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Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a LibreText biochemistry book. One is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs. time) for simple reactions and complex metabolic and signal transduction pathways. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v[subscript 0]) versus substrate concentration.

This case study examines the political and social pressures high school social studies teachers face in rural areas. In the political sphere, many social studies teachers focus on the end of course exam. The resources that informed this study were public materials on the web. Findings indicate teachers stay to state tested content.

Sustainable crop cultivation is a crucial goal in modern agriculture, aiming to attain high productivity while conserving natural resources. This requires the implementation of rational cultivation techniques, with proper irrigation and fertilization practices playing a crucial role in ensuring plant well-being and providing natural protection against biotic and abiotic stresses. The health-promoting properties of crops are also significantly influenced by irrigation and fertilization. This study investigated the productivity, nutritional composition, bioactive compounds, and antioxidant capacity of Vineta early potato cultivar tubers under drip irrigation conditions, combined with nitrogen fertilization through fertigation or broadcasting. Two-factor trials included drip irrigation (control or drip) and nitrogen application (broadcast or fertigation). Precise treatments, such as drip irrigation and N-fertigation were found to enhance all productivity traits. Both practices positively impacted tuber nutrient content. The highest levels of total polyphenols and chlorogenic acid were observed in non-irrigated and broadcasted tubers. Drip-irrigated and N-fertigated tubers exhibited high levels of vitamin C and antioxidant activity. In summary, the combination of drip irrigation with appropriate fertilization methods positively influenced potato crops, as evidenced by an increase in productivity and the quality of tubers.

W artykule przedstawiono wybrane przypadki przestępstw w 2022 r. na tle statystyk Policji, Krajowej Administracji Skarbowej i Straży Granicznej. Będące częścią cyklu corocznych analiz opracowanie obrazuje tendencje i zagrożenia zabytków oraz dóbr kultury w danym roku. Komplementarne przedstawienie informacji o zagrożeniu dziedzictwa kulturowego przestępczością jest istotne dla badań mających na celu wypracowanie strategii jego ochrony. Na zagrożenie dziedzictwa kulturowego przestępczością mają wpływ szczególne wydarzenia, które oddziałują na poziom bezpieczeństwa w państwie. Wśród czynników, które trzeba wziąć pod uwagę, analizując zjawisko przestępczości przeciwko dziedzictwu kulturowemu w 2022 r., należy wskazać początek inwazji Rosji na Ukrainę.

This case study examines the intersection of rural education, new leadership, and supervising teachers when a power imbalance exists. Using a real-life example of supervision and professional interactions, this case study focuses future administrators on the real-life conflicts inherent in supervision and employee rights. The case study examines the inherent power dynamics in some rural school systems, where changing demographics have resulted in the dissonance between what the Board of Education, the superintendent, and a newly appointed principal see as an educational environment for cultural responsiveness which acknowledges changes in the community and the pre-existing, established norms. The interactions between the principal, a veteran teacher, and a classroom environment during contentious discussions among students in a civics education class debate launched faculty discontent towards the new administration. The debate occurs during an already contentious moment during the stalled teacher's collective bargaining agreement.

ObjectivesThe aim of the study was to assess the reimbursement policy for orphan drugs (ODs) in selected European countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedures and reimbursement decision-making.Materials and MethodsA list of authorized ODs was extracted from a web-based registry of the European Medicines Agency, including information on active substance, Anatomical Therapeutic Chemical (ATC) classification code, and therapeutic area. A country-based questionnaire survey was conducted between September 2022 and September 2023 among selected experts from 12 European countries. A descriptive and statistical analysis was performed to identify correlations between country characteristic, HTA procedures, drug indication and positive recommendations or reimbursement decisions for ODs.ResultsSafety assessment for ODs was mandatory in 10 countries, while it was optional in one country (Italy) and not required in one country (Iceland). Efficacy assessment for ODs was mandatory in 11 countries and not required in one country (Iceland). The impact of safety and efficacy assessment on reimbursement decisions was rated as high in 10 countries and as low in one country (Germany). Dedicated OD legislation and policies were reported in seven countries. In two countries (Belgium, Iceland), the HTA was not mandatory, and in one country (Germany), it only had an informative function. A positive recommendation (from an HTA agency or advisory body) guaranteed reimbursement in four countries, while a negative recommendation excluded reimbursement only in one country (Iceland). The proportion of reimbursed ODs ranged from 23.5% in Iceland to 86% in Germany (p < 0.001). ODs with ATC code L represented the largest group of medicines (n = 49). They were also very frequently reimbursed ODs in the countries studied, with a mean of 61.8% (p < 0.001).ConclusionEuropean countries differ in terms of the impact of clinical issues and additional clinical aspects on the reimbursement policy for ODs. Reimbursement decisions were affected by OD-specific legislation, policies, and EMA authorization status. HTA dossiers and procedures significantly influenced reimbursement decisions, although some ODs were reimbursed regardless of the positive or negative recommendations. ATC codes were significantly correlated with reimbursement status and positive recommendation.

