Employing core regulatory circuits to define cell identity.

The interplay between extrinsic signaling and downstream gene networks controls the establishment of cell identity during development and its maintenance in adult life. Advances in next-generation sequencing and single-cell technologies have revealed additional layers of complexity in cell identity. Here, we review our current understanding of transcription factor (TF) networks as key determinants of cell identity. We discuss the concept of the core regulatory circuit as a set of TFs and interacting factors that together define the gene expression profile of the cell. We propose the core regulatory circuit as a comprehensive conceptual framework for defining cellular identity and discuss its connections to cell function in different contexts.

Do the blood anti-Müllerian hormone concentrations in young females correlate with the ovarian follicular population later in life in water buffalo?

In this longitudinal study, the anti-Müllerian hormone (AMH) levels in blood were determined in 32 Murrah buffalo females at 8, 10, 12, 16 and 19 months of age when females were synchronized and the antral follicular population (AFP) was estimated. Correlations of AFP to the AMH level at 19 months of age and retrospectively to younger ages were investigated. Then females were split into high and low AFP, and their AMH levels were compared for all ages and tested as predictors of AFP categories. The highest AMH level (p < .05) was detected at 8 months, reducing but not differing (p > .05) at 10, 12 and 16 months then reducing again (p < .05) at 19 months of age. The mean AFP was 17.6 ± 6.3 follicles, and it was positively correlated with AMH in all ages tested. High AFP females had approximately two times more antral follicles than low AFP (p < .05) and their AMH levels were higher (p < .01) than in low AFP ones in all ages. Only at 8 months, AMH levels can be used to precociously detect high AFP heifers (a cut-off point of 464.7 pg/mL; p < .05), while low AFP heifers could be detected by AMH measurements at 8, 10, 12 and 16 months of age (p < .05). We conclude that AMH of buffalo calves correlates with AFP of heifers later in life and depending on the age, its levels could be used to identify future females with low or high AFP.

Fertilization with follicular fluid reduces HSP70 and BAX expression on bovine in vitro embryos.

The in vivo fertilization process occurs in the presence of follicular fluid (FF). The aim of this study was to evaluate the effect of in vitro fertilization medium supplementation with 5% or 10% bovine follicular fluid (BFF) on the production of in vitro bovine embryos. FF was collected from ovarian follicles with a diameter of 8-10 mm, and cumulus-oocyte complexes (COCs) were co-incubated with sperm for 24 h in the commercial medium BotuFIV® (BotuPharma©), being distributed among the experimental groups: oocytes fertilized in a control medium; oocytes fertilized in a medium supplemented with 5% BFF; and oocytes fertilized in a medium supplemented with 10% BFF. After fertilization, the zygotes were cultured in vitro for 8 days. Embryo development was assessed through cleavage rates (day 2) and blastocyst formation rates (day 8). The relative expression of the genes OCT4, IFNT2, BAX, HSP70 and SOD2 was measured using the real-time polymerase chain reaction method. There was no difference (p > .05) among the different experimental groups in terms of cleavage rates and blastocyst formation rates. Regarding the gene expression results, only the blastocysts from oocytes fertilized with 10% BFF showed significantly lower expression of IFNT2 (p = .003) and SOD2 (p = .01) genes compared to blastocysts from oocytes fertilized in control medium alone, while there was no difference between blastocyst from oocytes fertilized in control medium and the ones from oocytes fertilized with 5% BFF. In addition to this, the blastocysts from oocytes fertilized with 5% BFF showed significantly reduced levels of expression of the heat shock protein HSP70 (p < .001) and the pro-apoptotic protein BAX (p = .015) compared to blastocysts from oocytes fertilized with control medium. This may indicate that lower supplementation of BFF to the IVF medium creates a more suitable environment for fertilization and is less stressful for the zygote.

Designing peptide amphiphiles as novel antibacterials and antibiotic adjuvants against gram-negative bacteria.

Gram-negative strains are intrinsically resistant to most antibiotics due to the robust and impermeable characteristic of their outer membrane. Self-assembling cationic peptide amphiphiles (PAs) have the ability to disrupt bacteria membranes, constituting an excellent antibacterial alternative to small molecule drugs that can be used alone or as antibiotic adjuvants to overcome bacteria resistance. PA1 (C16KHKHK), self-assembled into micelles, which exhibited low antibacterial activity against all strains tested, and showed strong synergistic antibacterial activity in combination with Vancomycin with a Fractional Inhibitory Concentration index (FICi) of 0.15 against E. coli. The molecules, PA2 (C16KRKR) and PA3 (C16AAAKRKR), also self-assembled into micelles, displayed a broad-spectrum antibacterial activity against all strains tested, and low susceptibility to resistance development over 21 days. Finally, PA1, PA 2 and PA3 displayed low cytotoxicity against mammalian cells, and PA2 showed a potent antibacterial activity and low toxicity in preliminary in vivo models using G. mellonella. The results show that PAs are a great platform for the future development of effective antibiotics to slow down the antibiotic resistance and can act as antibiotic adjuvants with synergistic mechanism of action, which can be repurposed for use with existing antibiotics commonly used to treat gram-positive bacteria to treat infections caused by gram-negative bacteria.

Artesunate does not affect oocyte maturation and early embryo development of bovine.

Despite the cytotoxicity and embryotoxicity previously reported artesunate is a recommended drug to treat malaria for adults, children, and women in the first trimester of pregnancy. To address the putative effects of artesunate on female fertility and preimplantation embryo development, when the pregnancy is not detectable yet, artesunate was added to the oocyte in vitro maturation and in vitro embryo development of bovine. Briefly, in experiment 1 the cumulus-oocyte complexes (COCs) were in vitro matured for 18 h with 0.5, 1, or 2 µg/mL of artesunate or not (negative control) and then checked for nuclear maturation and subsequent embryo development. In experiment 2, the COCs were in vitro matured and fertilized without artesunate, which was added (0.5, 1, or 2 µg/mL) from the 1st to the 7th day of embryo culture along with a negative and a positive control group with doxorubicin. As a result, the use of artesunate on oocyte in vitro maturation did not differ from the negative control (p > 0.05) regarding nuclear maturation, cleavage, and blastocyst formation. Also, artesunate on in vitro embryo culture did not differ from negative control (p > 0.05) regarding cleavage and blastocyst formation, except for positive control, with doxorubicin (p < 0.05). In conclusion, under the conditions investigated, there was no evidence of artesunate toxicity on oocyte competence and the preimplantation period of in vitro embryo development in the bovine model, however, artesunate use still should be taken carefully as the outcome of implantation after oocytes and blastocysts exposure to artesunate remains unknown.

Artesunate added to in vitro maturation did not impair oocyte competence in bovine.Artesunate added to in vitro culture did not affect cleavage and blastocyst formation.No evidence of artesunate toxicity in oocytes and embryos of bovine was found.

Larval habitats, species composition and distribution of malaria vectors in regions with autochthonous and imported malaria in Roraima state, Brazil.

BACKGROUND: Malaria control requires local action. Assessing the vector diversity and abundance provides information on the local malariogenic potential or risk of transmission. This study aimed to determine the Anopheles species composition, habitats, seasonal occurrence, and distribution in areas with autochthonous and imported malaria cases in Roraima State. METHODS: A longitudinal study was conducted from January 2017 to October 2018, sampling larvae and adult mosquitoes in three municipalities of Roraima State: Boa Vista, Pacaraima and São João da Baliza. These areas have different risks of malaria importation. Four to six mosquito larval habitats were selected for larval sampling at each municipality, along with two additional sites for adult mosquito collection. All larval habitats were surveyed every two months using a standardized larval sampling methodology and MosqTent for adult mosquitoes. RESULTS: A total of 544 Anopheles larvae and 1488 adult mosquitoes were collected from the three municipalities studied. Although the species abundance differed between municipalities, the larvae of Anopheles albitarsis s.l., Anopheles nuneztovari s.l. and Anopheles triannulatus s.l. were collected from all larval habitats studied while Anopheles darlingi were collected only from Boa Vista and São João da Baliza. Adults of 11 species of the genus Anopheles were collected, and the predominant species in Boa Vista was An. albitarsis (88.2%) followed by An. darlingi (6.9%), while in São João da Baliza, An. darlingi (85.6%) was the most predominant species followed by An. albitarsis s.l. (9.2%). In contrast, the most abundant species in Pacaraima was Anopheles braziliensis (62%), followed by Anopheles peryassui (18%). Overall, the majority of anophelines exhibited greater extradomicile than peridomicile-biting preference. Anopheles darlingi was the only species found indoors. Variability in biting times was observed among species and municipalities. CONCLUSION: This study revealed the composition of anopheline species and habitats in Boa Vista, Pacaraima and São João da Baliza. The species sampled differed in their behaviour with only An. darlingi being found indoors. Anopheles darlingi appeared to be the most important vector in São João da Baliza, an area of autochthonous malaria, and An. albitarsis s.l. and An. braziliensis in areas of low transmission, although there were increasing reports of imported malaria. Understanding the diversity of vector species and their ecology is essential for designing effective vector control strategies for these municipalities.

Cytokines profile in patients with acute and chronic hepatitis B infection.

Hepatitis B virus (HBV) is one of the leading causes of acute and chronic hepatitis and represents a serious public health threat. Cytokines are important chemical mediators that regulate the differentiation, proliferation, and function of immune cells, with accumulating evidence indicating that the inadequate immune responses are responsible for the elimination or persistence of HBV. This study aimed to determine the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17A) during HBV infection and investigate their association with genotypes. A total of 66 plasma samples, 19 from patients with acute and 47 with chronic hepatitis B infection, were subjected to biochemical tests, nested-PCR, and real-time PCR, with cytokines evaluated using a commercial BD Cytometric Bead Array Human Th1/Th2/Th17 Cytokine Kit. Healthy controls (10 individuals) were selected from blood donors with no history of liver diseases. No correlation was found between genotypes, viral load, and cytokines analyzed. All cytokines showed higher levels of production among infected individuals when compared with the control group. A positive correlation classified as moderate to strong was found between cytokines IFN-γ, TNF, IL-10, IL-6, IL-4, and IL-2 through the Spearman correlation coefficient. TNF (P = 0.009), IL-10 (P < 0.001), and IL-6 (P < 0.001) levels were higher in acute individuals compared with chronic and control groups. Theses cytokines could be involved in the elimination of virus and protection against chronicity.

Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination: A literature review.

Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high-risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co-infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Seroprevalence of human alphaherpesvirus 1 and 2 among pregnant women infected or uninfected with Zika virus from Rio de Janeiro, Brazil.

Pregnant women are an important group to be monitored for infection due to the risk of transmitting infections to their babies. Both herpes simples virus (HSV) and Zika virus (ZIKV) are neurotropic viruses that can be transmitted congenitally. In this study, the prevalence and risk factors of HSV among Zika-positive and -negative pregnant women from Rio de Janeiro, Brazil, were evaluated and compared. About 167 serum samples included in our study were from pregnant women with ZIKV infection symptoms, who were attended to in different hospitals in Rio de Janeiro between November 2015 to February 2016. Blood samples collected from 167 pregnant women were used for this study. The presence of HSV antibodies and viremia were evaluated by commercial ELISA and quantitative real-time polymerase chain reaction analyses, respectively. The data obtained from medical records were statistically analyzed. The HSV-1 and HSV-2 prevalence among pregnant women was 80.2% and 12.5% for Zika-positive women and 84.5% and 5.6% for Zika-negative women, respectively. None of the pregnant women exhibited HSV viremia. Age, trimester of gestation, and skin color were associated with HSV-1 and HSV-2 prevalence among the groups studied. HSV-2 was more prevalent in Zika-positive pregnant women than in Zika-negative pregnant women, and this simultaneous infection should be better investigated in future studies.

Human alphaherpesvirus 2 (HSV-2) among female sex workers from Brazil: cross-sectional study using respondent-driven sampling.

OBJECTIVE: Female sex workers (FSWs) are vulnerable to human alphaherpesvirus 2 (HSV-2) infection due to their high numbers of sexual partners. The objective of this study was to evaluate the seroprevalence and risk behaviours associated with HSV-2. METHODS: A cross-sectional study was conducted in Mato Grosso do Sul, Brazil. A total of 376 FSWs were recruited by respondent-driven sampling (RDS) methodology and answered an epidemiological questionnaire. Blood samples were collected to test for HSV-2 antibodies using commercial ELISA and for HSV-2 DNA using real-time PCR. RESULTS: The seropositivity was 47.3% (178/376) for HSV-2 IgG and 10.1% (38/376) for HSV-2 IgM. HSV-2 viraemia was detected in two infected FSWs with primary infections. In bivariate and multivariate analyses, the OR for HSV-2 IgG increased with age (OR=2.53-7.90, OR=2.66-6.37) and the number of sexual partners (OR=2.30-3.25). On the other hand, daily alcohol consumption (OR=0.10) and the use of condoms during the last intercourse (OR=0.47) were protective factors against HSV-2 acquisition. CONCLUSION: Despite the impact of FSWs in public health policies with the dissemination of sexually transmitted infections, there have been few studies performed regarding the prevalence of HSV-2 in Brazil, making it difficult to implement any control or preventative measures. The results produced here using an RDS methodology demonstrated a high prevalence, risk behaviours and primary infection among the FSWs. These results reinforce the need to implement control and preventative measures for HSV-2 infection in this population.

Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients.

BACKGROUND: The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. METHODS: 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. RESULTS: Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. CONCLUSION: These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.

Control of Peptide Amphiphile Supramolecular Nanostructures by Isosteric Replacements.

Supramolecular nanostructures with tunable properties can have applications in medicine, pharmacy, and biotechnology. In this work, we show that the self-assembly behavior of peptide amphiphiles (PAs) can be effectively tuned by replacing the carboxylic acids exposed to the aqueous media with isosteres, functionalities that share key physical or chemical properties with another chemical group. Transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering studies indicated that the nanostructure's morphologies are responsive to the ionization states of the side chains, which are related to their pKa values. Circular dichroism studies revealed the effect of the isosteres on the internal arrangement of the nanostructures. The interactions between diverse surfaces and the nanostructures and the effect of salt concentration and temperature were assessed to further understand the properties of these self-assembled systems. These results indicate that isosteric replacements allow the pH control of supramolecular morphology by manipulating the pKa of the charged groups located on the nanostructure's surface. Theoretical studies were performed to understand the morphological transitions that the nanostructures underwent in response to pH changes, suggesting that the transitions result from alterations in the Coulomb forces between PA molecules. This work provides a strategy for designing biomaterials that can maintain or change behaviors based on the pH differences found within cells and tissues.

Sperm chromatin protamination influences embryo development in unsexed and sexed bull semen.

Sex selection through sperm sorting offers advantages in regards selection pressure in high-producing livestock. However, the sex-sorting process results in sperm membrane and DNA damage that ultimately decrease fertility. We hypothesized that given the role of protamines in DNA packaging, protamine deficiency could account, at least partially, for the DNA damage observed following sperm sex sorting. To test this, we compared protamine status between unsexed and sexed spermatozoa from two bulls using the fluorochrome chromomycin A3 (CMA3) and flow cytometry. Then, we assessed embryo development following in vitro fertilization (IVF) using the same sperm treatments. Overall, sperm protamination was not different between sexed and unsexed semen. However, one of the two bulls displayed higher rates of protamine deficiency for both unsexed and sexed semen (P < 0.05). Moreover, unsexed semen from this bull yielded lower blastocyst (P < 0.05) and blastocyst hatching rates than unsexed sperm from the other bull. CMA3-positive staining was negatively correlated with cleavage (R2 85.1, P = 0.003) and blastocyst hatching (R2 87.6, P = 0.006) rates in unsexed semen. In conclusion, while the sex-sorting process had no effect on sperm protamine content, we observed a bull effect for sperm protamination, which correlated to embryo development rates following IVF.

The impact of imported malaria by gold miners in Roraima: characterizing the spatial dynamics of autochthonous and imported malaria in an urban region of Boa Vista.

BACKGROUND The number of malaria cases in Roraima nearly tripled from 2016 to 2018. The capital, Boa Vista, considered a low-risk area for malaria transmission, reported an increasing number of autochthonous and imported cases. OBJECTIVES This study describes a spatial analysis on malaria cases in an urban region of Boa Vista, which sought to identify the autochthonous and imported cases and associated them with Anopheles habitats and the potential risk of local transmission. METHODS In a cross-sectional study at the Polyclinic Cosme e Silva, 520 individuals were interviewed and diagnosed with malaria by microscopic examination. Using a global positional system, the locations of malaria cases by type and origin and the breeding sites of anopheline vectors were mapped and the risk of malaria transmission was evaluated by spatial point pattern analysis. FINDINGS Malaria was detected in 57.5% of the individuals and there was a disproportionate number of imported cases (90.6%) linked to Brazilian coming from gold mining sites in Venezuela and Guyana. MAIN CONCLUSIONS The increase in imported malaria cases circulating in the west region of Boa Vista, where there are positive breeding sites for the main vectors, may represent a potential condition for increased autochthonous malaria transmission in this space.

Initial Characterization of the Two ClpP Paralogs of Chlamydia trachomatis Suggests Unique Functionality for Each.

