ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and NICE criteria according to risk by FMF algorithm.

OBJECTIVE: To report the incidence of preterm pre-eclampsia (PE) in women who are screen positive according to the criteria of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), and compare the incidence with that in those who are screen positive or screen negative by The Fetal Medicine Foundation (FMF) algorithm. METHODS: This was a secondary analysis of data from the ASPRE study. The study population consisted of women with singleton pregnancy who underwent prospective screening for preterm PE by means of the FMF algorithm, which combines maternal factors and biomarkers at 11-13 weeks' gestation. The incidence of preterm PE in women fulfilling the NICE and ACOG criteria was estimated; in these patients the incidence of preterm PE was then calculated in those who were screen negative relative to those who were screen positive by the FMF algorithm. RESULTS: A total of 34 573 women with singleton pregnancy delivering at ≥ 24 weeks' gestation underwent prospective screening for preterm PE, of which 239 (0.7%) cases developed preterm PE. At least one of the ACOG criteria was fulfilled in 22 287 (64.5%) pregnancies and the incidence of preterm PE was 0.97% (95% CI, 0.85-1.11%); in the subgroup that was screen positive by the FMF algorithm the incidence of preterm PE was 4.80% (95% CI, 4.14-5.55%), and in those that were screen negative it was 0.25% (95% CI, 0.18-0.33%), with a relative incidence in FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In 1392 (4.0%) pregnancies, at least one of the NICE high-risk criteria was fulfilled, and in this group the incidence of preterm PE was 5.17% (95% CI, 4.13-6.46%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93-10.89%) and 0.65% (95% CI, 0.25-1.67%), respectively, and the relative incidence was 0.075 (95% CI, 0.028-0.205). In 2360 (6.8%) pregnancies fulfilling at least two of the NICE moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28-2.35%); in the subgroups of screen positive and screen negative by the FMF algorithm the incidence was 4.91% (95% CI, 3.54-6.79%) and 0.42% (95% CI, 0.20-0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192). CONCLUSION: In women who are screen positive for preterm PE by the ACOG or NICE criteria but screen negative by the FMF algorithm, the risk of preterm PE is reduced to within or below background levels. The results provide further evidence to support the personalized risk-based screening method that combines maternal factors and biomarkers. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

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.

Results of an early intervention programme for patients with bacteraemia: analysis of prognostic factors and mortality.

BACKGROUND: Bacteraemia is a common cause of morbidity and mortality in patients admitted to hospital. The aim of this study is to analyse the results of a two-year programme for the early optimisation of antibiotic treatment in patients admitted to the Costa del Sol Hospital (Marbella. Spain). METHODS: A prospective two-year cohort study was conducted, evaluating all episodes of bacteraemia at the Costa del Sol Hospital. Epidemiological and microbiological characteristics, any modification of the initial antibiotic treatment, prognostic risk stratification, early mortality related to the episode of bacteraemia, and mortality after the seventh day, were included in the analysis. RESULTS: Seven hundred seventy-three episodes of bacteraemia were treated, 61.6% males and 38.4% females. The mean age was 65.2 years. The condition was most commonly acquired in the community (41.4%). The bacteraemia was most frequently urological in nature (30.5%), and E coli was the microorganism most frequently isolated (31.6%). In 51.1% of the episodes, a modification was made to optimise the treatment. In the first week, 8.2% died from bacteraemia, and 4.5% had died when they were located. The highest rates of death were associated with older patients, nosocomial acquisition, no source, McCabe score rapidly fatal, Charlson index ≥3, Pitt index ≥3 and treatment remained unmodified. CONCLUSION: The existence of bacteraemia control programmes and teams composed of clinicians who are experienced in the treatment of infectious diseases, can improve the disease outcome by enabling more severe episodes of bacteraemia to be recognised and their empirical treatment optimised.

Sleep disturbance, obesity, physical fitness and quality of life in older women: EXERNET study group.

