Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the future.

Enzymatic Degradation Behavior of Self-Degradable Lipase-Embedded Aliphatic and Aromatic Polyesters and Their Blends.

Over the past decade, the preparation of novel materials by enzyme-embedding into biopolyesters has been proposed as a straightforward method to produce self-degrading polymers. This paper reports the preparation and enzymatic degradation of extruded self-degradable films of three different biopolyesters: poly(lactic acid) (PLA), poly(butylene adipate-co-terephthalate) (PBAT), and poly(butylene succinate) (PBS), as well as three binary/ternary blends. Candida antarctica lipase B (CalB) has been employed for the enzyme-embedding procedure, and to the best of our knowledge, the use of this approach in biopolyester blends has not been reported before. The three homopolymers exhibited differentiated degradation and suggested a preferential attack of CalB on PBS films over PBAT and PLA. Moreover, the self-degradable films obtained from the blends showed slow degradation, probably due to the higher content in PLA and PBAT. These observations pave the way for exploring enzymes capable of degrading all blend components or an enzymatic mixture for blend degradation.

Neonatal point-of-care lung ultrasound: what should be known and done out of the NICU?

Lung ultrasound is rapidly becoming a useful tool in the care of neonates: its ease of use, reproducibility, low cost, and negligible side effects make it a very suitable tool for the respiratory care of all neonates. This technique has been extensively studied by different approaches in neonatal intensive care unit (NICU), both for diagnostic and prognostic aims and to guide respiratory treatments. However, many neonates are being born in level I/II hospitals without NICU facilities so all pediatricians, not just neonatal intensivists, should be aware of its potential. This is made possible by the increasing access to ultrasound machines in a modern hospital setting. In this review, we describe the ultrasonographic characteristics of the normal neonatal lung. We also discuss the ultrasound features of main neonatal respiratory diseases: transient tachypnea of the neonate (TTN), respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), pneumothorax (PNX), pleural effusion (PE), or pneumonia. Finally, we mention two functional approaches to lung ultrasound: 1. The use of lung ultrasound in level I delivery centers as a mean to assess the severity of neonatal respiratory distress and request a transport to a higher degree structure in a timely fashion. 2. The prognostic accuracy of lung ultrasound for early and targeted surfactant replacement. CONCLUSION:  LU is still a useful tool in level I/II neonatal units, both for diagnostic and functional issues. WHAT IS KNOWN: • Neonatal lung ultrasound has been recently introduced in the usual care in many Neonatal Intensive Care Units. WHAT IS NEW: • It also has many advantages in level I/II neonatal units, both for neonatologist or even pediatricians that treat neonates in those sites.

Circadian modulation of microglial physiological processes and immune responses.

Microglia is considered the central nervous system (CNS) resident macrophages that establish an innate immune response against pathogens and toxins. However, the recent studies have shown that microglial gene and protein expression follows a circadian pattern; several immune activation markers and clock genes are expressed rhythmically without the need for an immune stimulus. Furthermore, microglia responds to an immune challenge with different magnitudes depending on the time of the day. This review examines the circadian control of microglia function and the possible physiological implications. For example, we discuss that synaptic prune is performed in the cortex at a certain moment of the day. We also consider the implications of daily microglial function for maintaining biological rhythms like general activity, body temperature, and food intake. We conclude that the developmental stage, brain region, and pathological state are not the only factors to consider for the evaluation of microglial functions; instead, emerging evidence indicates that circadian time as an essential aspect for a better understanding of the role of microglia in CNS physiology.

Evaluation of Epithelial-Mesenchymal Transition Markers in Autoimmune Thyroid Diseases.

