Hospital General de Almansa

INTRODUCTION: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. METHODS: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. RESULTS: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. CONCLUSION: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

To study the feasibility, reliability, and validity, of a Spanish European version of the Health Assessment Questionnaire (SHAQ).A total of 170 patients with rheumatoid arthritis (RA) from 11 public general hospitals in Spain were included. We studied (a) the feasibility of the SHAQ by finding the proportion of patients able to self-administer it and the time they take to do so; (b) the test-retest reliability of the SHAQ when completed twice, with an interval of one week, calculating the Pearson correlation coefficient (r) between the first and second SHAQ scores; (c) the criterion validity of the SHAQ by comparing the clinician's assessment of the patient's activities (observed disability) with the scores noted by the patient in the questionnaire (referred disability); (d) cross sectional construct validity comparing the scores of the SHAQ with the other tests used in the assessment of RA; and (e) the longitudinal construct validity of the SHAQ comparing the difference between the initial and final SHAQ scores with the patient rating of improvement or worsening after a 3-month followup.The SHAQ was self-administered by 63% of patients, the rest needed the presence of an interviewer. The time taken to complete the questionnaire was 6.4 min. Test-retest reliability (r = 0.89), criterion validity (r = 0.87), cross sectional construct validity, and longitudinal construct validity were satisfactory and similar to other HAQ versions used in different countries.The SHAQ is a reliable, valid tool, but for use in Spain an interviewer may be necessary.

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain.

Two hundred forty-six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC-CYV) alternating at 4 weekly intervals. One hundred sixty-two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90-100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50-80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer's disease (AD), Parkinson's disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment.

The estimation of moisture content of dead fuels is a critical variable in fire danger assessment since it is strongly related to fire ignition and fire spread potential. This study evaluates the accuracy of two well-known meteorological moisture codes, the Canadian Fine Fuels Moisture Content and the US 10-h, to estimate fuel moisture content of dead fuels in Mediterranean areas. Cured grasses and litter have been used for this study. The study was conducted in two phases. The former aimed to select the most efficient code, and the latter to produce a spatial representation of that index for operational assessment of fire danger conditions. The first phase required calibration and validation of an estimation model based on regression analysis. Field samples were collected in the Cabañeros National Park (Central Spain) for a six-year period (1998–2003). The estimations were more accurate for litter (r2 between 0.52) than for cured grasslands (r2 0.11). In addition, grasslands showed higher variability in the trends among the study years. The two moisture codes evaluated in this paper offered similar trends, therefore, the 10-h code was selected since it is simpler to compute. The second phase was based on interpolating the required meteorological variables (temperature and relative humidity) to compute the 10-h moisture code. The interpolation was based on European Centre for Medium Range Weather Forecasting (ECMWF) predictions. Finally, a simple method to combine the estimations of dead fuel moisture content with other variables associated to fire danger is presented in this paper. This method estimates the probability of ignition based on the moisture of extinction of each fuel type.

Macrophages activated through Toll receptor triggering increase the expression of the A(2A) and A(2B) adenosine receptors. In this study, we show that adenosine receptor activation enhances LPS-induced pfkfb3 expression, resulting in an increase of the key glycolytic allosteric regulator fructose 2,6-bisphosphate and the glycolytic flux. Using shRNA and differential expression of A(2A) and A(2B) receptors, we demonstrate that the A(2A) receptor mediates, in part, the induction of pfkfb3 by LPS, whereas the A(2B) receptor, with lower adenosine affinity, cooperates when high adenosine levels are present. pfkfb3 promoter sequence deletion analysis, site-directed mutagenesis, and inhibition by shRNAs demonstrated that HIF1α is a key transcription factor driving pfkfb3 expression following macrophage activation by LPS, whereas synergic induction of pfkfb3 expression observed with the A(2) receptor agonists seems to depend on Sp1 activity. Furthermore, levels of phospho-AMP kinase also increase, arguing for increased PFKFB3 activity by phosphorylation in long term LPS-activated macrophages. Taken together, our results show that, in macrophages, endogenously generated adenosine cooperates with bacterial components to increase PFKFB3 isozyme activity, resulting in greater fructose 2,6-bisphosphate accumulation. This process enhances the glycolytic flux and favors ATP generation helping to develop and maintain the long term defensive and reparative functions of the macrophages.

Fecal carriage of extended-spectrum beta-lactamase (ESBL)-producing organisms was assessed in 272 inpatients, 162 outpatients, and 426 asymptomatic healthy individuals. Of 860 stool samples cultured, 152 (17.7%) yielded ESBL-producing organisms. Isolates were recovered from 71 (26.1%) of the inpatients, 25 (15.4%) of the outpatients, and 56 (13.1%) of the healthy individuals. These findings suggest that the community could be a reservoir of ESBL-producing organisms.

