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Long and very long chain fatty alcohols are produced from their corresponding acyl-CoAs through the activity of fatty acyl reductases (FARs). Fatty alcohols are important components of the cuticle that protects aerial plant organs, and they are metabolic intermediates in the synthesis of the wax esters in the hull of sunflower (Helianthus annuus) seeds. Genes encoding 4 different FARs (named HaFAR2, HaFAR3, HaFAR4 and HaFAR5) were identified using BLAST, and studies showed that four of the genes were expressed in seed hulls. In this study, the structure and location of sunflower FAR proteins were determined. They were also expressed exogenously in Saccharomyces cerevisiae to evaluate their substrate specificity based on the fatty alcohols synthesized by the transformed yeasts. Three of the four enzymes tested showed activity in yeast. HaFAR3 produced C18, C20 and C22 saturated alcohols, whereas HaFAR4 and HaFAR5 produced C24 and C26 saturated alcohols. The involvement of these genes in the synthesis of sunflower seed wax esters was addressed by considering the results obtained., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by loss-of-function (LOF) mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) gene. In these patients, performing a correct differential diagnosis of pulmonary infections is difficult and challenging, as they usually have atypical presentations. However, establishing a correct diagnostic and therapeutic approach is essential, as pulmonary complications are responsible for high morbidity and mortality rates in these patients. We report the case of a teenage girl with AD-HIES and respiratory symptoms and fever in whom performing a correct differential diagnosis was challenging., (© 2022 Wiley Periodicals LLC.)

A 93-year-old woman with a history of endometrial adenocarcinoma treated with surgery and pelvic radiotherapy that led to radicular stenosis in the sigma and acute biliary pancreatitis, without subsequent cholecystectomy. She attended the emergency department for abdominal pain, vomiting and abdominal distension, with metallic noises. An abdominal CT scan showed a gallbladder with cholelithiasis, in wide contact with the colonic framework and dilation of the colonic loops with hydro-aerial levels with a partially calcified image embedded in the known sigmoid stenosis, compatible with intestinal obstruction. Given the high surgical risk, colonoscopy was performed, which identified an impassable punctate stricture with a fibrous appearance. Pneumatic dilatation and subsequent removal of gallstones with biopsy forceps was performed, with an adequate evolution. While gallstone ileus is a rare condition that accounts for 5% of episodes of intestinal obstruction, its location in the colon is even rarer. It is usually managed surgically, with a significant impact on morbidity. This case is of interest because of the infrequent occurrence of obstruction secondary to these two concomitant causes and the possible usefulness of endoscopic treatment in patients at high surgical risk.

Main Conclusion: Decreased accumulation of polyphenol oxidase, H 2 O 2 accumulation, effective regulation of programmed cell death, and a protein predicted as allergenic can play key roles in cacao defense against Ceratocystis cacaofunesta. Ceratocystis wilt, caused by the fungus Ceratocystis cacaofunesta, has destroyed millions of Theobroma cacao trees in several countries of the Americas. Through proteomics, systems biology, and enzymatic analyses of infected stems, it was possible to infer mechanisms used by resistant (TSH1188) and susceptible (CCN51) cacao genotypes during infection. Protein extraction from xylem-enriched tissue of stems inoculated with the fungus and their controls 1 day after inoculation was carried out, followed by separation through two-dimensional gel electrophoresis and identification by mass spectrometry. Enzyme activity was determined at 1, 3, 7 and 15 days after inoculation. A total of 50 differentially accumulated distinct proteins were identified in the treatments of both genotypes and were classified into 10 different categories. An interaction network between homologous proteins from Arabidospsis thaliana was generated for each genotype, using the STRING database and Cytoscape software. Primary metabolism processes were apparently repressed in both genotypes. The resistance factors suggested for genotype TSH1188 were: H 2 O 2 accumulation, effective regulation of programmed cell death, production of phytoalexins derived from tryptophan and furanocoumarins, and participation of a predicted allergenic protein with probable ribonuclease function inhibiting the germination and propagation of the fungus. In the susceptible genotype, it is possible that its recognition and signaling mechanism through proteins from the SEC14 family is easily overcome by the pathogen. Our results will help to better understand the interaction between cacao and one of its most aggressive pathogens, to create disease control strategies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Children represent a minority of total COVID-19 cases, but studies have reported severe disease and death in pediatric patients. Remdesivir (RDV) has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in children.A nationwide multicenter observational study was conducted on children with confirmed SARS-CoV-2 receiving compassionate treatment with RDV in Spain. Eight patients were included in the study, four infants and four older children [median age 5 years old; IQR 4 months-11.6 years old]. Half of them had complex underlying medical conditions, and the rest were mostly infants (3/4). Six out of eight children needed Pediatric Intensive Care Unit Admission. No RDV-related adverse outcomes were observed in our patients. Seven have reached successful clinical outcome, but one patient with serious clinical status died due to complications. However, she received RDV very late after the first COVID-19 symptom.Conclusions: In our cohort, most of the patients achieved successful clinical outcome, without observing adverse events. Clinical trials of RDV therapy for children with COVID-19 are urgently needed, to assess the safety, tolerability, efficacy, and pharmacokinetics of RDV in children, as this could be an effective treatment in severe cases. What is Known: • Remdesivir has not been approved to treat COVID-19 in children under 12 years old, although the drug is currently being prescribed in critically ill children. • Remdesivir has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in paediatric population. What is New: • We report a multicentre cohort of children with confirmed SARS-CoV-2 and severe COVID-19 disease receiving remdesivir during the first month of the pandemic in Spain. • No remdesivir-related adverse outcomes were observed in most of the cases. Seven patients reached successful clinical outcome, and one died due to complications (bacterial sepsis).

