TLR9 agonism differentially impacts human NK cell-mediated direct killing and antibody-dependent cell-mediated cytotoxicity.

There are two known mechanisms by which natural killer (NK) cells recognize and kill diseased targets: (i) direct killing and (ii) antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated an indirect NK cell activation strategy for the enhancement of human NK cell killing function. We did this by leveraging the fact that toll-like receptor 9 (TLR9) agonism within pools of human peripheral blood mononuclear cells (PBMCs) results in a robust interferon signaling cascade that leads to NK cell activation. After TLR9 agonist stimulation, NK cells were enriched and incorporated into assays to assess their ability to kill tumor cell line targets. Notably, differential impacts of TLR9 agonism were observed-direct killing was enhanced while ADCC was not increased. To ensure that the observed differential effects were not attributable to differences between human donors, we recapitulated the observation using our Natural Killer-Simultaneous ADCC and Direct Killing Assay (NK-SADKA) that controls for human-to-human differences. Next, we observed a treatment-induced decrease in NK cell surface CD16-known to be shed by NK cells post-activation. Given the essential role of CD16 in ADCC, such shedding could account for the observed differential impact of TLR9 agonism on NK cell-mediated killing capacity.

Considerations for deriving a safe intake of propylene glycol.

The use of propylene glycol (PG) in food and other applications is widespread, and some estimates of dietary exposure to PG approach or exceed the Acceptable Daily Intake (ADI) of 25 mg/kg bw-day. The current ADI for PG applies a cumulative uncertainty factor of 100, which includes factors of 10 for both interspecies and intraspecies differences. Available toxicology studies and human data, however, indicate a plausible mode of action (MoA) that would support a chemical-specific adjustment factor (CSAF) of 1 for interspecies toxicodynamic differences, reducing the total uncertainty factor from 100 to 40. The MoA involves an increase in serum PG concentrations after metabolic saturation, leading to serum hyperosmolarity, which can ultimately cause hemolytic changes and red blood cell damage. Therefore, the species similarities in toxicodynamic response for this critical effect could support increasing the ADI from 25 to 62.5 mg/kg bw-day, applicable to both children and adults.

Association of Neighborhood Characteristics and Chronic Pain in Children and Adolescents in the United States.

OBJECTIVE: To determine the associations between neighborhood characteristics and chronic pain during childhood and adolescence in the United States, 2020-2021. METHODS: Cross-sectional analysis of the 2020 and 2021 National Survey of Children's Health. National Survey of Children's Health grouped parents' responses to questions about neighborhood characteristics into 5 categories: neighborhood support, neighborhood safety, school support, neighborhood amenities, and the presence of detracting neighborhood elements. Chronic pain was defined as parents reporting their children had "frequent or chronic difficulty with repeated or chronic physical pain, including headache or other back or body pain during the past 12 months." Multivariable Poisson regression analyses estimated associations between neighborhood characteristics and chronic pain, adjusted for sociodemographic characteristics. RESULTS: The sample contained 55,387 children (6 to 17 years), weighted to represent 44 million nationally. Children had significantly increased rates of chronic pain if they lived in neighborhoods that were unsupportive, unsafe, had unsafe schools, fewer amenities, and greater numbers of detracting elements ( P <0.0001). After adjusting for covariates, children had significantly increased chronic pain if they lived in neighborhoods that were not supportive (adjusted prevalence rate ratio=1.7 (95% CI: 1.5-1.9, P <0.0001), with similar patterns observed for living in neighborhoods characterized as not safe, that did not have safe schools, with fewer amenities, and/or more detracting elements. DISCUSSION: Disadvantageous neighborhood characteristics are associated with pediatric chronic pain prevalence. Future research should investigate the underlying mechanisms of this association and guide neighborhood interventions aimed at preventing and decreasing childhood chronic pain and its associated burdens.

Development and implementation of natural killer cell simultaneous ADCC and direct killing assay.

