CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types.

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Human vs machine towards neonatal pain assessment: A comprehensive analysis of the facial features extracted by health professionals, parents, and convolutional neural networks.

Neonates are not able to verbally communicate pain, hindering the correct identification of this phenomenon. Several clinical scales have been proposed to assess pain, mainly using the facial features of the neonate, but a better comprehension of these features is yet required, since several related works have shown the subjectivity of these scales. Meanwhile, computational methods have been implemented to automate neonatal pain assessment and, although performing accurately, these methods still lack the interpretability of the corresponding decision-making processes. To address this issue, we propose in this work a facial feature extraction framework to gather information and investigate the human and machine neonatal pain assessments, comparing the visual attention of the facial features perceived by health-professionals and parents of neonates with the most relevant ones extracted by eXplainable Artificial Intelligence (XAI) methods, considering the VGG-Face and N-CNN deep learning architectures. Our experimental results show that the information extracted by the computational methods are clinically relevant to neonatal pain assessment, but yet do not agree with the facial visual attention of health-professionals and parents, suggesting that humans and machines can learn from each other to improve their decision-making processes. We believe that these findings might advance our understanding of how humans and machines code and decode neonatal facial responses to pain, enabling further improvements in clinical scales widely used in practical situations and in face-based automatic pain assessment tools as well.

The role of dermocosmetics in the management of cancer-related skin toxicities: international expert consensus.

Skin toxicities are very common in patients undergoing cancer treatment and have been found to occur with all types of cancer therapeutic interventions (cytotoxic chemotherapy, targeted therapies, immunotherapy, and radiotherapy). Further, skin toxicities can lead to interruption or even discontinuation of anticancer treatment in some patients, translating to suboptimal outcomes. Dermocosmetics (or cosmeceuticals)-defined as skincare solutions incorporating dermatologically active ingredients (beyond vehicle effects) that directly improve symptoms of various skin conditions-are increasingly being used in cancer care to prevent and manage skin toxicities. The active ingredients in these products have a measurable biological action in skin; they typically improve skin integrity (barrier function/hydration and other factors) while relieving skin symptoms. The Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC) partnered to select a multidisciplinary group of healthcare professionals involved in the management of patients with cancer and skin toxicities. The group reviewed existing literature and created a summary of recommendations for managing these toxicities through online meetings and communication. In this publication, the group (1) reviews new skin toxicities seen with oncology drugs and (2) evaluates the role of dermocosmetics in improving patient outcomes and minimizing cancer treatment interruptions. We provide general recommendations for initiation and selection of skin care in all oncology patients as well as recommendations for what factors should be considered when using dermocosmetics in specific types of skin toxicities.

Bifidobacterium animalis subspecies lactis HN019 can reduce the sequelae of experimental periodontitis in rats modulating intestinal parameters, expression of lipogenic genes, and levels of hepatic steatosis.

OBJECTIVE: To determine whether Bifidobacterium animalis subspecies lactis HN019 (B. lactis HN019) can reduce the sequelae of experimental periodontitis (EP) in rats modulating systemic parameters. BACKGROUND: This study evaluated the effects of probiotic therapy (PROB) in the prevention of local and systemic damage resulting from EP. METHODS: Forty-eight rats were allocated into four groups: C (control), PROB, EP, and EP-PROB. PROB (1 × 1010 CFU/mL) administration lasted 8 weeks and PE was induced on the 7th week by placing ligature on the animals' lower first molars. All animals were euthanized in the 9th week of the experiment. Biomolecular analyses, RT-PCR, and histomorphometric analyses were performed. The data obtained were analyzed statistically (ANOVA, Tukey, p < .05). RESULTS: The EP group had higher dyslipidemia when compared to the C group, as well as higher levels of insulin resistance, proteinuria levels, percentages of systolic blood pressure, percentage of fatty hepatocytes in the liver, and expression of adipokines was up-regulated (LEPR, NAMPT, and FABP4). All these parameters (except insulin resistance, systolic blood pressure, LEPR and FABP4 gene expression) were reduced in the EP-PROB group when compared to the EP group. The EP group had lower villus height and crypt depth, as well as a greater reduction in Bacteroidetes and a greater increase in Firmicutes when compared to the EP-PROB group. Greater alveolar bone loss was observed in the EP group when compared to the EP-PROB group. CONCLUSION: Bifidobacterium lactis HN019 can reduce the sequelae of EP in rats modulating intestinal parameters, attenuating expression of lipogenic genes and hepatic steatosis.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls.

Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

What Facial Features Does the Pediatrician Look to Decide That a Newborn Is Feeling Pain?

OBJECTIVE: The study aimed to analyze the gaze fixation of pediatricians during the decision process regarding the presence/absence of pain in pictures of newborn infants. STUDY DESIGN: Experimental study, involving 38 pediatricians (92% females, 34.6 ± 9.0 years, 22 neonatologists) who evaluated 20 pictures (two pictures of each newborn: one at rest and one during a painful procedure), presented in random order for each participant. The Tobii-TX300 equipment tracked eye movements in four areas of interest of each picture (AOI): mouth, eyes, forehead, and nasolabial furrow. Pediatricians evaluated the intensity of pain with a verbal analogue score from 0 to 10 (0 = no pain; 10 = maximum pain). The number of pictures in which pediatricians fixed their gaze, the number of gaze fixations, and the total and average time of gaze fixations were compared among the AOI by analysis of variance (ANOVA). The visual-tracking parameters of the pictures' evaluations were also compared by ANOVA according to the pediatricians' perception of pain presence: moderate/severe (score = 6-10), mild (score = 3-5), and absent (score = 0-2). The association between the total time of gaze fixations in the AOI and pain perception was assessed by logistic regression. RESULTS: In the 20 newborn pictures, the mean number of gaze fixations was greater in the mouth, eyes, and forehead than in the nasolabial furrow. Also, the average total time of gaze fixations was greater in the mouth and forehead than in the nasolabial furrow. Controlling for the time of gaze fixation in the AOI, each additional second in the time of gaze fixation in the mouth (odds ratio [OR]: 1.26; 95% confidence interval [CI]: 1.08-1.46) and forehead (OR: 1.16; 95% CI: 1.02-1.33) was associated with an increase in the chance of moderate/severe pain presence in the neonatal facial picture. CONCLUSION: When challenged to say whether pain is present in pictures of newborn infants' faces, pediatricians fix their gaze preferably in the mouth. The longer duration of gaze fixation in the mouth and forehead is associated with an increase perception that moderate/severe pain is present. KEY POINTS: · Neonatal pain assessment is intrinsically subjective.. · Visual tracking identifies the focus of attention of individuals.. · Adults' gaze in neonates' mouth and forehead is associated with pain perception..

High abscisic acid and low root hydraulic conductivity may explain low leaf hydration in 'Mandarin' lime exposed to aluminum.

The first symptom of aluminum (Al) toxicity is the inhibition of root growth, which has been associated with low leaf hydration, with negative consequences for leaf gas exchange including stomatal conductance (gs) observed in many plant species. Here we asked whether low leaf hydration occurs before or after the inhibition of root growth of Citrus × limonia Osbeck ('Mandarin' lime) cultivated for 60 days in nutrient solution with 0 and 1480 µM Al. The length, diameter, surface area and biomass of roots of plants exposed to Al were lower than control plants only at 30 days after treatments (DAT). Until the end of the study, estimated gs (measured by sap flow techniques) was lower than in control plants from 3 DAT, total plant transpiration (Eplant) and root hydraulic conductivity (Lpr) at 7 DAT, and midday leaf water potential (Ψmd) and relative leaf water content at 15 DAT. Abscisic acid (ABA) in leaves was twofold higher in Al-exposed plants 1 DAT, and in roots a twofold higher peak was observed at 15 DAT. As ABA in leaves approached values of control plants after 15 DAT, we propose that low gs of plants exposed to Al is primarily caused by ABA, and the maintenance of low gs could be ascribed to the low Lpr from 7 DAT until the end of the study. Therefore, the low leaf hydration in 'Mandarin' lime exposed to Al does not seem to be caused by root growth inhibition or by a simple consequence of low water uptake due to a stunted root system.

