Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. ...High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management.
Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.
Introduction: Medical students represent a new generation of medical thought, and if they have a favourable attitude towards organ donation this will greatly encourage its promotion.
Objective: To ...analyse the attitude of medical students in Spanish universities towards the donation of their own organs and to determine the factors affecting this attitude.
Material and Methods: Type of study: A sociological, interdisciplinary, multicentre, and observational study in Spain. Study population: Students studying a degree in medicine enrolled in Spain (n = 34,000). Sample size: A sample of 9598 students (confidence of 99% and precision of ±1%), stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ donation and transplantation (PCID-DTO RIOS) was self-administered and completed anonymously.
Results: The questionnaire completion rate was 95.7% (n = 9.275). 80% were in favour of donation, 2% against and 18% were undecided. The following main variables were related to a favourable attitude: being of the female sex (Odds Ratio = 1.739); being in the sixth year of the degree (OR = 2.506); knowing a donor (OR = 1.346); having spoken about the subject with one's family (OR = 2.132) and friends (OR = 1.333); having a family circle that is in favour, more specifically, having a father (OR = 1.841), mother (OR = 2.538) or partner in favour (OR = 2.192); being a blood donor (OR = 2.824); acceptance of the mutilation of the body if it were necessary (OR = 2.958); and being an atheist or an agnostic (OR = 1.766).
Conclusions: Spanish medical students generally have a favourable attitude towards organ donation, although 20% are not in favour.
Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This ...randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT.
Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT 7 weeks of radiotherapy (RT) with cisplatin 100 mg/m2 on days 1, 22 and 43; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF).
In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6–20.4), 14.3 (95% CI, 11.8–19.3) and 13.8 months (95% CI, 11.0–17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9–11.8), 7.9 (95% CI, 6.5–11.8) and 8.2 months (95% CI, 6.7–12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable.
Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN (ClinicalTrials.gov number, NCT00261703).
APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV ...(SDSS-IV). APOGEE-2 is expanding on APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.
There is a critical need for improved methane-oxidation catalysts to both reduce emissions of methane, a greenhouse gas, and improve the performance of gas turbines. However, materials that are ...currently available either have low activity below 400°C or are unstable at higher temperatures. Here, we describe a supramolecular approach in which single units composed of a palladium (Pd) core and a ceria (CeO(2)) shell are preorganized in solution and then homogeneously deposited onto a modified hydrophobic alumina. Electron microscopy and other structural methods revealed that the Pd cores remained isolated even after heating the catalyst to 850°C. Enhanced metal-support interactions led to exceptionally high methane oxidation, with complete conversion below 400°C and outstanding thermal stability under demanding conditions.
Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late ...stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.
Yebes 40m radio telescope is the main and largest observing instrument at Yebes Observatory and it is devoted to Very Long Baseline Interferometry (VLBI) and single dish observations since 2010. It ...has been covering frequency bands between 2 GHz and 90 GHz in discontinuous and narrow windows in most of the cases, to match the current needs of the European VLBI Network (EVN) and the Global Millimeter VLBI Array (GMVA).
Nanocosmos project, a European Union funded synergy grant, opened the possibility to increase the instantaneous frequency coverage to observe many molecular transitions with single tunnings in single dish mode. This reduces the observing time and maximises the output from the telescope.
We present the technical specifications of the recently installed 31.5 - 50GHz (Q band) and 72 - 90.5 GHz (W band) receivers along with the main characteristics of the telescope at these frequency ranges. We have observed IRC+10216, CRL 2688 and CRL 618, which harbour a rich molecular chemistry, to demonstrate the capabilities of the new instrumentation for spectral observations in single dish mode.
The results show the high sensitivity of the telescope in the Q band. The spectrum of IRC+10126 offers a signal to noise ratio never seen before for this source in this band. On the other hand, the spectrum normalised by the continuum flux towards CRL 618 in the W band demonstrates that the 40 m radio telescope produces comparable results to those from the IRAM 30 m radio telescope, although with a smaller sensitivity. The new receivers fulfil one of the main goals of Nanocosmos and open the possibility to study the spectrum of different astrophysical media with unprecedented sensitivity.
Summary
Background
Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment ...of low‐flow vascular malformations, but its usefulness in high‐flow vascular malformations is controversial.
Aim
To evaluate the efficacy and safety of sirolimus for the treatment of high‐flow vascular malformations in real‐life practice.
Methods
In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high‐flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed.
Results
Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1–4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high‐flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow‐up, five patients remained on treatment with oral sirolimus.
Conclusion
Our results show that oral sirolimus is a well‐tolerated therapeutic option, with an excellent safety profile, which can be useful in the long‐term stabilization of patients with high‐flow vascular malformations. Single‐daily dosage may improve long‐term adherence to treatment without worsening its effectiveness.
Aims/hypothesis We analysed the factors that determine the outcomes of surgical treatment of osteomyelitis of the foot in diabetic patients given early surgical treatment within 12 h of admission and ...treated with prioritisation of foot-sparing surgery and avoidance of amputation. Methods A consecutive series of 185 diabetic patients with foot osteomyelitis and histopathological confirmation of bone involvement were followed until healing, amputation or death. Results Probing to bone was positive in 175 cases (94.5%) and radiological signs of osteomyelitis were found in 157 cases (84.8%). Staphylococcus aureus was the organism isolated in the majority of cultures (51.3%), and in 35 cases (36.8%) it proved to be methicillin-resistant. The surgical treatment performed included 91 conservative surgical procedures, which were defined as those where no amputation of any part of the foot was undertaken (49.1%). A total of 94 patients received some degree of amputation, consisting of 79 foot-level (minor) amputations (42.4%) and 15 major amputations (8%). Five patients died during the perioperative period (2.7%). Histopathological analysis revealed 94 cases (50.8%) of acute osteomyelitis, 43 cases (23.2%) of chronic osteomyelitis, 45 cases (24.3%) of acute exacerbation of chronic osteomyelitis and three remaining cases (1.6%) designated as 'other'. The risks of failure in the case of conservative surgery were exposed bone, the presence of ischaemia and necrotising soft tissue infection. Conclusions/interpretation Conservative surgery without local or high-level amputation is successful in almost half of the cases of diabetic foot osteomyelitis. Prospective trials should be undertaken to determine the relative roles of conservative surgery versus other approaches.
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