A randomized controlled trial in KwaZulu-Natal (South Africa) of 428 primary-school pupils (stratified into 6 groups by age, sex and intervention) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year (1996/97). Half the pupils received iron supplementation (ferrous fumarate 200 mg weekly for 10 weeks). Pupils received 2 anthelmintic regimens, either (i) albendazole 400 mg plus praziquantel 40 mg/kg or (ii) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or (iii) placebo. Baseline prevalences of Ascaris 55.9%, Trichuris 83.6%, hookworm spp. 59.4%, were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4% (P < 0.005), Trichuris 61.5% (NS), hookworm spp. 0% (P < 0.005), and for triple-dose albendazole treatment to Ascaris 14.8% (P < 0.005), Trichuris 25.0% (P < 0.01), hookworm 0% (P < 0.005). Schistosoma haematobium 43.4% was reduced among treated groups to 8.3% (P < 0.005). There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment. Twelve months after treatment there was a significant increase in haemoglobin levels (P = 0.02) among pupils receiving triple-dose albendazole, praziquantel and ferrous fumarate; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron. Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris, hookworm spp. and S. haematobium infections (P < 0.05). Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg (P = 0.002). In areas with schistosomiasis, hookworm infection and high prevalence of Trichuris infection, combination treatment with praziquantel, triple-dose albendazole, plus iron supplementation, is likely to improve pupils' health and haemoglobin levels.

OBJECTIVE: To report the visual outcome after 4-year follow-up in a series of highly myopic eyes with choroidal neovascularisation (CNV) treated with antivascular endothelial growth factor (anti-VEGF) drugs. METHODS: A retrospective, non-randomised, multicentre, consecutive, interventional case series study was performed. 92 highly myopic eyes with subfoveal CNV were treated with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3 injections) was dictated by surgeons' preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyse BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives. RESULTS: The mean age of the patients was 57 years (SD 14, range 30-93). The mean number of letters read was 46.1 (SD 16.8, range 5-70) at baseline, 55.5 (SD 18.6, range 10-85) at 12 months, 50.1 (SD 20.1, range 5-82) at 24 months, 54.2 (SD 21.9, range 2-85) at 36 months and 53.1 (SD 22.5, range 1-83) at 48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months; Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4, range 1-29). SE and treating drug had no influence on the final visual outcome and number of injections required. CONCLUSIONS: Intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at 4-year follow-up.

<h3>Aims:</h3> The aim of the study was to examine the changes in visual acuity, fluorescein angiography (FA) and optical coherence tomography (OCT) macular thickness of subfoveal, and juxtafoveal choroidal neovascularisation (CNV) in highly myopic eyes treated by intravitreal bevacizumab. <h3>Methods:</h3> The study was a prospective, non-randomised, multicentre, interventional case series. Twenty-nine highly myopic eyes from 28 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections of 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and OCT at baseline and then monthly for 1 year. FA was performed at baseline, after 3 months, and whenever CNV activity was suspected. <h3>Results:</h3> The average age was 50 (SD 15, range 29–82) years. The mean LogMAR BCVA at baseline was 0.55 (SD 0.25, range 0.2–1.0) and 0.38 (SD 0.32, range 0.0–1.2) at 1 year. Sixteen eyes were naïve for treatment and 13 eyes had been previously treated by photodynamic therapy (average 2.5 sessions). Leakage from CNV had ceased in all eyes at month 3. OCT central foveal thickness decreased significantly from 282 (SD 68) μm at baseline to 224 (SD 46) μm at month 12 (p = 0.008, Student t test for paired data). Six eyes needed one re-injection during follow-up at month 4 (one eye), month 6 (four eyes) and month 12 (one eye). Neither ocular nor systemic adverse reactions appeared during follow-up. <h3>Conclusions:</h3> The results of this case series suggest that intravitreal bevacizumab seems to be an effective therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes at 1-year follow-up. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

