Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries.

Lead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.

microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns of sterol regulatory element binding protein (SREBP) genes are master regulators of sterol and fatty acid (FA) metabolism. miR-33 controls macrophage immunometabolic response and enhances mitochondrial biogenesis, FA oxidation, and cholesterol efflux. Here, we show that miR-33 levels are increased in bronchoalveolar lavage (BAL) cells isolated from patients with IPF compared with healthy controls. We demonstrate that specific genetic ablation of miR-33 in macrophages protects against bleomycin-induced pulmonary fibrosis. The absence of miR-33 in macrophages improves mitochondrial homeostasis and increases autophagy while decreasing inflammatory response after bleomycin injury. Notably, pharmacological inhibition of miR-33 in macrophages via administration of anti-miR-33 peptide nucleic acids (PNA-33) attenuates fibrosis in different in vivo and ex vivo mice and human models of pulmonary fibrosis. These studies elucidate a major role of miR-33 in macrophages in the regulation of pulmonary fibrosis and uncover a potentially novel therapeutic approach to treat this disease.

Invasive Versus Medical Management in Patients With Chronic Kidney Disease and Non-ST-Segment-Elevation Myocardial Infarction.

Background The role of invasive management compared with medical management in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and advanced chronic kidney disease (CKD) is uncertain, given the increased risk of procedural complications in patients with CKD. We aimed to compare clinical outcomes of invasive management with medical management in patients with NSTEMI-CKD. Methods and Results We identified NSTEMI and CKD stages 3, 4, 5, and end-stage renal disease admissions using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes from the Nationwide Readmission Database 2016 to 2018. Patients were stratified into invasive and medical management. Primary outcome was mortality (in-hospital and 6 months after discharge). Secondary outcomes were in-hospital postprocedural complications (acute kidney injury requiring dialysis, major bleeding) and postdischarge 6-month safety and major adverse cardiovascular events. Out of 141 052 patients with NSTEMI-CKD, 85 875 (60.9%) were treated with invasive management, whereas 55 177 (39.1%) patients were managed medically. In propensity-score matched cohorts, invasive strategy was associated with lower in-hospital (CKD 3: odds ratio [OR], 0.47 [95% CI, 0.43-0.51]; P<0.001; CKD 4: OR, 0.79 [95% CI, 0.69-0.89]; P<0.001; CKD 5: OR, 0.72 [95% CI, 0.49-1.06]; P=0.096; end-stage renal disease: OR, 0.51 [95% CI, 0.46-0.56]; P<0.001) and 6-month mortality. Invasive management was associated with higher in-hospital postprocedural complications but no difference in postdischarge safety outcomes. Invasive management was associated with a lower hazard of major adverse cardiovascular events at 6 months in all CKD groups compared with medical management. Conclusions Invasive management was associated with lower mortality and major adverse cardiovascular events but minimal increased in-hospital complications in patients with NSTEMI-CKD compared with medical management, suggesting patients with NSTEMI-CKD should be offered invasive management.

Absolute lymphocyte count as a predictor of mortality and readmission in heart failure hospitalization.

Background: There is renewed interest in pursuing frugal and readily available laboratory markers to predict mortality and readmission in heart failure. We aim to determine the relationship between absolute lymphocyte count (ALC) and clinical outcomes in patients with heart failure hospitalization. Methods: This was a retrospective cohort study of patients with heart failure. Patients were divided into two groups based on ALC, less than or equal to 1500 cells/mm3 and > 1500 cells/ mm3. The primary outcome was all-cause mortality. We did subgroup analysis based on ejection fraction and studied the association between ALC categories and clinical outcomes. Both ALC groups are matched by propensity score, outcomes were analyzed by Cox regression, and estimates are presented in hazard ratios (HR) and 95% confidence intervals (CI). Results: We included 1029 patients in the pre-matched cohort and 766 patients in the propensity-score matched cohort. The median age was 64 years (IQR, 54-75), and 60.78% were male. In the matched cohort, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality compared with ALC > 1500 cells/mm3 (HR 1.51, 95% CI: 1.17-1.95; P = 0.002). These results were reproducible in subgroups of heart failure. When ALC was divided into four groups based on their levels, the lowest group of ALC had the highest risk of mortality. Conclusions: In patients with heart failure and both subgroups, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality. Patients in lower groups of the ALC categories had a higher risk of mortality.

Non-Bleeding Colonic Ulcer as Initial Manifestation of Disseminated Cryptococcosis in a Patient With Human Immunodeficiency Virus.

Cryptococcosis is an invasive mycosis caused by Cryptococcus sp. Its presence is described closely with immunosuppressive states. Once it has reached the body, it has shown a predilection for two sites: the lungs and the central nervous system. Nonetheless, since it has hematogenous dissemination, it can colonize and yield disease at any organ. Hence, a patient will typically present with constitutional symptoms including fever, malaise, and weight loss, associated with cough, shortness of breath, chest pain, or associated headache, drowsiness, and meningeal irritation signs. We illustrate here one of the uncommon non-pulmonary non-cerebral forms of the disease of cryptococcosis, a newly diagnosed HIV/AIDS patient with a non-bleeding colon ulcer, who lacks respiratory or central nervous system (CNS)-related symptoms but endorses non-specific gastrointestinal complaints. The first evidence of the disease was the elevated cryptococcal antigen (CrAg). The direct visualization of the spores in the biopsy confirmed the infection.

Hypernatremia in Diabetic Ketoacidosis: Rare Presentation and a Cautionary Tale.

Hyponatremia in diabetic ketoacidosis (DKA) is common and can be due to several reasons. However, hypernatremia in DKA is rare and can be life-threatening. Its exact etiology is not clear and several mechanisms related to water deficit from inadequate oral intake and free water loss that supersedes the electrolyte loss through diarrhea or vomiting have been proposed. Treating the DKA more aggressively than the hypernatremia itself, choosing a hypoosmolar fluid, and switching to D5-0.45% saline, when glucose has decreased, are some of the vital considerations for the management of hypernatremia in DKA. We present a 44-year-old male patient with an unclear history of DKA with unusually severe hypernatremia that gradually responded to aggressive management of DKA with rigorous IV hydration and the above-mentioned strategies.

Daptomycin-Induced Hyperkalemia as an Early Sign of Rhabdomyolysis in a Diabetic Patient.

Daptomycin is a lipopeptide antibiotic that is active against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). It is less nephrotoxic than vancomycin. It has a unique bactericidal mechanism through destruction of bacterial membrane potential. However, one of the most clinically relevant adverse effects of daptomycin is reversible myopathy, especially when daptomycin is used in high doses. Here, we present a case of a patient with rhabdomyolysis preceded by hyperkalemia associated with daptomycin use. Soon after daptomycin administration, hyperkalemia was noticed before the acute rise in creatinine phosphokinase (CPK). The serum levels of potassium and CPK returned to normal after daptomycin was stopped which suggested the causal relationship between hyperkalemia and myopathy and daptomycin use. To our knowledge, this is the second case of hyperkalemia related to daptomycin use.

Fibrosis: Lessons from OMICS analyses of the human lung.

In recent decades there has been a significant shift in our understanding of idiopathic pulmonary fibrosis (IPF), a progressive and lethal disorder. While initially much of the mechanistic understanding was derived from hypotheses generated from animal models of disease, in recent decades new insights derived from humans with IPF have taken precedence. This is mainly because of the establishment of large collections of IPF lung tissues and patient cohorts, and the emergence of high throughput profiling technologies collectively termed 'omics' technologies based on their shared suffix. In this review we describe impacts of 'omics' analyses of human IPF samples on our understanding of the disease. In particular, we discuss the results of genomics and transcriptomics studies, as well as proteomics, epigenomics and metabolomics. We then describe how these findings can be integrated in a modified paradigm of human idiopathic pulmonary fibrosis, that introduces the 'hallmarks of aging' as a central theme in the IPF lung. This allows resolution of all the disparate cellular and molecular features in IPF, from the central role of epithelial cells, through the dramatic phenotypic alterations observed in fibroblasts and the numerous aberrations that inflammatory cells exhibit. We end with reiterating a call for renewed efforts to collect and analyze carefully characterized human tissues, in ways that would facilitate implementation of novel technologies for high resolution single cell omics profiling.

Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function.

Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-ß1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis.

A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries.

Staphylococcus aureus is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185 S. aureus) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec [SCCmec] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCCmec IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.

Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase-7 (MMP-7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP-7 was predictive of mortality in an independent cohort of IPF patients. METHODS: MMP-7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP-7 threshold of 12.1 ng/mL with all-cause mortality or transplant-free survival (TFS) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m-PCMI). RESULTS: MMP-7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 ± 6.55 ng/mL vs 6.03 ± 2.51 ng/mL, P < 0.001). The plasma MMP-7 threshold of 12.1 ng/mL was significantly associated with both all-cause mortality and TFS (unadjusted Cox proportional hazard ratio (HR) = 25.85 and 15.49, 95% CI: 10.91-61.23 and 5.41-44.34, respectively, P < 0.001). MMP-7 concentrations, split by 12.1 ng/mL, were significantly (P < 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP-7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DLCO ) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (r = 0.32, P = 0.001). CONCLUSION: This study confirms that MMP-7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.

Family structure and child food insecurity.

OBJECTIVES: We examined whether food insecurity was different for children in cohabiting or repartnered families versus those in single-mother or married-parent (biological) families. METHODS: We compared probabilities of child food insecurity (CFI) across different family structures in 4 national data sets: the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B), the Fragile Families and Child Wellbeing Study (FFCWS), the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), and the Panel Study of Income Dynamics-Child Development Supplement (PSID-CDS). RESULTS: Unadjusted probabilities of CFI in cohabiting or repartnered families were generally higher than in married-biological-parent families and often statistically indistinguishable from those of single-mother families. However, after adjustment for sociodemographic factors, most differences between family types were attenuated and most were no longer statistically significant. CONCLUSIONS: Although children whose biological parents are cohabiting or whose biological mothers have repartnered have risks for food insecurity comparable to those in single-mother families, the probability of CFI does not differ by family structure when household income, family size, and maternal race, ethnicity, education, and age were held at mean levels.

Evaluación cefalométrica del perfil de tejidos blandos en adultos jóvenes de Medellín / A cephalometric evaluation of the soft tissues profile in young adults from Medellin

El objetivo del tratamiento ortodóncico es el logro de una armonía facial óptima lamejor función oclusal posible dentro de los límites de la terapia. Cuando la deformidad maxilofacial sobrepasa estos límites, se hace necesaria la intervención del grupo interdisciplinario conformado por ortodoncistas y cirujanos maxilofaciales. Dicho grupo utiliza el análisis de Legan y Burstone de tejidos blandos para el diagnóstico, pero éste se basa en una muestra norteamericana y no toma en cuenta la variabilidad racial entre las poblaciones de las diferentes regiones del mundo. El objetivo de la presente investigación es determinar si existen diferencias entre una muestra de Medellín (Colombia) y una muestra norteamericana (USA), y una muestra de Bogotá (Colombia), al aplicar el análisis antes mencionado. Se utilizaron 102 sujetos de Medellín con padres y abuelos antioqueños (5 mujeres y 51 hombres) entre 18 y 29 años de edad, con buena armonía facial, a los cuales se les aplicó el análisis de Legan y Burstone. Los datos obtenidos se compararon con las muestras ya mencionadas, encontrándose diferencias significativas en los resultados, lo que amerita el uso de nuestros valores de tratamientos de pacientes locales

El Instituto Nacional de Ortopedia / The Instituto Nacional de Ortopedia

En este trabajo se presentan algunos aspectos relevantes de la organización y funcionamiento del Instituto Nacional de Ortopedia, destacando los aspectos relativos a la fundación del mismo y concluye con las perspectivas del Instituto para su futuro próximo