Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Chromium behavior in a highly urbanized coastal area (Bahía Blanca Estuary, Argentina).

The contamination of estuaries by heavy metals from anthropogenic activities in the industrial, domestic, and agricultural sectors is a global concern. In this study, the Cr, Fe, and Mn levels in the suspended particulate matter (SPM) were analyzed in estuarine waters from Bahia Blanca Estuary, during 2014-2015. The values of particulate Cr ranged from 7.33 to 35.20 µg g-1, which could be associated to several anthropogenic sources. The positive correlations found between Cr and Chlorophyll-a, and Cr and particulate organic carbon (POC) suggest the strong influence of phytoplankton on the adsorption of this metal and on the increase of particulate Cr. Negative correlations were found between Cr and DO and between Cr and pH, which could indicate an increasing trend in the dissolved form of Cr. This study suggests that the physical-chemical characteristics of the water column as well as phytoplankton and POC dynamics influence the behavior of Cr in this estuary.

Post-void residual and voiding dysfunction symptoms in women with pelvic organ prolapse before and after vaginal surgery. A multicenter cohort study. / Residuo posmiccional y síntomas de disfunción de vaciado en mujeres con prolapso de órganos pélvicos antes y después de la cirugía vaginal. Estudio de cohortes multicéntrico.

OBJECTIVES: The present study evaluates the impact of vaginal surgery for pelvic organ prolapse (POP) on voiding dysfunction (VD) symptoms and post-void residual (PVR) one year after the intervention. MATERIAL AND METHODS: Epidemiological, longitudinal, prospective study. Thirty-nine gynecology units included women with symptomatic POP grade 2 or higher according to the Pelvic Organ Prolapse Quantification (POP-Q) system, who would undergo surgery for vaginal prolapse (CIRPOP-IUE study). Sociodemographic and clinical variables were collected before and after the intervention. At both visits, patients completed the 'Epidemiology of Prolapse and Incontinence Questionnaire' (EPIQ) and 'Pelvic Floor Distress Inventory' (PFDI-20) questionnaire. PVR volume was measured by bladder catheterization immediately after spontaneous urination. RESULTS: VD symptoms were present in 50% cases before the intervention. PVR was measured in 277 women of which 116 (41.87%) were >50ml and 42/277 (15.2%) were >100ml. Objective and subjective reduction in VD symptoms was observed one year after the intervention. Mean PVR volume was reduced with statistical significance, from a mean (SD) of 66.4 (68.9)ml to 48.3 (51.3)ml. The number of patients who reported difficulty in emptying and sensation of incomplete emptying on the EPIQ and PFDI-20 questionnaires also decreased. CONCLUSIONS: In general, improved voiding functions were observed in the CIRPOP-IUE study through a decrease in specific VD symptoms and a reduction in mean PVR volume.

Quality of life and treatment persistence evaluation in Spanish patients treated with mirabegron. Results of the BELIEVE study. / Resultados de la subpoblación española del estudio BELIEVE. Evaluación de la calidad de vida y persistencia al tratamiento de pacientes tratados con mirabegrón.

INTRODUCTION AND OBJECTIVE: The BELIEVE study is a European, non-interventional study which includes patients with overactive bladder who were prescribed mirabegron as part of routine clinical practice. Data from the Spanish subpopulation has been obtained for the present study, aiming to analyze health-related quality-of-life (HRQoL) and treatment persistence of these patients. MATERIALS AND METHODS: Data from 11 Spanish hospitals of the BELIEVE study were analyzed. The primary endpoint was to evaluate change of HRQoL from baseline with overactive bladder questionnaire (OAB-q). Secondary endpoints included treatment persistence, HRQoL based on the EQ-5D-5L questionnaire and adverse events. Study follow-up was 12 months, with two visit windows at 2-4 months and 10-12 months. RESULTS: 153 Spanish patients were enrolled in the study. In the Full Analysis Set (FAS), 63.1% were women, and the mean age was 66 years. Symptom bother and HRQoL improved from baseline to 2-4 months and 10-12 months. EQ-5D-5L questionnaire also showed an improved patients' HRQoL. Treatment persistence was high, as 49% of patients remained with mirabegron at 10-12 months. Adverse events were consistent with previous safety profile results of mirabegron, and no unexpected safety issues were observed. CONCLUSIONS: Spanish patients treated with mirabegron in real clinical practice reported improvements in HRQoL, with a good tolerability and persistence to treatment.

