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Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.

A high school diploma should mean that all students are ready for college "and" a career, but in Rhode Island, it did not. According to a 2019 audit, just four in a hundred Rhode Island seniors were prepared for both college and a career, and more than half graduated without concrete career skills. When the author became commissioner of the Rhode Island Department of Education (RIDE) in 2019, she committed to ensuring that Rhode Island would start providing all its high school students with equitable opportunities for postsecondary success. RIDE pressed ahead during the pandemic. In June 2020, XQ and RIDE staff presented audit findings to the Rhode Island Council on Elementary and Secondary Education, or K-12 Council for short, which is organized under the state board of education and oversees K-12. This article presents how the council challenged educators to identify solutions and create a plan to address the barriers Rhode Island students faced.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Abstract Increasing biological nitrogen (N) fixation (BNF) in maize production could reduce the environmental impacts of N fertilizer use, but reactive N in the rhizosphere of maize limits the BNF process. Using non-transgenic methods, we developed gene-edited strains of Klebsiella variicola (Kv137-2253) and Kosakonia sacchari (Ks6-5687) bacteria optimized for root-associated BNF and ammonium excretion in N-rich conditions. The aim of this research was to elucidate the mechanism of action of these strains. We present evidence from in vitro, in planta and field experiments that confirms that our genetic remodeling strategy derepresses BNF activity in N-rich systems and increases ammonium excretion by orders of magnitude above the respective wildtype strains. BNF is demonstrated in controlled environments by the transfer of labeled 15N2 gas from the rhizosphere to the chlorophyll of inoculated maize plants. This was corroborated in several 15N isotope tracer field experiments where inoculation with the formulated, commercial-grade product derived from the gene-edited strains (PIVOT BIO PROVEN® 40) provided on average 21 kg N ha-1 to the plant by the VT-R1 growth stages. Data from small-plot and on-farm trials suggest that this technology can improve crop N status pre-flowering and has potential to mitigate the risk of yield loss associated with a reduction in synthetic N fertilizer inputs.

Abstract The impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on neuropsychiatric fluctuations in Parkinson´s disease (PD) remains unclear. The Neuropsychiatric Fluctuations Scale (NFS) can help to fill this gap, directly measuring fluctuations between the OFF- and ON-medication conditions. The NFS provides NFS-plus (hyperdopaminergic) and NFS-minus (hypodopaminergic) sub-scores. Based on these, the NFS global scores express the overall magnitude of neuropsychiatric symptoms in both the OFF- and ON-medication states. The total fluctuation score (TFS) represents the difference between ON- vs. OFF-medication NFS global scores, thus assessing fluctuations amplitude. The NFS was used to evaluate changes in neuropsychiatric fluctuations between the OFF- and ON-medication conditions before and 1-year after bilateral STN-DBS in 45 PD patients (32 males; mean age, 61.3 ± 7.2 years; PD duration, 10.2 ± 3.0 years). After surgery, the amplitude of neuropsychiatric fluctuations was significantly reduced (p

The main objective was to evaluate the use of common bean flour (CBF), corn flour, and semolina to obtain instant noodles by means of a hot dry and frying process. The hot drying process was conducted at 60 °C for 4 h, and frying was conducted at 140 °C and 160 °C for 1 and 3 min. Proximate analysis, total phenolic content (TPC), the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, the oxygen radical absorbance capacity (ORAC) assay, phenolic acids and flavonoids profile by UPLC-ESI-MS/MS, the optimal cooking time (OCT), and color and texture analysis (TPA) were conducted. The general linear model and regression analysis were used. The incorporation of CBF resulted in an elevated protein content and TPC of the noodles. The noodles (hot dry) with CBF exhibited an enhanced antioxidant capacity. The adhesiveness has a direct correlation with the cinnamic, chlorogenic, and caffeic acid content (r2 = 0.95 or higher), as well as an inverse relationship with the vanillic, ferulic, and sinapic acids (r2 = −0.80 to −0.85). The dry hot noodles exhibited the lowest value of hardness (31.0 ± 1.5 N). The incorporation of common bean flour and corn flour enhances the nutritional profile of noodles. However, hot dry process affects their mechanical characteristics in comparison to the frying process.

Far-Infrared Radiation (FIR) is emerging as a novel non-invasive tool for mitigating inflammation and oxidative stress, offering potential benefits for certain medical conditions such as cardiovascular disease and chronic inflammatory disorders. We previously demonstrated that the application of patch-based FIR therapy on human umbilical vein endothelial cells (HUVECs) reduced the expression of inflammatory biomarkers and the levels of reactive oxygen species (ROS). Several in vitro studies have shown the inhibitory effects of FIR therapy on cell growth in different cancer cells (including murine melanoma cells), mainly using the wound healing assay, without direct cell motility or tracking analysis. The main objective of the present study was to conduct an in-depth analysis of single-cell motility and tracking during the wound healing assay, using an innovative high-throughput technique in the human melanoma cell line M14/C2. This technique evaluates various motility descriptors, such as average velocity, average curvature, average turning angle, and diffusion coefficient. Our results demonstrated that patch-based FIR therapy did not impact cell proliferation and viability or the activation of mitogen-activated protein kinases (MAPKs) in the human melanoma cell line M14/C2. Moreover, no significant differences in cell motility and tracking were observed between control cells and patch-treated cells. Altogether, these findings confirm the beneficial effects of the in vitro application of patch-based FIR therapy in human melanoma cell lines, although such effects need to be confirmed in future in vivo studies.

Abstract Background The Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB’s widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute’s pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist’s role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors. Materials and methods Literature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024. Clinical Data: retrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test. Results Literature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors. Clinical data A total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months – 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes. Conclusion Thanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.

The virtualization of university teaching in Spain caused by the pandemic was a success, but the urgent nature of the transition from face-to-face teaching to online teaching meant that some peculiarities that should have been taken into account were omitted. Thus, in order to find out and analyze the factors causing the success of this virtualization and take measures to address the weak points of this process as teachers may want to maintain the use of online teaching as support for their face-to-face teaching, these factors were located through a literature review and were classified according to their level of importance in this success through a causal study carried out with the methodology of fuzzy cognitive maps. The results achieved indicated the determining factors in students, involving their attitude, aptitude and predisposition, which are factors where the work of the teacher is of main relevance (as it exerts the greatest influence on these factors). For this reason, technological attitude and aptitude, teaching style, and the creation and structuring of content should be reinforced in teachers.