Home Ultrasound: A Contemporary and Valuable Tool for Palliative Medicine.

This narrative review explores the application of point-of-care ultrasound (POCUS) in palliative care and its feasibility in home care settings. POCUS has the potential to streamline diagnostic strategies without patient transfer to the hospital, expedite timely symptomatic relief, and reduce complications from specific palliative interventions. The advent of handheld ultrasound devices has made it an attractive diagnostic and interventional adjunct in acute palliative care. POCUS has gained widespread acceptance as part of routine care in emergency medicine and intensive care, guiding certain procedures and increasing their safety. The modernization and miniaturization of ultrasound equipment have made ultra-portable devices available, allowing for better-quality images at affordable prices. Handheld devices have the potential to revolutionize everyday clinical practice in home-based palliative care, contributing to important bedside clinical decisions. Palliative care patients often require diagnostic examinations in the last months of their lives, with CT being the most frequently performed imaging procedure. However, CT imaging is associated with high costs and burdens, leading to increased suffering and impaired quality of life. Clinical ultrasound, a dialogic imaging modality, offers a safer and more efficient approach to palliative care. POCUS applications, which are cost-effective, non-invasive, and well-tolerated, can be used to improve patient satisfaction and diagnostic understanding. POCUS is a valuable tool in palliative care, improving diagnostic accuracy and reducing the time to diagnosis for various pathologies. It is a standard of care for many procedures and improves patient safety. However, there are limitations to POCUS in palliative care, such as operator-dependent examination variability and limited availability of trained professionals. To overcome these limitations, palliative care physicians should receive mandatory training in POCUS, which can be incorporated into the core curriculum. Additionally, ultrasound teleconsulting can assist less experienced examiners in real-time examinations. The literature on POCUS in palliative care is limited, but research on patient-oriented outcomes is crucial. POCUS should be considered a supplement to good clinical reasoning and regulated radiological evaluations.

A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

The prognostic value of early measures of the ventilatory ratio in the ARDS ROSE trial.

BACKGROUND: The ventilatory ratio (VR, [minute ventilation × PaCO2]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality. METHODS: This was a post hoc analysis of the PETAL-ROSE trial, which randomized moderate-to-severe ARDS patients to NMB or control. Survival among patients with different VR trajectories or VR cutoff above and below the median was assessed by Kaplan-Meier analysis. The relationships between single-day or 48-h VR trajectories with 28- or 90-day mortality were tested by logistic regression. Randomization allocation to NMB and markers of disease severity were tested as confounders by multivariable regression and interaction term analyses. RESULTS: Patients with worsening VR trajectories had significantly lower survival compared to those with improving VR (n = 602, p < 0.05). Patients with VR > 2 (median) at day 1 had a significantly lower 90-day survival compared to patients with VR ≤ 2 (HR 1.36, 95% CI 1.10-1.69). VR at day 1 was significantly associated with 28-day mortality (OR = 1.40, 95% CI 1.15-1.72). There was no interaction between NMB and VR for 28-day mortality. APACHE-III had a significant interaction with VR at baseline for the outcome of 28-day mortality, such that the relationship between VR and mortality was stronger among patients with lower APACHE-III. There was a significant association between rising VR trajectory and mortality that was independent of NMB, baseline PaO2/FiO2 ratio and generalized markers of disease severity (Adjusted OR 1.81, 95% CI 1.28-2.84 for 28-day and OR 2.07 95% CI 1.41-3.10 for 90-day mortality). APACHE-III and NMB were not effect modifiers in the relationship between VR trajectory and mortality. CONCLUSIONS: Elevated baseline and day 1 VR were associated with higher 28-day mortality. The relationship between baseline VR and mortality was stronger among patients with lower APACHE-III. APACHE-III was not an effect modifier for the relationship between VR trajectory and mortality, so that the VR trajectory may be optimally suited for prognostication and predictive enrichment. VR was not different between patients randomized to NMB or control, indicating that VR can be utilized without correcting for NMB.

Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition.

Organ-on-a-chip in vitro platforms accurately mimic complex microenvironments offering the ability to recapitulate and dissect mechanisms of physiological and pathological settings, revealing their major importance to develop new therapeutic targets. Bone diseases, such as osteoarthritis, are extremely complex, comprising of the action of inflammatory mediators leading to unbalanced bone homeostasis and de-regulation of sensory innervation and angiogenesis. Although there are models to mimic bone vascularization or innervation, in vitro platforms merging the complexity of bone, vasculature, innervation, and inflammation are missing. Therefore, in this study a microfluidic-based neuro-vascularized bone chip (NVB chip) is proposed to 1) model the mechanistic interactions between innervation and angiogenesis in the inflammatory bone niche, and 2) explore, as a screening tool, novel strategies targeting inflammatory diseases, using a nano-based drug delivery system. It is possible to set the design of the platform and achieve the optimized conditions to address the neurovascular network under inflammation. Moreover, this system is validated by delivering anti-inflammatory drug-loaded nanoparticles to counteract the neuronal growth associated with pain perception. This reliable in vitro tool will allow understanding the bone neurovascular system, enlightening novel mechanisms behind the inflammatory bone diseases, bone destruction, and pain opening new avenues for new therapies discovery.

Thrombomodulin is associated with increased mortality and organ failure in mechanically ventilated children with acute respiratory failure: biomarker analysis from a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome and death. Biomarkers may allow for risk stratification and prognostic enrichment in ARF. Thrombomodulin (TM) is a transmembrane antithrombotic mediator expressed in endothelial cells. It is cleaved into its soluble form (sTM) during inflammation and vascular injury. Levels of sTM correlate with inflammation and end organ dysfunction. METHODS: This was a prospective observational study of 432 patients aged 2 weeks-17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-h intervals within 5 days after intubation. sTM was assayed by ELISA. The Hazard ratio (HR) for 90-day mortality was determined by Cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses. RESULTS: sTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (n = 432, adjusted HR = 1.003, p = 0.02) and worse OI in the first 5 days after intubation (n = 252, Estimate = 0.02, p < 0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate = 0.003, p < 0.0001; and slope, Estimate = 0.01, p = 0.0009, n = 386). CONCLUSIONS: Plasma sTM is associated with mortality, severity of hypoxic respiratory failure and worsening extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in the pathogenesis of ARF and provides potential applicability towards targeted therapies. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00814099 . In healthy lung endothelium, thrombomodulin (TM) recruits thrombin to activate Protein-C (PC/APC), that inhibits plasminogen activator-1 (PAI-1) and thrombosis. In inflamed and damaged endothelium, TM is cleaved into its soluble form (sTM), precluding its usual regulation of thrombosis. In this study, we measured plasma sTM levels in pediatric patients with respiratory failure and found that sTM correlated with mortality and other clinical markers of poor outcomes.

miR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patients.

Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53.

CD8+ T cells from experimental in situ breast carcinoma interfere with bone homeostasis.

Before bone colonization, immune cells primed by breast primary tumor cells actively modify the bone microenvironment, disturbing the complex and tightly homeostatic signaling network regulated by osteoblasts and osteoclasts. Indeed, we have shown that RANKL+ CD4+ T cells specific for the 4T1 mammary carcinoma cell line, arrive at the bone marrow (BM) before metastatic cells and set the pre-metastatic niche. In the absence of RANKL expressed by T cells, there is no pre-metastatic osteolytic disease and bone metastases are blocked. Adding to the role of T cells, we have recently demonstrated that dendritic cells (DCs) provide a positive feedback loop to the osteolytic profile induced by the metastatic tumor. In this setting, DCs are able to differentiate into potent bone resorbing osteoclast-like cells keeping their antigen-presenting cell (APC) properties to maintain RANKL+ CD4+ Th17 T cells activities, via IL-23 expression. Here we show that 67NR non-metastatic tumor cells, a sibling of 4T1 tumor cell line, induce an increase in trabecular bone mass on day 11 post-tumor implant. This observation was associated with an expansion of the osteoblastic lineage cells accompanied by a reduction of osteoclasts numbers. Moreover, BM derived CD8+ T cells from 67NR tumor-bearing mice, express an anti-osteoclastogenic cytokine milieu enriched by IFN-γ, IL-10 and producing low levels of RANKL. The frequency of BM derived CD8+ FoxP3+ regulatory T cells, known as potent suppressors of osteoclastogenesis both in vitro and in vivo, was also increased in such animals. This milieu was capable to suppress 4T1 tumor-specific CD4+ T cells phenotype in vivo and in vitro and strongly inhibited bone metastases establishment, restoring trabecular bone mass volume. We concluded that the 67NR+ tumor derived CD8+ T cells phenotypes, either contributing to bone homeostasis and/or control of 4T1 breast tumor pre-metastatic disease, interfere with osteoclasts and osteoblasts activities inside BM. Our study highlights the opposing roles of subverted tumor CD4+ and CD8+ T cell subtypes in directing breast cancer progression and bone metastases establishment. For non-metastatic tumors, the role of T cells regarding bone remodeling has never been addressed before. As far as we know, this is the first description that an in situ carcinoma can modify distant sites. In the case showed here, modification of the distant bone site disfavors pre-metastatic bone niche formation.

