Closing the Sex-Based Differences in Stroke Care: Insights from a Large Telestroke Network on Treatment and Postacute Management.

Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. Methods: A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. Results: A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. Conclusions: No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia.

Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic.

Characterising glycosaminoglycans in human breastmilk and their potential role in infant health.

Human breastmilk is composed of many well researched bioactive components crucial for infant nutrition and priming of the neonatal microbiome and immune system. Understanding these components gives us crucial insight to the health and wellbeing of infants. Research surrounding glycosaminoglycans (GAGs) previously focused on those produced endogenously; however, recent efforts have shifted to understanding GAGs in human breastmilk. The structural complexity of GAGs makes detection and analysis complicated therefore, research is time consuming and limited to highly specialised teams experienced in carbohydrate analysis. In breastmilk, GAGs are present in varying quantities in four forms; chondroitin sulphate, heparin/heparan sulphate, dermatan sulphate and hyaluronic acid, and are hypothesised to behave similar to other bioactive components with suspected roles in pathogen defense and proliferation of beneficial gut bacteria. Chondroitin sulphate and heparin, being the most abundant, are expected to have the most impact on infant health. Their decreasing concentration over lactation further indicates their role and potential importance during early life.

The different response of Brassica napus genotypes to microspore embryogenesis induced by heat shock and trichostatin A is not determined by changes in cell wall structure and composition but by different stress tolerance.

During microspore embryogenesis, microspores are induced to develop into haploid embryos. In Brassica napus, microspore embryogenesis is induced by a heat shock (HS), which initially produces embryogenic structures with different cell wall architectures and compositions, and with different potentials to develop into embryos. The B. napus DH4079 and DH12075 genotypes have high and very low embryo yields, respectively. In DH12075, embryo yield is greatly increased by combining HS and the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). However, we show that HS + TSA inhibits embryogenesis in the highly embryogenic DH4079 line. To ascertain why TSA has such different effects in these lines, we treated DH4079 and DH12075 microspore cultures with TSA and compared the cell wall structure and composition of the different embryogenic structures in both lines, specifically the in situ levels and distribution of callose, cellulose, arabinogalactan proteins and high and low methyl-esterified pectin. For both lines, HS + TSA led to the formation of cell walls unfavorable for embryogenesis progression, with reduced levels of arabinogalactan proteins, reduced cell adhesion of inner walls and altered pectin composition. Thus, TSA effects on cell walls cannot explain their different embryogenic response to TSA. We also applied TSA to DH4079 cultures at different times and concentrations before HS application, with no negative effects on embryogenic induction. These results indicate that DH4079 microspores are hypersensitive to combined TSA and HS treatments, and open up new hypotheses about the causes of such hypersensitivity.

Human cerebral organoids: cellular composition and subcellular morphological features.

Introduction: Human cerebral organoids (hCOs) derived from pluripotent stem cells are very promising for the study of neurodevelopment and the investigation of the healthy or diseased brain. To help establish hCOs as a powerful research model, it is essential to perform the morphological characterization of their cellular components in depth. Methods: In this study, we analyzed the cell types consisting of hCOs after culturing for 45 days using immunofluorescence and reverse transcriptase qualitative polymerase chain reaction (RT-qPCR) assays. We also analyzed their subcellular morphological characteristics by transmission electron microscopy (TEM). Results: Our results show the development of proliferative zones to be remarkably similar to those found in human brain development with cells having a polarized structure surrounding a central cavity with tight junctions and cilia. In addition, we describe the presence of immature and mature migrating neurons, astrocytes, oligodendrocyte precursor cells, and microglia-like cells. Discussion: The ultrastructural characterization presented in this study provides valuable information on the structural development and morphology of the hCO, and this information is of general interest for future research on the mechanisms that alter the cell structure or function of hCOs.

1,2-Silyl Rearrangement in Gold Carbene Chemistry: Synthesis of Furyl-Decorated Tetrasubstituted Silylallene Derivatives.

