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1.
Sci Rep ; 14(1): 14798, 2024 06 26.
Article in English | MEDLINE | ID: mdl-38926427

ABSTRACT

Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998-0.999 vs. 0.982 95% CI 0.962-0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9-21.7) to 9.4 min (IQR 7.2-11.7) compared to when using the AI tool (p < 0.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.


Subject(s)
Critical Illness , Intensive Care Units , Muscular Atrophy , Ultrasonography , Humans , Male , Ultrasonography/methods , Female , Middle Aged , Aged , Muscular Atrophy/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Quadriceps Muscle/diagnostic imaging , Artificial Intelligence , Adult
2.
Cancers (Basel) ; 16(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38730637

ABSTRACT

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

3.
Inorg Chem ; 63(19): 8642-8653, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38690944

ABSTRACT

The synthesis, structure, and catalytic activity of a Ti(II)/Ti(III) inverted sandwich compound are presented in this study. Synthesis of the arene-bridged dititanium compound begins with the preparation of the titanium(IV) precursor [TiCl2(MesPDA)(thf)2] (MesPDA = N,N'-bis(2,4,6-trimethylphenyl)-o-phenylenediamide) (2). The reduction of 2 with sodium metal results in species [{Ti(MesPDA)(thf)}2(µ-Cl)3{Na}] (3) in oxidation state III. To achieve the lower oxidation state II, 2 undergoes reduction through alkylation with lithium cyclopentyl. This alkylation approach triggers a cascade of reactions, including ß-hydride abstraction/elimination, hydrogen evolution, and chemical reduction, to generate the Ti(II)/Ti(III) compound [Li(thf)4][(TiMesPDA)2(µ-η6: η6-C6H6)] (4). X-ray and EPR characterization confirms the mixed-valence states of the titanium species. Compound 4 catalyzes a mild, efficient, and regiospecific cyclotrimerization of alkynes to form 1,3,5-substituted arenes. Kinetic data support a mechanism involving a binuclear titanium arene compound, similar to compound 4, as the resting state. The active catalyst promotes the oxidative coupling of two alkynes in the rate-limiting step, followed by a rapid [4 + 2] cycloaddition to form the arene product. Computational analysis of the resting state for the cycloaddition of trimethylsilylacetylene indicates a thermodynamic preference for stabilizing the 1,3,5-arene within the space between the two [TiMesPDA] fragments, consistent with the observed regioselectivity.

4.
Acta Trop ; 256: 107270, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38795873

ABSTRACT

This study updates knowledge on historical geographic distribution of sand fly species through identifying altitudinal and bioclimatic patterns in leishmaniasis endemic areas in Mexico. We analyze and identify sand fly specimens obtained through national efforts by the Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE, Mexico), collected between 1995 and 2001, 2008-2012, and 2017-2023, and add bibliographic information (427 additional records). After a principal components analysis of WorldClim variables and altitudinal ranges, variables that better explain the distribution of sand fly species were chosen (BIO6, BIO12, and BIO16, explaining 72 % of variation). A total of 1,187 specimens of 22 species were retrieved from eight states, providing 29 new municipalities and 48 new localities, being Lutzomyia cruciata, Micropygomyia chiapanensis, and Psathyromyia shannoni the most common species. We presented new historical records of distribution for sand fly species from Morelos (3), Oaxaca (7) and Tabasco (1). The 82.7 % of sand fly species analyzed were distributed in areas with altitudinal ranges below 420 m. The anthropophilic species Psathyromyia shannoni, and Lutzomyia cruciata showed the greatest variability regarding altitudinal range, and climatic preferences, while several wild species showed abiotic preferences. It is likely that the effect of urbanization and climate change generate new beneficial biotopes for the proliferation of the vector sand fly species. Complementary studies that consider seasonality, vegetation types, and change in land use could provide new information to better understand the spread of vector-borne diseases.


Subject(s)
Altitude , Leishmaniasis , Psychodidae , Animals , Mexico/epidemiology , Psychodidae/classification , Psychodidae/physiology , Leishmaniasis/epidemiology , Leishmaniasis/transmission , Insect Vectors/physiology , Insect Vectors/classification , Climate , Animal Distribution , Endemic Diseases , Humans , Female , Male
5.
Environ Toxicol Pharmacol ; 108: 104455, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657881

ABSTRACT

This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4 ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.