Effects of oral administration of Bifidobacterium animalis subsp. lactis HN019 on the treatment of plaque-induced generalized gingivitis.

OBJECTIVES: This double-blind, randomized, placebo-controlled clinical trial evaluated the adjuvant effects of Bifidobacterium lactis HN019 on the treatment of plaque-induced generalized gingivitis. MATERIALS AND METHODS: Sixty patients were submitted to professional supragingival scaling and prophylaxis. They were randomly assigned to test (probiotic lozenges containing B. lactis HN019, n = 30) or control (placebo lozenges, n = 30) groups. Lozenges were consumed twice a day for 8 weeks. Bleeding on probing (BoP), Gingival Index (GI), Plaque Index (PI), probing depth (PD), and clinical attachment level (CAL) were evaluated at baseline and after 2 and 8 weeks. Gingival crevicular fluid (GCF) was collected at baseline and at 8 weeks for analysis of the inflammatory mediators IL-1ß, IL-1α, IL-8, MCP-1, and MIP-1ß. Data were statistically analyzed (p < 0.05). RESULTS: After 8 weeks, both groups showed reduction in the percentage of PI, with no significant difference between groups (p = 0.7423). The test group presented a lower percentage of BoP and a higher percentage of sites with GI ≤ 1 when compared with the control group at the end of the study (p < 0.0001). At 8 weeks, the test group had a greater number of patients without generalized gingivitis than the control group (20 and 11 patients, respectively; p < 0.05). The test group presented significantly lower levels of IL-1α, IL-1ß, and MCP-1 in GCF than the control group at the end of the study (p < 0.05). CONCLUSION: The adjunct use of B. lactis HN019 promotes additional clinical and immunological benefits in the treatment of generalized gingivitis. CLINICAL RELEVANCE: B. lactis HN019 can be an efficient and side-effect-free adjunct strategy in the treatment of generalized gingivitis.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

ABSTRACT Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

Looking at neonatal facial features of pain: do health and non-health professionals differ?

Abstract Objective: To analyze the regions that trigger the attention of adults' gaze when assessing pain in newborn infants' pictures and to verify if there are differences between health and non-health professionals. Method: Experimental study with 84 health professionals and 59 non-health professionals, who evaluated two images of 10 neonates, one at rest and the other during a painful procedure. Each image was shown for 7 seconds on a computer screen, while eye movements were tracked by the Tobii TX300 EyeTracker. After evaluating each image, participants gave a score from 0 (absent pain) to 10 (maximum pain), according to their perception of neonatal pain. For each image, the number and total time of gaze fixations in the forehead, eyes, nasolabial furrow, and mouth were studied. Comparisons between both groups of adults were made by an intraclass correlation coefficient, Student's t-test, and Bland Altman graphic. Results: Health professionals (93% female; 34 ± 9 years old), compared to non-health professionals (64% female; 35 ± 11 years old), gave lower scores for images at rest (0.81 ± 0.50 vs. 1.59 ± 0.76; p = 0.010), with no difference for those obtained during the painful procedure (6.98 ± 1.08 vs. 6.73 ± 0.82). There was a strong or almost perfect correlation for the number of fixations in the mouth, eyes, forehead, and for the total fixation time in the eyes and forehead. Conclusions: Adults, irrespective of their profession, showed a homogeneous gaze pattern when evaluating pictures of neonates at rest or during a painful procedures.

Carbonic Anhydrase IX: A Renewed Target for Cancer Immunotherapy.

