Vaccination status among COVID-19 patients and duration of Polymerase Chain Reaction test positivity: evaluation of immunization schedule and type of vaccine.

Background: The introduction of the vaccine against SARS-CoV-2 has represented a cornerstone in the containment of the pandemic. Our aim was to assess the vaccination schedules in relation to the infection free interval and to the duration of positivity in case of infection. Study design: This study involves the SARS-CoV-2 infected people managed by the Local Health Authority ASL 1 Abruzzo. The data collected included: vaccine administration date, vaccine type, information on the Polymerase Chain Reaction test positivity, and demographic variables, such as age and sex. Methods: The duration of Polymerase Chain Reaction test positivity was assessed in relation to the vaccination status, the vaccine type and the time interval between the last vaccination dose and the first nasopharyngeal positive swab over the considered period. Results: The infection duration (DAYS) was significantly shorter in subjects vaccinated with a booster dose than unvaccinated subjects (12.8 vs 14.6; p<0.0001) and subjects vaccinated with the primary series only (12.8 vs 14.1; p<0.0001). Duration of PCR positivity was shorter with heterologous immunisation than with other vaccination schedules (p=0.0317). Conclusions: This study highlights, in a large cohort of patients, the association between vaccination schedule and the response to infection.

Central role for hydrogen peroxide in P2Y1 ADP receptor-mediated cellular responses in vascular endothelium.

ADP activates a family of cell surface receptors that modulate signaling pathways in a broad range of cells. ADP receptor antagonists are widely used to treat cardiovascular disease states. These studies identify a critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) in mediating cellular responses activated by the G protein-coupled P2Y1 receptor for ADP. We found that ADP-dependent phosphorylation of key endothelial signaling proteins--including endothelial nitric oxide synthase, AMP-activated protein kinase, and the actin-binding MARCKS protein--was blocked by preincubation with PEG-catalase, which degrades H2O2. ADP treatment promoted the H2O2-dependent phosphorylation of c-Abl, a nonreceptor tyrosine kinase that modulates the actin cytoskeleton. Cellular imaging experiments using fluorescence resonance energy transfer-based biosensors revealed that ADP-stimulated activation of the cytoskeleton-associated small GTPase Rac1 was independent of H2O2. However, Rac1-dependent activation of AMP-activated protein kinase, the signaling phospholipid phosphatidylinositol-(4, 5)-bisphosphate, and the c-Abl-interacting protein CrkII are mediated by H2O2. We transfected endothelial cells with differentially targeted HyPer2 H2O2 biosensors and found that ADP promoted a marked increase in H2O2 levels in the cytosol and caveolae, and a smaller increase in mitochondria. We performed a screen for P2Y1 receptor-mediated receptor tyrosine kinase transactivation and discovered that ADP transactivates Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine kinase expressed in these cells. Our observation that P2Y1 receptor-mediated responses involve Flt3 transactivation may identify a unique mechanism whereby cancer chemotherapy with receptor tyrosine kinase inhibitors promotes vascular dysfunction. Taken together, these findings establish a critical role for endogenous H2O2 in control of ADP-mediated signaling responses in the vascular wall.

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance.

Immune cell trafficking requires the frequent breaching of the endothelial barrier either directly through individual cells ('transcellular' route) or through the inter-endothelial junctions ('paracellular' route). What determines the loci or route of breaching events is an open question with important implications for overall barrier regulation. We hypothesized that basic biomechanical properties of the endothelium might serve as crucial determinants of this process. By altering junctional integrity, cytoskeletal morphology and, consequently, local endothelial cell stiffness of different vascular beds, we could modify the preferred route of diapedesis. In particular, high barrier function was associated with predominantly transcellular migration, whereas negative modulation of junctional integrity resulted in a switch to paracellular diapedesis. Furthermore, we showed that lymphocytes dynamically probe the underlying endothelium by extending invadosome-like protrusions (ILPs) into its surface that deform the nuclear lamina, distort actin filaments and ultimately breach the barrier. Fluorescence imaging and pharmacologic depletion of F-actin demonstrated that lymphocyte barrier breaching efficiency was inversely correlated with local endothelial F-actin density and stiffness. Taken together, these data support the hypothesis that lymphocytes are guided by the mechanical 'path of least resistance' as they transverse the endothelium, a process we term 'tenertaxis'.

ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling.

BACKGROUND: Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. RESULTS: In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. CONCLUSIONS: These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.

Novel role of CD47 in rat microvascular endothelium: signaling and regulation of T-cell transendothelial migration.

OBJECTIVE: Although endothelial CD47, a member of the immunoglobulin superfamily, has been implicated in leukocyte diapedesis, its capacity for intracellular signaling and physical localization during this process has not been addressed in detail. This study examined endothelial CD47 spatiotemporal behavior and signaling pathways involved in regulating T-cell transendothelial migration. APPROACH AND RESULTS: By biochemical methods, transmigration assays, and live-cell microscopy techniques, we show that endothelial CD47 engagement results in intracellular calcium mobilization, increased permeability, and activation of Src and AKT1/phosphoinositide 3-kinase in brain microvascular endothelial cells. These signaling pathways converge to induce cytoskeleton remodeling and vascular endothelial cadherin phosphorylation, which are necessary steps during T-cell transendothelial migration. In addition, during T-cell migration, transmigratory cups and podo-prints enriched in CD47 appear on the surface of the endothelium, indicating that the spatial distribution of CD47 changes after its engagement. Consistent with previous findings of intercellular adhesion molecule 1, blockade of CD47 results in decreased T-cell transmigration across microvascular endothelium. The overlapping effect of intercellular adhesion molecule 1 and CD47 suggests their involvement in different steps of the diapedesis process. CONCLUSIONS: These data reveal a novel role for CD47-mediated signaling in the control of the molecular network governing endothelial-dependent T-cell diapedesis.

Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells.

Adaptive immunity requires that T cells efficiently scan diverse cell surfaces to identify cognate Ag. However, the basic cellular mechanisms remain unclear. In this study, we investigated this process using vascular endothelial cells, APCs that possess a unique and extremely advantageous, planar morphology. High-resolution imaging revealed that CD4 memory/effector T cells dynamically probe the endothelium by extending submicron-scale, actin-rich "invadosome/podosome-like protrusions" (ILPs). The intimate intercellular contacts enforced by ILPs consistently preceded and supported T cell activation in response to endothelial MHC class II/Ag. The resulting calcium flux stabilized dense arrays of ILPs (each enriched in TCR, protein kinase C-θ, ZAP70, phosphotyrosine, and HS1), forming what we term a podo-synapse. Similar findings were made using CD8 CTLs on endothelium. Furthermore, careful re-examination of both traditional APC models and professional APCs suggests broad relevance for ILPs in facilitating Ag recognition. Together, our results indicate that ILPs function as sensory organelles that serve as actuators of immune surveillance.

Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults.

Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better understanding of sepsis pathophysiology and increase the usefulness of soluble adhesion molecules as diagnostic and predictive biomarkers.

Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-α-activated endothelial cells via both leukocyte-like and novel mechanisms.

Systemically administered adult mesenchymal stem cells (MSCs), which are being explored in clinical trials to treat inflammatory disease, exhibit the critical ability to extravasate at sites of inflammation. We aimed to characterize the basic cellular processes mediating this extravasation and compare them to those involved in leukocyte transmigration. Using high-resolution confocal and dynamic microscopy, we show that, like leukocytes, human bone marrow-derived MSC preferentially adhere to and migrate across tumor necrosis factor-α-activated endothelium in a vascular cell adhesion molecule-1 (VCAM-1) and G-protein-coupled receptor signaling-dependent manner. As several studies have suggested, we observed that a fraction of MSC was integrated into endothelium. In addition, we observed two modes of transmigration not previously observed for MSC: Paracellular (between endothelial cells) and transcellular (directly through individual endothelial cells) diapedesis through discrete gaps and pores in the endothelial monolayer, in association with VCAM-1-enriched "transmigratory cups". Contrasting leukocytes, MSC transmigration was not preceded by significant lateral migration and occurred on the time scale of hours rather than minutes. Interestingly, rather than lamellipodia and invadosomes, MSC exhibited nonapoptotic membrane blebbing activity that was similar to activities previously described for metastatic tumor and embryonic germ cells. Our studies suggest that low avidity binding between endothelium and MSC may grant a permissive environment for MSC blebbing. MSC blebbing was associated with early stages of transmigration, in which blebs could exert forces on underlying endothelial cells indicating potential functioning in breaching the endothelium. Collectively, our data suggest that MSC transmigrate actively into inflamed tissues via both leukocyte-like and novel mechanisms.