A state of chronic inflammation is common in organs affected by autoimmune disorders, such as autoimmune thyroid diseases (AITD). Epithelial cells, such as thyroid follicular cells (TFCs), can experience a total or partial transition to a mesenchymal phenotype under these conditions. One of the major cytokines involved in this phenomenon is transforming growth factor beta (TGF-ß), which, at the initial stages of autoimmune disorders, plays an immunosuppressive role. However, at chronic stages, TGF- ß contributes to fibrosis and/or transition to mesenchymal phenotypes. The importance of primary cilia (PC) has grown in recent decades as they have been shown to play a key role in cell signaling and maintaining cell structure and function as mechanoreceptors. Deficiencies of PC can trigger epithelial-mesenchymal transition (EMT) and exacerbate autoimmune diseases. A set of EMT markers (E-cadherin, vimentin, α-SMA, and fibronectin) were evaluated in thyroid tissues from AITD patients and controls through RT-qPCR, immunohistochemistry (IHC), and western blot (WB). We established an in vitro TGF-ß-stimulation assay in a human thyroid cell line to assess EMT and PC disruption. EMT markers were evaluated in this model using RT-qPCR and WB, and PC was evaluated with a time-course immunofluorescence assay. We found an increased expression of the mesenchymal markers α-SMA and fibronectin in TFCs in the thyroid glands of AITD patients. Furthermore, E-cadherin expression was maintained in these patients compared to the controls. The TGF-ß-stimulation assay showed an increase in EMT markers, including vimentin, α-SMA, and fibronectin in thyroid cells, as well as a disruption of PC. The TFCs from the AITD patients experienced a partial transition to a mesenchymal phenotype, preserving epithelial characteristics associated with a disruption in PC, which might contribute to AITD pathogenesis.

Neonatal pneumothoraces with atypical location: the role of lung ultrasound.

Neonatal pneumothorax (NP) is a potentially life-threatening condition. Lung ultrasound (LUS) has shown higher sensitivity and specificity in diagnosis compared to x-rays, but evidence regarding its usefulness in complex NP is lacking. We report four neonates suffering from cardiac or esophageal malformations who developed lateral and/or posterior pneumothoraces, in which LUS helped, making NP diagnosis and management easier and faster. CONCLUSION: LUS is an easy-to-use, fast, simple, and accurate tool when evaluating newborns with NP, also in atypical positions such as in surgical patients. WHAT IS KNOWN: • Lung ultrasound (LUS) has higher sensitivity and specificity than x-rays in the diagnosis of pneumothorax in neonatal patients. WHAT IS NEW: • This is the first report about neonatal pneumothorax in non-conventional areas (lateral/posterior) diagnosed by lung ultrasound and how obtaining this information is critical in order to optimize management.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves' disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Common hematological values predict unfavorable outcomes in hospitalized COVID-19 patients.

COVID-19 can range from asymptomatic to life-threatening. Early identification of patients who will develop severe disease is crucial. A number of scores and indexes have been developed to predict severity. However, most rely on measurements not readily available. We evaluated hematological and biochemical markers taken on admission and determined how predictive they were of development of critical illness or death. We observed that higher values of readily available tests, including neutrophil:lymphocyte ratio; derived neutrophil index; and troponin I were associated with a higher risk of death or critical care admission (P < 0.001). We show that common hematological tests can be helpful in determining early in the course of illness which patients are likely to develop severe forms, as well as allocating resources to those patients early, while avoiding overuse of limited resources in patients with reduced risk of progression to severe disease.

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders.

Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p < 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR-19a and miR-143 were significantly increased in IMID patients with severe disease (p < 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.

Lung ultrasound in preterm infants with respiratory distress: experience in a neonatal intensive care unit.

