Limited impact of cancer-derived gangliosides on anti-tumor immunity in colorectal cancer.

Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance.

ß cell acetate production and release are negligible.

BACKGROUND: Studies suggest that short chain fatty acids (SCFAs), which are primarily produced from fermentation of fiber, regulate insulin secretion through free fatty acid receptors 2 and 3 (FFA2 and FFA3). As these are G-protein coupled receptors (GPCRs), they have potential therapeutic value as targets for treating type 2 diabetes (T2D). The exact mechanism by which these receptors regulate insulin secretion and other aspects of pancreatic ß cell function is unclear. It has been reported that glucose-dependent release of acetate from pancreatic ß cells negatively regulates glucose stimulated insulin secretion. While these data raise the possibility of acetate's potential autocrine action on these receptors, these findings have not been independently confirmed, and multiple concerns exist with this observation, particularly the lack of specificity and precision of the acetate detection methodology used. METHODS: Using Min6 cells and mouse islets, we assessed acetate and pyruvate production and secretion in response to different glucose concentrations, via liquid chromatography mass spectrometry. RESULTS: Using Min6 cells and mouse islets, we showed that both intracellular pyruvate and acetate increased with high glucose conditions; however, intracellular acetate level increased only slightly and exclusively in Min6 cells but not in the islets. Further, extracellular acetate levels were not affected by the concentration of glucose in the incubation medium of either Min6 cells or islets. CONCLUSIONS: Our findings do not substantiate the glucose-dependent release of acetate from pancreatic ß cells, and therefore, invalidate the possibility of an autocrine inhibitory effect on glucose stimulated insulin secretion.

Unraveling the Sweet Secrets of HCC: Glucometabolic Rewiring in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer. It causes ∼ 800 000 deaths per year, which is expected to increase due to increasing rates of obesity and metabolic dysfunction associated steatotic liver disease (MASLD). Current therapies include immune checkpoint inhibitors, tyrosine kinase inhibitors, and monoclonal antibodies, but these therapies are not satisfactorily effective and often come with multiple side effects and recurrences. Metabolic reprogramming plays a significant role in HCC progression and is often conserved between tumor types. Thus, targeting rewired metabolic pathways could provide an attractive option for targeting tumor cells alone or in conjunction with existing treatments. Therefore, there is an urgent need to identify novel targets involved in cancer-mediated metabolic reprogramming in HCC. In this review, we provide an overview of molecular rewiring and metabolic reprogramming of glucose metabolism in HCC to understand better the concepts that might widen the therapeutic window against this deadly cancer.

Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC. METHOD: In this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40. RESULT: The absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4+ and CD8+ T cells in the TME, and reduced frequencies of CD4+ regulatory T cells (Tregs) within the T-cell population. Importantly, CD8+ T cells were able to infiltrate the tumor islands in sialic acid-deficient tumors. These favorable alterations in the immune landscape sensitized sialic acid-deficient tumors to immunotherapy, which was ineffective in sialic acid-expressing KPC3 tumors. In addition, high expression of sialylation-related genes in human pancreatic cancer correlated with decreased CD8+ T-cell infiltration, increased presence of Tregs, and poorer survival probability. CONCLUSION: Our results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.

Violence and Related Health Outcomes in Sexual and Gender Minority Communities: Introduction to the Special Issue.

Violence affects every community but is particularly prevalent among sexual and gender minority (SGM) people. Although research on violence within SGM populations is increasing, knowledge gaps remain that limit development of evidence-based policy, prevention, and intervention efforts to reduce the violence disparities the SGM community faces. In 2021, the National Institutes of Health (NIH) hosted a multiphase scientific workshop to identify and prioritize key research needs to further our understanding of violence affecting SGM communities and its health outcomes. In this perspective, we summarize the research needs identified. NIH supports this special issue as an outcome of the scientific workshop.

Current state-of-the-art on ganglioside-mediated immune modulation in the tumor microenvironment.

