Is There a Link between the Molecular Basis of Juvenile Idiopathic Arthritis and Autoimmune Diseases? Systematic Review.

Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up. METHODS: We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases. RESULTS: A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed. CONCLUSIONS: Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.

Novel electrochemical strategies for the microbial conversion of CO2 into biomass and volatile fatty acids using a fluid-like bed electrode in a three-phase reactor.

Microbial electrosynthesis (MES) constitutes a bioelectrochemical process where bacteria uptake electrons extracellularly from a polarized electrode to incorporate them into their anabolic metabolism. However, the efficiency of current MES reactor designs can be lower than expected due to limitations regarding electron transfer and mass transport. One of the most promising bioreactor configurations to overcome these bottlenecks is the Microbial Electrochemical Fluidized Bed Reactor (ME-FBR). In this study, microbial CO2 fixation is investigated for the first time in a ME-FBR operated as a 3-phase reactor (solid-liquid-gas). An electroconductive carbon bed, acting as a working electrode, was fluidized with gas and polarized at different potentials (-0.6, -0.8 and -1 V vs. Ag/AgCl) so it could act as an electron donor (biocathode). Under these potentials, CO2 fixation and electron transfer were evaluated. Autotrophic electroactive microorganisms from anaerobic wastewater were enriched in a ME-FBR in the presence of 2-bromoethanosulfonic acid (BES) to inhibit the growth of methanogens. Cyclic voltammetry analysis revealed interaction between the microorganisms and the cathode. Furthermore, volatile fatty acids like propionate, formate and acetate were detected in the culture supernatant. Acetate production had a maximum rate of ca. 1 g L-1 day-1 . Planktonic cell biomass was produced under continuous culture at values as high as ca. 0.7 g L-1 dry weight. Overall, this study demonstrates the feasibility of employing a fluidized electrode with gaseous substrates and electricity as the energy source for generating biomass and carboxylic acids.

Is There an Adequate Therapeutic Approach to Thyroid Pathology in Patients with Down Syndrome?

Thyroid dysfunction stands as the most prevalent endocrine disorder in individuals with Down syndrome, particularly showcasing both clinical and subclinical hypothyroidism. TSH and FT4 blood values serve as common diagnostic and treatment adjustment markers. In Down syndrome (DS), hormone values may deviate from those observed in the general population, which may lead to overdiagnosis and consequent iatrogenesis of subclinical hypothyroidism. The objective of this study was to analyze the appropriateness of the replacement therapeutic approach by identifying the TSH and FT4 values that can be considered normal in these patients. METHODS: A cross-sectional study was conducted in 503 subjects with DS of both sexes and without age limit drawn from the Health Program for individuals with DS in Valencia (Spain) from February 1993 to November 2021. The exclusion criteria included hyperthyroidism, nodules, tumors, or individuals under treatment with drugs influencing iodine metabolism. The normality of data distribution was assessed using the Shapiro-Wilk test. Outliers were detected using the Reed's criterion. Hormone values were estimated using quantile regression models for the 2.5th and 97.5th percentiles. RESULTS: The normal values identified were 0.88-11.25 mIU/L for TSH and 0.71-1.63 ng/dL for FT4. The Wald test indicated no significant differences in the reference intervals based on age or sex. CONCLUSION: The establishment of these values, which, in people with DS, can be considered unique, is of great importance, allowing a watchful waiting attitude to be maintained before starting replacement therapy that is unnecessarily or adjusting medication in diagnosed cases.

Analysis of the Psychosocial Sphere of Older Adults in Extreme Poverty in the Peruvian Amazon.

The situation of social exclusion in which older adults live in extreme poverty is a problem that leads to psychological alterations such as depression or cognitive deterioration. Our objective was to analyze the living conditions and the psychosocial sphere of older adult people living in extreme poverty in Requena del Tapiche in Peru. This was an observational, descriptive, cross-sectional study. Sixty participants between 60 and 100 years of age of both sexes were included who gave their informed consent. Sociodemographic variables were analyzed, and the Gijón, family Apgar, Yesavage, and Pfeiffer scales were used. The sample was composed of 55% women and 45% men, with a mean age of 79.2 years (SD 6.67). More than half live alone or with their spouse. Fifty-seven percent sleep on the floor or on wood, and about 82% do not have safe water. Family dysfunction is found in 40%, and 98% are at social risk or with an established social problem and a precarious economic situation. More than 60% suffer from depressive symptoms, which are more frequent in women. We conclude that older adults perceive deficient family support, observing a deteriorated social situation. Most of them are at risk of social exclusion and loneliness, making them more vulnerable. They show sadness, with a high rate of depression. People with more cognitive impairment live alone, and those in social exclusion suffer a higher degree of depression. More cooperative projects and health promotion interventions developed in the peripheral neighborhoods of Requena del Tapiche are needed to improve the impact on the health of older adult people in extreme poverty.

Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study.

OBJECTIVE: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes. DESIGN: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation. SETTING: Three inner-city UK National Health Service hospitals in London. PARTICIPANTS: Pregnant women with gestational diabetes treated with medication. INTERVENTIONS: 2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention. SECONDARY OUTCOME MEASURES: Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs. RESULTS: Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders. CONCLUSIONS: It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention. TRIAL REGISTRATION NUMBER: ISRCTN20930880.

Assessing Nutritional Status and Frailty among Poor Elderly Individuals in Requena del Tapiche, Peru.

Frailty is a biological syndrome that leads to a loss of physiological reserve, increasing susceptibility to adverse health events. In the Peruvian Amazon, the elderly live with hardly any economic resources, presenting a caloric deficit that is related to functional and cognitive deterioration. Our objective was to identify the health needs of elderly people living in extreme poverty in Requena (Peru) by means of a geriatric assessment of the nutritional and functional spheres to design, in the future, a cooperation project appropriate to the needs detected. This is an observational, descriptive, and cross-sectional study. Sixty participants were included, and sociodemographic and functional status variables were analyzed using the MNA and Barthel scales and the Get Up and Go test. The mean age of the participants was 79 ± 6.67 (women 55% and men 45%), where 60% had frailty. A statistically significant relationship was found between the MNA scores and Barthel test. Eighty-five percent were malnourished or at risk and thirteen percent had total or moderate dependence. We conclude that the nutritional status of the elderly was deficient. The high degree of living alone in which they live forces them to maintain their independence and their walking stability is normal. The situation of frailty exceeds the national average, a situation that has repercussions for their quality of life. We found a statistically significant association between nutritional status, dependence, and frailty. The better-nourished elderly are less frail and less dependent.

COVID-19 mortality among veterans with serious mental illness in the veterans health administration.

OBJECTIVE: Persons with serious mental illness (SMI: schizophrenia-spectrum disorders, bipolar disorder) experience increased risk of mortality after contracting COVID-19 based on the results of several international evaluations. However, information about COVID-19 mortality risk among patients with SMI in the Veterans Health Administration (VHA) has been limited, precluding identification of protective factors. The current evaluation was conducted to assess COVID-19 mortality risk among VHA patients with SMI and to evaluate potential protective factors in mitigating mortality risk following a positive COVID-19 diagnosis. METHODS: National VHA administrative data was used to identify all patients (N = 52,916) who received a positive COVID-19 test result between March 1, 2020, and September 30, 2020. Mortality risk was assessed by SMI status via bivariate comparisons and multivariate regression analyses. RESULTS: In unadjusted analyses, VHA patients with SMI overall and patients with bipolar disorder in particular did not experience increased mortality risk in the 30 days following a positive COVID test, although patients with schizophrenia had increased risk. Within adjusted analyses, patients with schizophrenia remained at increased mortality risk (OR = 1.38), but at reduced levels relative to previous evaluations in other healthcare settings. CONCLUSIONS: Within VHA, patients with schizophrenia, but not those with bipolar disorder, experience increased mortality risk in the 30 days following a positive COVID-19 test. Large integrated healthcare settings such as VHA may offer services which may protect against COVID-19 mortality for vulnerable groups such as persons with SMI. Additional work is needed to identify practices which may reduce the risk of COVID-19 mortality among persons with SMI.

Enteroaggregative Escherichia coli as etiological agent of endemic diarrhea in Spain: A prospective multicenter prevalence study with molecular characterization of isolates.