Protocol for density gradient neutrophil isolation and flow cytometry-based characterization from human peripheral blood.

Neutrophils are the first immune responders to bacterial or viral infection and play key roles in the host immune response; however, handling and investigating fresh neutrophils can be challenging. Here, we present a protocol for isolating neutrophils from the peripheral blood of healthy donors using density gradient separation method. We describe steps for morphology analysis by cytospin and immunophenotyping by flow cytometry analysis. This protocol can be used for the isolation of neutrophils from healthy and diseased individuals. For complete details on the use and execution of this protocol, please refer to Parthasarathy et al.1.

Association between tongue, lips position and breathing in newborns. / Associação entre posição de língua, lábios e respiração em recém-nascidos.

PURPOSE: To verify the association between breathing nasal expiratory flow and posture of lips and tongue at rest, presence of repeated forward movements of the tongue and maternal complaint of respiratory difficulty in the newborn in the first days of life. METHOD: A observational study was carried out in 130 babies, in a university hospital. Included newborn with Apgar score greater than or equal to 8 in exclusive breast milk. It was the following data: position of lips and tongue at rest, nasal expiratory flow and maternal complaint of difficulty in breathing in the newborn. The data were subjected to statistical analysis using the tests, Fisher's exact test and the Chi-Square test, adopting a significance level of 5% . RESULTS: there was a significant association between maternal complaint of newborn difficulty breathing with repeated forward tongue movements and nasal expiratory flow; tongue position with resting lips position at rest, repeated tongue forward movements with nasal expiratory flow and tongue position at rest; nasal expiratory flow exit with tongue position at rest. CONCLUSION: Symmetrical nasal expiratory flow is associated with an elevated tongue position and closed lips at rest; on the other hand, increased and/or absent nasal expiatory flow in one nostril is associated with maternal complaints of difficulty in breathing, open/ half-open lips position and low tongue position during rest, as well as, repeated forward tongue movements.

OBJETIVO: verificar a associação entre fluxo expiratório nasal e postura de lábios e língua no repouso, presença de movimentos repetidos de anteriorização de língua e queixa materna de dificuldade respiratória do recém-nascido nos primeiros dias de vida. MÉTODO: estudo observacional, realizado com 130 recém-nascidos do alojamento conjunto de um hospital Universitário. Foram incluídos recém-nascidos a termo, com idade entre 1 e 5 dias de vida, APGAR maior ou igual a oito, em aleitamento materno exclusivo. Foram coletados os seguintes dados: posição de lábios e língua no repouso, fluxo expiratório nasal, presença de movimentos repetidos de anteriorização de língua e queixa materna de dificuldade do recém-nascido para respirar. Os dados foram submetidos à análise estatística, sendo aplicado o Teste Exato de Fisher e o Qui-Quadrado, adotando-se o nível de significância de 5%. RESULTADOS: Há uma associação significativa entre queixas maternas de dificuldade do recém-nascido para respirar pelo nariz com movimentos repetidos de anteriorização de língua e fluxo expiratório nasal; posição de língua com posição de lábios no repouso, movimentos repetidos de anteriorização de língua com fluxo expiratório nasal e posição de língua no repouso; fluxo expiratório nasal com posição de língua no repouso. CONCLUSÃO: O fluxo expiratório nasal simétrico está associado com a posição de língua elevada e lábios fechados no REPOUSO; por outro lado, o fluxo expiratório nasal maior e/ou ausente em uma narina está associado com queixa materna de dificuldade do recém-nascido para respirar, posição de lábios abertos/entreabertos E posição de língua baixa no repouso, bem como, com movimentos repetidos de anteriorização de língua.

Ankyloglossia in Monochorionic Diamniotic and Dichorionic Diamniotic Twins: A Cross-Sectional Study.

Objective: To determine the prevalence of ankyloglossia in diamniotic monochorionic and diamniotic dichorionic twins, as well as to verify the relationship between gender and type of pregnancy. Study Design: A cross-sectional observational study, carried out with 52 pairs of dichorionic/diamniotic twins and 49 monochorionic/diamniotic pairs. The data collection was carried out through the analysis of medical records and the results of the Neonatal Screening of the Tongue Frenulum Assessment Protocol in Babies, and corresponded to the period of 2 years (2020-2022). Statistical analysis of data was performed, considering the significance value of 5%. The study was approved by the Human Research Ethics Committee of the institution. Results: The statistical analysis of multiple logistic regression between the two groups of twins (Mono/Di and Di/Di) according to the socioeconomic, demographic, and clinical-epidemiological profile was statistically significant for some variables. The prevalence of ankyloglossia, according to the type of twin pregnancy, showed a statistically significant difference. There was no statistical difference in relation to sex and ankyloglossia, or between couples diagnosed with ankyloglossia according to the type of pregnancy. Conclusion: Monochorionic/diamniotic twins had a higher prevalence of ankyloglossia, regardless of gender.

Effects of lingual frenotomy on breastfeeding and electrical activity of the masseter and suprahyoid muscles.

PURPOSE: To analyze the effects of lingual frenotomy on the breastfeeding of infants, based on the electrical activity of the masseter and suprahyoid muscles and assessment of the breastfeeding. METHODS: Observational study developed between October 2017 and June 2018 with a sample of 20 newborns and infants who attended a dental clinic and were diagnosed with ankyloglossia. Another 20 were excluded for meeting some of the following exclusion criteria: babies more than 6 months old, who were not on exclusive or mixed breastfeeding, who had other clinical impairments that interfered with breastfeeding, who had other foods introduced into their diet, who had neurological changes and/or craniofacial deformities, and/or who did not finish all the stages of the study. Breastfeeding was assessed with the UNICEF Breastfeeding Assessment and Observation Protocol, while the muscle electrical activity was assessed with the Electrical Activity Assessment Protocol for the Masseter and Suprahyoid Muscles in Newborns During Breastfeeding. The same speech-language-hearing therapist conducted the two assessments both before the conventional frenotomy and 7 days after it. RESULTS: The signs suggestive of breastfeeding difficulties changed 7 days after the surgery, with a p-value ≤ 0.002 for general observation of the mother, position of the infant, latch, and sucking. The maximum voluntary contraction of the masseter was the only integral parameter with a difference, as the electrical activity had decreased. CONCLUSION: Behaviors favorable to breastfeeding increased 7 days after the frenotomy in all the breastfeeding assessment categories, whereas the electrical activity of the masseter decreased.

Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.

p120-Catenin prevents neutrophil transmigration independently of RhoA inhibition by impairing Src dependent VE-cadherin phosphorylation.

Leukocyte transendothelial migration (TEM) is regulated by several signaling pathways including Src family kinases (SFK) and the small RhoGTPases. Previous studies have shown that vascular endothelial-cadherin (VE-cad) forms a complex with ß-,γ-, and p120-catenins and this complex disassociates to form a transient gap during leukocyte TEM. Additionally, p120-catenin (p120-1A) overexpression in human umbilical vein endothelial cells (HUVEC) stabilizes VE-cad surface expression, prevents tyrosine phosphorylation of VE-cad, and inhibits leukocyte TEM. Based on reports showing that p120 overexpression in fibroblasts or epithelial cells inhibits RhoA and activates Rac and Cdc42 GTPases, and on other reports showing that RhoA activation in endothelial cells is necessary for leukocyte TEM, we reasoned that p120 overexpression inhibited TEM through inhibition of RhoA. To test this idea, we overexpressed a mutant p120 isoform, p120-4A, which does not interact with RhoA. p120-4A colocalized with VE-cad in HUVEC junctions and enhanced VE-cad surface expression, similar to overexpression of p120-1A. Interestingly, overexpression of either p120-4A or p120-1A dramatically blocked TEM, and overexpression of p120-1A in HUVEC did not affect RhoA basal activity or activation of RhoA and Rac induced by thrombin or ICAM-1 crosslinking. In contrast, biochemical studies revealed that overexpression of p120-1A reduced activated pY416-Src association with VE-cad. In summary, p120 overexpression inhibits neutrophil TEM independently of an effect on RhoA or Rac and instead blocks TEM by preventing VE-cad tyrosine phosphorylation and association of active Src with the VE-cad complex.

Lingual frenulum protocol with scores for infants.

An experimental protocol model for frenulum evaluation was first designed, and administered to ten infants in 2010. After obtaining the data and statistical analysis, the protocol was re-designed and administered to 100 infants. The aim of this study is to present an efficient and effective lingual frenulum protocol with scores for infants. From the experimental protocol model, a new protocol was designed. One speech-language pathologist, and specialist in orofacial myology, administered the new protocol to 100 full-term infants. All steps of the protocol were recorded and photographed. The data collected was sent to two specialists in the area, who evaluated the cases based on the recordings and photographs. The data from the three evaluations were compared. A two-part protocol was designed to evaluate the lingual frenulum in infants. The first part consists of clinical history with specific questions about family history and breastfeeding. The second part consists of clinical examination: anatomo-functional, non-nutritive and nutritive sucking evaluations. A new lingual frenulum protocol with scores for infants was designed, and has proved to be an effective tool for health professionals to assess and diagnose anatomical alterations of the lingual frenulum, and its possible interference with breastfeeding.

Anthropometric orofacial measures of newborns and their relationship with sex, weight and height. / Medidas antropométricas orofaciais de recém-nascidos e sua relação com sexo, peso e altura.

PURPOSE: To compare orofacial anthropometric measurements, with weight, height and sex of newborns. METHODS: Observational cross-sectional study carried out with 130 newborns on exclusive breastfeeding. Data collection was performed by properly trained and calibrated speech therapists. The orofacial measurements of the newborns were performed with flexible and transparent ruler 10 cm long, in the following segments: heights of the upper third(tr-g), the middle third(g-sn) and the lower third on the face (sn-gn); filter height (sn-Is), distance between the corner of the eye and the labial commissure on the right and left side (ex-ch). Weight and height measurements were collected from the newborns' medical records. The data were submitted to statistical analysis, using the Mann-Whitney test, adopting a significance level of 5%. RESULTS: Of the 130 newborns, 61 were male and 69 female. The median weight was 3.3 kg and the median height was 49 cm. There was significant difference between weight and measurement distance between the corner of the eye and the left and right labial commissure (ex-ch). There was no significant difference in orofacial measurements with sex and height. CONCLUSION: There was no difference in orofacial anthropometric measurements of full-term newborns when compared with sex and height; however, when compared to weight, there is a difference in the measurements of the distance between the corner of the eye and the labial commissure on the right and left side.

OBJETIVO: Comparar as medidas antropométricas orofaciais, com peso, altura e sexo de recém-nascidos. MÉTODO: Estudo transversal observacional realizado com 130 recém-nascidos em aleitamento materno exclusivo. A coleta de dados foi realizada por fonoaudiólogas devidamente treinadas e calibradas. As medidas orofaciais dos recém-nascidos foram realizadas com uma régua maleável e transparente de 10 cm de comprimento, nos seguintes segmentos: alturas do terço superior (tr-g), do terço médio (g-sn) e do terço inferior da face (sn-gn); altura do filtro (sn-Is); distância entre o canto do olho e a comissura labial do lado direito e esquerdo (ex-ch). A medida do peso e da altura foram coletadas nos prontuários dos recém-nascidos. Os dados foram submetidos à análise estatística, sendo aplicado o teste de Mann-Whitney, adotando nível de significância de 5%. RESULTADOS: Dos 130 recém-nascidos, 61 eram do sexo masculino e 69 do sexo feminino. A mediana do peso foi de 3,3 kg e da altura de 49 cm. Houve diferença significativa entre o peso e a medida da distância entre o canto do olho e a comissura labial do lado direito e esquerdo (ex-ch). Não foi encontrada diferença significativa das medidas orofaciais com sexo e altura. CONCLUSÃO: Não houve diferença nas medidas antropométricas orofaciais de recém-nascidos a termo quando comparadas com sexo e altura; porém, quando comparadas com peso, há diferença nas medidas da distância entre o canto do olho e a comissura labial do lado direito e esquerdo.

The impact of DAMP-mediated inflammation in severe COVID-19 and related disorders.

The host response to SARS-CoV-2, the virus that causes COVID-19, is highly heterogeneous, ranging from mild/asymptomatic to severe. The moderate to severe forms of COVID-19 often require hospitalization, are associated with a high rate of mortality, and appear to be caused by an inappropriately exaggerated inflammatory response to the virus. Emerging data confirm the involvement of both innate and adaptive immune pathways both in protection from SARS-CoV-2, and in driving the pathology of severe COVID-19. In particular, innate immune cells including neutrophils appear to be key players in the inflammation that causes the vicious cycle of damage and inflammation that underlies the symptomatology of severe COVID-19. Several recent studies support a link between damage and inflammation, with damage-associated molecular patterns (DAMPs) playing a key role in the pathology of severe COVID-19. In this review, we put into perspective the role of DAMPs and of components of the DAMP-signaling cascade, including Siglecs and their cognate ligands CD24 and CD52, in COVID-19. Further, we review clinical data on proposed therapeutics targeting DAMP pathways to treat SARS-CoV-2 infection and the regulation of these signaling cascades in COVID-19. We also discuss the potential impact of DAMP-mediated inflammation in other indications related to COVID-19, such as ARDS, endothelial dysfunction, hypercoagulation, and sepsis.

Effect of Lingual Frenotomy on Tongue and Lip Rest Position: A Nonrandomized Clinical Trial.

Introduction The tongue plays an important role in the development of craniofacial structures. At rest, the light and constant pressure of the tongue against the hard palate, counterbalanced by the pressure provided by proper lip sealing, serves as a guide for maxillary growth. Ankyloglossia makes tongue coupling against the hard palate difficult, impacting maxillary development, which may lead to breathing disorders. Objective To verify the effect of lingual frenotomy on the resting position of the tongue and lips in infants with ankyloglossia. Methods The sample consisted of 334 infants aged between 1 and 60 days old diagnosed with ankyloglossia. The groups were divided in: a) experimental group (EG), which consisted of infants whose mothers agreed with lingual frenotomy; b) control group (CG), which consisted of infants whose mothers either refused lingual frenotomy or were waiting for surgery. Both the position of the lips and of the tongue at rest were assessed while the infants were sleeping during the quiet sleep phase. For mothers who refused their infants to undergo the surgical procedure, a follow-up of the infants was proposed to verify possible interference of the frenulum with the resting position of the tongue and lips. Infants whose mothers agreed with surgery were referred for lingual frenotomy. Results Regarding the position of the tongue and lips at rest at the initial and final assessments, the statistical analysis demonstrated significant differences between both groups. Conclusion Lingual frenotomy enabled infants diagnosed with ankyloglossia to maintain both tongue coupling against the hard palate and closed lips at rest.

Position of lips and tongue in rest in newborns with and without ankyloglossia.

PURPOSE: Verify the position of lips and tongue at rest in newborns with and without ankyloglossia. METHODS: Cross-sectional study, carried out with 130 newborns in University Hospital. Data collection was performed by the researcher and speech-language pathologists from the Hospital. Information on gestational age, sex, weight, height and days of life was collected. The position of the lips and tongue at rest was evaluated through visual inspection with the newborns asleep. After the newborns were awakened, Neonatal Screening of the validated Protocol for the evaluation of the lingual frenulum for infants was performed to detect the alteration of the lingual frenulum. The data obtained were described and submitted to statistical analysis using the Chi-Square test to verify the association between the position of the lips with the tongue and to compare the position of the lips and tongue with and without ankyloglossia. The Mann-Whitney test was used to verify the behavior of the variables the differed between newborns with and without ankyloglossia. The significance level of 5% was adopted. RESULTS: When comparing the data, a significant difference was found between: weight and height with and without ankyloglossia; position of lips and tongue. An association between the position of the tongue and lips with and without ankyloglossia was also found. CONCLUSION: Newborns without alteration of the lingual frenulum have a tendency to remain with their lips closed and their tongue elevated during rest and newborns with ankyloglossia have a tendency to keep their lips parted and their tongue low during rest.