Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.

BACKGROUND: We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed. RESULTS: We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts. CONCLUSIONS: For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.

The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification.

Colistin resistance is acquired by different lipopolysaccharide (LPS) modifications. We proposed to evaluate the of effect in vivo colistin resistance acquisition on the innate immune response. We used a pair of ST11 clone Klebsiella pneumoniae strains: an OXA-48, CTX-M-15 K. pneumoniae strain susceptible to colistin (CS-Kp) isolated from a urinary infection and its colistin-resistant variant (CR-Kp) from the same patient after prolonged treatment with colistin. No mutation of previously described genes for colistin resistance (pmrA, pmrB, mgrB, phoP/Q, arnA, arnC, arnT, ugdH, and crrAB) was found in the CR-Kp genome; however, LPS modifications were characterized by negative-ion matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The strains were cocultured with human monocytes to determine their survival after phagocytosis and induction to apoptosis. Also, monocytes were stimulated with bacterial LPS to study cytokine and immune checkpoint production. The addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A of CR-Kp accounted for the colistin resistance. CR-Kp survived significantly longer inside human monocytes after being phagocytosed than did the CS-Kp strain. In addition, LPS from CR-Kp induced both higher apoptosis in monocytes and higher levels of cytokine and immune checkpoint production than LPS from CS-Kp. Our data reveal a variable impact of colistin resistance on the innate immune system, depending on the responsible mechanism. Adding Ara4N to LPS in K. pneumoniae increases bacterial survival after phagocytosis and elicits a higher inflammatory response than its colistin-susceptible counterpart.

Conventional versus extended-pulsed fidaxomicin dosing in patients at high risk of recurrence of Clostridioides difficile infection: a propensity score analysis.

INTRODUCTION: The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing. METHODS: To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk. RESULTS: In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22-1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27-2.04) by propensity score analysis. CONCLUSIONS: Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.

Anastomotic leak in colorectal cancer surgery: Contribution of gut microbiota and prediction approaches.

AIM: To monitor prospectively the occurrence of colorectal anastomotic leakage (CAL) in patients with colon cancer undergoing resectional surgery, characterizing the microbiota in both faeces and mucosal biopsies of anastomosis. In a second stage, we investigated the ability to predict CAL using machine learning models based on clinical data and microbiota composition. METHOD: A total of 111 patients were included, from whom a faecal sample was obtained, as well as biopsy samples from proximal and distal sites in the healthy margins of the tumour piece. The microorganisms present in the samples were investigated using microbial culture and 16S rDNA massive sequencing. Collagenase and protease production was determined, as well as the presence of genes responsible for expressing enzymes with these activities. Machine learning analyses were developed using clinical and microbiological data. RESULTS: The incidence of CAL was 9.0%, and CAL was associated with collagenase/protease-producing Enterococcus. Significant differences were found in the microbiota composition of proximal and distal biopsy samples, but not in faecal samples, among patients who developed CAL. Clinical predictors of CAL were 5-day C-reactive protein and heart disease, whereas 3-day C-reactive protein and diabetes were negative predictors. CONCLUSION: Biopsy samples from surgical margins, rather than faecal samples, are the most appropriate samples for exploring the contribution of the intestinal microbiota to CAL. Enterococci are only enriched in the anastomosis after surgery, and their collagenases and proteases are involved in the degradation of the anastomotic scar.

Folliculitis Decalvans Has a Heterogeneous Microbiological Signature and Impaired Immunological Response.

BACKGROUND: Folliculitis decalvans (FD) is a rare primary neutrophilic scarring alopecia whose etiology has not been completely elucidated yet. OBJECTIVE: The aim of the study was to determine if the follicular microbiota residing in FD-affected hair follicles had a distinct microbiological signature and if an aberrant immune response was present in the pathogenesis of FD. METHODS: We conducted a cross-sectional study of 10 patients affected by FD. Trichoscopy-guided follicular biopsies were taken from affected and healthy scalp to identify the follicular microbiome using next-generation sequencing. We searched for microbiological biomarkers of FD-affected follicles using the linear discriminant analysis (LDA) effect size (LEfSe) tool. Additionally, peripheral blood mononuclear cells were obtained, and their cytokine production was quantified after incubation with pathogen-associated molecular patterns isolated from patients' biopsies and compared with healthy controls. RESULTS: ß-diversity analysis showed statistically significant differences regarding bacteria comparing follicular microbiota of healthy and FD-affected hairs. Ruminococcaceae, Agathobacter sp., Tyzzerella sp., and Bacteriodales vadin HA21 family were good predictors of disease status. IL-10, TNF-α, and IL-6 levels were significantly decreased in patients after incubation with various strains of bacteria compared with controls. CONCLUSION: FD hair follicles have a specific heterogenous follicular bacterial microbiota signature. Additionally, these patients seem to have an impaired immunological response.

