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Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed. L. infantum presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of L. infantum internalization by hepatocytes was raised, but not confirmed. Hepatocytes were able to recognize parasite presence, inducing PRRs [nucleotide oligomerization domain (NOD)1, NOD2 and Toll-like receptor (TLR)2] gene expression and generating a mix pro- and anti-inflammatory cytokine response. Reduction of cytochrome P 450s enzyme activity was also observed concomitant with the inflammatory response. Addition of MgA increased NOD2, TLR4 and interleukin 10 gene expression, indicating an immunomodulatory role for MgA. Hepatocytes seem to have a major role in coordinating liver's innate immune response against L. infantum infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.
Our current global food system – from food production to consumption, including manufacture, packaging, transport, retail and associated businesses – is responsible for extensive negative social and environmental impacts which threaten the long-term well-being of society. This has led to increasing calls from science–policy organizations for major reform and transformation of the global food system. However, our knowledge regarding food system transformations is fragmented and this is hindering the development of co-ordinated solutions. Here, we collate recent research across several academic disciplines and sectors in order to better understand the mechanisms that ‘lock-in’ food systems in unsustainable states.
The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008–2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0–27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49–1.66, 0.90 (0.19) and 0–6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.
Evidence suggests that skin picking disorder (SPD) could be a prevalent condition associated with comorbidity and psychosocial dysfunction. However, just a few studies have assessed the prevalence and correlates of SPD in samples from low- and middle-income countries. In addition, the impact of SPD on quality of life (QoL) dimension after multivariable adjustment to potential confounders remains unclear.
Data were obtained from a Brazilian anonymous Web-based research platform. Participants provided sociodemographic data and completed the modified Skin Picking–Stanford questionnaire, the Hypomania Checklist (HCL-32), the Patient Health Questionnaire-9 (PHQ-9), the Fagerström Test for Nicotine Dependence, Alcohol Use Disorder Identification Test (AUDIT), Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report–short form, and the World Health Organization quality of life abbreviated scale (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models.
For our survey, 7639 participants took part (71.3% females; age: 27.2±7.9 years). The prevalence of SPD was 3.4% (95% CI: 3.0–3.8%), with a female preponderance (P<0.001). In addition, SPD was associated with a positive screen for a major depressive episode, nicotine dependence, and alcohol dependence, as well as suicidal ideation. Physical and psychological QoL was significantly more impaired in participants with SPD compared to those without SPD, even after adjustment for comorbidity.
In this large sample, SPD was a prevalent condition associated with co-occurring depression, nicotine, and alcohol dependence. In addition, SPD was independently associated with impaired physical and psychological QoL. Public health efforts toward the early recognition and treatment of SPD are warranted.
This work presents an energy criterion to define the halo of homogeneous and mismatched charged particle beams. In the simulations used in this work, the beam is considered to be azimuthally symmetric, initially cold and is confined by an external constant magnetic field inside a cylindrical conducting pipe. The energy criterion is established through the analysis of the beam energy distributions with time. The obtained results are in reasonable agreement with the past results that considered the beam phase-space topology, for many values of the beam initial envelope mismatch.
This study evaluated the impact of maternal vaccination against rubella on the levels of specific rubella IgG (rIgG) in 198 newborn cord sera samples. Detailed maternal vaccination data were available. Specific rIgG was measured using a commercial enzyme immunoassay. Most mothers (78.8%) had been vaccinated against rubella at least once in their lives. In 15 (7.6%) cord sera samples, the concentration of specific rIgG was below 11 IU/ml, which was classified as seronegative. Statistical analysis using multiple logistic regression (n = 198) showed that newborns of mothers born between 1986 and 1995, and those born to unvaccinated mothers, were more likely to be seronegative (odds ratio (ORs) 5.2 and 4.9, respectively, adjusted for sex and gestational age). For vaccinated mothers (n = 156), those born between 1986 and 1995 were more likely to have seronegative newborns (OR 11.5 adjusting for sex, gestational age and time since last vaccination). Mothers of the 15 (7.6%) seronegative newborns might have been susceptible to rubella during pregnancy. Checking the vaccination status therefore recommended.
Although a national programme for control of visceral leishmaniosis (VL) is being run in Brazil, the disease continues to spread. This programme is essentially based on culling infected dogs from endemic regions. Thus, there is an urgent need to develop other control measures against VL to deter its advance. Here, a subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the associations between these measures were evaluated for reducing the incidence of Leishmania infection in dogs. This was through a cohort study conducted in an endemic region of Brazil, considering the incidence and time of total exposure over a period of 1 year. The incidence of VL was estimated by means of serological and molecular diagnostic tests, 180 and 360 days after the application of the control measures. The estimates of the effectiveness (EF) were not significant in any cohort. The EF of the subunit vaccine, the recombinant vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95% confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In conclusion, under the conditions of this study, none of the immunogens for VL control was sufficiently effective to protect dogs against infection. On the other hand, use of collars impregnated with insecticide seems to constitute a method with better prognosis, corroborating other studies in this field.
Echocardiographic screening represents an opportunity for reduction in the global burden of rheumatic heart disease. A focussed single-view screening protocol could allow for the rapid training of healthcare providers and screening of patients.
The aim of this study was to determine the sensitivity and specificity of a focussed single-view hand-held echocardiographic protocol for the diagnosis of rheumatic heart disease in children.
A total of nine readers were divided into three reading groups; each interpreted 200 hand-held echocardiography studies retrospectively as screen-positive, if mitral regurgitation ⩾1.5 cm and/or any aortic insufficiency were observed, or screen-negative from a pooled study library. The performance of experts receiving focussed hand-held protocols, non-experts receiving focussed hand-held protocols, and experts receiving complete hand-held protocols were determined in comparison with consensus interpretations on fully functional echocardiography machines.
In all, 587 studies including 76 on definite rheumatic heart disease, 122 on borderline rheumatic heart disease, and 389 on normal cases were available for analysis. The focussed single-view protocol had a sensitivity of 81.1%, specificity of 75.5%, negative predictive value of 88.5%, and a positive predictive value of 63.2%; expert readers had higher specificity (86.1 versus 64.8%, p<0.01) but equal sensitivity. Sensitivity – experts, 96% and non-experts, 95% – and negative predictive value – experts, 99% and non-experts, 98% – were better for definite rheumatic heart disease. False-positive screening studies resulting from erroneous identification of mitral regurgitation and aortic insufficiency colour jets increased with shortened protocols and less experience (p<0.01).
Our data support a focussed screening protocol limited to parasternal long-axis images. This holds promise in making echocardiographic screening more practical in regions where rheumatic heart disease remains endemic.
Kefir is a fermented milk obtained by the activity of kefir grains which are composed of lactic and acetic acid bacteria, and yeasts. Many beneficial health effects have been associated with kefir consumption such as stimulation of the immune system and inhibition of pathogenic microorganisms. The biological activity of kefir may be attributed to the presence of a complex microbiota as well as the microbial metabolites that are released during fermentation. The aim of this work was to characterise the non-microbial fraction of kefir and to study its antagonism against Escherichia coli, Salmonella spp. and Bacillus cereus. During milk fermentation there was a production of organic acids, mainly lactic and acetic acid, with a consequent decrease in pH and lactose content. The non-microbial fraction of kefir added to nutrient broth at concentrations above 75% v/v induced a complete inhibition of pathogenic growth that could be ascribed to the presence of un-dissociated lactic acid. In vitro assays using an intestinal epithelial cell model indicated that pre-incubation of cells with the non-microbial fraction of kefir did not modify the association/invasion of Salmonella whereas pre-incubation of Salmonella with this fraction under conditions that did not affect their viability significantly decreased the pathogen's ability to invade epithelial cells. Lactate exerted a protective effect against Salmonella in a mouse model, demonstrating the relevance of metabolites present in the non-microbial fraction of kefir produced during milk fermentation.
Resource partitioning is considered one of the main processes driving diversification in ecological communities because it allows coexistence among closely related and ecologically equivalent species. We combined three complementary approaches, i.e. the evaluation of foraging behaviour, diet composition and nutritional condition (RNA:DNA ratio), to assess feeding by two closely related (sister) butterflyfishes that are syntopic in Puerto Rico. Chaetodon capistratus had a higher abundance and higher bite rate and selected octocorals and hard corals for feeding, whereas Chaetodon striatus fed preferentially on sandy substrates. Cnidarians and polychaetes were the most representative diet items for both species, but C. capistratus preferred the former (Feeding Index of 74.3%) and C. striatus the latter (Feeding Index of 60.4%). Similar RNA:DNA ratios for both species suggest that, although they differ in feeding rates and diet, C. capistratus and C. striatus have similar nutritional fitness. Therefore, these species are both zoobenthivores but show clear differences in their substrate selection. The differences in the use of foraging substrate by C. capistratus and C. striatus, despite their close phylogenetic relationship and similar diets, suggest that these species coexist by resource partitioning.
