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PurposeColorectal cancer (CRC) is the third leading cause of cancer death worldwide. Variability between patients in prognosis and treatment response is partially explained by traditional clinicopathological factors. We established a large population-based cohort of patients with CRC and their first-degree and second-degree relatives registered in the Canton of Geneva, to evaluate the role of family history and tumour biomarkers on patient outcomes.ParticipantsThe cohort includes all patients with CRC diagnosed between 1985 and 2013. Detailed information on patient and tumour characteristics, treatment and outcomes were extracted from the Geneva Cancer Registry database, completed by medical records review and linkage with administrative and oncogenetics databases. Next-generation tissue microarrays were constructed from tissue samples of the primary tumour. A prospective follow-up of the cohort is realised annually to collect data on outcomes. First-degree and second-degree relatives of patients are identified through linkage with the Cantonal Population Office database and information about cancer among relatives is retrieved from the Geneva Cancer Registry database. The cohort of relatives is updated annually.Findings to dateThe cohort includes 5499 patients (4244 patients with colon cancer and 1255 patients with rectal cancer). The great majority of patients were diagnosed because of occurrence of symptoms and almost half of the cases were diagnosed with an advanced disease. At the end of 2019, 337 local recurrences, 1143 distant recurrences and 4035 deaths were reported. At the same date, the cohort of first-degree relatives included 344 fathers, 538 mothers, 3485 children and 375 siblings. Among them, we identified 28 fathers, 31 mothers, 18 siblings and 53 children who had a diagnosis of CRC.Future plansThe cohort will be used for long-term studies of CRC epidemiology with focus on clinicopathological factors and molecular markers. These data will be correlated with the most up-to-date follow-up data.

Summary: Background: Nepal launched a visceral leishmaniasis (also known as kala-azar) elimination initiative in 2005. We primarily aimed to assess whether transmission of Leishmania donovani had decreased since the launch of the initiative. We also assessed the validity of the direct agglutination test (DAT) as a marker of infection, in view of future surveillance systems. Methods: We did a repeat survey in a population aged 2 years and older for whom baseline serological data were available from 2006. Data were from three districts in the eastern region of Nepal. The primary outcome of interest was prevalent infection with L donovani as measured with DAT (cutoff value ≥1:3200). We compared age group-specific and cluster-specific seroprevalences in 2016 with those in 2006, using χ2 tests, with a specific focus on the comparison of seroprevalences in children born between 1996 and 2005, and those born between 2006 and 2015. To estimate the overall adjusted risk ratio for being seropositive in 2016 compared with 2006, we fitted a Poisson model controlling for age, sex, and cluster. Findings: Between Oct 17, 2016, and Dec 26, 2016, we assessed 6609 individuals. DAT prevalence in children younger than 10 years was 4·1% (95% CI 3·2–5·4) in 2006 versus 0·5% (0·1–1·7) in 2016 (p

Background: Snakebite envenoming has a substantial health and socioeconomic effect in rural communities. However, there are insufficient epidemiological and animal data, which prevents accurate assessment on the effects of snakebite. We aimed to assess the health and socioeconomic effect of snakebite using a One Health perspective. Methods: In this cross-sectional survey-based study, we assessed the health and socioeconomic effects of snakebite data using a multicluster survey that was previously done as part of the SNAKE-BYTE project in the Terai region, Nepal. Health effect was measured in terms of disability-adjusted life years (DALYs). Livelihood losses encompassed out-of-pocket health-care expenditures, losses of productivity due to days off work, and the losses due to mortality and treatment costs in domestic animals. Mortality losses in domestic animals were also estimated as animal loss equivalents, and overall human and animal health effect expressed using modified DALYs for zoonotic disease (zDALYs). Findings: We estimate an annual snakebite burden of 200 799 DALYs (95% CI 103 137–357 805), mostly due to mortality in children and women. Snakebite is estimated to lead to US$2·8 million in yearly livelihood losses associated with human and animal cases. Overall, we estimate a yearly human and animal health burden of 202 595 zDALYs (104 300–360 284). Interpretation: These findings present robust evidence on the extent of snakebite's health and socioeconomic effect and emphasise the need for a One Health perspective. The results also stress how improved data collection at the community level is crucial for improved assessments of its effect.

A healthy young woman from Cameroon was addressed to the tropical medicine consultation of the University Hospitals of Geneva to investigate an asymptomatic eosinophilia of 1.22 G/l and a history of ‘eye worms’ during childhood. Direct microscopic observation found viable microfilariae, and the stained blood smear confirmed Loa loa species.

BackgroundPopulation-based serological surveys provide a means for assessing the immunologic landscape of a community, without the biases related to health-seeking behaviors and testing practices typically associated with rt-PCR testing. This study assesses SARS-CoV-2 seroprevalence over the first epidemic wave in Canton Geneva, Switzerland, as well as biological and socio-economic risk factors for infection and symptoms associated with IgG seropositivity.Methods and findingsBetween April 6 and June 30, 2020, former participants of a yearly representative cross-sectional survey of the 20-75-year-old population of the canton of Geneva were invited to participate in a seroprevalence study, along with household members five years and older. We collected blood and tested it for anti-SARS-CoV-2 immunoglobulins G (IgG). Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. We included 8344 participants (53.5% women, mean age 46.9 years). The population-level seroprevalence over the 12-week study period was 7.8 % (95% Credible Interval (CrI) 6.8-8.9), accounting for sex, age and household random effects. Seroprevalence was highest among 18-49 year olds (9.5%, 95%CrI 8.1-10.9), with young children (5-9 years) and those >65 years having significantly lower seroprevalence (4.3% and 4.7-5.4% respectively). Men were more likely to be seropositive than women (relative risk 1.2, 95%CrI 1.1-1.4). Odds of seropositivity were reduced for female retirees (0.46, 95%CI 0.23-0.93) and unemployed men (0.35, 95%CI 0.13-1.0) compared to employed individuals, and for current smokers (0.36, 95%CI 0.23-0.55) compared to never-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. Symptoms most strongly associated with seropositivity were anosmia/dysgeusia, loss of appetite, fever, fatigue and myalgia and/or arthralgia. Thirteen percent of seropositive participants reported no symptoms.ConclusionsOur results confirm a low population seroprevalence of anti-SARS-CoV-2 antibodies after the first wave in Geneva, a region hard hit by the COVID-19 pandemic. Socioeconomic factors were not associated with seropositivity in this sample. The elderly and young children were less frequently seropositive, though it is not clear how biology and behaviors shape these differences. These specificities should be considered when assessing the need for targeted public health measures.

Commercially available lipase fromPseudomonas stutzeri(lipase TL) is investigated as a biocatalyst for the formation of an acid–epoxy chemical network. Molecular model reactions are performed by reacting 2-phenyl glycidyl ether and hexanoic acid in bulk, varying two parameters: temperature and water content. Characterizations of the formed products by1H NMR spectroscopy and gas chromatography–mass spectrometry combined with enzymatic assays confirm that lipase TL is able to simultaneously promote acid–epoxy addition and transesterification reactions below 100 °C and solely the acid–epoxy addition after denaturation atT> 100 °C. A prototype bio-based chemical network with β-hydroxyester links was obtained using resorcinol diglycidyl ether and sebacic acid as monomers with lipase TL as catalyst. Differential scanning calorimetry, attenuated total reflection, and swelling analysis confirm gelation of the network.

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape in the population and guide public health measures. We aimed to estimate the seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and six months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between June 1 and July 7, 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins (Roche Elecsys immunoassays). We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).ResultsWe included 3355 individuals, of which 1814 (54.1%) were women, 697 (20.8%) were aged ConclusionsMost adults have developed anti-SARS-CoV-2 antibodies, while most teenagers and children remain vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and socioeconomically disadvantaged groups, and to minimize spread among children.

Oligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-lasting and EEC-derived peptides do regulate short-term food intake, we hypothesized that neonatal OS consumption could modulate early EECs, with possible consequences for adult eating behavior. Suckling rats were supplemented with fructo-oligosaccharides (FOS), beta-galacto-oligosaccharides/inulin (GOS/In) mix, alpha-galacto-oligosaccharides (&alpha, GOS) at 3.2 g/kg, or a control solution (CTL) between postnatal day (PND) 5 and 14/15. Pups were either sacrificed at PND14/15 or weaned at PND21 onto standard chow. The effects on both microbiota and EEC were characterized at PND14/15, and eating behavior at adulthood. Very early OS supplementation drastically impacted the intestinal environment, endocrine lineage proliferation/differentiation particularly in the ileum, and the density of GLP-1 cells and production of satiety-related peptides (GLP-1 and PYY) in the neonatal period. However, it failed to induce any significant lasting changes on intestinal microbiota, enteropeptide secretion or eating behavior later in life. Overall, the results did not demonstrate any OS programming effect on satiety peptides secreted by L-cells or on food consumption, an observation which is a reassuring outlook from a human perspective.

In low-resource hospitals of central Africa, neurological disorders are frequent and etiologies very diverse. The difficulty to identify invasive bacterial infections in this setting results in major antibiotic overuse. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may help discriminate these conditions. We retrospectively determined the concentrations of CRP and PCT in the sera of patients consecutively enrolled from 2012 to 2015 in an etiological study on neurological disorders at the rural hospital of Mosango, Democratic Republic of Congo. Invasive bacterial infection had been diagnosed by the demonstration of a bacterial pathogen in cerebrospinal fluid or blood cultures or the presence of radiological pneumonia. Sera of 313 (89.2%) and 317 (90.3%) of the 351 enrolled participants were available for determination of CRP and PCT concentrations respectively. Areas under the receiver operating characteristic curves for invasive bacterial infection, diagnosed in 19 tested cases, were 94.3% for CRP and 91.7% for PCT. No single case had a normal CRP concentration (

The aim of this study was to verify whether modifications made in a hard chairside reline resin by an ethyl-cyanoacrylate adhesive, ECA (Super Bonder®, Loctite, Itapevi, SP, Brazil) would be able to inhibit or reduce Candida albicans biofilm formation on its surface, comparing to a commercial surface sealant (BisCover®, Bisco, Schaumburg, USA). Reline resin specimens were fabricated and randomly divided into 6 groups (n=8): CG (control group), no surface treatment; ECA1, ECA coating on the surface before sterilization; ECA2, ECA coating after sterilization; ECA3, ECA incorporated in the resin bulk; DPE1, BisCover® coating before sterilization; DPE2, BisCover® coating after sterilization. Specimens were inoculated with C. albicans SC5314 (1x107 cells/mL) and incubated for 24 h. Then, the biofilm were stained with LIVE/DEAD® BaclightTM L7007 Kit and analyzed by Confocal Laser Scanning Microscopy. The images were evaluated by bioImageL® v.2.0 software and total biovolume (µm3), viable cells (%), and covered area (%) were calculated. Data were statistically analyzed by Kruskal-Wallis and Dunn tests (p

A healthy young man from Sri Lanka, currently living in Switzerland, consulted at the University Hospital of Geneva with a history of painful erythema and swelling of the left forearm. Laboratory tests showed a slight eosinophilia. Western blot serology for Gnathostoma spp, inconclusive at presentation, became positive 2 weeks later.

Hepatic alveolar echinococcosis (HAE) is a rare but severe zoonosis caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. HAE is present only in the Northern Hemisphere, predominantly in China. Currently, there is a significant resurgence of cases in historically endemic areas associated with emergence of HAE in countries not previously concerned. Today, in European countries, HAE is often discovered by chance; however, clinicians should be made aware of opportunistic infections that progressively emerged recently as a result of therapeutic or pathological immunosuppression. Ultrasonography is the key first-line diagnostic procedure, with specific serology providing confirmation in 95% of the cases. Albendazole, only parasitostatic, is the mainstay for treatment. Surgical resection, if feasible, is the gold standard for treatment, and more patients are currently eligible for this option because of an earlier diagnosis. The prognosis has considerably improved but remains poor in countries where access to care is less favorable.

Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. The reliability of serologic studies for quantifying the proportion of the population that have been infected depends on the extent of antibody decay as well as on assay performance in detecting both recent and older infections. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. In a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals tested with three widely-used immunoassays, antibodies persisted for at least 8 months after infection, although detection depended on immunoassay choice, with one of them missing up to 40% of past infections. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. As the immune landscape becomes more complex with naturally-infected and vaccinated individuals, assay choice and appropriate assay-performance-adjustment will become even more important for the interpretation of serologic studies.

The characteristics of the denture base surface, in combination with the oral environment, promote the colonization and development of Candida albicans biofilm, which is the main cause of denture stomatitis. This study evaluated the effectiveness of fibrin biopolymer with digluconate chlorhexidine or Punica granatum alcoholic extract to prevent C. albicans biofilm. Conventional heat polymerized and pre-polymerized poly(methyl methacrylate) (PMMA) circular specimens (10 × 2 mm) were fabricated (n = 504) and randomly divided into groups: no treatment (control—CT), fibrin biopolymer coating (FB), fibrin biopolymer with P. granatum (FBPg), or digluconate of chlorhexidine (FBCh) coating. The specimens were inoculated with C. albicans SC5314 (1 × 107 cells/mL) and incubated for 24, 48, and 72 h. Crystal violet and colony-forming unit assays were used to quantify the total biofilm biomass and biofilm-living cells. A qualitative analysis was performed using confocal laser scanning microscopy. Data obtained are expressed as means and standard deviations and were statistically analyzed using a three-way analysis of variance (α = 0.05). The FBPg and FBCh groups inhibited the growth of C. albicans biofilm in both PMMA materials analyzed, with FBCh performing better in all periods evaluated (p &lt, 0.0001). The colony forming unit (CFU) assay showed that the FB group favored the C. albicans biofilm growth at 24 h and 48 h (p &lt, 0.0001), with no differences with CT group at 72 h (p = 0.790). All groups showed an enhancement in biofilm development up to 72 h (p &lt, 0.0001), except the FBCh group (p = 0.100). No statistical differences were found between the PMMA base materials (p &gt, 0.050), except in the FB group (p &lt, 0.0001). Fibrin biopolymer, albeit a scaffold for the growth of C. albicans, when combined with chlorhexidine digluconate or P. granatum, demonstrated excellent performance as a drug delivery system, preventing and controlling the formation of denture biofilm.

This paper presents the Swiss guideline for genetic counselling and testing of individuals with an increased probability for carrying mutations in high risk cancer predisposition genes, particularly BRCA1 and BRCA2. It aims to help providers of genetic counselling to identify valuable candidates for testing and serves as a basis for reimbursement claims to Swiss insurance companies.

Background Up-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions. Aim We estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign. Methods We conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies). Results Among 3,355 individuals (54.1% women; 20.8% aged Conclusion Most of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.

Reactivation of latent tuberculosis infection (LTBI) or latent parasitic infection (LPI) during drug-induced immunosuppression can have serious consequences. The Division of tropical and humanitarian medicine of the Geneva University Hospitals runs a specific consultation for parasitic screening of immunosuppressed or pre-immunosuppressed patients. We sought to determine the seroprevalence of LTBI and LPI in such patients and explore its relationship with country of origin or previous travel in a retrospective, single-centre observational study from 2016 to 2019. Demographic data, travel history, ongoing treatments and results of the parasitological (Strongyloides stercoralis, Trypanosoma cruzi, Echinococcus multilocularis, Entamoeba histolytica and Leishmania spp.) and TB screening were collected to calculate LPI or LTBI prevalence. Risk factors for LTBI and strongyloidiasis were analysed using Poisson regression with robust variance. Among 406 eligible patients, 24/353 (6.8%) had LTBI, 8/368 (2.2%) were positive for Strongyloides stercoralis infection, 1/32 (3.1%) was positive for Entamoeba histolytica and 1/299 (0.3%) was positive for Leishmaniasis. No cases of Trypanosoma cruzi (0/274) or Echinococcus multilocularis (0/56) infection were detected. Previous travel to or originating from high-prevalence countries was a risk factor for LTBI (PR = 3.4, CI 95%: 1.4–8.2 and 4.0, CI 95%: 1.8–8.9, respectively). The prevalence of serological Strongyloidiasis in immunosuppressed patients is lower in comparison to those without immunosuppression (PR = 0.1, CI 95%: 0.01–0.8). In conclusion, screening before immunosuppression needs to be individualized, and LTBI and LPI need to be ruled out in patients who originate from or have travelled to high-prevalence countries. The sensitivity of strongyloidiasis serology is reduced following immunosuppression, so an algorithm combining different tests or presumptive treatment should be considered.