The carbonic anhydrase isoform IX (CAIX) enzyme is constitutively overexpressed in the vast majority of clear cell renal cell carcinoma (ccRCC) and can also be induced in hypoxic microenvironments, a major hallmark of most solid tumors. CAIX expression is restricted to a few sites in healthy tissues, positioning this molecule as a strategic target for cancer immunotherapy. In this review, we summarized preclinical and clinical data of immunotherapeutic strategies based on monoclonal antibodies (mAbs), fusion proteins, chimeric antigen receptor (CAR) T, and NK cells targeting CAIX against different types of solid malignant tumors, alone or in combination with radionuclides, cytokines, cytotoxic agents, tyrosine kinase inhibitors, or immune checkpoint blockade. Most clinical studies targeting CAIX for immunotherapy were performed using G250 mAb-based antibodies or CAR T cells, developed primarily for bioimaging purposes, with a limited clinical response for ccRCC. Other anti-CAIX mAbs, CAR T, and NK cells developed with therapeutic intent presented herein offered outstanding preclinical results, justifying further exploration in the clinical setting.

Comparison Between Different Delivery Vehicles for the Probiotic Bifidobacterium animalis subsp. lactis HN019 on Experimental Periodontitis in Rats.

This study aimed to assess the effects of the probiotic (PROB) Bifidobacterium animalis subsp. lactis HN019 in two different delivery vehicles in experimental periodontitis (EP), including the gene expression for IL-10, IFN-γ, and FOXP3. In total, 32 rats were assigned into groups (n=8): C (control), EP, EP-PROB/Water, and EP-PROB/Milk. The probiotic was administered for 4 weeks, from baseline to euthanasia. Periodontitis was induced by ligatures 14 days after baseline. Data were statistically analyzed (p<0.05). Both probiotic groups presented decreased alveolar bone loss and increased interproximal attachment level than group EP. Also, these parameters were significantly improved in the Milk group when compared with the Water group. EP-PROB/Milk showed higher gene expression for IL-10 and lower for FOXP3 in relation to EP-PROB/Water and EP groups. The use of milk was able to potentiate the protective effects of B. lactis HN019 in rats under EP.

Os principais erros da fase pré-analítica de exames laboratoriais / The main errors of the pre-analytical phase of laboratory exams

As análises clínicas laboratoriais possuem papel fundamental na saúde, pois é através de seus resultados que 70% dos diagnósticos são concluídos pelos médicos, e desta forma é necessário que se preze pela emissão de resultados confiáveis. Entretanto, uma das fases do processo de realização dos exames laboratoriais tem se destacado como a fase que concentra o maior percentual de erros no âmbito laboratorial até os dias atuais. Trata-se da fase pré-analítica, que se inicia com a solicitação do exame e finaliza quando se inicia a análise. Os erros pré-analíticos podem ser responsáveis por até 75% dos erros laboratoriais, o que mostra a vulnerabilidade desta fase. Portanto, este trabalho tem como objetivo identificar os principais erros que estão vinculados à fase pré-analítica, assim como os impactos que esses erros podem causar. Os tipos de erros pré-analíticos foram revisados na literatura entre os anos de 2011 a 2020. Os resultados apontaram que os principais erros pré-analíticos estão associados ao momento da coleta de amostras biológicas. Isto mostra a necessidade de gerar melhorias nos setores de coleta, através da realização de treinamentos voltados para as equipes de flebotomia, com o intuito de aperfeiçoar este processo e diminuir as taxas dos erros provocados nesta fase.

The clinical laboratory analyses have a fundamental role in health, because it is through their results that 70% of the diagnoses are concluded by the doctors, therefore, it is necessary to give priority to the issuance of reliable and safe results. However, one of the phases of the process of performing laboratory tests has been highlighted as the phase that concentrates the highest percentage of errors in the laboratory environment until the present day.It is the pre-analytical phase, which begins with the request of the exam and ends when the analysis begins.The pre-analytical errors can be responsible for up to 75% of laboratory errors, which shows the vulnerability of this phase. Therefore, this work aims to identify the main errors that are linked to the pre-analytical phase, as well as the impacts that these errors may cause. The types of pre-analytical errors were reviewed in the literature between 2011 and 2020. The results showed that the main pre-analytical errors are associated with the time of collection of biological samples. This shows the need to generate improvements in the collection sectors, through training for phlebotomy teams, in order to improve this process and decrease the rates of errors caused in this phase.

Conhecimento sobre anticoagulação oral de pacientes após correção cirúrgica de valvopatias: revisão integrativa / Conocimiento sobre la anticoagulación oral de los pacientes después de la corrección quirúrgica de valvulopatías: revisión integradora / Knowledge about oral anticoagulation of patients after surgical correction of valve diseases: integrative review

Objetivo: Verificar a existência de evidências científicas na literatura sobre o conhecimento dos pacientes em relação ao uso do anticoagulante oral após o implante de valva cardíaca metálica. Método: Revisão integrativa realizada nas bases de dados Embase, Scopus, Web of Science e Sistema Online de Busca e Análise de Literatura Médica (MEDLINE)/PubMed, utilizando descritores controlados e não controlados, sem delimitação temporal quanto à publicação, nos idiomas português, inglês e espanhol. A busca ocorreu em junho de 2022, por duas pesquisadoras de forma independente. Resultado: Verificou-se a existência de lacunas no conhecimento dos pacientes sobre os efeitos adversos relacionados ao uso dos anticoagulantes orais, às interações medicamentosas, às interações alimentares, aos fatores que interferem nos níveis do international normalized ratio e ao que deve ser feito em aso de esquecimento das doses diárias. Conclusão: A síntese elaborada enfatiza a necessidade de maior enfoque nas orientações aos pacientes sobre os anticoagulantes e suas implicações relacionadas aos hábitos de vida diária (AU)

Objective: To verify the existence of scientific evidence in the literature on patients regarding the use of oral anticoagulants after implantation of a metallic heart valve. Method: Integrative review carried out in the Embase, Scopus, Web of Science, and Online Medical Literature Search and Analysis System (MEDLINE)/PubMed databases, using controlled and uncontrolled descriptors, without temporal delimitation regarding publication, in Portuguese, English, and Spanish. The search took place in June 2022, by two researchers independently. Result: There were gaps in patients' knowledge about adverse effects related to the use of oral anticoagulants, drug interactions, food interactions, factors that interfere with international normalized ratio levels and what should be done in case of forgetting the daily doses. Conclusion: The synthesis elaborated emphasizes the need for greater focus on patient guidance on anticoagulants and their implications related to daily life habits (AU)

Objetivo: Verificar la existencia de evidencia científica en la literatura sobre el conocimiento de los pacientes sobre el uso de anticoagulantes orales después del implante de una válvula cardíaca metálica. Método: Revisión integradora realizada en las bases de datos Embase, Scopus, Web of Science y MEDLINE/PubMed, utilizando descriptores controlados y no controlados, sin delimitación temporal con respecto a la publicación, en portugués, inglés y español. La búsqueda tuvo lugar en junio de 2022, por dos investigadores de forma independiente. Resultado: Hubo lagunas en el conocimiento de los pacientes sobre los efectos adversos relacionados con el uso de anticoagulantes orales, interacciones medicamentosas, interacciones alimentarias, factores que interfieren con los niveles de la razón internacional normalizada y qué se debe hacer en caso de olvido de las dosis diarias. Conclusión: La síntesis elaborada enfatiza la necesidad de un mayor enfoque en la orientación del paciente sobre los anticoagulantes y sus implicaciones relacionadas con los hábitos de la vida diaria (AU)

Looking at neonatal facial features of pain: do health and non-health professionals differ?

