Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy.

Intracellular accumulation of misfolded proteins causes toxic proteinopathies, diseases without targeted therapies. Mucin 1 kidney disease (MKD) results from a frameshift mutation in the MUC1 gene (MUC1-fs). Here, we show that MKD is a toxic proteinopathy. Intracellular MUC1-fs accumulation activated the ATF6 unfolded protein response (UPR) branch. We identified BRD4780, a small molecule that clears MUC1-fs from patient cells, from kidneys of knockin mice and from patient kidney organoids. MUC1-fs is trapped in TMED9 cargo receptor-containing vesicles of the early secretory pathway. BRD4780 binds TMED9, releases MUC1-fs, and re-routes it for lysosomal degradation, an effect phenocopied by TMED9 deletion. Our findings reveal BRD4780 as a promising lead for the treatment of MKD and other toxic proteinopathies. Generally, we elucidate a novel mechanism for the entrapment of misfolded proteins by cargo receptors and a strategy for their release and anterograde trafficking to the lysosome.

Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection.

The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation.

Population dynamics of potentially harmful haplotypes: a pedigree analysis.

BACKGROUND: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level. RESULTS: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants. CONCLUSIONS: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.

Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion.

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Analysing the pedigree to identify undesirable losses of genetic diversity and to prioritize management decisions in captive breeding: a case study.

When prevention of species extinction is the priority, captive breeding is a key component in conservation programmes, allowing the recording of pedigree information in studbooks. The genealogical information registered in Cuvier's gazelle studbook between 1975 and 2023 was analysed to (a) assess if the implemented mating policy was successful in preserving the genetic background of the founders (1 male:3 females) in the present population, and b) improve future management and breeding decisions. Although the maternal contribution of one founder female was lost and the mean inbreeding of the total live population was high (0.305 ± 0.095), the breeding policy applied produced better results than expected from a population starting from four founders. It was successful in keeping the individual increase in inbreeding low (0.047 ± 0.021), and, notably, the inbreeding tended to decrease during the last three decades of the breeding programme, ensuring the viability of this highly inbred population. Historical dissemination of individuals among the zoos of Europe and North America caused population structuring and genetic differentiation of the live North American population. However, it did not risk the viability of the captive population. The average relatedness coefficients allowed the identification of individuals with underrepresented genotypes, which is relevant to plan future mating guidelines to keep the founders' representation balanced in the next generations. This study highlights the importance of keeping long-term pedigree information to monitor changes in the genetic diversity of captive populations, which is crucial to implement optimal mating decisions and assuring their long-term viability within an ex situ conservation programme.

The shape of cancer relapse: Topological data analysis predicts recurrence in paediatric acute lymphoblastic leukaemia.

Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and "empty spaces" in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as 'low risk'. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

OBJECTIVE: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. METHODS: With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA. RESULTS: In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p < .026) and controls (p < .03), suggesting differences in the state of endothelium. CONCLUSIONS: For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population.

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation.

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.

Nucleation dynamics of a model biomolecular liquid.

Liquid-liquid phase separation in biology has recently been shown to play a major role in the spatial control of biomolecular components within the cell. However, as they are phase transitions, these processes also display nontrivial dynamics. A model phase-separating system of DNA nanostars provides unique access to nucleation physics in a biomolecular context, as phase separation is driven near room temperature by highly thermo-responsive DNA hybridization and at modest DNA concentrations. By measuring the delay time for phase-separated droplets to appear, we demonstrate that the dynamics of DNA nanostar phase separation reflect that of a metastable binary mixture of patchy particles. For sufficiently deep temperature quenches, droplets undergo spinodal decomposition and grow spontaneously, driven by Brownian motion and coalescence of phase-separated droplets, as confirmed by comparing experimental measurements to particle-based simulations. Near the coexistence boundary, droplet growth slows substantially, indicative of a nucleation process. The temperature dependence of droplet appearance times can be predicted by a classical nucleation picture with mean field exponents and demonstrates that a theory previously used to predict equilibrium phase diagrams can also distinguish spinodal and nucleation dynamical regimes. These dynamical principles are relevant to behaviors associated with liquid-liquid phase separating systems, such as their spatial patterning, reaction coupling, and biological function.

Intramural coronary artery and myocardial pathology in captive tigers (Panthera tigris) and African lions (Panthera leo).

