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The COVID-19 pandemic has had a significant impact on the health and economy of the global population. Even after recovery from the disease, post-COVID-19 symptoms, such as pulmonary fibrosis, continue to be a concern. This narrative review aims to address pulmonary fibrosis (PF) from various perspectives, including the fibrotic mechanisms involved in idiopathic and COVID-19-induced pulmonary fibrosis. On the other hand, we also discuss the current therapeutic drugs in use, as well as those undergoing clinical or preclinical evaluation. Additionally, this article will address various biomarkers with usefulness for PF prediction, diagnosis, treatment, prognosis, and severity assessment in order to provide better treatment strategies for patients with this disease. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22–0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17–0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the malfunction of the hematopoietic system. This process is generated and perpetuated by several mechanisms that provide the disease with part of its malignancy potential and genetic and cytological characteristics. Disease pathological features are used for diagnosis and prognosis; however, most of them are obtained by a bone marrow aspirate, so it is crucial to find other less invasive methods to establish or complement the diagnosis, prognosis, and follow-up of the disease. A cancer biomarker is any measurable indicator demonstrating the presence of malignancy, tumor behavior, prognosis, or treatment responses. This review will summarize circulating diagnostic and prognosis biomarkers for B-cell progenitor ALL. Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer (EC) is one of the most common gynecological malignancies. Therefore, it is of great clinical importance to identify potential candidates for diagnostic and prognostic biomarkers in order to identify high-risk patients and obtain a more accurate prognosis in a timely manner. MicroRNAs (miRs) are small single-stranded RNAs that regulate gene expression and play a role in all steps of cancer development. The miRs expressed in endometrial tumor tissue are probably involved in cell proliferation and differentiation, apoptosis, and carcinogenesis. We reviewed the literature to identify potential miRs that may function as diagnostic, prognostic, or response to treatment markers in EC. In developed countries, endometrial cancer (EC) is one of the most common neoplasms of the female reproductive system. MicroRNAs (miRs) are a class of single-stranded noncoding RNA molecules with lengths of 19–25 nucleotides that bind to target messenger RNA (mRNA) to regulate post-transcriptional gene expression. Although there is a large amount of research focused on identifying miRs with a diagnostic, prognostic, or response to treatment capacity in EC, these studies differ in terms of experimental methodology, types of samples used, selection criteria, and results obtained. Hence, there is a large amount of heterogeneous information that makes it difficult to identify potential miR biomarkers. We aimed to summarize the current knowledge on miRs that have been shown to be the most suitable potential markers for EC. We searched PubMed and Google Scholar without date restrictions or filters. We described 138 miRs with potential diagnostic, prognostic, or treatment response potential in EC. Seven diagnostic panels showed higher sensitivity and specificity for the diagnosis of EC than individual miRs. We further identified miRs up- or downregulated depending on the FIGO stage, precursor lesions, and staging after surgery, which provides insight into which miRs are expressed chronologically depending on the disease stage and/or that are modulated depending on the tumor grade based on histopathological evaluation. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials. [ABSTRACT FROM AUTHOR]

The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the usefulness of the serum concentration of nine matrix metalloproteinases (MMPs) as biomarkers of spontaneous abortion.Methods: A retrospective nested cohort case-control study was carried out in Zacatecas, Mexico. MMP-1-3, MMP-7-10, and MMP-12-13 were analyzed in serum from women who had spontaneous abortion of unknown causes (n = 7), who suffered abortions attributed to urinary tract infection (n = 7) and from those with healthy pregnancies without complications (controls; n = 20). Protein profiles were determined between 11 and 13 weeks of gestation (GW) using the Bio-Plex Pro Human MMP Panel. Differences in serum MMP concentrations between the study groups and their correlation with clinical findings were evaluated statistically.Results: There were differences in serum concentrations of MMP-9 between groups of spontaneous abortion of unknown cause (13.2 ± 7.5 ng/µL), abortion attributed to urinary tract infection (11.6 ± 5.8 ng/µL) and the controls (11.8 ± 16.5 ng/µL) (p = .022). Compared with controls, higher serum concentrations of MMP-8, MMP-9, and MMP-10 were observed in the group of spontaneous abortions of unknown causes (p value < .05). A negative correlation between MMP-8 and MMP-9 and urine density was also identified (r = -0.949, p value = .0167; and r = -0.947, p = .0167).Conclusions: Elevated serum concentrations of MMP-8, MMP-9, and MMP-10 were associated and preceded by the appearance of spontaneous interruption of pregnancy of unknown causes. Our results support the hypothesis that altered MMP modulation may be related with the pathogenesis of spontaneous abortion. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non‑invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10‑protein profile (C‑peptide, ghrelin, gastric inhibitory polypeptide, glucagon‑like peptide‑1, glucagon, insulin, leptin, plasminogen activator inhibitor‑1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio‑Plex Pro Human Diabetes 10‑Plex Panel (Bio‑Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9x10‑4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8‑fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04‑53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8‑fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52‑22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non‑invasive biomarker of IBD severity. [ABSTRACT FROM AUTHOR]