Assays to quantify natural killer (NK) cell killing efficacy have traditionally focused on assessing either direct killing or antibody dependent cell-mediated cytotoxicity (ADCC) independently. Due to the probability that immunotherapeutic interventions affect NK cell-mediated direct killing and NK cell-mediated ADCC differently, we developed an assay with the capacity to measure NK cell-mediated direct killing and ADCC simultaneously with cells from the same human donor. Specifically, this design allows for a single NK cell population to be split into several experimental conditions (e.g., direct killing, ADCC), thus controlling for potential confounders associated with human-to-human variation when assessing immunotherapy impacts. Our Natural Killer cell Simultaneous ADCC and Direct Killing Assay (NK-SADKA) allows researchers to reproducibly quantify both direct killing and ADCC by human NK cells. Furthermore, this optimized experimental design allows for concurrent analysis of the NK cells via flow cytometric immunophenotyping of NK cell populations which will facilitate the identification of relationships between NK cell phenotype and the subsequent killing potential. This assay will be valuable for assessing the broader impact(s) of immunotherapy strategies on both modes of NK cell killing.

Perspectives on recent reviews of aspartame cancer epidemiology.

Aspartame is a dipeptide non-sugar sweetener that was first marketed in the US in carbonated beverages in 1983, before gaining prominence globally. The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) and the WHO International Agency for Research on Cancer (IARC) completed evaluations of aspartame and cancer in July 2023. JECFA reaffirmed the safety of aspartame, stating that epidemiology evidence is "not convincing," and that there are no consistent associations between aspartame and cancer (JECFA/IARC, 2023; JECFA, 2023). JECFA also noted "reverse causality, chance, bias and confounding by socioeconomic or lifestyle factors, or consumption of other dietary components, could not be completely ruled out" in relevant epidemiology studies (JECFA/IARC, 2023). In contrast, IARC stated that there are three "high quality" studies on liver cancer (Riboli, 2023), but that the evidence is limited because "chance, bias or confounding could not be ruled out as an explanation for the positive findings" (JECFA/IARC, 2023). IARC does not provide an explanation as to how these studies can be both high quality and have these weaknesses, most notably potential exposure misclassification, or how inconsistent associations from studies with these weaknesses constitute limited evidence. Further, when IARC concludes an agent has limited or inadequate human evidence (and no sufficient animal or strong mechanistic evidence), it classifies that agent as either Group 2B, a possible human carcinogen, or Group 3, not classifiable as to its carcinogenicity. Ultimately, the interpretations of Group 2B and Group 3 classifications are intended to be similar. However, a Group 2B designation may make it appear to scientists and non-scientists alike that the evidence is pointing in the direction of causality. This can lead to unnecessary confusion with respect to the evidence, as well as a perception of a disagreement within WHO regarding aspartame. This apparent contradiction could have been avoided by assigning the IARC classification most consistent with the conclusion that the human evidence for cancer is inadequate: Group 3.

Beverage Consumption Patterns among U.S. Adolescents and Adults from a New 24-h Beverage Recall Survey Compared to the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Beverages are major dietary components of the United States (U.S.) population. Understanding the current consumption pattern of beverages is an important element in supporting healthy diets. Our objective was to assess the validity of the 24-h beverage consumption recall data collected in 2021 through a self-administered online questionnaire (referred to as the American Beverage Association-Brandscapes Worldwide survey, ABA-BSW) by comparing it to the 24-h dietary recall data collected in the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Summary statistics on the reported consumption amounts and consumption occasions (COs) of 13 beverage types (e.g., bottled water, carbonated soft drinks (CSD), tea, and others) by participants aged 13-64 years were compared between ABA-BSW (n = 20,553) and NHANES (n = 4437). The average daily consumption amount among consumers of all 13 beverage types combined was higher in ABA-BSW than in NHANES (1903 mL/day vs. 1704 mL/day). Within each beverage type, the average daily consumption amounts among consumers were generally lower in ABA-BSW except for CSD, plant-based drinks, and still juices and fruit-flavored drinks. Compared to NHANES, ABA-BSW participants reported consuming a wider variety of beverage groups, a higher number of COs per day, and lower consumption amounts within a given CO. Overall, beverage consumption patterns observed in ABA-BSW and NHANES were generally similar, supporting the design and implementation of the former survey. Further, the ABA-BSW data provide additional information on the within-day temporal beverage consumption patterns among adolescents and adults in the U.S. Differences in the observed consumption patterns between the surveys may be the result of various factors, including the survey implementation method, a consumption pattern shift between the survey time periods, beverage type availability, and impact of the COVID-19 pandemic on dietary patterns.