Euthanasia of infected dogs is one of the measures adopted in Brazil to control visceral leishmaniasis (VL) in endemic areas. To detect infected dogs, animals are screened with the rapid test DPP® Visceral Canine Leishmaniasis for detection of antibodies against K26/K39 fusion antigens of amastigotes (DPP). DPP-positives are confirmed with an immunoenzymatic assay probing soluble antigens of promastigotes (ELISA), while DPP-negatives are considered free of infection. Here, 975 dogs from an endemic region were surveyed by using DPP, ELISA and real-time PCR (qPCR) for the diagnosis of VL. When DPP-negative dogs were tested by qPCR applied in blood and lymph node aspirates, 174/887 (19·6%) were positive in at least one sample. In a second sampling using 115 cases, the DPP-negative dogs were tested by qPCR in blood, lymph node and conjunctival swab samples, and 36/79 (45·6%) were positive in at least one sample. Low-to-moderate pairwise agreement was observed between all possible pair of tests. In conclusion, the official diagnosis of VL in dogs in Brazilian endemic areas failed to accuse an expressive number of infected animals and the impact of the low accuracy of serological tests in the success of euthanasia-based measure for VL control need to be assessed.
We prove an asymptotic formula for squarefree numbers in arithmetic progressions, improving previous results by Prachar and Hooley. As a consequence we improve a lower bound of Heath-Brown for the least squarefree number in an arithmetic progression.
The goals of this article are: (i) to understand how individual characteristics affect the likelihood of patients defaulting their pulmonary tuberculosis (PTB) treatment regimens; (ii) to quantify the predictive capacity of these risk factors; and (iii) to quantify and map spatial variation in the risk of defaulting. We used logistic regression models and generalized additive models with a spatial component to determine the odds of default across continental Portugal. We focused on new PTB cases, diagnosed between 2000 and 2013, and included some individual information (sex, age, residence area, alcohol abuse, intravenous drug use, homelessness, HIV, imprisonment status). We found that the global default rate was 4·88%, higher in individuals with well-known risk profiles (males, immigrants, HIV positive, homeless, prisoners, alcohol and drug users). Of specific epidemiological interest was that our geographical analysis found that Portugal's main urban areas (the two biggest cities) and one tourist region have higher default rates compared to the rest of the country, after adjusting for the previously mentioneded risk factors. The challenge of treatment defaulting, either due to other individual non-measured characteristics, healthcare system failure or patient recalcitrance requires further analysis in the spatio-temporal domain. Our findings suggest the presence of significant within-country variation in the risk of defaulting that cannot be explained by these classical individual risk factors alone. The methods we advocate are simple to implement and could easily be applied to other diseases.
Representative compounds of the new family of magnetic materials Gd5−xNdxSi4 were analyzed by X-ray diffraction at the XRD1 beamline at Laboratório Nacional de Luz Síncrotron. To reduce X-ray absorption, thin layers of the powder samples were mounted outside the capillaries and measured in Debye–Scherrer geometry as usual. The XRD analyses and the magnetometry results indicate that the behavior of the magnetic transition temperature as a function of Nd content may be directly related to the average of the four smallest interatomic distances between different rare earth sites of the majority phase of each compound. The quality and consistency of the results show that the XRD1 beamline is able to perform satisfactory XRD experiments on high-absorption materials even off the best conditions.
Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region. Meanwhile, the role of GSK-3 during R. prolixus embryogenesis or glycogen metabolism has not been investigated. Here we show that chemical inhibition of GSK-3 by alsterpaullone, an ATP-competitive inhibitor of GSK3, does not affect adult survival rate, though it alters oviposition and egg hatching. Specific GSK-3 gene silencing by dsRNA injection in adult females showed a similar phenotype. Furthermore, bright field and 4’−6-diamidino-2-phenylindole (DAPI) staining analysis revealed that ovaries and eggs from dsGSK-3 injected females exhibited specific morphological defects. We also demonstrate that glycogen content was inversely related to activity and transcription levels of GSK-3 during embryogenesis. Lastly, after GSK-3 knockdown, we observed changes in the expression of the Wingless (Wnt) downstream target β-catenin as well as in members of other pathways such as the receptor Notch. Taken together, our results show that GSK-3 regulation is essential for R. prolixus oogenesis and embryogenesis.
In Portugal, the recommended age for the second dose of MMR (MMR2) was changed from 10–13 years to 5–6 years for those born in 1994 and afterwards. This study aimed to assess if MMR schedule and time elapsed from the last dose are associated with the concentration of rubella and mumps IgG antibodies. Three Portuguese birth cohorts (convenience samples) were selected for this study (66, 59 and 41 participants born respectively in 1990–1993, 1994–1995 and 2001–2003). Geometric mean concentrations (GMC) for mumps IgG were respectively 36, 30 and 38 RU/ml (P = 0·236) and for rubella IgG were 18, 20 and 17 IU/ml (P = 0·641). For both specific antibodies, no differences were observed with time since MMR2. Receiving MMR2 at 5–6 or 10–13 years was not associated with concentration of both antibodies. The GMC of rubella IgG was lower in males (P = 0·029). Taking into account previous evidence and the logistics needed to change vaccination schedules, it seems reasonable that sustaining very high coverage with two doses of MMR is currently the most pragmatic way to control mumps and rubella rather than any changes to the schedule.