OBJECTIVE: To analyze the regions that trigger the attention of adults' gaze when assessing pain in newborn infants' pictures and to verify if there are differences between health and non-health professionals. METHOD: Experimental study with 84 health professionals and 59 non-health professionals, who evaluated two images of 10 neonates, one at rest and the other during a painful procedure. Each image was shown for 7 seconds on a computer screen, while eye movements were tracked by the Tobii TX300 EyeTracker. After evaluating each image, participants gave a score from 0 (absent pain) to 10 (maximum pain), according to their perception of neonatal pain. For each image, the number and total time of gaze fixations in the forehead, eyes, nasolabial furrow, and mouth were studied. Comparisons between both groups of adults were made by an intraclass correlation coefficient, Student's t-test, and Bland Altman graphic. RESULTS: Health professionals (93% female; 34 ± 9 years old), compared to non-health professionals (64% female; 35 ± 11 years old), gave lower scores for images at rest (0.81 ± 0.50 vs. 1.59 ± 0.76; p = 0.010), with no difference for those obtained during the painful procedure (6.98 ± 1.08 vs. 6.73 ± 0.82). There was a strong or almost perfect correlation for the number of fixations in the mouth, eyes, forehead, and for the total fixation time in the eyes and forehead. CONCLUSIONS: Adults, irrespective of their profession, showed a homogeneous gaze pattern when evaluating pictures of neonates at rest or during a painful procedures.

The use of probiotics can reduce the severity of experimental periodontitis in rats with metabolic syndrome: An immunoenzymatic and microtomographic study.

BACKGROUND: This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) in rats. METHODS: Ninety-six rats were grouped according to a food protocol: high-fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): C-**, CP-*, PE+**, PEP+*, MS- MSP-*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05). RESULTS: The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)-1ß and a higher receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)-α and IL-6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE. CONCLUSION: B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.

In vitro antiglycation and antioxidant properties of Eugenia pyriformis leaves and fruits.

Eight phenolic compounds were isolated from Eugenia pyriformis leaves fraction by semi-preparative HPLC and characterized by Nuclear Magnetic Resonance (NMR) and mass spectrometry (ESI-MS). Five compounds were isolated and identified for the first time in E. pyriformis species, while this is the first report of the accumulation of isoquercitrin, quercitrin, and the aglycone quercetin in its leaves. E. pyriformis leaves and fruits extracts, as well as the compounds isolated from the leaves most active fraction, were evaluated for their antiglycation and antioxidant activities. The mixture of myricetin-3-O-(2″-O-galloyl)-α-L-rhamnoside and myricetin-3-O-(4″-O-galloyl)-α-L-rhamnoside showed the highest antiglycation activity. These results suggest that this species is a promising source of bioactive compounds. Further studies to investigate the inhibition of the glycation process in vivo are necessary to evaluate its use in the treatment and/or prevention of advanced glycation end-products (AGEs)-associated diseases.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents.

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Atmospheric cold plasma frequency imparts changes on cashew apple juice composition and improves vitamin C bioaccessibility.

This study evaluated the atmospheric cold plasma (ACP) effect on cashew apple juice composition at different frequencies (200 and 700 Hz). The impact of this non-thermal technology on the organic juice compounds after the processing and along with the in vitro digestion carried out in a simulated digestion system at 37 °C/6 h was evaluated. The changes in the juice composition were determined by NMR spectroscopy and chemometric analyses. Vitamin C and total phenolic compounds were also quantified in processed and non-processed (control) juices and after each digestion phase. The results showed decreased glucose and fructose in samples treated by ACP and an increment in malic acid concentration for ACP700. ACP increased the amount of vitamin C in the juices and did not affect the total phenolic content. The gastric digestion highlighted the pronounced effect of plasma on the juice composition, increasing all of the components detected by NMR. Cashew apple juice processed by ACP700 presented a higher concentration of malic acid and phenylalanine. An increased bioaccessibility of vitamin C was also found for ACP700. Although ACP processing has decreased some compounds' concentration, this technology improved the bioaccessibility of vitamin C - the main bioactive compound of cashew apple juice.