OBJECTIVES: To investigate the association between physical fitness, obesity, health related quality of life (HRQoL) and sleep disturbance in 463 community-dwelling older Spanish women (66-91 years of age). STUDY DESIGN: Cross-sectional study. METHOD: Sleep disturbance was assessed with the Jenkins Sleep Scale. Active and sedentary behaviors were recorded by standardized questionnaires. HRQoL was assessed with the EuroQoL-5D. Anthropometric measurements were obtained using standardized techniques. Body fat was measured using bioelectrical impedance. Physical fitness was evaluated by a set of eight tests. RESULTS: Sleep disturbance was reported by 45.1% of women, being associated with higher body mass index (p < 0.05) and waist circumference (p < 0.01). Presence of insomnia was inversely associated with physical fitness. Women in the upper tertile of fitness index had 92.0% lower risk of sleep disturbance as compared to the lower tertile (p = 0.08), while women in the highest tertile of upper body strength had 76.4% lower risk of sleep disturbance as compared to the lower tertile (p < 0.05). Women without sleep disturbance showed better HRQoL. CONCLUSION: Sleep disturbance was associated with central obesity, lower physical fitness and reduced HRQoL. Interventions involving weight management and improvement of physical fitness may contribute to better sleep quality in older women.

Use of donor sperm in addition to oocyte donation after repeated implantation failure in normozoospermic patients does not improve live birth rates.

STUDY QUESTION: Does switching to donor semen after at least three failed oocyte donation (OD) cycles with the partner normozoospermic semen increase the live birth rate in a subsequent OD cycle? SUMMARY ANSWER: Switching to donor semen after at least three failed OD cycles with the partner normozoospermic semen does not increase the live birth rate. WHAT IS ALREADY KNOWN: In some patients, a viable pregnancy cannot be achieved after several OD cycles, despite normal diagnostic findings for the couple. The ESHRE Capri Workshop Group indicates that, in order to improve reproductive outcomes, a semen donation can be offered after three failed ICSI cycles. STUDY DESIGN, SIZE, DURATION: A retrospective cohort analysis of fourth and fifth OD cycles with either the partner's normozoospermic semen (OD) or double-donation cycles (DD), performed between January 2011 and December 2014 in a private fertility center. These couples did not have a known male factor. PARTICIPANTS/MATERIALS, SETTING, METHOD: The study included 228 cycles (159 OD and 69 DD). The fertilization method was ICSI in all cycles and embryos were transferred fresh. Fertilization rates were compared between groups using ANOVA while pregnancy outcomes were compared using Chi-square tests. Effect of DD on pregnancy outcomes was further analyzed using a logistic regression model adjusted for recipient's age and BMI, number of embryos transferred, day of embryo transfer and morphological embryo quality score. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in live birth rate between the DD and OD groups (38.2 versus 35.8%, P = 0.73), even after adjustment for confounding factors (odds ratio 1.41, 95% confidence interval 0.72, 2.76; P = 0.31). Rates of biochemical pregnancy (52.2 versus 54.1%, P = 0.79), clinical pregnancy (41.2 versus 45.9%, P = 0.51) and ongoing pregnancy (38.2 versus 37.1%, P = 0.87) were not different between the DD and the OD groups, as well as fertilization rate (75.3 versus 75.2%, P = 0.97). The DD and OD groups were comparable at baseline in all demographic and cycle variables analyzed (recipient's BMI, number of transferred embryos and embryo quality) with the exception of recipient's age (42.3 in DD versus 44.1 in OD, P = 0.005), and day of embryo transfer (56.5% of DD and 83.6% of OD embryo transfers were performed on blastocyst stage, P < 0.001); both variables were adjusted for in the multivariate analysis. LIMITATIONS, REASONS FOR CAUTION: The main limitations of this study are its retrospective nature, the relatively small sample size, the transfer of embryos of different developmental stages and the lack of extensive molecular testing, such as sperm DNA fragmentation test, in normozoospermic patients. WIDER IMPLICATIONS OF THE FINDINGS: After excluding several causes for the failed OD cycles, the partner's normozoospermic semen was a common factor in all of them. Nevertheless, the change to a donor's semen does not seem to improve the reproductive outcomes in the subsequent cycle. STUDY FUNDING/COMPETING INTERESTS: No extra-mural funding was obtained for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NA.

One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms.

Introduction: Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in ABCB1 and remission, recovery, and suicide risk. Methods: This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. Results: It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between ABCB1 and remission or recovery. However, a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts. Conclusion: Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.

Experimental North American West Nile Virus Infection in the Red-legged Partridge (Alectoris rufa).

