Kinetic and Mechanistic Modelling of Pyrimethanil Fungicide Adsorption onto Soils of Varying Physico-chemical Properties.

Pesticide transport in the environment is impacted by the kinetics of its adsorption onto soil. The adsorption kinetics of pyrimethanil was investigated in ten soil samples of varying physicochemical properties. The highest adsorption was in the soil having the maximum silt and CaCO3 contents, pH and electrical conductance but the lowest amorphous Fe oxides and CaCl2 extractable Mn. Pseudo-second order kinetics and intra-particle diffusion model best accounted the adsorption kinetics of pyrimethanil. The equilibrium adsorption estimated by pseudo-second order kinetics (q02) was significantly and positively correlated with CaCl2 extractable Cu content (r = 0.709) while rate coefficient (k02) had a negative correlation with crystalline iron oxides content (r = -0.675). The intra-particle diffusion coefficient (ki.d.) had inverse relationship with CaCl2 extractable Mn content in soils (r = -0.689). FTIR spectra showed a significant interaction of pyrimethanil with micronutrient cations. Adsorption kinetic parameters of pyrimethanil could be successfully predicted by soil properties. The findings may help to evolve fungicide management decisions.

Mental Health Evaluation of Younger and Older Adolescents Referred to the Center of Expertise on Gender Dysphoria in Amsterdam, The Netherlands.

The present study aimed to investigate whether differences exist between younger and older presenting adolescents at the Center of Expertise on Gender Dysphoria regarding psychological functioning and autistic traits. A total of 1487 consecutively assessed adolescents between 2000 and 2018 were divided in younger presenters (age ≤ 13.9 years) and older presenters (age ≥ 14 years). Of younger presenters, 227 (41.1%) were assigned male at birth and 325 (58.9%) assigned female at birth. In older presenters, 279 (29.8%) were assigned male at birth and 656 (70.2%) assigned female at birth. Behavioral and emotional problems were assessed with the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). For autism traits, the Social Responsiveness Scale (SRS) was used. Compared to younger presenters, on both the CBCL and YSR older presenters had higher Total Problem (ß = 1.75, p = .005, CI 0.53-2.97, R2 = .04 and ß = 4.20, p < .001, CI 2.99-5.40, R2 = .07, respectively) and Internalizing Problem (ß = 4.43, p < .001, CI 3.13-5.74, R2 = .06 and ß = 6.69, p < .001, CI 5.31-8.07, R2 = .12, respectively) scores. Regarding autistic traits, a higher mean SRS total score was found in older presenting assigned males at birth (ß = 4.55, p = .036, CI 0.30-8.81, R2 = .34). In assigned females at birth, no statistically significant difference between older and younger presenters was found in mean SRS total score (ß = 1.19, p = .063, CI - 0.07 to 2.45, R2 = .39). Differences in mental health exist between younger and older presenting adolescents and call for an individualized approach in the clinical care of transgender adolescents.

Eco-friendly Synthesis of N- Cholyl Mercapto Histidine Capped Silver Nanoparticles and its sensing of mercury (II) ions and photo catalytic degradation of Methyl orange.

In this report, we have developed highly water soluble and stable silver nanoparticles (Ag NPs) utilizing N-Cholyl Mercapto Histidine (NCMH) as a reducing and stabilizing agent with near the primary critical micellar concentration (CMC) under ambient sunlight irradiation. Moreover, The NCMH was firstly synthesized by demonstrating the reaction between cholic acid and 2- Mercapto Histidine through a simple acid amine coupling approach. The primary and secondary CMC of NCMH surfactant was measured by pyrene (1× 10-6 M) as a fluorescent probe, and values were found to be 3.2 and 13.1 mM respectively. The synthesised Ag NPs showed at neutral pH and highly stable for more than one year without any noticeable aggregation. The TEM analysis displays the synthesized Ag NPs having a spherical shape and average size of 9.6 ± 0.5 nm. The synthesis of stabilized Ag NPs was used for ultra-sensitive and selective detection of Hg2+ ions in aqueous medium were monitored by Uv-visible spectrometer and naked eyes with a lowest limit of detection (LOD) 7 nM. The photo-catalytic degradation of methyl orange (MO) by utilizing Ag NPs as nano-catalyst exhibits a potential degradation within a study period of 180 min. Concluding that, facile and cost effective green synthesis of NCMH capped Ag NPs possess excellent reducing ability towards the selective detection of Hg2+ ions along with photo-catalytic degradation of MO dye. These true findings detached an innovative pathway of Ag NPs towards the reactivity against the catalytic activity of dye degradation and selective sensing of Hg2+ ions. Thus it paves the way for extensive range of novel potential applications of Ag NPs in various environment friendly approaches of sensitive and analytical protocol in the future.

TB notifications among citizens and non-citizens in Taiwan.

Substantial under-notification of TB among non-citizens has been noted previously. Foreign workers with TB who were deported previously could stay for anti-TB treatment since 2014. We assessed whether TB notification improved.We used the National Health Insurance (NHI) reimbursement database to identify potential TB cases that required notification. We matched potential TB cases with the national TB registry to determine whether they had been notified. Cases notified within 7 days of the initiation of anti-TB treatment were classified as having timely notification.Of 53,208 potential TB cases identified in 2016-2020, 96.6% had been notified. The notification proportion increased from 95.5% in 2016 to 97.1% in 2020 among citizens and from 89.0% in 2016 to 96.9% in 2020 among non-citizens. Factors significantly associated with non-notification among non-citizens were previously notified TB (aOR 35.5, 95% CI 17.7-70.9), without health insurance (aOR 15.4, 95% CI 9.3-25.2) and having only one visit to health care facilities in 6 months (aOR 2.3, 95% CI 1.4-3.8). The proportion of TB cases notified within 7 days was 87% overall, 86.2% among citizens, and 96.5% among non-citizens.TB notification has improved, especially among non-citizens, following a policy change that allows foreign workers to stay for anti-TB treatment..

Effects of trichlorfon on ecotoxicological biomarkers in farmed Colossoma macropomum (tambaqui).

Producers of fish have been looking for viable alternatives for the management of Colossoma macropomum (tambaqui) in confinement systems in order to avoid the harm and subsequent losses caused by parasitic diseases. One alternative used by farmers is pesticides, such as trichlorfon, which has a genotoxic effect. Thus, this study aimed to evaluate the changes in gene expression due to the side effects of trichlorfon in tambaqui. Two treatments were used based on LC50-96h of 0.870 mg/L using 30% and 50% trichlorfon with exposure periods of 48, 72 and 96 h. For differential expression of the genes in the liver, real-time PCR was performed for the AChE, GST, CYP2J6, CYP2C8, 18S and GAPDH genes. After 96 h of exposure to trichlorfon, an alteration in the gene expression profile of the antioxidant defense system (GST) of the tambaqui was observed. It was also observed that this organophosphate did not affect the expression of genes related to the isoenzymes that are responsible for the biotransformation of xenobiotics in phase I (2J6 and 2C8) and cholinesterase AChE. It was concluded that the reduction in gene expression of GST suggests a decrease in metabolization capacity in phase II.

High-Density Lipoprotein Modifications: Causes and Functional Consequences in Type 2 Diabetes Mellitus.

High-density lipoprotein (HDL) is a group of small, dense, and protein-rich lipoproteins that play a role in cholesterol metabolism and various cellular processes. Decreased levels of HDL and HDL dysfunction are commonly observed in individuals with type 2 diabetes mellitus (T2DM), which is also associated with an increased risk for cardiovascular disease (CVD). Due to hyperglycemia, oxidative stress, and inflammation that develop in T2DM, HDL undergoes several post-translational modifications such as glycation, oxidation, and carbamylation, as well as other alterations in its lipid and protein composition. It is increasingly recognized that the generation of HDL modifications in T2DM seems to be the main cause of HDL dysfunction and may in turn influence the development and progression of T2DM and its related cardiovascular complications. This review provides a general introduction to HDL structure and function and summarizes the main modifications of HDL that occur in T2DM. Furthermore, the potential impact of HDL modifications on the pathogenesis of T2DM and CVD, based on the altered interactions between modified HDL and various cell types that are involved in glucose homeostasis and atherosclerotic plaque generation, will be discussed. In addition, some perspectives for future research regarding the T2DM-related HDL modifications are addressed.

A New Case Series Suggests That SCA48 (ATX/STUB1) Is Primarily a Monogenic Disorder.

