Biomarkers of Bipolar Disorder in Late Life: An Evidence-Based Systematic Review.

PURPOSE OF REVIEW: Review the current evidence on biomarkers for bipolar disorder in the older adults. We conducted a systematic search of PubMed MEDLINE, PsycINFO, and Web of Science databases using the MeSH search terms "Biomarkers", "Bipolar Disorder", "Aged" and and "Aged, 80 and over". Studies were included if they met the following criteria: (1) the mean age of the study population was 50 years old or older, (2) the study included patients with bipolar disorder, and (3) the study examined one type of biomarkers or more including genetic, neuroimaging, and biochemical biomarkers. Reviews, case reports, studies not in English and studies for which no full text was available were excluded. A total of 26 papers were included in the final analysis. RECENT FINDINGS: Genomic markers of bipolar disorder in older adults highlighted the implication of serotonin metabolism, while the expression of genes involved in angiogenesis was dysregulated. Peripheral blood markers were mainly related with low grade inflammation, axonal damage, endothelial dysfunction, and the dysregulation of the HPA axis. Neuroanatomical markers reflected a dysfunction of the frontal cortex, a loss of neurones in the anterior cingulate cortex and a reduction of the hippocampal volume (in patients older than 50 years old). While not necessarily limited to older adults, some of them may be useful for differential diagnosis (neurofilaments), disease staging (homocysteine, BDNF) and the monitoring of treatment outcomes (matrix metalloproteinases). Our review provides a comprehensive overview of the current evidence on biomarkers for bipolar disorder in the older adults. The identification of biomarkers may aid in the diagnosis, treatment selection, and monitoring of bipolar disorder in older adults, ultimately leading to improved outcomes for this population. Further research is needed to validate and further explore the potential clinical utility of biomarkers in this population.

Comparison of sediment bioavailable methods to assess the potential risk of metal(loid)s for river ecosystems.

A heavily impacted river basin (Caudal River, NW Spain) by Hg and Cu mining activities, abandoned decades ago, was used to evaluate the environmental quality of their river sediments. The obtained results compared with reference values established by the US EPA and the Canadian Council of Ministers of the Environment for river sediments, have shown that the main elements of environmental concern are arsenic (As), mercury (Hg) and, to a lesser extent, copper (Cu), which reach concentrations up to 1080, 80 and 54 mg kg-1, respectively. To understand the role that river sediments play in terms of risk to ecosystem health, a comparison has been made between the total content of metal(oid)s in the sediments and the bioavailable contents of the same elements in pore water, passive DGT (Diffusive Gradients in Thin films) samplers and the sediment extractant using acetic acid. A good correlation between the As and Cu contents in the DGTs and the pore water was found, resulting in a transfer from the pore water to the DGT of at least 47 % of the Cu and more than 75 % of the As when the concentrations were low, with a deployment time of 4 days. When As and Cu concentrations were higher, their transfer was not so high (above 23.6 % for As and 19.3 % for Cu). The transfer of Hg from the pore water to the DGT was practically nil and does not seem to depend on the content of this metal. The fraction extracted with acetic acid, conventionally accepted as bioavailable, was clearly lower than that captured by DGTs for As and Cu (≤5 % and ≤8.5 % of the total amount, respectively), while it was similar for Hg (0.2 %).

Low temperature nucleation of thermochromic VO2crystal domains in nanocolumnar porous thin films.

The low temperature formation of monoclinic VO2crystal domains in nanocolumnar vanadium/oxygen thin films prepared by magnetron sputtering at oblique angles is analyzed. The synthesis procedure involved the deposition of amorphous nanocolumnar VO1.9thin films at room temperature and its subsequent annealing at temperatures between 250 °C and 330 °C in an oxygen atmosphere. The thermochromic transition of these films was found at a temperature of 47 °C when the annealing temperature was 270 °C and 58 °C when the annealing temperature was 280 °C and 290 °C, presenting a clear drop of the optical transmittance in the infrared region of the spectrum. The significant downshift in the temperature window to obtain VO2in comparison with compact films and other strategies in literature is explained by the particular morphology of the nanocolumnar structures, which contains numerous defects along with open and embedded porosity.

Growth dynamics of nanocolumnar thin films deposited by magnetron sputtering at oblique angles.

