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.
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•A cooper complex with a tridentate ONO hydrazone was synthesized.•The hydrazone coordinates to the copper ion in the amido tautomeric form.•XRD reveals that the Cu(II) ion is in a ...distorted square pyramidal environment.•Calculated spectroscopic features show a good agreement with experimental data.•The anticancer activity of the complex is higher than the reported for cisplatin.
The new copper complex, Cu(HL)(OH2)2(NO3), including the tridentate N-acyhydrazone derived from 4-hydroxy-benzohydrazide and 2-hydroxy-3-methoxybenzaldehyde, (H2L), has been synthesized and characterized in the solid state and in solution by spectroscopic (FTIR, Ra, UV–vis, EPR) methods. The results were compared with those obtained for the hydrazone ligand and complemented with computational methods based on DFT. The crystal structure of the complex has been determined by X-ray diffraction. It crystallizes in the triclinic P1¯ space group with Z = 2. The Cu(II) ion is in a distorted square pyramidal environment, coordinated to a planar HL- anion acting as a tridentate ligand. The 5-fold coordination is completed with two water molecules. It is arranged in the lattice as H-bonded ribbon-like polymers that extends along the 1 2 1 crystal direction. The cytotoxicity of the complex together with that of the H2L ligand and the copper ion were evaluated in vitro against five different human cancer cell lines namely A549 (lung), MG-63 (bone), MCF-7 and MDA-MB-231 (breast) and Jurkat (leukemia). The copper complex inhibits the cell viability in a dose dependent manner with a greater potency than the H2L ligand and the free copper ion displaying even higher antitumor activity than the well-known anticancer metallodrug cisplatin.
Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are ...typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range IQR, 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 IQR, 4-18 versus 6 IQR, 3-14),
=0.03; (odds ratio, 1.69 95% CI, 1.08-2.65 for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 IQR, 2-6 versus 2 IQR, 1-4,
<0.001) and death (odds ratio, 4.3 95% CI, 2.22-8.30) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.
In the present paper, we have developed a capillary liquid chromatography with MS detection for the determination at ng
g
−1 levels of four heterocyclic aromatic amines (MeIQx, norharman, harman and ...harmine), a group of mutagenic and carcinogenic compounds that can potentially be produced in protein-rich food during processing operations. They have been determined in commercial ready-to-eat (RTE) smoked salmon and soft cheese treated with E-beam irradiation. On the basis of experimental design studies and operating conditions of MS detector, best chromatographic conditions were obtained using a Luna
® C
18 capillary column (150
mm
×
0.3
mm I.D.) with a mixture of acetonitrile–ammonium formate 5
mM pH 3.6 buffer (13:87, v/v) as mobile phase. To improve sensitivity, large injection volumes (20
μL) and injection solutions of low elution strength were employed. Sample preparation procedure included a previous treatment with 1
M NaOH, followed by two solid-phase extraction steps; firstly on diatomaceous earth and then on mixed-mode cartridges. Heterocyclic amines were detected neither in irradiated and in non-irradiated samples, indicating that they were not formed by the radiation effect even at doses higher than those indicated in the Food Safety Objective established by regulatory agencies. RTE food samples were spiked at concentration levels in the range 10–30
ng
g
−1. Recoveries higher than 85% (
n
=
3 for each spiked level) were obtained, showing the effectiveness of the proposed methodology.
•A new method was optimized to obtain multifunctional extracts from aged garlic.•MAE was more efficient than SLE and UAE for the extraction of bioactives.•Optimized HILIC-ELSD and HPLC-Q MS allowed ...the characterization of garlic extracts.•Sulfur compounds, carbohydrates, amino acids and antioxidant activity were measured.•Bioactive content of MAE extracts was highly dependent on aged garlic processing.
In this work, the simultaneous extraction of bioactives (organosulfur compounds, such as S-allyl-L-cysteine (SAC), carbohydrates, such as neokestose and neonystose, and total phenolic compounds) from aged garlic has been optimized for the first time to obtain multifunctional extracts for further application as food ingredients. Analytical methods using liquid chromatography coupled to mass spectrometry (HPLC-MS) and by hydrophilic interaction liquid chromatography with evaporative light scattering detection (HILIC-ELSD) were also previously optimized. High sensitivity (limits of detection between 0.013 and 0.77 µg mL−1) and appropriate repeatability (< 12%) and accuracy (> 92%) for the analysis of bioactives were achieved. After selecting water as the extraction solvent and microwave-assisted extraction (MAE) as the most efficient technique, operation conditions were optimized using a Box-Behnken experimental design (60 min; 120 °C; 0.05 g mL−1; 1 cycle) to maximize the content of bioactives from different aged garlic samples. Regarding organosulfur compounds, only SAC (traces-2.32 mg g−1 dry sample) and cycloalliin (1.23–3.01 mg g−1 dry sample) were detected in all samples, while amino acids such as arginine (0.24–3.45 mg g−1 dry sample) and proline (0.43–3.91 mg g−1 dry sample) were, in general, the most abundant. Bioactive carbohydrates (from trisaccharides to nonasaccharides) were only detected in fresh garlic and aged garlic processed under mild conditions, whereas all garlic extracts showed antioxidant activity. The developed MAE methodology is shown as a successful alternative to other procedures for the simultaneous extraction of aged garlic bioactives intended by the food and nutraceutical industries, among others.
