Torsional Strength and Stiffness of a Passenger Car Coupling System

Between September 2019 and June 2022, the Federal Railroad Administration (FRA) sponsored a research team from Sharma & Associates to model and test the torsional strength of a passenger car coupling system to understand the performance of coupling systems in train accidents and to enhance current specifications. The team designed a test fixture to apply a controlled torque to a complete coupling system comprising a coupler, yoke, draft gear, and draft sill, and developed a Finite Element (FE) model of the test fixture to assess its structural integrity and to predict the applied torque necessary for failure. The team identified two modes of failure, draft sill failure and coupler shank failure. The mode of failure was found to depend on the degree of constraint provided by the draft sill. Researchers found the results of full-scale testing agreed reasonably well with those measured in the FE model tests. Classical overturning calculations indicated that an applied torsional moment of 297 kip-ft, the lowest measured torsional capacity of the tested coupling system, would likely rollover a single rail car. Such an applied torsional moment will likely be near or beyond the yield capacity of modern car structures and would need to be evaluated on a case-by-case basis in possible future work

The Safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month follow-up, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse

Hemo-metabolic impairment in patients with ST-segment elevation myocardial infarction: Data from the INTERSTELLAR registry

Background: Not only hemo-dynamic (HD) factors but also hemo-metabolic (HM) risk factors reflecting multi-organ injuries are considered as important prognostic factors in ST-segment elevation myocardial infarction (STEMI). However, studies regarding HM risk factors in STEMI patients are currently limited. Method: Under analysis were 1,524 patients with STEMI who underwent primary percutaneous coronary intervention in the INTERSTELLAR registry. Patients were divided into HM (≥ 2 risk factors) and non-HM impairment groups. The primary outcome was in-hospital all-cause mortality, and the secondary outcome was 1-year all-cause mortality. Results: Of 1,524 patients, 214 (14.0%) and 1,310 (86.0%) patients were in the HM and non-HM impairment groups, respectively. Patients with HM impairment had a higher incidence of in-hospital mortality than those without (24.3% vs. 2.7%, p < 0.001). After adjusting for confounders, HM impairment was independently associated with in-hospital mortality (inverse probability of treatment weighting [IPTW]-adjusted odds ratio: 1.81, 95% confidence interval: 1.08–3.14). In the third door-to-balloon (DTB) time tertile (≥ 82 min), HM impairment was strongly associated with in-hospital mortality. In the first DTB time tertile ( < 62 min), indicating relatively rapid revascularization, HM impairment was consistently associated with increased in-hospital mortality. Conclusions: Hemo-metabolic impairment is significantly associated with increased risk of in-hospital and 1-year mortality in patients with STEMI. It remains a significant prognostic factor, regardless of DTB time

Nitrogen sources on TPOMW valorization through solid state fermentation performed by Yarrowia lipolytica

This manuscript reports the valorization of two-phase olive mill waste (TPOMW) as raw material and carbon source for solid state fermentation using Yarrowia lipolytica as biocatalyst. Due to its chemical characteristics, a combination of different raw materials (TPOMW and wheat bran, WB) was evaluated and two distinct nitrogen sources were applied as supplementation for lipase production. A TPOMW/WB ratio of 1:1 and supplementation with ammonium sulfate was chosen as the best condition. The productivity in 24 h reached 7.8 U/gh and, after four days of process, only decreased about 35%. Process pH ranged from 5.5-5.9, remaining in an acid range. Thus, the successful use of TPOMW, a watery solid by-product with high content of lipids, as raw material for Yarrowia lipolytica growth and lipase production provided an environmental friendly alternative to valorize such waste.The authors kindly acknowledge the financial aid and research scholarships given by CAPES. Maria Alice Zarur Coelho thanks CNPq (Proc. 308890/ 2013-2)

Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder and Changes after Medication

BACKGROUND: Abnormalities of myelin integrity have been reported in obsessive-compulsive disorder (OCD) using multi-parameter maps of diffusion tensor imaging (DTI). However, it was still unknown to what degree these abnormalities might be affected by pharmacological treatment. OBJECTIVE: To investigate whether the abnormalities of white matter microstructure including myelin integrity exist in OCD and whether they are affected by medication. METHODOLOGY AND PRINCIPAL FINDINGS: Parameter maps of DTI, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were acquired from 27 unmedicated OCD patients (including 13 drug-naïve individuals) and 23 healthy controls. Voxel-based analysis was then performed to detect regions with significant group difference. We compared the DTI-derived parameters of 15 patients before and after 12-week Selective Serotonin Reuptake Inhibitor (SSRI) therapies. Significant differences of DTI-derived parameters were observed between OCD and healthy groups in multiple structures, mainly within the fronto-striato-thalamo-cortical loop. An increased RD in combination with no change in AD among OCD patients was found in the left medial superior frontal gyrus, temporo-parietal lobe, occipital lobe, striatum, insula and right midbrain. There was no statistical difference in DTI-derived parameters between drug-naive and previously medicated OCD patients. After being medicated, OCD patients showed a reduction in RD of the left striatum and right midbrain, and in MD of the right midbrain. CONCLUSION: Our preliminary findings suggest that abnormalities of white matter microstructure, particularly in terms of myelin integrity, are primarily located within the fronto-striato-thalamo-cortical circuit of individuals with OCD. Some abnormalities may be partly reversed by SSRI treatment

Differentiation of Schizophrenia Patients from Healthy Subjects by Mismatch Negativity and Neuropsychological Tests

BACKGROUND: Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%). CONCLUSIONS/SIGNIFICANCE: MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population

Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10-8). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies