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BACKGROUND: Malocclusions are usually diagnosed around 3-4 years of age according to specific criteria. The purpose of this protocol is to validate a method to understand how the type of delivery can influence the development of malocclusions. MATERIALS: This pilot study, conducted at the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico of Milan, evaluated the relationship between the type of delivery, fetal presentation, and the presence of malocclusions in children. The sample included 5 healthy term newborns, all born to healthy mothers with uncomplicated pregnancies by vaginal delivery. Measurements were taken, via ultrasound, at the 37th week of gestation (T0) and on the second day of life (T1), using a craniometer, caliper and goniometer, including head circumference, lower facial angle, frontonasal angle, labial fissure length, and interpupillary distance. CONCLUSION: The results suggest that further research is necessary to better understand the influence of delivery mode and fetal presentation on the development of malocclusions. This study represents an important first step, highlighting the need for larger samples and more in-depth investigation methods to obtain more conclusive results.
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Chemical communication in terrestrial vertebrates is often built on complex blends, where semiochemical and structural compounds may form an integrated functional unit. In lizards, many species have specialized epidermal glands whose secretions are waxy, homogeneous blends of lipids and proteins, both active in communication. The intimate co-occurrence of such compounds allows us to hypothesize that they should undergo a certain degree of covariation, considering both their semiochemical role and the support-to-lipid function hypothesized for the protein fraction. In order to assess the occurrence and level of protein-lipid covariation, we compared the composition and complexity of the two fractions in the femoral gland secretions of 36 lizard species, combining phylogenetically-informed analysis with tandem mass spectrometry. We found the composition and complexity of the two fractions to be strongly correlated. The composition of the protein fraction was mostly influenced by the relative proportion of cholestanol, provitamin D3, stigmasterol, and tocopherol, while the complexity of the protein pattern increased with that of lipids. Additionally, two identified proteins (carbonic anhydrase and protein disulfide isomerase) increased their concentration as provitamin D3 became more abundant. Although our approach does not allow us to decrypt the functional relations between the proteinaceous and lipid components, nor under the semiochemical or structural hypothesis, the finding that the proteins involved in this association were enzymes opens up to new perspectives about protein role: They may confer dynamic properties to the blend, making it able to compensate predictable variation of the environmental conditions. This may expand the view about proteins in the support-to-lipid hypothesis, from being a passive and inert component of the secretions to become an active and dynamic one, thus providing cues for future research.
(Italian) RiassuntoLa comunicazione chimica nei vertebrati terrestri è spesso costituita da miscele complesse, in cui composti semiochimici e strutturali possono formare un"unità funzionale integrata. Nelle lucertole, molte specie hanno ghiandole epidermiche specializzate le cui secrezioni sono miscele cerose e omogenee di lipidi e proteine, entrambe attive nella comunicazione. L"intima coesistenza di tali composti lascia ipotizzare che essi debbano subire un certo grado di co-variazione, sia considerando il loro ruolo semiochimico, sia la funzione di supporto ai lipidi ipotizzata per la frazione proteica. Per valutare la presenza e il livello di covariazione proteine-lipidi, abbiamo confrontato la composizione e la complessità delle due frazioni nelle secrezioni della ghiandola femorale di 36 specie di lucertole, combinando l"analisi filogenetica comparativa con la spettrometria di massa. Abbiamo riscontrato una forte correlazione tra la composizione e la complessità delle due frazioni. La composizione della frazione proteica è stata influenzata soprattutto dalla proporzione relativa di colestanolo, provitamina D3, stigmasterolo e tocoferolo, mentre la complessità del pattern proteico è aumentata con quella dei lipidi. Inoltre, due proteine identificate (anidrasi carbonica e disolfuro isomerasi) hanno aumentato la loro concentrazione al crescere dell'abbondanza della provitamina D3. Sebbene il nostro approccio non consenta di decifrare le relazioni funzionali tra le componenti proteiche e lipidiche, né secondo l"ipotesi semiochimica né secondo quella strutturale, la scoperta che le proteine coinvolte in questa associazione sono enzimi apre a nuove prospettive sul ruolo delle proteine stesse: esse potrebbero conferire proprietà dinamiche alla miscela, rendendola capace di compensare le prevedibili variazioni delle condizioni ambientali. Questo può ampliare la visione delle proteine nell'ipotesi che esse siano di supporto ai lipidi, da componente passiva e inerte delle secrezioni a componente attiva e dinamica, fornendo così spunti per ricerche future.
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Timely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need lifesaving neurosurgical intervention. Although the detection of infratentorial hemorrhage by ultrasound scanning is often considered as difficult, the use of additional acoustic windows and recognition of characteristic ultrasound features facilitate early diagnosis. In this case series, we report on newborns with severe, symptomatic infratentorial hemorrhage detected primarily by cranial ultrasound. We demonstrate the characteristic ultrasound features present in all cases and discuss how ultrasound diagnosis contributed to early diagnosis and treatment.
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Ecoencefalografía , Hidrocefalia , Hemorragia Cerebral/diagnóstico por imagen , Humanos , Hidrocefalia/cirugía , Recién Nacido , Procedimientos NeuroquirúrgicosRESUMEN
INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Síndrome del Maullido del Gato/diagnóstico por imagen , Síndrome del Maullido del Gato/patología , Adolescente , Adulto , Niño , Preescolar , Síndrome del Maullido del Gato/genética , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética/métodos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions. METHODS: Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. DISCUSSION: This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas. TRIAL REGISTRATION: Trial registration: clinicaltrials.gov platform (Multisession Radiosurgery in Large Meningiomas -MuRaLM- identifier NCT02974127). Registered: November 28, 2016. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02974127?term=radiosurgery&cond=Intracranial+Meningioma&draw=2&rank=1.
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Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radiocirugia/métodos , Fraccionamiento de la Dosis de Radiación , Humanos , Neoplasias Meníngeas/patología , Meningioma/patología , Estudios Prospectivos , Radiocirugia/efectos adversos , Seguridad , Resultado del TratamientoRESUMEN
The successful production of recombinant enzymes by tobacco transplastomic plants must maintain compatibility of the heterologous enzyme with chloroplast metabolism and its long-time enzyme stability. Based on previous reports, it has been taken for granted that following biolistic-transformation, homoplasticity could be obtained from the initially heteroplastic state following successive rounds of selection in the presence of the selection agent. However, several studies indicated that this procedure does not always ensure the complete elimination of unmodified wild-type plastomes. The present study demonstrates that CelK1 transplastomic plants, which were photosyntetically as active as untransformed ones, remain heteroplastomic even after repeated selection steps and that this state does not impair the relatively high-level production of the recombinant enzyme. In fact, even in the heteroplastomic state, the recombinant protein represented about 6% of the total soluble proteins (TSP). Moreover, our data also show that, while the recombinant endoglucanase undergoes phosphorylation, this post-translation modification does not have any significant impact on the enzymatic activity. Biomass storage might be required whenever the enzyme extraction process could not be performed immediately following the harvest of tobacco mature plants. In this respect, we have observed that enzyme activity in the detached leaves stored at 4 °C is maintained up to 20 weeks without significant loss of activity. These findings may have major implications in the future of chloroplast genetic engineering-based molecular farming to produce industrial enzymes in transplastomic plants.
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Celulasa/biosíntesis , Cloroplastos/genética , Agricultura Molecular , Nicotiana/enzimología , Nicotiana/genética , Celulasa/genética , Ingeniería Genética , Microbiología Industrial/métodos , Hojas de la Planta/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Proteoma , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genéticaRESUMEN
Cosmological simulations predict that the Universe contains a network of intergalactic gas filaments, within which galaxies form and evolve. However, the faintness of any emission from these filaments has limited tests of this prediction. We report the detection of rest-frame ultraviolet Lyman-α radiation from multiple filaments extending more than one megaparsec between galaxies within the SSA22 protocluster at a redshift of 3.1. Intense star formation and supermassive black-hole activity is occurring within the galaxies embedded in these structures, which are the likely sources of the elevated ionizing radiation powering the observed Lyman-α emission. Our observations map the gas in filamentary structures of the type thought to fuel the growth of galaxies and black holes in massive protoclusters.