BackgroundAssessing the burden of COVID-19 based on medically-attended case counts is suboptimal given its reliance on testing strategy, changing case definitions and the wide spectrum of disease presentation. Population-based serosurveys provide one avenue for estimating infection rates and monitoring the progression of the epidemic, overcoming many of these limitations.MethodsTaking advantage of a pool of adult participants from population-representative surveys conducted in Geneva, Switzerland, we implemented a study consisting of 8 weekly serosurveys among these participants and their household members older than 5 years. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available enzyme-linked immunosorbent assay (Euroimmun AG, Lübeck, Germany). We estimated seroprevalence using a Bayesian regression model taking into account test performance and adjusting for the age and sex of Geneva’s population.ResultsIn the first three weeks, we enrolled 1335 participants coming from 633 households, with 16% InterpretationAssuming that the presence of IgG antibodies is at least in the short-term associated with immunity, these results highlight that the epidemic is far from burning out simply due to herd immunity. Further, no differences in seroprevalence between children and middle age adults are observed. These results must be considered as Switzerland and the world look towards easing restrictions aimed at curbing transmission.

Human infection with the nematode Strongyloides stercoralis, which may have a life-threatening course, primarily occurs in tropical settings. Epidemiological data on the occurrence of strongyloidiasis are scarce, and microscopic stool-based detection methods are insensitive. Polymerase chain reaction (PCR) assays have been developed, yet conflicting results have been reported. Our goal was to determine whether there was diagnostic agreement between an in-house PCR and two microscopic techniques, the Baermann funnel (BM) and the Koga agar plate culture (KAP) for the detection of S. stercoralis in stool samples. Eighty ethanol-fixed stool samples stemming from a cross-sectional survey in Maluku, Indonesia, were purposefully selected for PCR analysis. The final sample size comprised four groups, each with 20 samples: group 1, positive for S. stercoralis on both BM and KAP; group 2, positive only by BM; group 3, positive only by KAP; and group 4, negative on both BM and KAP. A Strongyloides-specific PCR targeting the internal transcribed spacer 2 (ITS2) region was carried out in an Indonesian reference laboratory. The overall agreement between PCR and microscopy was 61% (49/80 samples), being highest in group 1 (15/20, 75%) and lowest in group 3 (9/20, 45%). PCR revealed eight additional S. stercoralis infections in group 4. Future studies should elucidate the 'true' infection status of samples that are negative by PCR, but positive upon microscopy. Taken together, there is a lack of agreement between microscopy and PCR results for the diagnosis of human S. stercoralis infection in Indonesia. ClinicalTrials.gov (identifier: NCT02105714).

Advances in biomaterials science and implant surface technology have made dental implants more predictable and implant therapy more attractive to patients. Surgical interventions are becoming less invasive, and patients heal faster and suffer less morbidity. In this preclinical in vivo study, we compared a new ultra-fine grained titanium (ufgTi) implant material with a hydrophilic nano-patterned surface to commercially pure titanium (cpTi) in a well-established animal model. CpTi grade 4 was subjected to Equal Channel Angular Pressing (ECAP), followed by a cold drawing process that provided ultra-fine-grained titanium (ufgTi) with a mean grain size of 300 nm. After metallographic assessment, the surface topography was characterized by laser confocal microscopy and atomic force microscopy. UfgTi and cpTi implants were inserted in the mandible and maxilla of miniature pigs that healed for 4 and for 8 weeks. Osseointegration was assessed by biomechanical torque out analysis, histomorphometric evaluation, and micro-CT analysis. The metallographic properties of UfgTi were significantly better than those of cpTi. Their surface topographies had similar hydrophilic nano-patterned characteristics, with no significant differences in the nanometre range. Histomorphometric and biomechanical torque out analysis revealed no significant differences between ufgTi and cpTi in environments of either low (maxilla) or high (mandible) bone density. We obtained high bone-to-implant contact values irrespective of the bony microarchitecture even when the bone mineral density was low. Overall, this investigation suggests that ufgTi forms a hydrophilic nano-patterned surface with superior metallographic properties compared to cpTi and high levels of osseointegration. Thus, ufgTi has therapeutic potential as a future strategy for the development of small diameter implants to enable less invasive treatment concepts, reduce patient morbidity and may also lower the costs of patient care.

Objectives Serological studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-CoV-2 infections as a function of time since infection for three commercially available SARS-CoV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence. Methods We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n = 354) at least 8 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays: Roche-N, Roche-RBD and EuroImmun-S1. We developed a latent class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates. Results Antibodies were detected at follow-up in 74–100% of participants, depending on immunoassays. Both Roche assays maintain high sensitivity, with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. Discussion Antibodies persist for at least 8 months after infection in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay performance adjustment is important for the interpretation of serological studies in the case of diminishing sensitivity after infection.

Background The use of platelet rich plasma (PRP, GLO) has been used as an adjunct to various regenerative dental procedures. The aim of the present study was to characterize the influence of PRP on human gingival fibroblasts, periodontal ligament (PDL) cells and osteoblast cell behavior in vitro. Methods Human gingival fibroblasts, PDL cells and osteoblasts were cultured with conditioned media from PRP and investigated for cell migration, proliferation and collagen1 (COL1) immunostaining. Furthermore, gingival fibroblasts were tested for genes encoding TGF-β, PDGF and COL1a whereas PDL cells and osteoblasts were additionally tested for alkaline phosphatase (ALP) activity, alizarin red staining and mRNA levels of osteoblast differentiation markers including Runx2, COL1a2, ALP and osteocalcin (OCN). Results It was first found that PRP significantly increased cell migration of all cells up to 4 fold. Furthermore, PRP increased cell proliferation at 3 and 5 days of gingival fibroblasts, and at 3 days for PDL cells, whereas no effect was observed on osteoblasts. Gingival fibroblasts cultured with PRP increased TGF-β, PDGF-B and COL1 mRNA levels at 7 days and further increased over 3-fold COL1 staining at 14 days. PDL cells cultured with PRP increased Runx2 mRNA levels but significantly down-regulated OCN mRNA levels at 3 days. No differences in COL1 staining or ALP staining were observed in PDL cells. Furthermore, PRP decreased mineralization of PDL cells at 14 days post seeding as assessed by alizarin red staining. In osteoblasts, PRP increased COL1 staining at 14 days, increased COL1 and ALP at 3 days, as well as increased ALP staining at 14 days. No significant differences were observed for alizarin red staining of osteoblasts following culture with PRP. Conclusions The results demonstrate that PRP promoted gingival fibroblast migration, proliferation and mRNA expression of pro-wound healing molecules. While PRP induced PDL cells and osteoblast migration and proliferation, it tended to have little to no effect on osteoblast differentiation. Therefore, while the effects seem to favor soft tissue regeneration, the additional effects of PRP on hard tissue formation of PDL cells and osteoblasts could not be fully confirmed in the present in vitro culture system.

Este artículo contiene 14 páginas, 4 figuras, 7 tablas, 1 apéndice., [EN]We studied the habitat structure (macrofaunal assemblages and bottom types) and zonation patterns of 29 unvegetated shoreline strands along the 900-km coast of Catalonia (NW Mediterranean Sea). Organisms were sampled with grabs, pitfall traps, sticky traps, clam nets and spades to ensure capture of the different proportions of macrofaunal assemblages from the supra-, medio- and infralittoral levels. We collected 211 taxa: 194 animals and 17 algae. The most abundant and dominant organisms collected with van Veen grabs were Nematoda, Oligochaeta and Collembola at the supralittoral level; the polychaetes Saccocirrus spp. and Pisione remota, the amphipod Corophium orientale, Nematoda, and Turbellaria at the mediolittoral level; and Nematoda at the upper infralittoral level. SIMPER analysis revealed great dissimilarity between the organisms inhabiting the supralittoral and the other littoral levels. Regarding the epifauna, the sticky traps used at the supralittoral level mainly collected Collembola, which were nearly absent in pitfall traps. The qualitative study performed with a clam net and a small spade revealed that Nematoda, Saccocirrus spp., Turbellaria, Nemertea and the polychaete P. remota were the most abundant animals at both the medio- and the infralittoral levels and no differences were found between these levels. Different qualitative sampling methodologies showed that in fine sediments the bivalves Donax trunculus and D. semistriatus determined more than 97% of dissimilarity from coarse-sand sites. Richness increased in protected sandy and cobble shores. Littoral level and bottom-type features were only to a certain extent valid indicators of specific biotic components for a specific habitat. [ES]Se ha estudiado la estructura de los hábitats (comunidades de macrofauna y tipos de sedimento) y los patrones de zonación de 29 playas desprovistas de vegetación a lo largo de los 900 km de la costa de Cataluña (Mediterráneo noroccidental). El muestreo de los organismos se realizó mediante dragas, trampas de caída, trampas adhesivas, redes de marisqueo y palas para asegurar una captura exhaustiva de los organismos presentes en las comunidades de macrofauna de los niveles supralitoral, mediolitoral e infralitoral. Se colectaron 211 taxones: 194 animales y 17 algas. Los organismos más abundantes y dominantes recolectados con dragas van Veen fueron: Nematodos, Oligoquetos y Colémbolos en el nivel supralitoral; los poliquetos Saccocirrus spp. y Pisione remota, el anfípodo Corophium orientale, Nematodos y Turbelarios en el nivel mediolitoral; y Nematodos en la parte menos profunda del nivel infralitoral. Los análisis SIMPER detectaron grandes diferencias entre los organismos del nivel supralitoral y los de los otros niveles. Respecto a la epifauna, las trampas adhesivas usadas en el nivel supralitoral capturaron principalmente Colémbolos, los cuales estaban ausentes en las trampas de caida. El estudio cualitativo realizado con una red de marisqueo y una pala pequeña reveló que Nematodos, los poliquetos Saccocirrus spp. y Pisione remota, Turbelarios y Nemertinos eran los animales más abundantes tanto en el nivel mediolitoral como en el nivel infralitoral y que no había diferencias entre ambos niveles. Diferentes métodos cualitativos de muestreo revelaron que en los sedimentos finos los bivalvos Donax trunculus y D. semistriatus determinaban más del 97% de la disimilitud con los sedimentos gruesos. La riqueza en especies aumentaba en playas mixtas de arenas y cantos. El nivel y el tipo de sedimento fueron solo hasta cierto punto indicadores válidos de la composición de especies para cada hábitat concreto., Financial support came from the projects “Cartografia dels Hàbitats Litorals a Catalunya” (Departament de Territori i Sosteniblitat and Institut Cartogràfic, Generalitat de Catalunya) and INTRAMURAL CSIC 201330E065.

Background Alveolar echinococcosis is a potentially lethal zoonosis caused by larval forms of the tapeworm Echinococcus multilocularis. Humans are aberrant intermediate hosts who become infected by ingestion of egg-contaminated food or water or via physical contact with domestic or wild animals that carry the parasite in their small intestine. In humans, the disease usually affects the liver and can spread to other organs causing metastatic infiltration. In this report, we describe an advanced presentation of human alveolar echinococcosis mimicking metastatic malignancy. Case presentation A 62-year-old white woman was evaluated for fever, jaundice, and abdominal pain, associated with significant weight loss. She lived in a rural area in Switzerland and used to eat wild forest fruits and mushrooms. She owned cats that used to hunt rodents. On physical examination, she appeared severely ill with cachexia, altered mental status, jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with preserved liver function. An abdominal computed tomography scan showed an enlarged liver with a huge cystic mass in the right lobe extending into the left lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and occlusion of her right portal vein. A chest computed tomography scan showed multiple calcified bilateral pulmonary nodules. Her clinical and radiological presentation resembled an advanced neoplastic disease. Serologic tests for Echinococcus multilocularis were positive. The diagnosis of alveolar echinococcosis was established on her past history of exposure, imaging, and serology results. Conclusions Clinical presentation and radiologic imaging findings of disseminated alveolar echinococcosis can mimic metastatic malignancy, and diagnosis can be challenging in atypically advanced cases. As the incidence of human alveolar echinococcosis appears to be increasing in Europe and Switzerland, physicians should be aware of alveolar echinococcosis, its epidemiology, and its clinical features.

Purpose This was a 20-year follow-up study to assess long-term persistence of protective antibody levels against the hepatitis A virus (HAV) in healthy participants vaccinated with 2 doses of inactivated hepatitis A vaccine (Epaxal®) between 1992 and 1995. Methods Blood samples for anti-HAV antibody concentrations were obtained during a follow-up visit 20 years after vaccination and were analyzed in parallel with samples still available from previous visits using AxSYM® HAVAB 2.0 assay. Results Mean (SD) age of the participants was 44.71 (3.905) years at year 20 follow-up (N = 95). Participants completing 0/12-month Epaxal® immunization regimen (N = 94) had seroprotection rate of 100% (95% CI: 96.2, 100.0) with ⩾10 mIU/mL seropositivity cut-off and 98.9% (95% CI: 94.2, 100.0) with ⩾20 mIU/mL cut-off. With ⩾10 mIU/mL cut-off, the estimated median duration of protection was 77.3 years (95% CI: 71.8, 83.5) with 95% of the vaccinated participants predicted to be protected for at least 41.5 years. At ⩾20 mIU/mL cut-off, the estimated median duration of protection was 64.8 years (95% CI: 60.1, 68.4) with 95% of the vaccinated participants predicted to be protected for at least 33 years. Anti-HAV antibody geometric mean concentrations were higher in women (277.9; 95% CI: 217.7, 354.7) than in men (167.7; 95% CI: 125.2, 224.6). Conclusion The data from this 20-year follow-up study confirm previous observations that two doses of Epaxal® provide protection against hepatitis A infection for at least 30 years in over 95% of healthy participants.

Este artículo contiene 13 páginas, 5 figuras, 2 tablas., Recovery of the submersed vegetation is a target for the management of soft-water shallow lakes if they are to meet water quality and biodiversity standards. Knowledge of patterns of macrophyte space occupation and time to recovery is poor and mostly restricted to free floating species or riparian vegetation. Here we use pre- and post-impact monitoring data over 20 years showing the evolution of submersed aquatic vegetation of lake Baciver (Pyrenees), and develop models to infer space occupation and time to recovery. We use pre-impact macrophyte distribution in relation to bathymetry-derived data to fit logistic models to further simulate lake equilibrium scenarios. Depth and slope were found to be the best predictors, and models suggested that an assemblage dominated by Sparganium angustifolium was, at time of this study, over 95% of its potential distribution area. A dense, newly grown monospecific Isoetes lacustris population occupied\10% of its potential area and model projections suggest that it will take decades to recover. An I. lacustris residual population remains below the estimated depth threshold for survival and is bound to disappear. The lake appears to evolve towards a new steady-state where the current lake hypsography promotes the expansion of algae (Nitella sp.) over angiosperms., This study was funded by the Red de Parques Nacionales of the Spanish Ministry of the Environment (PN I?D?I ref. 118/2003 and AQUAREST ref. OAPN 212/2010) and Intramural CSIC (Consejo Superior de Investigaciones Cientı´ficas) ref. 0065.