Members of Chlamydia are obligate intracellular bacteria that differentiate between two distinct functional and morphological forms during their developmental cycle, elementary bodies (EBs) and reticulate bodies (RBs). EBs are nondividing small electron-dense forms that infect host cells. RBs are larger noninfectious replicative forms that develop within a membrane-bound vesicle, termed an inclusion. Given the unique properties of each developmental form of this bacterium, we hypothesized that the Clp protease system plays an integral role in proteomic turnover by degrading specific proteins from one developmental form or the other. Chlamydia spp. have five uncharacterized clp genes, clpX, clpC, two clpP paralogs, and clpB In other bacteria, ClpC and ClpX are ATPases that unfold and feed proteins into the ClpP protease to be degraded, and ClpB is a deaggregase. Here, we focused on characterizing the ClpP paralogs. Transcriptional analyses and immunoblotting determined that these genes are expressed midcycle. Bioinformatic analyses of these proteins identified key residues important for activity. Overexpression of inactive clpP mutants in Chlamydia spp. suggested independent function of each ClpP paralog. To further probe these differences, we determined interactions between the ClpP proteins using bacterial two-hybrid assays and native gel analysis of recombinant proteins. Homotypic interactions of the ClpP proteins, but not heterotypic interactions between the ClpP paralogs, were detected. Interestingly, protease activity of ClpP2, but not ClpP1, was detected in vitro This activity was stimulated by antibiotics known to activate ClpP, which also blocked chlamydial growth. Our data suggest the chlamydial ClpP paralogs likely serve distinct and critical roles in this important pathogen.IMPORTANCEChlamydia trachomatis is the leading cause of preventable infectious blindness and of bacterial sexually transmitted infections worldwide. Chlamydiae are developmentally regulated obligate intracellular pathogens that alternate between two functional and morphologic forms, with distinct repertoires of proteins. We hypothesize that protein degradation is a critical aspect to the developmental cycle. A key system involved in protein turnover in bacteria is the Clp protease system. Here, we characterized the two chlamydial ClpP paralogs by examining their expression in Chlamydia spp., their ability to oligomerize, and their proteolytic activity. This work will help understand the evolutionarily diverse Clp proteases in the context of intracellular organisms, which may aid in the study of other clinically relevant intracellular bacteria.

A review of the molecular design and biological activities of RXR agonists.

An attractive approach to combat disease is to target theregulation of cell function. At the heart of this task are nuclear receptors (NRs); which control functions such as gene transcription. Arguably, the key player in this regulatory machinery is the retinoid X receptor (RXR). This NR associates with a third of the NRs found in humans. Scientists have hypothesized that controlling the activity of RXR is an attractive approach to control cellular functions that modulate diseases such as cancer, diabetes, Alzheimer's disease and Parkinson's disease. In this review, we will describe the key features of the RXR, present a historic perspective of the first RXR agonists, and discuss various templates that have been reported to activate RXR with a focus on their molecular structure, biological activity, and limitations. Finally, we will present an outlook of the field and future directions and considerations to synthesize or modulate RXR agonists to make these compounds a clinical reality.

Ulcers of the fingers and dorsum of the left hand caused by venous hypertension after construction of a brachiocephalic arteriovenous fistula: case report.

Venous ulcers caused by venous hypertension secondary to arteriovenous fistulae are rare. Their etiology can be confirmed by vascular Doppler ultrasonography, which can differentiate between stenosis of central vessels and hemodynamic overload caused by development of tributaries from the vein responsible for the arteriovenous fistula. We present a case caused by hemodynamic overload of a tributary, which diverted the primary flow from the fistula to the distal limb. We chose to ligate the fistula to treat the ulcers and create another arteriovenous fistula in the contralateral limb.

Efficacy of a high concentration of nano silver fluoride in preventing caries: A randomized controlled trial.

Background: To investigate the effectiveness of a novel agent containing Nano Silver Fluoride 1500 (NSF 1500) and chitosan to inactivate carious lesions in children. Material and Methods: The study included eighty children. While both groups had fluoride dentifrice applied to their teeth, only the experimental group received treatment with the NSF 1500-ppm solution. The first and sixth-month interval examinations were conducted by two calibrated dentists (k = 0.85). Results: The NSF 1500 group had 69.2% of their teeth with arrested decay, while the control group had 24.1%. The difference was statistically significant (p 0.001), with a preventive fraction of 59.4%. The number needed to treat (NNT) was approximately two. The NSF 1500 formulation was more effective than toothbrushing alone with fluoridated dentifrice in preventing dental caries. Conclusions: The effectiveness of NSF 1500 is determined by the size and depth of the dental cavity. Its ability to arrest caries lesions was comparable to previously tested products, NSF 400 and NSF 600. Key words:Preventive dentistry, dental caries, nanoparticles.