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1.
Heliyon ; 10(11): e32330, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961931

ABSTRACT

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.

2.
Rev Esp Enferm Dig ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958154

ABSTRACT

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.
Drug Deliv ; 31(1): 2372285, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38952133

ABSTRACT

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.


Subject(s)
Achillea , Cell Proliferation , Chitosan , Chlorogenic Acid , Colorectal Neoplasms , Nanoparticles , Particle Size , Plant Extracts , Chitosan/chemistry , Humans , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Achillea/chemistry , Chlorogenic Acid/pharmacology , Chlorogenic Acid/administration & dosage , Chlorogenic Acid/chemistry , Nanoparticles/chemistry , Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Cell Line, Tumor , Quinic Acid/analogs & derivatives , Quinic Acid/pharmacology , Quinic Acid/chemistry , Quinic Acid/administration & dosage , Drug Liberation , Drug Delivery Systems/methods , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Colon/drug effects , Colon/metabolism , Drug Carriers/chemistry , Molecular Weight
4.
Front Med (Lausanne) ; 11: 1407812, 2024.
Article in English | MEDLINE | ID: mdl-38983363

ABSTRACT

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.

5.
Rev Esp Enferm Dig ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967269

ABSTRACT

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.

7.
Animals (Basel) ; 14(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38929383

ABSTRACT

This study assessed the analgesic and motor effects of the GIN-TONIC block, a combination of the greater ischiatic notch plane block and the caudal lateral quadratus lumborum block, in 24 dogs undergoing pelvic limb surgery. Dogs were randomly divided into two equal groups: GA received acepromazine [(20 µg kg-1 intravenously (IV)] as premedication, and GD received dexmedetomidine (2 µg kg-1 IV). General anesthesia was maintained with isoflurane, and both groups received a GIN-TONIC block using 2% lidocaine. Nociception during surgery and postoperative pain [assessed using the Glasgow Composite Measure Pain Score (GCMPS-SF)] were assessed. Fentanyl (2 µg kg-1 IV) was administered if nociception was noted and morphine (0.5 mg kg-1 IV) was administered during recovery if the pain scores exceeded the predefined threshold. Motor function was assessed during the recovery period using descriptors previously reported. All dogs received analgesics at the 4 h mark before being discharged. Three and two dogs in GD and GA required fentanyl once. Postoperative pain scores remained ≤4/20 for all dogs except one. Dogs achieved non-ataxic ambulation within 38.9 ± 10.3 and 35.1 ± 11.1 min after extubation in GD and GA, respectively. This study highlighted the potential of the GIN-TONIC block as a feasible regional anesthesia method for delivering perioperative analgesia in dogs undergoing pelvic limb orthopedic surgery.

8.
J Clin Med ; 13(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38930052

ABSTRACT

Background: There is an increasing demand for body contouring and gender-affirming surgeries, and so is the need to compare outcomes between techniques. Gender dysphoria is a discrepancy between gender identity and the sex assigned at birth. One way to address this is to perform procedures to enable patients to look according to their desired gender identity. Gaps in knowledge regarding the best approaches and which surgical techniques yield the most patient satisfaction remain. This article summarizes up-to-date studies, including upper and lower body contouring procedures. Methods: A systematic review was performed using terms related to body contouring in gender-affirming surgery for transgender patients. All articles included surgical and patient-reported outcomes following either chest or lower body contouring procedures. Results: 15 studies, including trans male chest wall contouring, trans female breast augmentation, and lower body contouring, with 1811 patients, fulfilled the inclusion criteria. The double incision (DI) techniques consistently resected more tissue and had better BODY Q scores than non-overweight patients. Bleeding was increased in periareolar, semicircular, and obese patients with DI techniques. Nipple depigmentation and sensation loss were more common with double-incision-free nipple graft techniques (DIFNG). Lower body contouring patients had average implant sizes bigger than 200 mL and reported 2 gluteal implant displacements, 1 exposure, and one rupture. Eight percent of patients who underwent large-volume fat grafting reported dissatisfaction due to fat reabsorption. Conclusions: The debate between the double incision and periareolar techniques continues. Variations of the DIFNG technique continue to be the most common approach; however, nipple depigmentation and loss of sensation are also more common with it. Regarding increased bleeding with periareolar techniques, there is still no evidence that hormonal therapy may be playing a role in it. For lower-body trans female contouring, implants could help with the longevity of contouring results in patients needing large-volume fat grafting. There is an increasing evaluation of gender-affirming body contouring patient-reported outcomes; however, there is still a need for a validated way to report satisfaction scores in lower body contouring. Validated surveys could help identify surgical candidates based on satisfaction patterns, specifically for transgender and non-binary patients.