Background: Enteroaggregative Escherichia coli (EAEC) is increasingly associated with domestically acquired diarrheal episodes in high-income countries, particularly among children. However, its specific role in endemic diarrhea in this setting remains under-recognized and information on molecular characteristics of such EAEC strains is limited. We aimed to investigate the occurrence of EAEC in patients with non-travel related diarrhea in Spain and molecularly characterize EAEC strains associated with illness acquired in this high-income setting. Methods: In a prospective multicenter study, stool samples from diarrheal patients with no history of recent travel abroad (n = 1,769) were collected and processed for detection of EAEC and other diarrheagenic E. coli (DEC) pathotypes by PCR. An additional case-control study was conducted among children ≤5 years old. Whole-genome sequences (WGS) of the resulting EAEC isolates were obtained. Results: Detection of DEC in the study population. DEC was detected in 23.2% of patients aged from 0 to 102 years, with EAEC being one of the most prevalent pathotypes (7.8%) and found in significantly more patients ≤5 years old (9.8% vs. 3.4%, p < 0.001). Although not statistically significant, EAEC was more frequent in cases than in controls. WGS-derived characterization of EAEC isolates. Sequence type (ST) 34, ST200, ST40, and ST10 were the predominant STs. O126:H27, O111:H21, and O92:H33 were the predominant serogenotypes. Evidence of a known variant of aggregative adherence fimbriae (AAF) was found in 89.2% of isolates, with AAF/V being the most frequent. Ten percent of isolates were additionally classified as presumptive extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), or both, and belonged to clonal lineages that could be specifically associated with extraintestinal infections. Conclusion: EAEC was the only bacterial enteric pathogen detected in a significant proportion of cases of endemic diarrhea in Spain, especially in children ≤5 years old. In particular, O126:H27-ST200, O111:H21-ST40, and O92:H33-ST34 were the most important subtypes, with all of them infecting both patients and asymptomatic individuals. Apart from this role as an enteric pathogen, a subset of these domestically acquired EAEC strains revealed an additional urinary/systemic pathogenic potential.

Fluid-like cathode enhances valuable biomass production from brewery wastewater in purple phototrophic bacteria.

The climate crisis requires rethinking wastewater treatment to recover resources, such as nutrients and energy. In this scenario, purple phototrophic bacteria (PPB), the most versatile microorganisms on earth, are a promising alternative to transform the wastewater treatment plant concept into a biorefinery model by producing valuable protein-enriched biomass. PPB are capable of interacting with electrodes, exchanging electrons with electrically conductive materials. In this work, we have explored for mobile-bed (either stirred or fluidized) cathodes to maximize biomass production. For this purpose, stirred-electrode reactors were operated with low-reduced (3.5 e-/C) and high-reduced (5.9 e-/C) wastewater under cathodic polarization (-0.4 V and -0.8 V vs. Ag/AgCl). We observed that cathodic polarization and IR irradiation can play a key role in microbial and phenotypic selection, promoting (at -0.4 V) or minimizing (at -0.8 V) the presence of PPB. Then, we further study how cathodic polarization modulates PPB biomass production providing a fluid-like electrode as part of a so-called photo microbial electrochemical fluidized-bed reactor (photoME-FBR). Our results revealed the impact of reduction status of carbon source in wastewater to select the PPB photoheterotrophic community and how electrodes drive microbial population shifts depending on the reduction status of such carbon source.

Thrombocytopaenia and COVID-19 infection during pregnancy increases the risk of preeclampsia: a multicentre study.

RESEARCH QUESTION: Is a low platelet count related to an increased risk of severe disease in pregnant women with active severe acute respiratory syndrome coronavirus 2 infection? DESIGN: A cross-sectional multicentre study in pregnant women with COVID-19 confirmed by polymerase chain reaction, antigen test, antibody test, or all. RESULTS: A total of 153 pregnant women with COVID-19 were included in the study, of whom 12.4% had thrombocytopaenia. Pregnant women with thrombocytopaenia were on average 3.1 years older (95% CI 0.18 to 6.38) than women without thrombocytopaenia. Pregnant smokers had a higher risk of thrombocytopaenia than non-smokers (OR 6.55, CI 95% 1.29 to 33.13). B Rh negative (B Rh-) pregnant women had a much higher risk of thrombocytopaenia than pregnant women with other blood groups (OR 16.83, CI 95% 1.42 to 199.8). Pregnant women with thrombocytopaenia had a much higher risk of suffering from preeclampsia (OR 16.2, CI 95% 1.35 to 193.4). CONCLUSIONS: COVID-19 infection is not a risk factor for a low platelet count in pregnant women, although the risk is increased by smoking and in women with blood group B Rh-. In case of pregnancy with thrombocytopaenia, COVID-19 infection leads to an increased risk of preeclampsia.

Prevalence and temporal dynamics of Cryptosporidium spp., Giardia duodenalis, and Blastocystis sp. among toddlers attending day-care centres in Spain. A prospective molecular-based longitudinal study.

Giardia duodenalis, Cryptosporidium spp., and Blastocystis sp. are common intestinal eukaryotic parasites affecting children in developed and resource-limited countries. Lack of information on the epidemiology and long-term stability in asymptomatic children complicates interpretation of transmission and pathogenesis. To assess the occurrence, genetic diversity, and temporal dynamics of intestinal eukaryotic parasites in young children, 679 stool samples from 125 toddlers attending six public day-care centres in Central Spain were collected bimonthly within a 1-year period. Detection and identification of species/genotypes were based on PCR and Sanger sequencing methods. Four eukaryotic species were identified: G. duodenalis (2.5‒31.6%), Cryptosporidium spp. (0.0‒2.4%), Blastocystis sp. (2.5‒6.4%), and Entamoeba dispar (0.0‒0.9%). Entamoeba histolytica and Enterocytozoon bieneusi were undetected. Sequence analyses identified assemblage A (63.6%) and B (36.4%) within G. duodenalis (n = 11), C. hominis (40%), C. parvum (40%), and C. wrairi (20%) within Cryptosporidium spp. (n = 5), and ST1 (3.8%), ST2 (46.2%), ST3 (15.4%), and ST4 (34.6%) within Blastocystis sp. (n = 26). Giardia duodenalis sub-assemblage AII/AIII was detected in a toddler for 10 consecutive months. Stable carriage of Blastocystis ST2 allele 9, ST3 allele 34, and ST4 allele 42 was demonstrated in five toddlers for up to 1 year.   Conclusions: Giardia duodenalis and Blastocystis sp. were common in toddlers attending day-care centres in Central Spain. Long-term infection/colonization periods by the same genetic variant were observed for G. duodenalis (up to 10 months) and Blastocystis sp. (up to 12 months). What is Known: • Asymptomatic carriage of G. duodenalis and Blastocystis sp. is frequent in toddlers. • The epidemiology and long-term stability of these eukaryotes in asymptomatic young children is poorly understood. What is New: • Long-term colonization/infection periods by the same genetic variant were described for Blastocystis sp. (up to 12 months) and G. duodenalis (up to 10 months).

Microbial photoelectrosynthesis: Feeding purple phototrophic bacteria electricity to produce bacterial biomass.

Purple phototrophic bacteria are one of the main actors in chemolithotrophic carbon fixation and, therefore, fundamental in the biogeochemical cycle. These microbes are capable of using insoluble electron donors such as ferrous minerals or even carbon-based electrodes. Carbon fixation through extracellular electron uptake places purple phototrophic bacteria in the field of microbial electrosynthesis as key carbon capturing microorganisms. In this work we demonstrate biomass production dominated by purple phototrophic bacteria with a cathode (-0.6 V vs. Ag/AgCl) as electron donor. In addition, we compared the growth and microbial population structure with ferrous iron as the electron donor. We detect interaction between the cathode and the consortium showing a midpoint potential of 0.05 V (vs. Ag/AgCl). Microbial community analyses revealed different microbial communities depending on the electron donor, indicating different metabolic interactions. Electrochemical measurements together with population analyses point to Rhodopseudomonas genus as the key genus in the extracellular electron uptake. Furthermore, the genera Azospira and Azospirillum could play a role in the photoelectrotrophic consortium.

Atezolizumab and Bevacizumab Combination Therapy in the Treatment of Advanced Hepatocellular Cancer.

Liver cancer, particularly hepatocellular carcinoma, is a global concern. This study focuses on the evaluation of Atezolizumab and Bevacizumab combination therapy as a promising alternative in the treatment of advanced hepatocellular carcinoma. The objectives of this systematic review include evaluating the efficacy of Atezolizumab and Bevacizumab combination therapy compared to conventional therapies with Sorafenib and other conventional therapies, analyzing the associated adverse effects, and exploring prognostic factors in the setting of advanced hepatocellular carcinoma. A systematic literature review was carried out using the PubMed and Web of Science databases. Fifteen related articles were included and evaluated according to their level of evidence and recommendation. Results: The combination therapy of Atezolizumab and Bevacizumab, along with Sorafenib, showed positive results in the treatment of patients with advanced hepatocellular carcinoma. Significant adverse effects were identified, such as gastrointestinal bleeding, arterial hypertension, and proteinuria, which require careful attention. In addition, prognostic factors, such as transforming growth factor beta (TGF-ß), alpha-fetoprotein (AFP), and vascular invasion, were highlighted as key indicators of hepatocellular carcinoma progression. Conclusions: The combination of Atezolizumab and Bevacizumab is shown to be effective in the treatment of advanced hepatocellular carcinoma, although it is essential to take into consideration the associated adverse effects. The prognostic factors identified may provide valuable information for the clinical management of this disease. This study provides a comprehensive overview of a promising emerging therapy for liver cancer.

Nutritional Assessment of the Infant Population of the Chirikyacu Indigenous Community of Peru.

Malnutrition is one of the main public health problems affecting early childhood development, compromising the health and quality of life of thousands of Peruvian children. The main contribution of this work is the analysis of the nutritional status of the infant population of the Chirikyacu Indigenous Community of Peru in order to evaluate current and future food policies. It is a cross-sectional study with a sample of 19 children between 6 months and 6 years of age. Sociodemographic, anthropometric, clinical variables and dietary habits were analyzed from 7 January to 4 February 2018. The mean age of the children was 29.74 months (SD = 23.91). We found statistically significant differences between the BMI values of boys and girls (p < 0.05; Mann−Whitney test). According to the z-scores, 35.29% suffer from malnutrition, although in no case is it severe. Hair, nails and skin were in good condition in general, except for some cases showing signs of nutritional deficiency. Dietary patterns are based on legumes, vegetables, dairy products, ice cream, cookies and sweets, and are considered insufficient to cover basic needs; water intake was also insufficient. Breastfeeding lasted an average of 14 months (SD = 2.9). We found a prevalence of malnutrition higher than that established by the WHO in Latin America among the children of Chirikyacu. The dietary pattern is insufficient to cover basic needs, so it is necessary to continue with nutritional educational interventions to improve it.

Differences in Classification Standards For the Prevalence of Overweight and Obesity in Children. A Systematic Review and Meta-Analysis.

The prevalence of childhood obesity has increased dramatically all over the world in recent years. While obesity in adults can be easily measured using the BMI calculation, determining overweight and obesity in children is more controversial. The aim was to compare the three most used international classification systems (WHO 2007, CDC 2000 and Cole-IOTF) to determine overweight and obesity in infant and adolescent populations. We performed a systematic review in accordance with the PRISMA 2020 guidelines of articles comparing any of the three classification systems. The main findings were that the WHO 2007 criteria show the highest prevalence of overweight and obesity in the child and youth population. The prevalence of childhood overweight and obesity was determined to be higher in boys than in girls in most studies, when analysing the classifications of the WHO 2007, CDC 2000 and Cole-IOTF together. However, there was a higher prevalence of overweight and obesity in girls than in boys when only the CDC 2000 and Cole-IOTF criteria were considered. Both the results of the review and the great heterogeneity found in the meta-analysis show that it is necessary to unify the criteria for the classification of childhood overweight and obesity. International standards are insufficient for working with the current population. A working group should be created to address this issue and agree on the unification of a gold standard, taking into account the geographical region, the ethnic groups and the age groups of the child and youth population and above all, the secular growth.

The Validity and Reliability of the FANTASTIC Questionnaire for Nutritional and Lifestyle Studies in University Students.