A method for the analysis of serotonin (5-HT) and its precursors, 5-hydroxytryptophan (5-HTP) and l-tryptophan (TP) in chocolate samples by capillary liquid chromatography–mass spectrometry (cLC–MS) ...has been developed. Optimum chromatographic conditions were established by using a personalized multifactorial experimental design. Finally the cLC separation was achieved through a mixture of acetonitrile and 5mM ammonium formate at pH 4 (3:97, v/v) as mobile phase in gradient elution, setting the injection volume at 10μL and using pure water as injection solvent for focusing purposes on the head of the capillary column. For extraction of targets in chocolate samples a new, fast and simple procedure based on the use of acidic extraction medium and sonication was developed. Working in selected ion mode (m/z 177 for 5-HT, m/z 205 for l-tryptophan and m/z 221 for 5-HTP) detection limits were between 0.01 and 0.11μgg−1 and linearity was in the concentration range of 0.5–25μgg−1. Recoveries higher than 76% with RSDs lower than 8% were obtained from spiked samples for all analytes, showing the effectiveness of the proposed method. Serotonin and its precursors were determined in 5 kinds of commonly consumed chocolates with different cocoa contents (70–100%). The highest serotonin content was found in chocolate with a cocoa content of 85% (2.93μgg−1). Regarding l-tryptophan, the highest content of this amino acid (13.27–13.34μgg−1) was found in chocolate samples with the lowest cocoa content (70–85%). 5-Hydroxytryptophan was not detected in any chocolate samples.
This paper describes a multivariate approach to study the effect on chromatographic conditions and to optimize such conditions in capillary liquid chromatography when high injection volumes are ...required. Several separations have been evaluated by using isocratic and gradient solvent elution, as well as isocratic elution combined with temperature programming. In this study, easily ionisable organic compounds with low log
P have been used as representative analytes. Injection volume and nature of the injection solution have been evaluated in order to increase the sensitivity (peak area) and column performance (
N values). The equations obtained by multiple linear regressions and response surfaces allow achieving the optimum on-column focusing conditions for chlorophenoxy acids, carbamates and heterocyclic amines.
Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness ...of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant.
Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex.
This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up 95% confidence interval (CI) 54.5-70.8, there were no statistically significant differences between the sexes in progression-free survival 6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8 or in overall survival 10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5.
This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.
•Sex and gender are determinants of health inequalities and may affect treatments, tolerability, and therapeutic outcomes.•According to sex, subtle biological and clinical differences exist in advanced gastroesophageal adenocarcinoma.•Women with advanced gastroesophageal adenocarcinoma experience greater toxicity with therapeutic results comparable with men.•Stratification and analysis by sex in studies of gastroesophageal adenocarcinoma should be considered.
The pandemic caused by SARS-COV-2 has caused an increase in the need of tracheostomies in patients affected with respiratory distress syndrome. In this article we report our experience during a year ...of pandemic, we develop our surgical technique to perform percutaneous tracheostomy with the patient in apnea and we compare our results with those of other centers through a bibliographic review.
A one-year retrospective clinical study was carried out on tracheotomies performed on patients admitted to the intensive care unit with severe SARS-CoV-2, with difficulty for ventilation or weaning. The technique performed was percutaneous, with fibroscopic control through the endotracheal tube, keeping the patient under apnea during the opening of the airway, reducing by this method the risk of exposure to the virus.
From 35 percutaneous tracheotomies performed, 31% of the patients died from respiratory complications due to SARS-COV-2, but none due to the surgical procedure. The most frequent complication (8.5% of patients) was bleeding around the tracheostoma, resolved with local measures. No healthcare provider involved in the performance of the technique had symptoms or was diagnosed with COVID-19.
Our technique of performing percutaneous tracheostomy maintaining apnea during the procedure, under fibroscopic control, has proven to be safe for all those involved in the procedure, and for the patient.
In this paper, the enantiomeric separation of two aryloxyphenoxypropionic esters (fluazifop-butyl and quizalofop-ethyl) and a safener herbicide (mefenpyr-diethyl), which is widely used for protecting ...crop plants, has been studied by direct liquid chromatography (LC) with UV detection on an α
1
-acid glycoprotein as chiral stationary phase. Optimization of separation conditions was done by factorial experimental design. Experimental factors and ranges selected were propanol (5–10%), phosphate buffer pH (6.5–7.0), and column temperature (15–25 °C). Responses were expressed in terms of enantioresolution (
R
s
) and adjusted retention time of the second eluted enantiomer (
t
r2
′). The chemometric method used to explore data was response surface analysis. Multiple response analyses were carried out to determine the combination of experimental factors which simultaneously optimize experimental responses. Under optimum conditions for enantioseparation of each herbicide, partially overlapped or fully resolved enantiomers were obtained. Deconvolution tools were employed as an integration method to fit chromatographic data and to achieve a more precise enantiomeric ratio (ER) and enantiomeric fraction (EF) values. Applicability of both direct chiral LC and peak deconvolution methods was evaluated in spiked soil samples at different R/S enantiomeric ratios. Acceptable and reproducible recoveries between 71% and 96% with precision in the range 1–6% were achieved for herbicide-spiked levels from 0.50 to 9.0 μg g
–1
. In addition, parameters such as
R
s
, ER, and EF were calculated and compared with values obtained using the common valley drop integration method.
Figure
Experimental and deconvolved chromatograms obtained for quizalofop-ethyl at two different experimental conditions"
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