The gold-catalyzed reaction of 2-en-4-ynones with alkynylsilanes provides fully substituted allene derivatives bearing furyl and silyl groups. This transformation would involve generation of a gold furyl carbene intermediate, which regioselectively undergoes a nucleophilic attack by the alkynylsilane at the electrophilic carbene carbon atom with the formation of a ß-gold vinyl cation species. The subsequent release of the gold catalyst, accompanied by a 1,2-silyl shift, leads to the formation of tetrasubstituted allene products.

Bleeding risk in hemophilia A and B carriers: comparison of factor levels determined using chronometric and chromogenic assays.

BACKGROUND: Predicting the bleeding risk in hemophilia A and B carriers (HAC, HBC) is challenging. OBJECTIVE: The objectives of this study were to describe the bleeding phenotype in HAC and HBC using the standardized Tosetto bleeding score (BS); to determine whether the BS correlates better with factor levels measured with a chromogenic assay than with factor levels measured with chronometric and thrombin generation assays; and to compare the results in HAC and HBC. METHODS: This ambispective, noninterventional study included obligate and sporadic HAC and HBC followed at a hemophilia treatment center between 1995 and 2019. RESULTS AND CONCLUSION: The median BS (3, range 0-21 vs. 3.5, range 0-15, P  = ns, respectively) and the abnormal BS rate (35.6% vs. 38.2%, P  = ns) were not significantly different in 104 HAC and 34 HBC (mean age: 38 years, 6-80 years). However, some differences were identified. The risk of factor deficiency was higher in HBC than HAC. Specifically, Factor VIII activity (FVIII):C/Factor IX activity (FIX):C level was low (<40 IU/dl) in 18.3% (chronometric assay) and 17.5% (chromogenic assay) of HAC and in 47% and 72.2% of HBC ( P  < 0.001). Moreover, the FIX:C level thresholds of 39.5 IU/dl (chronometric assay) and of 33.5 IU/dl (chromogenic assay) were associated with very good sensitivity (92% and 100%, respectively) and specificity (80% for both) for bleeding risk prediction in HBC. Conversely, no FVIII:C level threshold could be identified for HAC, probably due to FVIII:C level variations throughout life.

Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy.

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC-apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain-caspase 1, caspase 5, caspase 8, and interleukin 1ß) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Sexually Transmitted Infections in the Emergency Department.

As the United States faces a worsening epidemic of sexually transmitted infections (STIs), emergency departments (EDs) play a critical role in identifying and treating these infections. The growing health inequities in the distribution and disproportionate impact of STIs add to the urgency of providing high-quality sexual health care through the ED. Changes in population health are reflected in the new Centers for Disease Control recommendations on screening, diagnostic testing, and treatment of STIs. This review covers common, as well as and less common or emerging STIs, and discusses the state-of-the-art guidance on testing paradigms, extragenital sampling, and antimicrobial treatment and prevention of STIs.

Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy.

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

New Paralogs of the Heliothis virescens ABCC2 Transporter as Potential Receptors for Bt Cry1A Proteins.

The ATP-binding cassette (ABC) transporters are a superfamily of membrane proteins. These active transporters are involved in the export of different substances such as xenobiotics. ABC transporters from subfamily C (ABCC) have also been described as functional receptors for different insecticidal proteins from Bacillus thuringiensis (Bt) in several lepidopteran species. Numerous studies have characterized the relationship between the ABCC2 transporter and Bt Cry1 proteins. Although other ABCC transporters sharing structural and functional similarities have been described, little is known of their role in the mode of action of Bt proteins. For Heliothis virescens, only the ABCC2 transporter and its interaction with Cry1A proteins have been studied to date. Here, we have searched for paralogs to the ABCC2 gene in H. virescens, and identified two new ABC transporter genes: HvABCC3 and HvABCC4. Furthermore, we have characterized their gene expression in the midgut and their protein topology, and compared them with that of ABCC2. Finally, we discuss their possible interaction with Bt proteins by performing protein docking analysis.

