Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review

The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline [PubMed], Scopus,Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (CYP2R1, CYP27B1), transport (GC), and metabolism (CYP24A1), as well as in the vitamin D receptor (VDR), are associated with OS and/or PFS in patients with NSCLC. The SNPs in VDR have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the VDR, CYP27B1, CYP24A1, GC, and CYP2R1 genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.The Virgen de las Nieves University Hospital Biobank was supported by grants co-funded by ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039)

Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies

A surgical model of short bowel syndrome induces a long-lasting increase in pancreatic beta-cell mass

Several surgical techniques are used nowadays as a severe treatment for obesity and diabetes mellitus type 2. These techniques are aggressive due to drastic changes in the nutrient flow and non-reversible modifications on the digestive tube. In this paper we present the effects of a massive intestinal resection on the pancreas. Results have shown that short bowel technique is less aggressive to normal anatomy and physiology of the intestinal tract than Gastric bypass or biliopancreatic diversion (e.g.). In this paper we reproduce a model of short bowel syndrome (SIC), with similar surgical conditions and clinical complications as seen in human cases. This work was conducted on normal Wistar rats, with no other concurrent factors, in order to determine the effects on normal pancreas islets. We measured pancreatic implications by histomorphometric studies, which included beta-cell mass by immunocytochemistry, and apoptosis/proliferation test with TUNEL technique and Ki-67. Briefly, we reported on an increased relative area of the islets of the pancreas, as well as an increase in the average size of islets in the SIC versus the control group. Furthermore we stated that this increase in size of the pancreatic islets is due to the mechanisms of proliferation of beta cells in animals undergoing SIC. These goals could reveal a direct influence of surgical modification of the digestive tract over the pancreatic beta cell homeostasis. In this sense, there are many potential stimulators of intestinal adaptation, including peptide hormones and growth components which are associated or involved as effectors of the endocrine pancreas

Role of age and sex in the diagnosis of early-stage malignant melanoma: A cross-sectional study

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). The aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2,430 patients with MM were recruited. Cases of in situ (Tis) and T1 MM were more frequent than T2–T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0–29 years (1.18), and 30–59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis–T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM

Design of two-stage class AB CMOS buffers: a systematic approach

A systematic approach for the design of two-stage class AB CMOS unity-gain buffers is proposed. It is based on the inclusion of a class AB operation to class A Miller amplifier topologies in unity-gain negative feedback by a simple technique that does not modify quiescent currents, supply requirements, noise performance, or static power. Three design examples are fabricated in a 0.5 μm CMOS process. Measurement results show slew rate improvement factors of approximately 100 for the class AB buffers versus their class A counterparts for the same quiescent power consumption (< 200 μW)

El análisis de riesgos del patrimonio histórico como herramienta de gestión

España, Junta de Andalucía RIVUPH (HUM 6775

±0.25-V Class-AB CMOS Capacitance Multiplier and Precision Rectifiers

Reduction of minimum supply requirements is a crucial aspect to decrease the power consumption in VLSI systems. A high-performance capacitance multiplier able to operate with supplies as low as ±0.25 V is presented. It is based on adaptively biased class-AB current mirrors which provide high current efficiency. Measurement results of a factor 11 capacitance multiplier fabricated in 180-nm CMOS technology verify theoretical claims. Moreover, low-voltage precision rectifiers based on the same class-AB current mirrors are designed and fabricated in the same CMOS process. They generate output currents over 100 times larger than the quiescent current. Both proposed circuits have 300-nW static power dissipation when operating with ±0.25-V supplies

An Op-Amp Approach for Bandpass VGAs With Constant Bandwidth

Two approaches to implement variable gain amplifiers based on Miller op-amps are discussed. One has true constant bandwidth while the other has essentially reduced bandwidth variations with varying gain. Servo-loops and ac coupling techniques with quasi floating gate transistors are used to provide a bandpass response with very low cutoff frequency in the range of hertz. In practice, one of the schemes is shown to have bandwidth variations close to a factor two while the second one has true constant bandwidth over the gain tuning range. Experimental results of test chip prototypes in 180-nm CMOS technology verify the theoretical claims