Mannose-coated polydiacetylene (PDA)-based nanomicelles: synthesis, interaction with concanavalin A and application in the water solubilization and delivery of hydrophobic molecules.

Carbohydrate-lectin interactions are involved in a number of relevant biological events including fertilization, immune response, cell adhesion, tumour cell metastasis, and pathogen infection. Lectins are also tissue specific, making carbohydrates not only promising drug candidates but also excellent low molecular weight ligands for active drug delivery system decorations. In order for these interactions to be effective multivalency is essential, as the interaction of a lectin with its cognate monovalent carbohydrate epitope usually takes place with low affinity. Unlike the covalent approach, supramolecular self-assembly of glyco-monomers mediated by non-covalent forces allows accessing multivalent systems with diverse topology, composition, and assembly dynamics in a single step. In order to fine-tune the size and sugar adaptability of spherical micelles at the nanoscale for an optimal glycoside cluster effect, herein we report the synthesis of mannose-coated static micelles from diacetylene-based mannopyranosyl glycolipids differing in the length of the poly(ethyleneglycol) (PEG) chains and the oxidation state of the anomeric sulfur atom. The reported shot-gun like synthetic approach for the synthesis of dilution-insensitive micelles is based on the ability of diacetylenic-based neoglycolipids to self-assemble into micelles in water and to undergo an easy photopolymerization by a simple irradiation at 254 nm. The affinity of the obtained 6 nanosystems was assessed by enzyme-linked lectin assay (ELLA) using the mannose-specific concanavalin A lectin as a model receptor. Relative binding potency enhancements, compared to methyl α-d-mannopyranoside used as control, from 20-, to 29- to 300-fold on a sugar molar basis were observed for micelles derived from sulfonyl-, sulfinyl- and thioglycoside monomers with a tatraethyleneglycol spacer, respectively, indicative of a significant cluster glycoside effect. Moreover, pMic1 micelles are able to solubilize and slowly liberate lipophilic clinically relevant drugs, and show the enhanced cytotoxic effect of docetaxel toward prostate cancer cells. These findings highlight the potential of mannose-coated photopolymerized micelles pMic1 as an efficient nanovector for active delivery of cytotoxic hydrophobic molecules.

Sexual activity and function of women with severe pelvic organ prolapse subjected to a classical vaginal surgery. A Multicentre study. / Actividad y función sexual en mujeres con prolapso de órganos pélvicos avanzado sometidas a cirugía vaginal clásica. Estudio multicéntrico.

INTRODUCTION AND OBJECTIVE: Pelvic organ prolapse (POP) is related with female sexual dysfunction. The present study aimed to determine the impact of POP corrective surgery on the sexual life of women with advanced POP. MATERIALS AND METHODS: A prospective, multicentre cohort study was designed, including patients with grade≥II, symptomatic POP, who underwent vaginal surgery with traditional procedures. Sexual activity and function were assessed by PISQ-IR before surgery and 12 months after. RESULTS: We included 355 women; 322 had data from the follow-up visit. The mean (SD) age was 64.8 (9.9) years. At baseline, 170 women were sexually active and 185 were not. After surgery, 29 women (16.8%) became sexually active and 20 (12.8%) ceased sexual activity. Before surgery, 42.3% reported not having sexual intercourse due to bladder, bowel or POP problems; and 11.4% after surgery. At baseline visit, 25.3% had no sexual activity due to pain, however, at follow-up visits, this percentage was 8.5%. A statistically significant improvement was observed in 5 out of 6 scales of the PISQ-IR in sexually active women. CONCLUSIONS: Symptomatic POP is associated with female sexual dysfunction. Surgical intervention seems to have a positive impact on sexual life among sexually inactive and active women.

Conformationally-locked C-glycosides: tuning aglycone interactions for optimal chaperone behaviour in Gaucher fibroblasts.

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver ß-glucosidase/ß-galactosidase and specific inhibition of human ß-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound Ambroxol.

Tuning of glyconanomaterial shape and size for selective bacterial cell agglutination.

Multivalent glycosystems are potential candidates for anti-adhesive therapy, a non-lethal approach against the ever increasing antibiotic resistance of pathogenic bacteria. In order to fine-tune the glyconanomaterial size and shape for selective bacterial cell agglutination, herein we report the synthesis of sugar-coated dynamic and polymeric 3D-micelles and 1D-carbon nanotubes. The reported shot-gun like synthetic approach is based on the ability of diacetylenic-based neoglycolipids to self-assemble into micelles in water and hierarchically self-assemble into hemimicelles on a single-walled carbon nanotube surface. The affinity of the nanosystems was preliminarily assessed by enzyme-linked lectin assay (ELLA) using the mannose-specific Concanavalin A lectin as a model receptor. Relative binding potency enhancements, compared to methyl α-d-mannopyranoside used as control, from 10- to 25- to 2340-folds in sugar molar basis were observed when passing from 3D dynamic micelles to static micelles, to 1D-mannose coated carbon nanotubes, respectively, indicative of a significant cluster glycoside effect. Importantly, these results were confirmed in vivo showing that the 1D-glyconanoring-coated carbon nanotubes efficiently and selectively regulate the agglutination and proliferation of the enterobacteria Escherichia coli type 1 fimbriae. These findings highlight the potential of sugar coated nano-materials as novel and effective tools in the control of bacterial pathogenesis.

Assessment of the physicochemical conditions sediments in a polluted tidal flat colonized by microbial mats in Bahía Blanca Estuary (Argentina).

The aim of this work is to assess the physicochemical conditions of the supratidal sediments colonized by microbial mats at two sites from Rosales Harbor (Bahía Blanca Estuary, Argentina) close to sewage discharge. Both sites differed in the size grain. No differences in pH, Eh and temperature were observed. Moisture retention and chlorophyll a concentration were significantly different between sites and sediment layers. Heavy metals and organic matter content were significantly higher in SII. No statistical differences were found in porewater nutrients concentration, being higher in SI (except DSi). The presence of Escherichia coli in water and sediment (1000 CFU/100 mL - uncountable and 35-40 CFU g(-1) dw, respectively) evidenced microbial contamination in the study area. The relationships between the physicochemical parameters evaluated and the influence of the sewage discharge allow defining two different areas in the Rosales Harbor despite the proximity and the presence of microbial mats.

Universal transition state scaling relations for (de)hydrogenation over transition metals.

We analyse the transition state energies for 249 hydrogenation/dehydrogenation reactions of atoms and simple molecules over close-packed and stepped surfaces and nanoparticles of transition metals using Density Functional Theory. Linear energy scaling relations are observed for the transition state structures leading to transition state scaling relations for all the investigated reactions. With a suitable choice of reference systems the transition state scaling relations form a universality class that can be approximated with one single linear relation describing the entire range of reactions over all types of surfaces and nanoclusters.

Obstruction of the bypassed stomach treated with percutaneous drainage: an alternative treatment for selected cases.

Biliopancreatic limb obstruction in Roux-en-Y gastric bypass is an infrequent complication that should be recognized early to avoid the risk of peritonitis and death. In this manuscript, we report a case of acute gastric remnant dilatation secondary to intraabdominal hematoma provoked by trocar injury that was compressing the second portion of duodenum lumen. To treat this problem, we decided on a less invasive treatment consisting of percutaneous decompression of the stomach. The procedure was performed using sonographic guidance with local anesthesia, thus, avoiding a new surgical procedure. In this selected case, percutaneous radiological catheter placement provided an effective decompression of the excluded gastric remnant until spontaneous resolution of the obstruction.

Effectiveness of colorectal laparoscopic surgery on patients at high anesthetic risk: an intervention cohort study.

AIMS: The aim of the study was to assess the effectiveness of laparoscopic colorectal surgery in patients at high preoperative anesthetic risk because of associated pathologies. MATERIALS AND METHODS: From January 2003 until January 2005, 116 patients were systematically assigned at a ratio of 1:1 to one of two groups: laparoscopy surgery (n=59, of which 31 were American Society of Anesthesiologists score [ASA] I-II [L1] and 28 ASA III-IV [L2]) or open surgery (n=57, of which 30 were ASA I-II [O1] and 27 ASA III-IV [O2]). Data on patient demographics and clinical and anesthetic variables were collected prospectively. Informed consent was obtained from the patients, and approval was obtained from the designated review board of the institution involved. RESULTS: The number of minor anesthetic complications during surgery was higher in L2 patients. No differences were observed in blood gas parameters studied during surgery (pCO(2), pH, and pO(2)/FiO(2)). Transfusion rates in the laparoscopy group at greater anesthetic risk (L2) were lower than those of the high-risk conventional surgery group (O2; 21.4 vs 63%, P<0.02). Duration of stay in the surgical recovery room and the inpatient ward were also shorter in the L2 group than in the O2 group (8.7+/-4.5 vs 12.2+/-6 days, P=0.02). There was no difference in perioperative clinical variables between laparoscopy groups (L1, L2). CONCLUSION: Postoperative recovery of ASA III-IV patients is better after laparoscopic surgery for colorectal cancer, at the expense of a higher rate of minor anesthetic occurrences during surgery.

[Temporal and bacteriological comparison of neonatal urinary infections]. / Comparación temporal y bacteriológica de la infección urinaria neonatal.

OBJECTIVE: To find out the epidemiological and management changes of urinary tract infection over the last years. PATIENTS AND METHODS: Descriptive retrospective review of patients with urinary tract infections (UTIs) admitted to our neonatal unit over an 11 year period. A temporal, microorganism group and voiding cystourethrography (VCUG) group comparison. RESULTS: We studied 106 cases (5 cases/1,000 alive newborns). The most commonly isolated microorganisms were Escherichia coli (81.1%), Enterococcus faecalis (6.6%) and Enterobacter cloacae (4.7%). Gentamicin had an overall sensitivity of 93.2%, followed by cefotaxime 91.3% and amoxicillin-clavulanic acid 89.5%. We did not found temporal differences in microorganisms or sensitivities. We found differences in C reactive protein, nitrate and leucocyte values in E. coli versus non-E. coli UTIs, as well as patterns of antibiotic sensitivity with more resistances by non-E. coli microorganisms. No differences were found in patients with normal and pathological VCUG. We found ultrasound and VCGU disturbances in 35.2% and 21.4%, respectively. CONCLUSIONS: UTI is a common problem in our area. The most frequently isolated microorganism is E. coli. Non-E. coli UTIs have more resistances to usual therapies, although these did not show any increase in disease in the imaging tests. We found no increase in resistances throughout the study.

Carcinoid syndrome misdiagnosed as a malabsorptive syndrome after biliopancreatic diversion.

A case is reported of a woman who developed untreatable diarrhea after a prior biliopancreatic diversion (BPD), attributed to the malabsorptive component. Abdominal ultrasound incidentally found focal liver lesions. On fine needle aspiration biopsy, atypia was found, and these hepatic lesions were resected with free margins. The specimen showed liver metastases of an aggressive malignant neuroendocrine neoplasm. The primary site was subsequently identified to be in the pancreas. The physician and surgeon must realize that non-related diseases can develop after bariatric surgery, as in the general population.

[Mesenteric panniculitis: experience in our center]. / Paniculitis mesentérica: experiencia en nuestro centro.

Although several etiological factors have been associated with mesenteric panniculitis, the exact etiology in some cases remains unknown. Herein, we present a retrospective analysis of 8 patients affected with this disorder performed between May 2000 and December 2006. In our series the mean age at which patients presented was 63 years. The majority of the patients were male (with a male: female ratio of 3:1). The most common clinical manifestations were abdominal pain (n = 4) and asthenia (n = 4). Three cases presented with obstructive symptoms and three had a history of abdominal surgery. Notably, seven had a background of tobacco use (five smokers and two ex-smokers) and one patient developed follicular lymphoma. A literature research was carried out to analyze our results and formulate a new hypothesis. In our opinion, we believe that the study of causal factors such as tobacco and its components is required due to the strong association found in this study.