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We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged.
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Neoplasias de los Genitales Femeninos/terapia , Guías de Práctica Clínica como Asunto/normas , Complicaciones Neoplásicas del Embarazo/terapia , Efectos Tardíos de la Exposición Prenatal/prevención & control , Femenino , Humanos , Cooperación Internacional , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Pronóstico , Sociedades MédicasRESUMEN
Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.
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Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/mortalidad , Recien Nacido Prematuro/fisiología , Adolescente , Adulto , Enfermedades Cerebelosas/fisiopatología , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Meningioma are the second most common brain tumors in adults and can cause significant morbidity and mortality. The scarcity of in vitro and in vivo models represents the major obstacle to understand the molecular basis of meningioma tumorigenesis. The main aim of this study was to assess a method for radiobiology of meningioma cells colture by means of well-known meningioma lines. NEW METHOD: We carried out a protocol of cells culture for irradiation of meningioma cells. We used the immortalized cell lines IOMM-Lee and CH-157 to study their radiation-reponse by means of clonogenic assays and to evaluate their proliferation and apoptosis. We irradiated the cells with different total doses using two different linear accelerators. RESULTS: We observed a more radiation resistance of the IOMM-Lee than the CH-157. Indeed, the cellular death of CH-157 was obtained at a very low dose irradiation. Moreover, we showed a dose-response effect due to the early and late apoptosis, in fact the rate of apoptotic cells is greater than that of the necrotic cells at any dose of irradiation and at any time of analysis. COMPARISON WITH EXISTING METHODS: There is not a standardized method for radiobiology of meningioma experiments. CONCLUSIONS: Our method of cells culture appears suitable for radiosensitivity studies on meningioma. We can confirm that the response to radiotherapy depends not only on irradiation features, but also on tumor radiosensitivity.
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Línea Celular Tumoral/efectos de la radiación , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de la radiación , Humanos , Proyectos PilotoRESUMEN
Once considered a single species, the whitefly, Bemisia tabaci, is a complex of numerous morphologically indistinguishable species. Within the last three decades, two of its members (MED and MEAM1) have become some of the world's most damaging agricultural pests invading countries across Europe, Africa, Asia and the Americas and affecting a vast range of agriculturally important food and fiber crops through both feeding-related damage and the transmission of numerous plant viruses. For some time now, researchers have relied on a single mitochondrial gene and/or a handful of nuclear markers to study this species complex. Here, we move beyond this by using 38,041 genome-wide Single Nucleotide Polymorphisms, and show that the two invasive members of the complex are closely related species with signatures of introgression with a third species (IO). Gene flow patterns were traced between contemporary invasive populations within MED and MEAM1 species and these were best explained by recent international trade. These findings have profound implications for delineating the B. tabaci species status and will impact quarantine measures and future management strategies of this global pest.
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Hemípteros/genética , Agricultura , Animales , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: The heel stick is the method of choice in most neonatal units for capillary blood sampling, and it represents the most common event among all painful procedures performed on newborns. The type and design of heel stick device and the clinical procedure to collect a blood sample may have an impact on newborn pain response as well. OBJECTIVE: To compare the pain response and efficiency of different automated devices for capillary blood collection in newborns. DESIGN: Randomized clinical trial. SETTING: Postnatal ward of a tertiary-care university hospital in Italy. PARTICIPANTS: Newborn infants at gestational age ≥34 weeks undergoing the metabolic screening test after the 49th hour of life. METHODS: A total of 762 neonates were recruited and randomized into 6 groups (127 babies in each group) assigned to 6 different capillary blood collection devices (Ames Minilet™ Lancet; Cardinal Health Gentleheel®; Natus Medical NeatNick™; BD Quikheel™ Lancet; Vitrex Steriheel® Baby Lancet; Accriva Diagnostics Tenderfoot®). MAIN OUTCOME MEASURES: The following data were collected and assessed for each of the 6 groups evaluated: a) number of heel sticks, b) pain score according to the Neonatal Infant Pain Scale (NIPS) and c) need to squeeze the heel. RESULTS: The Ames Minilet™ Lancet device was found to perform by far the worst compared to the five device underexamination: it required the highest number of sticks (mean=3.91; 95% CI: 3.46-4.36), evoked the most intense pain (mean=3.98; 95% CI: 3.77-4.20), and most frequently necessitated squeezing the heel (92.9%; 95% CI: 86.9-96.3). The five devices under examination appeared to be similar in terms of the number of sticks required, but differed slightly in NIPS score and in need to squeeze the heel. CONCLUSION: The Accriva Diagnostics Tenderfoot® device demonstrated the greatest efficiency for blood sampling and evoked the least pain. With this device, the metabolic screening test could be performed with a single skin incision in the large majority of infants (98.4%), heel squeezing was limited to only 6.3% of infants, and the NIPS score turns out to be lower than other devices in our study (1.22; 95% CI 1.05-1.39).
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Automatización , Dolor/etiología , Flebotomía/instrumentación , Talón , Humanos , Recién Nacido , Dolor/prevención & controlRESUMEN
Background. Chronic neonatal pain can lead to long-term adverse effects on the immature brain. EDIN scale for prolonged pain might not be fully suitable for premature infants. We aimed to test a modified EDIN scale, adding postmenstrual age (PMA) as a sixth item (EDIN6). Methods. In a two-phase prospective study, pain was assessed in all neonates admitted in our NICU. In T1 EDIN was applied; in T2 EDIN6 with additional scores of 2, 1, and 0, respectively, for 25-32, 33-37, and >37 weeks PCA was tested. Scores > 6 suggested pain. The nursing staff was given a questionnaire to evaluate EDIN and EDIN6. Results. A total of 15960 pain assessments were recorded (8693 in T1; 7267 in T2). With EDIN6, cumulative detection of pain almost tripled (117/7267 versus 52/8693, p = 0.001). Main differences were found among less mature categories (50/1472 versus 17/1734, p = 0.001 in PCA 25-32; 26/2606 versus 10/4335, p = 0.001 in PMA 33-37; 41/3189 versus 25/2624, p = 0.26 in PMA > 37). Adequacy of pain assessment in lower PMA was judged "medium-high" in 13,4% of nurses in T1 and 71,4% in T2. Conclusions. EDIN6 may allow improved evaluation of pain in preterm infants.
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Edad Gestacional , Recien Nacido Prematuro/fisiología , Dimensión del Dolor/métodos , Demografía , Encuestas de Atención de la Salud , Humanos , Recién Nacido , Personal de Enfermería/estadística & datos numéricos , Estudios ProspectivosRESUMEN
Experimental vaccine candidates have been evaluated to prevent leishmaniasis, but no commercial vaccine has been proved to be effective against more than one parasite species. LiHyT is a Leishmania-specific protein that was firstly identified as protective against Leishmania infantum. In this study, LiHyT was evaluated as a vaccine to against two Leishmania species causing tegumentary leishmaniasis (TL): Leishmania major and Leishmania braziliensis. BALB/c mice were immunized with rLiHyT plus saponin and lately challenged with promastigotes of the two parasite species. The immune response generated was evaluated before and 10 weeks after infection, as well as the parasite burden at this time after infection. The vaccination induced a Th1 response, which was characterized by the production of IFN-γ, IL-12 and GM-CSF, as well as by high levels of IgG2a antibodies, after in vitro stimulation using both the protein and parasite extracts. After challenge, vaccinated mice showed significant reductions in their infected footpads, as well as in the parasite burden in the tissue and organs evaluated, when compared to the control groups. The anti-Leishmania Th1 response was maintained after infection, being the IFN-γ production based mainly on CD4(+) T cells. We described one conserved Leishmania-specific protein that could compose a pan-Leishmania vaccine.
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Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Antígenos de Protozoos/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Interleucina-12/inmunología , Leishmania braziliensis/inmunología , Leishmania major/inmunología , Leishmaniasis/parasitología , Leishmaniasis/prevención & control , Vacunas contra la Leishmaniasis/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Proteínas Protozoarias/inmunología , Saponinas/administración & dosificación , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To assess the need for respiratory support in late preterm infants treated with sustained lung inflation (SLI) at birth. STUDY DESIGN: In this controlled trial, we randomly assigned infants born at 34(+0) to 36(+6) weeks of gestation to receive SLI (25 cmH2O for 15 s) at birth, followed by continuous positive airway pressure (CPAP) or assistance according to the recommendations of the American Academy of Pediatrics. The primary outcome was the need for any type of respiratory support. The secondary outcomes included neonatal intensive care unit (NICU) admission for respiratory distress and length of stay. The risk ratios (RRs) and 95% confidence intervals (CIs) of the outcomes were calculated for the SLI group in reference to the control group. RESULTS: A total of 185 infants were enrolled: 93 in the SLI group and 92 in the control group. No difference was found in the need for any type of respiratory support between the infants treated with SLI and the control group (10.6 vs 8.7%, RR 1.24, 95% CI 0.51 to 2.99). The NICU admission for respiratory distress and the length of stay did not differ between the groups. CONCLUSION: Providing SLI at birth in late preterm infants does not affect their need for respiratory support.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Síndrome de Dificultad Respiratoria del Recién Nacido , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Italia/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Nacimiento Prematuro/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/terapiaRESUMEN
In this work, the effect of vaccination of a newly described Leishmania infantum antigenic protein has been studied in BALB/c mice infected with this parasite species. The LiHyD protein was characterized after a proteomic screening performed with the sera from dogs suffering visceral leishmaniasis (VL). Its recombinant version was expressed, purified and administered to BALB/c mice in combination with saponin. As a result of vaccination and 10 weeks after challenge using an infective dose of L. infantum stationary promastigotes, vaccinated mice showed lower parasite burdens in different organs (liver, spleen, bone marrow and footpads' draining lymph nodes) than mice inoculated with the adjuvant alone or the vaccine diluent. Protected mice showed anti-Leishmania IgG2a antibodies and a predominant IL-12-driven IFN-γ production (mainly produced by CD4(+) T cells) against parasite proteins, whereas unprotected controls showed anti-Leishmania IgG1 antibodies and parasite-mediated IL-4 and IL-10 responses. Vaccinated mice showed an anti-LiHyD IgG2a humoral response, and their spleen cells were able to secrete LiHyD-specific IFN-γ, IL-12 and GM-CSF cytokines before and after infection. The protection was correlated with the Leishmania-specific production on nitric oxide. Altogether, the results indicate that the new LiHyD protein could be considered in vaccine formulations against VL.
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Citocinas/metabolismo , Leishmania infantum/inmunología , Leishmaniasis Visceral/veterinaria , Proteínas Protozoarias/inmunología , Vacunación/veterinaria , Adyuvantes Inmunológicos , Animales , Modelos Animales de Enfermedad , Perros , Femenino , Leishmaniasis Visceral/prevención & control , Ratones , Ratones Endogámicos BALB C , Proteínas RecombinantesRESUMEN
Botanicals are widely consumed all over the world for health purposes, with increased usage in the general population, in many different types of products, including foods and plant food supplements. Several reports support for the beneficial effects of botanicals against gastrointestinal inflammation. However, no studies regarding the anti-inflammatory activity in the gastrointestinal tract of red vine leaves have been reported so far. The present work investigates the biological activity of Vitis vinifera L. water extract (VVWE) from dried leaves in two in vitro models of gastric and intestinal inflammation. The extract was characterized by a validated HPLC-DAD method, and tested on human epithelial gastric (AGS) and intestinal (Caco-2) cells with the aim to investigate the inhibitory effect on IL-8 secretion and promoter activity, before and after in vitro gastric or gastrointestinal digestion. Our results show that the water extract from red vine leaves inhibits TNFα-induced IL-8 secretion and expression in human gastric epithelial cells; the effect should be maintained, although to a lesser extent, after gastric digestion. In contrast, the effect after intestinal digestion is dramatically decreased since degradation of the active components in the gut does not allow the extract to efficiently counteract TNFα or IL-1ß induced IL-8 expression and the NF-κB pathway. The main molecular target of VVWE at the gastric level includes TNFα-induced activation of NF-κB and occurs at concentrations easily reachable after PFS consumption based on red vine leaf water extract as the ingredient. Our findings suggest that PFS containing water extracts from Vitis vinifera L. leaves could be useful to inhibit/attenuate gastric inflammation inhibiting IL-8 secretion and expression through impairment of the NF-κB pathway.