Complicaciones por cirugía oncológica mamaria / Complications due to oncological breast surgery

RESUMEN Introducción: Cada año en América Latina, más de 200,000 mujeres son diagnosticadas con cáncer de mama. Como parte del tratamiento de esta enfermedad, la cirugía es uno de los pilares fundamentales. El acto quirúrgico es una experiencia extrema para el paciente y el cirujano, necesaria en esta patología para el tratamiento completo y, como todo acto médico, no está exento de complicaciones. En Paraguay no se cuentan con estadísticas sobre la prevalencia de las complicaciones debidas a cirugías por cáncer de mama, por lo que este trabajo tiene como principal objetivo establecer dicha frecuencia en un hospital de cuarto nivel de complejidad. Materiales y métodos: Estudio retrospectivo, observacional, de corte transversal. Muestreo no probabilístico de casos consecutivos. La selección de sujetos de estudios se realizó de la población de pacientes que fueron sometidos a cirugía por cáncer de mama, en el Hospital de Clínicas en el periodo enero de 2018 a agosto 2022, y que cumplan con los criterios de inclusión y exclusión. Todas las variables han sido extraídas de la ficha clínica y fueron documentadas en el formulario de registro de datos. Se esperaba una frecuencia de 42 % de complicaciones post quirúrgicas utilizando el programa estadístico EPIINFO 7 para un IC de 95% a precisión de 5%, el tamaño mínimo a incluir debía ser de 143 pacientes. Resultados: Se analizaron 203 historias clínicas de pacientes con diagnóstico de cáncer de mama que fueron sometidas a cirugía como parte del tratamiento, correspondientes al periodo comprendido entre enero de 2018 a agosto de 2022. Cumplieron con los criterios de inclusión 201 pacientes. Se registraron un total de 92 pacientes que presentaron alguna complicación relacionada a la cirugía, que corresponden 46 % del total de pacientes en el periodo de tiempo estudiado. De las complicaciones encontradas, 40 desarrollaron seromas, representando el 43% del total de pacientes con complicaciones; 18 pacientes tuvieron infección de la herida operatoria, representando el 20%. 7 pacientes presentaron dehiscencia de la herida operatoria, siendo el 7,5% del total; y 5 desarrollaron un hematoma, siendo el 5,3%. Entre otras complicaciones encontradas, 4 pacientes presentaron linfedema (4,3%), 4 dolor crónico (4,3%), 3 extrusión de prótesis mamaria (3,2 %), 2 de celulitis del miembro superior afecto (2,1%), 2 presentaron necrosis del complejo areola-pezón (2,1%), 1 sufrimiento de piel sin necrosis, 1 sufrimiento del complejo areola-pezón sin necrosis (1% ambos), 1 presentó fistula (1%), 1 disfunción del miembro superior homolateral (1%), y una contractura capsular (1%). Discusión: Se registraron 92 pacientes con una complicación post quirúrgica luego de una cirugía por cáncer de mama; representa así el 46% del total de pacientes estudiados. Esta prevalencia se corresponde con lo publicado en la literatura. En cuanto a las complicaciones encontradas, la más frecuente en nuestra revisión fue el seroma, que se presentó en un 40% de las complicaciones. Las publicaciones describen a esta como una de las complicaciones más frecuentemente relacionadas a la cirugía mamaria, con frecuencias que varían desde 18 al 86% según diversos autores. Conclusión: De 201 pacientes que cumplieron con los criterios de inclusión y exclusión, se registraron un total de 92 pacientes que presentaron alguna complicación relacionada a la cirugía, que corresponden 46 % del total de pacientes en el periodo de tiempo estudiado. La complicación más frecuente fue el seroma. Todos los hallazgos de este estudio se correlacionan con lo encontrado en la literatura.

