The gut microbiota in adults with cystic fibrosis compared to colorectal cancer.

BACKGROUND: Gut dysbiosis is implicated in colorectal cancer (CRC) pathogenesis. Cystic fibrosis (CF) is associated with both gut dysbiosis and increased CRC risk. We therefore compared the faecal microbiota from individuals with CF to CRC and screening samples. We also assessed changes in CRC-associated taxa before and after triple CF transmembrane conductance regulator (CFTR) modulator therapy. METHODS: Bacterial DNA amplification comprising V4 16S rRNA analysis was conducted on 84 baseline and 53 matched follow-up stool samples from adults with CF. These data were compared to an existing cohort of 430 CRC and 491 control gFOBT samples from the NHS Bowel Cancer Screening Programme. Data were also compared to 26 previously identified CRC-associated taxa from a published meta-analysis. RESULTS: Faecal CF samples had a lower alpha diversity and clustered distinctly from both CRC and control samples, with no clear clinical variables explaining the variation. Compared to controls, CF samples had an increased relative abundance in 6 of the 20 enriched CRC-associated taxa and depletion of 2 of the 6 taxa which have been reported as reduced in CRC. Commencing triple modulator therapy had subtle influence on the relative abundance of CRC-associated microbiota (n = 23 paired CF samples). CONCLUSIONS: CF stool samples were clearly dysbiotic, clustering distinctly from both CRC and control samples. Several bacterial shifts in CF samples resembled those observed in CRC. Studies assessing the impact of dietary or other interventions and the longer-term use of CFTR modulators on reducing this potentially pro-oncogenic milieu are needed.

Antineoplastic agents exacerbating Charcot Marie Tooth disease: red flags to avoid permanent disability.

BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common form of hereditary neuropathy. Due to the high prevalence of mild and undiagnosed forms, patients with CMT disease may be exposed to severe neurotoxicity following the administration of neurotoxic chemotherapies. The aim of this report is to alert oncologists to the potential to precipitate severe irreversible peripheral neuropathies when administering neurotoxic compounds to undiagnosed CMT patients. MATERIAL AND METHODS: A retrospective research in the OncoNeuroTox database was performed (2010-2016), searching for patients with the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN) and CMT disease. A comprehensive literature review for previously published cases was performed using the Pubmed and Cochrane databases (1972-2017). RESULTS: Among 428 patients with CIPN, we identified eight patients with concomitant CMT disease. Seven patients out of the eight had no previous diagnosis of CMT disease, although accurate familial history disclosed mild signs of peripheral neuropathy in five cases. Patients themselves had minor stigmata of long-standing peripheral damage. Patients received chemotherapy regimens based on vinca alkaloids, taxanes or a combination of vinca alkaloids and platinum compounds. In two cases, cumulative doses were below or equal to the expected neurotoxic threshold. Following chemotherapy administration, patients developed severe length-dependent sensory-motor deficits. Despite early drug discontinuation, most patients remained severely disabled. CONCLUSION: A brief checklist to disclose long-standing signs of peripheral neuropathy could be helpful to detect patients with undiagnosed hereditary neuropathies who could be at risk of developing severe irreversible neurotoxicity following the administration of neurotoxic agents.

Src, a potential target for overcoming trastuzumab resistance in HER2-positive breast carcinoma.

BACKGROUND: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. METHODS: We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. RESULTS: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. CONCLUSIONS: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.

Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1.

Hindbrain rhombomeres in general are differentially specified molecularly by unique combinations of Hox genes with other developmental genes. Rhombomere 1 displays special features, including absence of Hox gene expression. It lies within the hindbrain range of the Engrailed genes (En1, En2), controlled by the isthmic organizer via diffusion of FGF8. It is limited rostrally by the isthmus territory, and caudally by rhombomere 2. It is double the normal size of any other rhombomere. Its dorsal part generates the cerebellar hemispheres and its ventral part gives rise to several populations, such as some raphe nuclei, the interpeduncular nucleus, the rhabdoid nucleus, anterior, dorsal, ventral and posterodorsal tegmental nuclei, the cholinergic pedunculopontine and laterodorsal tegmental nuclei, rostral parts of the hindbrain reticular formation, the locus coeruleus, and part of the lateral lemniscal and paralemniscal nuclei, among other formations. Some of these populations migrate tangentially before reaching their final positions. The morphogen Sonic Hedgehog (Shh) is normally released from the local floor plate and underlying notochord. In the present report we explore, first, whether Shh is required in the specification of these r1 populations, and, second, its possible role in the guidance of tangentially migrating neurons that approach the midline. Our results indicate that when Shh function is altered selectively in a conditional mutant mouse strain, most populations normally generated in the medial basal plate of r1 are completely absent. Moreover, the relocation of some neurons that normally originate in the alar plate and migrate tangentially into the medial basal plate is variously altered. In contrast, neurons that migrate radially (or first tangentially and then radially) into the lateral basal plate were not significantly affected.

Eduardo Primo Yúfera, founder of Revista de Agroquímica y Tecnología de Alimentos and pioneer on food science and technology research in Spain.

Eduardo Primo Yúfera was the founder and director of the Instituto de Agroquímica y Tecnología de Alimentos (IATA, 1957-1974) until he was appointed president of the Consejo Superior de Investigaciones Científicas (CSIC). His aim to publicize food science led him to create the Revista de Agroquímica y Tecnología de Alimentos in 1961, the forerunner of this journal, Food Science and Technology International, which he directed until 1977. Of his scientific output, 50% has been published in this journal. He is considered to be the promoter and exponent of Food Science and Technology and Chemical Ecology in Spain as well as the instigator of the country's innovation model (R&D and innovation). In his work, he was able to combine basic research excellence and socially relevant applied research to move both science and society forward. He was an example and inspiration to many colleagues and followers. The aim of this study is to highlight the influence and importance of Primo Yúfera in the formation, development and consolidation of the journal Revista de Agroquímica y Tecnología de Alimentos, and to appraise his scientific contribution to this journal.

[Algorithm for an etiological classification of prematurity]. / Algoritmo para la asignación etiológica de la prematuridad.

UNLABELLED: The etiology of preterm birth is difficult to classify. It is usually divided into three clinical types according to its clinical presentation: medically indicated; caused by ruptured membranes; and spontaneous or idiopathic. However, this classification is controversial, imprecise and can result in multiple interpretations when applied. OBJECTIVE: To design an etiologically based classification of preterm birth, and to design a system to easily assign each case during the perinatal period. METHODS: Review of literature, qualitative analysis using consensus methods through nominal group technique, and quantitative analysis of a pilot study using a first version of the algorithm. RESULTS: A classification is made to establish a general division between the "primary cause" and "associated causes" of preterm birth, that allows remote causes or risk factors to be included. The primary cause includes seven categories: inflammatory (ruptured membranes and related); vascular (intrauterine growth restriction and related); maternal-local; maternal-systemic; fetal pathology; fetal distress; idiopathic. The medically indicated preterm birth is defined as a previous or independent category and so is compatible with the other, previously mentioned causes . An algorithm was designed to make it easier to classify the primary cause of preterm birth using a flowchart. CONCLUSIONS: A pragmatic classification of preterm birth is proposed that may help to achieve better precision and agreement between clinicians.

Cauterization of meso-ovarian vessels, a new model of intrauterine growth restriction in rats.

Intrauterine growth restriction (IUGR) remains an important cause of perinatal morbidity and mortality. Both IUGR and low birth weight have been identified as risk factors for increased incidence of cardiovascular disease, dyslipemia, and other diseases in the adulthood. Several animal models have been developed to study the underlying mechanisms of IUGR and its later consequences, with utero-placental ischemia by uterine artery ligation (UAL) being the most frequently used in rats. The relevance of this model lies in the fact that it induces altered placental perfusion, the main cause of IUGR in humans in Western countries. However, there is also controversy over the grade and homogeneity of IUGR obtained. In this study, we propose a new animal model of IUGR related to placental ischemia through the cauterization of meso-ovarian vessels. We aimed to test the feasibility of meso-ovarian vessel cauterization (CMO), and to compare it with uterine artery ligation (UAL). The CMO group had similar incidence of perinatal mortality, percentage of IUGR, and evolution of body weight during early extrauterine life to the UAL group, indicating that both methods are similarly efficient for inducing IUGR. Moreover, both of them affect the ratio of fetal to placental weight, and the weight of vital organs, supporting the hypothesis of a fetal compensatory response or "brain- and heart-sparing effect". Both operative models suffer approximately 50% perinatal mortality, implying that they are both more efficient in the production of IUGR when C-section is performed. On the other hand, CMO was significantly faster to perform than UAL and seemed to produce a more uniform ischemia throughout the uterus than the UAL method, resulting in a more homogeneous group of IUGR pups.