IntroductionWe examined the perceptions of the Master of Public Health (MPH) degree graduates regarding their personal competencies, job performance and professional development using a mixed method, explanatory sequential design.MethodsA cross-sectional, self-administered questionnaire of the Haifa School of Public Health alumni who graduated between 2005 and 2022 was disseminated to 849 graduates between March and June 2022, from which 127 responded (response rate: 14.90%). This was followed by 24 in-depth interviews with alumni from the same sample (conducted between November 2022 and March 2023).ResultsThe sample included 74.8% of females with a mean age of 40.7 years, 35% of alumni agreed that the MPH degree helped them attain a promotion in their present position (in rank or salary), and 63.8% felt that the degree helped them improve their job performance and contribute to their current workplace. Most (80.3%) alumni reported not changing jobs after graduation. The interview themes revealed that the MPH contributed to their personal and professional lives, provided them with a holistic view of public health and health systems, and improved their in-depth scientific skills. The main reported barriers to professional development included missing core competencies, low salaries, and a lack of information regarding suitable jobs. Surprisingly, an MPH was not a requirement for some public health sector jobs. Alumni reported that the MPH degree contributed to improving many graduates’ careers and satisfaction levels and to build their leadership competencies in public health.DiscussionThere seems to be a lack of coordination between the academic curriculum and the jobs available for alumni, hindering better alumni professional development. Regular discussions, information sharing, and curriculum refinements between MPH program leaders and health sector leaders might help address many of the concerns of MPH degree graduates.

Abstract BackgroundConcussion, or mild traumatic brain injury, is a growing public health concern, affecting approximately 1.2% of the population annually. Among children aged 1‐17 years, concussion had the highest weighted prevalence compared to other injury types, highlighting the importance of addressing this issue among the youth population. ObjectiveThis study aimed to assess adherence to Return to Activity (RTA) protocols among youth with concussion and to determine if better adherence affected time to recovery and the rate of reinjury. MethodsChildren and youth (N=139) aged 5‐18 years with concussion were recruited. Self-reported symptoms and protocol stage of recovery were monitored every 48 hours until symptom resolution was achieved. Daily accelerometry was assessed with the ActiGraph. Data were collected to evaluate adherence to the RTA protocol based on physical activity cutoff points corresponding to RTA stages. Participants were evaluated using a battery of physical, cognitive, and behavioral measures at recruitment, upon symptom resolution, and 3 months post symptom resolution. ResultsFor RTA stage 1, a total of 13% of participants were adherent based on accelerometry, whereas 11% and 34% of participants were adherent for stage 2 and 3, respectively. The median time to symptom resolution was 13 days for participants who were subjectively reported adherent to the RTA protocol and 20 days for those who were subjectively reported as nonadherent (P ConclusionsOverall, adherence to staged protocols post concussion was minimal when assessed with accelerometers, but adherence was higher by self-report. More physical activity restrictions, as specified in the RTA protocol, resulted in lower adherence. Although objective adherence was low, reinjury rate was lower than expected, suggesting a protective effect of being monitored and increased youth awareness of protocols. The results of this study support the move to less restrictive protocols and earlier resumption of daily activities that have since been implemented in more recent protocols.

