Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

Immunoglobulin G4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant.

BACKGROUND: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. METHODS: We studied seven relatives with autoimmune/inflammatory diseases and lymphoproliferative diseases. We analysed biopsy results and performed whole-exome sequencing and immunological studies. RESULTS: Disease onset occurred at a mean age of 25.2 years (range: 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, four had confirmed immunoglobulin G4-related disease (IgG4-RD), and five developed B-cell malignancies: lymphoma in four and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening COVID-19 pneumonia, one of whom had autoantibodies neutralizing interferon (IFN)-α. The recently described IKZF1 gain-of-function p.R183H variant was found in the five affected relatives tested and in a six-year-old asymptomatic girl. Immunological analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, TEMRA and CD28-CD57+ CD4+ and CD8+ T cells, Th2 and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in three patients. CONCLUSION: Heterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses.

Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N2 adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses.

Assessing SARS-CoV-2 Testing Adherence in a University Town: Recurrent Event Modeling Analysis.

BACKGROUND: Healthy Davis Together was a program launched in September 2020 in the city of Davis, California, to mitigate the spread of COVID-19 and facilitate the return to normalcy. The program involved multiple interventions, including free saliva-based asymptomatic testing, targeted communication campaigns, education efforts, and distribution of personal protective equipment, community partnerships, and investments in the local economy. OBJECTIVE: This study identified demographic characteristics of individuals that underwent testing and assessed adherence to testing over time in a community pandemic-response program launched in a college town in California, United States. METHODS: This study outlines overall testing engagement, identifies demographic characteristics of participants, and evaluates testing participation changes over 4 periods of the COVID-19 pandemic, distinguished by the dominant variants Delta and Omicron. Additionally, a recurrent model is employed to explore testing patterns based on the participants' frequency, timing, and demographic characteristics. RESULTS: A total of 770,165 tests were performed between November 18, 2020, and June 30, 2022, among 89,924 (41.1% of total population) residents of Yolo County, with significant participation from racially or ethnically diverse participants and across age groups. Most positive cases (6351 of total) and highest daily participation (895 per 100,000 population) were during the Omicron period. There were some gender and age-related differences in the pattern of recurrent COVID-19 testing. Men were slightly less likely (hazard ratio [HR] 0.969, 95% CI 0.943-0.996) to be retested and more likely (HR 1.104, 95% CI 1.075-1.134) to stop testing altogether than women. People aged between 20 and 34 years were less likely to be retested (HR 0.861, 95% CI 0.828-0.895) and more likely to stop testing altogether (HR 2.617, 95% CI 2.538-2.699). However, older age groups were less likely to stop testing, especially those aged between 65-74 years and 75-84 years, than those aged between 0 and 19 years. The likelihood of stopping testing was lower (HR 0.93, 95% CI 0.889-0.976) for the Asian group and higher for the Hispanic or Latino (HR 1.185, 95% CI 1.148-1.223) and Black or African American (HR 1.198, 95% CI 1.054-1.350) groups than the White group. CONCLUSIONS: The unique features of a pandemic response program that supported community-wide access to free asymptomatic testing provide a unique opportunity to evaluate adherence to testing recommendations and testing trends over time. Identification of individual and group-level factors associated with testing behaviors can provide insights for identifying potential areas of improvement in future testing initiatives.

Hydrothermal processing of Sarcopeltis skottsbergii and study of the potential of its carrageenan for tissue engineering.

The red macroalga Sarcopeltis skottsbergii was subjected to hydrothermal processing to maximize the solubilization and recovery of carrageenan. Once isolated by ethanol precipitation, the carrageenan was further chemically (oligosaccharides composition), and structurally (TGA/DTG, DSC, HPSEC, FTIR-ATR, 1H NMR, SEM, etc.) characterized, as well as employed as source for the synthesis of hydrogels. The rheological properties of the carrageenan showed promising results as biopolymer for food applications due to the high molecular weight (500 kDa) presenting higher cell viability than 70 %. The evaluation of immune activation using ELISA test reflected a lower inflammatory response for concentrations of 0.025 % of carrageenan. Conversely, the cell viability of the synthesized hydrogels did not surpass 50 %. This work represents a considerable step forward to obtain a biopolymer from natural sources and a thorough study of their chemical, structural and biological properties.

Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer in women is 3-4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. METHODS: Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. RESULTS: In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. CONCLUSIONS: Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. METHODS: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4 , IgA1 and IgA2 ) and their inhibitory capacity were measured at multiple timepoints. RESULTS: The allergen concentration tolerated increased significantly at 6 months (Group A; p = .047) and 24 months (Group B; p = .049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71-fold, p = .027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p = .047 and p = .0039) and sIgA2 to Phl p in Group B (p = .032 and p = .0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen-IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra-nasally in Group A (serum; 𝜌 = -.47, p = .0006, nasal; 𝜌 = -.38, p = .0294). CONCLUSIONS: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR.

Calcification patterns and morphology of Sella turcica are related to anteroposterior skeletal malocclusions: A cross-sectional study.

BACKGROUND: The sphenoid bone is an irregular, unpaired, symmetrical bone located in the middle of the anterior skull and is involved in craniofacial growth and development. Since the morphology of Sella turcica (ST) is associated with different craniofacial patterns, this study aimed to investigate if there is a correlation between ST morphology on the one hand and sagittal craniofacial patterns on the other hand. METHODS: This study was conducted with a convenience sample that included Brazilian individuals undergoing orthodontic treatment. Lateral cephalograms were used to evaluate the calcification pattern and morphology of ST, as well as skeletal class by analyzing the ANB angle. Pearson's chi-square test with Bonferroni post-hoc test was performed to evaluate the association between ST calcification pattern and morphology, and anteroposterior skeletal malocclusion. The established significance level was 0.05. RESULTS: The study collective was comprised of 305 orthodontic patients (178 (58.4 %) female, 127 (41.6 %) male), who had a mean age of 23.2 (±10.6) years. 131 participants (42.9 %) presented skeletal class I, 142 (46.6%) skeletal Class II, and 32 (10.5%) had a skeletal class III. The degree of prognathism of the mandible showed a homogenous distribution within the study collective (91 (29.9 %) orthognathic, 100 (32.9 %) retrognathic, 113 (37.2 %) prognathic mandible). Concerning the maxilla, 92 (30.2%) individuals presented an orthognathic upper jaw, whereas 60 (19.7%) showed maxillary retrognathism and 153 (50.2%) maxillary prognathism. Compared to patients with skeletal class I, skeletal class III individuals presented significantly more hypertrophic posterior clinoid process (p<0.007) and pyramidal shape of the dorsum of the ST (p<0.038). CONCLUSIONS: Our results suggest that the hypertrophic posterior clinoid process and pyramidal shape of the ST dorsum are more prevalent in individuals with skeletal class III malocclusion.

Where Should I Draw the Line: PET-Driven, Data-Driven, or Manufacturer Cut-Off?

Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial. Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aß1-42, pTau, tTau, and Aß1-42/Aß1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification. Methods: CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aß1-42/Aß1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification. Results: One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aß1-42/Aß1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used. Conclusions: We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.

Effect of High Sodium Intake on Gut Tight Junctions' Structure and Permeability to Bacterial Toxins in a Rat Model of Chronic Kidney Disease.

INTRODUCTION: Uremic toxicity changes the gut structure and permeability, allowing bacterial toxins to translocate from the lumen to the blood during chronic kidney failure (CKD). Clinical fluid overload and tissue edema without uremia have similar effects but have not been adequately demonstrated and analyzed in CKD. AIMS: To investigate the effect of sodium intake on the plasma concentration of gut-derived uremic toxins, indoxyl sulfate (IS), and p-cresyl sulfate (pCS) and the expression of genes and proteins of epithelial gut tight junctions in a rat model of CKD. METHODS: Sham-operated (control group, CG) and five-sixths nephrectomized (5/6Nx) Sprague-Dawley rats were randomly assigned to low (LNa), normal (NNa), or high sodium (HNa) diets., Animals were then sacrificed at 8 and 12 weeks and analyzed for IS and pCS plasma concentrations, as well as for gene and protein expression of thigh junction proteins, and transmission electron microscopy (TEM) in colon fragments. RESULTS: The HNa 5/6Nx groups had higher concentrations of IS and pCS than CG, NNa, and LNa at eight and twelve weeks. Furthermore, HNa 5/6Nx groups had reduced expression of the claudin-4 gene and protein than CG, NNa, and LNa. HNa had reduced occludin gene expression compared to CG. Occludin protein expression was more reduced in HNa than in CG, NNa, and LNa. The gut epithelial tight junctions appear dilated in HNa compared to NNa and LNa in TEM. CONCLUSION: Dietary sodium intake and fluid overload have a significant role in gut epithelial permeability in the CKD model.

Composite Zonal Scaffolds of Collagen I/II for Meniscus Regeneration.

The meniscus is divided into three zones according to its vascularity: an external vascularized red-red zone mainly comprising collagen I, a red-white interphase zone mainly comprising collagens I and II, and an internal white-white zone rich in collagen II. Known scaffolds used to treat meniscal injuries do not reflect the chemical composition of the vascular areas of the meniscus. Therefore, in this study, four composite zonal scaffolds (named A, B, C, and D) were developed and characterized; the developed scaffolds exhibited the main chemical components of the external (collagen I), interphase (collagens I/II), and internal (collagen II) zones of the meniscus. Noncomposite scaffolds were also produced (named E), which had the same shape as the composite scaffolds but were entirely made of collagen I. The composite zonal scaffolds were prepared using different concentrations of collagen I and the same concentration of collagen II and were either cross-linked with genipin or not cross-linked. Porous, biodegradable, and hydrophilic scaffolds with an expected chemical composition were obtained. Their pore size was smaller than the size reported for the meniscus substitutes; however, all scaffolds allowed the adhesion and proliferation of human adipose-derived stem cells (hADSCs) and were not cytotoxic. Data from enzymatic degradation and hADSC proliferation assays were considered for choosing the cross-linked composite scaffolds along with the collagen I scaffold and to test if composite zonal scaffolds seeded with hADSC and cultured with differentiation medium produced fibrocartilage-like tissue different from that formed in noncomposite scaffolds. After 21 days of culture, hADSCs seeded on composite scaffolds afforded an extracellular matrix with aggrecan, whereas hADSCs seeded on noncomposite collagen I scaffolds formed a matrix-like fibrocartilage without aggrecan.

Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams.

BACKGROUND: Amoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs). METHODS: mDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3+, CD4+, CD8+, CD4+Th1, and CD4+Th2, by flow cytometry. RESULTS: Higher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV. CONCLUSIONS: mDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction.

A Genetic Tool to Identify Predators Responsible for Livestock Attacks in South America and Recommendations for Human-Wildlife Conflict Mitigation.

Livestock predation induces global human-wildlife conflict, triggering the retaliatory killing of large carnivores. Although domestic dogs (Canis familiaris) contribute to livestock depredation, blame primarily falls on wild predators. Dogs can also transmit pathogens between wildlife, domestic animals, and humans. Therefore, the presence of free-ranging dogs can have negative consequences for biodiversity conservation, smallholder economy, food supply, and public health, four of the United Nations' Sustainable Developed Goals (SDGs) for 2030. In Ecuador, where livestock sustains rural households, retaliatory poaching threatens Andean bear (Tremarctos ornatus), jaguar (Panthera onca), and puma (Puma concolor) populations. However, the role of dogs in these incidents remains underexplored. The present study evaluates the possibility of reliable molecular identification of predatory species from DNA traces in bite wounds. Our results revealed the presence of dog saliva on four out of six livestock carcasses presumably attacked by wild predators. These findings highlight the importance of rectifying misinformation about large carnivores in Ecuador and the need to control dog populations. We recommend that local administrations incorporate DNA analysis into livestock predation events to examine how common the problem is, and to use the analysis to develop conflict mitigation strategies which are essential for the conservation of large carnivores.

High Prevalence of Familial Hypercholesterolemia Due to the Founder Effect of the LDLR c.2271del Variant in Communities of Oaxaca, Mexico.

INTRODUCTION: In Mexico, familial hypercholesterolemia (FH) is underdiagnosed, but population screening in small communities where at least one homozygous patient has already been detected results in a useful and inexpensive approach to reduce this problem. Considering that we previously reported nine homozygous cases from the state of Oaxaca, we decided to perform a population screening to identify patients with FH and to describe both their biochemical and genetic characteristics. METHODS: LDL cholesterol (LDLc) was quantified in 2,093 individuals from 11 communities in Oaxaca; either adults with LDLc levels ≥170 mg/dL or children with LDLc ≥130 mg/dL were classified as suggestive of FH and therefore included in the genetic study. LDLR and APOB (547bp fragment of exon 26) genes were screened by sequencing and MLPA analysis. RESULTS: Two hundred and five individuals had suggestive FH, with a mean LDLc of 223 ± 54 mg/dL (range: 131-383 mg/dL). Two pathogenic variants in the LDLR gene were detected in 149 individuals: c.-139_-130del (n = 1) and c.2271del (n = 148). All patients had a heterozygous genotype. With the cascade screening of their relatives (n = 177), 15 heterozygous individuals for the c.2271del variant were identified, presenting a mean LDLc of 133 ± 35 mg/dL (range: 60-168 mg/dL). CONCLUSIONS: The FH frequency in this study was 7.8% (164/2093), the highest reported worldwide. A founder effect combined with inbreeding could be responsible for the high percentage of patients with the LDLR c.2271del variant (99.4%), which allowed us to detect both significant biochemical heterogeneity and incomplete penetrance; hence, we assumed the presence of phenotype-modifying variants.

Decline in pubertal timing and its relationship with excess weight. A study of the secular trend in age at menarche in girls from La Plata district (Buenos Aires, Argentina).

OBJECTIVE: To provide information on the secular trend in age at menarche (AgM) in Argentinean girls in relation to excess weight (EW) and body adiposity. METHODS: Two cohorts (C) (C1, 2005-2007 and C2, 2015-2019) of children aged 8-14 years from La Plata district were studied using identical methodological criteria. Each participating child was asked about menarche (M) status: M presence (MP) or absence (MA). The AgM was estimated using the status quo method and logistic regression analysis. Body weight, height, and tricipital and subscapular skinfolds were collected to estimate EW (overweight + obesity) according to WHO criteria, and body adiposity (sum of skinfolds, SSK = [tricipital + subscapular]). The prevalence of EW by C was estimated and compared using the Chi-square test. The MP probability in relation to age, C, and EW was analyzed by applying logistic regression. Parents completed a questionnaire to assess family socioeconomic conditions. Data were compared using the Chi-square test. RESULTS: Differences in MP prevalence between C were significant (C1: 21.1% vs. C2: 28.7%). Median AgM was 12.81 years in C1 and 12.22 in C2. The prevalence of EW was higher in C2 (35.3%) than in C1 (24.6%). The probability of MP was higher in C2 than in C1 and children with EW. Both BMI and SSK showed inter-cohort increases. Socioeconomic conditions were substantially deteriorated between C. CONCLUSION: In an obesogenic context marked by the significant increase in body adiposity and EW, M prevalence exhibited a positive secular trend and AgM reduced by nearly seven months between the cohorts studied.

Descripción de las intervenciones broncoscópicas en estenosis traqueales posterior a infección por COVID-19 / Description of Bronchoscopic Interventions in Post-COVID Tracheal Stenosis

Introducción: La infección por SARS-CoV-2 puede presentar síndrome de distrés res-piratorio agudo con requerimiento de ventilación mecánica prolongada y retraso en la realización de traqueostomía. Esto trae como consecuencia un incremento en casos de estenosis traqueal y la necesidad de métodos menos invasivos para su abordaje. Métodos: Estudio descriptivo de corte transversal, desde marzo 2020 hasta diciem-bre 2021 en el Hospital Universitario Nacional de Colombia, en adultos con estenosis traqueal postintubación asociado SARS-CoV-2. Se realizó análisis univariado entre los grupos con infección o no por SARS-CoV-2 como control, y reintervención, grado de estenosis, uso de inyección intramucosa con dexametasona intratraqueal o múltiples estenosis como desenlaces de importancia. Se usó test exacto de Fisher, t Student y Man-Whitney según la naturaleza de variables. Se consideró p estadísticamente significativo menor a 0.05.Resultados: Se identificaron 26 pacientes, 20 tenían COVID-19 y 6 no. Se encontraron diferencias en edad (p=0,002), epilepsia (p=0,007) y estenosis múltiple (p= 0,04). En 85% de los casos se utilizó láser blue más dilatación con balón pulmonar, en 35% inyección intramucosa con dexametasona intratraqueal y reintervención en 35%, sin diferencias significativas entre grupos. Conclusiones: Se observó un incremento tres veces mayor de pacientes con estenosis múltiple en el grupo de infección por COVID-19, así mismo se encontró que el método más utilizado en este grupo para la recanalización fue el uso de láser blue más dilatación con balón pulmonar y la innovación en el uso de inyección intramucosa.

Introduction: SARS-CoV-2 infection can lead to acute respiratory distress syndrome with a prolonged need for mechanical ventilation and delayed tracheostomy, resulting in an increase in cases of tracheal stenosis and the necessity for less invasive approaches.Methods: A descriptive cross-sectional study was conducted from March 2020 to December 2021 at the Hospital Universitario Nacional de Colombia, focusing on adults with post-intubation tracheal stenosis associated with SARS-CoV-2. Univariate analysis was performed between groups with or without SARS-CoV-2 infection as a control, considering reintervention, degree of stenosis, use of intratracheal steroids, or multiple stenoses as important outcomes. Fisher's exact test, Student's t-test, and Mann-Whit-ney test were employed based on the nature of variables. A p-value less than 0.05 was considered statistically significant.Results: A total of 26 patients were included, with 20 having COVID-19 and 6 without. Significant differences were found in age (p=0.002), epilepsy (p=0.007), and multiple stenosis (p=0.04). In 85% of cases, laser blue plus balloon pulmonary dilation was used, intratracheal dexamethasone in 35%, and reintervention in 35%, with no significant differences between groups.Conclusions: A threefold increase in subglottic stenosis was observed during the SARS-CoV-2 pandemic, with more instances of multiple stenosis and predominantly the use of laser blue plus balloon pulmonary dilation as a successful recanalization technique. There was a higher use of intratracheal dexamethasone in this group compared to oth-er pathologies causing tracheal stenosis.

The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. METHODS: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. RESULT: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. CONCLUSIONS: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment.

Machine Learning to Predict Enzyme-Substrate Interactions in Elucidation of Synthesis Pathways: A Review.

Enzyme-substrate interactions play a fundamental role in elucidating synthesis pathways and synthetic biology, as they allow for the understanding of important aspects of a reaction. Establishing the interaction experimentally is a slow and costly process, which is why this problem has been addressed using computational methods such as molecular dynamics, molecular docking, and Monte Carlo simulations. Nevertheless, this type of method tends to be computationally slow when dealing with a large search space. Therefore, in recent years, methods based on artificial intelligence, such as support vector machines, neural networks, or decision trees, have been implemented, significantly reducing the computing time and covering vast search spaces. These methods significantly reduce the computation time and cover broad search spaces, rapidly reducing the number of interacting candidates, as they allow repetitive processes to be automated and patterns to be extracted, are adaptable, and have the capacity to handle large amounts of data. This article analyzes these artificial intelligence-based approaches, presenting their common structure, advantages, disadvantages, limitations, challenges, and future perspectives.

Artificial neural networks reconstruct missing perikymata in worn teeth.

Dental evolutionary studies in hominins are key to understanding how our ancestors and close fossil relatives grew from the early stages of embryogenesis into adults. In a sense, teeth are like an airplane's 'black box' as they record important variables for assessing developmental timing, enabling comparisons within and between populations, species, and genera. The ability to discern this type of nuanced information is embedded in the nature of how tooth enamel and dentin form: incrementally and over years. This incremental growth leaves chronological indicators in the histological structure of enamel, visible on the crown surface as perikymata. These structures are used in the process of reconstructing the rate and timing of tooth formation. Unfortunately, the developmentally earliest growth lines in lateral enamel are quickly lost to wear once the tooth crown erupts. We developed a method to reconstruct these earliest, missing perilymata from worn teeth through knowledge of the later-developed, visible perikymata for all tooth types (incisors, canines, premolars, and molars) using a modern human dataset. Building on our previous research using polynomial regressions, here we describe an artificial neural networks (ANN) method. This new ANN method mostly predicts within 2 counts the number of perikymata present in each of the first three deciles of the crown height for all tooth types. Our ANN method for estimating perikymata lost through wear has two immediate benefits: more accurate values can be produced and worn teeth can be included in dental research. This tool is available on the open-source platform R within the package teethR released under GPL v3.0 license, enabling other researchers the opportunity to expand their datasets for studies of periodicity in histological growth, dental development, and evolution.