We describe the case of a 12-year-old boy from Sudan who presented with fever of 1-week duration, headache, cough, and vomiting. A set of diagnostic tests led to the diagnosis of three infectious diseases: visceral leishmaniasis (probable diagnosis based on positive direct agglutination test), enteric fever (blood culture grown with Salmonella Paratyphi), and brucellosis (blood culture grown with Brucella melitensis). The patient received specific treatment of the three infections and recovered. This case illustrates the occurrence and possible implications of coinfections in patients with persistent fever, including conditions that are hard to diagnose in field settings, such as brucellosis and enteric fever. ispartof: AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE vol:99 issue:5 pages:1150-1152 ispartof: location:United States status: published

Background Expression of mitochondrial proteins is reduced within hibernating myocardium (HM). It is unclear whether dietary supplementation with CoQ10 can increase expression of mitochondrial electron transport chain (ETC) and antioxidant proteins within this tissue. In a swine model of HM, we tested whether dietary administration of CoQ10 for four weeks enhances the expression of ETC and antioxidant proteins within the mitochondria via increased PGC1α signaling. Methods 12 swine were instrumented with a fixed constrictor around the LAD artery to induce gradual stenosis. At three months, transthoracic ECHO was performed to confirm the presence of a wall motion abnormality in the anterior wall. Animals were then randomly assigned to receive daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo for four weeks. At this time, animals underwent a final ECHO and terminal procedure. Expression of nuclear-bound PGC1α (Western blots) and mitochondrial proteins (Tandem Mass Tag) were determined. Results Mitochondrial and nuclear membranes were isolated from the LAD region. Nuclear-bound PGC1α levels were > 200-fold higher with administration of four weeks of CoQ10 treatment (p = 0.016). Expression of ETC proteins was increased in those animals that received CoQ10. Compared with mitochondria in the LAD region from placebo-treated pigs, CoQ10-treated pigs had higher levels of Complex I (p = 0.03), Complex IV (p = 0.04) and Complex V (p = 0.028) peptides. Conclusions Four weeks of dietary CoQ10 in HM pigs enhances active, nuclear-bound PGC1α and increases the expression of ETC proteins within mitochondria of HM tissue.

Genomic duplications and fusion involving BRAF and KIAA1549 that create fusion proteins with constitutive B-RAF kinase activity are a hallmark of pilocytic astrocytomas (PAs). The detection of KIAA1549–BRAF fusion transcripts is of paramount importance to classify these tumors and to identify patients who could benefit from BRAF inhibitors. In a clinical setting, the available material for molecular analysis from these pediatric tumors is often limited to formalin-fixed paraffin-embedded (FFPE) tissue. The aim of the present study was to develop a new method to detect the three most frequent KIAA1549–BRAF fusion transcripts, 15–9, 16–11, and 16–9, where numbers refer to the exons fused together, using a FFPE-compatible multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR). We compared performance of the assay to a reference singleplex method on a collection of 46 FFPE PAs. The results showed that both methods are comparable. The multiplex method had an overall 97% sensitivity and 100% specificity compared to the singleplex method, and agreement between the two techniques was almost perfect (Cohen’s kappa: 0.97). There was no evidence of a significant difference between the qRT-PCR efficiencies of the multiplex technique and of the singleplex assay for all fusion transcripts and for GAPDH, the latter used as a reference gene. The multiplex method consumed four times less complementary DNA (cDNA), cost less, and required half the hands-on technical time. The results show that it could be beneficial to implement the multiplex method in a clinical setting, where samples presenting low quantity of degraded RNA are not unusual.

Acetic acid bacteria (AAB) are widespread microorganisms in nature, extensively used in food industry to transform alcohols and sugar alcohols into their corresponding organic acids. Specialized strains are used in the production of vinegar through the oxidative transformation of ethanol into acetic acid. The main AAB involved in the production of high-acid vinegars using the submerged fermentation method belong to the genus Komagataeibacter, characterized by their higher ADH stability and activity, and higher acetic acid resistance (15-20%), compared to other AAB. In this work, the bacteria involved in the production of high-acid spirit vinegar through a spontaneous acetic acid fermentation process was studied. The analysis using a culture-independent approach revealed a homogeneous bacterial population involved in the process, identified as Komagataeibacter spp. Differentially expressed proteins during acetic acid fermentation were investigated by using 2DDIGE and mass spectrometry. Most of these proteins were functionally related to stress response, the TCA cycle and different metabolic processes. In addition, scanning and transmission electron microscopy and specific staining of polysaccharide SDS-PAGE gels confirmed that Komagataeibacter spp. lacked the characteristic polysaccharide layer surrounding the outer membrane that has been previously reported to have an important role in acetic acid resistance in the genus Acetobacter.

SUMMARYPlants sense different parts of the sun’s light spectrum using specialized photoreceptors, many of which signal through the E3 ubiquitin ligase COP1. Photoreceptor binding modulates COP1’s ubiquitin ligase activity towards transcription factors. Here we analyze why many COP1-interacting transcription factors and photoreceptors harbor sequence-divergent Val-Pro (VP) peptide motifs. We demonstrate that VP motifs enable different light signaling components to bind to the WD40 domain of COP1 with various binding affinities. Crystal structures of the VP motifs of the UV-B photoreceptor UVR8 and the transcription factor HY5 in complex with COP1, quantitative binding assays and reverse genetic experiments together suggest that UVR8 and HY5 compete for the COP1 WD40 domain. Photoactivation of UVR8 leads to high-affinity cooperative binding of its VP domain and its photosensing core to COP1, interfering with the binding of COP1 to its substrate HY5. Functional UVR8 – VP motif chimeras suggest that UV-B signaling specificity resides in the UVR8 photoreceptor core, not its VP motif. Crystal structures of different COP1 – VP peptide complexes highlight sequence fingerprints required for COP1 targeting. The functionally distinct blue light receptors CRY1 and CRY2 also compete with downstream transcription factors for COP1 binding using similar VP-peptide motifs. Together, our work reveals that photoreceptors and their components compete for COP1 using a conserved displacement mechanism to control different light signaling cascades in plants.

Background Strongyloidiasis can be fatal in immunocompromised patients, but few epidemiological studies investigated the burden of this neglected tropical disease among these populations, particularly in low- and middle-income countries such as Bolivia. This study aimed to fill in this gap by estimating prevalence rate and risk factors associated with strongyloidiasis among patients at high risk of complications Methods A cross-sectional study was carried out in Santa Cruz (elevation 400 meters, tropical climate) and Cochabamba (elevation 2,500 meters, temperate climate), among patients with cancer, HIV infection and rheumatic or hematologic disease, using four coproparasitological techniques and one serological (ELISA) test. Results In total, 1,151 patients participated in this study, including individuals who were HIV-positive (30%) or with rheumatic (29%), oncologic (32%) or hematologic (9%) diseases. The serological and coproparasitological prevalence was 23.0% (95% confidence interval [CI], 20.7–25.5; n = 265/1151) and 7.6% (95% CI, 6.2–9.3; n = 88/1151), respectively, with an estimated actual prevalence of 20.2% (95% CI, 17.9–22.5). Positive serology and positive coproparasitology were associated with younger age and lower education levels. There was no significant difference in prevalence between Cochabamba and Santa Cruz as defined by coproparasitology (6.4% vs. 8.9%; p = 0.11) or serology (24.0% vs. 22.0%; p = 0.4). Among 64 patients in Cochabamba who had never travelled to the tropical lowlands, 5 (7.8%) had a positive coproparasitology. Conclusions Strongyloidiasis is widely prevalent in Bolivia among vulnerable patients at increased risk of life-threatening complications. Transmission of the parasite occurs both in tropical lowlands and temperate elevation (≥ 2,500 m). Control strategies to prevent transmission and complications of this serious parasitic disease should be urgently reinforced., Author summary Strongyloidiasis is an understudied chronic intestinal infection and one of the most overlooked of the neglected tropical diseases, particularly in countries such as Bolivia. The strongyloidiasis usually remains paucisymptomatic for decades in immunocompetent persons, but may lead to severe conditions with high mortality rates in immunocompromised individuals. We carried out a study to explore the epidemiology of strongyloidiasis among Bolivian patients with cancer, HIV infection, and rheumatic or hematologic diseases. Our study highlighted that strongyloidiasis was widely prevalent in tropical and inter-Andean temperate areas of Bolivia among patients at high risk of life-threatening complications. One in five participants was infected. We showed that strongyloidiasis was highly prevalent in both tropical and temperate regions. Improved access to adequate diagnosis, treatment, and preventive measures are therefore urgently required in Bolivia, and most likely elsewhere in the region. Treatment of uncomplicated strongyloidiasis is simple, highly effective, and potentially life-saving.

Plants sense different parts of the sun's light spectrum using distinct photoreceptors, which signal through the E3 ubiquitin ligase COP1. Here, we analyze why many COP1‐interacting transcription factors and photoreceptors harbor sequence‐divergent Val‐Pro (VP) motifs that bind COP1 with different binding affinities. Crystal structures of the VP motifs of the UV‐B photoreceptor UVR8 and the transcription factor HY5 in complex with COP1, quantitative binding assays, and reverse genetic experiments together suggest that UVR8 and HY5 compete for COP1. Photoactivation of UVR8 leads to high‐affinity cooperative binding of its VP motif and its photosensing core to COP1, preventing COP1 binding to its substrate HY5. UVR8–VP motif chimeras suggest that UV‐B signaling specificity resides in the UVR8 photoreceptor core. Different COP1–VP peptide motif complexes highlight sequence fingerprints required for COP1 targeting. The blue‐light photoreceptors CRY1 and CRY2 also compete with transcription factors for COP1 binding using similar VP motifs. Thus, our work reveals that different photoreceptors and their signaling components compete for COP1 via a conserved mechanism to control different light signaling cascades.

Este artículo contiene 18 páginas, 8 figuras, 1 tabla., Historical information on marine organisms needs to be incorporated to develop effective management plans and conservation targets. In the Mediterranean Sea most species of brown seaweeds of the order Fucales are threatened or endangered and need protection. Here we merge data on historical and current records to create the first reference dataset on past and present distributions of Fucales from shallow and sheltered shores of Catalonia (NW Mediterranean Sea). Most Cystoseira sensu lato populations were found in the northern shores, where the most suitable environments exist. Carpodesmia mediterranea and Cystoseira compressa are far more abundant in exposed than in shallow, sheltered shores. Populations of most of the taxa (i.e. Carpodesmia crinita, Treptacantha elegans, T. sauvageauana, T. barbata f. aurantia) have suffered an important regression and two taxa have apparently become locally extinct (Cystoseira foeniculacea, Treptacantha barbata f. barbata). Carpodesmia caespitosa is still widespread in sheltered environments from the northern shores and a previously unreported taxon has been found (T. ballesterosii var. tenuior). Our regional-scale study makes available a solid, comprehensive baseline for future monitoring and application of conservation measures for the several threatened species of Fucales., Financial support to this research came from the projects ‘‘Cartografia dels Hàbitats Litorals a Catalunya’’ (Departament de Territori i Sosteniblitatand Institut Cartogàfic, Generalitat de Catalunya, Spain), CTN1500528 of the Agència Catalana de l’Aigua, Spain, and the INTRAMURAL CSIC PIE201730E033. Jana Verdura and Alba Medrano benefitted of funding from the Horizon 2020 EU Research and Innovation Program under grant agreement No. 689518 (MERCES). Partial funding came from the Sustainable Blue Economy program, European Union under the grant agreement AFRIMED EASME/EMFF/2017/1.2.1.12/S4/01/SI2.789059 to Jana Verdura.

Burrowing is an energetically costly form of locomotion that has evolved multiple times in mammals. Burrowing performance is associated with varying degrees of morphological specialization and is also affected by the characteristics of the substrate that animals burrow in. Moles (Talpidae) are well known for their specialized forelimbs and extreme dedication to life underground. In this study, we investigated how soil compactness affects burrowing performance in two sympatric mole species, eastern moles (Scalopus aquaticus) and hairy-tailed moles (Parascalops breweri). We measured burrowing speed, the amount of soil moved, rate of soil transport, tunnel length, activity level and the tendency to burrow over long distances, and tested how these variables changed in response to loose, intermediate and compact soils. We found that increasing soil compactness impedes tunneling performance as evidenced by reduced burrowing speed, increased soil transport, shorter tunnels, shorter activity time and less time spent burrowing continuously. Eastern moles built longer tunnels than hairy-tailed moles as soil compactness increased. This difference is linked to burrowing for longer times and distances, not higher burrowing speeds or rates of soil transport. Differences in performance between the two species may be associated with differences in the structure and extent of their burrow systems or the morphology of their forelimbs. They may also reflect preferences for loose (hairy-tailed moles) or compact soils (eastern moles).

© 2016, National Academy of Sciences. All rights reserved. Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here, we report in the green alga Chlamydomonas reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast.

Oriental fruit moth (Grapholita molesta) is the most important pest of apple orchards in Brazil. For many years, insecticides have been the only tool used for its control. The aim of this work was to characterize the management of apple orchards by the system for Assessment of Environment Impact of Agricultural Technology Innovations (AMBITEC-AGRO) and to relate it with the resistance status of G. molesta populations. Insecticide resistance was estimated by toxicology and enzymatic activities of glutathione S-transferase (GST), esterases (a-ß EST), and acetylcholinesterase (AChE). The phytosanitary strategies adopted by the four apple production orchards in southern Brazil were analyzed in: Vacaria (RS population), Fraiburgo (SC1 population), São Joaquim (SC2 population), and Porto Amazonas (PR population). Oriental fruit moth field populations were reared in laboratory for bioassays with chlorpyriphos, carbaryl, deltamethrin, and tebufenozide insecticides and were compared with a reference susceptible population. Larval mortality rates were recorded for seven days. GST, a-ß EST, and AChE assays were performed with third- and fourth-instar larvae. Results indicated that oriental fruit moth populations collected in Vacaria, Fraiburgo, and São Joaquim showed tolerance to carbaryl and chlorpyriphos, whereas the population collected in Porto Amazonas was more susceptible. SC2 and PR populations were more tolerant to deltamethrin, while RS and SC1 populations were more susceptible. No population was tolerant to tebufenozide. RS population showed the highest activity for AChE, GST, and a-EST. The findings of this study suggest that the AMBITEC-AGRO system was a suitable method to evaluate the phytosanitary activity of apple orchards and to relate it to the resistance status of G. molesta populations. Resumo Mariposa-oriental (Grapholita molesta) é a praga mais importante de pomares de maçã no Brasil. Por muitos anos, o inseticida foi a única ferramenta usada como controle. O objetivo deste trabalho foi caracterizar o manejo dos pomares por meio da Avaliação de Impacto Ambiental da Inovação Tecnológica Agropecuária (AMBITEC-AGRO) e relacionar com o status da resistência de populações de G. molesta nos pomares de maçã, por bioensaios toxicológicos e atividades enzimáticas de glutatione S-transferase (GST), esterases (a-ß EST) e acetilcolinesterase (AChE). A estratégia fitossanitária adotada por quatro pomares de maçã no Sul do Brasil foi analisada em: Vacaria (população RS), Fraiburgo (população SC1), São Joaquim (população SC2) e Porto Amazonas (população PR). As populações foram criadas em laboratório para bioensaios com clorpirifós, carbaril, deltametrina e tebufenozide. A mortalidade larval foi avaliada durante sete dias. A atividade das enzimas GST, a-ßEST e AChE foi realizada com larvas de terceiro e quarto instares. O resultado indicou que as populações coletadas em Vacaria, Fraiburgo e São Joaquim mostraram tolerância ao carbaril e ao clorpirifós, enquanto em Porto Amazonas se mostraram mais suscetíveis. As populações de SC2 e PR foram mais tolerantes à deltametrina, enquanto que nenhuma foi tolerante a tebufenozide. A população RS foi a que apresentou maior atividade para AChE, GST e a-EST. Os resultados deste estudo podem sugerir que o sistema AMBITEC-AGRO foi um método adequado para avaliar as atividades fitossanitárias de um pomar de maçã e relacioná-lo ao estado de resistência das populações de G. molesta.

Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral (DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P, Regenerative therapy: A cell culture medium that promotes bone formation ‘Bone-conditioned medium’ could improve oral bone regeneration therapy by promoting the proliferation and maturation of bone-forming cells. Building on recent research demonstrating the benefits of using cell culture medium prepared with bone chips (BCM) in such treatments, researchers led by Maria Asparuhova of the University of Bern, Switzerland, set out to elucidate the medium’s mechanisms. The team found that BCM incubated with bone chips for short periods—as little as ten minutes—contained heightened levels of signaling protein TGF-β1, which enhanced mouse bone marrow cell proliferation while downregulating maturation. BCM incubated for longer periods also generated increased levels of another protein, BMP-2, which boosted the maturation of bone-forming cells. This study reveals a sequential role of these two factors in oral bone development, and the potential physiological actions of BCM when used in regenerative therapies.

Germline pathogenic variants in the breast cancer type 1 susceptibility gene BRCA1 are associated with a 60% lifetime risk for breast and ovarian cancer. This overall risk estimate is for all BRCA1 variants; obviously, not all variants confer the same risk of developing a disease. In cancer patients, loss of BRCA1 function in tumor tissue has been associated with an increased sensitivity to platinum agents and to poly-(ADP-ribose) polymerase (PARP) inhibitors. For clinical management of both at-risk individuals and cancer patients, it would be important that each identified genetic variant be associated with clinical significance. Unfortunately for the vast majority of variants, the clinical impact is unknown. The availability of results from studies assessing the impact of variants on protein function may provide insight of crucial importance. We have collected, curated, and structured the molecular and cellular phenotypic impact of 3654 distinct BRCA1 variants. The data was modeled in triple format, using the variant as a subject, the studied function as the object, and a predicate describing the relation between the two. Each annotation is supported by a fully traceable evidence. The data was captured using standard ontologies to ensure consistency, and enhance searchability and interoperability. We have assessed the extent to which functional defects at the molecular and cellular levels correlate with the clinical interpretation of variants by ClinVar submitters. Approximately 30% of the ClinVar BRCA1 missense variants have some molecular or cellular assay available in the literature. Pathogenic variants (as assigned by ClinVar) have at least some significant functional defect in 94% of testable cases. For benign variants, 77% of ClinVar benign variants, for which neXtProt Cancer variant portal has data, shows either no or mild experimental functional defects. While this does not provide evidence for clinical interpretation of variants, it may provide some guidance for variants of unknown significance, in the absence of more reliable data. The neXtProt Cancer variant portal ( https://www.nextprot.org/portals/breast-cancer ) contains over 6300 observations at the molecular and/or cellular level for BRCA1 variants.

Este artículo contiene 16 páginas, 3 tablas, 2 figuras., We studied community–environment relationships of lake macrophytes at two metacommunity scales using data from 16 regions across the world. More specifically, we examined (a) whether the lake macrophyte communities respond similar to key local environmental factors, major climate variables and lake spatial locations in each of the regions (i.e., within-region approach) and (b) how well can explained variability in the community–environment relationships across multiple lake macrophyte metacommunities be accounted for by elevation range, spatial extent, latitude, longitude, and age of the oldest lake within each metacommunity (i.e., across-region approach). In the within-region approach, we employed partial redundancy analyses together with variation partitioning to investigate the relative importance of local variables, climate variables, and spatial location on lake macrophytes among the study regions. In the across-region approach, we used adjusted R2 values of the variation partitioning to model the community–environment relationships across multiple metacommunities using linear regression and commonality analysis. We found that niche filtering related to local lake-level environmental conditions was the dominant force structuring macrophytes within metacommunities. However, our results also revealed that elevation range associated with climate (increasing temperature amplitude affecting macrophytes) and spatial location (likely due to dispersal limitation) was important for macrophytes based on the findings of the across-metacommunities analysis. These findings suggest that different determinants influence macrophyte metacommunities within different regions, thus showing context dependency. Moreover, our study emphasized that the use of a single metacommunity scale gives incomplete information on the environmental features explaining variation in macrophyte communities., Open access funding provided by University of Oulu including Oulu University Hospital. JA appreciates financial support from the Ella and Georg Ehrnrooth Foundation. BAL was supported by National Research, Development and Innovation Office—NKFIH, OTKA PD120775 Grant and by the Bolyai János Research Scholarship of the Hungarian Academy of Sciences. S.K. was supported by NWO Veni grant 86312012. Sampling of the coastal Brazilian lakes was financed by NWO grant W84-549; The National Geographic Society grant 7864-5; and CNPq grants 480122, 490409, 311427.

In Swiss prisons, more than 70% of detained people are foreigners and over one-third originate from sub-Saharan Africa or Latin America. These two regions are endemic for various tropical diseases and viral infections, which persist after migration to nonendemic countries. Parasitic infections (schistosomiasis; strongyloidiasis) and cooccurrent viral infections (HIV, hepatitis B (HBV), and hepatitis C (HCV)) are especially of concern for clinical care but have been neglected in empirical research. These diseases often remain silent for years before causing complications, especially if they occur concomitantly. Our research aimed to study the prevalence rates and coinfections of two neglected tropical diseases, namely, Strongyloides stercoralis and Schistosoma sp. and viral infections among sub-Saharan Africans (SSA) and Latin Americans (LA) in Switzerland’s largest pretrial prison. We carried out a cross-sectional prevalence study using a standardized questionnaire and serological testing. Among the 201 participants, 85.6% were SSA and 14.4% LA. We found the following prevalence ratios: 3.5% of HIV (4.1% in SSA, 0% in LA), 12.4% of chronic HBV (14.5% in SSA, 0% in LA), 2.0% of viraemic HCV (1.7% in SSA, 3.4% in LA), and 8.0% of strongyloidiasis (8.1% in SSA, 6.9% in LA). The serological prevalence of schistosomiasis among SSA was 20.3% (not endemic in Latin America). Two infections were simultaneously detected in SSA: 4.7% were coinfected with schistosomiasis and chronic HBV. Four other coinfections were detected among SSA: schistosomiasis-HIV, HIV-chronic HBV, HIV-HCV, and schistosomiasis-strongyloidiasis. To conclude, the high prevalence rates of persistent viral and parasitic infections and their potential coinfections among SSA and LA detained migrants highlight the need to implement control strategies and programs that reach people in detention centers in nonendemic countries.

Root functional diversity of submerged vegetation exerts a major effect on nitrogen (N) cycling in lake sediments. This fact, however, is neglected in current N-balance models because the links between the engineering role of plants and in situ microbial N cycling are poorly understood. We hypothesized that macrophyte species with high root oxygen loss (ROL) capacity promote the highest denitrification because of a higher abundance of ammonia oxidizers and tighter coupling between nitrifiers and denitrifier communities. We sampled five small ultraoligotrophic shallow lakes with abundant macrophyte cover including sediments dominated either by Isoetes spp. (high ROL), mixed communities of natopotamids (low ROL), and unvegetated sandy sediments. At each site, we quantified denitrification (DNT) rates and proxies for the abundance of denitrifiers (nirS and nirK genes), and both ammonia oxidizing archaea (AOA) and ammonia oxidizing bacteria (AOB) and the diversity of nirS-harboring bacteria. Vegetated sediments showed significantly higher abundances of N-cycling genes than bare sediments. Plant communities dominated by Isoetes generated sediments with higher redox and NO3− concentrations and significantly higher DNT rates than natopotamids-dominated landscapes. Accordingly, increasing DNT rates were observed along the gradient from low ROL plants-bare sediments-high ROL plants. Significantly higher abundance of the archaeal amoA gene was recorded in sediments colonized by high ROL plants unveiling a key biogeochemical role for AOA in coupling macrophyte landscape and ecosystem denitrification.