BACKGROUND: Monoallelic, pathogenic STUB1 variants cause autosomal dominant cerebellar ataxia (ATX-STUB1/SCA48). Recently, a genetic interaction between STUB1 variants and intermediate or high-normal CAG/CAA repeats in TBP was suggested, indicating digenic inheritance or a disease-modifying role for TBP expansions. OBJECTIVE: To determine the presence and impact of intermediate or high-normal TBP expansions in ataxic patients with heterozygous STUB1 variants. METHODS: We describe 21 patients with ataxia carrying a heterozygous STUB1 variant and determined TBP repeat length. RESULTS: A total of 15 of 21 patients (71%) carried a normal TBP<40 allele, 4 (19%) carried an intermediate TBP41-42 allele, and two carried a high-normal TBP40 allele (9.5%). Five of six carriers (83%) of both STUB1 variants and TBP40-42 alleles showed marked cognitive impairment. CONCLUSIONS: SCA48 is predominantly a monogenic disorder, because most patients carried an isolated, heterozygous STUB1 variant and presented with the typical combined phenotype of ataxia and cognitive dysfunction. Still, co-occurrence of TBP41-42 or high-normal TBP40 alleles was relatively frequent and associated with marked cognitive defects (28.5%), suggesting a modifying effect on clinical expression in some cases. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Expression patterns of melanin-related genes are linked to crypsis and conspicuousness in a pumpkin toadlet.

Colour signals play pivotal roles in different communication systems, and the evolution of these characters has been associated with behavioural ecology, integumentary production processes and perceptual mechanisms of the species involved. Here, we present the first insight into the molecular and histological basis of skin colour polymorphism within a miniaturized species of pumpkin toadlet, potentially representing the lowest size threshold for colour polytypism in tetrapods. Brachycephalus actaeus exhibits a coloration ranging from cryptic green to conspicuous orange skin, and our findings suggest that colour morphs differ in their capability to be detected by potential predators. We also found that the distribution and abundance of chromatophores are variable in the different colour morphs. The expression pattern of coloration related genes was predominantly associated with melanin synthesis (including dct, edn1, mlana, oca2, pmel, slc24a5, tyrp1 and wnt9a). Up-regulation of melanin genes in grey, green and brown skin was associated with higher melanophore abundance than in orange skin, where xanthophores predominate. Our findings provide a significant foundation for comparing and understanding the diverse pathways that contribute to the evolution of pigment production in the skin of amphibians.

The Coexistence of Carotico-Clinoid Foramen and Interclinoidal Osseous Bridge: An Anatomo-Radiological Study With Surgical Implications.

BACKGROUND AND OBJECTIVES: The coexistence of complete carotico-clinoid bridge (CCB), an ossification between the anterior (ACP) and the middle clinoid (MCP), and an interclinoidal osseous bridge (ICB), between the ACP and the posterior clinoid (PCP), represents an uncommonly reported anatomic variant. If not adequately recognized, osseous bridges may complicate open or endoscopic surgery, along with the pneumatization of the ACP, especially when performing anterior or middle clinoidectomies. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, a systematic scoping review was conducted up to June 5, 2023. PubMed, Scopus, Web of Science databases, and additional citations were searched. Two hundred high-resolution noncontrast computed tomography (CT) scans (400 sides) and 41 dry skulls (82 sides) were analyzed to identify the different morphology of sellar bridges, focusing on the coexistence of complete CCF and ICB. Two embalmed latex-injected heads with coexisting CCF and ICB were dissected step-by-step to show the anatomic relationship with the surrounding structures from an endoscopic and microscopic perspective. RESULTS: A total of 19 articles were included. The review identified a complete CCF and ICB rate ranging from 4.92% to 6.3%. The analysis of 200 CT scans revealed a rate of coexistence in 4% of the cases, all encountered in White women. Two different types of interclinoid bridges were identified based on the degree of bone mineralization. Both endoscopic and macroscopic step-by-step dissections highlighted variability in morphology and consistency of the sellar bridges and the close relationship with the cavernous sinus neurovascular structures. CONCLUSION: The coexistence of CCF and ICB is an anatomic variation found in 4% of cases. Preoperative knowledge of the degree of mineralization and its relationship with surrounding structures is essential to performing safe surgery and minimizing cranial nerve and vascular injuries. Preoperative high-resolution CT scans can adequately identify these anatomic variations.