Natural Compound Boldine Lessens Myotonic Dystrophy Type 1 Phenotypes in DM1 Drosophila Models, Patient-Derived Cell Lines, and HSALR Mice.

Myotonic dystrophy type 1 (DM1) is a complex rare disorder characterized by progressive muscle dysfunction, involving weakness, myotonia, and wasting, but also exhibiting additional clinical signs in multiple organs and systems. Central dysregulation, caused by an expansion of a CTG trinucleotide repeat in the DMPK gene's 3' UTR, has led to exploring various therapeutic approaches in recent years, a few of which are currently under clinical trial. However, no effective disease-modifying treatments are available yet. In this study, we demonstrate that treatments with boldine, a natural alkaloid identified in a large-scale Drosophila-based pharmacological screening, was able to modify disease phenotypes in several DM1 models. The most significant effects include consistent reduction in nuclear RNA foci, a dynamic molecular hallmark of the disease, and noteworthy anti-myotonic activity. These results position boldine as an attractive new candidate for therapy development in DM1.

Dynamic Adsorption of H2S onto a Goethite-Based Material.

The use of adsorption technology to remove H2S from synthetic gas (H2S and N2) using a goethite-based adsorbent was investigated. The influence of the H2S feed concentration (150-600 mg), the adsorbent dosage (1-4 g), and the gas flow rate (210-540 cm3/min) on the breakthrough curves and H2S adsorption on the adsorbent at the breakthrough point was investigated. Dynamic column experiments were performed to provide data for the theoretical models and to verify the performance of the system in the adsorption process. The theoretical models used in the present work were found to predict the adsorption breakthrough performance reasonably well.

Dual Mobility Cups as the Routine Choice in Total Hip Arthroplasty.

Background and Objectives: Total hip arthroplasty (THA) is considered the most successful surgical procedure in orthopedics. However, dislocation remains the main indication for surgical revision. New designs of dual mobility cups (DMC) have lowered the classical complications and have extended the indications of DMC in elective surgeries. Our aim is to assess the trend of DMC indications in THA as well as the incidence of their dislocation. Materials and Methods: We retrospectively reviewed all patients undergoing THA with DMC during the years 2015 and 2021. The original indication for DMC included patients sustaining neck of femur fractures (NOF#) and associated risk factors for dislocations. Five years later, DMC was considered our standard of care in total hip arthroplasty. The approach (anterolateral or posterolateral) was chosen by the surgeon according to his/her preferences, as was the implant. Data collected included patients' demographics, diagnosis, admission time, surgical approach, cup models, and inclination and complications. Patients sustaining a hip dislocation were prospectively reviewed and assessed for treatment received, new dislocations, and need for surgical revision. Two groups were created for the analysis according to the presence or absence of dislocation during follow-up. Results: In the analysis, 531 arthroplasties were included (mean age 72.2 years) with a mean follow-up of 2.86 years. The trend of indications for DMC increased from 16% of THA in 2015 to 78% of THA in 2021. We found a total of 8 dislocations (1.5%), none of them associated with elective surgery. Closed reduction was unsatisfactory in four cases (50%). There was one case of intraprosthetic dislocation. Dislocations were associated to smaller heads (22 mm) (1.5% vs. 25%, p = 0.008) and cups (51.2 mm vs. 48.7 mm, p = 0.038) and posterior approach (62.5% vs. 37.5%, p = 0.011). Conclusion: Dual mobility cups are a great option to reduce the risk of dislocation after a THA both in the neck of femur fractures and elective cases. The use of an anterolateral approach in THA after a neck or femur fracture might considerably decrease the risk of dislocation.