There is limited published data regarding cardiovascular disease in nondomestic felid populations. To address this knowledge gap, necropsy cases of tigers and lions with representative myocardial samples submitted to a diagnostic laboratory were histologically assessed with hematoxylin and eosin and Sirius red stains. A total of 32 submissions (15 tigers, 17 lions) were identified in a 4-year period. All tigers and lions had some degree of coronary artery lesions in the left ventricle and/or interventricular septum. Major findings included moderate to marked arteriosclerosis in 8 tigers (53%) and 4 lions (24%) and moderate to marked perivascular fibrosis in 10 tigers (67%) and 9 lions (53%). Moreover, 10 tigers (67%) and 8 lions (47%) had coronary artery lesions with variable degrees of perivascular cardiomyocyte degeneration and/or loss. To our knowledge, this is the first report describing coronary artery pathology in captive tigers and lions.

Macro level system mapping of the provision of mental health services to young people living in a conflict context in Colombia.

Colombia has one of the longest running internal armed conflicts, which has significantly impacted the mental health of the population. This article is the first to present a national level mapping of the provision of mental health services to young people living in Colombia, through detailed review of documentation, interviews with key stakeholders and quantitative analysis of existing data on mental health and suicide. It explores the existing public mental health provision in the country, focussing on where mental health resources are concentrated and how these are implemented. We use this mapping to understand how the current mental health system in Colombia fits with international approaches to youth mental health. We show that whilst mental health policy is variously framed (biomedical, biosocial, psychologically or through human rights), Colombian policy clearly focusses on a differential approach. This differential approach shapes service provision to target support at those in need, consequently neglecting whole population level mental health support. This means that not all stakeholders were clearly articulated or included in policy and that key institutional stakeholders, such as the education sector, were not linked to implementation plans or activity. Policy approaches were also over-centralised with little cross-institutional collaboration. Youth were specifically missing from services, as was explicit understanding of the intergenerational effects and impact of conflict. This was exacerbated by unequal distribution of mental health care services concentrated in populous, urban areas away from conflict-affected regions. Suicide is the second most prevalent cause of death with 10% of population who were recorded as dying by violence, dying from completed suicide. Triangulation implies a strong relationship between suicide and poorer access to professional support in conflict-affected areas and suggests that international frameworks and policy approaches to supporting youth mental health have been insufficiently adapted for conflict and post conflict contexts.

Segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS): Case series and review of literature.

BACKGROUND: Next-generation sequencing has greatly increased our understanding of vascular birthmarks. Many port-wine birthmarks are due to somatic mutations in GNAQ/GNA11 exon 183, but other genomic causes have been identified. Most congenital hemangiomas are due to somatic mutations in GNAQ/GNA11 at exon 209. Although genomically distinct, clinical overlap of congenital hemangiomas and port-wine birthmarks has occasionally been described. OBJECTIVE: We report a case series of a unique segmentally distributed vascular anomaly with overlapping characteristics of port-wine birthmarks and congenital hemangiomas with other distinctive features including ulceration, atrophy, and scarring. METHODS: This was a multicenter study with retrospective identification of patients via a detailed review of medical records. We also reviewed previously published cases. RESULTS: The clinical, histological, radiological, and genomic characteristics of 19 new and 13 previously reported cases characterized by segmental distribution, sharply demarcated borders, with variable thickening are presented. All cases had central atrophy with or without episodic ulceration. Those with genomic studies (13 out of 32) had somatic activating missense mutations in GNA11 or GNAQ codon 209. CONCLUSIONS: We describe the features and propose a descriptive name segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS) for this condition.

Causal association between environmental variables and the excess cases of cutaneous leishmaniasis in Colombia: are we looking to the wrong side?

Our main aim was to estimate and compare the effects of six environmental variables (air temperature, soil temperature, rainfall, runoff, soil moisture, and the enhanced vegetation index) on excess cases of cutaneous leishmaniasis in Colombia. We used epidemiological data from the Colombian Public Health Surveillance System (January 2007 to December 2019). Environmental data were obtained from remote sensing sources including the National Oceanic and Atmospheric Administration, the Global Land Data Assimilation System (GLDAS), and the Moderate Resolution Imaging Spectroradiometer. Data on population were obtained from the TerriData dataset. We implemented a causal inference approach using a machine learning algorithm to estimate the causal association of the environmental variables on the monthly occurrence of excess cases of cutaneous leishmaniasis. The results showed that the largest causal association corresponded to soil moisture with a lag of 3 months, with an average increase of 8.0% (95% confidence interval [CI] 7.7-8.3%) in the occurrence of excess cases. The temperature-related variables (air temperature and soil temperature) had a positive causal effect on the excess cases of cutaneous leishmaniasis. It is noteworthy that rainfall did not have a statistically significant causal effect. This information could potentially help to monitor and control cutaneous leishmaniasis in Colombia, providing estimates of causal effects using remote sensor variables.

Differential patterns in runs of homozygosity in two mice lines under divergent selection for environmental variability for birth weight.

Runs of homozygosity (ROH) are defined as long continuous homozygous stretches in the genome which are assumed to originate from a common ancestor. It has been demonstrated that divergent selection for variability in mice is possible and that low variability in birth weight is associated with robustness. To analyse ROH patterns and ROH-based genomic inbreeding, two mouse lines that were divergently selected for birth weight variability for 26 generations were used, with: 752 individuals for the high variability line (H-Line), 766 individuals for the low variability line (L-Line) and 74 individuals as a reference population. Individuals were genotyped using the high density Affymetrix Mouse Diversity Genotyping Array. ROH were identified using both the sliding windows (SW) and the consecutive runs (CR) methods. Inbreeding coefficients were calculated based on pedigree (FPED ) information, on ROH identified using the SW method (FROHSW ) and on ROH identified using the CR method (FROHCR ). Differences in genomic inbreeding were not consistent across generations and these parameters did not show clear differences between lines. Correlations between FPED and FROH were high, particularly for FROHSW . Moreover, correlations between FROHSW and FPED were even higher when ROH were identified with no restrictions in the number of heterozygotes per ROH. The comparison of FROH estimates between either of the selected lines were based on significant differences at the chromosome level, mainly in chromosomes 3, 4, 6, 8, 11, 15 and 19. ROH-based inbreeding estimates that were computed using longer homozygous segments had a higher relationship with FPED . Differences in robustness between lines were not attributable to a higher homozygosis in the L-Line, but maybe to the different distribution of ROH at the chromosome level between lines. The analysis identified a set of genomic regions for future research to establish the genomic basis of robustness.

Genetic parameters for different types of medullated fibre in Alpacas.

The quality of alpaca textile fibre has great potential, especially if objectionable fibres (coarse and medullated fibres) that cause itching are reduced, considering that objectionable fibres can be identified by diameter and medullation types. The objective of this study was to estimate genetic parameters for medullar types and their respective diameters to evaluate the possibility of incorporating them as selection criteria in alpaca breeding programmes. The research used 3149 alpaca fibre samples collected from 2020 to 2022, from a population of 1626 Huacaya type alpacas. The heritability and correlations of the percentages of non-medullated (NM), fragmented medulle (FM), uncontinuous medullated (UM), continuous medullated (CM), and strongly medullated (SM) fibres were analysed, also the fibre diameter (FD) for each of the medullation types. The heritability estimated for medullation types were 0.25 ± 0.01, 0.18 ± 0.01, 0.10 ± 0.01, 0.20 ± 0.01 and 0.11 ± 0.01 for NM, FM, UM, CM and SM, respectively. The genetic correlations for medullation categories ranged from 0.15 ± 0.03 to 0.66 ± 0.02 (in absolute values). The heritabilility estimated for fibre diameter (FD) of each of the medullation types were 0.29 ± 0.03, 0.27 ± 0.02, 0.35 ± 0.02, 0.30 ± 0.02, 0.25 ± 0.02 and 0.10 ± 0.02 for FD, FD_NM, FD_FM, FD_UM, FD_CM and FD_SM, respectively. The genetic correlations for fibre diameter of the medullation types ranged from 0.04 ± 0.04 to 0.97 ± 0.01. FD, NM and FM are the main traits to be used as selection criteria under a genetic index, since they would reduce fibre diameter, and also increase NM and FM, and, in addition reducing indirectly CM, SM, and SM_FD. Therefore, the quality of alpaca fibre could be improved.

Synthesis, Structural Characterisation, and Electrochemical Properties of Copper(II) Complexes with Functionalized Thiosemicarbazones Derived from 5-Acetylbarbituric Acid.

The reaction between 5-acetylbarbituric acid and 4-dimethylthiosemicarbazide or 4-hexamethyleneiminyl thiosemicarbazide produces 5-acetylbarbituric-4-dimethylthiosemicarbazone (H2AcbDM) and 5-acetylbarbituric-4N-hexamethyleneiminyl thiosemicarbazone (H2Acbhexim). Eight new complexes with different copper(II) salts have been prepared and characterized using elemental analysis, molar conductance, UV-Vis, ESI-HRMS, FT-IR, magnetic moment, EPR, and cyclic voltammetry. In addition, three-dimensional molecular structures of [Cu(HAcbDM)(H2O)2](NO3)·H2O (3a), [Cu(HAcbDM)(H2O)2]ClO4 (4), and [Cu(HAcbHexim)Cl] (6) were determined by single crystal X-ray crystallography, and an analysis of their supramolecular structure was carried out. The H-bonded assemblies were further studied energetically using DFT calculations and MEP surface and QTAIM analyses. In these complexes, the thiosemicarbazone coordinates to the metal ion in an ONS-tridentate manner, in the O-enolate/S-thione form. The electrochemical behavior of the thiosemicarbazones and their copper(II) complexes has been investigated at room temperature using the cyclic voltammetry technique in DMFA. The Cu(II)/Cu(I) redox system was found to be consistent with the quasi-reversible diffusion-controlled process.

Chemical Characterization and Assessment of Public Health Risk due to Inhalation of PM2.5 in the City of Salamanca, Guanajuato.

In this study, we conducted an analysis of health risks faced by residents of Salamanca, Mexico, who were exposed to fine particulate matter with a diameter of 2.5 µm (PM2.5) through inhalation. The characterization and analysis of these particulate matter samples were undertaken. A total of 131 samples were collected from two different sites: 65 from the Red Cross site (RC) and 66 from the Integral Family Development site (DIF) in 2014-2015. These samples were analyzed for a set of chemical components, including metals and ions. Non-cancerous health risk levels associated with PM2.5 exposure through the human respiratory system, as per the WHO benchmark (assigned a value of 1), revealed notable risk values for two elements: Manganese (Mn) with a range of 1.19-2.12 in the adult population and 1.59-2.84 in the child population, and Nickel (Ni) with a uniform risk value of 1.39 for both evaluated population groups. However, concerns arose regarding potential non-cancerous effects as the cumulative risk levels for various assessed elements showed elevated indices. These ranged from 3.81 to 4.4 in adults and 4.48-5.24 in children. This study provided comprehensive data on composition and its potential impact on human health, offering valuable insights for the implementation of mitigation measures aimed at reducing inhalation-related exposure.

[Determinants of avoidable hospitalization for type2 diabetes. Narrative review]. / Factores determinantes de las hospitalizaciones evitables por diabetes tipo2. Revisión narrativa.

OBJECTIVE: To identify the structural and intermediate determinants associated with avoidable hospitalizations (AH) of patients with type2 diabetes mellitus (T2DM). DESIGN: Literature review based on narrative synthesis. DATA SOURCES: Databases: PubMed, Science Direct, and Latin American and Caribbean Literature in Health Sciences (LILACS). STUDY SELECTION: Documents were selected and analyzed under a critical literature review, considering inclusion and exclusion criteria. DATA EXTRACTION: Information extracted from each selected article was synthesized based on the countries' income levels and the social determinants of health framework. RESULTS: A total of 4,166 articles were relevant, 36 were selected for review. From this selection, 21 were publications conducted in high-income countries, 14 in upper-middle-income countries, and one in lower-middle-income countries. The review identified that the coverage of health services -mainly primary health care- and health insurance contribute to reducing the risk of AH for T2DM, while social inequalities tend to increase the risk. CONCLUSIONS: The AH due to T2DM are susceptible to reduction through policies that contribute to increasing effective access to health services (availability, insurance), since they express social inequality, occurring to a greater extent in socioeconomically vulnerable populations. This review also provides evidence of the need to expand research on this topic in middle and low-income countries.

Prehospital Stroke Care Part 2: On-Scene Evaluation and Management by Emergency Medical Services Practitioners.

The prehospital phase is a critical component of delivering high-quality acute stroke care. This topical review discusses the current state of prehospital acute stroke screening and transport, as well as new and emerging advances in prehospital diagnosis and treatment of acute stroke. Topics include prehospital stroke screening, stroke severity screening, emerging technologies to aid in the identification and diagnosis of acute stroke in the prehospital setting, prenotification of receiving emergency departments, decision support for destination determination, and the capabilities and opportunities for prehospital stroke treatment in mobile stroke units. Further evidence-based guideline development and implementation of new technologies are critical for ongoing improvements in prehospital stroke care.