The FANTASTIC questionnaire is a scientific instrument that can be used by health professionals for quickly and effectively measuring the quality of life and lifestyle of people. It is a simple questionnaire that measures different dimensions including nutritional status, but the possibility of using it as a resource for studies in the nutritional field (regardless of its correlation with this) has never been considered, nor has it been used for studies in university populations. The aim was to validate the FANTASTIC questionnaire to report on the participant's lifestyle in a Spanish university population by using a cross-sectional study. A sample of 501 participants was obtained. The study was approved by the Ethics Research Committee of Catholic University of Valencia, and written informed consent was obtained from all participants. Sociodemographic, lifestyle variables, habitual diet, and nutrition-related lifestyle were collected individually. Participants also completed the self-administered FANTASTIC questionnaire. The reliability analysis of the FANTASTIC questionnaire revealed a Cronbach's Alpha statistic result of 0.797. The Kaiser-Meyer-Olkin (KMO) value was 0.786, with a significant Bartlett's Test of Sphericity (p = 0.000). This shows that the FANTASTIC questionnaire has good internal consistency and good construct validity. A retest was performed in four weeks' time, showing excellent intraclass correlation values. We consider the applicability of the FANTASTIC questionnaire for nutritional studies in Spanish university students to be appropriate, and most students have high scores in the nutritional aspects of the questionnaire, showing correct diet implementation and good cooking skills.

First report of rodent-adapted Cryptosporidium wrairi in an immunocompetent child, Spain.

Cryptosporidiosis is a leading cause of childhood diarrhoea. Two species, Cryptosporidium hominis and Cryptosporidium parvum, are responsible for most confirmed cases globally. Close contact with pet animals can be an unnoticed source of children infections. We describe a case of infection by rodent-adapted Cryptosporidium wrairi in a 22-month-old immunocompetent toddler with no clinical manifestations in close contact with a pet guinea pig and poor personal hygiene practices in Majadahonda (Madrid, Spain). Attempts to determine the C. wrairi genotype family at the 60-kDa glycoprotein marker failed repeatedly. This is the first description of C. wrairi in a human host. Although a spurious infection cannot be completely ruled out, data presented here suggest that C. wrairi can be transmitted zoonotically.

Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study.

OBJECTIVES: To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women. DESIGN: A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation. SETTING: Five inner city UK National Health Service hospitals PARTICIPANTS: Multiethnic pregnant women at 12+0 and 15+6 weeks' gestation with risk factors for gestational diabetes. INTERVENTIONS: 2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, adherence and follow-up. SECONDARY OUTCOME MEASURES: Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs. RESULTS: Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks' and 34% (SD 41) at 36 weeks' gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference -0.6, 95% CI -1.2 to 0.0 and -2.69, 95% CI -5.26 to -0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence. CONCLUSIONS: A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol. TRIAL REGISTRATION NUMBER: ISRCTN48872100.

Epithelial-to-Mesenchymal Transition Mediates Resistance to Maintenance Therapy with Vinflunine in Advanced Urothelial Cell Carcinoma.

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients.

Microbial Electrochemical Fluidized Bed Reactor: A Promising Solution for Removing Pollutants From Pharmaceutical Industrial Wastewater.

The capacity of electroactive bacteria to exchange electrons with electroconductive materials has been explored during the last two decades as part of a new field called electromicrobiology. Such microbial metabolism has been validated to enhance the bioremediation of wastewater pollutants. In contrast with standard materials like rods, plates, or felts made of graphite, we have explored the use of an alternative strategy using a fluid-like electrode as part of a microbial electrochemical fluidized bed reactor (ME-FBR). After verifying the low adsorption capacity of the pharmaceutical pollutants on the fluid-bed electrode [7.92 ± 0.05% carbamazepine (CBZ) and 9.42 ± 0.09% sulfamethoxazole (SMX)], our system showed a remarkable capacity to outperform classical solutions for removing pollutants (more than 80%) from the pharmaceutical industry like CBZ and SMX. Moreover, the ME-FBR performance revealed the impact of selecting an anode potential by efficiently removing both pollutants at + 200 mV. The high TOC removal efficiency also demonstrated that electrostimulation of electroactive bacteria in ME-FBR could overcome the expected microbial inhibition due to the presence of CBZ and SMX. Cyclic voltammograms revealed the successful electron transfer between microbial biofilm and the fluid-like electrode bed throughout the polarization tests. Finally, Vibrio fischeri-based ecotoxicity showed a 70% reduction after treating wastewater with a fluid-like anode (+ 400 mV), revealing the promising performance of this bioelectrochemical approach.