Testing protocols to optimize DNA extraction from tough leaf tissue: A case study in Encephalartos.

Premise: Plants with stiff, leathery leaves pose a challenge for standard DNA extraction protocols. These tissues are recalcitrant to mechanical disruption via TissueLyser (or analogous devices) and are often high in secondary metabolites. These compounding factors result in low yields, which may be sufficient for PCR amplification but are generally inadequate for genomic applications that require large quantities of high-quality DNA. Cycads in the genus Encephalartos exemplify these challenges, as this group of plants is fortified for life in harsh, dry habitats with notoriously thick and rigid leaves. Methods and Results: Using a DNA extraction kit, we tested three methods of mechanical disruption and examined the differences between stored vs. freshly collected samples and mature vs. senescing leaflets. We found that the manual method of pulverizing tissue yields the highest concentrations of DNA, and that both senescing leaflets and leaflet tissue that has been stored for extended periods yield sufficient DNA for genomic analyses. Conclusions: These findings shed light on the feasibility of using senescing leaves and/or tissue that has been stored on silica for long periods of time when attempting to extract large amounts of DNA. We provide here an optimized DNA extraction protocol that can be applied to cycads and other plant groups with tough or rigid leaves.

Low- and no-calorie sweetener intakes from beverages - an up-to-date assessment in four regions: Brazil, Canada, Mexico and the United States.

The current assessment estimated exposure to four low- and no-calorie sweeteners (LNCS) (aspartame, acesulfame potassium (AceK), steviol glycosides and sucralose) from beverages in Brazil, Canada, Mexico and the United States, using up-to-date nationally representative consumption data and industry reported-use level information. Two modelling scenarios were applied - the probabilistic model was guided by reported use level data, with estimated intake for an individual leveraging market-weighted average use level of a particular LNCS in any given LNCS-sweetened beverage type, while the distributional (brand-loyal) model assumed consumer behaviour-led patterns, namely that an individual will be brand loyal to a pre-determined beverage type. Consumer-only and general population intake estimates were derived for the overall population and individual age categories, and compared to the respective acceptable daily intake (ADI) as established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) for each LNCS. The mean, 90th percentile and 95th percentile intake estimates were substantially lower than the ADI in both modelling scenarios, regardless of the population group or market. In the probabilistic model, the highest consumer-only intake was observed for AceK in Brazilian adolescents (95th percentile, 12.4% of the ADI), while the highest 95th percentile intakes in the distributional model were observed for sucralose in Canadian adults at 20.9% of the ADI. This study provides the latest insights into current intakes of LNCS from water-based non-alcoholic LNCS-sweetened beverages in these regions, aligning well with those published elsewhere.

Current status of the reporting quality of abstracts in systematic reviews related to implant dentistry: a literature survey.