BackgroundDespite evidence of the beneficial effects of skilled birth attendance (SBA) on maternal health and childbirth outcomes, there are disparities in access across counties in Kenya. These include Migori County which has historically recorded high maternal mortality rates. In 2007, the Lwala Community Alliance was founded to improve health outcomes in this county. The objective of this study is to provide a baseline status of facility childbirth and SBA in Migori and to characterize the effect of Lwala intervention on these outcomes.MethodsA cross-sectional household survey was designed for a 10-year study to evaluate the effectiveness of Lwala initiatives. The 2019 and 2021 household surveys were conducted in Lwala intervention wards and in comparison wards with sample sizes of 3,846 and 5,928 mothers, respectively. The survey captured demographic, health, and socioeconomic data at each household, data on SBA and facility childbirth, and explanatory variables. A generalized linear model was used to determine factors associated with SBA. A secondary trend analysis was conducted to determine change over time in the explanatory variables and SBA. To determine the change in SBA rate due to Lwala intervention, controlling for background temporal trends, a difference-in-differences (DiD) model compared SBA rates in intervention wards and comparison wards.ResultsSBA increased in all surveyed wards and across all explanatory variables from 2019 to 2021. The DiD analysis showed that the SBA rate increased more in Lwala intervention wards than in comparison wards (Adjusted Prevalence Rate Ratio 1.05, p

OBJECTIVE: Over a third of women in the United States report a lifetime history of intimate partner violence. Although a recent review found that intimate partner violence is related to poor subjective sleep, the majority of studies involved reproductive-aged women and used suboptimal measures of interpersonal violence and/or insomnia. We examined the relationship between lifetime intimate partner violence and current clinical insomnia in a cross-sectional sample of midlife women veterans. METHODS: Cross-sectional data were drawn from the Midlife Women Veterans Health Survey. Women Veterans (N = 232) aged 45 to 64 years enrolled in Department of Veterans Affairs health care in Northern California completed an adapted version of the Extended-Hurt, Insult, Threaten, Scream to assess lifetime history of intimate partner violence (screening threshold score and any physical, sexual, and psychological intimate partner violence) and the Insomnia Severity Index to assess current insomnia. RESULTS: In multivariable analyses, lifetime history of intimate partner violence was associated with twofold to fourfold odds of current clinical insomnia, including overall intimate partner violence (odds ratio, 3.24; 95% confidence interval, 1.57-6.69), physical intimate partner violence (odds ratio, 2.01; 95% confidence interval, 1.09-3.70), psychological intimate partner violence (odds ratio, 3.98; 95% confidence interval, 2.06-7.71), and sexual intimate partner violence (odds ratio, 2.09; 95% confidence interval, 1.08-4.07). CONCLUSIONS: Lifetime history of intimate partner violence is common and may be associated with clinical insomnia during midlife. Findings highlight the importance of screening midlife women for intimate partner violence and recognizing the potential role of this traumatic exposure on womens health.

Abstract Homocysteine (Hcy) and Hcy-thiolactone (HTL) affect fibrin clot properties and are linked to cardiovascular disease. Factors that influence fibrin clot properties and stroke are not fully understood. To study sulfur-containing amino acid metabolites, fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to stroke, we analyzed plasma and urine from 191 stroke patients (45.0% women, age 68 ± 12 years) and 291 healthy individuals (59.7% women, age 50 ± 17 years). Plasma and urinary levels of sulfur-containing amino acid metabolites and fibrin clot properties were significantly different in stroke patients compared to healthy individuals. Fibrin CLT correlated with fibrin Absmax in healthy males (R2 = 0.439, P = 0.000), females (R2 = 0.245, P = 0.000), female stroke patients (R2 = 0.187, P = 0.000), but not in male stroke patients (R2 = 0.008, P = ns). Fibrin CLT correlated with age in healthy females but not males while fibrin Absmax correlated with age in both sexes; these correlations were absent in stroke patients. In multiple regression analysis in stroke patients, plasma (p)CysGly, pMet, and MTHFR A1298C polymorphism were associated with fibrin Absmax, while urinary (u)HTL, uCysGly, and pCysGly were significantly associated with fibrin CLT. In healthy individuals, uHTL and uGSH were significantly associated with fibrin Absmax, while pGSH, and CBS T833C 844ins68 polymorphism were associated with fibrin CLT. In logistic regression, uHTL, uHcy, pCysGly, pGSH, MTHFR C677T polymorphism, and Absmax were independently associated with stroke. Our findings suggest that HTL and other sulfur-containing amino acid metabolites influence fibrin clot properties and the risk of stroke.

