A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response.

Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 individuals daily due to these causes, and correspond to the 4th to 5th place of all causes. The global prevalence of MASLD is estimated to 25 % of the world's population, while in pediatric population could be higher. In Mexican population is more prevalent since estimations are up to 41.3 % in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9 %, with a mortality rate of 23.9 %, primarily due to liver-related causes. In Mexico, ALD is present in 23 % of all cirrhosis cases. already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.

Reverse transcription loop­mediated isothermal amplification has a high performance in the detection of SARS­CoV­2 in saliva samples and nasal swabs from asymptomatic and symptomatic individuals.

The detection of coronavirus disease 2019 cases represents a significant challenge at the epidemiological level. Limitations exist in effectively detecting asymptomatic cases, achieving good follow-up in hospitals without the infrastructure for reverse transcription-quantitative PCR (RT-qPCR) or in difficult-to-access areas and developing methods with the need for less invasive sampling procedures. Therefore, the present study evaluated the performance of the direct reverse transcription loop-mediated isothermal amplification (RT-LAMP) test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the saliva and nasal samples of asymptomatic individuals belonging to the university population. In addition, this test was also assessed for effectiveness in symptomatic individuals referred from a hospital with poor infrastructure in molecular biology and located outside the urban area. The RT-LAMP assay was compared with the results obtained from the RT-qPCR nasopharyngeal swab test, where the diagnosis was confirmed by lateral flow immunoassay test for rapid antigen detection. A total of 128 samples were analyzed, of which 43% were symptomatic positive individuals, 25% were asymptomatic positive individuals and 32% were SARS-CoV2-negative control individuals. Among positive individuals, no differences were found between the Cq values determined by RT-qPCR. A sensitivity of 96.5% and a specificity of 97.6% was reported for the detection of SARS-CoV-2 in symptomatic individuals by salivary and nasal RT-LAMP, as well as a sensitivity of 100% and a specificity of 97.6% for the detection of SARS-CoV-2 in asymptomatic individuals. These findings indicated that performance of the direct RT-LAMP test using saliva and nasal samples has high sensitivity and specificity, which in turn suggest that it is a viable and reliable alternative for use in epidemiological monitoring.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published studies that examine FAK isoforms in ovarian cancer. The aim of the present study was to analyze the expression level of FAK and its isoforms in ovarian cancer. The expression of FAK kinase and focal adhesion targeting (FAT) domains was determined with immunohistochemistry in healthy ovary, and serous and mucinous cystadenoma, borderline tumor and carcinoma samples. Additionally, the expression of FAK and its isoforms were investigated in three ovarian cancer-derived cell lines with western blotting and reverse transcription-semi-quantitative polymerase chain reaction. An increased expression of FAK kinase domain was determined in serous tumor samples and was associated with advancement of the lesion. FAK kinase domain expression was moderate-to-low in mucinous tumor samples. The expression of the FAK FAT domain in tumor samples was reduced, compared with healthy ovary samples; however, the FAT domain was localized to the cellular nucleus. Expression of alternative transcripts FAK°, FAK28,6 and FAK28 was determined in all three cell lines investigated. In conclusion, FAK kinase and FAT domains are differentially expressed among ovarian tumor types. These results indicated the presence of at least two isoforms of FAK (FAK and the putative FAK-related non-kinase) in tumor tissue, which is supported by the cells producing at least three FAK alternative transcripts. These results may support the use of FAK and its isoforms as biomarkers for ovarian cancer.