Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts.

Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models.

Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity. Pep 14 functions via modulation of PP2A, an understudied holoenzyme that promotes genomic stability and is involved in DNA repair and senescence pathways. At the single-cell level, Pep 14 modulates genes that prevent senescence progression by arresting the cell cycle and enhancing DNA repair, which consequently reduce the number of cells progressing to late senescence. When applied on aged ex vivo skin, Pep 14 promoted a healthy skin phenotype with structural and molecular resemblance to young ex vivo skin, decreased the expression of senescence markers, including SASP, and reduced the DNA methylation age. In summary, this work shows the safe reduction of the biological age of ex vivo human skins by a senomorphic peptide.

4-Nerolidylcatechol (4-NC) and Docetaxel Synergize in Controlling Androgen- independent Prostate Cancer Cells.

BACKGROUND: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC). OBJECTIVES: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells. METHODS: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). RESULTS: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4- NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells. CONCLUSION: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells.

Hookah Smoking among Brazilian University Students: An Exploratory Survey on the Prevalence and Perceptions of Addiction and its Harmfulness.

Background: This study aimed to determine the prevalence, beliefs, attitudes, and perceptions of hookah use in a population of undergraduate students at a large public university in Brazil. Methods: The sample consisted of 1348 undergraduate students aged over 18-year-old. They completed structured questionnaires on demographic information and close-ended questions on the past and current experiences of smoking hookah. The data underwent descriptive analysis and binary logistic regression. Findings: Finally, 1298 valid survey forms were obtained from printed and digital questionnaires. More than half (53.9%) of participants reported having tried hookah at least once, however, only 10.8% reported they had experienced it within the last 30 days. The majority of the studied population presented acceptable beliefs about the harmfulness and addictive capacity of hookah smoking. However, when comparing the perceptions of those who had smoked and those who had never smoked hookah, and also, the perceptions of users and non-users, significant differences were observed. Students who were users or had already tried hookah showed a tendency to underestimate the deleterious effects of this type of smoking. Conclusion: It could be concluded that hookah smoking was common among Brazilian university students. In addition, preoccupying misperceptions of hookah's harmfulness and addictive capacity were found. The results showed that the epidemic of hookah smoking, especially among young people, has spread far beyond the Arab world and the Persians. Accordingly, preventive measures must be taken if this population is to be protected from addiction and other serious health problems.

Impaired expression of serine/arginine protein kinase 2 (SRPK2) affects melanoma progression.

Melanoma is one of the most aggressive tumors, and its lethality is associated with the ability of malignant cells to migrate and invade surrounding tissues to colonize distant organs and to generate widespread metastasis. The serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2) are classically related to the control of pre-mRNA splicing through SR protein phosphorylation and have been found overexpressed in many types of cancer, including melanoma. Previously, we have demonstrated that the pharmacological inhibition of SRPKs impairs pulmonary colonization of metastatic melanoma in mice. As the used compounds could target at least both SRPK1 and SRPK2, here we sought to obtain additional clues regarding the involvement of these paralogs in melanoma progression. We analyzed single-cell RNA sequencing data of melanoma patient cohorts and found that SRPK2 expression in melanoma cells is associated with poor prognosis. Consistently, CRISPR-Cas9 genome targeting of SRPK2, but not SRPK1, impaired actin polymerization dynamics as well as the proliferative and invasive capacity of B16F10 cells in vitro. In further in vivo experiments, genetic targeting of SRPK2, but not SRPK1, reduced tumor progression in both subcutaneous and caudal vein melanoma induction models. Taken together, these findings suggest different functional roles for SRPK1/2 in metastatic melanoma and highlight the relevance of pursuing selective pharmacological inhibitors of SRPK2.

Hepatitis B Surface Antibody (Anti-HBs) Kinetics during Rituximab Chemotherapy and Performance of Hepatitis B Vaccine before Immunosuppression: Two Prospective Studies.

Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R risk. However, guidelines claim that additional data are necessary before recommending spare drug prophylaxis in patients with high anti-HBs titers. On the other hand, in patients with no previous contact with HBV, guidelines recommend vaccine before immunosuppression despite minimal evidence available. To shed light on these knowledge gaps, two prospective studies were conducted to evaluate anti-HBs in hematological cancer patients treated with rituximab. In the first study, anti-HBs-positive patients were referred for following up antibody titers before and during immunosuppression. Patients with anti-HBs ≥ 100 mIU/mL before immunosuppression had no negative seroconversion (anti-HBs loss), in contrast to 18% of those with anti-HBs < 100 mIU/mL. In the second study, patients with no previous contact with HBV were invited to receive HBV vaccine before rituximab chemotherapy. None seroconverted with anti-HBs. In conclusion, both studies reinforce the need to review concepts about HBV prevention during immunosuppression on current guidelines. Narrowing the use of drug prophylaxis and improving vaccine indications are recommended.

The SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl) isonicotinamide (SRPIN340) increases the immune response against metastatic melanoma in mice.

Cancers have a strong relationship with immune cells in their microenvironment, which significantly influences tumor proliferation and progression. Thus, pharmacological strategies that stimulate the immune system to combat tumor cells are promising for better therapeutic efficacy. Deregulated expression of the splicing regulatory serine arginine protein kinases (mostly SRPK1 and SRPK2) has been found in different cancer types, leading to the expression of isoforms related to tumor growth and metastasis. The microenvironment of melanoma exhibits a strong presence of immune cells, which significantly influences tumor progression, and around 50% of cutaneous melanoma patients benefit from targeted immunotherapy. Here, we analyzed human malignant melanoma single-cell gene expression data and observed that SRPK1/2 overexpression correlates with immune system pathway alterations. In further analysis, we observed an increased presence of immune cells in biopsies from mice bearing metastatic melanoma treated with SRPIN340, a well-known SRPK1/2 pharmacological inhibitor. Local treatments increased the expression of proinflammatory cytokines at the tumor lesions and the activity of the spleen, accompanied by reduced pulmonary metastasis foci, edema formation, and alveolar congestion. In in vitro assays, SRPIN340 also potentiated immunological susceptibility, by increasing the expression of the antigen presenting MHCI and MHCII molecules and by increasing the ability of B16F10 cells to attract splenic cells in transwell assays. Taken together, these results reveal that the antimetastatic effect of SRPIN340 can also involve an increased immune response, which suggests additional functional clues for SRPKs in tumor biology.

Associations of human papillomavirus (HPV) genotypes and related risk factors in a cohort of women living with HIV in a Brazilian countryside city.

The human papillomavirus (HPV) is associated with cervical abnormalities. People living with HIV are more susceptible to HPV. Campos dos Goytacazes implemented the quadrivalent HPV vaccine (4vHPV) for women living with HIV (WLWH) in 2011, 4 years before the Brazilian public vaccination program. We aimed to characterize the genomic diversity and predictors of HPV infection in WLWH through a prospective cohort study. After the consent form was received, a questionnaire was applied and an endocervical sample was collected. For genotyping, a microarray HPV technique was performed. Two intervention moments were performed: T1, the initial moment, with collection and vaccination; T2 moment, 2 years after T1. Univariate and multivariate analyses were performed. The T1 moment cohort was formed by 146 women,107 belonging to Group 1(HPV-negative) and 39 to Group 2 (HPV-positive). The variables age, marital status, number of children, number of sexual partners, and CD4 count were protective against HPV. The variables number of sexual partners, marital status, and the number of children lost significance in multivariate analysis. Concerning T2 moment, 42 patients were followed with three positive cases. The use of 4vHPV is beneficial for this population and should also be recommended at an age from 26 to 45 years inside the public vaccination program.

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging.

The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.

Strategies to Improve the Antimicrobial Efficacy of Photodynamic, Sonodynamic, and Sonophotodynamic Therapies.

BACKGROUND AND OBJECTIVES: This work evaluated antimicrobial photodynamic therapy (PDT), sonodynamic therapy (SDT), and the association of both therapies (sonophotodynamic therapy [SPDT]), mediated by curcumin (Cur) against Staphylococcus aureus biofilm. Next, additional strategies for these treatments were assessed. MATERIALS AND METHODS: S. aureus biofilms received PDT, SDT, and SPDT, mediated by Cur (80 µM), LED light (450 nm), and 1 MHz ultrasound. The same treatments were also performed adding a strategy: Cur with sodium dodecyl sulfate (SDS), Cur with potassium iodide (KI) or a pre-treatment with ultrasound. Cell viability was determined and biofilm architecture was evaluated under confocal microscopy. RESULTS: SPDT was more effective to inactivate the bacteria than PDT and SDT. SDS achieved the greatest viability reductions, followed by KI and ultrasound pre-treatment. Confocal images revealed biofilm disruption and a reduced number of cells in all treatments. However, SPDT exhibited a pronounced effect and it was greater using SDS. CONCLUSION: SPDT was more effective and additional strategies potentiated its effectiveness. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Cytogenotoxic effects of nitrogen on hydroponic lettuce / Efeitos citogenotóxicos do nitrogênio em alface hidropônica

Nitrogen accumulation in hydroponically-grown lettuce may pose a health risk to consumers. Thus, the objective of this study was to analyze different concentrations of nitrogen applications in hydroponic lettuce cultivation and their effect on toxicity, cytotoxicity and genotoxicity. A nutrient film technique (NFT) hydroponic system was used to grow the lettuce variety "Vanda." The treatments consisted of different concentrations of nitrogen (in the form of calcium nitrate) in Furlani solution (75, 100, 125 and 150%), a negative and a positive control. The following commercial characteristics were measured: plant fresh weight (PFW), root fresh weight (RFW), shoot fresh weight (SFW), shoot diameter (SD), root dry weight (RDW), shoot dry weight (SDW) and leaf nitrogen (LN). Cytogenotoxicity was indicated by toxicity, cytotoxicity and genotoxicity, which were in turn determined by root length, the mitotic index, chromosomal aberrations and the presence of micronuclei. The nitrogen concentrations used in this experiment did not cause phenotypic toxicity or cytotoxicity in lettuce roots. The most severe genotoxicity was observed at the 125% nitrogen concentration, which nevertheless did not affect commercial characteristics. Although nitrogen fertilization provides great benefits to agriculture, such as greater yields, indiscriminate use should be avoided since concentrations above recommended rates may induce genotoxicity.

O acúmulo de nitrogênio em alface cultivada hidroponicamente pode representar um risco à saúde dos consumidores. Assim, o objetivo deste estudo foi analisar diferentes concentrações de aplicações de nitrogênio no cultivo de alface hidropônica e seus efeitos na toxicidade, citotoxicidade e genotoxicidade. Em sistema hidropônico do tipo filme de nutrientes (NFT) foi usado para cultivar a variedade de alface "Vanda". Os tratamentos consistiram em diferentes concentrações de nitrogênio (na forma de nitrato de cálcio) na solução Furlani (75, 100, 125 e 150%), um controle negativo e um positivo. Foram medidas as seguintes características comerciais: peso fresco da planta (PFW), peso fresco da raiz (RFW), peso fresco da parte aérea (SFW), diâmetro da parte aérea (SD), peso seco da raiz (RDW), peso seco da parte aérea (SDW) e nitrogênio foliar (LN). A citogenotoxicidade foi indicada por toxicidade, citotoxicidade e genotoxicidade, que por sua vez foram determinadas pelo comprimento da raiz, índice mitótico, aberrações cromossômicas e presença de micronúcleos. As concentrações de nitrogênio utilizadas neste experimento não causaram toxicidade fenotípica ou citotoxicidade em raízes de alface. A genotoxicidade mais severa foi observada na concentração de nitrogênio de 125%, que, no entanto, não afetou as características comerciais. Embora a fertilização nitrogenada traga grandes benefícios à agricultura, como maiores rendimentos, o uso indiscriminado deve ser evitado, pois concentrações acima das taxas recomendadas podem induzir genotoxicidade.

Annexin A1 promotes the nuclear localization of the epidermal growth factor receptor in castration-resistant prostate cancer.

Epidermal growth factor receptor is a cancer driver whose nuclear localization has been associated with the progression of prostate cancer to the castration-resistant phenotype. Previous reports indicated a functional interaction between this receptor and the protein Annexin A1, which has also been associated with aggressive tumors. The molecular pathogenesis of castration-resistant prostate cancer remains largely unresolved, and herein we have demonstrated the correlation between the expression levels and localization of the epidermal growth factor receptor and Annexin A1 in prostate cancer samples and cell lines. Interestingly, a higher expression of both proteins was detected in castration-resistant prostate cancer cell lines and the strongest correlation was seen at the nuclear level. We verified that Annexin A1 interacts with the epidermal growth factor receptor, and by using prostate cancer cell lines knocked down for Annexin A1, we succeeded in demonstrating that Annexin A1 promotes the nuclear localization of epidermal growth factor receptor. Finally, we showed that Annexin A1 activates an autocrine signaling in castration-resistant prostate cells through the formyl peptide receptor 1. The inhibition of such signaling by Cyclosporin H inhibits the nuclear localization of epidermal growth factor receptor and its downstream signaling. The present work sheds light on the functional interaction between nuclear epidermal growth factor receptor and nuclear Annexin A1 in castration-resistant prostate cancer. Therefore, strategies to inhibit the nuclear localization of epidermal growth factor receptor through the suppression of the Annexin A1 autocrine loop could represent an important intervention strategy for castration-resistant prostate cancer.

Parthenolide and its Analogues: A New Potential Strategy for the Treatment of Triple-Negative Breast Tumors.

Triple Negative Breast Cancers (TNBC) are heterogeneous and aggressive pathologies, with distinct morphological and clinical characteristics associated with their genetic diversity, epigenetics, transcriptional changes and aberrant molecular patterns. Treatment with anti-neoplastic drugs exerts systemic effects with low specificity, and incipient improvement in overall survival due to chemoresistance and recurrence. New alternatives for TNBC treatment are urgent and parthenolide or its analogues have been explored. Parthenolide is a sesquiterpene lactone with promising antitumor effects against TNBC cell lines. This review highlights the importance of parthenolide and its analogue drugs in TNBC treatment.

Immunoproteasome Subunits Are Required for CD8+ T Cell Function and Host Resistance to Brucella abortus Infection in Mice.

The immunoproteasome is a specific proteasome isoform composed of three subunits, termed ß1i, ß2i, and ß5i. Its proteolytic activity enhances the quantity and quality of peptides to be presented by major histocompatibility complex class I (MHC-I) molecules to CD8+ T cells. However, the role of the combined deficiency of the three immunoproteasome subunits in protective immunity against bacterial pathogens has not been investigated. In this study, we addressed the role of the immunoproteasome during infection by Brucella abortus, an intracellular bacterium that requires CD8+ T cell responses for the control of infection. Here, we demonstrate that immunoproteasome triple-knockout (TKO) mice were more susceptible to Brucella infection. This observed susceptibility was accompanied by reduced interferon gamma (IFN-γ) production by mouse CD4+ and CD8+ T lymphocytes. Moreover, the absence of the immunoproteasome had an impact on MHC-I surface expression and antigen presentation by dendritic cells. CD8+ T cell function, which plays a pivotal role in B. abortus immunity, also presented a partial impairment of granzyme B expression and, consequently, reduced cytotoxic activity. In conclusion, these results strongly suggest that immunoproteasome subunits are important components in host resistance to B. abortus infection by impacting both the magnitude and quality of CD8+ T cell responses.

Ghrelin therapy improves lung and cardiovascular function in experimental emphysema.

BACKGROUND: Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance. Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema. METHODS: Forty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA). In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. C animals (n=20) received saline alone (50 µL) using the same protocol. Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks. Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed. RESULTS: In elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-ß, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass. CONCLUSION: In the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass. These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema.

TLR7 and TLR3 Sense Brucella abortus RNA to Induce Proinflammatory Cytokine Production but They Are Dispensable for Host Control of Infection.

Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle. The immune response against this bacterium relies on the recognition of microbial pathogen-associated molecular patterns, such as lipoproteins, lipopolysaccharides, and DNA; however, the immunostimulatory potential of B. abortus RNA remains to be elucidated. Here, we show that dendritic cells (DCs) produce significant amounts of IL-12, IL-6, and IP-10/CXCL10, when stimulated with purified B. abortus RNA. IL-12 secretion by DCs stimulated with RNA depends on TLR7 while IL-6 depends on TLR7 and partially on TLR3. Further, only TLR7 plays a role in IL-12 production induced by B. abortus infection. Moreover, cytokine production in DCs infected with B. abortus or stimulated with bacterial RNA was reduced upon pretreatment with MAPK/NF-κB inhibitors. By confocal microscopy, we demonstrated that TLR7 is colocalized with B. abortus in LAMP-1+Brucella-containing vacuoles. Additionally, type I IFN expression and IP-10/CXCL10 secretion in DCs stimulated with bacterial RNA were dependent on TLR3 and TLR7. Our results suggest that TLR3 and TLR7 are not required to control Brucella infection in vivo, but they play an important role on sensing B. abortus RNA in vitro.

Instituição de um protocolo de higiene bucal em pacientes internados no CTI do HUSF / Establishment of a oral hygiene protocol in hospitalized patients at the ICU HUSF

Oral health caring in hospitalized patients is very important, considering the risks of complications that non disinfection of oral cavity can cause to your general health. Several risk of periodontal disease associations have been described in the literature, such as nosocomial pneumonia and cardiovascular disorders, among others. The introduction of oral hygiene protocols in hospitalized patients has been recommended by the simplicity and the potential they represent in preventing some systemic stages. The objective of this study was to apply the adjusted protocol oral hygiene in patients admitted to the Intensive Care Cento (ICU) of the Hospital Universitário Sul Fluminense (HUSF), Vassouras-RJ to improve the quality of dental care for hospitalized patients, preventing so its systemic complications of health. The disinfection of the oral cavity was made by the introduction of the use of 0.12% chlorhexidine gluconate, as well as proper oral hygiene instruction. Nursing professionals (students, assistants and technicians) were invited to participate in the project using the mouthwash (PerioPlak, Reymer) for routine and effective use in the prevention of oral infections. A comparison was conducted using two graphs showed a decrease of 0.44% in the number of mechanical ventilation infection from the use of the oral care protocol. It is concluded that it is extremely important the presence of a dentist in intensive care units to take care of the oral health of patients thus preventing risks of infection due to their health status (AU)

O cuidado com a saúde bucal em pacientes internados é muito importante, considerando os riscos de complicações que a não desinfecção da cavidade bucal possa causar no seu estado de saúde geral. Várias associações de risco da doença periodontal foram descritas na literatura, tais como alterações cardiovasculares e pneumonia nosocomial, dentre outras. A introdução de protocolos de higiene bucal em pacientes internados tem sido recomendada pela simplicidade e pelo potencial que representam na prevenção de alguns quadros sistêmicos. O objetivo deste trabalho foi aplicar o protocolo de higiene bucal em pacientes internados no Cento de Terapia Intensiva (CTI) do hospital Universitário Sul Fluminense (HUSF), Vassouras-RJ, visando melhorar a qualidade de atenção em saúde bucal ao paciente hospitalizado, prevenindo assim complicações do seu estado sistêmico de saúde. A desinfecção da cavidade bucal foi feita através da instituição do uso de gluconato de clorexidina a 0,12%, assim como instrução de higiene bucal adequada. Os profissionais da área de enfermagem (estudantes, auxiliares e técnicos) foram convidados a participar do projeto sendo disponibilizado o enxaguatório bucal (PerioPlak, REYMER) para uso rotineiro e efetivo na prevenção de infecções bucais. Foi realizado um comparativo através de dois gráficos que mostrou uma redução em 0,44% do número de infecção por ventilação mecânica a partir da utilização do protocolo de higiene bucal. Conclui-se que é de extrema importância a presença de um cirurgião-dentista nas unidades de terapia intensiva para cuidar da saúde bucal dos pacientes prevenindo assim riscos de infecções devido a seu estado de saúde (AU)

Lack of IL-1 Receptor-Associated Kinase-4 Leads to Defective Th1 Cell Responses and Renders Mice Susceptible to Mycobacterial Infection.

The Toll-like and IL-1 family receptors play critical roles in innate and adaptive immunity against intracellular pathogens. Although previous data demonstrated the importance of TLRs and IL-1R signaling events for the establishment of an effective immune response to mycobacteria, the possible function of the adaptor molecule IL-1R-associated kinase (IRAK)-4 against this pathogen has not been addressed. In this study, we determined the role of IRAK-4 in signaling pathways responsible for controlling mycobacterial infections. This kinase is important for the production of IL-12 and TNF-α by macrophages and dendritic cells exposed to mycobacteria. Moreover, Mycobacterium bovis-infected IRAK-4-knockout macrophages displayed impaired MAPK and NF-κB activation. IL-1ß secretion and caspase-1 activation were also dependent on IRAK-4 signaling. Mice lacking IRAK-4 showed increased M. bovis burden in spleen, liver, and lungs and smaller liver granulomas during 60 d of infection compared with wild-type mice. Furthermore, 80% of IRAK-4(-/-) mice succumbed to virulent M. tuberculosis within 100 d following low-dose infection. This increased susceptibility to mycobacteria correlated with reduced IFN-γ/TNF-α recall responses by splenocytes, as well as fewer IL-12p70-producing APCs. Additionally, we observed that IRAK-4 is also important for the production of IFN-γ by CD4(+) T cells from infected mice. Finally, THP-1 cells treated with an IRAK-4 inhibitor and exposed to M. bovis showed reduced TNF-α and IL-12, suggesting that the results found in mice can be extended to humans. In summary, these data demonstrate that IRAK-4 is essential for innate and adaptive immunity and necessary for efficient control of mycobacterial infections.

Individualization of controlled ovarian stimulation in vitro fertilization using markers of ovarian reserve: a systematic review / Individualização da estimulação ovariana controlada na fertilização in vitro com o uso de marcadores da reserva ovariana: uma revisão sistemática

Introduction: The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response. Objective: To summarize the predictive ability of ovarian reserve markers, and the therapeutic strategies that have been proposed in IVF after this prediction. Methods: A systematic review of the existing literature was performed by searching Medline, LILACS, SciELO and Pubmed, for publications related to ovarian reserve markers and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Results: 251 articles were found. Ten articles published between 2010 and 2015 were selected. Conclusion: Antral follicle count (AFC) and anti-Mullerian hormone (AMH), the most sensitive markers of ovarian reserve, are ideal in planning personalized COS protocols. These markers permit prediction of the ovarian response with reliable accuracy. Following the categorization of expected ovarian response clinicians can adopttailored therapeutic strategies for each patient.(AU)

Introdução: O principal objetivo da individualização do tratamento na fertilização in vitro é oferecer a cada mulher o melhor tratamento sob medida para suas próprias características únicas, maximizar, assim, as chances de gravidez e eliminar os riscos de iatrogenia durante a estimulação ovariana. A personalização do tratamento na fertilização in vitro deve basear-se na predição da resposta ovariana. Objetivo: Avaliar o uso de marcadores da reserva ovariana para individualização da dose inicial do FSH nos ciclos de FIV. Métodos: Revisão sistemática da literatura feita por meio de pesquisa Medline, Lilacs, SciELO e PubMed, para publicações relacionadas com marcadores reserva ovariana e sua incorporação, estimulação ovariana (COS) e protocolos controlados em fertilização in vitro. Resultados: Foram achados 251 artigos. Foram selecionados dez artigos publicados entre 2010 e 2015. Conclusão: Contagem de folículos antrais (AFC) e hormônio anti-Müulleriano (AMH), os marcadores mais sensíveis da reserva ovariana, são ideais no planejamento de protocolos individualizados. Esses marcadores permitem previsão da resposta ovariana com confiança De acordo com a resposta ovariana esperada, os clínicos podem adotar estratégias terapêuticas sob medida para cada paciente.(AU)