Abstract Nutritional and genetic deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis, which is a major cause of cardiovascular disease (CVD). Impaired autophagy causes the accumulation of damaged proteins and organelles and is associated with CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone and N-Hcy-protein. However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of Hcy-thiolactone, N-Hcy-protein, and Hcy on autophagy human umbilical vein endothelial cells. We found that treatments with Hcy-thiolactone, N-Hcy-protein, or Hcy significantly downregulated beclin 1 (BECN1), autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and microtubule-associated protein 1 light chain 3 (LC3) mRNA and protein levels. We also found that these changes were mediated by upregulation by Hcy-thiolactone, N-Hcy-protein, and Hcy of autophagy-targeting microRNA (miR): miR-21, miR-155, miR-216, and miR-320c. The effects of these metabolites on levels of miR targeting autophagy as well as on the levels of BECN1, ATG5, ATG7, and LC3 mRNA and protein were abrogated by treatments with inhibitors of miR-21, miR-155, miR-216, and mir320c. Taken together, our findings show that Hcy metabolites can upregulate miR-21, miR-155, miR-216, and mir320c, which then downregulate autophagy in human endothelial cells, important for vascular homeostasis.

Determination of blood flow parameters in the ophthalmic artery and central retinal artery using Doppler ultrasound in patients with type 1 diabetes mellitus without fundus signs of diabetic retinopathy and with mild non-proliferative retinopathy.

Due to the consequences of fires, new and environmentally friendly firefighting techniques are constantly being sought. There are many methods of extinguishing flames around the world. One of them is a technique that uses acoustic waves for extinguishing, which can be seen as repeated sequences of molecular compression and dilation (acoustic waves transfer energy due to the movements of molecules and atoms). This research shows a new approach to the extinguishing of flames. In practice, the extinguishing capabilities of low-frequency modulated and unmodulated acoustic waves were tested on a laboratory station, the main component of which was a high-powered acoustic extinguisher (the nominal power was equal to 1700 W). A B&C 21DS115 woofer was applied as a sound source. A Rigol DG4102 and a Proel HPX2800 were used as an acoustic generator with a modulator and as a power amplifier, respectively. In this paper, the presented results are limited to extinguishing candle flames. The tests made it clear that flames can be extinguished using properly generated and directed acoustic waves. As the results indicate, it becomes possible to effectively extinguish flames with both low-frequency modulated and unmodulated acoustic waves, which brings many benefits.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention relevanceUnderstanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Which auditory features drive listeners’ everyday perception of their favorite music? To test this, we created a novel corpus of covers of 50 popular songs from 2008 to 2019, capturing a wide variety of genres and styles. Cover versions of popular songs offer a rich space of natural musical stimuli that match original songs on some dimensions (e.g., lyrics) but not others (e.g., genre). We pseudo-randomly selected one cover per song and asked subjects to rate similarity between clips of original and cover versions. We measured differences between originals and covers in terms of tempo, key, gender, timbre (MFCCs), and genre. While all of the features had significant relationships with similarity ratings, similarity ratings were driven most strongly by tempo, timbre, and genre (R^2 = 0.5076). Our uniquely naturalistic and holistic approach links listeners' everyday, subjective impressions of popular music with fine-grained acoustic features.

This work contains a description of the modified Henning operation. This technique can be proven especially useful in difficult cases of damaged meniscus (complex injuries). It consists of three stages: stable suturing of the meniscus, placement of the graft from the iliotibial band on the meniscus, and covering the graft with a collagen membrane. Stitching the meniscus provides initial stabilization, the graft from the iliotibial band provides scaffolding for the reconstructed tissue, and the collagen membrane provides biological stimulation for healing.

Background: Enabling, supporting and promoting positive health-related behaviours is critical in addressing the major public health challenges of our time, and the multifaceted nature of behaviours requires an evidence-based approach. This statement seeks to suggest how a much-needed enhanced use of behavioural and cultural science and insights for health could be advanced. Study design and methods: and methods: Public health authorities of Europe and Central Asia and international partner organizations in September 2023 met in Copenhagen, Denmark, to discuss the way forward. Drawing on 1) country reporting to WHO, 2) interview study with public health authorities and 3) the meeting deliberations, this meeting statement was developed. Results: The meeting statement presents a joint call for step-change accelerated use of evidence-based approaches for health behaviours. Actionable next steps for public health authorities and international and regional development partners in health are presented. Conclusions: The way forward involves increased resource allocation, integration of behavioural insights into health strategies, advocacy through case and cost-effectiveness examples and capacity building.