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.

Hepatitis B virus (HBV) infection is estimated to affect 292 million people worldwide, 90% of them are unaware of their HBV status. The Determine HBsAg 2 (Alere Medical Co, Ltd Chiba Japan [Now Abbott]) is a rapid test that meets European Union (EU) regulatory requirements for Hepatitis B surface antigen 2 (HBsAg) analytical sensitivity, detecting the 0.1 IU/mL World Health Organization (WHO) International HBsAg Standard. This prospective, multicentre study was conducted to establish its clinical performance. 351 evaluable subjects were enrolled, 145 HBsAg-positive. The fingerstick whole blood sensitivity and specificity were 97.2% and 98.5% (15' reading, reference assay cut-off 0.05 IU/mL), sensitivity increasing to 97.9% with the prespecified cut-off 0.13 IU/mL (EU regulations). The venous whole blood, serum and plasma sensitivity was 97.2%, 97.9%, and 98.6%, respectively (15' reading); reaching 99%, 99.5% and 100% specificity. A testing algorithm following up an initial positive fingerstick test result with plasma/serum test demonstrates 100% specificity. The Determine HBsAg 2 test gives 15-minute results with high sensitivity and specificity, making it an ideal tool for point-of-care testing, with the potential to enable large-scale population-wide screening to reach the WHO HBV diagnostic targets. The evaluated test improves the existing methods as most of the reviewed rapid tests do not meet the EU regulatory requirements of sensitivity., (© 2020 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.)

Background: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation., Methods: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1β, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1β, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV 1 , pulmonary exacerbations, antibiotic use, nutritional status and quality of life)., Results: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups., Conclusion: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs., Methods: We conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1<40%, chosen from CF units country-wide. For the purposes of the study, they were treated with lumacaftor/ivacaftor 200/125mg two tablets twice a day on a compassionate use programme throughout 2016. The primary endpoint was measured in all of the sample patients. Data were analysed from ppFEV1 at baseline and was measured every 6 months., Results: The mean age was 26.65 (range of 10-45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9kg/m 2 . We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p=0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p=0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment., Conclusions: While treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Cystic Fibrosis (CF) is a genetic disease with equal prevalence across sexes. However, women present worse lung function with faster function decline, earlier onset of bacterial colonization, more frequent pulmonary exacerbations (PE), greater bronchial hyper-responsiveness, and higher mortality rates after puberty than men. The etiology of this gender disparity remains elusive but female hormones have been implicated in several studies., Case Presentation: A 20-year-old female with CF with severe recurrent PE, always related to the menstrual cycle since menarche, combined with lung function decline requiring multiple courses of intravenous antibiotics. We report the cessation of PE and recovery of pulmonary function following the insertion of a subcutaneous implant with 68 mg of etonogestrel (Implanon®, Organon Española S.A. Laboratories, Madrid, Spain)., Conclusion: Our case report supports the key role of female hormones in the development of PE and in the decline of lung function in a woman with CF. When appropriate, hormonal manipulation through contraceptive methods should be considered as potential treatment.

Cough during childhood is very common, and is one of the most frequent reasons for consultation in daily pediatric practice. The causes differ from those in adults, and specific pediatric guidelines should be followed for correct diagnosis and treatment. The most common cause of cough in children is viral infection producing "normal cough", but all children with persistent cough, i.e. a cough lasting more than 4-8weeks or "chronic cough", must be carefully evaluated in other to rule out specific causes that may include the entire pediatric pulmonology spectrum. The treatment of cough should be based on the etiology. Around 80% of cases can be diagnosed using an optimal approach, and treatment will be effective in 90% of them. In some cases of "nonspecific chronic cough", in which no underlying condition can be found, empirical treatment based on the cough characteristics may be useful. There is no scientific evidence to justify the use of over-the-counter cough remedies (anti-tussives, mucolytics and/or antihistamines), as they could have potentially serious side effects, and thus should not be prescribed in children., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