Introduction: Every year in Latin America, more than 200,000 women are diagnosed with breast cancer. As part of the treatment of this disease, surgery is one of the fundamental pillars. The surgical act is an extreme experience for the patient and the surgeon, necessary in this pathology for complete treatment and, like any medical act, it is not exempt from complications. In Paraguay there are no statistics on the prevalence of complications due to surgeries for breast cancer, so the main objective of this work is to establish said frequency in a hospital of fourth level of complexity. Materials and methods: retrospective, observational, cross-sectional study. non-probabilistic sampling of consecutive cases. The selection of study subjects was made from the population of patients who underwent surgery for breast cancer, at the Hospital de Clínicas in the period January 2018 to August 2022, and who met the inclusion and exclusion criteria. All the variables have been extracted from the clinical record and were documented in the data recording form. A frequency of 42% of post-surgical complications was expected using the statistical program EPIINFO 7 for a CI of 95% with a precision of 5%, the minimum size to include had to be 143 patients. Results: 203 medical records of patients diagnosed with breast cancer who underwent surgery as part of the treatment, corresponding to the period from January 2018 to August 2022, were analyzed. 201 patients met the inclusion criteria. A total of 92 patients who presented some complication related to surgery were registered, corresponding to 46% of the total number of patients in the period of time studied. Of the complications found, 40 developed seromas, representing 43% of all patients with complications; 18 patients had surgical wound infection, representing 20%. 7 patients presented dehiscence of the surgical wound, being 7.5% of the total; and 5 developed a hematoma, being 5.3%. Among other complications found, 4 patients presented lymphedema (4.3%), 4 chronic pain (4.3%), 3 extrusion of breast prosthesis (3.2%), 2 cellulitis of the affected upper limb (2.1%), 2 presented necrosis of the nipple-areola complex (2.1%), 1 suffering from skin without necrosis, 1 suffering from the nipple-areola complex without necrosis (1% both), 1 presented fistula (1%), 1 homolateral upper limb dysfunction (1%), and capsular contracture (1%). Discussion: 92 patients with a post-surgical complication after surgery for breast cancer were registered; thus represents 46% of all patients studied. This prevalence corresponds to what has been published in the literature. Regarding the complications found, the most frequent in our review was seroma, which occurred in 40% of the complications. The publications describe this as one of the complications most frequently related to breast surgery, with frequencies ranging from 18 to 86% according to various authors. Conclusion: Of 201 patients who met the inclusion and exclusion criteria, a total of 92 patients who presented some complication related to surgery were registered, corresponding to 46% of the total number of patients in the period of time studied. The most frequent complication was seroma. All the findings of this study correlate with what is found in the literature.

Mastitis linfocítica en la mujer joven. La importancia del diagnóstico histológico. Reporte de caso / Lymphocytic mastitis in young women. The importance of histological diagnosis. Case report

La mastitis linfocítica o mastitis diabética es una patología benigna rara, caracterizada por una inflamación fibrótica de la mama, causando gran preocupación por la simulación de un carcinoma. Está asociada por lo general a la diabetes tipo 2, aunque pueden presentarse en otras patologías autoinmunes y además en pacientes sin comorbilidades. Se presenta en caso clínico de una paciente joven sin comorbilidades que consulto en consultorio de patología mamaria por tumor mamario. Se realizó una biopsia percutánea por trucut con confirmación histológica de mastitis linfocítica, se realizó control cercano observándose remisión clínica e imagenológica de la lesión en 6 meses de seguimiento. Se presenta el caso a fin de recalcar la importancia del diagnóstico histológico percutáneo de la lesión para determinar la naturaliza de la misma, constatándose una patología benigna que no requiere resección, evitando así causar deformidades que podrían afectar psicológicamente a la paciente.

Lymphocytic mastitis or diabetic mastitis is a rare benign pathology, characterized by fibrotic inflammation of the breast, causing great concern due to the simulation of carcinoma. It is generally associated with type 2 diabetes, although it can occur in other autoimmune pathologies and also in patients without comorbidities. The clinical case of a young patient without comorbidities who consulted in the breast pathology clinic due to a breast tumor. A percutaneous trucut biopsy was performed with histological confirmation of lymphocytic mastitis, close control was performed, observing clinical and imaging remission of the lesion in 6 months of follow-up. The case is presented in order to emphasize the importance of percutaneous histological diagnosis of the lesion, to determine its nature, confirming a benign pathology that does not require resection, thus avoiding causing deformities that could psychologically affect the patient.

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

Efficient generation of human cerebral organoids directly from adherent cultures of pluripotent stem cells.

Human cerebral organoids (hCOs) offer the possibility of deepening the knowledge of human brain development, as well as the pathologies that affect it. The method developed here describes the efficient generation of hCOs by going directly from two-dimensional (2D) pluripotent stem cell (PSC) cultures to three-dimensional (3D) neuroepithelial tissue, avoiding dissociation and aggregation steps. This has been achieved by subjecting 2D cultures, from the beginning of the neural induction step, to dual-SMAD inhibition in combination with CHIR99021. This is a simple and reproducible protocol in which the hCOs generated develop properly presenting proliferative ventricular zones (VZs) formed by neural precursor and radial glia (RG) that differentiate to give rise to mature neurons and glial cells. The hCOs present additional cell types such as oligodendrocyte precursors, astrocytes, microglia-like cells, and endothelial-like cells. This new approach could help to overcome some of the existing limitations in the field of organoid biotechnology, facilitating its execution in any laboratory setting.

Dorsal motor vagal neurons can elicit bradycardia and reduce anxiety-like behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMV anatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNA and CVNDMV through the vagus nerve. Using whole-cell patch-clamp, CVNDMV demonstrated greater hyperexcitability and spontaneous action potential firing ex vivo despite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs and is capable of cardioinhibition and robust anxiolysis.

Human Trypanosoma cruzi infection in the Argentinean Chaco: risk factors and identification of households with infected children for treatment.

BACKGROUND: Chagas disease is a neglected tropical disease (NTD). Cost-effective strategies for large-scale implementation of diagnosis and etiological treatment are urgently needed to comply with NTD control goals. We determined the seroprevalence of Trypanosoma cruzi infection and associated risk factors in a well-defined rural population of Pampa del Indio municipality including creole and indigenous (Qom) households and developed two indices to identify houses harboring infected children. METHODS: We serodiagnosed and administered a questionnaire to 1337 residents (48.2% of the listed population) in two sections of the municipality (named Areas II and IV) 6-9 years after deploying sustained vector control interventions. Multiple logistic regression models were used to evaluate the relationship between human infection and a priori selected predictors. Two risk indices were constructed based on environmental and serostatus variables, and we used spatial analysis to test whether households harboring T. cruzi-seropositive children were randomly distributed. RESULTS: The global seroprevalence of T. cruzi infection was 24.8%. Human infection was positively and significantly associated with exposure time to triatomines, the household number of seropositive co-inhabitants, maternal seropositivity for T. cruzi, recent residence at the current house and the presence of suitable walls for triatomine colonization in the domicile. The pre-intervention mean annual force of infection (FOI) was 1.23 per 100 person-years. Creoles from Area IV exhibited the highest seroprevalence and FOI; Qom people from both areas displayed intermediate ones and creoles from Area II the lowest. Three hotspots of infected children were spatially associated with hotspots of triatomine abundance at baseline and persistent house infestation. No child born after vector control interventions was T. cruzi seropositive except for one putative transplacental case. Two simple risk indices (based on self-reported inhabiting an infested house and suitable walls for triatomines or maternal serostatus) identified 97.3-98.6% of the households with at least one T. cruzi-seropositive child. CONCLUSIONS: We showed strong heterogeneity in the seroprevalence of T. cruzi infection within and between ethnic groups inhabiting neighboring rural areas. Developed indices can be used for household risk stratification and to improve access of rural residents to serodiagnosis and treatment and may be easily transferred to primary healthcare personnel.

Correlates of Toddlers' Physical Activity Levels and Sedentary Behavior During Unstructured Outdoor Play in Early Childhood Education and Daycare Settings.

Despite recent research showing that early childhood education and daycare settings (ECEC) have an important role in promoting toddlers' physical activity (PA), crucial information gaps remain regarding toddlers' PA and sedentary behavior (SB) in these outdoor settings. We aimed in this study to: (a) analyze PA patterns and SB during unstructured outdoor play time in preschool and daycare environments using accelerometry and systematic observation; (b) provide concurrent accelerometry and observational data to help validate the Observational System for Recording Physical Activity in Children-Preschool Version (OSRAC-P); and (c) examine individual, social and environmental correlates of PA and SB during toddlers' unstructured outdoor play time. We found that: (a) toddlers displayed high amounts of PA with no sex, BMI, and/or age differences in PA and SB levels,; (b) environmental variables (e.g., fixed equipment and playground density) were not associated with PA levels or SB intensity; (c) the OSRAC-P was a reliable and valid means of observing and analyzing toddlers' PA patterns during unstructured outdoor play time; and (e) different social patterns between boys and girls did not impact PA levels or patterns. Combining different measurement methods permitted an improved understanding of unstructured outdoor play in preschool and daycare settings.

A newly identified ferritin L-subunit variant results in increased proteasomal subunit degradation, impaired complex assembly, and severe hypoferritinemia.

Ferritin is a hetero-oligomeric nanocage, composed of 24 subunits of two types, FTH1 and FTL. It protects the cell from excess reactive iron, by storing iron in its cavity. FTH1 is essential for the recruitment of iron into the ferritin nanocage and for cellular ferritin trafficking, whereas FTL contributes to nanocage stability and iron nucleation inside the cavity. Here we describe a female patient with a medical history of severe hypoferritinemia without anemia. Following inadequate heavy IV iron supplementation, the patient developed severe iron overload and musculoskeletal manifestations. However, her serum ferritin levels rose only to normal range. Genetic analyses revealed an undescribed homozygous variant of FTL (c.92A > G), which resulted in a Tyr31Cys substitution (FTLY31C ). Analysis of the FTL structure predicted that the Y31C mutation will reduce the variant's stability. Expression of the FTLY31C variant resulted in significantly lower cellular ferritin levels compared with the expression of wild-type FTL (FTLWT ). Proteasomal inhibition significantly increased the initial levels of FTLY31C , but could not protect FTLY31C subunits from successive degradation. Further, variant subunits successfully incorporated into hetero-polymeric nanocages in the presence of sufficient levels of FTH1. However, FTLY31C subunits poorly assembled into nanocages when FTH1 subunit levels were low. These results indicate an increased susceptibility of unassembled monomeric FTLY31C subunits to proteasomal degradation. The decreased cellular assembly of FTLY31C -rich nanocages may explain the low serum ferritin levels in this patient and emphasize the importance of a broader diagnostic approach of hypoferritinemia without anemia, before IV iron supplementation.

Cut-off points of neck and waist circumference as predictors of obstructive sleep apnea in the Colombian population: a comparison with polysomnography

ABSTRACT BACKGROUND: Neck circumference (NC) is a useful anthropometric measure for predicting obstructive sleep apnea (OSA). Ethnicity and sex also influence obesity phenotypes. NC cut-offs for defining OSA have not been established for the Latin American population. OBJECTIVES: To evaluate NC, waist circumference (WC), and body mass index (BMI) as predictors of OSA in the Colombian population and to determine optimal cut-off points. DESIGN AND SETTING: Diagnostic tests were conducted at the Javeriana University, Bogota. METHODS: Adults from three cities in Colombia were included. NC, WC, and BMI were measured, and a polysomnogram provided the reference standard. The discrimination capacity and best cut-off points for diagnosing OSA were calculated. RESULTS: 964 patients were included (57.7% men; median age, 58 years) and 43.4% had OSA. The discrimination capacity of NC was similar for men and women (area under curve, AUC 0.63 versus 0.66, P = 0.39) but better for women under 60 years old (AUC 0.69 versus 0.57, P < 0.05). WC had better discrimination capacity for women (AUC 0.69 versus 0.57, P < 0.001). There were no significant differences in BMI. Optimal NC cut-off points were 36.5 cm for women (sensitivity [S]: 71.7%, specificity [E]: 55.3%) and 41 cm for men (S: 56%, E: 62%); and for WC, 97 cm for women (S: 65%, E: 69%) and 99 cm for men (S: 53%, E: 58%). CONCLUSIONS: NC and WC have moderate discrimination capacities for diagnosing OSA. The cut-off values suggest differences between Latin- and North American as well as Asian populations.