14 páginas, 4 figuras, 3 tablas., Light reduction and increased organic matter load often occur together in lakes undergoing eutrophication. We aimed at experimentally testing the relative importance of light availability, organic matter enrichment and their interactions in the collapse of healthy populations of Isoetes lacustris. We conducted an in situ shading (65 and 35% of incident light) and organic matter enrichment (10% enrichment) experiment in a Pyrenean pond (NE Spain). We followed plant performance using growth indicators, carbon balance indicators and individual survival. Severe light reduction (35%) resulted in a lengthening of the new leaves and no effects on mortality. Organic matter enrichment resulted in lower production and increased individual mortality. The combination of both stresses resulted in stronger negative effects and the highest mortality rate, which helps explaining I. lacustris die-offs observed after damming. Under severe light reduction (35%), plants used corm starch to keep growing. Consequently, starch percentage decreased and sucrose percentage increased as it was transported to the growing leaves. The most extreme changes were observed under severe light reduction and fertilization, which extremely increased the ratio between sucrose and total non-structural carbohydrates (TNC). Thus, I. lacustris sucrose:TNC ratio is a good indicator of light reduction and organic matter enrichment stresses., This study was funded by the Red de Parques Nacionales of the Spanish Ministry of the Environment (ref. 118/2003) and Intramural CSIC (Consejo Superior de Investigaciones Cientı´ficas) ref. 0065.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that they would exert benefits on the development of metabolic syndrome and associated NAFLD in a rodent model. C57Bl/6J mice were fed a high-fat diet until they developed metabolic syndrome and were then orally treated either with α-GOS at a physiological dose (2.2 g/kg BW/d) or the vehicle over 7 weeks. α-GOS induced a reduction in food intake, but without affecting body weight during the first week of treatment, when compared to the vehicle. Fasting glycaemia was improved after 4 weeks of treatment with α-GOS, whereas insulin sensitivity (assessed with HOMA-IR) was unaffected at the end of the experiment. Plasma non-esterified fatty acids, low-density lipoprotein (LDL) and total cholesterol were lowered by α-GOS while high-density lipoprotein (HDL) and triglycerides levels remained unaffected. α-GOS markedly improved liver steatosis as well as free fatty acid and triglyceride accumulation in the liver. α-GOS improved plasma lipids and prevented NAFLD development through mechanisms which are independent of body weight management and glycemic control.

Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P = 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has proved useful in categorization and identification of microbes, especially for routine identification of environmental and clinical microorganisms, and was considered as a good alternative for quick and accurate identification of Acetic acid bacteria (AAB). The accuracy of bacterial identification, using MALDI-TOF MS, largely depends on the robustness of the reference database and therefore, the construction and validation of such a reference database for the identification of AAB is crucial. The number of AAB new taxa has increased exponentially since the application of molecular techniques to replace the phenotypic methods traditionally used. With the number of AAB species rapidly increasing and the decreasing costs of sequencing, restriction fragment length polymorphism analysis of polymerase chain reaction-Amplified fragments analysis has become obsolete for the identification of novel isolates. A. E. Yetiman and Z. Kesmen applied denaturing gradient gel electrophoresis to investigate the bacterial population of different traditionally-produced vinegars and mothers of vinegar.

Background\ud \ud More than 30,000 malaria cases are reported annually among international travellers. Despite improvements in malaria control, malaria continues to threaten travellers due to inaccurate perception of risk and sub-optimal pre-travel preparation.\ud \ud Methods\ud \ud Records with a confirmed malaria diagnosis after travel from January 2003 to July 2016 were obtained from GeoSentinel, a global surveillance network of travel and tropical medicine providers that monitors travel-related morbidity. Records were excluded if exposure country was missing or unascertainable or if there was a concomitant acute diagnosis unrelated to malaria. Records were analyzed to describe the demographic and clinical characteristics of international travellers with malaria.\ud \ud Results\ud \ud There were 5689 travellers included; 325 were children

Este artículo contiene 12 páginas, 6 figuras, 3 tablas., 1. Variability in C and N stable isotopes has been acknowledged to hinder their use as tracers of food sources in the study of trophic interactions in ecosystems. This is particularly so whenever benthic primary production is substantial (variability in d13C) and the ecosystem under study is affected by human impacts (variability in d15N) in aquatic ecosystems. 2. In this study, we aim to better understand the large and often unexplained variability in the natural abundance of d13C and d15N signatures of aquatic plants by analyzing the isotopic composition of plants from 81 lentic systems from NE Spain in relation to extrinsic (alkalinity, pH, nutrient concentrations, water body typology and basin land use) and intrinsic (functional group, carbon assimilation metabolism, elemental composition) predictors. 3. We have encountered significant plasticity in isotopic signatures of aquatic plants associated with the variation in local conditions at the regional scale. The d13C signature varied from 43.1& to 7.5& (35.7& range) and drivers were both intrinsic and extrinsic. The functional group was the most important factor as it is influenced by different carbon sources. Aquatic plants with leaves in contact with the atmosphere (helophytes, free floating and floating attached; 34.8& to 14.6&) responded in a similar way as terrestrial plants. This contrasted with the enriched mean values of rooted submerged plants ( 16.7& to 10.5&) that were more enriched than the described terrestrial C3 range ( 34& to 22&) and completely overlapped the terrestrial C4 range ( 20& to 8&). Concentration of DIC and pH also emerged as important extrinsic factors driving d13C variability. 4. The d15N signature ranged from 5.2& to 20.1& (25.2& range) and the variability was mostly associated with extrinsic factors such as water body type and basin land use, as they influence both the d15N signature and concentration of the dissolved inorganic nitrogen in the aquatic ecosystems. 5. Only one multifactorial model including the functional group (with the largest contribution), DIC and pH was selected as the best model explaining the variability in d13C signatures of aquatic plants. The final model had a relatively large explained deviance and was consistent with the previous unifactorial results. Two different models were selected as the best models explaining variability in d15N signatures of aquatic plants. The models included the geomorphological type of water body as the variable with the largest contribution, and the percentage of either natural or agricultural coverage in the basin. These results are summarized in a conceptual model showing the predictors and their range and direction of variation. 6. This study shows that extrinsic factors are of greater importance in influencing the stable-isotope signatures of aquatic plants compared to terrestrial plants, because of varied sources and an often limited isotopic discrimination., This study has been funded by the Consejo Superior de Investigaciones Cient ıficas through the project Intramural CSIC ref. 0065 and by the Spanish Ministry of Science and Innovation through the project entitled Nitrogen stable isotopes in fluvial ecosystems, the role of biotic components as indicators of nitrogen sources and processes (ISONEF, CGL2008-05504-C02-02/BOS).

A short inflammatory phase and fast ingrowth of blood vessels and mesenchymal cells are essential for tissue integration of a biomaterial. Macrophages play a key role in this process. We investigated invasion of macrophages, blood vessels, and proliferating cells into a highly porous and volume-stable collagen matrix (VCMX) used for soft tissue augmentation around teeth and dental implants. The biomaterial was implanted in submucosal pouches in the canine maxilla, and the tissue response was analyzed at six different time points. Immunohistochemistry was done for proliferating cells (PCNA), macrophages (MAC387), multinucleated giant cells (CD86), and blood vessels (TGM2). Blood rapidly filled the VCMX pores. During the first week, MAC387+ cells populated the VCMX pores, blood vessels and PCNA+ cells invaded the VCMX, and CD86+ scattered cells were observed. At 15 days, MAC387+ cells were scanty, blood vessels had completely invaded the VCMX, the number of proliferating cells peaked, and fibroblasts appeared. At 30 days, MAC387+ were absent, the numbers of proliferating and CD86+ cells had declined, while blood vessel and fibroblast numbers were high. At 90 days, residual VCMX was well-integrated in soft connective tissue. In conclusion, the VCMX elicited a short inflammatory phase followed by rapid tissue integration.