Stochastic modeling of Dalbulus maidis, vector of maize diseases.

We developed a simple linear stochastic model for Dalbulus maidis dependent exclusively on temperature, whose parameters were determined from published field and laboratory studies performed at different temperatures. This model takes into account the principal stages and events of the life cycle of this pest, which is vector of maize diseases. We implemented the effect of distributed delays or Linear Chain Trick (LCT) considering a fixed number of sub-stages for egg and nymph stages of Dalbulus maidis in order to accurately represent what is observed in nature. A sensitivity analysis allows us to observe that the speed of the dynamics is sensitive to changes in the development rates, but not to the longevity of each stage or the fecundity, which almost exclusively affect insect abundance. We used our model to study its predictive and explanatory capacity considering a published experiment as a case study. Although the simulation results show a behavior qualitatively equivalent to that observed in the experimental results it is not possible to explain accurately the magnitude, nor the times in which the maximum abundances of second-generation nymphs and adults are reached. Therefore, we evaluated three possible scenarios for the insect that allow us to glimpse some of the advantages of having a computational model in order to find out what processes, taken into account in the model, may explain the differences observed between published experimental results and model results. The three proposed scenarios, based on variations in the parameterized rates of the model, can satisfactorily explain the experimental observations. We observed that in order to better simulate the experimental results it is not necessary to modify fecundity or mortality rates. However, it is necessary to accelerate the average development rates of our model by 20 to 40 %, compatible with extreme values of the rates close to the upper edges of the confidence bands of our parameterization rate curves, according to insects with faster development rates already reported in literature.

Dynamic adsorption of diclofenac onto a magnetic nanocomposite in a continuous stirred-tank reactor.

In this study, a waste-based magnetic activated carbon (MAC) was used for the first time in a continuous-flow stirred tank reactor (CSTR). The aim was to evaluate the dynamic removal of diclofenac (DCF) from water and wastewater. Firstly, the breakthrough curves corresponding to DCF adsorption from distilled water at different feed flow rates and doses of MAC were determined. After selecting the most favourable conditions, namely 0.18 h L-1 flow rate and 400 mg L-1 of MAC, the effect of different aqueous matrices was studied, with the breakthrough curves evidencing a performance decline in wastewater in comparison with distilled water. Finally, the exhausted MAC was magnetically recovered, regenerated by microwave-assisted heating and applied in two subsequent adsorption cycles. The regeneration studies pointed to a decrease of the specific surface area and an improvement of the magnetic retrievability of MAC. After the first regeneration step, just mild effects were observed in the dynamic adsorptive performance of MAC. However, after a second regeneration step, the performance declined ca. 50%. Overall, the results highlight the feasibility of producing waste-based magnetic composites that simultaneously combine high adsorption efficiency under dynamic operation in a CSTR, with easy retrievability and successful one-stage regeneration for further reutilization.

Informed consent in dentistry and medicine in Spain: Practical considerations and legality.

BACKGROUND: The healthcare practice of dentistry, as well as medicine, is framed within a legal environment. Patients have the right to know all the information related to any action performed on them and dental or medical doctors are obliged to obtain their patient's prior written informed consent (IC) before undertaking any healthcare procedures. MATERIAL AND METHODS: Here we reviewed the legality and jurisprudence in Spain regarding IC. We also used INFLESZ text readability analysis software to analyse a sample of official Spanish informed consent documents (ICDs) from different surgical and interventional procedures related to dentistry and oral cavity interventions. RESULTS: It is a mistake to confound IC with ICDs. This error prevents physicians from considering the former as a care process in which the patient's authorisation signature is the last link in a chain formed, almost in its entirety, by the informative process and deliberation alongside the patient. Multiple factors can influence communication between practitioners and their patients. Importantly, treatment adherence is greater when patients feel involved and autonomous in shared decision-making and when the circumstances of their lives are adequately considered. We concluded that although the ICDs we analysed conformed to the requirements set out in international law, they were somewhat difficult to read according to the reading habits of the general Spanish population. CONCLUSIONS: Knowledge about the legality of IC helps professionals to understand the problems that may arise from their non-compliance. This is because the omission or defective fulfilment of IC obligations is the origin of legal responsibility for medical practitioners. In this sense, to date, there have been more convictions for defective ICs than for malpractice. The information provided in ICs should include the risks, benefits, and treatment alternatives and must be tailored to the needs and capabilities of the patient to enable autonomous decision-making.

Acaricidal activity of the hexanic and hydroethanolic extracts of three medicinal plants against southern cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

The southern cattle tick Rhipicephalus microplus is a major problem for the cattle industry in tropical and subtropical areas worldwide. Chemical products are commonly applied to control it; however, their indiscriminate use has resulted in the appearance of resistant lineages. In the last decades, plants have been used as an alternative to conventional acaricidal drugs, as several plant compounds repel activity, decrease the reproductive potential and reduce the survival rate of ticks. For this reason, the in vitro efficacy of hexanic and hydroalcoholic extracts of Randia aculeata, Moringa oleifera and Carica papaya were evaluated against the larvae and engorged females of R. microplus. Larval packet tests and adult immersion tests were performed with seven concentrations of each of the extracts. The extracts obtained with hydroethanolic solution (polar solvent) exhibited a higher acaricidal activity than extracts prepared with n-hexane (non-polar solvent). Hydroethanolic extracts of R. aculeata seed and shell showed the highest larvicidal activity against R. microplus (100 and 91% mortality, respectively) at a concentration of 100 mg/mL. Randia aculeata (seed and shell), M. oleifera and C. papaya treatments at the same concentration (100 mg/mL) also resulted in adult mortality of 85, 75, 66 and 55%, respectively. The adult immersion test showed that hydroethanolic extracts derived from R. aculeata seed significantly reduced the index of egg laying and increased the percentage inhibition of oviposition of female ticks at a concentration of 100 mg/mL. These results indicate that the tested extracts exhibit acaricidal activity and could be considered as potential agents for the development of alternative natural acaricides against R. microplus.

Compost Tea Reduces the Susceptibility of Pinus radiata to Fusarium circinatum in Nursery Production.

Nutrition is one of the factors that most limits forestry plant growth; thus, current production in nurseries is based on conventional fertilization focused on enhancing vigor. However, an excessive intake of mineral nitrogen can cause morphological imbalances and the formation of more succulent tissues which, consequently, increase susceptibility to plant pathogens. Fusarium circinatum is the causal agent of pitch canker in plants of the Pinus genus, with Pinus radiata being the species most susceptible to this disease. This study compares the response of P. radiata seedlings to infection by F. circinatum as influenced by two fertilizers-conventional and aerated compost tea (ACT)-applied during the nursery phase. The potential of ACT against F. circinatum was first tested in vitro, where it was found to inhibit the pathogen's mycelial growth and conidial germination. In the greenhouse, infected plants fertilized with ACT exhibited less severe internal and external symptoms of pitch canker and lower levels of pathogen colonization of both stems and needles than with conventional fertilizer. An analysis of the hormone content and defense-related gene expression shows greater salicylic acid production and phenylalanine ammonium-lyase and chalcone synthase expression in ACT-fertilized pine. All of the parameters assessed are consistent in showing that biofertilization with ACT reduces the susceptibility of pine seedlings to the disease compared with conventional fertilization.

Impact of creating a haemodynamics room, a coronary unit and a primary angioplasty programme on the prognosis of acute coronary syndrome in a district hospital. / Impacto de la creación de una sala de hemodinámica, una unidad coronaria y un programa de angioplastia primaria en el pronóstico del síndrome coronario agudo en un hospital comarcal.