Subject(s)
Environmental Pollutants , Oxidative Stress , Prostate-Specific Antigen , Prostatic Neoplasms , Xenobiotics , Male , Humans , Prostatic Neoplasms/genetics , Oxidative Stress/drug effects , Middle Aged , Aged , Environmental Pollutants/urine , Environmental Pollutants/toxicity , Prostate-Specific Antigen/blood , Case-Control Studies , Environmental Exposure/adverse effects , Glutathione Transferase/genetics
6.
ACS Appl Mater Interfaces ; 16(17): 22379-22390, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38636939

ABSTRACT

Structural colors offer a myriad of advantages over conventional pigment-based colors, which often rely on toxic chemical substances that are prone to UV degradation. To take advantage of these benefits in demanding environments, there is growing interest in producing structural colors from ceramics. Polymer-derived ceramics (PDCs) emerge as a compelling choice, presenting two distinct advantages: their enhanced shape ability in their polymeric state associated with impressive temperature resistance once converted to ceramics. This study pioneers the fabrication of noniridescent structural colors from silicon oxycarbide (SiOC) PDC, enabled by the nanostructuring of an inverse photonic glass within the PDC material. This design, a functionally graded material with an inverse photonic glass (FGM-PhG) structure, leverages the innate light-absorbing properties of SiOC, yielding a vivid structural color that maintains its saturation even in white surroundings. This study elucidates the process-structure-properties relationship for the obtained structural colors by investigating each layer of the functionally graded material (FGM) in a stepwise coating deposition process. To further emphasize the exceptional processing flexibility of PDCs, the three-step process is later transferred to an additive manufacturing approach. Finally, the FGM-PhG structural colors are demonstrated to have remarkable thermal stability up to 1000 °C for 100 h, possibly making them the most thermally stable ceramic structural colors to date.

7.
Front Public Health ; 12: 1304310, 2024.
Article in English | MEDLINE | ID: mdl-38450140

ABSTRACT

Introduction: Workplace Mental health promotion in healthcare sector, is a global priority due to the stress associated with caregiving environments and the increase of mental health problems among health professionals and students. The role of emotional intelligence (EI) and sense of coherence (SOC) have been identified as critical health protectors. However, the relationship between them as well as the underlying mechanisms of these relationships on health benefits in this population is still unclear. Aim: To synthetize the existing literature on the relationship between emotional intelligence and sense of coherence, as well as their mutual impact on healthcare workers' and student's well-being. Method: A scoping review was conducted following the Joanna Briggs Institute guidelines. A systematic search was conducted in PsyCINFO, CINHAL, SCOPUS and PUBMED databases, using key-terms such as students, health professionals, emotional intelligence, and sense of coherence. Results: A total of 11 articles were included, with a range of years from 2014 to 2022. Evidence was found to support the positive relationship between sense of coherence and emotional intelligence. The use of EI as a training pathway to improve SOC and health promoting behaviors is suggested. The benefits of intervening on these factors contribute to improved health professionals' and students' general well-being and motivation for a better performance, either in their studies or clinical work. Conclusion: The positive relationship between emotional intelligence and a sense of coherence has direct and indirect benefits on students' and healthcare professionals' well-being. Future studies should address longitudinal and experimental analysis to confirm these findings.


Subject(s)
Emotional Intelligence , Sense of Coherence , Humans , Delivery of Health Care , Health , Health Personnel , Health Promotion , Students
8.
J Clin Invest ; 134(8)2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376918

ABSTRACT

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.