Purpose: Sipoglitazar was a novel, azolealkanoic acid derivative that possesses selective activity for the peroxisome proliferator-activated receptors (PPAR) PPARγ, PPARα, and PPARδ. The compound undergoes phase II biotransformation by conjugation catalyzed by UDP-glucuronosyltransferase (UGT). The aim of this analysis was to explore the influence of genetic polymorphism in UGT on the pharmacokinetics of sipoglitazar., Methods: Three preliminary phase I clinical pharmacology studies were conducted in tandem in healthy human subjects. Genotyping was undertaken in a total of 82 subjects in the phase I program for the purpose of genotyping UGT polymorphisms. Plasma samples were collected for up to 48 h post-dose to characterize the pharmacokinetic profile following a single oral dose of the drug., Results: Plasma concentrations of sipoglitazar and the distribution of dose-normalized individual values for area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) before any stratification were considerably skewed with a multi-modal distribution. The proportion of variability in AUC(0-∞) explained by UGT2B15 was 66.7 % (P < 0.0001); the addition of other genetic or demographic factors was not statistically significant. Subjects homozygous for the UGT2B15 D85Y variant (UGT2B15*2/*2) were exposed to greater plasma concentrations of sipoglitazar than subjects homozygous for the wild-type allele UGT2B15*1/*1 (3.26-fold higher) or heterozygous allele UGT2B15*1/*2 (2.16-fold higher)., Conclusions: These results indicate that sipoglitazar clearance is substantially modified by UGT2B15 enzyme variants, with higher exposure observed in the UGT2B15*2/*2 genotype group.

Objectives: To compare subjective tolerance and secondary adverse events to bowel cleansing prior to colonoscopy with polyethylene glycol (PEG) and sodium phosphate (NaP) in adult patients and in those 65 or more years old., Material and Methods: Retrospective matched study, choosing 140 patients among all of those who underwent colonoscopy from March 2004 to May 2005. We investigated the presence of the next adverse events during bowel preparation: Fever, low digestive bleeding, abdominal pain, perianal pain, nausea, vomiting, thirst, somnolence, agitation, tremor and convulsions. We considered bad objective tolerance if the patient presented any one of these events. We also asked patients about subjective tolerance to preparation., Results: Seventy patients prepared with PEG and seventy with NaP were included (69 women and 71 men, mean age 60.6 +/- 14.8 years). There was no relationship between subjective tolerance or the presence of adverse events and bowel cleansing with any of the products in general population or in elderly patients (p = 0.09 and p = 0.45 in the elderly). However, patients prepared with NaP showed more nausea than those who employed PEG (p < 0.009), overall women of 65 or more years old. There were no severe adverse events in patients prepared with NaP. Elderly showed better tolerance than younger patients, and women worst tolerance than men, irrespective of the lavage preparation employed. Patients prepared with PEG unfinished bowel cleansing more frequently than those with NaP. Cleanliness achieved with NaP was significantly better than that obtained with PEG., Conclusions: Bowel cleansing prior to colonoscopy with NaP is as well tolerated, safe and effective as with PEG, even in elderly healthy patients, although it causes more nausea. Cleanliness with NaP is better than that achieved with PEG.

Purpose: The purpose of this study was to evaluate the radiologic findings in helical CT (HCT) that can be useful to differentiate patients with active Crohn disease (CD) from those in the remission phase., Method: Fifty patients diagnosed with cases of CD were classified into active or remission phases (n = 37 and n = 13, respectively) according to clinical criteria and laboratory data. All of them underwent an abdominal HCT exploration. The following radiologic findings were evaluated: thickness, density and enhancement of the bowel wall, presence of "target" or "double halo," mesenteric involvement, and possible complications., Results: All patients in the active phase had pathologic findings on HCT. The wall thickness was 8.5 (SD 3.2) and 6.5 mm (SD 4 mm) in active and remission phases, respectively (p = 0.06). Target was present in seven patients (19%) with active disease and in five patients (38.5%) in the remission phase (p = 0.15). Density of the wall in the active phase was 95 HU and in the remission phase 65 HU (p < 0.002). Mesentery was involved in 89.2% of patients in the active phase and 38% of patients in the remission phase (p < 0.001). The complications observed in patients with active-phase disease were abscesses in nine (24%), phlegmons in two, fistulas in three, intestinal obstruction in two, and pancreatitis in one., Conclusion: A normal HCT rules out that a patient with CD is in the active phase of disease. The presence of significant bowel wall enhancement and mesentery involvement assists in the differentiation of patients in the active phase from those in remission. HCT is also effective to assess the presence of complications, which are indicative of the active phase.

Aim: To prospectively evaluate the validity of a rapid office-based diagnostic serological test (using capillary blood) in our population, taking as reference a combination of standard diagnostic methods, as well as to compare the results of this technique with those of "classic" serological tests (using venous blood)., Patients and Methods: We prospectively studied 39 consecutive patients with symptoms of the upper digestive tract who had undergone oral gastroscopy. Gastric biopsies were taken for histology and rapid urease testing, and a 13C-urea breath test was performed. An enzyme-linked immunoassay that detects IgG antibodies against Helicobacter pylori was used as a "classic" serological test and the commercial kit FlexPack HP was used as a "rapid" serological test. The endoscopist, the pathologist and those responsible for reading the rapid urease test, the 13C-urea breath test and both serological tests did not know the results of the other diagnostic methods. Patients were considered H. pylori positive when at least two of the three validated tests (rapid urease test, histology, and 13C-urea breath test) revealed infection and were considered free of infection when all tests were negative., Results: Thirty-nine patients were studied. Thirty-eight per cent were male (mean age 48 +/- 15 years). The prevalence of H. pylori infection detected by the gold standard was 69.2%. The sensitivity and specificity of the "classic" serological test was 96% 95% (CI: 79-99) and 91% (59-100). "Rapid" serological testing was positive in nine patients, negative in 28 and indeterminate in two. A single digital puncture was sufficient in 80% of the patients, 15% needed two and 5% needed three. Most patients (77%) had no preference for either type of serological test while 20.5% preferred digital puncture and 2.5% venous puncture. The sensitivity, specificity, positive predictive value and negative predictive value were 31% (16-50), 91% (59-100), 89% (52-100) and 36% (19-56) respectively. Sensitivity was unaffected by age but specificity was lower in patients older than 40 years (89% vs. 100%; McNemar's test: 8; p < 0.01). Kappa's coefficient between the "classic" and the "rapid" serological tests was 0.16 (SE 0.1) and McNemar's test was 12.2 (p < 0.001), which indicates that the prevalence of infection diagnosed by both methods was not homogeneous., Conclusion: The "rapid" office-based serological test used in our study is of insufficient diagnostic accuracy to be used in clinical practice to identify H. pylori infection.

Aim: to analyze the epidemiology, prognosis and treatment of those diagnosed as having cholangiocarcinoma of the extrahepatic biliary tree., Methods: a prospective study including all cases diagnosed over a period of 26 months. Fifteen patients with primary bile duct carcinoma were included., Results: the incidence rate was 3.23 cases/10(4). The tumor locations were: 40% proximal bile duct, 33% distal bile duct, and 27% mid-duct. The treatments used were: curative resection in 1 case (7%); palliative surgery in 3 cases (20%); internal drainage through a prosthetic biliary stent by endoscopic retrograde cholangiopancreatography in 6 cases (40%) and by percutaneous transhepatic cholangiography in 2 cases (13%); external bile drainage in case (7%), and in the remaining 2 patients (13%) no treatment was possible. The 1-month, 6-month and 10-month survival rates were 67%, 40% and 33% respectively. Factors associated with a worse survival in this study were age over 70 years and female sex. The worst prognostic location was the mid-duct compared to the distal and proximal thirds., Conclusions: the incidence of the primary bile duct carcinoma is high in our population. The commonest location is the proximal bile duct. Curative surgical resection is possible in only a few cases, and thus the overall prognosis is very bad.

Purpose: To report on the usefulness of the Activities of Daily Vision Scale (ADVS) questionnaire for assessing visual functioning, a population-based sample of elderly Americans., Methods: The ADVS questionnaire was administered to a population-based sample of 2520 community-dwelling individuals 65 to 84 years of age in Salisbury, MD. Items and subscales were evaluated for internal consistency, item discrimination, and content validity. Published subscale groupings and item associations in our population were compared for coherence using correlation, factor, and cluster analyses. Whole-sample and race- and gender-specific analyses were conducted. External validity was explored by regressing ADVS scores on standard psychophysical vision measures., Results: ADVS scores were skewed to high visual functioning levels; approximately 60% of the population had function scores of 95 or better (of a possible 100). The overall, night driving, and near vision scales were internally consistent and had strong item-subscale associations; the day driving and glare subscales were not acceptable regarding these properties. The far vision subscale was acceptably scalable but only weakly differentiated from the other subscales. Overall, night driving, near vision, and far vision scores were all statistically and independently associated with multiple psychophysical vision measures. Findings were consistent across race and gender subgroups., Conclusions: As assessed by the ADVS, reported visual functioning is high in our representative older population. The overall scale and selected subscales effectively distinguish persons along a spectrum of ability. They correlate with measures of visual impairment in a reasonable way and thus hold promise for risk factor investigations. The published day driving and glare subscales should be examined for relevance and consistency before being applied in population-based settings. Methods specific to population-based settings should be investigated for their ability to better elicit additional visual function dimensions and early visual disability.