Lung ultrasound (LUS) has been described as a useful tool in early prognosis of several respiratory diseases of the newborn, especially preterm infant newborns (PTNB) with respiratory distress syndrome (RDS), but still, it is not a standard of care in many neonatal units. We have conducted a descriptive, prospective study in a tertiary neonatal unit during 1 year. PTNB less than 35 weeks with respiratory distress at birth on non-invasive ventilation were recruited. A LUS was performed in the first 12 h of life and scored from 6 to 18 points (6 areas, 1 to 3 points each). They were followed until discharge. Main outcomes: need for surfactant treatment. Sixty-four preterm infants, median gestational age 29 weeks. Median LUS score in surfactant group was significantly higher than in no surfactant group (p < 0.0001). LUS ROC curve for surfactant treatment shows AUC 0.97 (IC 95% 0.92-1). LUS Odds ratio for surfactant treatment 3.17 (IC 95% 1.36-7.35).Conclusion: Early high LUS score correlates with surfactant necessity in preterm infants with respiratory distress at birth.What is Known:• Lung ultrasound (LUS) is a useful tool in determining prognosis of preterm infants with respiratory distress at birth.What is New:• This study adds evidence about LUS and preterm infants with respiratory distress, early predicting surfactant need and mechanical ventilation.

AMPA receptors modulate the reorganization of F-actin in Bergmann glia cells through the activation of RhoA.

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors have been shown to modulate the morphology of the lamelar processes of Bergmann glia cells in the molecular layer of the cerebellum. Here we suggest that reorganization of F-actin may underlay the changes in the morphology of the lamelar processes. Using the fluorescent staining of F-actin with Phalloidin and the quantification of RhoA activation through immunoprecipitation or pull-down assays, we show that RhoA is activated after stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors and leads to the reorganization of the actin cytoskeleton of Bergmann fibers. This reorganization of the actin cytoskeleton is reflected in the form of an increase in the intensity of the F-actin staining as well as in the loss of the number of Bergmann fibers stained with Phalloidin. Moreover, using a pharmacological approach, we show that activation of RhoA and the change in the intensity of the F-actin staining depends on the activation of PI3-K, focal adhesion kinase, and protein kinase C, whereas changes in the number of Bergmann fibers depend on external calcium in a RhoA independent manner. Our findings show that glutamate may induce a form of structural plasticity in Bergmann glia cells through the reorganization of the actin cytoskeleton. This may have implications in the way the synaptic transmission is processed in the cerebellum.

Photoresponsive Nanometer-Scale Iron Alginate Hydrogels: A Study of Gel-Sol Transition Using a Quartz Crystal Microbalance.

Alginate/Fe3+ hydrogels were fabricated on hyaluronic acid (HA) and poly(allylamine hydrochloride) (PAH) multilayers to yield photoresponsive nanometer-scale hydrogels. Light irradiation of the resulting hydrogels induced the photoreduction of "hard" Fe3+ to "soft" Fe2+ cations, leading to changes in the mechanical properties of the hydrogels related to their cross-linking behavior. The buildup and the phototriggered response of the supported alginate hydrogels were followed in situ with a quartz crystal microbalance (QCM) using an open cell allowing light irradiation from an LED source on top of the hydrogel. The results were correlated to the release profiles of folic acid, employed herein as a drug model, obtained from light-irradiated supported iron alginate hydrogels.

Neuropsychiatric symptoms as risk factors of dementia in a Mexican population: A 10/66 Dementia Research Group study.

INTRODUCTION: Cognitive and/or memory impairment are the main clinical markers currently used to identify subjects at risk of developing dementia. This study aimed to explore the relationship between the presence of neuropsychiatric symptoms and dementia incidence. METHODS: We analyzed the association between neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older adults from the general population over 3 years of follow-up, modeling cumulative incidence ratios using Poisson models. RESULTS: Five neuropsychiatric symptoms were associated with incident dementia: delusions, hallucinations, anxiety, aberrant motor behavior, and depression. The simultaneous presence of two symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes, indicators of cognitive function, and sociodemographic factors, of 1.9 (95% confidence interval, 1.2-2.9), whereas the presence of three to five, similarly adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9-4.8). DISCUSSION: Neuropsychiatric symptoms are common in predementia states and may independently contribute as risk factors for developing dementia.