After the introduction of West Nile virus (WNV) into North America, bird mortalities associated with West Nile disease have dramatically increased in this continent and, to a lesser extent, in Europe. The different West Nile disease incidence in birds in these 2 continents demands an explanation, and experimental studies can provide important information. The authors inoculated thirteen 9-week-old red-legged partridges (Alectoris rufa) with 10(7)plaque-forming units of a WNV strain isolated in New York in 1999. The objective was to study the pathogenesis of the infection in a native Euro-Mediterranean bird species with a WNV strain known to be highly pathogenic for numerous native American bird species. Additionally, the authors evaluated the dynamics of inflammatory cell activation and recruitment into the brain. WNV was detected in tissues 3 days postinoculation (dpi), and the birds developed macroscopic and microscopic lesions. Two partridges succumbed to the disease. The most affected tissues were the heart, brain, and spinal cord. The main microscopic findings were the presence of mononuclear infiltrates in the heart and brain, gliosis, and degeneration and necrosis of cardiomyocytes and neurons. These lesions were aggravated in the birds that died or were euthanized 7 dpi or later. In the brain, there was an upregulation of microglial cells and astrocytes and an increase in the number of T cells, especially after 7 dpi. These results show that this WNV strain is of moderate virulence for the red-legged partridge and that WNV-infected red-legged partridges develop an immune cell response in the brain similar to that of mammals.

Short-term outcome of percutaneous posterior tibial nerve stimulation (PTNS) for the treatment of faecal incontinence.

BACKGROUND: The aim of the present study was to establish the efficacy of percutaneous posterior tibial nerve stimulation (PTNS) in treating flatal, urge and passive faecal incontinence (FI). METHODS: A prospective study with 55 patients with FI was carried out. Clinical anamnesis, physical examination, a reverse visual analogue scale (VAS) score, Wexner score and the American Society of Colon and Rectal Surgeons quality of life score were recorded at baseline and 6 months, along with an incontinence diary. Subjects underwent one weekly session for 12 consecutive weeks and then continued with six additional fortnightly sessions. An intention-to-treat analysis was performed. RESULTS: Fifty-five patients (44 females; mean age 58.62 ± 10.74 years) with FI were treated with PTNS. The origins of the incontinence were obstetric (52.7 %) and perineal surgery (34.5 %). Eight patients did not continue with the second stage of treatment. The median Wexner baseline value was 9.98. After 6 months, it had decreased to 4.55 (p < 0.001). The visual analogue scale (VAS) increased from 4.94 to 6.80 (p < 0.001). There was a significant improvement in lifestyle, coping/behaviour, depression/self-perception and embarrassment scores. With respect to different types of FI, there was an improvement in the Wexner score both in patients with true passive FI and in those with urge or mixed FI. CONCLUSIONS: PTNS is an effective treatment for FI. Patients with passive or urge FI can benefit from this therapy, with improvement of the Wexner score and quality of life variables.

Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

Basophil response to peanut allergens in Mediterranean peanut-allergic patients.

Ara h 1, Ara h 2, and Ara h 3 are important sensitizers in peanut allergy. Ara h 9 has also been shown to be relevant in the Mediterranean area. We evaluated the basophil response to peanut allergens and Pru p 3 in Mediterranean patients: Group 1, peanut and peach allergy; Group 2, peanut allergy and tolerance to peach; Group 3, peach allergy and tolerance to peanut; Group 4, nonallergic subjects that tolerate both peanut and peach. Compared to controls (Group 4), there was an increased basophil activation with Ara h 2 (P = 0.031) and Pru p 3 (P = 0.009) in Group 1 and with Ara h 1 (P = 0.016), Ara h 2 (P = 0.001), and Ara h 9 (P = 0.016) in Group 2. Importantly, only Ara h 2 showed an increased activation (P = 0.009) in Group 2 compared to Group 3. Ara h 2 is the best discriminating allergen for peanut allergy diagnosis in a Mediterranean population showing two patterns: patients also allergic to peach, responding to Ara h 2 and Pru p 3, and patients allergic only to peanut, responding to Ara h 1, Ara h 2, and Ara h 9.

Oculopathologic findings in flavivirus-infected gallinaceous birds.

Using eye samples of nine 9-week-old experimentally West Nile virus (WNV)-infected red-legged partridges (Alectoris rufa), time course of lesions and WNV antigen appearance in ocular structures were examined. In addition, eye samples of 6 red-legged partridges and 3 common pheasants (Phasianus colchicus) naturally infected with Bagaza virus (BAGV) were used to study lesions and flavivirus antigen distribution in relation to apparent blindness in the former. The rapid onset of microscopic lesions and early presence of viral antigen in the eye of experimentally WNV-infected partridges, prior to the central nervous system involvement, suggested hematogenous spread of the virus into the eye. BAGV-infected partridges had a more pronunced inflammatory reaction and more widespread flavivirus antigen distribution in the retina compared with pheasants and experimentally fatally WNV-infected partridges. Our results suggest that flavivirus replication and development of lesions in ocular structures of gallinaceous game birds vary with the specific virus and host species involved.

Comparative evaluation of Vitek 2 identification and susceptibility testing of urinary tract pathogens directly and isolated from chromogenic media.

We evaluated the use of urine specimens for direct identification and antibiotic testing of urinary tract pathogens using the Vitek system. A total of 343 urine specimens from patients with suspected UTI were selected by pyuria and screened by Gram staining to detect bacteriuria. Of those, 132 were analysed after Gram staining, showing a high number of micro-organisms of a single morphological type. Direct susceptibility testing and identification were performed by using the Vitek system. Results were compared using the standard inoculation method based on the incubation of solid media. After sub-culture, 107 specimens grew a significant count of a single species and were used for the comparative analysis. The direct method correctly identified 88 isolates (82.3 %). When compared according to antibiotic susceptibility testing, the error rate was 2.4 % overall with 0.2 % very major, 0.4 % major and 1.8 % minor errors. 84.7 % of the Gram-negative bacilli had a complete susceptibility report in ≤ 8 h. This method offers the advantage of prompt processing and earlier reporting of complete results for positive urine specimens.

Monitoring West Nile virus (WNV) infection in wild birds in Serbia during 2012: first isolation and characterisation of WNV strains from Serbia.

West Nile virus (WNV), a neurovirulent mosquito-transmissible zoonotic virus, has caused recent outbreaks in Europe, including Serbia from August until October 2012. Although humans can be infected, birds are the main natural WNV reservoir. To assess WNV circulation in northern Serbia, 133 wild birds were investigated. These comprised resident and migratory birds, collected between January and September 2012 in the Vojvodina province. The birds belonged to 45 species within 27 families. Blood sera (n=92) and pooled tissues from respective birds (n=81) were tested by enzyme-linked immunosorbent assay (ELISA), plaque reduction neutralisation test (PRNT) and real-time reverse transcription-polymerase chain reaction (RT-qPCR). WNV antibodies were detected in seven (8%) sera: four from Mute Swans (Cygnus olor), two from White-tailed Eagles (Haliaeetus albicillas), and one from a Common Pheasant (Phasianus colchicus). Five sera neutralised WNV but not Usutu virus. For the first time in Serbia, WNV RNA was detected by RT-qPCR in pooled tissue samples of eight respective birds. WNV RNA was also derived from an additional bird, after a serum sample resulted infective in cell culture. The total nine WNV RNA positive birds included three Northern Goshawks (Accipiter gentilis), two White-tailed Eagles, one Legged Gull (Larus michahelis), one Hooded Crow (Corvus cornix), one Bearded Parrot-bill (Panarus biramicus), and one Common Pheasant. Phylogenetic analysis of partial E region sequences showed the presence of, at least, two lineage 2 Serbian clusters closely related to those responsible for recent human and animal outbreaks in Greece, Hungary and Italy. Full genomic sequence from a goshawk isolate corroborated this data. These results confirm WNV circulation in Serbia and highlight the risk of infection for humans and horses, pointing to the need for implementing WNV surveillance programmes.

Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells.

BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin (LT)α(1)ß(2), cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP, factors involved in the differentiation (decidualization) of DSC. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, α-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LTα(1)ß(2). DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and cAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy.

Environmental evidence of Valencia lagoon coastal barrier stabilization from 8500 BP to Present. Climate and eustatic variations.

The Albufera de Valencia is one of the largest lagoon in the Spanish Mediterranean. Two continuous borehole cores reaching depths of 8 and 14 m in the northern part of the lagoon underwent sedimentological, micropaleontological and biological study. The organic content was also analysed, and 14C radiometric dating and amino acid racemization were performed. Study of the content of benthic foraminifera and n-alkanes and alkanoic acids in the lagoon sedimentary record identified several periods. The core records showed seven different environments: alluvial; freshwater marsh; brackish marsh; brackish lagoon; brackish lagoon with marine connection, backbarrier flat, and backshore. These environments changed due to eight phases associated with the transgression and regression of the barrier system, which caused the shift from exposed environments as the backshore with washover, to the typical low-energy lagoon and marsh deposition. The paleoenvironmental evolution described above is interpreted as a response to global climate changes. The shift from an alluvial setting to a brackish lagoon is probably related to the late of Early Holocene sea level rise ending at the Holocene Climate Optimum, when the highest sea level was reached. The persistence of the brackish lagoon, with no marine connection, is probably synchronous with dry conditions in the area (Booth et al., 2005) at the time of Bond event 3 (i.e., 4.2 ka) in the North Atlantic region (Bond et al., 2001). Finally, the arrival of large amounts of sediment triggered the accretion of the barrier, also enhancing coastal progradation until the present day. These results allow an evaluation of the impact of anthropic action on the Valencia lagoon, especially since the eighteenth century, and a short- and medium-term projection of the consequences of present-day climate change.

Resource use and healthcare costs in patients with overactive bladder who initiate treatment with mirabegron or antimuscarinic monotherapy in Catalonia: the MIRACAT study.

INTRODUCTION AND AIM: Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB. MATERIALS AND METHODS: Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (є, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change. RESULTS: The mean cost per patient (SD) was є 1,640.20 (є 1,227.60) with MB and є 2,159.20 (є 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250). CONCLUSIONS: Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients' quality of life.

Mitochondrial bioenergetics and dynamics interplay in complex I-deficient fibroblasts.

BACKGROUND: Complex I (CI) deficiency is the most frequent cause of OXPHOS disorders. Recent studies have shown increases in reactive oxygen species (ROS) production and mitochondrial network disturbances in patients' fibroblasts harbouring mutations in CI subunits. OBJECTIVES: The present work evaluates the impact of mutations in the NDUFA1 and NDUFV1 genes of CI on mitochondrial bioenergetics and dynamics, in fibroblasts from patients suffering isolated CI deficiency. RESULTS: Decreased oxygen consumption rate and slow growth rate were found in patients with severe CI deficiency. Mitochondrial diameter was slightly increased in patients' cells cultured in galactose or treated with 2'-deoxyglucose without evidence of mitochondrial fragmentation. Expression levels of the main proteins involved in mitochondrial dynamics, OPA1, MFN2, and DRP1, were slightly augmented in all patients' cells lines. The study of mitochondrial dynamics showed delayed recovery of the mitochondrial network after treatment with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (cccp) in patients with severe CI deficiency. Intracellular ROS levels were not increased neither in glucose nor galactose medium in patients' fibroblasts. CONCLUSION: Our main finding was that severe CI deficiency in patients harbouring mutations in the NDUFA1 and NDUFV1 genes is linked to a delayed mitochondrial network recovery after cccp treatment. However, the CI deficiency is neither associated with massive mitochondrial fragmentation nor with increased ROS levels. The different genetic backgrounds of patients with OXPHOS disorders would explain, at least partially, differences in the pathophysiological manifestations of CI deficiency.

[Epidemic outbreak of Pseudomonas aeruginosa carbepenem-resistant producing metallo-beta-lactamase]. / Detección de un brote epidémico por Pseudomonas aeruginosa multirresistente productora de metalo-beta-lactamasa.

OBJECTIVE: To describe the nosocomial outbreak of multiresistant Pseudomonas aeruginosa producing metallo-beta-lactamase (MBL) in Cartagena (Murcia, Spain). MATERIAL AND METHODS: In May 2009, six consecutive isolations of multiresistant Pseudomonas aeruginosa were detected. These were characterized by their profile of resistance to imipenem and cephalosporins and sensibility to aztreonam, this suggesting the production of carbapenemases. The isolations were screened for MBL and a PCR for the detection of the VIM gene was performed. Secondary, all of the isolations having the same characteristics in the year 2009 were analyzed retrospectively in order to establish the possibility of an endemic infection. RESULTS: The molecular typing of the isolates revealed two clones in Pulsed Field Gel Electrophoresis (PFGE), the most frequent (Type 1) being represented by 4 isolates. All of them came from patients who were in the Intensive Care Unit. All (100%) of the isolates of the outbreak were considered to be multiresistant. PCR confirmed the presence of the VIM gene related with the production of MBL in 100% of the isolates corresponding to pulsotype 1. CONCLUSIONS: We detected the existence of an outbreak of carbapenem-resistant Pseudomonas aeruginosa producing metallo-beta-lactamase. Am evident therapeutic problem as well as a problem of nosocomial infection was considered. The isolation means should be maximized and routine controls performed for the presence of MBL given its elevated prevalence in our setting.

[Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units]. / Síndrome de fatiga crónica: estudio de una serie consecutiva de 824 casos evaluados en dos unidades especializadas.

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units. PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment. RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment. CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.

A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.