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Purpose The Spanish Early-onset Colorectal Cancer (SECOC) study is a multicentre prospective cohort established in Spain to investigate the molecular basis of early-onset colorectal cancer (EOCRC), including metabolic alterations.Participants 220 patients with EOCRC have been enrolled since January 2019 through 18 centres across Spain. Individual-level data were collected by questionnaire, including lifestyle and other colorectal cancer-related factors. Medical record review was performed to capture clinical, histopathological and familial cancer history data. Biospecimen collection (blood, stool, tissue) at diagnosis and at various time points across treatment, as applicable, is also completed.Findings to date Participants had a median age of 44 years (range 14–49), and the majority are men (60%), with individuals age 40–49 years at EOCRC diagnosis being over-represented. Forty-three per cent of participants were diagnosed with a tumour in the rectosigmoid junction/rectum. Nearly two-thirds of EOCRC cases (64%) were diagnosed with advanced stage (III–IV) disease, and 28% of cases had no reported familial history of cancer.Future plans We are actively recruiting and observing participants; we plan to administer follow-up questionnaires and perform additional biospecimen collection. This prospective cohort offers a unique, rich resource for research on EOCRC aetiologies and will contribute to larger international efforts to disentangle the rising disease burden.

Introduction: Early and accurate Alzheimer’s disease (AD) diagnosis has evolved in recent years by the use of specific methods for detecting its histopathological features in concrete cases. Currently, biomarkers in cerebrospinal fluid (CSF) and imaging techniques (amyloid PET) are the most used specific methods. However, some results between both methods are discrepant. Therefore, an evaluation of these discrepant cases is required. Objective: The aim of this work is to analyze the characteristics of cases showing discrepancies between methods for detecting amyloid pathology. Methodology: Patients from the Neurology Department of La Fe Hospital (n = 82) were diagnosed using both methods (CSF biomarkers and amyloid-PET). Statistical analyses were performed using logistic regression, and sex and age were included as covariables. Additionally, results of standard neuropsychological evaluations were taken into account in our analyses. Results: The comparison between CSF biomarker (Aβ42) and amyloid PET results showed that around 18% of cases were discrepant—mainly CFS-negative and PET-positive cases had CSF levels close to the cut-off point. In addition, a correlation between the episodic memory test and CSF biomarkers levels was observed. However, the same results were not obtained for other neuropsychological domains. In general, CSF- and PET-discrepant cases showed altered episodic memory in around 66% of cases, while 33% showed normal performance. Conclusions: In common clinical practice at tertiary memory centers, result discrepancies between tests of amyloid status are far more common than expected. However, episodic memory tests remain an important support method for AD diagnosis, especially in cases with discrepant results between amyloid PET and CSF biomarkers.

Los materiales sustitutivos de los tejidos óseos representan en la actualidad un área de gran interés en la investigación relacionada con productos médicos. A pesar de la capacidad de autorenovación de los tejidos duros del cuerpo humano, la alta incidencia de patologías y lesiones traumáticas con grandes pérdidas óseas exige la búsqueda de materiales que puedan de forma permanente o transitoria servir de sustitutos óseos o de plantillas para la osteosíntesis. Dentro de los biomateriales en estudio, actualmente destacan vidrios y cerámicas vítreas, las que además de ser biocompatibles, osteoinductivas y osteoconductivas han demostrado la habilidad de enlazarse al hueso directamente sin que medie interface alguna (bioactivos). Estos materiales aparte de estimular la osteosíntesis pueden contribuir con el proceso de angiogénesis y favorecen la adhesión, proliferación y diferenciación celular imprescindible en matrices diseñadas para la Ingeniería de Tejidos. Este trabajo se refiere a generalidades en el desarrollo de vidrios y vitrocerámicos con aplicaciones en medicina, su diversidad de formulaciones, métodos de síntesis, propiedades, ventajas, limitaciones y sus principales aplicaciones en diferentes especialidades médicas, así como en la Ingeniería de Tejidos.

Publicaciones recientes reflejan la preocupación de las autoridades antidopaje por el uso de sistemas simuladores de altitud y la posibilidad de considerarlos métodos dopantes. El objetivo de nuestro estudio fue el de comparar las modificaciones hematológicas inducidas por dos tratamientos con eritropoyetina recombinante humana (rHuEpo) a diferentes dosis, frente a un protocolo de hipoxia normobárica intermitente (HNI) en un modelo animal. Veinticuatro ratas Wistar macho jóvenes fueron divididas en 3 grupos experimentales: grupo sometido a HNI (12h pO2 12% /12h pO2 21%) (n=8); grupo tratado con una dosis de 300 UI de rHuEpo (n=8) y grupo tratado con 500 UI de rHuEpo (n=8). Se extrajeron dos muestras de sangre a cada uno de los grupos experimentales (antes y después de los tratamientos). Nuestros resultados muestran incrementos muy similares, y estadísticamente significativos, en los valores de hemoglobina, de hematocrito y de reticulocitos, tanto en el grupo HNI como en el grupo tratado con 300 UI de rHuEpo tras los 15 días de tratamiento. El tratamiento con 500 UI de rHuEpo produjo un incremento significativamente mayor. La principal conclusión de nuestro estudio es que las modificaciones de los parámetros hematológicos obtenidas mediante un protocolo de HNI son similares a las obtenidas con un tratamiento con 300 UI de rHuEpo.Palabras clave: Hemoglobina, hematocrito, reticulocitos, dopajeRecent publications reflect the anti-doping authorities’ concern about the use of altitude simulator systems, since these technologies could be considered as doping methods. The major aim of our study was to compare the effect of two different rHuEpo treatments with a normobaric intermittent hypoxic (NIH) protocol regarding the modifications of hemoglobin, hematocrit and reticulocytes values in an animal model. Although these hematological parameters are of secondary nature, some international sport federations currently exclude athletes, who show aberrant values of these parameters, from competition.Twenty-four young male Wistar rats (3 months and ~300g weight) were randomly divided in 3 experimental groups: normobaric intermittent hypoxic group (12h pO2 12% /12h pO2 21%) (n=8); the group treated with 300 UI of rHuEpo (n=8) and the group treated with 500 UI of rHuEpo (n=8).The rHuEpo was administered subcutaneously 3 times/week. All the treatments lasted 15 days. Two blood samples were obtained in every experimental group. The first one before the treatments and the second one 15 days after the treatments. Our results show similar and statistically significant increments in the hemoglobin, hematocrit and reticulocytes values after 15 days of treatment with 300 UI of rHuEpo or NIH. The treatment with 500 UI of rHuEpo induced a higher increase in the hematological parameters determined in our study when compared with the other treatments (NIH and rHuEpo 300 UI). The main conclusion of our study is that the hematological modifications achieved with a NIH protocol were comparable with those that imply a treatment with 300 UI of rHuEpo.Key Words: Hemoglobin, hematocrit, reticulocytes, doping

Recent publications reflect the anti-doping authorities’ concern about the use of altitude simulator systems, since these technologies could be considered as doping methods. The major aim of our study was to compare the effect of two different rHuEpo treatments with a normobaric intermittent hypoxic (NIH) protocol regarding the modifications of hemoglobin, hematocrit and reticulocytes values in an animal model. Although these hematological parameters are of secondary nature, some international sport federations currently exclude athletes, who show aberrant values of these parameters, from competition. Twenty-four young male Wistar rats (3 months and ~300g weight) were randomly divided in 3 experimental groups: normobaric intermittent hypoxic group (12h pO2 12% /12h pO2 21%) (n=8); the group treated with 300 UI of rHuEpo (n=8) and the group treated with 500 UI of rHuEpo (n=8).The rHuEpo was administered subcutaneously 3 times/week. All the treatments lasted 15 days. Two blood samples were obtained in every experimental group. The first one before the treatments and the second one 15 days after the treatments. Our results show similar and statistically significant increments in the hemoglobin, hematocrit and reticulocytes values after 15 days of treatment with 300 UI of rHuEpo or NIH. The treatment with 500 UI of rHuEpo induced a higher increase in the hematological parameters determined in our study when compared with the other treatments (NIH and rHuEpo 300 UI). The main conclusion of our study is that the hematological modifications achieved with a NIH protocol were comparable with those that imply a treatment with 300 UI of rHuEpo. Key Words: Hemoglobin, hematocrit, reticulocytes, doping

Background: The Valencian Cognitive Diseases Study (VALCODIS) provides a large cohort of cases suffering from neurodegenerative diseases causing cognitive problems in their initial phases. This cohort is being obtained from admitted patients at Cognitive Disorders Unit Hospital Universitari i Politècnic La Fe (Valencia, Spain), as a basis to contribute on the Alzheimer's disease (AD) diagnosis and prognosis research. Method: Patients who come to the Cognitive Disorders Unit at Neurology Department of Hospital La Fe can be recruited to the VALCODIS cohort after their informed consent have been obtained. Patients with moderate and severe dementia are not proposed to participate. Included patients were studied with standard analytical and neuroimaging procedures, commonly brain MR, and CSF biomarkers determination (β‐amyloid‐42, β‐amyloid‐40, p‐Tau, t‐Tau, neurofilament light chain). Patients on anticoagulation, other contraindications or not suitable for LP can be included if an amyloid brain PET can be obtained. In some patients, brain PET with FDG is also obtained. After amyloid status is assured, a detailed neuropsychological evaluation is obtained in every patient using at least MMSE, CDR, RBANS and GDS scales. Finally, blood samples were taken to determine some potential biomarkers (lipid peroxidation, lipids, proteins, microRNAs) and stored simultaneously with CSF samples. Result: A total of 1100 participants aged 50 to 80 years, who were on follow up from January 2017 to August 2022 have been included in the VALCODIS cohort. This cohort is composed by early AD patients (mild cognitive impairment (MCI), mild dementia), other dementias in their initial phases (frontotemporal dementia, Lewy body dementia, vascular dementia) and cognitively healthy persons. Also, some of MCI‐AD patients were followed‐up at 2 years to carry out a prognosis study, by means of neuropsychological evaluation and blood biomarkers. Conclusion: The VALCODIS cohort represents a valuable infrastructure describing 6‐year experience about early and specific AD diagnosis, and prognosis. This cohort will provide a large number of patients, biologically diagnosed by CSF biomarkers, as well as their demographical, clinical and biochemical data. In addition, the biological samples (blood, plasma, urine, saliva, CSF) were stored to carry out further biomarkers studies. [ABSTRACT FROM AUTHOR]

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant disorder characterized by the predisposition to develop a number of cancers, especially colorectal cancer (CRC). We present a HNPCC family with CRC at age 12 years. Our observations suggest that the germline mutation of the both copies of the MLH1 gene may play a role in the early onset of CRC. [Copyright &y& Elsevier]

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 ( NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1 , there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC-IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial-mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.