Subject(s)
HIV Infections , HIV-1 , Humans , HIV-1/genetics , Leukocytes, Mononuclear , Proviruses/genetics , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic use
9.
Front Microbiol ; 15: 1346021, 2024.
Article in English | MEDLINE | ID: mdl-38374922

ABSTRACT

Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis, a rapid and acute infection of the central nervous system with a fatal outcome in >97% of cases. Due to the infrequent report of cases and diagnostic gaps that hinder the possibility of recovering clinic isolates, studies related to pathogenesis of the disease are scarce. However, the secretion of cytolytic molecules has been proposed as a factor involved in the progression of the infection. Several of these molecules could be included in extracellular vesicles (EVs), making them potential virulence factors and even modulators of the immune response in this infection. In this work, we evaluated the immunomodulatory effect of EVs secreted by two clinic isolates of Naegleria fowleri using in vitro models. For this purpose, characterization analyses between EVs produced by both isolates were first performed, for subsequent gene transcription analyses post incubation of these vesicles with primary cultures from mouse cell microglia and BV-2 cells. Analyses of morphological changes induced in primary culture microglia cells by the vesicles were also included, as well as the determination of the presence of nucleic acids of N. fowleri in the EV fractions. Results revealed increased expression of NOS, proinflammatory cytokines IL-6, TNF-α, and IL-23, and the regulatory cytokine IL-10 in primary cultures of microglia, as well as increased expression of NOS and IL-13 in BV-2 cells. Morphologic changes from homeostatic microglia, with small cellular body and long processes to a more amoeboid morphology were also observed after the incubation of these cells with EVs. Regarding the presence of nucleic acids, specific Naegleria fowleri DNA that could be amplified using both conventional and qPCR was confirmed in the EV fractions. Altogether, these results confirm the immunomodulatory effects of EVs of Naegleria fowleri over microglial cells and suggest a potential role of these vesicles as biomarkers of primary acute meningoencephalitis.

10.
Chemistry ; 30(1): e202303230, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-37947164

ABSTRACT

Solar energy utilization has gained considerable attention due to its abundance and renewability. However, its intermittent nature presents a challenge in harnessing its full potential. The development of energy storing compounds capable of capturing and releasing solar energy on demand has emerged as a potential solution. These compounds undergo a photochemical transformation that results in a high-energy metastable photoisomer, which stores solar energy in the form of chemical bonds and can release it as heat when required. Such systems are referred to as MOlecular Solar Thermal (MOST)-systems. Although the photoisomerization of MOST systems has been vastly studied, its back-conversion, particularly using heterogeneous catalysts, is still underexplored and the development of effective catalysts for releasing stored energy is crucial. Herein we compare the performance of 27 heterogeneous catalysts releasing the stored energy in an efficient Norbornadiene/Quadricyclane (NBD/QC) MOST system. We report the first benchmarking of heterogeneous catalysts for a MOST system using a robust comparison method of the catalysts' activity and monitoring the conversion using UV-Visible (UV-Vis) spectroscopy. Our findings provide insights into the development of effective catalysts for MOST systems. We anticipate that our assay will reveal the necessity of further investigation on heterogeneous catalysis.

11.
Anal Bioanal Chem ; 416(4): 1085-1099, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38108843

ABSTRACT

Endocrine-disrupting chemicals are environmental pollutants that can enter our bodies and cause diverse pathologies. Some bisphenols and parabens have been shown to be capable of modifying proper functioning of the endocrine system. Among other dysfunctions, endocrine-disrupting chemicals can cause changes in intestinal microbiota. Faeces are a convenient matrix that can be useful for identifying the quantity of endocrine disruptors that reach the intestine and the extent to which the organism is exposed to these pollutants. The present work developed a new analytical method to determine 17 compounds belonging to the paraben and bisphenol families found in human faeces. The extraction method was optimized using an ultrasound-assisted extraction technique followed by a clean-up step based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) technique. Optimization was performed using the design of experiments technique. In validation analysis, the method was proven to be linear over a wide range. R-squared outcomes were between 95 and 99%. Selectiveness and sensitivity outcomes were acceptable, with detection limits being between 1 and 10 ng g-1 in all cases, whilst quantification limits were between 3 and 25 ng g-1 in all instances, with the exception of bisphenol AF. The method was deemed accurate, with recovery values being close to 100% and relative standard deviations being lower than 15% in all cases. Applicability was examined by analysing 13 samples collected from volunteers (male and female). All samples were contaminated with at least one of the analytes studied. The most commonly found compounds were methylparaben and bisphenol A, which were detected in almost all samples and quantitatively determined in 11 and 12 samples, respectively. Of the 17 compounds analysed, 11 were found in at least one sample. Outcomes demonstrate that faeces can be a good matrix for the determination of exposure to contaminants of interest here.