Gangliosides are sialylated glycolipids, mainly present at the cell surface membrane, involved in a variety of cellular signaling events. During malignant transformation, the composition of these glycosphingolipids is altered, leading to structural and functional changes, which are often negatively correlated to patient survival. Cancer cells have the ability to shed gangliosides into the tumor microenvironment, where they have a strong impact on anti-tumor immunity and promote tumor progression. Since most ganglioside species show prominent immunosuppressive activities, they might be considered checkpoint molecules released to counteract ongoing immunosurveillance. In this review, we highlight the current state-of-the-art on the ganglioside-mediated immunomodulation, specified for the different immune cells and individual gangliosides. In addition, we address the dual role that certain gangliosides play in the tumor microenvironment. Even though some ganglioside species have been more extensively studied than others, they are proven to contribute to the defense mechanisms of the tumor and should be regarded as promising therapeutic targets for inclusion in future immunotherapy regimens.

Accuracy of a Computer-Aided Dynamic Navigation System in the Placement of Zygomatic Dental Implants: An In Vitro Study.

The objective of this in vitro study was to evaluate and compare the accuracy of zygomatic dental implant (ZI) placement carried out using a dynamic navigation system. Materials and Methods: Forty (40) ZIs were randomly distributed into one of two study groups: (A) ZI placement via a computer-aided dynamic navigation system (n = 20) (navigation implant (NI)); and (B) ZI placement using a conventional free-hand technique (n = 20) (free-hand implant (FHI)). A cone-beam computed tomography (CBCT) scan of the existing situation was performed preoperatively to plan the surgical approach for the computer-aided study group. Four zygomatic dental implants were placed in anatomically based polyurethane models (n = 10) manufactured by stereolithography, and a postoperative CBCT scan was performed. Subsequently, the preoperative planning and postoperative CBCT scans were added to dental implant software to analyze the coronal entry point, apical end point, and angular deviations. Results were analyzed using the Student's t-test. Results: The results showed statistically significant differences in the apical end-point deviations between FHI and NI (p = 0.0018); however, no statistically significant differences were shown in the coronal entry point (p = 0.2617) or in the angular deviations (p = 0.3132). Furthermore, ZIs placed in the posterior region showed more deviations than the anterior region at the coronal entry point, apical end point, and angular level. Conclusions: The conventional free-hand technique enabled more accurate placement of ZIs than the computer-assisted surgical technique. In addition, placement of ZIs in the anterior region was more accurate than that in the posterior region.

Diversity and composition of macroinvertebrate communities in a rare inland salt marsh.

Inland salt marshes are rare habitats in the Great Lakes region of North America, formed on salt deposits from the Silurian period. These patchy habitats are abiotically stressful for the freshwater invertebrates that live there, and provide an opportunity to study the relationship between stress and diversity. We used morphological and COI metabarcoding data to assess changes in diversity and composition across both space (a transect from the salt seep to an adjacent freshwater area) and time (three sampling seasons). Richness was significantly lower at the seep site with both datatypes, while metabarcoding data additionally showed reduced richness at the freshwater transect end, consistent with a pattern where intermediate levels of stress show higher diversity. We found complementary, rather than redundant, patterns of community composition using the two datatypes: not all taxa were equally sequenced with the metabarcoding protocol. We identified taxa that are abundant at the salt seep of the marsh, including biting midges (Culicoides) and ostracods (Heterocypris). We conclude that (as found in other studies) molecular and morphological work should be used in tandem to identify the biodiversity in this rare habitat. Additionally, salinity may be a driver of community membership in this system, though further ecological research is needed to rule out alternate hypotheses.

Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells.

Autotaxin (ATX; ENPP2) produces lysophosphatidic acid (LPA) that regulates multiple biological functions via cognate G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor cell migration and metastasis via LPAR1 and T cell motility via LPAR2, yet its actions in the tumor immune microenvironment remain unclear. Here, we show that ATX secreted by melanoma cells is chemorepulsive for tumor-infiltrating lymphocytes (TILs) and circulating CD8+ T cells ex vivo, with ATX functioning as an LPA-producing chaperone. Mechanistically, T cell repulsion predominantly involves Gα12/13-coupled LPAR6. Upon anti-cancer vaccination of tumor-bearing mice, ATX does not affect the induction of systemic T cell responses but, importantly, suppresses tumor infiltration of cytotoxic CD8+ T cells and thereby impairs tumor regression. Moreover, single-cell data from melanoma tumors are consistent with intratumoral ATX acting as a T cell repellent. These findings highlight an unexpected role for the pro-metastatic ATX-LPAR axis in suppressing CD8+ T cell infiltration to impede anti-tumor immunity, suggesting new therapeutic opportunities.