Dendritic cells development into osteoclast-type APCs by 4T1 breast tumor T cells milieu boost bone consumption.

Bone metastases occur in 70% of patients with advanced breast cancer, causing severe morbidity and increased mortality due to osteolytic lesions driven by osteoclasts (OCs) inside the bone marrow (BM) microenvironment. A reciprocal vicious cycle between bone remodeling system and the tumor itself is established by the release of growth factors stored in the mineralized matrix, which in turn feed the tumor, changing tumor behavior and growth. However, BM is not a passive host microenvironment for circulating tumor cells, but instead can be actively modified by the primary tumor before metastatic spread occurs. Indeed, we have shown that T cells specific for the 4T1 mammary carcinoma cell line, are characteristically RANKL+ IL-17F+ CD4+ T cells. Those cells arrive in the BM before metastatic cells and set the pre-metastatic niche. In the absence of T cell derived RANKL, there is no pre-metastatic osteolytic disease and bone metastases do not take place. Recently, dendritic cells (DCs), the main T cell partner at the beginning of the immune response, came into the spotlight as a potential source of OCs progenitors under inflammatory conditions. Regarding bone metastasis, nothing is currently known about DCs plasticity or even its partnership with tumor induced T cells for BM pre-metastatic niche formation. Here, we show that splenic CD11c+ DCs stimulated with 4T1 conditioned media (CM) efficiently differentiated into mature and activated multinucleated giant cells (DC-OC) expressing TRAP and IL-23 cytokine. More important, 4T1 CM derived DC-OCs build a positive loop which amplifies the osteolytic phenomena by maintaining the RANKL+ Th17 T cells and by its own osteoclastic activity. In conclusion, our results indicate that differentiation of OCs from DCs may be achievable in the bone pre osteolytic disease context representing an alternative OC differentiation pathway. Besides being induced by high levels of T cells pro osteoclastogenic cytokines, especially by RANKL, DC-OC keep a positive feedback loop towards osteolysis, maintaining the pro-osteoclastogenic T cell phenotype in the BM.

Caracterização dos episódios de queda em uma unidade de cardiologia: estudo retrospectivo / Caracterización de episodios de caídas en una unidad de cardiogolía: estudio restrospectivo / Characterization of falls in a cardiology unit: a retrospective study

Objetivo: Caracterizar os episódios de queda em pacientes internados em uma unidade cardiológica, quanto à ocorrência, fatores relacionados e risco. Método: Estudo descritivo, retrospectivo, por meio da análise de prontuários de pacientes internados em uma unidade de cardiologia que apresentaram episódio de queda entre janeiro de 2015 a dezembro 2016. O risco médio para quedas foi avaliado, conforme a Escala de Morse. Resultados: No período de estudo houve 32 episódios de quedas. A queda foi mais frequente em idosos (81,3%) e naqueles que faziam uso crônico de medicamentos , para controle e tratamento de comorbidades preexistentes. Dentre os fatores de risco, 34,4% apresentavam delirium, comprometimento neurológico e déficit de locomoção. O risco médio para quedas foi classificado como elevado (> 45), 25% das quedas resultaram em algum tipo de dano (leve ou moderado) e ocorreram em períodos matutinos. Conclusão: As contribuições fornecidas pelos registros de eventos adversos, deste estudo, facilitaram a identificação dos fatores de risco, demonstrando a necessidade de se propor intervenções de enfermagem preventivas, uma vez que assumir o evento e identificar suas causas são maneiras de praticar uma assistência de enfermagem segura ao paciente(AU)

Objective: To characterize the episodes of falls in patients hospitalized in a cardiology unit, regarding occurrence, related factors and risk. Method: This is a descriptive, retrospective study, analyzing medical records of patients admitted to a cardiology unit who experienced a fall episode between January 2015 and December 2016. The average risk for falls was assessed according to the Morse Scale. Results: During the study period, there were 32 episodes of falls. Falls were more frequent in the elderly people (81.3%) and in those people who used chronic drugs to control and treat pre-existing comorbidities. Among the risk factors, 34.4% had delirium, neurological impairment and impaired mobility. The average risk for falls was classified as high (> 45), 25% of the falls resulted in some type of damage (mild or moderate) and occurred in the morning. Conclusion: The contributions provided by the records of adverse events in this study facilitated the identification of risk factors, demonstrating the need to propose preventive nursing interventions, since assuming the event and identifying its causes are ways to practice safe nursing care to the patient(AU)

Objetivo: Caracterizar los episodios de caídas en pacientes hospitalizados en una unidad de cardiología, en cuanto a ocurrencias, factores relacionados y riesgo. Método: Estudio descriptivo, retrospectivo, mediante el análisis de las historias clínicas de los pacientes ingresados en una unidad de cardiología que experimentaron un episodio de caída entre enero de 2015 y diciembre de 2016. El riesgo promedio de caídas se evaluó según la escala de Morse. Resultados: Durante el período de estudio hubo 32 episodios de caídas. La caída fue más frecuente en los ancianos (81,3%) y en los que usaban fármacos crónicos para controlar y tratar las comorbilidades preexistentes. Entre los factores de riesgo, el 34,4% presentaba delirio, deterioro neurológico y movilidad reducida. El riesgo promedio de caídas se clasificó como alto (> 45), el 25% de las caídas resultaron en algún tipo de daño (leve o moderado) y ocurrieron en la mañana. Conclusión: Los aportes que brindan los registros de eventos adversos en este estudio facilitaron la identificación de factores de riesgo, demostrando la necesidad de proponer intervenciones de enfermería preventivas, y a que asumir el evento e identificar sus causas son formas de practicar al paciente cuidados de enfermería seguros(AU)

Epigenetic Regulation of p21cip1/waf1 in Human Cancer.

p21cip1/waf1 is a central regulator of cell cycle control and survival. While mutations are rare, it is commonly dysregulated in several human cancers due to epigenetic mechanisms influencing its transcriptional control. These mechanisms include promoter hypermethylation as well as additional pathways such as histone acetylation or methylation. The epigenetic regulators include writers, such as DNA methyltransferases (DNMTs); histone acetyltransferases (HATs) and histone lysine methyltransferases; erasers, such as histone deacetylases (HDACs); histone lysine demethylases [e.g., the Lysine Demethylase (KDM) family]; DNA hydroxylases; readers, such as the methyl-CpG-binding proteins (MBPs); and bromodomain-containing proteins, including the bromo- and extraterminal domain (BET) family. We further discuss the roles that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play in the epigenetic control of p21cip1/waf1 expression and its function in human cancers.

Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma.

The high mortality rate of melanoma is broadly associated with its metastatic potential. Tumor cell dissemination is strictly dependent on vascularization; therefore, angiogenesis and lymphangiogenesis play an essential role in metastasis. Hence, a better understanding of the players of tumor vascularization and establishing them as new molecular biomarkers might help to overcome the poor prognosis of melanoma patients. Here, we further characterized a linear murine model of melanoma progression and showed that the aggressiveness of melanoma cells is closely associated with high expression of angiogenic factors, such as Vegfc, Angpt2, and Six1, and that blockade of the vascular endothelial growth factor pathway by the inhibitor axitinib abrogates their tumorigenic potential in vitro and in the in vivo chicken chorioallantoic membrane assay. Furthermore, analysis of The Cancer Genome Atlas data revealed that the expression of the angiogenic factor ANGPT2 (P-value = 0.044) and the lymphangiogenic receptor VEGFR-3 (P-value = 0.002) were independent prognostic factors of overall survival in melanoma patients. Enhanced reduced representation bisulfite sequencing-based methylome profiling revealed for the first time a link between abnormal VEGFC, ANGPT2, and SIX1 gene expression and promoter hypomethylation in melanoma cells. In patients, VEGFC (P-value = 0.031), ANGPT2 (P-value < 0.001), and SIX1 (P-value = 0.009) promoter hypomethylation were independent prognostic factors of shorter overall survival. Hence, our data suggest that these angio- and lymphangiogenesis factors are potential biomarkers of melanoma prognosis. Moreover, these findings strongly support the applicability of our melanoma progression model to unravel new biomarkers for this aggressive human disease.

Intestinal parasitism and related risk factors for primary school students in João Pessoa, northeast Brazil / Parasitismo intestinal e fatores de risco relacionados entre os escolares do ensino fundamental I e II na cidade de João Pessoa, no nordeste do Brasil

The goal of the present study was to determine both prevalence and risk factors associated with intestinal parasitism in school students. A cross-sectional study was conducted in a single primary school located in João Pessoa, from February to August in 2016. The students were selected from the age group of 5-16 years. Of the school total of 341 students, 150 fecal specimens (from participants) were collected and were evaluated by three methods: Hoffman, Pons, and Janer (HPJ); Rugai; and the Paratest® Kit. A questionnaire concerning socio-demographic, environmental and behavioral variables was also applied. A logistic regression model was used to explain the occurrence of intestinal parasitism and the associated risk factors. The prevalence was 38.7% of students, with positive samples being more prevalent in the male students (47.0%). The most common parasite was Giardia lamblia 13 (14.8%), followed by Entamoeba histolytica/dispar 8 (9%), Enterobius vermicularis 5 (5.7%), Strongyloides stercolaris 2 (2.3%), Ascaris lumbricoides 2 (2.3%) and Trichuris trichiura 2 (2.3%). Among the enterocommensals, the most frequent was Endolimax nana 36 (40.9%) followed by Entamoeba coli 20 (22.7%). The variables that presented statistical significance (pvalue< 0.05) ) together with the Odds Ratio (OR) were: gender (female) (OR=2.4; 95% CI, 0.19-0.98), family allowance participant (yes) (OR=4.4; 95% CI, 1.84-10.66), number of rooms in the residence (OR=3.5; 95% CI, 1.13-10.64), family nucleus (OR=7.0; 95% CI, 1.46-12.43), fruit and vegeTable hygiene (OR=2.0; 95% CI, 1.23-3.36), use of anthelmintic (OR= 0.02; 95% CI, 0.001-0.30) and detection of worms (OR=25.0; 95% CI, 20.6-30.10). Diseases caused by protozoa were more prevalent. The analyzed risk factors demonstrate that disease transmission happens through differing routes. Thus, appropriate health intervention strategies should be implemented to reduce the burden of intestinal parasites for school students and their families.

O presente estudo tem como objetivo determinar a prevalência e os fatores de risco associados ao parasitismo intestinal em escolares. Este estudo transversal foi conduzido em uma escola primária localizada na cidade de João Pessoa, de fevereiro a agosto de 2016. As crianças foram selecionadas entre 5 a 16 anos de idade. De 341 alunos, foram coletados 150 espécimes fecais e foram avaliados por três métodos: Método de Hoffman, Pons e Janer (HPJ); Kit Rugai e Paratest®. Foi preenchido um questionário sobre dados de variáveis sociodemográficas, ambientais e de comportamento. O modelo de regressão logística foi utilizado para explicar a ocorrência de parasitismo intestinal e os fatores de risco associados. A prevalência foi de 38,7% das crianças, sendo a amostra positiva mais predominante nas crianças do sexo masculino (47,0%). O parasita mais comum foi Giardia lamblia 13 (14,8%), seguido de Entamoeba histolytica / dispar 8 (9%), Enterobius vermicularis 5 (5,7%), Strongyloides stercolaris 2 (2,3%), Ascaris lumbricoides 2 (2,3%) e Trichuris Trichiura 2 (2,3%). Entre os enterocomensais, a maioria das freqüências foi Endolimax nana 36 (40,9%) seguido de Entamoeba coli 20 (22,7%). As variáveis que apresentaram significância estatística (p-valor <0,05) foram: gênero (feminino) (OR = 2,4; IC 95%; 0,19-0,98), recebe subsídio familiar (sim) (OR = 4,4; 95% CI, 1,84-10,66), número de quartos na residência (OR = 3,5; IC 95%, 1,13-10,64), núcleo familiar (OR = 7,0; IC 95%; 1,46- 12,43), higiene das frutas e legumes (OR = 2,0, IC 95%, 1,23-3,36), uso de vermifugio (OR = 0,02, IC 95%, 0,001-0,30) e visualização de vermes (OR = 25,0; IC 95%, 20,6-30,10). As doenças causadas por protozoários foram mais prevalentes. Os fatores de risco analisados demonstram que a transmissão de doenças ocorre por rotas diferentes. Portanto, as estratégias de intervenção em saúde devem ser implementadas para as crianças da escola e suas famílias para reduzir o peso dos parasitas intestinais.

High prevalence of iodine deficiency in pregnant women living in adequate iodine area.

OBJECTIVES: Iodine deficiency during pregnancy is associated with obstetric and neonatal adverse outcomes. Serum thyroglobulin (sTg) and thyroid volume (TV) are optional tools to urinary iodine concentration (UIC) for defining iodine status. This cross-sectional study aims to evaluate the iodine status of pregnant women living in iodine-adequate area by spot UIC and correlation with sTg, TV and thyroid function. METHODS: Two hundred and seventy-three pregnant women were evaluated at three trimesters. All had no previous thyroid disease, no iodine supplementation and negative thyroperoxidase and thyroglobulin antibodies. Thyroid function and sTg were measured using electrochemiluminescence immunoassays. TV was determined by ultrasonography; UIC was determined using a modified Sandell-Kolthoff method. RESULTS: Median UIC was 146 µg/L, being 52% iodine deficient and only 4% excessive. TSH values were 1.50 ± 0.92, 1.50 ± 0.92 and 1.91 ± 0.96 mIU/L, respectively, in each trimester (P = 0.001). sTg did not change significantly during trimesters with median 11.2 ng/mL and only 3.3% had above 40 ng/mL. Mean TV was 9.3 ± 3.4 mL, which positively correlated with body mass index, but not with sTg. Only 4.5% presented with goitre.When pregnant women were categorized as iodine deficient (UIC < 150 µg/L), adequate (≥150 and <250 µg/L) and excessive (≥250 µg/L), sTg, thyroid hormones and TV at each trimester showed no statistical differences. CONCLUSIONS: Iodine deficiency was detected frequently in pregnant women living in iodine-adequate area. sTg concentration and TV did not correlate to UIC. Our observation also demonstrated that the Brazilian salt-iodization programme prevents deficiency, but does not maintain iodine status within adequate and recommended ranges for pregnant women.

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

INTRODUCTION: Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. METHODS: Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). RESULTS: Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. CONCLUSION: Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families.

Efficient method for comprehensive computation of agent-level epidemic dissemination in networks.

Susceptible-infected (SI) and susceptible-infected-susceptible (SIS) are simple agent-based models often employed in epidemic studies. Both models describe the time evolution of infectious diseases in networks whose vertices are either susceptible (S) or infected (I) agents. Precise estimation for disease spreading is one of the major goals in epidemic studies but often restricted to heavy numerical simulations. Analytic methods using operatorial content are subject to the asymmetric eigenvalue problem, limiting the use of perturbative methods. Numerical methods are limited to small populations, since the vector space increases exponentially with population size N. Here, we propose the use of the squared norm of the probability vector to obtain an algebraic equation, which permits the evaluation of stationary states in Markov processes. The equation requires the eigenvalues of symmetrized time generators and takes full advantage of symmetries, reducing the time evolution to an O(N) sparse problem. The calculation of eigenvalues employs quantum many-body techniques, while the standard perturbation theory accounts for small modifications to the network topology.

Effects of cytoskeletal drugs on actin cortex elasticity.

Mechanical properties of cells are known to be influenced by the actin cytoskeleton. In this article, the action of drugs that interact with the actin cortex is investigated by tether extraction and rheology experiments using optical tweezers. The influences of Blebbistatin, Cytochalasin D and Jasplakinolide on the cell mechanical properties are evaluated. The results, in contradiction to current views for Jasplakinolide, show that all three drugs and treatments destabilize the actin cytoskeleton, decreasing the cell membrane tension. The cell membrane bending modulus increased when the actin cytoskeleton was disorganized by Cytochalasin D. This effect was not observed for Blebbistatin and Jasplakinolide. All drugs decreased by two-fold the cell viscoelastic moduli, but only Cytochalasin D was able to alter the actin network into a more fluid-like structure. The results can be interpreted as the interplay between the actin network and the distribution of myosins as actin cross-linkers in the cytoskeleton. This information may contribute to a better understanding of how the membrane and cytoskeleton are involved in cell mechanical properties, underlining the role that each one plays in these properties.

A T Cell View of the Bone Marrow.

The majority of T cells present in the bone marrow (BM) represent an activated/memory phenotype and most of these, if not all, are circulating T cells. Their lodging in the BM keeps them activated, turning the BM microenvironment into a "memory reservoir." This article will focus on how T cell activation in the BM results in both direct and indirect effects on the hematopoiesis. The hematopoietic stem cell niche will be presented, with its main components and organization, along with the role played by T lymphocytes in basal and pathologic conditions and their effect on the bone remodeling process. Also discussed herein will be how "normal" bone mass peak is achieved only in the presence of an intact adaptive immune system, with T and B cells playing critical roles in this process. Our main hypothesis is that the partnership between T cells and cells of the BM microenvironment orchestrates numerous processes regulating immunity, hematopoiesis, and bone remodeling.