The aim of this study was to assess the reporting quality of abstracts in systematic reviews (SRs) related to implant dentistry and to assess the possible factors associated with the reporting quality. Abstracts of SRs in the field of implant dentistry, published in the last 5 years, were searched. The reporting quality was assessed and scored using the PRISMA for Abstracts checklist (PRISMA-A). The overall PRISMA-A score (OPS) and relative score (OPS%) per review were calculated according to adherence to the criteria presented in the checklist. Multivariable linear regression was performed to identify possible factors associated with reporting quality. Overall, 310 SRs were eligible for this study. Based on the maximum PRISMA-A score (score of 12), the mean OPS was 6.5 and OPS% was 54.2%. The items 'title', 'objectives', and 'number of included studies' were those most frequently reported in the abstracts, while the items 'registration' and 'funding' were the least reported. According to multivariable linear regression, the geographical origin of the articles was the only factor associated with better quality of abstract reporting, with higher OPS for SRs from Europe when compared to North America (coefficient 0.73; P = 0.049). The reporting quality of abstracts in SRs related to implant dentistry is suboptimal and needs to be improved. Journals should encourage adherence to reporting checklists in SRs.

[Vibrio vulnificus infection of the skin and soft parts. Communication of a case diagnosed in Argentina]. / Infección de piel y partes blandas por Vibrio vulnificus. Comunicación de un caso diagnosticado en Argentina.

Vibrio vulnificus is one of the most virulent Vibrio species known. It is a bacterium with universal distribution. The first case registered in Uruguay occurred in 2001 and, since then, several infections have occurred per year. Recently, in this country, V. vulnificus was responsible for a fatal soft tissue infection. Although no cases of human infection with this species have been reported in Argentina, researchers have recently identified V. vulnificus in samples associated with microplankton in the Rio Negro estuary. We present the case of a severe skin and soft tissue infection by V. vulnificus from an open wound in a patient in contact with a marine aquatic environment on the coast of the River Plate, in Uruguay. Isolation of vibrios from wound specimens can cause rapidly progressing tissue damage, particularly V. vulnificus which has a high mortality rate without early and appropriate intervention. In our case, the rapid identification of the microorganism allowed us to support the empirical treatment used, which a good clinical evolution.

Vibrio vulnificus es una de las especies de Vibrio más virulentas que se conocen. Es una bacteria de distribución universal. El primer caso registrado en Uruguay se produjo en 2001, y desde entonces ocurren varias infecciones por año. Recientemente, en ese país, V. vulnificus fue responsable de una infección de partes blandas de curso letal. Aunque no han sido comunicados casos de infección humana por esta especie en Argentina, se ha identificado recientemente Vibrio vulnificus en muestras asociadas con microplancton en el estuario del Río Negro. Presentamos el caso de una infección grave de piel y partes blandas por V. vulnificus a partir de una herida abierta en un paciente en contacto con medio acuático marino en la costa de Uruguay del Río de la Plata. El aislamiento de vibrios en muestras de heridas puede causar un daño en los tejidos con rápida progresión, en particular V. vulnificus, que tiene una alta mortalidad sin la precoz y apropiada intervención. En nuestro caso, la rápida identificación del microorganismo permitió avalar el tratamiento empírico utilizado, con una buena evolución clínica.

Infección de piel y partes blandas por Vibrio vulnificus. Comunicación de un caso diagnosticado en Argentina / Vibrio vulnificus infection of the skin and soft parts. Communication of a case diagnosed in Argentina

Resumen Vibrio vulnificus es una de las especies de Vibrio más virulentas que se conocen. Es una bacteria de distribución universal. El primer caso registrado en Uruguay se produjo en 2001, y desde entonces ocurren varias infecciones por año. Recientemente, en ese país, V. vulnificus fue responsable de una infección de partes blandas de curso letal. Aunque no han sido comunicados casos de infección humana por esta especie en Argentina, se ha identificado recientemente Vibrio vulnificus en muestras asociadas con microplancton en el estuario del Río Negro. Presentamos el caso de una infección grave de piel y partes blandas por V. vulnificus a partir de una herida abierta en un paciente en contacto con medio acuático marino en la costa de Uruguay del Río de la Plata. El aislamiento de vibrios en muestras de heridas puede causar un daño en los tejidos con rápida progresión, en particular V. vulnificus, que tiene una alta mortalidad sin la precoz y apropiada intervención. En nuestro caso, la rápida identificación del microorganismo permitió avalar el tratamiento empírico utilizado, con una buena evolución clínica.