OBJECTIVE: To analyse the prognosis and mortality of patients hospitalised for acute coronary syndrome before and after the implementation of a coronary unit, haemodynamics room and the Código corazón primary angioplasty programme. METHODS: We conducted an observational and retrospective study that analysed the epidemiological characteristics, reperfusion strategies, adverse cardiovascular events and mortality for 5 years of follow-up. The results of the post-code period (March 1 - December 31, 2012; n=471) were compared with those of the pre-code stage (March 1 - December 31, 2009; n=432). RESULTS: There were no differences in the baseline characteristics of the 2 groups; however, an increase in ST-segment elevation acute coronary syndrome (STE-ACS) from 17.6% to 34.8% (P<.001) was observed during the post-code phase. The use of percutaneous coronary intervention was made widespread at the hospital, achieving rates of 64.8% in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and of 95.5% in STE-ACS. Readmissions were reduced (from 38.2% to 25.1% for NSTE-ACS [P=.001] and from 23.7% to 11.0% for STE-ACS [P=.018]), the combined prognostic variable of adverse cardiovascular events and mortality at 5 years of follow-up was reduced (from 58.7% to 45% [P=.001] for NSTE-ACS and from 40.8% to 23.8% [p=.009] for STE-ACS), and 30-day mortality was decreased for STE-ACS (from 11.8% to 3.7%; P=.021). CONCLUSIONS: With the structural changes in the hospital, the use of percutaneous coronary intervention was made widespread and improved the prognosis of patients with acute coronary syndrome, decreasing admissions, adverse cardiovascular events and mortality.

Low-level cyclic tibial compression attenuates early osteoarthritis progression after joint injury in mice.

OBJECTIVE: Mechanical loading and joint health have a unique relationship in osteoarthritis (OA) onset and progression. Although high load levels adversely affect cartilage health, exercise that involves low to moderate load levels can alleviate OA symptoms. We sought to isolate the beneficial effects of mechanical loading using controlled in vivo cyclic tibial compression. We hypothesized that low-level cyclic compression would attenuate post-traumatic OA symptoms induced by destabilization of the medial meniscus (DMM). METHODS: 10-week-old C57Bl/6J male mice underwent DMM surgery (n = 51). After a 5-day post-operative recovery period, we applied daily cyclic tibial compression to the operated limbs at low (1.0N or 2.0N) or moderate (4.5N) magnitudes for 2 or 6 weeks. At the completion of loading, we compared cartilage and peri-articular bone features of mice that underwent DMM and loading to mice that only underwent DMM. RESULTS: Compared to DMM alone, low-level cyclic compression for 6 weeks attenuated DMM-induced cartilage degradation (OARSI score, P = 0.008, 95% confidence interval (CI): 0.093 to 0.949). Low-level loading attenuated DMM-induced osteophyte formation after 2 weeks (osteophyte size, P = 0.033, 95% CI: 3.27-114.45 µm), and moderate loading attenuated subchondral bone sclerosis after 6 weeks (tissue mineral density (TMD), P = 0.011, 95% CI: 6.32-70.60 mg HA/ccm) compared to limbs that only underwent DMM. Finally, loading had subtle beneficial effects on cartilage cellularity and aggrecanase activity after DMM. CONCLUSION: Low-level cyclic compression is beneficial to joint health after an injury. Therefore, the progression of early OA may be attenuated by applying well controlled, low-level loading shortly following joint trauma.

A critical review on the use of artificial neural networks in olive oil production, characterization and authentication.

Artificial neural networks (ANN) are computationally based mathematical tools inspired by the fundamental cell of the nervous system, the neuron. ANN constitute a simplified artificial replica of the human brain consisting of parallel processing neural elements similar to neurons in living beings. ANN is able to store large amounts of experimental information to be used for generalization with the aid of an appropriate prediction model. ANN has proved useful for a variety of biological, medical, economic and meteorological purposes, and in agro-food science and technology. The olive oil industry has a substantial weight in Mediterranean's economy. The different steps of the olive oil production process, which include olive tree and fruit care, fruit harvest, mechanical and chemical processing, and oil packaging have been examined in depth with a view to their optimization, and so have the authenticity, sensory properties and other quality-related properties of olive oil. This paper reviews existing literature on the use of bioinformatics predictive methods based on ANN in connection with the production, processing and characterization of olive oil. It examines the state of the art in bioinformatics tools for optimizing or predicting its quality with a view to identifying potential deficiencies or aspects for improvement.

Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: results from the prospective BioCAPTURE registry.

BACKGROUND: Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates. OBJECTIVES: To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily-practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes. RESULTS: We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for 'side-effects' (P = 0.05) and 'global satisfaction' (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005). CONCLUSIONS: This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side-effects and global satisfaction. Differences in treatment satisfaction and side-effects might add to the fact that women discontinue biological treatments more often.

ITEMAS ontology for healthcare technology innovation.

BACKGROUND: The Platform for Innovation in Medical and Health Technologies (ITEMAS) is a network of 66 healthcare centres focused on fostering innovation in medical and health technologies as an essential tool for increasing the sustainability of the Spanish healthcare system. The present research is focused on defining a formal representation that details the most relevant concepts associated with the creation and adoption of innovative medical technology in the Spanish healthcare system. METHODS: The methodology applied is based on the methontology process, including peer-review identification and selection of concepts from the ITEMAS innovation indicators and innovation management system standards. This stage was followed by an iterative validation process. Concepts were then conceptualised, formalised and implemented in an ontology. RESULTS: The ontology defined describes how relationships between employees, organisations, projects and ideas can be applied to generate results that are transferrable to the market, general public and scientific forums. Overall, we identified 136 concepts, 138 object properties and 30 properties in a five-level hierarchy. The ontology was tested and validated as an appropriate framework for calculating the ITEMAS innovation indicators. CONCLUSIONS: The consensus concepts were expressed in the form of an ontology to be used as a single communication format between the members of the ITEMAS network. Healthcare centres can compare their innovation results and obtain a better understanding of their innovation context based on the reasoning techniques of artificial intelligence. As a result, they can benefit from advanced analytical capabilities to define the most appropriate innovation policies for each centre based on the common experience of the large number of healthcare centres involved. The results can be used to create a map of agents and knowledge to show capabilities, projects and services provided by each of the participating centres. The ontology could also be applied as an instrument to match needs with existing projects and capabilities from the community of organisations working in healthcare technology innovation.

Reduced optimism and a heightened neural response to everyday worries are specific to generalized anxiety disorder, and not seen in social anxiety.

BACKGROUND: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder. METHOD: Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future. RESULTS: As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t 17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both). CONCLUSIONS: The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE.

BACKGROUND: As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. OBJECTIVES: To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. METHODS: Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. RESULTS: We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. CONCLUSIONS: Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone.

Validation of the Simplified Psoriasis Index in Dutch children and adolescents with plaque psoriasis.

BACKGROUND: The Simplified Psoriasis Index (SPI) is a three-domain assessment measure for psoriasis, including separate indicators of current severity (SPI-s), psychosocial impact (SPI-p), and past history and interventions (SPI-i). There are two complementary versions available designed for completion by a health professional (proSPI) or by patient self-assessment (saSPI). The validity and reliability of the proSPI vs. saSPI have already been demonstrated in adults. To date, validated severity measures for paediatric psoriasis do not exist. OBJECTIVES: To validate the current severity (SPI-s) and psychosocial impact (SPI-p) domains of the proSPI and saSPI in children and adolescents with psoriasis. METHODS: All patients aged < 18 years with plaque psoriasis visiting the dermatology outpatient department of Radboud University Medical Center, the Netherlands, between September 2013 and April 2014 were asked to complete Dutch versions of the saSPI and the Children's Dermatology Life Quality Index (CDLQI). The original English versions of the proSPI and Psoriasis Area and Severity Index (PASI) were completed by the physician at the same visit. RESULTS: In total, 113 patients (median age 12·0 years, range 4-17) were included. There was a close correlation between the proSPI-s and PASI (r = 0·87), which was higher than between the saSPI-s and PASI (r = 0·69). The correlation between the SPI-p and CDLQI was 0·78. The full range of scores was utilized in both proSPI-s and SPI-p, although the highest saSPI-s score was 30 (maximum 50). CONCLUSIONS: In paediatric psoriasis, the proSPI and saSPI are shown to be valid and usable. The SPI-s and SPI-p can be readily introduced into routine clinical practice.

Comparison of the 1- and 5-year effectiveness of adalimumab, etanercept and ustekinumab in patients with psoriasis in daily clinical practice: results from the prospective BioCAPTURE registry.

BACKGROUND: The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. OBJECTIVES: To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. METHODS: Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. RESULTS: We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). CONCLUSIONS: Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.

Frequency and predictors of a high clinical response in patients with psoriasis on biological therapy in daily practice: results from the prospective, multicenter BioCAPTURE cohort.

BACKGROUND: It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. OBJECTIVES: To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. METHODS: Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni- and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. RESULTS: In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. CONCLUSIONS: A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.

Paracetamol and salicylic acid removal from contaminated water by microalgae.

The biomass growth, pharmaceutical removal and light conversion efficiency of Chlorella sorokiniana under the presence of paracetamol (PC) and salicylic acid (SaC) were assessed and compared at two different concentrations of these pharmaceuticals (I: 25 mg l-1, II: 250 mg l-1). Microalgae were resistant to these concentrations and, moreover, their growth was significantly stimulated (p ≤ 0.05) under these drugs (biomass concentration increased above 33% PCI, 35% SaCI, 13% PCII and 45% SaCII, as compared with the respective positive controls). At the steady state of the semicontinuous culture, C. sorokiniana showed removal efficiencies above 41% and 69% for PCI and PCII, respectively; and above 93% and 98% for SaCI and SaCII, respectively. Under an irradiance of 370 µE m-2 s-1, higher quantum yields were reached by microalgae under the presence of drugs, either at dose I or II, than by the respective positive controls. These results point to C. sorokiniana as a robust strain for the bioremediation of paracetamol and salicylic acid concentrated wastewaters.

Clinical and endoscopic features in patients with hospital-acquired diarrhea associated with Clostridium difficile infection. / Características clínicas y endoscópicas en diarrea hospitalaria asociada a infección por Clostridium difficile.

INTRODUCTION AND AIMS: Clostridium difficile infection is the main cause of hospital-acquired diarrhea, and the clinical and endoscopic findings in those patients have been studied very little in Mexico. The aim of the present study was to describe those findings. MATERIALS AND METHODS: A prospective cohort study was conducted that included patients with hospital-acquired diarrhea associated with Clostridium difficile diagnosed through polymerase chain reaction. The hypervirulent NAP027 strain was also determined. The clinical and endoscopic findings in the study patients, as well as the variables associated with severity, were analyzed. RESULTS: Of the 127 patients with hospital-acquired diarrhea, 97 were excluded from the study due to lack of colonoscopy. The remaining 39 study patients had a mean age of 48 years, and their most common signs/symptoms were abdominal pain (49%), mucus in stools (41%), and blood in stools (10%). The most common alterations in the laboratory results were leukocytosis in 49%, fecal leukocytes (61%), and hypoalbuminemia (67%). The main risk factor was antibiotic use in 62%, and ceftriaxone was the most widely used. The hypervirulent strain was present in 54% of the cases. Endoscopic abnormalities were found in 87% of the patients. Thirty-eight percent presented with pseudomembranous colitis, with lesions in the left colon in 53%, and in the right colon in 13%. No association was found between proton-pump inhibitor use and Clostridium difficile-associated diarrhea. There was a significant association between hypoalbuminemia (< 3.3g/dL) and a greater risk for severe colitis, with a RR of 8.2 (p=0.008). CONCLUSIONS: Pseudomembranous colitis lesions associated with the hypervirulent Clostridium difficile strain were predominant in the left colon. Hypoalbuminemia was a significant severity predictor.

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in OA progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN: Knee joints of WT and Phlpp1(-/-) mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression were evaluated in human articular cartilage and chondrocyte cell lines. RESULTS: Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1(-/-) mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures (FNFxs). Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION: Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory cytokines promote PHLPP1 expression.

Z-scan for thin media with more than one nonlocal nonlinear response.

A model to characterize the response of a thin media that can exhibit more than one nonlocal nonlinear response when it is illuminated with a Gaussian beam in a z-scan experiment is proposed. The model considers that these nonlocal contributions can be treated as independent contributions in the refractive or absorptive nonlinear response. Numerical results for two nonlocal nonlinear contributions with different magnitudes between them are presented. Experimental results obtained from a hydrogenated amorphous silicon sample are used to corroborate this model.

Learning from other people's fear: amygdala-based social reference learning in social anxiety disorder.

BACKGROUND: Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions? METHOD: A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others' fearful, angry, happy or neutral reactions. RESULTS: During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others' fearful reactions, and a trend towards decreased amygdala activation to objects associated with others' happy and neutral reactions. CONCLUSIONS: These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.