Purpose: To perform serum microRNA expression profiling to identify members of chromosome 19 miRNA cluster involved in preeclampsia development. Methods: Serum chromosome 19 miRNA cluster microRNA expression profiling was evaluated at 12, 16, and 20 gestational weeks and at the time of preeclampsia diagnosis, in women who developed preeclampsia (WWD-PE; n = 16) and controls ( n = 18) using TaqMan low density array plates. Results: A total of 51 chromosome 19 microRNA cluster members were evaluated. The circulating hsa-miRs 512-3p, 518f-3p, 520c-3p, and 520d-3p, were differentially expressed between groups ( P < 0.05). Compared with controls, serum levels of hsa-miR-518f-3p at 20 GW were useful for identifying WWD-Mild-PE ( P = 0.035) and WWD-Severe-PE ( P = 0.007). Conclusions: Serum hsa-miRs 512-3p, 518f-3p, 520c-3p, and 520d-3p, are differentially expressed between WWD-PE and controls and their role in the development of preeclampsia should be investigated further. [ABSTRACT FROM AUTHOR]

Despite the implementation of programmes to improve maternal health, maternal and foetal mortality rates still remain high. The presence of maternal distress and its association with the development of pregnancy hypertensive disorders is not well established. The aim of this study was to evaluate the association between maternal distress and the development of hypertensive disorders in pregnancy in a prospective cohort of 321 Mexican women. Symptoms of maternal distressing were evaluated at week 20th of gestation using the General Health Questionnaire. The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the odds of developing a pregnancy hypertensive disorder by 5.1-26.4 times in study population (p values < .05). Our results support the participation of maternal distress in the development of hypertensive disorders of pregnancy. The implementation of effective programmes prioritising risk factors during pregnancy including the presence of maternal distressing factors is recommended. Impact statement What is already known on this subject: Changes in the nervous, endocrine, and immune systems have been observed in pregnant women with distress conditions leading to gestational disorders. What do the results of this study add: The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the developing of hypertensive disorders in Mexican population. What are the implications of these findings for clinical practice and/or further research: These findings may contribute to a better understanding of the role of the maternal stress in the development of hypertensive disorders of pregnancy, and in the implementation of effective programmes for clinical practice prioritising risk factors during pregnancy, including the presence of maternal distressing factors. [ABSTRACT FROM AUTHOR]

Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. [ABSTRACT FROM AUTHOR]