Abstract Vibrio vulnificus is one of the most virulent Vibrio species known. It is a bacterium with universal distribution. The first case registered in Uruguay occurred in 2001 and, since then, several infections have occurred per year. Recently, in this country, V. vulnificus was responsible for a fatal soft tissue infection. Although no cases of human infection with this species have been reported in Argentina, researchers have recently identified V. vulnificus in samples associated with microplankton in the Rio Negro estuary. We present the case of a severe skin and soft tissue infection by V. vulnificus from an open wound in a patient in contact with a marine aquatic environment on the coast of the River Plate, in Uruguay. Isolation of vibrios from wound specimens can cause rapidly progressing tissue damage, particularly V. vulnificus which has a high mortality rate without early and appropriate intervention. In our case, the rapid identification of the microorganism allowed us to support the empirical treatment used, which a good clinical evolution.

Recomendaciones en el abordaje del hematoma intracerebral espontáneo durante la internación / Recommendations for the management of spontaneous intracerebral hemorrhage during hospitalization

Resumen El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neuro- lógico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualiza- das del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.

Abstract Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracere- bral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.

Optical computing of quantum revivals.

Interference is the mechanism through which waves can be structured into the most fascinating patterns. While for sensing, imaging, trapping, or in fundamental investigations, structured waves play nowadays an important role and are becoming the subject of many interesting studies. Using a coherent optical field as a probe, we show how to structure light into distributions presenting collapse and revival structures in its wavefront. These distributions are obtained from the Fourier spectrum of an arrangement of aperiodic diffracting structures. Interestingly, the resulting interference may present quasiperiodic structures of diffraction peaks on a number of distance scales, even though the diffracting structure is not periodic. We establish an analogy with revival phenomena in the evolution of quantum mechanical systems and illustrate this computation numerically and experimentally, obtaining excellent agreement with the proposed theory.

[Recommendations For The Management Of Spontaneous Intracerebral Hemorrhage During Hospitalization]. / Recomendaciones en el Abordaje del Hematoma Intracerebral Espontáneo Durante la Internación.

Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracerebral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.

El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neurológico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualizadas del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.

Systematic review of medication related osteonecrosis of the jaw (MRONJ) in patients undergoing only antiangiogenic drug therapy: surgery or conservative therapy?

Osteonecrosis of the jaw is a severe adverse condition affecting patients exposed to specific types of medications. Previous studies have highlighted that osteonecrosis of the jaw is triggered by invasive dental procedures and can be very challenging to manage, especially in patients with cancer. The primary aim of this review was to analyse all available evidence on the management (surgical and/or conservative) of medication related osteonecrosis of the jaws (MRONJ) in patients with a history of antiangiogenic drugs therapy and who had not been previously exposed to any antiresorptive drug treatments. A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until November 2020. Data were extracted from relevant papers and analysed according to the outcomes selected in this review. The search generated 28 studies eligible for the analysis. The total number of patients included in the analysis was 36. Sixteen patients were treated with anti-vascular endothelial growth factor drugs (anti-VEGF) while the remaining patients were administered a combination of antiangiogenic drugs. The most common MRONJ site was the mandible in 29 patients. MRONJ recurrence after treatment was only reported in six patients, the majority of which were treated conservatively. The data reviewed confirmed that an invasive procedure was the most common trigger of MRONJ with relatively high frequency of postoperative recurrence following treatment. However, due to the low quality of available research in the literature, it is difficult to draw a definitive conclusion on the validity of the presented treatment to manage patients affected by MRONJ associated with angiogenic therapy.

Transpiration-powered desalination water bottle.