Reducing errors in the management of hyperbilirubinaemia: validating a software application.

OBJECTIVE: To verify the usefulness and reliability of a software tool we developed to help to apply the American Academy of Pediatrics (AAP) Guidelines 2004 on hyperbilirubinaemia according to the infant's age in hours and their clinical risk factors. DESIGN: Randomised, cross-over, controlled trial with 20 simulated clinical cases comparing the "manual" application of the guidelines with our software application. PARTICIPANTS: Fifteen doctors (eight final-year residents and seven consultants) from two hospitals in Spain. MAIN OUTCOME MEASURES: Major errors (defined a priori as any deviation from the AAP guidelines that involve a risk of morbidity or mortality for the patient), minor errors (those that cause discomfort and/or, in extremely rare cases, morbidity) and time spent. RESULTS: Fifteen doctors each managed 20 simulated cases, half by using the guidelines alone and half using the software tool. Without the software application, 42 "minor" errors were made. With it, only 25 errors were made. "Major" errors also decreased from 10 to 2 with the software. As a group, the residents benefited most; they made an average of 1.8 errors fewer per 10 cases. Use of the software reduced the time taken by the residents to resolve the cases, although the mean reduction in time was not significant for the group of consultants. CONCLUSIONS: The use of simulated clinical cases revealed many errors in the routine management of hyperbilirubinaemia. The software helped clinicians make fewer errors and saved time for residents, but not consultants.

A solid-phase extraction and size-exclusion liquid chromatographic method for polyethylene glycol 25 p-aminobenzoic acid determination in urine: validation for urinary excretion studies of users of sunscreens.

No previous publications about percutaneous absorption of polyethylene glycol 25 p-aminobenzoic acid (PEG-25 PABA) have been found in the literature and the expected levels to be found in human urine after sunscreens use are unknown. The method proposed here is suitable to determine PEG-25 PABA in the urine of sunscreens users in order to carry out studies on body accumulation/excretion. It is based on solid-phase extraction (SPE) with size-exclusion liquid chromatography determination. Solid-phase extraction allows the analyte to be retained and subsequently eluted for a clean-up, using a silica-based cartridge. The size-exclusion liquid chromatography of the eluted allows the rest of matrix interferences to be avoided. Fluorescence intensity was measured at lambda(em)=350 nm (lambda(exc)=300 nm). The sensitivity of the proposed method is in the order of 450+/-5 mLng(-1) and the detection limit (3S(y/x)/b) in the measured solutions is in the order of 13 ngmL(-1), that is 2.6 ngmL(-1) in urine samples. The method enables PEG-25 PABA to be determined in both, spiked and unspiked human urine samples. Results obtained for spiked human urine samples (11-100 ngmL(-1)) demonstrated the accuracy of the method. The mean relative standard deviation of the results was in the order of 3-10%. Three volunteers applied a sunscreen lotion containing a 8% PEG-25 PABA sunscreen cream and their urinary excretion was controlled from the moment of application until the excreted amounts were no longer detectable.

A reversed-phase ion-interaction chromatographic method for in-vitro estimation of the percutaneous absorption of water-soluble UV filters.

An analytical method based on ion-interaction chromatography with UV detection for simultaneous in-vitro estimation of the percutaneous absorption of the most used water-soluble UV filters in sunscreen cosmetics is proposed. These UV filters were phenylbenzimidazole sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, benzophenone-4, and terephthalylidene dicamphor sulfonic acid. The methodology is based on applying the sunscreen containing the target UV filters to human epidermis in a diffusion cell. Analytes are determined in the receptor solution. To ensure skin integrity, screening of the cells was carried out by analytical determination of a marker. Analytical variables such as percentage ethanol, concentration of ion-pairing agent, pH of the mobile phase, and temperature were studied in order to achieve high resolution of the chromatographic peaks in the lowest possible time of analysis. The conditions selected consisted of a mobile phase composed of 35:65 (v/v) ethanol-ammonium acetate buffer solution (pH 4, containing 50 mmol L(-1) tetra-n-butylammonium bromide). The chromatographic determination was carried out with the analytical column at 50 degrees C. UV detection was carried out at the maximum absorption wavelength for each analyte. The limit of detection (3s(y/x)/b) ranged from 16 to 65 ng mL(-1), depending on the analyte.

Infant position in neonates receiving mechanical ventilation.

BACKGROUND: Several body positions other than standard supine position have been used in patients undergoing intensive care for reducing the incidence of pressure ulcers of the skin, contractures or ankylosis and for improving the patient's well being. In patients from different age groups undergoing mechanical ventilation (MV), it has been observed that particular positions, such as prone position, may improve some respiratory parameters. Benefits from these positions have not been clearly defined in critically ill newborns who may require mechanical ventilation for extended periods of time. OBJECTIVES: To assess the effects of different positioning of newborn infants receiving MV on short term respiratory outcomes and complications of prematurity. SEARCH STRATEGY: Databases searched (up to May 2006) were the Oxford Database of Perinatal Trials, CINAHL, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006). Hand searches of proceedings of the Society for Pediatric Research from 1990 to May 2006 were used to identify unpublished studies. SELECTION CRITERIA: Randomised or quasi randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. DATA COLLECTION AND ANALYSIS: Three independent and unblinded reviewers assessed the trials for inclusion in the review and extracted the data. Data were double-checked and entered into the Review Manager software. MAIN RESULTS: Eleven trials involving 206 infants were included in this review. Several positions were compared: prone vs. supine, prone vs. lateral right, lateral right vs. supine, lateral left vs. supine, lateral right vs. lateral left and good lung dependent vs. good lung uppermost. Apart from one of the two studies that compared lateral right vs. lateral left positions, and one comparing prone vs. supine position, all the included studies had a crossover design. Comparing prone vs. supine position, an increase in arterial P02 in the prone position of between 2.75 and 9.72 mm Hg (95% CI) was observed (one trial). When % hemoglobin oxygen saturation was measured with pulse oximetry, improvement in the prone position was from 1.18 to 4.36% (typical effect based on four trials). In addition, there was a slight improvement in the number of episodes of desaturation. It was not possible to establish whether this effect remained once the intervention was stopped. Negative effects from the interventions were not described, although this issue was not studied in sufficient detail. Effects of position on other outcomes were not statistically significant; however, either positive nor negative effects cannot be excluded considering the small numbers that were studied. AUTHORS' CONCLUSIONS: The prone position was found to slightly improve the oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence concerning whether particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvements.

A liquid chromatography-fluorimetric method for the in vitro estimation of the skin penetration of disodium phenyldibenzimidazole tetrasulfonate from sunscreen formulations through human skin.

Disodium phenyldibenzimidazole tetrasulfonate (PDT) is a new organic UV filter with hydrophilic properties used in modern sunscreen spray formulations. The aim of this work was to develop and validate an analytical method that can be used to study skin absorption of PDT from sunscreens. Results obtained in vitro for human skin showed a low level of absorption. The proposed in vitro method employs a diffusion cell. Sunscreen lotion was applied onto pretreated human skin, which was then placed in the cell. PDT was collected in a receptor liquid, the surface of which was in contact with the skin. The solutions obtained were diluted appropriately and analyzed by liquid chromatography without any interference. The analytical features of chromatographic determination with fluorimetic detection were suited to this analytical problem, since this method gave a limit of detection of 1 ng ml(-1). Phenol red (PR) was used as a marker to check the skin integrity, and a sensitive method based on sequential injection on-line solid-phase extraction coupled with spectrophotometric detection was developed for determining this marker in the receptor liquid in order to screen the cells.

Sequential-injection determination of traces of disodium phenyl dibenzimidazole tetrasulphonate in urine from users of sunscreens by on-line solid-phase extraction coupled with a fluorimetric detector.

A sensitive and selective method to determine disodium phenyl dibenzimidazole tetrasulphonate (PDT) in the urine of sunscreen users, which is suitable for studies on body accumulation/excretion is proposed. On-line solid-phase extraction allows the analyte to be retained and subsequentely eluted, using a strong anion exchange (SAX) microcolumn. Standard addition calibration was carried out with only one standard. The wavelengths of excitation and emission were 330 and 454 nm, respectively. The method allows PDT to be determined in both, spiked and unspiked human urine samples, without any pre-treatment. Results obtained for spiked urine samples (40-200 ng ml(-1)) showed the accuracy of the method. The mean relative standard deviations (R.S.D.) of the results was 7%. Five volunteers applied a sunscreen lotion containing 5% PDT and their urinary excretion was controlled from the moment of application until the excreted amounts were no longer detectable. The sensitivity of the proposed method is in the order of 1900 ml microg(-1) and the detection limit (3S(y/x)/b) is in the order of 5 ng of PDT, which means 10 ng ml(-1) for a 500 microl injected volume, and this is suitable for the PDT levels found in the urine.

Infant position in neonates receiving mechanical ventilation.

BACKGROUND: Several body positions other than standard supine position have been used in patients undergoing intensive care for reducing the incidence of pressure ulcers of the skin, contractures or ankylosis and for improving the patient's well being. In patients from different age groups undergoing mechanical ventilation (MV), it has been observed that particular positions such as prone position may improve some respiratory parameters. Benefits from these positions have not been clearly defined in Neonatology, a field where it is common that patients require mechanical ventilation sometimes during extended time periods. OBJECTIVES: To assess the effects on both short and long-term outcomes of different positioning of newborn infants receiving MV. SEARCH STRATEGY: Databases searched (up to January 2002) were the Oxford Database of Perinatal Trials, CINAHL, MEDLINE, EMBASE and Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002). Hand searches of proceedings of the Society for Pediatric Research from 1990 to January 2002 were used to identify unpublished studies. SELECTION CRITERIA: Randomised or quasi randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. DATA COLLECTION AND ANALYSIS: Three independent and unblinded reviewers assessed the trials for inclusion in the review and extracted the data. Data were double-checked and entered into the Review Manager software. MAIN RESULTS: Ten trials involving 164 infants were included in this review. Several positions were compared: prone vs. supine, prone vs. lateral right, lateral right vs. supine, lateral left vs. supine, lateral right vs. lateral left and good lung dependent vs. good lung uppermost. Apart from one of the two studies that compared lateral right vs. lateral left positions, all the included studies had a crossover design. Comparing prone vs. supine position, an increase in arterial P02 in the prone position of between 2.75 and 9.72 mm Hg (95%CI) was observed (one trial). When % hemoglobin oxygen saturation was measured with pulse oximetry, improvement in the prone position was from 1.17 to 4.36% (typical effect based on four trials). It was not possible to establish whether this effect remained once the intervention was stopped. Negative effects from the interventions were not described, although this issue was not studied enough. Effects of position on other outcomes were not statistically significant; however, these cannot be excluded considering the small numbers that were studied. REVIEWER'S CONCLUSIONS: The prone position was found to slightly improve the oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence concerning whether particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvements.

Chilaiditi syndrome associated with transverse colon volvulus: first report in a paediatric patient and review of the literature.

A hepatodiaphragmatic interposition of the colon, known as Chilaiditi's sign, is usually discovered by chance during the study of another event, given that its presentation is normally asymptomatic. When this finding is accompanied by clinical symptoms, either intermittent or persistent, it is known as Chilaiditi syndrome. It may be associated with intestinal obstruction due to twisting. The association of Chilaiditi syndrome and transverse colon volvulus is exceptional. To date only three cases have been reported, all in adult males. Among the common predisposing factors were anatomical alterations of the intestine such as elongation of the colon and a history of prior abdominal surgery. The clinical symptoms were due to the intestinal obstruction. We present the first description in the paediatric population of an association of transverse colon volvulus and Chilaiditi syndrome whose predisposing factors, clinical symptoms and treatment differed from those reported in the non-paediatric cases published to date.

Attractiveness of 79 compounds and mixtures to wild Ceratitis capitata (Diptera: Tephritidae) in field trials.

Seventy-nine volatile compounds chosen from those emitted by Mediterranean fruit fly males, fruits and food baits, were tested for their attractiveness to females of Ceratitis capitata (Wiedemann) in field trials with a wild population. To correct for density fluctuations, the results were presented as a percentage of males caught in the same type of traps baited with trimedlure, a known male attractant. The mixtures of corn steep liquor with ammonia compounds and amines were the most effective attractants for females. Other compounds exhibiting C. capitata attraction were a mixture ethyl acetate+acetic acid+ethanol for both sexes, and p-cymene, 1,3-diethylbenzene and borneol for females.