The use of derivatives of natural and synthetic origin has gained attention because of their therapeutic effects against human diseases. Coumarins are one of the most common organic molecules and are used in medicine for their pharmacological and biological effects, such as anti-inflammatory, anticoagulant, antihypertensive, anticonvulsant, antioxidant, antimicrobial, and neuroprotective, among others. In addition, coumarin derivates can modulate signaling pathways that impact several cell processes. The objective of this review is to provide a narrative overview of the use of coumarin-derived compounds as potential therapeutic agents, as it has been shown that substituents on the basic core of coumarin have therapeutic effects against several human diseases and types of cancer, including breast, lung, colorectal, liver, and kidney cancer. In published studies, molecular docking has represented a powerful tool to evaluate and explain how these compounds selectively bind to proteins involved in various cellular processes, leading to specific interactions with a beneficial impact on human health. We also included studies that evaluated molecular interactions to identify potential biological targets with beneficial effects against human diseases. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is the first worldwide cause of death in pregnant women, intra-uterine growth retardation, and fetal prematurity. Some vascular endothelial grown factor gene (VEGF) polymorphisms have been associated to PE and other pregnancy disturbances. We evaluated the associations between VEGF genotypes/ haplotypes and PE in Mexican women. Methods: 164 pregnant women were enrolled in a case-control study (78 cases and 86 normotensive pregnant controls). The rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (+405G/C), and rs25648 (-7C/T), VEGF variants were discriminated using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) methods or Taqman single nucleotide polymorphism (SNP) assays. Results: The proportions of the minor allele for rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs were 0.33, 0.2, 0.39, and 0.17 in controls, and 0.39, 0.23, 0.41, and 0.15 in cases, respectively (P values > 0.05). The most frequent haplotypes of rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs, were C-G-C-C and C-G-G-C with frequencies of 0.39, 0.21 in cases and 0.37, 0.25 in controls, respectively (P values > 0.05) Conclusion: There was no evidence of an association between VEGF alleles, genotypes, or haplotypes frequencies and PE in our study. [ABSTRACT FROM AUTHOR]

Stem cells are defined by their self-renewal capacity and their ability to generate diverse kinds of specialized progeny. Stem cells can be classified by their differentiation potential as totipotent, pluripotent, or multipotent, and by their tissue of origin in embryonic or adult stem cells. A great deal of interest has risen regarding their distinct differentiation models, from the conventional straightforward mother stem cell-daughter cell, to the considerably more complex transdifferentiation and undifferentiation models. These models are currently being applied to understand the phenomenon of cell plasticity that characterizes these cells. Stem cell plasticity accounts for the capacity to generate cells types different from their original tissue, a good example being the hematopoietic stem cells, which can give origin to hepatocytes and myocytes under highly regulated conditions. There are challenges and controversies regarding diverse aspects of research in stem cell plasticity studies, as a great deal of them are performed on donated ova from human fertility centers, leading to heated ethic arguments that require being dealt with in order to further improve stem cell research. Currently, it is possible to obtain pluripotent stem cells from sources other than human embryos, for example the amniotic fluid. New and spectacular developments in stem cell therapy and regenerative medicine are continuously being investigated. International legislation regarding manipulation and research on stem cells is heterogeneous and frequently divergent, whereas national laws are limited in their capacity to deal with the evolving challenges in these research and therapeutic field. [ABSTRACT FROM AUTHOR]

microRNAs are important regulators of cell processes and have been proposed as potential preeclampsia biomarkers. We evaluated serum microRNA expression profiling to identify microRNAs involved in preeclampsia development. Serum microRNA expression profiling was evaluated at 12, 16, and 20 weeks of gestation (WG), and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan low-density array plates: a control group with 18 normotensive pregnant women and a case group with 16 patients who developed preeclampsia during the follow-up period. Fifty-three circulating microRNAs were differentially expressed between groups (p < 0.05). Compared with controls, hsa-miR-628-3p showed the highest relative quantity values (at 12 WG = 7.7 and at 20 WG = 3.45) and the hsa-miRs -151a-3p and -573 remained differentially expressed from 16 to 20 WG (p < 0.05). Signaling pathways including cancer-related, axon guidance, Neurotrophin, GnRH, VEGF, and B/T cell receptor, were most commonly altered. Further target gene prediction revealed that nuclear factor of activated T-cells 5 gene was included among the transcriptional targets of preeclampsia-modulated microRNAs. Specific microRNAs including hsa-miRs -628-3p, -151a-3p, and -573 were differentially expressed in serum of pregnant women before they developed preeclampsia compared with controls and their participation in the preeclampsia development should be considered. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia increases the risk of developing severe COVID-19 symptoms, but the related mechanisms are unclear. A mean glucose level upon hospital admission >166 mg/dl correlates positively with acute respiratory distress syndrome in patients with hyperglycemia. The objective of this study was to evaluate the relationship between sustained hyperglycemia and the outcome of hospitalized patients with severe COVID-19. We also evaluated the effect of high glucose concentrations on the expression of angiotensin-converting enzyme 2 (ACE2). We carried out a case-control study with hospitalized patients with severe COVID-19 with and without sustained hyperglycemia. In a second stage, we performed in vitro assays evaluating the effects of high glucose concentrations on ACE2 gene expression. Fifty hospitalized patients with severe COVID-19 were included, of which 28 (56%) died and 22 (44%) recovered. Patients who died due to COVID-19 and COVID-19 survivors had a high prevalence of hyperglycemia (96.4% versus 90.9%), with elevated central glucose upon admission (197.7 mg/dl versus 155.9 mg/dl, p = 0.089) and at discharge (185.2 mg/dl versus 134 mg/dl, p = 0.038). The mean hypoxemia level upon hospital admission was 81% in patients who died due to COVID-19 complications and 88% in patients who survived (p = 0.026); at the time of discharge, hypoxemia levels were also different between the groups (68% versus 92%, p ≤ 0.001). In vitro assays showed that the viability of A549 cells decreased (76.41%) as the glucose concentration increased, and the ACE2 gene was overexpressed 9.91-fold after 72 h (p ≤ 0.001). The relationship between hyperglycemia and COVID-19 in hospitalized patients with COVID-19 plays an important role in COVID-19-related complications and the outcome for these patients. In patients with chronic and/or sustained hyperglycemia, the upregulation of ACE2, and its potential glycation and malfunction, could be related to complications observed in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered. [ABSTRACT FROM AUTHOR]

Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3'UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3'UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3'UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3'UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3'UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7–15.4; p < 0.05). Genetic variants into the 3'UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7–15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3′UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC. [ABSTRACT FROM AUTHOR]

Introduction: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. Methods: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5′-nuclease assay with TaqMan probes. Results: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15–0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2–0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Conclusions: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes. [ABSTRACT FROM AUTHOR]

The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC50=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC50=11.11 µM) and HeLa (IC50=13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose: To perform serum microRNA expression profiling to identify members of chromosome 19 miRNA cluster involved in preeclampsia development.Methods: Serum chromosome 19 miRNA cluster microRNA expression profiling was evaluated at 12, 16, and 20 gestational weeks and at the time of preeclampsia diagnosis, in women who developed preeclampsia (WWD-PE; n = 16) and controls (n = 18) using TaqMan low density array plates.Results: A total of 51 chromosome 19 microRNA cluster members were evaluated. The circulating hsa-miRs 512-3p, 518f-3p, 520c-3p, and 520d-3p, were differentially expressed between groups (P < 0.05). Compared with controls, serum levels of hsa-miR-518f-3p at 20 GW were useful for identifying WWD-Mild-PE (P = 0.035) and WWD-Severe-PE (P = 0.007).Conclusions: Serum hsa-miRs 512-3p, 518f-3p, 520c-3p, and 520d-3p, are differentially expressed between WWD-PE and controls and their role in the development of preeclampsia should be investigated further. [ABSTRACT FROM AUTHOR]

Proclotting enzymes (PCE) are a serine protease-containing CLIP domain and play roles in development of embryonic and innate immune response. Little is known about PCE in mosquitoes, but only three melanization regulatory modules that involve proteases with the CLIP domain have been reported. We cloned the PCE gene and reported the nucleotide sequence encoding a proclotting enzyme in Aedes aegypti L. We did in-silico protein translation, alignment with proclotting proteinase sequences of the other species of different taxonomic orders, and phylogenetic analysis where PCE in Ae. aegypti fit the hypotheses of positive or adaptive evolution. The fundamental information could be applied in strategies for biological control of medically important insects. [ABSTRACT FROM AUTHOR]

Obesity is considered the main risk factor associated with the development of insulin resistance (IR). The aim of this study was to evaluate the influence of obesity on puberty onset and IR in Mexican children. A total of 378 children (189 boys and 189 girls) aged 8–14 years participated in the study. IR was estimated using the homeostasis model assessment for IR (HOMA-IR). The mean fasting glucose (FG) and basal insulin levels were 82 mg/dl and 11.0 μIU/ml in boys and 77.3 mg/dl and 12.3 μIU/ml in girls (P<0.05). Subjects with obesity at Tanner stages II–V showed increased FG levels (P<0.05). In boys with obesity, there was a decrease in HOMA-IR in Tanner stage IV and differences in age between boys with normal weight and those with obesity in Tanner V, being older the boys with obesity. Obesity in children and adolescents was associated with higher HOMA-IR values. In boys with obesity, IR increased at the end of pubertal maturation, with a delay in puberty. These findings should be considered on the establishment of IR cutoff values for pubertal population in Mexico and in the establishment of strategies to prevent the health problems related to obesity. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.Methods: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex ProTM Human Cancer Biomarker Panels 1 and 2.Results: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8-29.8 times in the study population.Conclusion: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered. [ABSTRACT FROM AUTHOR]

Background:Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia. Objective:The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development. Methods:MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA). Results:Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population. Conclusion:Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is the first worldwide cause of death in pregnant women, intra-uterine growth retardation, and fetal prematurity. Some vascular endothelial grown factor gene (VEGF) polymorphisms have been associated to PE and other pregnancy disturbances. We evaluated the associations between VEGF genotypes/haplotypes and PE in Mexican women.Methods: 164 pregnant women were enrolled in a case-control study (78 cases and 86 normotensive pregnant controls). The rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (+405G/C), and rs25648 (-7C/T), VEGF variants were discriminated using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) methods or Taqman single nucleotide polymorphism (SNP) assays.Results: The proportions of the minor allele for rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs were 0.33, 0.2, 0.39, and 0.17 in controls, and 0.39, 0.23, 0.41, and 0.15 in cases, respectively (P values > 0.05). The most frequent haplotypes of rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs, were C-G-C-C and C-G-G-C with frequencies of 0.39, 0.21 in cases and 0.37, 0.25 in controls, respectively (P values > 0.05)Conclusion: There was no evidence of an association between VEGF alleles, genotypes, or haplotypes frequencies and PE in our study. [ABSTRACT FROM AUTHOR]

The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students. [ABSTRACT FROM AUTHOR]

Bacterial coinfections, which increase the severity of respiratory viral infections, are frequent causes of mortality in influenza pandemics but have not been well characterized in patients with Coronavirus disease 2019 (COVID-19). Moreover, the association of COVID-19 infection with pulmonary Mycobacterium tuberculosis disease (TB) and concurrent pulmonary fungal infection is not well known. The classification of patients with COVID-19-associated pulmonary aspergillosis (CAPA) using the current definitions for invasive fungal diseases has proven difficult. In this study, we aimed to provide information about three patients with underlying diseases ongoing with COVID-19 and co-infection with pulmonary TB, and with COVID-19-associated pulmonary aspergillosis (CAPA). At the time of hospital admission, each patient presented complications such as decompensated T2DM with diabetic ketoacidosis and/or hypertension. Findings of chest computed tomography and serum galactomannan by radioimmunoassay were useful for classifying them as possible CAPA. One of the three possible CAPA cases was fatal. These three cases are rare and are the first of their kind reported worldwide. The generation of reliable algorithms, early diagnosis, standardization of classification criteria, and the selection of specific and personalized treatments for COVID-19-associated opportunistic infections, including CAPA, are necessary to improve outcomes in these kinds of patients. [ABSTRACT FROM AUTHOR]

• We analyzed the gene variants of the angiotensin-aldosterone system in COVID-19. • Renin-angiotensin-aldosterone system gene variants were associated with severity and death in COVID-19. • The T/T genotype of AGTR1 rs5182 variant increased the odds of symptomatic COVID-19. • The T/T genotype of AGTR1 rs5182 variant increased the odds of hospitalization. • The haplotype CTG decreased the odds of death due to COVID-19. To analyze the gene variants of the renin-angiotensin-aldosterone system and determine their association with the severity and outcome of COVID-19. A total of 104 patients were included in the study: 34 asymptomatic patients with COVID-19 as controls and 70 symptomatic patients as cases. The genetic variants ACE rs4343, ACE2 rs2074192, AGTR1 rs5182, and AGT rs4762 were identified using TaqMan genotyping tests. Patients with the T/T genotype of AGTR1 rs5182 have a higher probability of developing symptomatic COVID-19 (odds ratio [OR] 12.25, 95% confidence interval [CI] 1.34-111.9, P ≤0.001) and a higher risk of hospitalization because of disease (OR 14.00, 95% CI 1.53-128.49, P = 0.012). The haplotype CTG (AGTR1 rs5182, ACE2 rs2074192, ACE rs4343) decreased the odds of death related to COVID-19 in the study population (OR 0.03, 95% CI 0.0-0.06, P = 0.026). The T/T genotype of the AGTR1 rs5182 variant increased the probability of symptomatic COVID-19 and hospitalization, whereas the haplotype CTG (consisting of AGTR1 rs5182, ACE2 rs2074192, and ACE rs4343) decreased the odds of death related to COVID-19 by 97% in the hospitalized patients with COVID-19. These results support the participation of renin-angiotensin-aldosterone system gene variants as modifiers of the severity of symptoms associated with SARS-CoV-2 infection and the outcome of COVID-19. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is the etiological agent of COVID-19 and may evolve from asymptomatic disease to fatal outcomes. Real-time reverse-transcription polymerase chain reaction (RT-PCR) screening is the gold standard to diagnose severe accurate respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but this test is not 100% accurate, as false negatives can occur. We aimed to evaluate the potential false-negative results in hospitalized patients suspected of viral respiratory disease but with a negative previous SARS-CoV-2 RT-PCR and analyze variables that may increase the success of COVID-19 diagnosis in this group of patients. A total of 55 hospitalized patients suspected of viral respiratory disease but with a previous negative RT-PCR result for SARS-CoV-2 were included. All the participants had clinical findings related to COVID-19 and underwent a second SARS-CoV-2 RT-PCR. Chest-computed axial tomography (CT) was used as an auxiliary tool for COVID-19 diagnosis. After the second test, 36 patients (65.5%) were positive for SARS-CoV-2 (COVID-19 group), and 19 patients (34.5%) were negative (controls). There were differences between the groups in the platelet count and the levels of D-dimer, procalcitonin, and glucose (p < 0.05). Chest CT scans categorized as COVID-19 Reporting and Data System 5 (CO-RADS 5) were more frequent in the COVID-19 group than in the control group (91.7% vs. 52.6%; p = 0.003). CO-RADS 5 remained an independent predictor of COVID-19 diagnosis in a second SARS-CoV-2 screening (p = 0.013; odds ratio = 7.0, 95% confidence interval 1.5–32.7). In conclusion, chest CT classified as CO-RADS 5 was an independent predictor of a positive second SARS-CoV-2 RT-PCR, increasing the odds of COVID-19 diagnosis by seven times. Based on our results, in hospitalized patients with a chest CT classified as CO-RADS 5, a second SARS-CoV-2 RT-PCR test should be mandatory when the first one is negative. This approach could increase SARS-CoV-2 detection up to 65% and could allow for isolation and treatment, thus improving the patient outcome and avoiding further contagion. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 19 (COVID-19) has been a global public health emergency, with 209.89 million cases of infection with SARS-CoV-2 recorded, resulting in 4,401,675 deaths. After recuperation, it is probable that COVID-19 patients have sequelae of the disease. This study aimed to evaluate the respiratory anatomical-functional sequelae in Mexican patients who recovered from COVID-19. Methodology: This study included twenty-four patients who recovered from COVID-19 and eight non-infected patients (controls). Participants were screened for SARS-CoV-2 and the presence of IgM/IgG antibodies. Pulmonary function and lung anatomical abnormalities were evaluated by spirometry and computerized tomography. Results: A total of 45.8% of the patients had pulmonary function with obstructive patterns: 70.8% of recovered cases had COVID-19 Reporting and Data System (CO-RADS) 1, 20.8% CO-RADS 3 and 16.7% CO-RADS 4. A total of 35.3% of patients with CO-RADS 1 also showed bilateral nodal growth; 70.8% of patients tested positive for IgG and 8.4% for IgG/IgM, and 20.8% tested negative for both antibodies. Conclusions: There were respiratory anatomical and functional sequelae in Mexican patients who recovered from COVID-19, with a high occurrence of pulmonary obstructive patterns in the study population. These observations indicate the importance of the routine evaluation of sequelae in Mexican patients who recovered from COVID-19 and the need for strict follow-up to improve the quality of life of these patients. [ABSTRACT FROM AUTHOR]

The primary function of the skin is that of a physical barrier against the environment and diverse pathogens; therefore, its integrity is essential for survival. Skin regeneration depends on multiple stem cell compartments within the epidermis, which, despite their different transcriptional and proliferative capacity, as well as different anatomical location, fall under the general term of skin stem cells (SSCs). Skin wounds can normally heal without problem; however, some diseases or extensive damage may delay or prevent healing. Non-healing wounds represent a serious and life-threatening scenario that may require advanced therapeutic strategies. In this regard, increased focus has been directed at SSCs and their role in wound healing, although emerging therapeutical approaches are considering the use of other stem cells instead, such as mesenchymal stem cells (MSCs). Given its extensive and broad nature, this review supplies newcomers with an introduction to SSCs, wound healing, and therapeutic strategies for skin regeneration, thus familiarizing the reader with the subject in preparation for future in depth reading. [ABSTRACT FROM AUTHOR]

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10−11). Additional studies are necessary to validate these findings as hallmarks of MD. [ABSTRACT FROM AUTHOR]

Introduction: Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. Methodology: The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3' end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. Results: Amplification was achieved for the positive control and specific regions in both techniques. Conclusions: This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-β, according to an intracellular detection) is higher in patients with DM2 (P<0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P<0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-β and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5. [ABSTRACT FROM AUTHOR]

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a hematological malignancy of immature B-cell precursors, affecting children more often than adults. The etiology of BCP-ALL is still unknown, but environmental factors, sex, race or ethnicity, and genomic alterations influence the development of the disease. Tools based on protein detection, such as flow cytometry, mass spectrometry, mass cytometry and reverse phase protein array, represent an opportunity to investigate BCP-ALL pathogenesis and to identify new biomarkers of disease. This review aims to document the recent advancements with respect to applications of proteomic technologies to study mechanisms of leukemogenesis, how this information could be used in the discovery of biological targets, and finally we describe the challenges of application of proteomic tools for the approach of BCP-ALL. [ABSTRACT FROM AUTHOR]

Introduction: Introduction: worldwide, hospital malnutrition constitutes an important issue of morbidity and mortality. Although the prevalence of malnutrition has been calculated as between 7% and 27% in hospitalized patients, its real prevalence remains unknown or underestimated because of the different criteria for its identification and diagnosis. The aim of this study was to determine the prevalence of nutritional risk in a cohort of hospitalized patients and to identify the significance of the predictors associated with nutritional risk. Methods: the evaluation of the presence of nutritional risk was carried out in 247 individuals hospitalized at the second-level care institution Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE) Zacatecas, Hospital General Nº 26, in Mexico. Nutritional screening was evaluated during the first 24 hours of stay with the NRS 2002. The weighing of associated variables with nutritional risk was calculated statistically using the software Sigma Plot v11. Results: forty-two percent of patients were at risk of malnutrition. Significant associations between nutritional risk and a reduction in food ingestion (during the last week), the illness severity of the patient, as well as age and sex (p < 0.05), were observed. A reduction in food ingestion during the previous week increased the likelihood of having nutritional risk 6.67 times more (95% CI: 3.4-13.2; p < 0.001) in the studied population. Conclusion: the risk of malnutrition in hospitalized patients at ISSSTE-Zacatecas, Hospital General Nº 26 is frequent (42%). Therefore, early detection of nutritional risk is important to offer for proper nutritional intervention with the objective of decreasing the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a hematological malignancy of immature B-cell precursors, affecting children more often than adults. The etiology of BCPALL is still unknown, but environmental factors, sex, race or ethnicity, and genomic alterations influence the development of the disease. Tools based on protein detection, such as flow cytometry, mass spectrometry, mass cytometry and reverse phase protein array, represent an opportunity to investigate BCP-ALL pathogenesis and to identify new biomarkers of disease. This review aims to document the recent advancements with respect to applications of proteomic technologies to study mechanisms of leukemogenesis, how this information could be used in the discovery of biological targets, and finally we describe the challenges of application of proteomic tools for the approach of BCP-ALL. [ABSTRACT FROM AUTHOR]

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions. [ABSTRACT FROM AUTHOR]

The process of unfolding the neutron energy spectrum has been subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the research of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in neutron spectrometry and dosimetry domains, however, the structure and learning parameters are factors that highly impact in the networks performance. In ANN domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, requiring no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training on the development data. In the network development phase, the only hurdle is to optimize the hyper-parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained it can be observed that despite the very similar results, GRNN performs better than BPNN. [ABSTRACT FROM AUTHOR]

The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. Novel methods based on Artificial Neural Networks have been widely investigated. In prior works, back propagation neural networks (BPNN) have been used to solve the neutron spectrometry problem, however, some drawbacks still exist using this kind of neural nets, i.e. the optimum selection of the network topology and the long training time. Compared to BPNN, it's usually much faster to train a generalized regression neural network (GRNN). That's mainly because spread constant is the only parameter used in GRNN. Another feature is that the network will converge to a global minimum, provided that the optimal values of spread has been determined and that the dataset adequately represents the problem space. In addition, GRNN are often more accurate than BPNN in the prediction. These characteristics make GRNNs to be of great interest in the neutron spectrometry domain. This work presents a computational tool based on GRNN capable to solve the neutron spectrometry problem. This computational code, automates the pre-processing, training and testing stages using a k-fold cross validation of 3 folds, the statistical analysis and the post-processing of the information, using 7 Bonner spheres rate counts as only entrance data. The code was designed for a Bonner Spheres System based on a 6 LiI(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. [ABSTRACT FROM AUTHOR]

Background: Inadequate trophoblast invasion and the subsequent inflammatory response have been implicated in preeclampsia (PE) pathogenesis. Because MYC-induced nuclear antigen (MINA) gene expression is involved in cell proliferation and differentiation, inflammatory response modulation, and the unpaired regulation of which is associated with human diseases, we sought to investigate the connection between MINA and PE.Objective: The aim of this study was to evaluate the possible relationship between the MINA rs4857304 variant and susceptibility to PE development as well as to estimate placental MINA gene expression and its association with PE.Methods: About 242 pregnant women (126 PE cases and 116 controls) were included. MINA genotyping and gene expression were evaluated by quantitative real-time polymerase chain reaction using TaqMan probes.Results: The G/G genotype of the MINA rs4857304 variant was associated with severe PE (p = 0.027, OR = 1.8, 95% CI = 1.8-3.2). Carriers of one G allele of the MINA rs4857304 variant exhibited a 1.7-fold increased risk of severe PE (p = 0.029, 95% CI = 1.1-3.0). MINA was underexpressed in preeclamptic placentas and MINA expression differed between the mild and severe PE groups. Differences in the expression levels of MINA were found among women with the T/T genotype of the rs4857304 polymorphism and carriers of at least one G allele (p = 0.024).Conclusion: PE and its severity are associated with the underexpression of placental MINA, and the G/G genotype of the MINA rs4857304 variant may modify the risk of severe PE among the PE cases evaluated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a highly diverse disease characterized by cytogenetic and molecular abnormalities, including altered microRNA (miRNA) expression signatures. AIM: We perform and validate a plasma miRNA expression profiling to identify potential miRNA involved in leukemogenesis. METHODS: MiRNA expression profiling assay was realized in 39 B-ALL and 7 normal control plasma samples using TaqMan Low Density Array (TLDA) plates on Applied Biosystems 7900 HT Fast Real-Time PCR System. MiRNA validation was done for six miRNA differentially expressed by quantitative real-time PCR. RESULTS: Seventy-seven circulating miRNA differentially expressed: hsa-miR-511, -222, and -34a were overexpressed, whereas hsa-miR-199a-3p, -223, -221, and -26a were underexpressed (p values < 0.005 for both sets). According to operating characteristic curve analysis, hsa-miR-511 was the most valuable biomarker for distinguishing B-ALL from normal controls, with an area under curve value of 1 and 100% for sensitivity, and specificity respectively. CONCLUSIONS: Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL. [ABSTRACT FROM AUTHOR]

Background Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. Results A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values < 0.05). Conclusion General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE. [ABSTRACT FROM AUTHOR]

Background: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. Methods: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. Results: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. Conclusions: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage. [ABSTRACT FROM AUTHOR]