OBJECTIVE: To evaluate the prevalence and antimicrobial susceptibility of extended spectrum beta-lactamase (ESBL) producing gram-negative organisms isolated from patients with urinary tract infection (UTI). METHODS: We carried out this study at Almana General Hospital, Eastern Province, Kingdom of Saudi Arabia, during the period August 2003 to October 2004. We studied urinary isolates of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Enterobacter spp and Pseudomonas aeruginosa (P. aeruginosa) for ESBL production and antimicrobial susceptibility. RESULTS: We studied a total of 2302 urinary gram-negative isolates for the presence of ceftazidime resistance and ESBL. The isolates included E. coli (1238), K. pneumoniae (522), Enterobacter spp (138) and P. aeruginosa (404). Of the 2302 isolates, 232 (10%) were ceftazidime resistant and 204 (8.9%) were ESBL producers. We detected ESBL in 119 (9.6%) E. coli, 59 (11.3%) K. pneumoniae, 14 (10.14%) Enterobacter species and 12 (2.97%) P. aeruginosa isolates. The ESBL-producing strains were most commonly isolated from patients with indwelling Foley s catheter [131 (64.2%)] and those in the long-term care ward [90 (44.2%)]. Only 26 (12.7%) ESBL-producing isolates were from outpatients. More than 89% of the ESBL producers were susceptible to imipenem and meropenem. Amikacin and piperacillin/tazobactam were active against 68% and 45% of the isolates. Susceptibility to gentamicin and ciprofloxacin was 22.5% and 14%. The least active antibiotic was cefepime (11.8%). CONCLUSION: This study shows the presence of ESBL producers in uropathogens from both inpatients and outpatients and demonstrates their high resistance to various classes of antimicrobial agents.

AIMS: To report the visual outcome in a series of eyes with myopic choroidal neovascularisation treated by photodynamic therapy (PDT) followed during 48 months. METHODS: Prospective, consecutive, non-randomised interventional case series. Thirty-nine eyes from 36 highly myopic patients treated by PDT were evaluated. Best corrected visual acuity (BCVA) and fluorescein angiography were performed every 3 months. Multiple regression analysis was used to analyse changes in BCVA in relationship with initial BCVA, spherical equivalent, age, diameter of CNV and chorioretinal atrophy. RESULTS: Mean initial BCVA was 9.0 Early Treatment Diabetic Retinopathy Study lines (SD 4.3). BCVA was 10.4 lines (3.6) at month 12, 9.7 lines (SD 3.9) at month 24, 9.6 lines (SD 3.8) at month 36 and 9.6 lines (SD 4.2) at month 48. BCVA improvement was associated with initial BCVA (p<0.002), lesion diameter (p<0.04) and age (p<0.04) (multiple regression analysis). CONCLUSIONS: Our results suggest a better visual outcome for those eyes with better initial BCVA and larger lesions in younger patients treated by PDT. The poorer results for elderly patients with lower initial BCVA might lead us to consider other therapeutic approaches.

Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and has been approved for the treatment of rheumatoid arthritis (RA) patients who have had an inadequate response to previous biological therapies. Psoriasiform skin lesions, especially palmoplantar pustulosis lesions, are well described following anti-tumour necrosis factor therapy. We describe a 79-year-old woman with rheumatoid factor-positive, anti-citrullinated protein antibody-positive erosive RA, who developed a psoriasiform palmoplantar pustulosis reaction following treatment with TCZ therapy (IL-6 receptor). The rash showed histological features compatible with psoriasis and disappeared following discontinuation of TCZ.

Brucellosis is usually acquired by humans through contact with infected animals or the consumption of raw milk from infected ruminants. Brucella suis biovar 2 (BSB2) is mainly encountered in hares and wild boars (Sus scrofa), and is known to have very low pathogenicity to humans with only two case reports published in the literature. Human cases of brucellosis caused by BSB2 were identified through the national mandatory notification of brucellosis. The identification of the bacterium species and biovar were confirmed by the national reference laboratory. Epidemiological data were obtained during medical follow-up visits. Seven human cases were identified between 2004 and 2016, all confirmed by the isolation of BSB2 in clinical specimens. All patients had direct contact with wild boars while hunting or preparing wild boar meat for consumption. Five patients had chronic medical conditions possibly responsible for an increased risk of infection. Our findings suggest that BSB2 might be an emerging pathogen in hunters with massive exposure through the dressing of wild boar carcasses. Hunters, especially those with chronic medical conditions, should be informed about the risk of BSB2 infection and should receive information on protective measures.

This study has pursued to find the efficacy values in the playing microsituations in the counterattack and in the defensive adjustment and to analyse the relation between these and the condition of winner or loser. We analysed the matches of the 10th World Championship of Water polo which did not ended in a draw. Playing microsituations in the counterattack and in the defensive adjustment were evaluated by means of coefficients, obtaining efficacy values. Differences were revealed in male category in the following coefficients: possibility (p=.025), concretion (p=.006), definition (p=.029) and precision (p=.047). In female category differences were found in the following coefficients: possibility, concretion, definition, resolution and precision (p=.000) and accuracy (p=.001); taking as reference a value of p <.05. To conclude with, we can say that in eight, in male category, and twelve, in female category, out of the fourteen efficacy coefficients proposed for evaluating the playing microsituations in the counterattack and defensive adjustment in water polo, there are significant differences between the condition of winner or loser.

Background: Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale. Methods: To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted. Cases with childhood-onset cardiomyopathy were consecutively recruited. Based on the likelihood of founder mutation and on the clinical diagnosis, genetic test was categorized to either (1) targeted genetic test with targeted mutation test, single-gene test, or multigene panel for Noonan syndrome, or (2) untargeted genetic test with whole-exome sequencing or whole-genome sequencing. Several bioinformatics tools were used to filter the variants. Results: Two-hundred five unrelated probands with various forms of cardiomyopathy were evaluated. The median age of presentation was 10 months. In 30.2% (n=62), targeted genetic test had a yield of 82.7% compared with 33.6% for whole-exome sequencing/whole-genome sequencing (n=143) giving an overall yield of 53.7%. Strikingly, 96.4% of the variants were homozygous, 9% of which were found in 4 dominant genes. Homozygous variants were also detected in 7 novel candidates ( ACACB, AASDH, CASZ1, FLII, RHBDF1, RPL3L, ULK1 ). Conclusions: Our work demonstrates the impact of consanguinity on the genetics of childhood-onset cardiomyopathy, the value of adopting a categorized population-sensitive genetic approach, and the opportunity of uncovering novel genes. Our data suggest that if a founder mutation is not suspected, adopting whole-exome sequencing/whole-genome sequencing as a first-line test should be considered.

BACKGROUND: Flavonol glucosides constitute the second group of secondary metabolites that accumulate in Crocus sativus stigmas. To date there are no reports of functionally characterized flavonoid glucosyltransferases in C. sativus, despite the importance of these compounds as antioxidant agents. Moreover, their bitter taste makes them excellent candidates for consideration as potential organoleptic agents of saffron spice, the dry stigmas of C. sativus. RESULTS: Using degenerate primers designed to match the plant secondary product glucosyltransferase (PSPG) box we cloned a full length cDNA encoding CsGT45 from C. sativus stigmas. This protein showed homology with flavonoid glucosyltransferases. In vitro reactions showed that CsGT45 catalyses the transfer of glucose from UDP_glucose to kaempferol and quercetin. Kaempferol is the unique flavonol present in C. sativus stigmas and the levels of its glucosides changed during stigma development, and these changes, are correlated with the expression levels of CsGT45 during these developmental stages. CONCLUSION: Findings presented here suggest that CsGT45 is an active enzyme that plays a role in the formation of flavonoid glucosides in C. sativus.

Substandard dates were used as a cheep source for juice production. The seedless dates solution was mixed well, decanted, clarified and microfiltrated. The total sugar concentrations in the prepared date juice were adjusted to 13.5, 18.0 and 22.5%. Date juice with 18% sugars was the more suitable and economic concentration could be fermented to ethanol by using each of Saccharomyces cerevisiae or S. bayamus in submerged fermenters. Also S. bayamus was more active than S. cerevisiae in the fermentation of the date juice. The higher yield ethanol production was recorded by using S. bayamus grown on date juice with 18% sugars concentration at 30°C and pH 3.5. The fermentation rate under these conditions was 2.0 Brix consumed per 12 hours and the fermentation was completed in 84 hours, with resulting in an ethanol concentration of 9.2%. This concentration of ethanol was nearly equal to the theoretical value. It was represented 50.9% of the total sugars in the date juice which was 18%. Addition of different concentrations of Di-ammonium phosphate (1, 2 or 3 g/l of date juice) had no effect on the efficiency of fomentation. At the end of fermentation, the fermented date juice was distilled and alcohol with nearly 93% concentration was produced.

γ-Aminobutyric acid type B (GABAB) receptors play a critical role in neuronal excitability and modulation of synaptic neurotransmission in the central nervous system. They are G protein-coupled receptors that signal primarily through activation of G proteins (i.e. pertussis toxin sensitive Gαi/o family) to modulate the function of inwardly-rectifying K⁺ and voltage-gated Ca²⁺ channels, and to trigger cyclic adenosine monophosphate cascades. Functional GABAB receptors are obligated heterodimers formed by the co-assembly of two subunits, the GABAB1 and the GABAB2, which interact via coiled-coil domains in their C-terminal tails. It is now quite well established that GABAB receptors interact not only with heterotrimeric G proteins and effector ion channels but also with a plethora of accessory proteins that might impinge into the receptor's biology. Indeed, these proteins have been implicated in several key functional aspects of the receptor, namely to link functional GABAB receptors with components of the relevant signalling pathways, to target the receptor into specific subcellular compartments, to participate in their trafficking to and from the plasma membrane, and to regulate their signalling properties. Overall, in this review we focus on those proteins that interact with GABAB receptors. Thus, understanding how the interaction between GABAB receptors and its accessory proteins takes place will definitively open new opportunities for pharmacological tool assessment of novel therapeutic targets for the treatment of several neurological diseases involving these receptors.