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Driving school was born from an education system that was worried about the occurrence of loss learning during the Covid 19 pandemic. The purpose of this study was to examine qualitatively descriptively about the implementation of literacy and numeracy learning in the students of SD Negeri 16 Siantan, North Pontianak, as one of the selected driving schools in the province of West Kalimantan. This research method is qualitative, by collecting primary data generated from field observations (schools), interviews with several related parties such as school principals, classroom teachers, students, and campus ambassadors teaching 3 (KM 3) and supported by data secondary data obtained from references or literature relevant to the research topic. Based on the research activities carried out, it can be concluded that the implementation of driving curriculum-based learning related to literacy and numeracy skills has been carried out well even though it requires adjustments to room conditions and the limited supporting facilities available. The number of students in the study group and the learning support model tools determine the effectiveness of learning with an independent curriculum.

Highlights Females show a significant increase in the expression of MED31 in the frontal cortex. This gene is involved in lipid metabolism and neural diseases. We found 237 genes having sex-based significantly differential expression in substantia nigra. Functional profiling of these genes reveals a differential sex-related behavior in PD regarding their biological functions, protein-protein interaction networks, and transcription factors activation. There are remarkable sex based differential mechanisms in typical PD hallmarks: inflammation, mitochondrial dysfunction, and oxidative stress. Studies on sex differences in PD are needed to improve more targeted interventions.

The paper presents the core aims and objectives of the teaching materials developed within the IEREST (Intercultural Education Resources for Erasmus Students and their Teachers) project, and shows how the innovative approach adopted for these activities can be implemented in the classroom. The IEREST teaching modules are innovative in that the approach adopted draws strongly on the notions of "critical cosmopolitanism" (Holliday 2012) and "intercultural communicative competence" (Byram 1997 and 2012). The activities in the modules promote a view of culture as a negotiated "process" among individuals, small or large groups and intercultural communication as a co-construction of meaning conveyed across linguistic and cultural boundaries, thus rejecting explicitly any "essentialist" attitudes and simplistic over-generalisation of "otherness." The approach to language use in intercultural encounters observes how the above concepts are expressed in a number of contexts, while also building on the view that intercultural communication among bilinguals often takes advantage of a "lingua franca," a foreign language that all the participants in the communicative activity have in common because they had learned it. Taking into account the concept of "linguaculture" (Risager 2012) the modules seek to raise awareness of the negotiating process in rendering meaning through a linguistic and cultural blend of both the target language and the speaker's first language. The paradigm shift proposed by the IEREST Modules indicates a need to rethink current practices in intercultural education and to acknowledge societal changes in multilingual Europe and beyond.

Purpose To understand the systemic effect of major spine surgery, we investigated stress, anabolic and catabolic hormonal levels and their association with interleukin 6 (IL-6) in patients undergoing elective lumbar spine fusion surgery. Methods Blood samples were collected preoperatively, and at 1, 3, 42, 90 days postoperatively (POD) from 49 patients who underwent elective lumbar spine fusion surgery. Results Serum concentration of cortisol was below the preoperative value at POD 1 but did not differ from the baseline values thereafter. Adrenocorticotropic hormone (ACTH) decreased at PODs 1 and 3. Testosterone decreased at PODs 1 and 3 in men, and at POD 3 in women. Sex hormone-binding globulin decreased at PODs 1 and 3 in both genders. No changes were observed in free testosterone or growth hormone concentrations. Insulin-like growth factor 1 increased significantly above the preoperative level at PODs 42 and 90 in women, and at POD 42 in men. IL-6 was significantly elevated at PODs 1 and 3. Increases in IL-6 from the preoperative level to POD 1 correlated significantly with decreases of cortisol at POD 1 but not with ACTH. Conclusions There were only short-term stress hormonal changes after elective lumbar spine fusion surgery. Cortisol changes after elective lumbar spine surgery are transient and might be partly cytokine induced and non-ACTH driven since there was association between cortisol and IL-6 but not with ACTH and IL-6.

ABSTRACT Mice are refractory to infection with human-tropic hepatitis C virus (HCV), although distantly related rodent hepaciviruses (RHV) circulate in wild rodents. To investigate whether liver intrinsic host factors can exhibit broad restriction against these distantly related hepaciviruses, we focused on Shiftless (Shfl), an interferon (IFN)-regulated gene (IRG) which restricts HCV in humans. Unusually, and in contrast to selected classical IRGs, human and mouse SHFL orthologues (hSHFL and mSHFL, respectively) were highly expressed in hepatocytes in the absence of viral infection, weakly induced by IFN, and highly conserved at the amino acid level (>95%). Replication of both HCV and RHV subgenomic replicons was suppressed by ectopic expression of mSHFL in human or rodent hepatoma cell lines. Gene editing of endogenous mShfl in mouse liver tumor cells increased HCV replication and virion production. Colocalization of mSHFL protein with viral double-stranded RNA (dsRNA) intermediates was confirmed and could be ablated by mutational disruption of the SHFL zinc finger domain, concomitant with a loss of antiviral activity. In summary, these data point to an evolutionarily conserved function for this gene in humans and rodents: SHFL is an ancient antiviral effector which targets distantly related hepaciviruses via restriction of viral RNA replication. IMPORTANCE Viruses have evolved ways to evade or blunt innate cellular antiviral mechanisms within their cognate host species. However, these adaptations may fail when viruses infect new species and can therefore limit cross-species transmission. This may also prevent development of animal models for human-pathogenic viruses. HCV shows a narrow species tropism likely due to distinct human host factor usage and innate antiviral defenses limiting infection of nonhuman liver cells. Interferon (IFN)-regulated genes (IRGs) partially inhibit HCV infection of human cells by diverse mechanisms. Here, we show that mouse Shiftless (mSHFL), a protein that interferes with HCV replication factories, inhibits HCV replication and infection in human and mouse liver cells. We further report that the zinc finger domain of SHFL is important for viral restriction. These findings implicate mSHFL as a host factor that impairs HCV infection of mice and provide guidance for development of HCV animal models needed for vaccine development.

Type 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation and the underlying microvascular circulation. The study included 119 T2DM patients (91 male/28 female). TcPO2 measurements were conducted with the Tina TCM4 Series transcutaneous monitor (Radiometer, Copenhagen, Sweden) and skin electrodes. Patients with TcPO2 < 40 mmHg were younger (p = 0.001), had significantly higher systolic blood pressure (SBP) (p = 0.023), glycated hemoglobin (HbA1c) (p = 0.013), fasting plasma glucose (fPG) (p = 0.038), total cholesterol (p = 0.006), LDL cholesterol (p = 0.004), and had more frequent smoking habits (p = 0.001) than those with TcPO2 ≥ 40 mmHg. The main predictors for the TcPO2 value (R2 = 0.211) obtained via stepwise regression analysis were age, smoking, SBP, HbA1c, fPG, and total and LDL cholesterol. Among all the listed predictors, smoking, HbA1c, and LDL cholesterol were found to be the most significant, with negative parameter estimates of −3.051310 (p = 0.0007), −2.032018 (p = 0.0003), and −2.560353 (p = 0.0046). The results of our study suggest that in association with other risk factors, smoking is the main predictor for lower TcPO2 in T2DM.

Type 2 diabetes mellitus (T2DM) significantly increases the risk of atherosclerotic cardiovascular disease. Ankle brachial index (ABI) and carotid artery stenosis are non-invasive indicators of generalized atherosclerosis. This study aimed to explore the risk factors for ABI and carotid artery stenosis and discover which factors simultaneously influence both conditions in T2DM. The study included a total of 101 patients with T2DM. ABI was performed via Doppler ultrasound, and both common carotid arteries were examined via ultrasound to obtain the percentage of carotid artery stenosis. A negative correlation was noted between the ABI and the percentage of carotid artery stenosis (p = 0.043). ABI correlated significantly negatively with waist circumference (p = 0.031), total cholesterol (p = 0.003), low-density lipoprotein (LDL) cholesterol (p = 0.003), and C-reactive protein (CRP) (p = 0.017), whereas the percentage of carotid artery stenosis correlated with the smoking habit (p = 0.017) and CRP (p = 0.042). The best model for predicting the ABI value (R2 = 0.195) obtained from stepwise regression analysis included waist circumference, LDL cholesterol, triglycerides, and CRP, while the best model for the percentage of the carotid artery stenosis (R2 = 0.112) included smoking and CRP. CRP influenced the ABI value with a negative parameter estimate of −0.008962 (p = 0.053) and the percentage of the carotid artery stenosis with a positive parameter estimate of 0.443655 (p = 0.006) relative to a one-unit change of it, presenting the negatively significant impact of CRP on the association between carotid artery stenosis and low ABI. Our results suggest that CRP is the most important risk factor that connects ABI and carotid artery stenosis, which are important non-invasive indicators of generalized atherosclerosis in T2DM.

Background: Multiple sclerosis (MS), a chronic auto-immune, inflammatory, and degenerative disease of the central nervous system, affects both males and females; however, females suffer from a higher risk of developing MS (2–3:1 ratio relative to males). The precise sex-based factors influencing risk of MS are currently unknown. Here, we explore the role of sex in MS to identify molecular mechanisms underlying observed MS sex differences that may guide novel therapeutic approaches tailored for males or females. Methods: We performed a rigorous and systematic review of genome-wide transcriptome studies of MS that included patient sex data in the Gene Expression Omnibus and ArrayExpress databases following PRISMA statement guidelines. For each selected study, we analyzed differential gene expression to explore the impact of the disease in females (IDF), in males (IDM) and our main goal: the sex differential impact of the disease (SDID). Then, for each scenario (IDF, IDM and SDID) we performed 2 meta-analyses in the main tissues involved in the disease (brain and blood). Finally, we performed a gene set analysis in brain tissue, in which a higher number of genes were dysregulated, to characterize sex differences in biological pathways. Results: After screening 122 publications, the systematic review provided a selection of 9 studies (5 in blood and 4 in brain tissue) with a total of 474 samples (189 females with MS and 109 control females; 82 males with MS and 94 control males). Blood and brain tissue meta-analyses identified, respectively, 1 (KIR2DL3) and 13 (ARL17B, CECR7, CEP78, IFFO2, LOC401127, NUDT18, RNF10, SLC17A5, STMP1, TRAF3IP2-AS1, UBXN2B, ZNF117, ZNF488) MS-associated genes that differed between males and females (SDID comparison). Functional analyses in the brain revealed different altered immune patterns in females and males (IDF and IDM comparisons). The pro-inflammatory environment and innate immune responses related to myeloid lineage appear to be more affected in females, while adaptive responses associated with the lymphocyte lineage in males. Additionally, females with MS displayed alterations in mitochondrial respiratory chain complexes, purine, and glutamate metabolism, while MS males displayed alterations in stress response to metal ion, amine, and amino acid transport. Conclusion: We found transcriptomic and functional differences between MS males and MS females (especially in the immune system), which may support the development of new sex-based research of this disease. Our study highlights the importance of understanding the role of biological sex in MS to guide a more personalized medicine.

Through this action research project, we endeavour to reconfigure pedagogical encounters involving children and the natural world to be more reciprocal and respectful, as well as responsive to the ecological crisis. The goal of our research is to advance understandings of how to educate children to become good relatives to all the beings on these Lands. We are guided by the question: How can we educate children to live like Salmon People (those Indigenous to this place), which is the sacred responsibility of all those residing on the Coast Salish territories? Practices that contributed to shifting relationship between people and the Land and moved our community beyond our human-centric engagement were participatory and embodied. They included acts to care for Salmon and other beings as relatives, as well as experiencing Land as agential and existing independently of human desire. We see our research as a site for what Kari Grain calls “critical hope.”