[Odontología en entorno COVID-19. Adaptación de las Unidades de Salud Bucodental en los centros de salud de la Comunidad de Madrid.] / Dentistry in the COVID-19 environment. Adaptation of the dental health units in Madrid's public primary health centres.

The COVID-19 respiratory manifestations go from mild symptoms similar to those of a common cold to severe pneumonia with respiratory distress syndrome, septic shock and multiorgan failure. The disease is caused by the SARS-CoV-2 virus, whose transmission mechanism most relevant to dentistry is through respiratory droplets and possibly also aerosols, as well as direct contact with mucous membranes of the nose, mouth or eye via contaminated hands or objects. The professionals of the dental health units have a high risk exposure since they work at short distances (less than 1 m from the head of the patient) in the oral cavity, where a maximal expression of possible cell receptors for the virus has been reported. Also, most procedures in the dental cabinet imply aerosol generation. Cross-infection is possible during dental care, not only with diagnosed COVID-19-positive patients but also with patients who remain undetected due to asymptomatic or presymptomatic disease. For all these reasons, dental care in the primary health setting has had to change in order to adapt to the pandemic. The changes affect both the appointment scheduling and the care itself and imply the establishment of general and specific barrier protections as well as measures related to ventilation, cleaning, disinfection and sterilization, reinforced with additional infection prevention and control measures. This article summarizes the available scientific evidence about this adaptation.

En el término COVID-19 se incluyen cuadros respiratorios que varían desde el resfriado común hasta cuadros de neumonía grave con síndrome de distrés respiratorio, shock séptico y fallo multiorgánico. Esta enfermedad está causada por el virus SARS-CoV-2, cuyo mecanismo de transmisión más importante en odontología es, fundamentalmente, respiratorio, mediante gotitas, probablemente aerosoles y, también, por contacto directo con mucosas (nasales, orales u oculares) a través de manos o fómites contaminados. Los profesionales de las Unidades de Salud Bucodental representan una categoría laboral con un riesgo de exposición muy alto, ya que trabajan a una distancia de trabajo reducida (menos de un metro de la cabeza del paciente) en la cavidad oral, donde se ha descrito la máxima expresión de los posibles receptores celulares de dicho virus. Además, la mayoría de los procedimientos odontológicos conllevan la generación de aerosoles. Durante la atención odontológica puede producirse infección cruzada, tanto con pacientes diagnosticados positivos por COVID-19 como con aquellos no detectados por encontrarse asintomáticos o en fase presintomática. Por estas razones, la actividad odontológica en Atención Primaria ha tenido que adaptarse a la pandemia. Dichos cambios afectan a la distribución de la agenda de citación, a la atención odontológica, e implican el establecimiento de medidas universales y específicas de protección de barrera y otras relativas a ventilación, limpieza, desinfección y esterilización, reforzadas con medidas adicionales de control de infecciones. Este artículo resume la evidencia científica disponible relativa a dicha adaptación.

PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates.

Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival (OS) and a dramatic improvement in patient quality of life. Despite the success of this approach, the number of benefitting patients is limited and there is a need for predictive biomarkers as well as a deeper mechanistic analysis of the cellular populations involved in clinical responses. With the aim to find predictive biomarkers for PD-1 checkpoint blockade, an in-depth immune monitoring study was conducted in 36 advanced melanoma patients receiving pembrolizumab or nivolumab treatment at Karolinska University Hospital. Blood samples were collected before treatment and before administration of the second and fourth doses. Peripheral blood mononuclear cells were isolated and stained for flow cytometric analysis within 2 h of sample collection. Overall survival and progression-free survival (PFS) were inversely correlated with CD69 expression NK cells. In the myeloid compartment, high frequencies of non-classical monocytes and low frequencies of monocytic myeloid derived suppressor cells (MoMDSCs) correlated with response rates and OS. A deeper characterization of monocytic subsets showed that PD-L1 expression in MDSCs, non-classical and intermediate monocytes was significantly increased in patients with shorter PFS in addition to correlating inversely with OS. Our results suggest that cellular populations other than T cells can be critical in the outcome of PD-1 blockade treatment. Specifically, the frequencies of activated NK cells and monocytic subsets are inversely correlated with survival and clinical benefit, suggesting that their role as predictive biomarkers should be further evaluated.

FUT9-Driven Programming of Colon Cancer Cells towards a Stem Cell-Like State.

Cancer stem cells (CSCs) are located in dedicated niches, where they remain inert to chemotherapeutic drugs and drive metastasis. Although plasticity in the CSC pool is well appreciated, the molecular mechanisms implicated in the regulation of cancer stemness are still elusive. Here, we define a fucosylation-dependent reprogramming of colon cancer cells towards a stem cell-like phenotype and function. De novo transcriptional activation of Fut9 in the murine colon adenocarcinoma cell line, MC38, followed by RNA seq-based regulon analysis, revealed major gene regulatory networks related to stemness. Lewisx, Sox2, ALDH and CD44 expression, tumorsphere formation, resistance to 5-FU treatment and in vivo tumor growth were increased in FUT9-expressing MC38 cells compared to the control cells. Likewise, human CRC cell lines highly expressing FUT9 displayed phenotypic features of CSCs, which were significantly impaired upon FUT9 knock-out. Finally, in primary CRC FUT9+ tumor cells pathways related to cancer stemness were enriched, providing a clinically meaningful annotation of the complicity of FUT9 in stemness regulation and may open new avenues for therapeutic intervention.

Mascarillas y máscaras de protección respiratoria en entorno COVID-19 / Surgical masks and respirators in COVID-19 environment

Coronavirus Disease 2019, COVID-19, es una enfermedad respiratoria causada por un coronavirus, el SARS-CoV-2. La ruta de trasmisión es a través de gotas y salpicaduras procedentes del tracto aerodigestivo de personas infectadas, así como por el contacto con superficies contaminadas y la posterior deposición en la mucosa de los ojos, nariz o boca, siendo probable su transmisión por aerosoles. Por otra parte, el trabajo dental no permite mantener una distancia de 2 metros, ni el uso por parte del paciente de mascarilla. Por esta razón, dentro del esquema de Equipos de Protección Individual (EPI), la protección respiratoria es fundamental, junto con la ocular, y con ello la selección de la mascarilla y, sobre todo, el uso que se haga de ella. La razón del presente artículo es describir los diferentes tipos de mascarillas y el uso apropiado de cada una de ellas según el objetivo buscado. Para ello, se recomendarán las mascarillas higiénicas y las quirúrgicas en usuarios generales, con la función de disminuir la trasmisión viral por medio de la minoración de la contaminación ambiental cuando es alta la trasmisión comunitaria. Las máscaras de protección respiratoria estarán indica-das en trabajadores sanitarios y otros en contacto con pacientes potencialmente infecciosos, al menos cuando los procedimientos de trabajo impliquen un riesgo elevado para el profesional

COVID-19 is a respiratory illness caused by a new coronavirus, SARS-CoV-2. The virus spreads through droplets and spray from the respiratory tracts of infected persons, and through contact with contaminated surfaces followed by touching the eyes, nose or mouth. It is also likely that the virus can be spread through aerosols. However, dentistry does not allow for a distance of two metres to be maintained, and nor does it allow for the patient to wear a mask. As such, within the scope of Personal Protective Equipment (PPE), respiratory protection is of fundamental importance, along with eye protection and the correct usage of available masks. The purpose of this article is to describe different types of masks and the appropriate use of each one according to the required need. To this end, it is recommended that hygienic and surgical masks are used with a view to decreasing viral transmission through the reduction of environmental contamination whilst community transmission is high. Respiratory protection masks will be shown on health workers and others who are in contact with potentially infectious patients, when the work involved brings with it an increased level of risk for the worker

Odontología en entorno COVID-19. adaptación de las Unidades de Salud Bucodental en los centros de salud de la Comunidad de Madrid / Dentistry in the COVID-19 environment. Adaptation of the dental health units in Madrid's public primary health centres

The COVID-19 respiratory manifestations go from mild symptoms similar to those of a common cold to severe pneumonia with respiratory distress syndrome, septic shock and multiorgan failure. The disease is caused by the SARS-CoV-2 virus, whose transmission mechanism most relevant to dentistry is through respiratory droplets and possibly also aerosols, as well as direct contact with mucous membranes of the nose, mouth or eye via contaminated hands or objects. The professionals of the dental health units have a high risk exposure since they work at short distances (less than 1 m from the head of the patient) in the oral cavity, where a maximal expression of possible cell receptors for the virus has been reported. Also, most procedures in the dental cabinet imply aerosol generation. Cross-infection is possible during dental care, not only with diagnosed COVID-19-positive patients but also with patients who remain undetected due to asymptomatic or presymptomatic disease. For all these reasons, dental care in the primary health setting has had to change in order to adapt to the pandemic. The changes affect both the appointment scheduling and the care itself and imply the establishment of general and specific barrier protections as well as measures related to ventilation, cleaning, disinfection and sterilization, reinforced with additional infection prevention and control measures. This article summarizes the available scientific evidence about this adaptation

The COVID-19 respiratory manifestations go from mild symptoms similar to those of a common cold to severe pneumonia with respiratory distress syndrome, septic shock and multiorgan failure. The disease is caused by the SARS-CoV-2 virus, whose transmission mechanism most relevant to dentistry is through respiratory droplets and possibly also aerosols, as well as direct contact with mucous membranes of the nose, mouth or eye via contaminated hands or objects. The professionals of the dental health units have a high risk exposure since they work at short distances (less than 1 m from the head of the patient) in the oral cavity, where a maximal expression of possible cell receptors for the virus has been reported. Also, most procedures in the dental cabinet imply aerosol generation. Cross-infection is possible during dental care, not only with diagnosed COVID-19-positive patients but also with patients who remain undetected due to asymptomatic or presymptomatic disease. For all these reasons, dental care in the primary health setting has had to change in order to adapt to the pandemic. The changes affect both the appointment scheduling and the care itself and imply the establishment of general and specific barrier protections as well as measures related to ventilation, cleaning, disinfection and sterilization, reinforced with additional infection prevention and control measures. This article summarizes the available scientific evidence about this adaptation

Thermoregulation protocol implementation for newborns in surgical procedures. / Implantação do protocolo de termorregulação para recém-nascido em procedimentos cirúrgicos.

OBJECTIVE: To describe the thermoregulation protocol implementation for newborns (NB). METHODS: An experimental report, conducted at a neonatal unit in Salvador, Bahia, from January 2016 to January 2017. The Plan, Do, Check, Action cycle guided the construction, implementation and applicability of the protocol. RESULTS: Implementation of the protocol that allowed the reduction of adverse events due to thermal instability during surgical procedures and introduction of new technologies. CONCLUSION: The protocol could improve and strengthen the care practices related to safe surgery in newborns.

Evaluating Antibody-Dependent Cell-Mediated Cytotoxicity by Chromium Release Assay.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism in which immune cell activation is induced by the cross-linking of CD16 with the Fc region of antibodies that at the same time bind specifically to cell surface antigens. ADCC stimulates the secretion of perforin, granzymes, and cytokines leading to lysis of the malignant cells. Natural killer (NK) cells express the CD16 receptor and can therefore be activated by ADCC to kill tumor cells. To study the cytotoxicity of NK cells against cancer cells, an ADCC-based assay is described: the chromium release assay. In this method, the antibody trastuzumab, which binds specifically to HER2-positive malignant cells, is used to trigger ADCC.

Evaluating Antibody-Dependent Cell-Mediated Cytotoxicity by Flow Cytometry.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism in which immune cell activation is induced by the cross-linking of CD16 with the Fc region of antibodies that at the same time bind specifically to cell surface antigens. ADCC stimulates the secretion of perforin, granzymes, and cytokines leading to lysis of the malignant cells. Natural killer (NK) cells express the CD16 receptor and can therefore be activated by ADCC to kill tumor cells. To study the cytotoxicity of NK cells against cancer cells, an ADCC-based assay is described: the flow cytometry-based cytotoxicity assay. In this method, the antibody trastuzumab, which binds specifically to HER2-positive malignant cells, is used to trigger ADCC.

Implantação do protocolo de termorregulação para recém-nascido em procedimentos cirúrgicos / Implantación del protocolo de termorregulación para recién nacido en procedimientos quirúrgicos / Thermoregulation protocol implementation for newborns in surgical procedures

Resumo OBJETIVO Descrever a implantação do protocolo de termorregulação para procedimentos cirúrgicos em recém-nascido (RN). MÉTODOS Relato de experiência, realizado em uma unidade neonatal em Salvador-BA, no período de janeiro de 2016 a janeiro 2017. O ciclo Plan, Do, Check, Action norteou a construção, a implantação e a aplicabilidade do protocolo. RESULTADOS Implantação do protocolo que possibilitou a redução de eventos adversos por instabilidade térmica durante procedimentos cirúrgicos e introdução de novas tecnologias. CONCLUSÃO O protocolo possibilitou a melhoria e o fortalecimento das práticas assistenciais relacionadas com a cirurgia segura em RN.

Resumen OBJETIVO Describir la implementación del protocolo de termorregulación para procedimientos quirúrgicos en recién nacido (RN). MÉTODOS Relato de experiencia, realizado en una unidad neonatal en Salvador-BA, en el período de enero de 2016 a enero de 2017. El ciclo Plan, Do, Check, Action orientó la construcción, la implementación y la aplicabilidad del protocolo. RESULTADOS Se pudo implementar el protocolo que permitió reducir eventos adversos por inestabilidad térmica durante procedimientos quirúrgicos y se introdujo nuevas tecnologías. CONCLUSIÓN El protocolo permitió una mejora y un fortalecimiento de las prácticas asistenciales, relacionadas con la cirugía segura en RN.

Abstract OBJECTIVE To describe the thermoregulation protocol implementation for newborns (NB). METHODS An experimental report, conducted at a neonatal unit in Salvador, Bahia, from January 2016 to January 2017. The Plan, Do, Check, Action cycle guided the construction, implementation and applicability of the protocol. RESULTS Implementation of the protocol that allowed the reduction of adverse events due to thermal instability during surgical procedures and introduction of new technologies. CONCLUSION The protocol could improve and strengthen the care practices related to safe surgery in newborns.

Basal forebrain neuronal inhibition enables rapid behavioral stopping.

Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. Although most studies on inhibitory control have focused on the fronto-basal-ganglia circuit, we found that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were nearly completely inhibited by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a previously unknown subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition.

Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy.

PURPOSE: There is limited information on hemorrhagic complications during invasive dental procedures in patients treated with double antiplatelet therapy. The objective of this study is to assess the frequency of hemorrhagic complications of patients taking dual antiplatelet medication undergoing dental extractions. PATIENTS AND METHODS: An observational, multicenter, prospective, cohort study was performed in 11 oral and dental care units of primary care. The study sample was derived from the population of patients aged 18 years or older who were undergoing double antiplatelet therapy and presented to the oral and dental care units requiring dental extraction. Double antiplatelet therapy is the combination of 100 mg per day of acetylsalicylic acid and a second antiplatelet agent. The predictor variables were type of extraction performed, number of extracted teeth, number of extracted roots, and presence of inflammation. The primary outcome variable was intraoperative hemorrhage, and the secondary outcome variables were hemorrhage at 24 hours and hemorrhage at 10 days. First, a univariate analysis that considered all studied variables was performed. All variables with P < .25 in the univariate analysis were included in a multivariate analysis. The association between hemorrhage severity and its relevant factors was evaluated using logistic regression analysis. RESULTS: The study included 181 patients. Light hemorrhage (<30 minutes) was observed in 165 patients (91.2%). Intraoperative hemorrhage lasted more than 30 minutes in 15 patients (8.3%) and more than 60 minutes in only 1 patient, whose hemorrhage was controlled by local hemostatic measures. The presence of inflammation and 3-root extractions increased the probability of hemorrhage persisting for more than 30 minutes by factors of 10 and 7.3, respectively. CONCLUSIONS: In 8.3% of patients treated with dual antiplatelet therapy, dental extractions cause hemorrhagic complications lasting more than 30 minutes are resolved using local hemostatic measures. The results of this study support the safety of dental extraction without withdrawal double antiplatelet therapy.