility, quality and efficiency of the intervention can be performed. The cohorts formed in this way will be followed longitudinally for 4 years., Ethics and Dissemination: The project, as well as all consent forms and research tools, have been accepted by 2 health sciences research ethics committees. The procedures used will conform to best practices regarding the anonymity of patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI)., Methods: Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression., Results: A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age ≥ 80 years, heart rate >90/minute, respiratory rate >20/minute, white cell count <4 × 10(9)/L or ≥ 20 × 10(9)/L, albumin <25 g/L, blood urea nitrogen >7 mmol/L, and C-reactive protein ≥ 150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis., Conclusions: CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The importance of recombination in the evolution and genetic diversity of the hepatitis C virus (HCV) is currently uncertain. Only a small number of intergenotypic recombinants have been identified so far, and each has core and envelope genes classified as belonging to genotype 2. Here, we investigated two putative genotype 4/1 recombinants from southern Cameroon using a number of approaches, including standard Sanger sequencing, genotype-specific PCR amplification, and non-HCV-specific Illumina RNA sequencing (RNA-seq). Recombination between genotypes 1 and 4 was confirmed in both samples, and the parental lineages of each recombinant belong to HCV subtypes that are cocirculating at a high prevalence in Cameroon. Using the RNA-seq approach, we obtained a complete genome for one sample, which contained a recombination breakpoint at the E2/P7 gene junction. We developed and applied a new method, called Deep SimPlot, which can be used to visualize and identify viral recombination directly from the short sequence reads created by next-generation sequencing in conjunction with a consensus sequence., (Copyright © 2015, Iles et al.)

The social contribution of nurses to the health of the population is mainly defined by the knowledge supporting their actions. Conceptualization in nursing guides the production and utilisation of scientific knowledge within the discipline. The purpose of this paper is to present the recent thoughts on nursing theory and to provide some strategies to integrate them within the activities of knowledge mobilization, in practice, research, and education. When nurses are engaged in mobilizing theoretical and empirical knowledge in answering nursing practice questions and in discussing social health issues, they participate in persons, families, and communities health improvement, while affirming their disciplinary and social identity. Called to be change agents in health care systems, with other professional team members, it is important that nurses be prepared to mobilize knowledge and to engage in critical reasoning, and ethical conduct. Their social contribution will be as strong as the value they assign to nursing knowledge and their participation in producing it.

Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations., (Copyright © 2014, American Association for the Advancement of Science.)

Background: In 2000, the World Health Organization estimated that, in developing and transitional countries, unsafe injections accounted for respectively 5%, 32% and 40% of new infections with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Safe injection campaigns were organized worldwide. The present study sought to measure the progress in reducing the transmission of these viruses through unsafe injections over the subsequent decade., Methods: A mass action model was updated, to recalculate the number of injection-related HIV, HCV and HBV infections acquired in 2000 and provide estimates for 2010. Data about the annual number of unsafe injections were updated. HIV prevalence in various regions in 2000 and 2010 were calculated from UNAIDS data. The ratio of HIV prevalence in healthcare settings compared to the general population was estimated from a literature review. Improved regional estimates of the prevalence of HCV seropositivity, HBsAg and HBeAg antigenemia were used for 2000 and 2010. For HIV and HCV, revised estimates of the probability of transmission per episode of unsafe injection were used, with low and high values allowing sensitivity analyses., Results: Despite a 13% population growth, there was a reduction of respectively 87% and 83% in the absolute numbers of HIV and HCV infections transmitted through injections. For HBV, the reduction was more marked (91%) due to the additional impact of vaccination. While injections-related cases had accounted for 4.6%-9.1% of newly acquired HIV infections in 2000, this proportion decreased to 0.7%-1.3% in 2010, when unsafe injections caused between 16,939 and 33,877 HIV infections, between 157,592 and 315,120 HCV infections, and 1,679,745 HBV infections., Conclusion: From 2000 to 2010, substantial progress was made in reducing the burden of HIV, HCV and HBV infections transmitted through injections. In some regions, their elimination might become a reasonable public health goal.

Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age., Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD) in relation to PPSV23 and PCV7 use., Study Design and Methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997-2010., Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997-2001 vs. 10/100,000 in 2004-2010 (p<0.01). Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11)., Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.

Objective: Since 1999, substantial efforts have been made by the international community to reduce the risks associated with unsafe injections, through ministries of health, international donors, the World Health Organization and the Safe Injection Global Network. The present study attempted to measure the progress, or lack thereof, made over the 2000-2010 decade in reducing unsafe injections in ten regions of the world corresponding to developing and transitional economies., Methods: Data about the number of injections per person per year and the proportion of re-use of syringes and needles were obtained for 2010, mainly from population surveys, and compared with previous estimates for 2000 which had used various sources of information including injection safety assessments, population surveys and published studies on injection practices., Results: From 2000 to 2010, in developing countries and transitional economies, the average number of injections per person per year decreased from 3.40 to 2.88, while the proportion of re-use of injection devices dropped from 39.8% to 5.5%. Combining both factors the number of unsafe injections per person per year decreased from 1.35 to 0.16. Even if substantial progress has been made, the Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per person per year. In sub-Saharan Africa and Latin America, people now receive on average only 0.04-0.05 unsafe injections per year., Conclusion: Substantial progress has been made in reducing the number of unsafe injections in developing countries and transitional economies, essentially through a reduction in the re-use of injection devices. In some regions, elimination of unsafe injections might become a reasonable goal.

In this study, we characterized the full-length genome sequences of seven hepatitis C virus (HCV) isolates belonging to genotype 1. These represent the first complete genomes for HCV subtypes 1e, 1h, 1l, plus one novel variant that qualifies for a new but unassigned subtype. The genomes were characterized using 19-22 overlapping fragments. Each was 9400-9439 nt long and contained a single ORF encoding 3019-3020 amino acids. All viruses were isolated in the sera of seven patients residing in, or originating from, Cameroon. Predicted amino acid sequences were inspected and unique patterns of variation were noted. Phylogenetic analysis using full-length sequences provided evidence for nine genotype 1 subtypes, four of which are described for the first time here. Subsequent phylogenetic analysis of 141 partial NS5B sequences further differentiated 13 subtypes (1a-1m) and six additional unclassified lineages within genotype 1. As a result of this study, there are now seven HCV genotype 1 subtypes (1a-1c, 1e, 1g, 1h, 1l) and two unclassified genotype 1 lineages with full-length genomes characterized. Further analysis of 228 genotype 1 sequences from the HCV database with known countries is consistent with an African origin for genotype 1, and with the hypothesis of subsequent dissemination of some subtypes to Asia, Europe and the Americas.