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1.
Front Med (Lausanne) ; 11: 1407812, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983363

RESUMEN

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

2.
Rev Esp Enferm Dig ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958154

RESUMEN

INTRODUCTION: The early diagnosis of achalasia requires a high degree of clinical suspicion, and delays in diagnosis are frequent. High-resolution oesophageal manometry (HRM) is the gold standard for its diagnostic confirmation. There are two HRM systems, perfusion and solid-state, which allow its classification into three subtypes: I, or classical; II, or with pan-oesophageal pressurization; and III, or spastic. OBJECTIVE: To determine the clinical and manometric characteristics of the three subtypes with high-resolution perfusion and solid-state equipment and the time of evolution until diagnosis. METHODS: This was a multicentre, observational, retrospective study of patients from the INTEGRA database of the Spanish Association of Neurogastroenterology and Motility who were diagnosed with primary achalasia confirmed by HRM, who fell under the Chicago Classification v3.0, and who had not been treated. RESULTS: The study included 110 patients (subtype I, N = 14; subtype II, N = 73; subtype III, N = 23). The HRM equipment was perfusion for 49 and solid-state for 61. The mean age was 61.8 ± 14 years (age range 44-81), the age was lower in subtype II, and the sex distribution was similar. The time of clinical evolution until diagnosis was > 12 months (51.6%), subtype II being the one that was diagnosed earlier and the most often (66.3%). Dysphagia was the most frequent symptom (90.5%). According to the comparative analysis by high-resolution perfusion and solid-state oesophageal manometry equipment, the baseline pressure of the lower oesophageal sphincter was higher in the solid-state oesophagus, but the difference was not statistically significant. The median integrated relaxation pressure at 4 seconds (IRP4) was similar (21 mmHg) between the perfusion and solid-state measurements. We describe the ranges of IRP4 in achalasia patients with both systems and confirm the possibility of achalasia even when IRP4 is within the normal range. CONCLUSIONS: Achalasia in our environment has a significant diagnostic delay. No significant differences were observed in the oesophagogastric junction between the two groups diagnosed with perfusion and solid-state equipment.

3.
Heliyon ; 10(11): e32330, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38961931

RESUMEN

The evaluation of the university experience of students is an increasingly frequent field of analysis among the academic community, as they represent one of the most important groups in universities and it is essential to know their opinion and satisfaction with the different services and resources that the university institution makes available to them. In this sense, the two objectives of the study were the following: 1) To analyse the undergraduate university experience of the different groups of students (graduates, students, drop-outs). 2) To identify which aspects of the academic training received predict each of the student groups. To this end, a study was carried out specifically aimed at undergraduate education students at the University of Granada (Spain), distinguishing between graduates, students, and those who had dropped out of their studies. A total of 292 students participated (82 female and 210 male), of whom 123 were graduates, 98 were still students and 71 were drop-outs. After the application of three questionnaires, it was found that the three aforementioned groups of participants coincided in particularly valuing characteristic dimensions of the formal teaching-learning scenario in the university experience. In addition, the linear regression analysis carried out identified the personalised attention factor as having the highest predictive value as regards student type. Thus, the results of the study point to an assessment of academic training focused on the need on the part of all three groups of participants for teacher support and individualised guidance. The study may be useful in providing universities with new data to help improve the teaching performance of Education degree teaching staff concerning students; for example, by encouraging their participation in tutorial action programmes.

4.
Rev Esp Enferm Dig ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967269

RESUMEN

Acute pancreatitis is a common condition in Gastroenterology. Among its possible etiologies are ampullary tumors, rare neoplasms whose growth can hinder pancreatic drainage. Although they are usually epithelial, adenomas and adenocarcinomas, less commonly other histological types have been reported, such as neuroendocrine tumors. They constitute a small percentage of both ampullary tumors and neuroendocrine tumors of the digestive tract, classified into three histological grades based on mitotic count and Ki-67. Although the diagnosis is usually incidental, its main form of presentation is clinical or analytical cholestasis, with acute pancreatitis being an exceptional initial presentation. Endoscopic resection is the treatment of choice for well-differentiated tumors without evidence of local infiltration of the duodenal wall or intraductal growth greater than 10mm, with endoscopic ultrasound playing a key role in this assessment. We present the case of a 45-year-old cholecystectomized woman who was admitted to our service with a condition compatible with acute pancreatitis, initially suspected to be of biliary origin. After several radiological and endoscopic studies, an enlargement of the duodenal papilla suggestive of ampulloma was detected. Histological examination demonstrated a well-differentiated neuroendocrine tumor of the duodenal papilla which, lacking evidence of local duodenal infiltration or intraductal growth, was successfully resected endoscopically.

5.
Drug Deliv ; 31(1): 2372285, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38952133

RESUMEN

In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.


Asunto(s)
Achillea , Proliferación Celular , Quitosano , Ácido Clorogénico , Neoplasias Colorrectales , Nanopartículas , Tamaño de la Partícula , Extractos Vegetales , Quitosano/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Achillea/química , Ácido Clorogénico/farmacología , Ácido Clorogénico/administración & dosificación , Ácido Clorogénico/química , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Línea Celular Tumoral , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacología , Ácido Quínico/química , Ácido Quínico/administración & dosificación , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Colon/efectos de los fármacos , Colon/metabolismo , Portadores de Fármacos/química , Peso Molecular
6.
Foods ; 13(11)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38890841

RESUMEN

Food fraud is a major threat to the integrity of the nut supply chain. Strategies using a wide range of analytical techniques have been developed over the past few years to detect fraud and to assure the quality, safety, and authenticity of nut products. However, most of these techniques present the limitations of being slow and destructive and entailing a high cost per analysis. Nevertheless, near-infrared (NIR) spectroscopy and NIR imaging techniques represent a suitable non-destructive alternative to prevent fraud in the nut industry with the advantages of a high throughput and low cost per analysis. This review collects and includes all major findings of all of the published studies focused on the application of NIR spectroscopy and NIR imaging technologies to detect fraud in the nut supply chain from 2018 onwards. The results suggest that NIR spectroscopy and NIR imaging are suitable technologies to detect the main types of fraud in nuts.

7.
Mol Biol Rep ; 51(1): 763, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874813

RESUMEN

BACKGROUND: Arabidopsis thaliana primary root growth has become a model for evo-devo studies due to its simplicity and facility to record cell proliferation and differentiation. To identify new genetic components relevant to primary root growth, we used a Genome-Wide Association Studies (GWAS) meta-analysis approach using data published in the last decade. In this work, we performed intra and inter-studies analyses to discover new genetic components that could participate in primary root growth. METHODS AND RESULTS: We used 639 accessions from nine different studies under control conditions and performed different GWAS tests. We found that primary root growth changes were associated with 41 genes, of which six (14.6%) have been previously described as inhibitors or promoters of primary root growth. The knockdown lines of two genes, Suppressor of Gene Silencing (SGS3), involved in tasiRNA processing, and a gene with a Sterile Alpha Motif (SAM) motif named NOJOCH MOOTS (NOJO), confirmed their role as repressors of primary root growth, none has been shown to participate in this developmental process before. CONCLUSIONS: In summary, our GWAS analysis of different available studies identified new genes that participate in primary root growth; two of them were identified as repressors of primary root growth.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Estudio de Asociación del Genoma Completo , Raíces de Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Estudio de Asociación del Genoma Completo/métodos , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas/genética , Polimorfismo de Nucleótido Simple/genética , Fenotipo , Genes de Plantas/genética
8.
J Clin Med ; 13(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38892848

RESUMEN

Background/Objectives: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease leading to significant morbidity and mortality. Despite advances in genetic diagnosis, the underlying pathophysiology remains incompletely understood. Proteomic studies offer insights into disease mechanisms by identifying altered protein expression patterns. Here, we conducted a proteomic analysis to elucidate molecular pathways associated with CADASIL. Methods: We enrolled genetically diagnosed CADASIL patients and healthy, genetically related controls. Plasma samples were subjected to proteomic analysis using the Olink platform, measuring 552 proteins across six panels. The data were analyzed from several approaches by using three different statistical methods: Exploratory Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), differential expression with moderated t-test, and gene set enrichment analysis (GSEA). In addition, bioinformatics analysis, including volcano plot, heatmap, and Variable Importance on Projection (VIP) scores from the PLS-DA model were drawn. Results: Significant differences in protein expression were observed between CADASIL patients and controls. RSPO1 and FGF-19 exhibited elevated levels (p < 0.05), while PPY showed downregulation (p < 0.05) in CADASIL patients, suggesting their involvement in disease pathogenesis. Furthermore, MIC-A/B expression varied significantly between patients with mutations in exon 4 versus exon 11 of the NOTCH3 gene (p < 0.05), highlighting potential immunological mechanisms underlying CADASIL. We identified altered pathways using GSEA, applied after ranking the study data. Conclusions: Our study provides novel insights into the proteomic profile of CADASIL, identifying dysregulated proteins associated with vascular pathology, metabolic dysregulation, and immune activation. These findings contribute to a deeper understanding of CADASIL pathophysiology and may inform the development of targeted therapeutic strategies. Further research is warranted to validate these biomarkers and elucidate their functional roles in disease progression.

9.
Materials (Basel) ; 17(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38893887

RESUMEN

The European Fusion Reactor (DEMO, Demonstration Power Plant) relies significantly on joining technologies in its design. Current research within the EUROfusion framework focuses on developing materials for the first wall and divertor applications, emphasizing the need for suitable joining processes, particularly for tungsten. The electric field-assisted sintering technique (FAST) emerges as a promising alternative due to its high current density, enabling rapid heating and cooling rates for fast sintering or joining. In this study, FAST was employed to join tungsten and EUROFERE97 steel, the chosen materials for the first wall, using 50-µm-thick Cu foils as interlayers. Three distinct joining conditions were tested at 980 °C for 2, 5, and 9 min at 41.97 MPa to optimize joint properties and assess FAST parameters influence. Hardness measurements revealed values around 450 HV0.1 for tungsten, 100 HV0.1 for copper, and 390 HV0.1 for EUROFER97 under all joining conditions. Increasing bonding time improved joint continuity along the EUROFER97/Cu and W/Cu interfaces. Notably, the 5 min bonding time resulted in the highest shear strength, while the 9 min sample exhibited reduced strength, possibly due to Kirkendall porosity accumulation at the EUROFER97/Cu interface. This porosity facilitated crack initiation and propagation, diminishing interfacial adhesion properties.

10.
Sensors (Basel) ; 24(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38894428

RESUMEN

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.


Asunto(s)
Espectroscopía Dieléctrica , Electrodos , Insuficiencia Cardíaca , Textiles , Dispositivos Electrónicos Vestibles , Humanos , Insuficiencia Cardíaca/fisiopatología , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Espectroscopía Dieléctrica/métodos , Espectroscopía Dieléctrica/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Edema/diagnóstico , Anciano
11.
Obes Sci Pract ; 10(3): e759, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38903852

RESUMEN

Background: The prevalence of excess weight and obesity is increasing in an extremely concerning manner worldwide, with highly diverse therapies for current treatment. This review evaluated the scientific evidence of the past 10 years on the use of probiotics in treating excess weight and obesity in the absence of dieting. Materials: A systematic review was conducted by searching for clinical trials on humans published in English in the PubMed, Scopus and Cochrane Central databases, using the combination of keywords "Overweight", "Probiotics" and "Obesity", and published between 2012 and 2022. Results: Six published studies met the inclusion criteria. The review showed that, although there is a lack of consensus in the literature, the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies, a significant reduction in waist circumference in 80.0% of the reviewed studies, and an improvement in total body fat mass and waist circumference. Conclusions: This review showed evidence of a trend in preventing body weight gain and reducing weight through the use of probiotics in individuals with excess weight or obesity. A combination of various strains of the genera Bifidobacterium and Lactobacillus was the most effective.

12.
PLoS One ; 19(6): e0304268, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38838004

RESUMEN

American tegumentary leishmaniasis (ATL) diagnosis is an open question, and the search for a solution is urgent. The available tests that detect the etiological agent of the infection are specific for ATL diagnosis. However, they present disadvantages, such as low sensitivity and the need for invasive procedures to obtain the samples. Immunological methods (leishmanin skin test and search for anti-Leishmania antibodies) are good alternatives to the etiological diagnosis of ATL. Presently, we face problems with disease confirmation due to the discontinuity in the production of leishmanin skin test antigen, particularly in resource-poor settings. Aiming to diagnose ATL, we validated rLb6H-ELISA for IgG antibodies using 1,091 samples from leishmaniasis patients and healthy controls, divided into four panels, living in 19 Brazilian endemic and non-endemic states. The rLb6H-ELISA showed a sensitivity of 98.6% and a specificity of 100.0%, with the reference panel comprising 70 ATL patient samples and 70 healthy controls. The reproducibility evaluation showed a coefficient of variation of positive samples ≤ 8.20% for repeatability, ≤ 17,97% for reproducibility, and ≤ 8.12% for homogeneity. The plates sensitized with rLb6H were stable at 4°C and -20°C for 180 days and 37°C for seven days, indicating 12 months of validity. In samples of ATL patients from five research and healthcare centers in endemic and non-endemic areas, rLb6H-ELISA showed a sensitivity of 84.0%; no significant statistical difference was observed among the five centers (chi-square test, p = 0.13). In samples of healthy controls from four areas with different endemicity, a specificity of 92.4% was obtained; lower specificity was obtained in a visceral leishmaniasis high endemicity locality (chi-square test, p<0.001). Cross-reactivity was assessed in 166 other disease samples with a positivity of 13.9%. Based on the good diagnostic performance and the reproducibility and stability of the antigen, we suggest using ELISA-rLb6H to diagnose ATL.


Asunto(s)
Antígenos de Protozoos , Ensayo de Inmunoadsorción Enzimática , Leishmaniasis Cutánea , Humanos , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/epidemiología , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos de Protozoos/inmunología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Sensibilidad y Especificidad , Adolescente , Reproducibilidad de los Resultados , Proteínas Recombinantes/inmunología , Adulto Joven , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Anciano , Niño , Estudios de Casos y Controles , Brasil/epidemiología
13.
J Clin Nurs ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38932443

RESUMEN

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

14.
Nat Commun ; 15(1): 5321, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909051

RESUMEN

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.


Asunto(s)
Alucinógenos , Núcleo Hipotalámico Paraventricular , Psilocibina , Ratas Sprague-Dawley , Animales , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Masculino , Psilocibina/análogos & derivados , Psilocibina/farmacología , Psilocibina/administración & dosificación , Femenino , Ratas , Alucinógenos/farmacología , Alucinógenos/administración & dosificación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Conducta Animal/efectos de los fármacos , Estrés Psicológico/fisiopatología , Estrés Psicológico/tratamiento farmacológico
15.
Genes (Basel) ; 15(6)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38927623

RESUMEN

HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.


Asunto(s)
Claudinas , Humanos , Masculino , Claudinas/genética , Adulto , Ictiosis/genética , Ictiosis/patología , Hipohidrosis/genética , Displasia Ectodérmica/genética , Displasia Ectodérmica/patología , Linaje , Fenotipo
17.
BMC Cancer ; 24(1): 676, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831273

RESUMEN

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Persona de Mediana Edad , Estudios de Casos y Controles , Estudios Prospectivos , Europa (Continente)/epidemiología , Anciano , Factores de Riesgo , Biomarcadores de Tumor/sangre , Péptidos Similares a la Insulina
18.
Drug Des Devel Ther ; 18: 1933-1945, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38831868

RESUMEN

Introduction: Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling nature and the need for prolonged therapies to cure them. Objective: To evaluate the use and efficacy of the rhEGF in the epithelialization of patients with a diagnosis of CEAP stage 6 venous insufficiency, in the two regimes of the health system in Colombia, the contributive (equivalent to a health system where citizens with payment capacity contribute a percentage of their salary) and the subsidized (equivalent to a health system where the state covers the vulnerable population and low socioeconomic level) versus the other treatments used. Methodology: Observational, descriptive, retrospective, multicenter study, in which 105 medical records with 139 ulcers were reviewed, in 2 centers, one belonging to the subsidized system and the other to the contributive system in Colombia. Results: The association with the epithelialization variable of the different treatment groups for ulcers according to the application of the mixed effect model test, for both regimes was for the Biologicals (EC 34.401/p = 0.000), Bioactive Agents (Hydrogels) (EC 24.735/p = 0.005) groups; for the rest of the treatment groups, the results were neither associated nor statistically significant. Conclusion: Intra- and perilesional therapy with rhEGF expands the therapeutic spectrum in patients with venous ulcers, regardless of the type of health system in which it will be applied, shortening the healing time and reaching a possible therapeutic goal, which according to this study there is an association with epithelialization regardless of the regime applied.


Asunto(s)
Úlcera Varicosa , Humanos , Colombia , Úlcera Varicosa/tratamiento farmacológico , Úlcera Varicosa/economía , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Factor de Crecimiento Epidérmico , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Anciano
19.
Pediatr Allergy Immunol ; 35(6): e14167, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38860435

RESUMEN

BACKGROUND: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. METHODS: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. RESULTS: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain. CONCLUSIONS: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.


Asunto(s)
Citocinas , Sangre Fetal , Hipersensibilidad , Poliaminas , Humanos , Femenino , Embarazo , Recién Nacido , Sangre Fetal/inmunología , Citocinas/sangre , Citocinas/metabolismo , Hipersensibilidad/inmunología , Hipersensibilidad/sangre , Adulto , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/sangre , Células Th2/inmunología , Espermidina/sangre
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