10.
Adv Lab Med ; 5(2): 189-196, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38939205

ABSTRACT

Objectives: Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods: Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results: The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00-2.07], central laboratory: 11.63 h [6.09-25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5-79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions: POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.

11.
Nat Commun ; 15(1): 5321, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909051

ABSTRACT

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.


Subject(s)
Hallucinogens , Paraventricular Hypothalamic Nucleus , Psilocybin , Rats, Sprague-Dawley , Animals , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/metabolism , Male , Psilocybin/analogs & derivatives , Psilocybin/pharmacology , Psilocybin/administration & dosage , Female , Rats , Hallucinogens/pharmacology , Hallucinogens/administration & dosage , Proto-Oncogene Proteins c-fos/metabolism , Behavior, Animal/drug effects , Stress, Psychological/physiopathology , Stress, Psychological/drug therapy
12.
An Pediatr (Engl Ed) ; 100(6): 438-447, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38851979

ABSTRACT

The flu is a constant threat that can sometimes cause severe forms of disease. The highest incidence rates by age group occur in children under 15 years of age, especially in those under 5 years, in whom the rate of hospitalization is also similar to the population aged 65 years and older. In addition, children are the main transmitters of the infection. In Spain, 5 influenza vaccines are authorized for the paediatric age group: three inactivated tetravalent vaccines harvested from fertilised eggs, one tetravalent inactivated vaccine obtained from cell cultures and one attenuated tetravalent vaccine for intranasal administration, which will become trivalent in the 2024-2025 season by excluding the B Yamagata lineage as recommended by the WHO. The CAV-AEP recommends systematic vaccination in children aged 6-59 months, children and adolescents belonging to risk groups, people who can transmit the flu to groups at risk of complicated flu, and household contacts or close family of infants under 6 months. From 2 years of age, the intranasal attenuated vaccine is preferred due to its greater acceptability and thus contribution to greater vaccination coverage. The CAV-AEP also considers that vaccination against influenza of healthy children and adolescents aged 5-18 years is advisable, as it provides individual protection and promotes protection at the family and community levels. It is especially important to vaccinate all health care professionals against influenza as well as pregnant women at any time during pregnancy.


Subject(s)
Influenza Vaccines , Influenza, Human , Vaccination , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Child , Adolescent , Child, Preschool , Spain/epidemiology , Infant , Vaccination/statistics & numerical data , Seasons , Female
13.
Genes (Basel) ; 15(6)2024 May 26.
Article in English | MEDLINE | ID: mdl-38927623

ABSTRACT

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.


Subject(s)
Claudins , Humans , Male , Claudins/genetics , Adult , Ichthyosis/genetics , Ichthyosis/pathology , Hypohidrosis/genetics , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/pathology , Pedigree , Phenotype
14.
Rev. esp. patol ; 57(2): 133-136, Abr-Jun, 2024. ilus
Article in Spanish | IBECS | ID: ibc-232419

ABSTRACT

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)


Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)


Subject(s)
Humans , Esophagitis , Pharmaceutical Preparations , Autoimmune Diseases , Endoscopy, Gastrointestinal , Comorbidity
15.
Materials (Basel) ; 17(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38893887

ABSTRACT

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.

16.
Sensors (Basel) ; 24(11)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38894428

ABSTRACT

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.


Subject(s)
Dielectric Spectroscopy , Electrodes , Heart Failure , Textiles , Wearable Electronic Devices , Humans , Heart Failure/physiopathology , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Dielectric Spectroscopy/methods , Dielectric Spectroscopy/instrumentation , Male , Female , Middle Aged , Edema/diagnosis , Aged
17.
Foods ; 13(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38890841

ABSTRACT

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.

18.
J Clin Med ; 13(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38892848

ABSTRACT

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.

19.
Drug Des Devel Ther ; 18: 1933-1945, 2024.
Article in English | MEDLINE | ID: mdl-38831868

ABSTRACT

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.


Subject(s)
Varicose Ulcer , Humans , Colombia , Varicose Ulcer/drug therapy , Varicose Ulcer/economics , Retrospective Studies , Male , Female , Middle Aged , Epidermal Growth Factor , Recombinant Proteins/economics , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Aged
20.
PLoS One ; 19(6): e0304268, 2024.
Article in English | MEDLINE | ID: mdl-38838004

ABSTRACT

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.


Subject(s)
Antigens, Protozoan , Enzyme-Linked Immunosorbent Assay , Leishmaniasis, Cutaneous , Humans , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Antigens, Protozoan/immunology , Female , Male , Adult , Middle Aged , Sensitivity and Specificity , Adolescent , Reproducibility of Results , Recombinant Proteins/immunology , Young Adult , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Aged , Child , Case-Control Studies , Brazil/epidemiology
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