Genetic Interventions for Spinocerebellar Ataxia and Huntington's Disease: A Qualitative Study of the Patient Perspective.

Background: For various genetic disorders characterized by expanded cytosine-adenine-guanine (CAG) repeats, such as spinocerebellar ataxia (SCA) subtypes and Huntington's disease (HD), genetic interventions are currently being tested in different clinical trial phases. The patient's perspective on such interventions should be included in the further development and implementation of these new treatments. Objective: To obtain insight into the thoughts and perspectives of individuals with SCA and HD on genetic interventions. Methods: In this qualitative study, participants were interviewed using semi-structured interview techniques. Topics discussed were possible risks and benefits, and logistic factors such as timing, location and expertise. Data were analyzed using a generic thematic analysis. Responses were coded into superordinate themes. Results: Ten participants (five with SCA and five with HD) were interviewed. In general, participants seemed to be willing to undergo genetic interventions. Important motives were the lack of alternative disease-modifying treatment options, the hope for slowing down disease progression, and preservation of current quality of life. Before undergoing genetic interventions, participants wished to be further informed. Logistic factors such as mode and frequency of administration, expertise of the healthcare provider, and timing of treatment are of influence in the decision-making process. Conclusions: This study identified assumptions, motives, and topics that require further attention before these new therapies, if proven effective, can be implemented in clinical practice. The results may help in the design of care pathways for genetic interventions for these and other rare genetic movement disorders.

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. METHODS: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. RESULTS: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. DISCUSSION: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Cognitive impairment in young adults following cerebellar stroke: Prevalence and longitudinal course.

INTRODUCTION: Cognitive impairment is a well-known result of a stroke, but for cerebellar stroke in young patients detailed knowledge on the nature and extent of cognitive deficits is limited. This study examined the prevalence and course of cognitive impairment in a large cohort of patients with cerebellar stroke. METHODS: Sixty young (18-49 years) cerebellar stroke patients completed extensive neuropsychological assessments in the subacute (<9 months post-stroke) and/or chronic phase (≥9 months post-stroke). Performance and course were assessed using standardized scores and Reliable Change Index analyses. Associations between cognitive deficits and lesion locations were explored using subtraction analyses, and associations with subjective cognitive complaints and fatigue were examined. RESULTS: Sixty patients (52% male) were included with a mean age at event of 43.1 years. Cognitive impairment was observed in 60.3% of patients in the subacute phase and 51.2% during the chronic phase. Deficits were most frequent for visuo-spatial skills and executive functioning (42.5-54.6%). Both improvement and decline were observed over time, in 17.9% and 41.0% of participants, respectively. Cognitive deficits seem to be associated with lesions in certain cerebellar regions, however, no distinct correlation was found for a specific subregion. Subjective cognitive complaints were present in the majority of participants (61-80.5%) and positively correlated with fatigue in both phases (ρ = -.661 and ρ = -.757, p < .001, respectively). DISCUSSION: Cognitive impairment in cerebellar stroke patients is common, with deficits most pronounced for visuo-spatial skills and executive functioning, as in line with the Cerebellar Cognitive Affective Syndrome. The course of cognitive performance was heterogenous, with cognitive decline despite the fact that no recurrent strokes occurred. No clear association between lesion location and cognitive deficits was observed. Subjective cognitive complaints and fatigue were prevalent and positively correlated. Clinicians could use this information to actively screen for and better inform patients about possible cognitive sequalae.

Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.

BACKGROUND: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI. METHODS: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8). RESULTS: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes. CONCLUSION: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability.

BACKGROUND: Metabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking. METHODS: In this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque. RESULTS: Our study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH-) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment. CONCLUSIONS: This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.

A systematic review on the effectiveness of robot-assisted minimally invasive gastrectomy.

BACKGROUND: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed. METHODS: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized. RESULTS: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5-9.2% RAMIG versus 17.6-19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7-8.5 days RAMIG versus 6.4-8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423-15,262 versus $10,165-10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG. CONCLUSION: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs.

Bushy-Tailed QACs: The development of multicationic quaternary ammonium compounds with a high degree of alkyl chain substitution.

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4 µM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains.