Can Intubation Be Improved with Endotracheal Tubes Marked with a Color Scale? Randomized Controlled Study.

OBJECTIVE: This study aimed to assess if a color scale in the endotracheal tube (ETT) can help operators to correctly select the size and depth of placement of the ETT and decrease the time required to complete the procedure and compared with the usual numeric ETT scale in a mannequin model. STUDY DESIGN: The study was conducted in eight centers. Each size of the ETT was identified with a different color. The experimental ETTs had two different colored areas, one for the mouthpiece and another to identify where the ETT should be taped above the lip (an area of 1 cm. The operators were trained as part of the protocol using an instructional video. Four clinical scenarios requiring endotracheal intubation were designed and randomly assigned. Each operator had to select the size and depth of ETT based on the birth weight (BW), and then had to perform four intubations. RESULTS: A total of 108 operators performed 432 intubations. No differences were found in the correct placement and selection of the ETT. Median time (in seconds) required for intubation using numeric versus experimental tube was: for ETT Ø NRP (Neonatal Resuscitation Program) 2.5, 11.5 versus 8 (p < 0.001), ETT Ø 3, 12 versus 10 (p < 0.001), ETT Ø 3.5, 15.5 versus12 (p = 0.003), ETT Ø 4, 12 versus11 (p = 0.019). CONCLUSION: No significant difference was observed in the selection and correct placement of the ETT. However, the intubation time was significantly shorter using the experimental ETT. This device could improve the effectiveness of intubation by reducing the time needed to properly place the ETT at mid trachea. KEY POINTS: · It is an innovative intervention to try to solve a great inconvenience of daily practice.. · The study also raises the difficulty in maintaining the ability of endotracheal intubation.. · It proposes a scale that ensures the correct location with a safe fixation zone..

Phylogeography of Nasutitermes corniger (Isoptera: Termitidae) in the Neotropical Region.

BACKGROUND: The Neotropical Region is known for its biodiversity and ranks third in number of known termite species. However, biogeographic and phylogeographic information of termites of this region is limited compared to other world geographic regions. Nasutitermes corniger is widely distributed in the region and is of considerable economic importance. The goal of this study was to describe the phylogeography of N. corniger in the Neotropical Region, to better understand its evolutionary processes. RESULTS: The sampled populations of N. corniger showed high genetic variation. Results indicated strong geographic structure among N. corniger populations, with most haplotypes not broadly shared among separated locations. Phylogeographic analyses showed a dispersal route for N. corniger from Central America into South America via the Isthmus of Panama, with subsequent dispersal through the highlands east of the Andes and into eastern regions of the continent. The majority of haplotypes were limited in distribution to proximal regions, corresponding to particular biomes (Atlantic Forest, Amazonia, Chaco, Cerrado and Caatinga). CONCLUSIONS: Nasutitermes corniger is suggested to be a good model for biogeographic and phylogeographic studies in the Neotropical Region. This study clarified the phylogeographic history of N. corniger and can contribute to the understanding of biogeographic dispersion processes in the Neotropical Region.

Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome.

BACKGROUND: SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. METHODS: We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. RESULTS: We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. CONCLUSIONS: We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype.

Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC) and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model.

Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidation and Lectin-like oxidized LDL receptor-1 (LOX-1) induction, leading to a pathological hippocampal response, namely, ischemic long-term potentiation (i-LTP). These events may correlate with the progressive neural loss observed in NPCD. To test these hypotheses, hippocampal slices from Wild Type (WT) and NPC1-/- mice were prepared, and field potential in the CA1 region was analyzed during transient oxygen/glucose deprivation (OGD). Moreover, LOX-1 expression was evaluated by RT-qPCR, immunocytochemical, and Western blot analyses before and after an anoxic episode. Our results demonstrate the development of a precocious i-LTP in NPC1-/- mice during OGD application. We also observed a higher expression of LOX-1 transcript and protein in NPC1-/- mice with respect to WT mice; after anoxic damage to LOX-1 expression, a further increase in both NPC1-/- and WT mice was observed, although the protein expression seems to be delayed, suggesting a different kinetic of induction. These data clearly suggest an elevated susceptibility to neurodegeneration in NPC1-/- mice due to oxidative stress. The observed up-regulation of LOX-1 in the hippocampus of NPC1-/- mice may also open a new scenario in which new biomarkers can be identified.

Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome.

Mutations in ANKRD11 have recently been reported to cause KBG syndrome, an autosomal dominant condition characterized by intellectual disability (ID), behavioral problems, and macrodontia. To understand the pathogenic mechanism that relates ANKRD11 mutations with the phenotype of KBG syndrome, we studied the cellular characteristics of wild-type ANKRD11 and the effects of mutations in humans and mice. We show that the abundance of wild-type ANKRD11 is tightly regulated during the cell cycle, and that the ANKRD11 C-terminus is required for the degradation of the protein. Analysis of 11 pathogenic ANKRD11 variants in humans, including six reported in this study, and one reported in the Ankrd11 (Yod/+) mouse, shows that all mutations affect the C-terminal regions and that the mutant proteins accumulate aberrantly. In silico analysis shows the presence of D-box sequences that are signals for proteasome degradation. We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.

Seizures induced by desloratadine, a second-generation antihistamine: clinical observations.

Some clinical experiences indicate that H1-antihistamines, especially first-generation H1-antagonists, occasionally provoke convulsions in healthy children as well as epileptic patients. Desloratadine is a frequently used second-generation antihistamine considered to be effective and safe for the treatment of allergic diseases. We describe four children who experienced epilepsy associated with the nonsedating H(1)-antagonist desloratadine and discuss the neurophysiologic role of the central histaminergic system in seizure susceptibility. In conclusion, we recommend caution in treating epileptic patients with the histamine H(1)-antagonists, including second- and third-generation drugs that are frequently referred because they are considered to be nonsedating antihistamines.

Neurobehavioral phenotype observed in KBG syndrome caused by ANKRD11 mutations.

KBG syndrome is a rare disease characterized by typical facial dysmorphism, macrodontia of upper central incisors, skeletal abnormalities, and developmental delay. Recently, mutations in ANKRD11 gene have been identified in a subset of patients with KBG syndrome, while a contiguous gene deletion syndrome involving 16q24.3 region (including ANKRD11) was delineated in patients with facial dysmorphism, autism, intellectual disability, and brain abnormalities. Although numerous evidences point to a central causative role of ANKRD11 in the neurologic features of these patients, their neurocognitive and behavior phenotypes are still poorly characterized. Herein, we report the complete neurological and psychiatric features observed in two patients with KBG syndrome due to ANKRD11 mutations. Both patients show intellectual disabilities, severe impairment in communication skills, deficits in several aspects of executive functions and working memory and anxious traits. Their features are compared with those of previously reported patients with KBG syndrome aiding in the delineation of neurocognitive phenotype associated to ANKRD11 mutations.

Subjective effects of racism and care: lives and memories of black women. / Efeitos subjetivos do racismo e cuidado: vivências e memórias de mulheres negras.

Understanding racism as an integral part of Brazilian reality, constituting a social determinant of the health-disease process, this article seeks to reflect on the impacts of racism on subjectivity and contemplate the health care offered to black women. The reflections derive from a qualitative study using the biographical method, in which black women provided a narrative of their lives and experiences with racism. The narratives give visibility to the negative effects of living systematically under structural racism in the self-images of the interviewed women, as well as the lack of and/or poor effectiveness of public policies of integral health care to transform the status quo.

Compreendendo que o racismo integra a realidade brasileira constituindo um determinante social do processo saúde-doença, este artigo procura refletir acerca dos efeitos do racismo na subjetividade e sobre o cuidado ofertado às mulheres negras. As reflexões derivam de uma pesquisa qualitativa, utilizando o método biográfico, em que mulheres negras narraram suas vidas e suas experiências com o racismo. As narrativas visibilizam os efeitos negativos das vivências sistemáticas do racismo estrutural nas imagens sobre si das mulheres ouvidas e a falta e/ou pouca efetivação das políticas públicas existentes de saúde integral para transformar o status quo.

Levetiracetam, from broad-spectrum use to precision prescription: A narrative review and expert opinion.

Levetiracetam (LEV) is an antiseizure medication (ASM) whose mechanism of action involves the modulation of neurotransmitters release through binding to the synaptic vesicle glycoprotein 2A. It is a broad-spectrum ASM displaying favorable pharmacokinetic and tolerability profiles. Since its introduction in 1999, it has been widely prescribed, becoming the first-line treatment for numerous epilepsy syndromes and clinical scenarios. However, this might have resulted in overuse. Increasing evidence, including the recently published SANAD II trials, suggests that other ASMs are reasonable therapeutic options for generalized and focal epilepsies. Not infrequently, these ASMs show better safety and effectiveness profiles compared to LEV (partially due to the latter's well-known cognitive and behavioral adverse effects, present in up to 20% of patients). Moreover, it has been shown that the underlying etiology of epilepsy is significantly linked to ASMs response in particular scenarios, highlighting the importance of an etiology-based ASM choice. In the case of LEV, it has demonstrated an optimal effectiveness in Alzheimer's disease, Down syndrome, and PCDH19-related epilepsies whereas, in other etiologies such as malformations of cortical development, it may show negligible effects. This narrative review analyzes the current evidence related to the use of LEV for the treatment of seizures. Illustrative clinical scenarios and practical decision-making approaches are also addressed, therefore aiming to define a rational use of this ASM.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

BACKGROUND: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). OBJECTIVES: Assess FSL2 accuracy in cats with hypoglycemia. ANIMALS: Nine healthy, purpose-bred cats. METHODS: Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). RESULTS: Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). CONCLUSIONS: Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.

Electric hand warmer versus observation to avoid discomfort during scalp cooling for chemotherapy-induced alopecia prevention: a randomized study.

Chemotherapy-induced alopecia (CIA) is a challenge in the management of cancer patients. Scalp cooling (SC) leads to reduction in CIA, however it is associated with significant adverse events, leading to 3-13% discontinuation rates. This pilot study evaluated the role of Electric Hand Warmers (EHW) on thermal (TC), sensorial (SCo) and general comfort (GC) in patients with breast cancer (BC) undergoing chemotherapy and SC to reduce CIA. Patients were randomly assigned to EHW use or observation. TC, SCo and GC were evaluated after each chemotherapy infusion. Favorable outcomes in both TC and SCo defined a positive result on GC. We analysed the impact of age, alopecia, chemotherapy regimen and EHW use in the different comfort scales using a Logistic Regression (LR) model. Forty women with early breast cancer were randomly assigned to EHW (n = 20) or observation (n = 20) during neo(adjuvant) chemotherapy. Median age was 53 years. In the EHW arm, favorable thermal response was reported by 79% versus 50% in the control arm (odds ratio [OR] 3.79, p < 0.001). SCo was satisfactory in 82% in the EHW arm versus 74% in the control arm (OR 1.62, p = 0.1). Overall, 73% in the EHW arm had favorable GC versus 44% in the control arm (OR 3.4, p < 0.001). Age, alopecia, and chemotherapy regimen did not impact on comfort measures. Conclusion: Our study suggests that the use of an EHW has a consistent favorable impact on TC and GC of BC patients under SC technology to prevent CIA.

Detecting anxiety symptoms in children and youths with neurofibromatosis type I.

Children with Neurofibromatosis type 1 (NF1) are known to have cognitive, social, and behavioral deficits. Fifteen NF1-subjects (5 boys, 10 girls, mean age = 13.4), and 15 healthy controls matched for age and sex were assessed on the presence of anxiety symptoms, using the Multidimensional Anxiety Scale for Children (MASC), self-report questionnaire. Significant group differences emerged with regard to MASC total (Z = -2.058, P = 0.041) and anxiety disorder index (ADI; Z = -2.202, P = 0.026), but not with regard to single scales. When the severity and visibility of NF1 were considered, correlation between severity and social anxiety, and severity and MASC total was found. This is the first study assessing anxiety symptoms in NF1 children and youths. A precocious psychological survey and intervention in NF1 subjects, may contribute to reduce the risk of psychiatric disorders in adulthood.

"We All Get Raped": Sexual Violence Against Latin American Women in Migratory Transit in Mexico.

The article addresses some forms of sexual violence suffered by Latin American women during migratory transit through Mexico. In-depth, semi-structured, qualitative-phenomenological interviews were conducted with 10 women in different stages of major transmigration states. The findings demonstrate the ubiquity of sexual violence during the migration. Five themes were identified: (a) The migration dimension of "being a woman"; (b) Recognition of contextual factors associated with the migratory process: "Intermediaries, road, shelters and sisterhood"; (c) The costs of migration: Abuse, discrimination, and persecution: "Criminal groups, physical violence, and "La Bestia"; (d) Triggers and supports: "Escape and future expectations"; and (e) God as a support.

Self-directed video versus instructor-based neonatal resuscitation training: a randomized controlled blinded non-inferiority multicenter international study.

OBJECTIVE: To compare the efficacy of video-assisted self-directed neonatal resuscitation skills course with video-assisted facilitator-led course. METHODS: This multicenter, randomized, blinded, non-inferiority-controlled trial compared two methods of teaching basic neonatal resuscitation skills using mask ventilation. Groups of novice providers watched an instructional video. One group received instructor facilitation (Ins-Video). The other group did not (Self-Video). An Objective Structured Clinical Exam (OSCE) measured skills performance, and a written test gauged knowledge. RESULTS: One hundred and thirty-four students completed the study. Sixty-three of 68 in the Self-Video Group (92.6%) and 59 of 66 in the Ins-Video Group (89.4%) achieved post-training competency in positive pressure ventilation (primary outcome). OSCE passing rates were low in both groups. Knowledge survey scores were comparable between groups and non-inferior. CONCLUSIONS: Video self-instruction taught novice providers positive pressure ventilation skills and theoretical knowledge, but it was insufficient for mastery of basic neonatal resuscitation in simulation environment.

How Long Does a Neutrophil Live?-The Effect of 24 h Whole Blood Storage on Neutrophil Functions in Pigs.

Neutrophils are important effector cells of the innate immune system, traditionally regarded to have a short life span. The goal of this study was to evaluate the effect of the whole blood storage on neutrophil functions, e.g., viability, antimicrobial effect, neutrophil extracellular trap (NET) formation and phagocytosis. Therefore, fresh porcine whole blood was compared to whole blood stored for 24 h in the dark at room temperature. Different cell parameters in whole blood and in isolated neutrophils were analyzed. The following parameters were analyzed: cell count, band and segmented neutrophil count, viability, cholesterol content, release of free DNA as a marker for cell death, phagocytic activity in whole blood and in isolated neutrophils, the transmigration rate of neutrophils to IL8 stimulus, the production of reactive oxygen species (ROS), and the formation of NETs. It was observed that the number of isolated neutrophils decreased over time, indicating cell death occurs during 24 h of blood storage. However, the surviving neutrophils isolated from stored blood reacted comparably or even showed enhanced antimicrobial activity in the case of phagocytosis of Streptococcus (S.) suis, ROS production, and transmigration. The slightly altered cholesterol level of the harvested neutrophils in stored blood when compared to fresh blood partially explains some of the detected differences.

Regional variability in reproductive traits of the Acropora hyacinthus species complex in the Western Pacific Region.

Understanding natural variations in the life history traits of reef-building corals under different environmental conditions is an area of active research. This study compares variability in the reproductive and genetic traits of the hermaphroditic broadcast spawning coral Acropora hyacinthus, from the Western Pacific Region, across six different latitudes [Japan (33° and 31°N), Taiwan (23°, 22° and 21°N), and Indonesia (5°S)]. Egg sizes among corals in the lowest latitude studied were significantly larger than those at high latitudes, while the mean number of eggs were significantly different only among high latitude and two out of the three mid latitude locations studied. Egg numbers were significantly negatively correlated with egg and testis volumes, indicating reproductive trade-offs across locations. Female gonad volumes were smaller at high latitudes but significantly larger at lower latitudes, being positively correlated with seawater temperatures. Furthermore, high genetic similarities among populations suggest active gene flow among low-, mid- and high-latitude locations. An exception to this trend, the mid-latitude location of Penghu (off western Taiwan) formed an independent group with highly similar genetic and reproductive traits, suggesting reproductive isolation with local adaptations. This study reports natural spatial variations in the reproductive traits of A. hyacinthus at different latitudinal locations, which may serve as baseline information to predict how the life histories of corals in general respond to the impacts of climate change.

Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

Utopia interditada: APS como antídoto contra a desdemocratização e a necropolítica neoliberal / Interdicted utopia: PHC as an antidote against de-democratization and neoliberal necropolitics

RESUMO Este ensaio reflete sobre o desmonte de uma Atenção Primária à Saúde (APS) abrangente como etapa fundamental à desdemocratização que avança a passos largos no Brasil e no mundo nos últimos anos, sendo condição de possibilidade da consolidação de uma necropolítica neoliberal que busca se institucionalizar e silenciar quaisquer potências de vida. Ao mesmo tempo, este texto reafirma também que é por meio mesmo da APS que se pode inflexionar o timão - alterando a rota da barbárie para a qual se navega - em direção à utopia inspiradora do Sistema Único de Saúde e ao seu projeto civilizatório solidário e cidadão. Considerados os atributos e as diretrizes que fundam e organizam a APS brasileira e a concertação de vozes que enseja, esta reflexão propõe, por fim, que seja ali uma trincheira estratégica na luta para investir em uma sociedade efetivamente democrática, em que todos se reconheçam e afirmem como sujeitos políticos e de direitos em defesa da vida.

ABSTRACT This essay reflects on the dismantling of a comprehensive Primary Health Care (PHC) as a fundamental step in the de-democratization that has advanced in large steps both in Brazil and in the world in recent years. It asserts that this process is one of the conditions for the consolidation of a neoliberal necropolitics that seeks to institutionalize and silence any life potencies. At the same time, this text also reaffirms that it is through PHC itself that the helm can be inflected - altering the barbarism route to which we navigate - towards the inspiring utopia of the Unified Health System (SUS) and its solidary and citizen civilization project. Considering the attributes and guidelines that found and organize the Brazilian PHC and the concertation of voices that it entails, this reflection proposes, lastly, that PHC can be a strategic trench in the struggle to invest in an effectively democratic society, in which everyone recognizes and affirms themselves as political subjects, subjects who have rights, in defense of life.