The morphology of numerous nanocolumnar thin films deposited by the magnetron sputtering technique at oblique geometries and at relatively low temperatures has been analyzed for materials as different as Au, Pt, Ti, Cr, TiO2, Al, HfN, Mo, V, WO3and W. Despite similar deposition conditions, two characteristic nanostructures have been identified depending on the material: a first one defined by highly tilted and symmetric nanocolumnar structures with a relatively high film density, and a second one characterized by rather vertical and asymmetric nanocolumns, with a much lower film density. With the help of a model, the two characteristic nanostructures have been linked to different growth dynamics and, specifically, to different surface relaxation mechanisms upon the incorporation of gaseous species with kinetic energies above the surface binding energy. Moreover, in the case of Ti, a smooth structural transition between the two types of growths has been found when varying the value of the power used to maintain the plasma discharge. Based on these results, the existence of different surface relaxation mechanisms is proposed, which quantitatively explains numerous experimental results under the same conceptual framework.

A review of three decades of use of the cattle brucellosis rough vaccine Brucella abortus RB51: myths and facts.

Cattle brucellosis is a severe zoonosis of worldwide distribution caused by Brucella abortus and B. melitensis. In some countries with appropriate infrastructure, animal tagging and movement control, eradication was possible through efficient diagnosis and vaccination with B. abortus S19, usually combined with test-and-slaughter (T/S). Although S19 elicits anti-smooth lipopolysaccharide antibodies that may interfere in the differentiation of infected and vaccinated animals (DIVA), this issue is minimized using appropriate S19 vaccination protocols and irrelevant when high-prevalence makes mass vaccination necessary or when eradication requisites are not met. However, S19 has been broadly replaced by vaccine RB51 (a rifampin-resistant rough mutant) as it is widely accepted that is DIVA, safe and as protective as S19. These RB51 properties are critically reviewed here using the evidence accumulated in the last 35 years. Controlled experiments and field evidence shows that RB51 interferes in immunosorbent assays (iELISA, cELISA and others) and in complement fixation, issues accentuated by revaccinating animals previously immunized with RB51 or S19. Moreover, contacts with virulent brucellae elicit anti-smooth lipopolysaccharide antibodies in RB51 vaccinated animals. Thus, accepting that RB51 is truly DIVA results in extended diagnostic confusions and, when combined with T/S, unnecessary over-culling. Studies supporting the safety of RB51 are flawed and, on the contrary, there is solid evidence that RB51 is excreted in milk and abortifacient in pregnant animals, thus being released in abortions and vaginal fluids. These problems are accentuated by the RB51 virulence in humans, lack diagnostic serological tests detecting these infections and RB51 rifampicin resistance. In controlled experiments, protection by RB51 compares unfavorably with S19 and lasts less than four years with no evidence that RB51-revaccination bolsters immunity, and field studies reporting its usefulness are flawed. There is no evidence that RB51 protects cattle against B. melitensis, infection common when raised together with small ruminants. Finally, data acumulated during cattle brucellosis eradication in Spain shows that S19-T/S is far more efficacious than RB51-T/S, which does not differ from T/S alone. We conclude that the assumption that RB51 is DIVA, safe, and efficaceous results from the uncritical repetition of imperfectly examined evidence, and advise against its use.

Cognitive outcomes following functional neurosurgery in refractory OCD patients: a systematic review.

Neurosurgery is a therapeutic option for patients with refractory obsessive-compulsive disorder who do not respond to previous treatments. Although its efficacy in reducing clinical symptomatology has been proven, few studies have analyzed its effects at the cognitive level. The aim of this systematic review was to describe the cognitive outcomes of functional neurosurgery in patients that went through capsulotomies or cingulotomies. PubMed, Medline, Scopus, PsycInfo, PsyArticles, and Web of Knowledge were searched for studies reporting cognitive outcomes in refractory obsessive-compulsive patients after capsulotomies and cingulotomies. The risk of bias was assessed with the Assessment Tool for Before-After (Pre-Post) Studies With No Control Group tool; 13 studies met inclusion criteria, including 205 refractory obsessive-compulsive disorder patients for both surgical procedures. Results showed a substantial number of studies that did report significant cognitive improvement after surgery, being this improvement specially related to memory and executive functions. The second-most frequent finding is the maintenance of cognitive performance (nor improvement or worsening). From a neuropsychological point of view, this outcome might be considered a success, given that it is accompanied by amelioration of obsessive-compulsive symptoms. Subtle cognitive adverse effects have also been reported. Neurosurgery procedures appear to be safe from a cognitive point of view. Methodological issues must be improved to draw clearer conclusions, but capsulotomies and cingulotomies constitute an effective alternative treatment for refractory obsessive-compulsive disorder patients.

Effect of carbon source and metal toxicity for potential acid mine drainage (AMD) treatment with an anaerobic sludge using sulfate-reduction.

This study compares sulfate-reduction performance in an anaerobic sludge with different carbon sources (ethanol, acetate, and glucose). Also, the toxic effect of copper was evaluated to assess its feasibility for possible acid mine drainage (AMD) treatment. Serological bottles with 1.5 g VSS/L and 150 mL of basal medium (0.67 g COD/g SO42- at a 7-8 pH) were used to determine the percentage of electron equivalents, maximum specific methanogenic (SMA), and sulfide generation activities (SGA). The copper effect was evaluated in a previously activated sludge in batch bioassays containing different concentrations of copper (0-50 mg/L), 3 gVSS/L, and 150 mL of basal medium (0.67 g COD/g SO42-). Carbon source bioassays with glucose obtained the best results in terms of the SGA (1.73 ± 0.34 mg S2-/g VSS•d) and SMA (10.41 mg COD-CH4/g VSS•d). The electron flow in the presence of glucose also indicated that 21.29 ± 5.2% of the metabolic activity of the sludge was directed towards sulfidogenesis. Copper toxicity bioassays indicated that a considerable decline in metabolic activity occurs above 10 mg/L. The 20%IC, 50%IC, and 80%IC were 4.5, 14.94, and 35.31 mg Cu/L. Compared to the other carbon sources tested, glucose proved to be a suitable electron donor since it favors sulfidogenesis. Finally, copper concentrations above 15 mg/L inhibited metabolic activity in the toxicity bioassays.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Kinetic energy-induced growth regimes of nanocolumnar Ti thin films deposited by evaporation and magnetron sputtering.

We experimentally analyze different growth regimes of Ti thin films associated to the existence of kinetic energy-induced relaxation mechanisms in the material's network when operating at oblique geometries. For this purpose, we have deposited different films by evaporation and magnetron sputtering under similar geometrical arrangements and at low temperatures. With the help of a well-established growth model we have found three different growth regimes: (i) low energy deposition, exemplified by the evaporation technique, carried out by species with typical energies in the thermal range, where the morphology and density of the film can be explained by solely considering surface shadowing processes, (ii) magnetron sputtering under weak plasma conditions, where the film growth is mediated by surface shadowing mechanisms and kinetic-energy-induced relaxation processes, and (iii) magnetron sputtering under intense plasma conditions, where the film growth is highly influenced by the plasma, and whose morphology is defined by nanocolumns with similar tilt than evaporated films, but with much higher density. The existence of these three regimes explains the variety of morphologies of nanocolumnar Ti thin films grown at oblique angles under similar conditions in the literature.

Effect of antibiotic treatment on the formation of non-spore Clostridium difficile persister-like cells.

Background: The spore is the virulence factor identified to be involved in the recurrence of the disease caused by Clostridium difficile. Objectives: To demonstrate that lethal antibiotic concentrations induce the appearance of C. difficile persister-like non-spore cells. Methods: C. difficile and derivative spo0A mutant strains were tested for their susceptibility to antibiotics, as determined using an agar dilution method. Persister-cell generation was determined for all strains using up to 10â€Š× the MIC of every antibiotic for up to 6 days. Results: Using up to 10â€Š× the MIC of every antibiotic, we were able to induce the appearance of persister-like behaviour since biphasic killing curves could be observed in response to treatment antibiotics. Conclusions: To the best of our knowledge, this work provides, for the first time, experimental evidence of the appearance of C. difficile persister-like cells, opening a new research avenue in the pathogenesis of this nosocomial pathogen.

Transcriptional Studies on a Streptomyces clavuligerus oppA2 Deletion Mutant: N-Acetylglycyl-Clavaminic Acid Is an Intermediate of Clavulanic Acid Biosynthesis.

The oppA2 gene encodes an oligopeptide-binding protein similar to the periplasmic substrate-binding proteins of the ABC transport systems. However, oppA2 is an orphan gene, not included in an ABC operon. This gene is located in the clavulanic acid (CA) gene cluster of Streptomyces clavuligerus and is essential for CA production. A transcriptomic study of the oppA2-null mutant S. clavuligerus ΔoppA2::aac showed changes in the expression levels of 233 genes from those in the parental strain. These include genes for ABC transport systems, secreted proteins, peptidases, and proteases. Expression of the clavulanic acid, clavam, and cephamycin C biosynthesis gene clusters was not significantly affected in the oppA2 deletion mutant. The genes for holomycin biosynthesis were upregulated 2-fold on average, and the level of upregulation increased to 43-fold in a double mutant lacking oppA2 and the pSCL4 plasmid. Strains in which oppA2 was mutated secreted into the culture the compound N-acetylglycyl-clavaminic acid (AGCA), a putative intermediate of CA biosynthesis. A culture broth containing AGCA, or AGCA purified by liquid chromatography-mass spectrometry (LC-MS), was added to the cultures of various non-CA-producing mutants. Mutants blocked in the early steps of the pathway restored CA production, whereas mutants altered in late steps did not, establishing that AGCA is a late intermediate of the biosynthetic pathway, which is released from the cells when the oligopeptide-binding protein OppA2 is not available.IMPORTANCE The oppa2 gene encodes an oligopeptide permease essential for the production of clavulanic acid. A transcriptomic analysis of S. clavuligerus ΔoppA2::aac in comparison to the parental strain S. clavuligerus ATCC 27064 is reported. The lack of OppA2 results in different expression of 233 genes, including genes for proteases and genes for transport systems. The expression of the clavulanic acid genes in the oppA2 mutant is not significantly affected, but the genes for holomycin biosynthesis are strongly upregulated, in agreement with the higher holomycin production by this strain. The oppA2-mutant is known to release N-acetylglycyl-clavaminic acid to the broth. Cosynthesis assays using non-clavulanic acid-producing mutants showed that the addition of pure N-acetylglycyl-clavaminic acid to mutants in which clavulanic acid formation was blocked resulted in the recovery of clavulanic acid production, but only in mutants blocked in the early steps of the pathway. This suggests that N-acetylglycyl-clavaminic acid is a previously unknown late intermediate of the clavulanic acid pathway.

Brucella central carbon metabolism: an update.

The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner-Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites.

Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response.

STUDY QUESTION: Does the type of cancer influence on the ovarian response to stimulation for fertility preservation (FP) in female oncology patients? SUMMARY ANSWER: Patients with gynaecological cancer have less number of retrieved mature oocytes compared with haematological and breast cancer patients. WHAT IS KNOWN ALREADY: Concerns about the impact of cancer therapy on future fertility have been raised and FP has become an important component in cancer management. Previous studies analysing FP results in cancer patients have shown conflicting findings. STUDY DESIGN, SIZE, DURATION: This was a retrospective analytical study performed in the Centre for Reproductive Medicine, at St Bartholomew's Hospital, between January 2000 and December 2014. The aim of this study was to analyse the response to ovarian stimulation in cancer patients before undergoing cancer treatment and to determine whether any difference can be attributed to underlying cancer diagnosis. We also report the pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 531 female patients recently diagnosed with cancer were referred for counselling on FP. A total of 306 patients underwent ovarian stimulation for oocyte or embryo cryopreservation. We compared the baseline characteristics and ovarian response in five main subgroups: breast cancer, haematological cancer, gynaecological cancer, gastrointestinal cancer and others. The primary outcome was the total number of mature oocytes retrieved and pregnancy outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: The main cancer diagnosis was breast cancer with 145 patients (47.4%); 79 patients (25.8%) had haematological malignancies; 42 (13.7%) had gynaecological malignancies; 20 (6.5%) had gastrointestinal cancer and 20 (6.5%) had other types of cancer. Patients with breast cancer were older (P < 0.001). Patients with haematological malignancies had higher number of mature oocytes retrieved (P = 0.003). The number of mature oocytes retrieved was lower in patients with gynaecological malignancy compared with haematological and breast cancer patients (P = 0.005 and P = 0.045, respectively). The fertilization rate and the number of cycles cancelled were comparable between all the groups. Thirty-two embryo transfer cycles have been done in 22 patients who have returned to attempt pregnancy. Pregnancy rate per transfer cycle was 43.75%, and cumulative pregnancy rate per patient was 54.5%. Live birth rate per patient was 22.72%. LIMITATIONS, REASONS FOR CAUTION: Apart from the retrospective nature of the study, patients were included over the period of 15 years, and over that time technology has changed and protocols have evolved. The results obtained from subcategory analyses should be interpreted with caution, as in each subgroup there are different types of malignancies with different number of patients in different age groups. Different ovarian stimulation protocols were applied. Only a few patients have come back to attempt pregnancy after being cured from their disease. We do not have follow-up data on these patients; as a result, we are not able to report the survival rate and the reason for non-return for embryo transfer. In addition, we cannot report information on spontaneous conceptions and births. Slow freezing used for embryo cryopreservation, high miscarriage rate and low live birth rate per transfer are other limitations of this study. WIDER IMPLICATIONS OF THE FINDINGS: The current study is the largest series analysing each group of cancer separately and showing pregnancy outcomes in oncology patients undergoing FP. These results provide valuable information about the success of this technique in oncology patients. STUDY FUNDING/COMPETING INTEREST(S): The authors have not received any funding to support this study. There are no conflicts of interest to declare.

Inferring Whether Officials Are Corruptible From Looking at Their Faces.

While inferences of traits from unfamiliar faces prominently reveal stereotypes, some facial inferences also correlate with real-world outcomes. We investigated whether facial inferences are associated with an important real-world outcome closely linked to the face bearer's behavior: political corruption. In four preregistered studies ( N = 325), participants made trait judgments of unfamiliar government officials on the basis of their photos. Relative to peers with clean records, federal and state officials convicted of political corruption (Study 1) and local officials who violated campaign finance laws (Study 2) were perceived as more corruptible, dishonest, selfish, and aggressive but similarly competent, ambitious, and masculine (Study 3). Mediation analyses and experiments in which the photos were digitally manipulated showed that participants' judgments of how corruptible an official looked were causally influenced by the face width of the stimuli (Study 4). The findings shed new light on the complex causal mechanisms linking facial appearances with social behavior.

MRI measurement of residual cervical length after radical trachelectomy for cervical cancer and the risk of adverse pregnancy outcomes: a blinded imaging analysis.

OBJECTIVE: To determine the association between the residual cervix measured on postoperative MRI after radical vaginal trachelectomy (RVT) and adverse obstetrical outcomes. DESIGN: Observational study. SETTING: Referral Cancer centre. POPULATION: Women who conceived after RVT for cervical cancer at the Royal Marsden Hospital, London, between 1995 and 2015. METHODS: Postoperative MRI scans were analysed by three researchers. The agreement between researchers was assessed by Pearson's correlation coefficient and Bland-Altman plot. Patients were divided into two groups (<10 and ≥10 mm residual cervix) for the analysis of adverse obstetrical outcomes. MAIN OUTCOME MEASURES: Late miscarriage, premature delivery, premature rupture of membranes (PROM) and chorioamnionitis. RESULTS: Thirty-one MRI scans were available; 29 of these women had a pregnancy that progressed beyond the first trimester. There was a strong reproducibility of the measurement of residual cervix (P < 0.001). Nineteen women (65.5%) had <10 mm residual cervix and 10 (34.5%) had ≥10 mm. Among women with <10 mm residual cervix, seven (36.8%) experienced PROM and ten (66.7%) had a preterm birth; No women with ≥10 mm residual cervix had PROM and two (22.2%) had a preterm birth (P = 0.028 and P = 0.035, respectively). Overall, there were nine (16.7%) first-trimester miscarriages, six (11.1%) late fetal losses, 12 (31.6%) preterm births and 36 (66.7%) live births. After a mean follow up of 78.1 months, 36 women were disease-free and one woman had died. CONCLUSIONS: MRI measurements of the residual cervix are reproducible between observers. The incidence of PROM and premature delivery is higher when the residual cervix after RVT is <10 mm. TWEETABLE ABSTRACT: The risk of prematurity after RVT can be predicted from measurements of residual cervical length on postoperative MRI scan.

Is eosinophilic esophagitis an equivalent of pollen allergic asthma? Analysis of biopsies and therapy guided by component resolved diagnosis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by esophageal dysfunction and, histologically, by eosinophilic inflammation. There is not a clear etiologic treatment. Biopsies analysis using plant histology methods may show callose and pollen tubes in the esophageal mucosa. Component-resolved diagnosis (CRD) with microarrays could detect possible allergens involved and indicate an elimination diet and allergen immunotherapy (AIT). METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. CRD, histological and botanical analysis were performed. Clinical scores and endoscopic biopsy were performed every six months for three years. Fifty healthy patients, 50 asthmatics due to pollen, and 53 celiac disease patients were included as comparison groups. CRD-directed AIT was administered in 91 EoE patients and elimination diet in 140 patients (87 EoE and all 53 CD patients). RESULTS: CRD detected allergen hypersensitivity in 87.6% of patients with EoE. The predominant allergens were grass group 1 (55%), lipid transfer proteins (LTP) of peach and mugwort, hazelnuts and walnuts. Callose from pollen tubes was found in 65.6% of biopsies. After CRD-guided elimination diet and/or AIT, 101 (78.3%) EoE patients showed significant clinical improvement (p<0.017) and 97 (75.2%) were discharged (negative biopsy, no symptoms, no medication) without relapse. AIT-treated patients had better outcomes (odds ratio 177.3, 95% CI 16.2-1939.0). CONCLUSION: CRD-directed AIT and/or elimination diet was efficient in treating EoE patients and was well tolerated.

Pharmacological Treatment of Insomnia Symptoms in Individuals with Substance Use Disorders in Spain: A Quasi-Experimental Study.

INTRODUCTION: Pharmacological treatment of insomnia in patients with addictions has been hardly investigated and there are few researches about it in an inpatient detoxification. The aim of this study was to describe the outcomes of the pharmacological treatment of insomnia in SUD patients admitted to a detoxification unit in Spain, with a focus on the primary substance of abuse and co-occurring mental disorders. METHODS: A quasi-experimental study was conducted in 481 addicted in patients, who were admitted for substances detoxification in Vall d´Hebron University Hospital, Barcelona, Spain, from 2010 to 2015. The patients underwent systematic evaluation of axes I and II psychiatric disorders (SCID-I, SCID-II, and CAADID). Insomnia was evaluated using a night time sleep log. Substance-dependent patients, who had insomnia during hospital detoxification, received a psychotropic medication with hypnotic effect, keeping the regular clinical practice without randomization. RESULTS: At discharge, insomnia was considered to have been alleviated in 63.8% (n = 204) of patients while 36.2% (n = 116) of patients remained with insomnia disturbances. Comparing hypnotic treatments it was observed that mirtazapine and clotiapine were the treatment that corrected the insomnia more frequently. DISCUSSION: Since insomnia is not corrected in all patients, it should be further investigated in medications with hypnotic purpose. Based on the results of this work, randomized clinical trials might be proposed.

Environmental risk assessment of cobalt and manganese from industrial sources in an estuarine system.

A total of 74 samples of soil, sediment, industrial sludge, and surface water were collected in a Mediterranean estuarine system in order to assess the potential ecological impact of elevated concentrations of Co and Mn associated with a Terephthalic (PTA) and Isophthalic (PIPA) acids production plant. Samples were analyzed for elemental composition (37 elements), pH, redox potential, organic carbon, and CaCO3 content, and a group of 16 selected samples were additionally subjected to a Tessier sequential extraction. Co and Mn soil concentrations were significantly higher inside the industrial facility and around its perimeter than in background samples, and maximum dissolved Co and Mn concentrations were found in a creek near the plant's discharge point, reaching values 17,700 and 156 times higher than their respective background concentrations. The ecological risk was evaluated as a function of Co and Mn fractionation and bioavailability which were controlled by the environmental conditions generated by the advance of seawater into the estuarine system during high tide. Co appeared to precipitate near the river mouth due to the pH increase produced by the influence of seawater intrusion, reaching hazardous concentrations in sediments. In terms of their bioavailability and the corresponding risk assessment code, both Co and Mn present sediment concentrations that result in medium to high ecological risk whereas water concentrations of both elements reach values that more than double their corresponding Secondary Acute Values.

The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome.

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.