Inspired by mangrove trees, we present a theoretical design and analysis of a portable desalinating water bottle powered by transpiration. The bottle includes an annular fin for absorbing solar heat, which is used to boost the evaporation rate of water from the interior synthetic leaf. This synthetic leaf comprises a nanoporous film deposited atop a supporting micromesh. Water evaporating from the leaf generates a highly negative Laplace pressure, which pulls the overlying source water across an upstream reverse osmosis membrane. Evaporated water is re-condensed in the bottom of the bottle for collection. The benefit of our hybrid approach to desalination is that reverse osmosis is spontaneously enabled by transpiration, while the thermal evaporation process is enhanced by heat localization and made more durable by pre-filtering the salt. We estimate that a 9.4 cm diameter bottle, with a 10 cm wide annular fin, could harvest about a liter of fresh water per day from ocean water.

Is there any biomaterial substitute for peri-implant soft tissue phenotype modification? A network meta-analysis of the appraisal literature.

Evidence shows that an increased width and thickness of the keratinized mucosa favours peri-implant health. The aim of this network meta-analysis was to compare the clinical effects of alternative biomaterials for peri-implant soft tissue phenotype modification (PSPM) in patients with dental implants when compared to autologous tissue grafts. An electronic search without language or date limitations was performed in four databases and the grey literature for articles published until November 2020. The eligibility criteria included randomized clinical trials (RCTs) evaluating the clinical outcomes of biomaterials for PSPM. A pairwise and network meta-analysis was conducted for each parameter to assess and compare the outcomes between the different treatment arms for the primary and secondary outcomes. A total of 11 RCTs were included in this review. The free gingival graft (FGG) showed the best clinical effect for increasing keratinized mucosa width (KMW). When compared in a network, the FGG demonstrated the best treatment ranking of probability results, followed by connective tissue graft (CTG), acellular dermal matrix (ADM), and xenogeneic collagen matrix (XCM). For the parameters 'mucosa thickness' and 'participant satisfaction with aesthetics', the results were CTG > ADM > XCM and XCM > ADM > CTG, respectively. Autogenous tissue grafts (FGG/CTG) demonstrate the best results in increasing KMW and mucosa thickness when compared to the other biomaterials.

Emerging Role of miR-345 and Its Effective Delivery as a Potential Therapeutic Candidate in Pancreatic Cancer and Other Cancers.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying mechanism(s) and delivery strategies of miR-345 have been investigated by us previously. Here, we summarize the potential therapeutic roles of miR-345 in different cancers, with emphasis on PDAC, for miRNA drug discovery, development, status, and implications. Further, we focus on miRNA nanodelivery system(s), based on different materials and nanoformulations, specifically for the delivery of miR-345.

Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 µg, 25 µg and 50 µg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.

Streptococcus pneumoniae prevalence in nasopharynx, oropharynx and gingival sulcus in Brazilian adults:A preliminary study.

AIM: This study aimed to evaluate the prevalence of S. pneumoniae colonization in three different sites in healthy adults: nasopharynx, oropharynx and gingival sulcus. METHODS: Two-hundred and sixty five adults, aged 20-60 years, who attended dental clinics in one public university (n = 106) and one military institution (n = 159) were enrolled in this study. Pneumococcal detection was performed by direct culture (DC) and PCR for lytA gene after a broth enrichment step. Capsular types were determined by sequential multiplex PCR. RESULTS: We identified 18 (6.8%) pneumococcal carriers among 265 adults by PCR, but only one (0.4%) pneumococcal strain was isolated by DC method. Oropharynx (17; 6.4%) was the main source of S. pneumoniae. Colonization of gingival sulcus and nasopharynx was found in 4 (1.5%) and 2 (0.8%) adults, respectively. Nine distinct capsular types were detected from 9 adults and co-colonization with 2 serotypes was confirmed in 4 (1.5%) subjects. Factors associated with carriage were being females, low level of schooling, non-military and regular medication. We observed a low (6.8%) pneumococcal carriage prevalence, but oropharyngeal samples yielded more sensitive results, especially by the PCR-based detection methodology. CONCLUSION: Gingival sulcus was found to be a possible reservoir for S. pneumoniae independently of the oropharynx or nasopharynx colonization.