Characterization of carbapenemase-producing Serratia marcescens and whole-genome sequencing for plasmid typing in a hospital in Madrid, Spain (2016-18).

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) are increasingly recognized in nosocomial infections, also affecting ICU patients. We aimed to characterize the carbapenemase-producing Serratia marcescens (CPSm) isolates recovered in our hospital in Madrid (Spain) between March 2016 and December 2018. METHODS: Overall, 50 isolates from clinical and epidemiological surveillance samples were recovered from 24 patients admitted to the medical ICU and 10 non-ICU-related patients based on their phenotypic resistance. Carbapenemase characterization, antibiotic susceptibility, PFGE clonal relatedness, plasmid characterization, WGS (Illumina-NovaSeq 6000) and phylogenetic analysis were performed. RESULTS: A single isolate was finally considered for each patient, except for Patient 8 that was colonized by two different isolates (n = 35). Isolates were characterized as VIM-1 (n = 29) or OXA-48 producers (n = 6). Up to seven genetic lineages were found by PFGE, with dominance of two clones. Plasmid characterization confirmed that almost all CPSm carried the same ∼60 kb IncL OXA-48- or VIM-1-encoding plasmid, which was related to the globally disseminated IncL-pOXA-48a. WGS allowed plasmid reconstruction with two variants: IncL-pVIM-1 (∼65 kb) and IncL-pOXA-48 (∼62 kb). blaOXA-48-Tn1999 (∼5 kb) was the unique antibiotic resistance gene in pOXA-48, whereas pVIM-1 plasmids (∼8 kb) harboured a class 1 integron containing 5'-blaVIM-1+aacA4+dfrB1+aadA1+catB2+qacEDelta1+sul1-3'. CONCLUSIONS: Our results confirm the dissemination of CPSm within our institution in both ICU and non-ICU environments, representing two prevalent CPSm clones, and the same IncL-pOXA-48 plasmid previously described in other Enterobacterales, but containing the blaVIM-1 gene. This also reinforces the relevance of species different from Klebsiella pneumoniae or Escherichia coli in the CPE landscape and circulating lineages and plasmids in local CPE epidemiology.

A retrospective analysis and literature review of neoplastic appendiceal mucinous lesions.

BACKGROUND: At present, the term mucocele is outdated, and mucinous appendiceal neoplasm is preferred. Mucinous appendiceal neoplasm is an uncommon pathology that occurs predominantly in middle-aged women. Its classification and management have been the subject of debate in recent decades. The aim of this study was to analyse the incidence, clinical management and survival of these tumours diagnosed in our centre in the last 10 years. METHODS: This was a retrospective observational study of patients with a diagnosis of appendiceal neoplasms between 2009 and 2018 in our centre. Variables such as sex, age, tumour type, clinical status, diagnosis, treatment and survival were collected. All data were analysed using the statistical program IBM SPSS Statistic® version 25. RESULTS: Twenty-nine patients with a diagnosis of appendiceal neoplasm were identified, and 24 corresponded to neoplastic appendiceal mucinous lesions (85.7%). The average age was 59.7 ± 17.6 years. Most patients were women (15 cases; 62.5%). Most of them presented with chronic abdominal pain (37.5%), and the diagnosis was performed by computed tomography (CT) (50%). The treatment was surgical in all cases. The surgical technique depended on the findings and histology of the tumour. CONCLUSION: Mucinous appendiceal neoplasms are an uncommon entity, and their pathological classification and management have recently changed.

Infectivity of Norovirus GI and GII from Bottled Mineral Water during a Waterborne Outbreak, Spain.

During a waterborne outbreak of norovirus in Spain, we estimated 50% illness doses for a group of exposed (secretor) persons to be 556 (95% CI 319-957) genome copies/day for norovirus GI and 2,934 (95% CI 1,683-5,044) genome copies/day for norovirus GII. Use of a propidium monoazide viability assay reduced these values.

Drug-Coated Balloon Angioplasty in Clinical Practice for Below-the-Knee, Popliteal, and Crural Artery Lesions Causing Critical Limb Ischemia: 1-Year Results from the Spanish Luminor Registry.

BACKGROUND: Luminor is a new drug-coated angioplasty balloon, which is approved by the European Conformity market. The aim of the present study is to analyze the 1-year results, in terms of effectiveness and safety, of the Luminor® 14/14M and 35 drug-coated balloons (iVascular, Sant Vicenç dels Horts, Barcelona, Spain) in a special cohort of critical limb ischemia (CLI) of the Luminor registry. METHODS: Luminor is phase IV, nonrandomized, prospective, observational, and multicenter clinical study. The present study includes patients with CLI to analyze the effectiveness, in terms of primary patency, and the safety defined by the major adverse effects: any cause mortality, major amputation, and/or clinically driven target lesion revascularization (TLR). Both femoropopliteal and below-the-knee infrapopliteal lesions were treated. All the end points were assessed after the procedure, at 30 days, 6 and 12 months thereafter. RESULTS: About 148 patients (101 males; mean age, 73.2 ± 11.4 years) with CLI were included. About 83.3% were classified as Rutherford's class 5. Diabetes mellitus was diagnosed in 71.6%; hypertension, hyperlipidemia, renal insufficiency, and coronary disease were present in 87.2%, 57.4%, 29.7%, and 39.2% of the sample, respectively. The average follow-up was 11.2 ± 3.27 months. The primary patency and the freedom of clinically driven TLR, at 1 year, were 87.7% and 92.1%, respectively. Survival and freedom from major amputations were 85.1% and 84.7%, respectively. CONCLUSIONS: Even with a very sick population, the results at 12 months are highly satisfactory with reference to survival, freedom from amputation, patency, and the absence of reintervention.

Analysis of the Increase in Bone Mineral Density After Surgical Treatment of Primary Hyperparathyroidism.

AIM: To analyze the effect of the surgery in bone mineral density (BMD) and to study the value of preoperative clinical and analytical factors as predictors of bone increase. MATERIAL AND METHODS: Prospective observational study. Postmenopausal women who were operated for primary hyperparathyroidism were included. A bone densitometry of the lumbar spine and femoral neck and analytical determinations (parathyroid hormone [PTH], alkaline phosphatase, albumin, phosphate, creatinine, 25-hydroxy-vitamin D3, creatinine clearance, and calciuria) were performed previous to the intervention and after 12 months from surgery. RESULTS: Two hundred and twenty-eight patients were operated on for primary hyperparathyroidism were considered for study, 108 postmenopausal women entered in the final analysis. The mean age was 63 ± 7 yr. After the intervention, a significant increase in BMD was observed in the two locations analyzed, although this increase was significant greater at the level of the lumbar spine. In the lumbar spine, 68 patients (63%) recorded a significant postoperative increase in bone density. Median postoperative BMD was 0.860 g/cm2 (interquartile range: 0.93). The observed average percentage of density increase was 6.63 ± 17.9. In femoral neck, 61 patients (56.6%) registered a significant increase in bone density. Median postoperative BMD value was 0.741 g/cm2 (interquartile range: 0.76). The average percentage of density increase was 3.19 ± 17.9. In the lumbar spine, patients with osteoporosis before surgery increased postoperative BMD more frequently than those with osteopenia or normal density. Patients who increased BMD preoperatively presented lower bone density levels both in the lumbar spine (median: 0.775, interquartile range: 0.882) and in the hip (median: 0.655, interquartile range: 0.562) than patients in whom it was not observed postoperative increase. PTH preoperative serum was lower among patients who increased bone density in the femur (median: 141 pg/ml, interquartile range: 291) than among those who did not (median: 152 pg/ml, interquartile range: 342) (p = 0.01). In the multivariate analysis, the increase in BMD in the lumbar spine was related to preoperative BMD (odds ratio [OR] 0.084, 95% confidence interval [CI]: 0.007-0.961); in femoral neck it was related to preoperative BMD (OR 0.001; 95% CI: 0.0-0.028) and to the preoperative PTH serum concentration (OR 0.99; 95% CI: 0.98-0.99). CONCLUSIONS: After surgery, a significant increase in BMD was observed in the lumbar spine and femoral neck. In the multivariate analysis, preoperative bone density was the factor that showed the highest predictive value of the increase in BMD after surgery.

Endovascular Repair of Iliac Vein Laceration Associated with Complex Pelvic Fracture.

BACKGROUND: Iliac vein injury associated with pelvic fracture due to blunt trauma is an uncommon and difficult diagnosis but a life-threatening condition which often requires an emergent management. Although open repair has been traditionally used as the treatment of choice in unstable patients, it is controversial, given the difficulty due to injured vessel exposure in patients with significant retroperitoneal hematoma as well as tamponade effect loss associated with laparotomy. We present a challenging case of iliac vein laceration successfully treated by placement of a self-expanding covered stent. METHODS: A 15-year-old male was hemodynamically unstable and was transferred to our emergency department after a severe polytrauma due to a motorcycle accident. Contrast-enhanced computed tomography showed a left external iliac vein laceration with active bleeding and retroperitoneal hematoma as well as complex pelvic and left supracondylar femoral fractures. A 13 × 100 mm self-expanding covered stent was successfully deployed through duplex ultrasound-guided percutaneous approach of both femoral veins. RESULTS: The patient's blood pressure was normalized as soon as the stent graft was placed, and then femoral fracture was reduced and fixed. At 12-month follow-up, the patient remained asymptomatic, and stent-graft patency was confirmed. CONCLUSIONS: Covered stent-graft placement can be an effective and rapid treatment for life-threatening iliac vein injury.

Gold nanorods for in-drop colorimetric determination of thiomersal after photochemical decomposition.

This work reports on the implementation of gold nanorods (AuNRs) in headspace solvent microextraction for colorimetric determination of volatile analyte derivatives in a single drop. The exposure of AuNRs to both H2Se and elemental mercury (Hg0) results in a shift of the longitudinal plasmonic band, unlike a number of volatiles. Accordingly, a method is reported for the determination of Hg0 with potential applicability to the determination of thiomersal (sodium ethylmercurithiosalicylate). It is based on the photochemical decomposition of thiomersal into Hg(II) and subsequent exposure of AuNRs-containing microdrop to in situ generated Hg0. Colorimetric analysis of the enriched drop was carried out without dilution by means of a cuvetteless microvolume UV-vis spectrometer. Under optimal conditions, the limit of detection was 0.5 ng mL-1 (as Hg). The repeatability, expressed as relative standard deviation, was 8.4% (for n = 10). AuNRs exposed to increasing concentrations of the analyte were characterized by means of transmission electron microscopy and UV-vis spectrophotometry to ascertain the mechanism of detection. The method was finally applied to the determination of thiomersal in various pharmaceutical samples and showed quantitative recoveries. Graphical abstract Schematic illustration of a miniaturized colorimetric method based on the use of a microdrop of gold nanorods (AuNRs) for thiomersal determination in pharmaceuticals. It is based on the photochemical decomposition of thiomersal and subsequent Hg0 generation with in-drop amalgamation.

Indigenous tropical spastic paraparesis in Madrid (Spain). Experience on screening of human T-lymphotropic virus. / Paraparesia espástica tropical autóctona en la Comunidad de Madrid. Experiencia en el cribado del virus linfotrópico de células T humanas tipo I.

We have recently documented a case of tropical spastic paraparesis by HTLV-I in a Spanish patient. HTLV-I infection is rare in Europe, and hardly ever is accompanied by symptoms, but if it does it could trigger a major health issue. This case is presented here, as well as a discussion on the situations in which HTLV-I detection is justified. An analysis was made of the HTLV diagnostic requests at our centre during 2014-2015 (n=123). The diagnostic algorithm was: 1) Enzyme immunoassay, 2) Reverse hybridization, and 3) Proviral DNA detection by PCR. The results showed several situations of HTLV screening, emphasising those related to paraparesis (22%). Seven cases of HTLV-I infection were found: five in patients from endemic regions, one in an HIV-infected patient, and the case of TSP mentioned above. HTLV-I surveillance in non-endemic regions is a challenging issue, as the cost-benefit ratio is not well-established. This case report emphasises the importance of including HTLV within the differential diagnosis of insidious spastic paraparesis.

Spontaneous haematoma of the anterior rectus abdominis muscle. / Hematoma espontáneo del músculo recto anterior del abdomen.

INTRODUCTION: Spontaneous haematoma of the rectus abdominis muscle is an uncommon cause of abdominal pain. It occurs mostly in anticoagulated patients. The objective of this paper is to analyse the onset, diagnosis and treatment in patients under anticoagulant therapy. METHODS: A retrospective analysis of a prospectively maintained database of all patients with a diagnosis of spontaneous hematoma of the abdominal rectus muscle between March 2003 and December 2014. RESULTS: The study included 34 patients, of whom 28 were women, with an average age of 80 years old. All the patients showed a unilateral infraumbilical haematoma. Twenty- 8 patients had received long-term anticoagulant treatment (26 with acenocumarol and 2 low molecular weight heparin); and 6 patients were under anticoagulant prophylaxis with low molecular weight heparin. The diagnosis was performed with ultrasound in 7 cases, computed tomography angiography in 27 patients, and with both methods in 6 cases. The treatment consisted of stopping the anticoagulant drug, correcting haemostasis parameters and blood transfusion when required. Ten patients displayed active bleeding in the computed tomography angiography, and 8 underwent selective arterial embolization. The evolution was successful in 34 patients, however, 2 patients required surgery and, finally, died due to persistent haemorrhage. CONCLUSION: Spontaneous haematoma of the rectus abdominis muscle is more frequent in elderly women under oral anticoagulant treatment. Non-operative treatment is successful in most cases. Computed tomography angiography is useful to determine which patients could benefit from selective arterial embolization.

Expanded CTG repeats trigger miRNA alterations in Drosophila that are conserved in myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. Several missplicing events and transcriptional alterations have been described in DM1 patients. A large number of these defects have been reproduced in animal models expressing CTG repeats alone. Recent studies have also reported miRNA dysregulation in DM1 patients. In this work, a Drosophila model was used to investigate miRNA transcriptome alterations in the muscle, specifically triggered by CTG expansions. Twenty miRNAs were differentially expressed in CTG-expressing flies. Of these, 19 were down-regulated, whereas 1 was up-regulated. This trend was confirmed for those miRNAs conserved between Drosophila and humans (miR-1, miR-7 and miR-10) in muscle biopsies from DM1 patients. Consistently, at least seven target transcripts of these miRNAs were up-regulated in DM1 skeletal muscles. The mechanisms involved in dysregulation of miR-7 included a reduction of its primary precursor both in CTG-expressing flies and in DM1 patients. Additionally, a regulatory role for Muscleblind (Mbl) was also suggested for miR-1 and miR-7, as these miRNAs were down-regulated in flies where Mbl had been silenced. Finally, the physiological relevance of miRNA dysregulation was demonstrated for miR-10, since over-expression of this miRNA in Drosophila extended the lifespan of CTG-expressing flies. Taken together, our results contribute to our understanding of the origin and the role of miRNA alterations in DM1.

Results of transanal endorrectal descent in Hirschprung's disease.

OBJECTIVE: To present our experience of patients with Hirschsprung disease (HD) operated by transanal endorrectal descent (TED). METHODS: A retrospective study performed of TEDs. We correlate fundamentally the aganglionic segment length with: Complications, need for colostomy and surgical approach. RESULTS: Between 2003 and 2012 we performed 73 TED (57 men), 78.6% diagnosed in the neonatal period. The aganglionic segment length evidenced in the enema was correlated with surgical findings in 68.9% of cases, being higher in the short forms than in the long segments (80.9 vs. 44%, P<.001). Four patients required preoperative colostomy. The mean age of surgery was 6.3 months (4.5 to 33.7). Short forms represented 64.4% of cases. The abdominal approach was necessary in 10 patients, 9 of these were long/total colonic aganglionic segment. Postoperative enterocolitis presented in 10,9% (9 patients), with no relation with the length of aganglionic or the existence of residual dysplasia. Obstructions occurred in 19.2% of the long form or pancolonic forms. Currently, of the evaluable patients, 5 present constipationand 12 present occasional leakage. CONCLUSIONS: TED is the surgery of choice for patients with HD. The majority can be handled by preoperative «nursing¼ without colostomy. The diagnostic tests of choice are manometry with suction biopsy. No significant correlation was found between enterocolitis and length of aganglionic segment, although we observed a drastic reduction of postoperative enterocolitis, since the introduction of technical changes, such as the use of postoperative rectal tubes and the posterior section of the cuff muscles.