Subject(s)
Benzhydryl Compounds , Endocrine Disruptors , Environmental Pollutants , Phenols , Humans , Male , Female , Tandem Mass Spectrometry/methods , Endocrine Disruptors/analysis , Gas Chromatography-Mass Spectrometry/methods , Limit of Detection , Environmental Pollutants/analysis
12.
Rev. cuba. med. mil ; 52(4)dic. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1559850

ABSTRACT

Introducción: En Cuba, las enfermedades cerebrovasculares (ECV) son padecimientos crónicos no trasmisibles muy frecuentes. Objetivos: Caracterizar a pacientes de la unidad de cuidados intensivos, con diagnóstico anatomopatológico de ECV. Métodos: Estudio observacional, descriptivo y transversal en una muestra de 176 pacientes. Variables estudiadas: edad (19-39 años, 40-59 años, 60-100 años), sexo, tipo de ECV (hemorrágica, isquémica), escala APACHE II (≤ 15, > 15 puntos) y de coma Glasgow al ingreso (≤ 8, > 8 puntos), ventilación mecánica (sí, no), estadía (≤ 7, > 7 días) y causa directa de muerte. Se calcularon las frecuencias, medidas de tendencia central, pruebas de ji cuadrado y t de Student (nivel de significación el 5 %). Resultados: Predominaron la enfermedad cerebrovascular hemorrágica, el sexo masculino (52,8 %) y el grupo de edad de 60-100 años (64,8 %). La edad media fue de 63,8 años. La media del valor de las escalas APACHE II y Glasgow fue de 21,6 y 6,5 puntos. El 97,6 % recibió ventilación mecánica. La estadía media fue de 7,0 días. El edema cerebral intenso constituyó la principal causa de muerte directa (79,3 %). Conclusiones: Existe predominio de la ECV de tipo hemorrágica, en pacientes del sexo masculino, de 60-100 años, con APACHE II > 15 puntos, Glasgow ≤ 8 puntos, ventilados, estadía ≤ 7 días y edema cerebral intenso.


Introduction: In Cuba, cerebrovascular diseases (CVD) are very common non-communicable chronic conditions. Objectives: Characterize patients from intensive care unit with a pathological diagnosis of CVD. Methods: Observational, descriptive and transversal study in a sample of 176 patients. Variables: age (19-39 years, 40-59 years, 60-100 years), sex, type of CVD (hemorrhagic, ischemic), APACHE II scale (≤ 15, > 15 score) and Glasgow coma on admission (≤ 8, > 8 score), mechanical ventilation (yes, no), length of stay (≤ 7, > 7 days) and direct cause of death. Frequencies, measures of central tendency, chi-square and Student's t tests (significance level of 5%) were calculated. Results: Hemorrhagic cerebrovascular disease, male sex (52.8%) and the age group of 60-100 years (64.8%) predominated. The mean age was 63.8 years. The average value of the APACHE II and Glasgow scales was 21.6 and 6.5. 97.6% received mechanical ventilation. The mean stay was 7.0 days. Severe cerebral edema was the main cause of direct death (79.3%). Conclusions: There is a predominance of hemorrhagic CVD, in male patients, aged 60-100 years, APACHE II score > 15, Glasgow score ≤ 8, ventilated patients, stay ≤ 7 days and intense cerebral edema.

13.
Prenat Diagn ; 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37776084

ABSTRACT

BACKGROUND: Artificial intelligence (AI) has the potential to improve prenatal detection of congenital heart disease. We analysed the performance of the current national screening programme in detecting hypoplastic left heart syndrome (HLHS) to compare with our own AI model. METHODS: Current screening programme performance was calculated from local and national sources. AI models were trained using four-chamber ultrasound views of the fetal heart, using a ResNet classifier. RESULTS: Estimated current fetal screening programme sensitivity and specificity for HLHS were 94.3% and 99.985%, respectively. Depending on calibration, AI models to detect HLHS were either highly sensitive (sensitivity 100%, specificity 94.0%) or highly specific (sensitivity 93.3%, specificity 100%). Our analysis suggests that our highly sensitive model would generate 45,134 screen positive results for a gain of 14 additional HLHS cases. Our highly specific model would be associated with two fewer detected HLHS cases, and 118 fewer false positives. CONCLUSION: If used independently, our AI model performance is slightly worse than the performance level of the current screening programme in detecting HLHS, and this performance is likely to deteriorate further when used prospectively. This demonstrates that collaboration between humans and AI will be key for effective future clinical use.

14.
Front Nutr ; 10: 1226820, 2023.
Article in English | MEDLINE | ID: mdl-37645630

ABSTRACT

Introduction: A growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case-control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

15.
Front Immunol ; 14: 1215913, 2023.
Article in English | MEDLINE | ID: mdl-37600828

ABSTRACT

American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite Trypanosoma cruzi and is characterized by the presence of cardiac or gastrointestinal symptoms in a large number of patients during the chronic phase of the disease. Although the origin of the symptoms is not clear, several mechanisms have been described involving factors related to T. cruzi and the host immune response. In this sense, the extracellular vesicles (EVs) secreted by the parasite and the immune complexes (ICs) formed after their recognition by host IgGs (EVs-IgGs) may play an important role in the immune response during infection. The aim of the present work is to elucidate the modulation of the immune response exerted by EVs and the ICs they form by analyzing the variation in the subpopulations of small and large peritoneal macrophages after intraperitoneal inoculation in mice and to evaluate the role of the sialylation of the host IgGs in this immunomodulation. Both macrophage subpopulations were purified and subjected to cytokine expression analysis by RT-qPCR. The results showed an increase in the small peritoneal macrophage subpopulation after intraperitoneal injection of parasite EVs, but a greater increase in this subpopulation was observed when sialylated and non-sialylated ICs were injected, which was similar to inoculation with the trypomastigote stage of the parasite. The cytokine expression results showed the ability of both subpopulations to express inflammatory and non-inflammatory cytokines. These results suggest the role of free EVs in the acute phase of the disease and the possible role of immune complexes in the immune response in the chronic phase of the disease, when the levels of antibodies against the parasite allow the formation of immune complexes. The differential expression of interleukins showed after the inoculation of immune complexes formed with sialylated and non-sialylated IgGs and the interleukins expression induced by EVs, demonstrates that the IgG glycosilation is involved in the type of immune response that dominates in each of the phases of the Chagas disease.


Subject(s)
Chagas Disease , Extracellular Vesicles , Trypanosoma cruzi , Animals , Mice , Antigen-Antibody Complex , Macrophages, Peritoneal , Cytokines
16.
Inorg Chem ; 62(37): 14873-14887, 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37651747

ABSTRACT

Titanium compounds in low oxidation states are highly reducing species and hence powerful tools for the functionalization of small molecules. However, their potential has not yet been fully realized because harnessing these highly reactive complexes for productive reactivity is generally challenging. Advancing this field, herein we provide a detailed route for the formation of titanium(III) orthophenylendiamido (PDA) species using [LiBHEt3] as a reducing agent. Initially, the corresponding lithium PDA compounds [Li2(ArPDA)(thf)3] (Ar = 2,4,6-trimethylphenyl (MesPDA), 2,6-diisopropylphenyl (iPrPDA)) are combined with [TiCl4(thf)2] to form the heterobimetallic complexes [{TiCl(ArPDA)}(µ-ArPDA){Li(thf)n}] (n = 1, Ar = iPr 3 and n = 2, Ar = Mes 4). Compound 4 evolves to species [Ti(MesPDA)2] (6) via thermal treatment. In contrast, the transformation of 3 into [Ti(iPrPDA)2] (5) only occurs in the presence of [LiNMe2], through a lithium-assisted process, as revealed by density functional theory (DFT). Finally, the Ti(IV) compounds 3-6 react with [LiBHEt3] to give rise to the Ti(III) species [Li(thf)4][Ti(ArPDA)2] (Ar = iPr 8, Mes 9). These low-valent compounds in combination with [PPN]Cl (PPN = bis(triphenylphosphine)iminium) are proved to be highly selective catalysts for the copolymerization of CO2 and cyclohexene epoxide. Reactions occur at 1 bar pressure with activity/selectivity levels similar to Salen-Cr(III) compounds.

17.
iScience ; 26(7): 107214, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37456859

ABSTRACT

Some HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

18.
Med Image Anal ; 89: 102793, 2023 10.
Article in English | MEDLINE | ID: mdl-37482034

ABSTRACT

The diagnostic value of ultrasound images may be limited by the presence of artefacts, notably acoustic shadows, lack of contrast and localised signal dropout. Some of these artefacts are dependent on probe orientation and scan technique, with each image giving a distinct, partial view of the imaged anatomy. In this work, we propose a novel method to fuse the partially imaged fetal head anatomy, acquired from numerous views, into a single coherent 3D volume of the full anatomy. Firstly, a stream of freehand 3D US images is acquired using a single probe, capturing as many different views of the head as possible. The imaged anatomy at each time-point is then independently aligned to a canonical pose using a recurrent spatial transformer network, making our approach robust to fast fetal and probe motion. Secondly, images are fused by averaging only the most consistent and salient features from all images, producing a more detailed compounding, while minimising artefacts. We evaluated our method quantitatively and qualitatively, using image quality metrics and expert ratings, yielding state of the art performance in terms of image quality and robustness to misalignments. Being online, fast and fully automated, our method shows promise for clinical use and deployment as a real-time tool in the fetal screening clinic, where it may enable unparallelled insight into the shape and structure of the face, skull and brain.


Subject(s)
Fetus , Imaging, Three-Dimensional , Humans , Ultrasonography , Imaging, Three-Dimensional/methods , Fetus/diagnostic imaging , Brain/diagnostic imaging , Brain/anatomy & histology , Head/diagnostic imaging , Image Processing, Computer-Assisted/methods
19.
Crit Care ; 27(1): 257, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37393330

ABSTRACT

BACKGROUND: Interpreting point-of-care lung ultrasound (LUS) images from intensive care unit (ICU) patients can be challenging, especially in low- and middle- income countries (LMICs) where there is limited training available. Despite recent advances in the use of Artificial Intelligence (AI) to automate many ultrasound imaging analysis tasks, no AI-enabled LUS solutions have been proven to be clinically useful in ICUs, and specifically in LMICs. Therefore, we developed an AI solution that assists LUS practitioners and assessed its usefulness in  a low resource ICU. METHODS: This was a three-phase prospective study. In the first phase, the performance of four different clinical user groups in interpreting LUS clips was assessed. In the second phase, the performance of 57 non-expert clinicians with and without the aid of a bespoke AI tool for LUS interpretation was assessed in retrospective offline clips. In the third phase, we conducted a prospective study in the ICU where 14 clinicians were asked to carry out LUS examinations in 7 patients with and without our AI tool and we interviewed the clinicians regarding the usability of the AI tool. RESULTS: The average accuracy of beginners' LUS interpretation was 68.7% [95% CI 66.8-70.7%] compared to 72.2% [95% CI 70.0-75.6%] in intermediate, and 73.4% [95% CI 62.2-87.8%] in advanced users. Experts had an average accuracy of 95.0% [95% CI 88.2-100.0%], which was significantly better than beginners, intermediate and advanced users (p < 0.001). When supported by our AI tool for interpreting retrospectively acquired clips, the non-expert clinicians improved their performance from an average of 68.9% [95% CI 65.6-73.9%] to 82.9% [95% CI 79.1-86.7%], (p < 0.001). In prospective real-time testing, non-expert clinicians improved their baseline performance from 68.1% [95% CI 57.9-78.2%] to 93.4% [95% CI 89.0-97.8%], (p < 0.001) when using our AI tool. The time-to-interpret clips improved from a median of 12.1 s (IQR 8.5-20.6) to 5.0 s (IQR 3.5-8.8), (p < 0.001) and clinicians' median confidence level improved from 3 out of 4 to 4 out of 4 when using our AI tool. CONCLUSIONS: AI-assisted LUS can help non-expert clinicians in an LMIC ICU improve their performance in interpreting LUS features more accurately, more quickly and more confidently.


Subject(s)
Artificial Intelligence , Intensive Care Units , Humans , Prospective Studies , Retrospective Studies , Ultrasonography
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