Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.     

Aspartame—True or False? Narrative Review of Safety Analysis of General Use in Products

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180–200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.     

Proposals for person‐centred care in the COVID‐19 era. Delphi study

BackgroundIn this COVID‐19 era, we need to rethink the criteria used to measure the results of person‐centred care strategies.ObjectiveTo identify priorities, and criteria that health services can use to pursue actually the goal of achieving person‐centred care.DesignThree‐phase online qualitative study performed during May–July of 2020 using the Delphi technique.Setting and ParticipantsAn online platform was used for a consensus meeting of 114 participants, including health planning experts, health‐care institution managers, clinicians and patients.Main Outcome MeasuresCriteria and indicators for the achievement of person‐centred care.Main ResultsThe first round began with 125 proposals and 11 dimensions. After the second round, 28 ideas reached a high level of consensus among the participants. Ultimately, the workgroup agreed on 20 criteria for goals in the implementation of person‐centred care during the COVID‐19 era and 21 related indicators to measure goal achievement.DiscussionNine dimensions and 28 priorities were identified. These priorities are also in accordance with the quadruple aim approach, which emphasizes the need for care for health‐care professionals, without whom it is impossible to achieve a better quality of care.ConclusionsPerson‐centred care continues to be a key objective. However, new metrics are needed to ensure its continued development during the restoration of public health services beyond the control of COVID‐19.Patient or Public ContributionTwelve professionals and patient representatives participated voluntarily in the construction of the baseline questionnaire and in the selection of the criteria and indicators using an online platform for consensus meetings.     

Time‐dependent risk of depression,anxiety, and stress‐related disorders in patients with invasive and in situ breast cancer

Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress‐related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001–2010, median follow‐up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001–2013, median follow‐up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress‐related disorders [overall SIR (95% CI) = 1.57 (1.46–1.69), 1.55 (1.43–1.68) and 1.77 (1.60‐1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher‐grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher‐grade disease conferring short‐term risk only, while comorbidities were mainly associated with late‐onset events. No clinical risk factors were identified for stress‐related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress‐related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31‐5.79)]. The time‐dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho‐oncologic interventions.     

A combined analysis of genome-wide association studies in breast cancer

In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention.     

Construction and Validation of Simulation Models of Samples Made from 316L Steel by Applying Additive Technique

The main aim of the study includes research concerning the strength of samples printed out of 316L steel in the form of laminates and the creation of reflective simulation models with regard to the results obtained during the research. In addition, the tests addressed the effect of the arrangement of the printed layers on the final strength of the object. Static tensile tests allowed the material constants of 316L steel in the form of dimensionally printed laminate to be determined. Tests were conducted on samples with different printed angles. The tests also covered the impact of the printing envelope on samples with the printing angles. Based on the determined material constants, simulation models for calculations using the finite element method were created. Furthermore, the study includes analytical and simulation calculations of plain laminate in order to verify the accuracy of the Composite Layup module in Abaqus CAE software. The study was summarized by compiling and commenting on the results obtained from the conducted research. Tests showed that there is a possibility of simulating the strength of the printouts from 316L steel using the FEM calculations. It was shown that the FEM model results are similar to those obtained in the tests. The calculated errors were from 3.6 to 14.4%. The linear model describes well the first part of the stress–strain curve, but in further research, it is strongly recommended that a proper and checked nonlinear anisotropic one is presented.     

Correlation between KRAS,NRAS and BRAF mutations and tumor localizations in patients with primary and metastatic colorectal cancer

IntroductionDetection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, are limited.Material and methodsWe examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age 66 years). DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues using a Qiagen QIAamp DNA FFPE-kit. Analysis of mutations was carried out using the KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) with the Cobas 480 real-time PCR apparatus (Roche Diagnostics).ResultsKRAS mutations were detected in 190 (38%) patients, NRAS mutations in 20 (4%) patients, and BRAF mutations in 24 (4.8%) patients. There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF gene mutations. These mutations were significantly more often diagnosed in women (55.5%) than in men (41%, p < 0.005). Tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations.ConclusionsOur study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.     

Longer Times of Receipt of Adjuvant Endocrine Therapy Correspond to Improved Functional Capacity and Lower Adiposity in Women Receiving Adjuvant Therapy

Purpose

To study the use of functional capacity (FC) level and duration of aromatase inhibitor (AI) therapy with adiposity parameters in women with breast cancer.