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

NEW FINDINGS: What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression suggests this as a possible mediator of the mechanism linking the SCN and day-night variations in TG uptake. These findings show that the SCN has a major role in day-night variations in plasma TGs by promoting TG uptake into skeletal muscle and brown adipose tissue. Consequently, disturbance of the biological clock might be an important risk factor contributing to the development of hyperlipidaemia.

Quantitative Nanomechanical Properties of Multilayer Films Made of Polysaccharides through Spray Assisted Layer-by-Layer Assembly.

Nanomechanical properties of alginate/chitosan (Alg/Chi) multilayer films, obtained through spray assisted layer-by-layer assembly, were studied by means of PeakForce quantitative nanomechanical mapping atomic force microscopy (PF-QNM AFM). Prepared at two different alginate concentrations (1.0 and 2.5 mg/mL) and a fixed chitosan concentration (1.0 mg/mL), Alg/Chi films have an exponential growth in thickness with a transition to a linear growth toward a plateau by increasing the number of deposited bilayers. Height, elastic modulus, deformation, and adhesion maps were simultaneously recorded depending on the number of deposited bilayers. The elastic modulus of Alg/Chi films was found to be related to the mechanism of growth in contrast to the adhesion and deformation. A comparison of the nanomechanical properties obtained for non-cross-linked and thermally cross-linked Alg/Chi films revealed an increase of the elastic modulus after cross-linking regardless alginate concentration. The incorporation of iron oxide nanoparticles (NPs), during the spray preparation of the films, gave rise to nanocomposite Alg/Chi films with increased elastic moduli with the number of incorporated NPs layers. Deformation maps of the films strongly suggested the presence of empty spaces associated with the method of preparation. Finally, adhesion measurements point out to a significant role of NPs on the increase of the adhesion values found for nanocomposite films.

Kaposiform Hemangioendothelioma Presenting as Hydrops Fetalis.

We describe the case of a 33-week preterm infant who developed nonimmune hydrops fetalis secondary to a kaposiform hemangioendothelioma (KHE). The tumor was successfully treated with vincristine, prednisone, ticlopidine, and aspirin. KHE can be an unusual cause of hydrops fetalis; in such cases, diagnosis can be challenging since generalized edema can obscure KHE.

Association of hypertension-related distress with lack of self-care among hypertensive patients.

Research on factors associated with poor adherence to self-care focuses primarily on psychiatric emotional disorders such as depression and anxiety, whereas non-psychiatric chronic-disease-related emotional distress has received little attention in hypertensive patients. The objective of this study was to evaluate the association of hypertension-related distress with the lack of self-care including low adherence to pharmacological treatment, lack of regular physical activity, low intake of fruits and vegetables and frequent intake of high-salt foods. A cross-sectional survey was conducted in 2014 in two family medical units affiliated with the Mexican Institute of Social Security. The study included 487 hypertensive patients >19 years of age. The conceptual framework for the study was based on the Health Promotion Model. The analysis included multiple Poisson regression models. We found that 21.1% of participants had hypertension-related distress. Low adherence to pharmacological treatment was identified in 45.8% of patients, whereas 46.8% lacked regular physical activity, 30.8% reported a low consumption of fruits and vegetables, and 54.6% frequently consumed foods high in salt content. Hypertension-related distress was associated with lack of regular physical activity and low intake of fruits and vegetables. These findings highlight the importance of addressing distress in order to improve self-care of hypertensive patients.

Needs of caregivers of cancer patients: validation of the Mexican version of the Support Person Unmet Needs Survey (SPUNS-SFM).

PURPOSE: The purpose of this study was to validate the Mexican version of the Support Person Unmet Needs Survey (SPUNS-SFM). METHODS: A cross-sectional survey that included 826 primary caregivers of cancer patients was conducted from June to December 2013 at the Oncology Hospital of the Mexican Institute of Social Security in Mexico City. The validation procedure comprised (1) content validity through a group of experts; (2) construct validity through an exploratory factor analysis based on the polychoric correlation matrix; (3) internal consistency using Cronbach's alpha; (4) convergent validity between SPUNS-SFM and quality of life, anxiety-and-depression scales by calculating Spearman's rank correlation coefficient;( 5) discriminative validity through the Wilcoxon rank-sum test; and (6) test-retest reliability using intraclass correlation coefficient. RESULTS: SPUNS-SFM has 23 items with six factors accounting for 65 % of the total variance. The domains were concerns about the future, access and continuity of healthcare, information, work and finance, and personal and emotional needs. Cronbach's alpha values ranged from 0.70 to 0.88 among factors. SPUNS-SFM had moderate convergent validity compared with quality of life and depression-and-anxiety scales and good discriminative validity, revealing high needs for younger caregivers and more emotional needs for caregivers of patients with advanced cancer stages. Intraclass correlation coefficient between SPUNS-SFM measurements was 0.78. CONCLUSION: SPUNS-SFM is a valid and reliable tool to identify needs of caregivers of cancer patients.

Supportive care needs of Mexican adult cancer patients: validation of the Mexican version of the Short-Form Supportive Care Needs Questionnaire (SCNS-SFM).

PURPOSE: The purpose of this study is to validate the Mexican version of the Short-Form Supportive Care Needs survey (SCNS-SFM). METHODS: A cross-sectional survey was conducted from June to December 2013 at the Oncology Hospital of the Mexican Institute of Social Security in Mexico City. The study included 825 subsequent cancer patients >20 years of age with all forms of solid cancer. Patients had prior surgical removal of histologically confirmed cancer and attended outpatient consultations. Validation of SCNS-SFM included the following: (1) content validity through a group of experts; (2) construct validity through an exploratory factor analysis based on the polychoric correlation matrix; (3) internal consistency using Cronbach's alpha; (4) convergent validity between SCNS-SFM and quality of life, anxiety, and depression scales by calculating Pearson's correlation coefficient; (5) discriminative validity through analysis of MANOVAs; and (6) test-retest reliability using intraclass correlation coefficient calculations. RESULTS: SCNS-SFM has 33 items with five factors accounting for 59 % of total variance. Cronbach's alpha values ranged from 0.78 to 0.90 among factors. SCNS-SFM has good convergent validity compared with quality of life and depression and anxiety scales and good discriminative validity, revealing great information, psychological support, and physical daily living needs for women, patients <60 years, and high physical daily living needs for those with <1 year since cancer diagnosis, with advanced disease stages and current chemo- or radiotherapy. Intraclass correlation coefficient between SCNS-SFM measurements was 0.9. CONCLUSION: SCNS-SFM has acceptable psychometric properties and is suitable to evaluate supportive care needs of cancer patients.

Relaxation processes in a lower disorder order transition diblock copolymer.

The dynamics of lower disorder-order temperature diblock copolymer leading to phase separation has been observed by X ray photon correlation spectroscopy. Two different modes have been characterized. A non-diffusive mode appears at temperatures below the disorder to order transition, which can be associated to compositional fluctuations, that becomes slower as the interaction parameter increases, in a similar way to the one observed for diblock copolymers exhibiting phase separation upon cooling. At temperatures above the disorder to order transition TODT, the dynamics becomes diffusive, indicating that after phase separation in Lower Disorder-Order Transition (LDOT) diblock copolymers, the diffusion of chain segments across the interface is the governing dynamics. As the segregation is stronger, the diffusive process becomes slower. Both observed modes have been predicted by the theory describing upper order-disorder transition systems, assuming incompressibility. However, the present results indicate that the existence of these two modes is more universal as they are present also in compressible diblock copolymers exhibiting a lower disorder-order transition. No such a theory describing the dynamics in LDOT block copolymers is available, and these experimental results may offer some hints to understanding the dynamics in these systems. The dynamics has also been studied in the ordered state, and for the present system, the non-diffusive mode disappears and only a diffusive mode is observed. This mode is related to the transport of segment in the interphase, due to the weak segregation on this system.