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Antiinflamatorios/metabolismo , Tracto Gastrointestinal/metabolismo , Inflamación/metabolismo , Extractos Vegetales/metabolismo , Hojas de la Planta/metabolismo , Vitis/metabolismo , Antiinflamatorios/química , Células CACO-2 , Digestión , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Tracto Gastrointestinal/inmunología , Humanos , Inflamación/dietoterapia , Inflamación/genética , Inflamación/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Modelos Biológicos , FN-kappa B/genética , FN-kappa B/inmunología , Hojas de la Planta/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Vitis/químicaRESUMEN
We report a small-angle neutron scattering study of liquid water sorption in Nafion membranes. The swelling of hydrophilic domains was measured on the nanoscale by combining in situ time-resolved and long-term static experiments, yielding kinetic curves recorded over an unprecedented time scale, from hundreds of milliseconds to several years. At low water content, typically below 5 water molecules per ionic group, a limited subdiffusive regime was observed and ascribed to nanoconfinement and local interactions between charged species and water molecules. Further ultrafast and thermally activated swelling due to massive liquid water sorption was observed and analyzed by using Fick's equation. The extracted mutual water diffusion coefficients are in good agreement with pulsed field gradient NMR self-diffusion coefficient values, evidencing a water diffusion-driven process due to concentration gradients within the Nafion membrane. Finally, after completion of the ultrafast regime, the kinetic swelling curves exhibit a remarkable long-term behavior scaling as the logarithm of time, showing that the polymer membrane can continuously accommodate additional water molecules upon hydration stress. The present nanoscale kinetics results provide insights into the vapor-versus-liquid sorption mechanisms, the nanostructure of Nafion, and the role of polymer reorganization modes, highlighting that the membrane can never reach a steady state.
RESUMEN
AIM: Thyroiditis is often associated with nodules based on the Bethesda classification system, and the presence of thyroiditis can make thyroid surgery difficult using both conventional techniques and minimally invasive videoassisted approaches (MIVAT). METHODS: We analyzed 326 patients who underwent total thyroidectomy in 2012. We collected all data in dedicated database. The patients were divided in 4 groups: group 1 no affected by thyroiditis, group 2 affected by thyroiditis, group 3 only histological diagnosis of thyroiditis, group 4all patients affected by thyroiditis. RESULTS: Group 1 included 201 cases, group 2 included 64 patients, group 3 included 61 patients. No statistically significant difference between group 2 and 3 about Ultrasound (US) examination. Statistically significant difference in incidence of "THYR 3-4" between group 1 and group 4. No differences in MIVAT vs. Conventional group. CONCLUSION: US examination of the thyroid is essential for the diagnostic study of the gland also in the selection of a surgical approach. Thyroiditis is a relative contraindication to MIVAT but the experience of the endocrine surgeon is the most important factor to reduce intra and postoperative complications together a correct collaboration in multidisciplinart endocrinological team.
Asunto(s)
Glándula Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/cirugía , Tiroidectomía , Tiroiditis/diagnóstico , Adulto , Anciano , Biopsia con Aguja Fina , Disfonía/etiología , Disfonía/prevención & control , Femenino , Bocio Nodular/complicaciones , Bocio Nodular/diagnóstico por imagen , Humanos , Incidencia , Hallazgos Incidentales , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/lesiones , Selección de Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Neoplasias de la Tiroides/complicaciones , Nódulo Tiroideo/complicaciones , Tiroidectomía/métodos , Tiroiditis/complicaciones , Tiroiditis/diagnóstico por imagen , Tiroiditis/epidemiología , Ultrasonografía , Cirugía Asistida por Video , Parálisis de los Pliegues Vocales/etiología , Parálisis de los Pliegues Vocales/prevención & controlRESUMEN
Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents.