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Although several devices are available for small bowel capsule endoscopy, few studies have compared their visualization quality and diagnostic yield, despite users reporting subjective differences between them. This study aims to compare two widely used systems (Mirocam® MC1600 and OMOM® HD). Patients who underwent OMOM® HD capsule enteroscopy between August 2022 and February 2023 were prospectively included consecutively (cases). Controls were retrospectively selected from a database of patients who underwent Mirocam® MC1600 enteroscopy between March 2018 and July 2022 in a 1:1 ratio. Controls were matched for potential confounders (age, sex, indication, hospitalization, comorbidities, and opioid prescription). The small bowel cleanliness (global and divided by tertiles), the diagnostic yield (positive findings) and the transit times (TT) were compared. Overall, 214 patients were included (107:107). Global bowel preparation was similar between the OMOM® and Mirocam® groups. However, the average scores for each tertile were significantly higher when the OMOM® HD capsule was used (p < 0.05). Small bowel TT was shorter for OMOM® HD (265 ± 118 versus 307 ± 87 min, p = 0.020), while the diagnostic yield (55.0%) and relative distribution of lesions were similar. This study suggests that capsule characteristics, namely resolution, and illumination, systematically interfere with the perception of preparation quality. However, this did not affect the diagnostic yield. [ABSTRACT FROM AUTHOR]

Marine microplastics are emerging as a growing environmental concern due to their potential harm to marine biota. The substantial variations in their physical and chemical properties pose a significant challenge when it comes to sampling and characterizing small-sized microplastics. In this study, we introduce a novel microfluidic approach that simplifies the trapping and identification process of microplastics in surface seawater, eliminating the need for labeling. We examine various models, including support vector machine, random forest, convolutional neural network (CNN), and residual neural network (ResNet34), to assess their performance in identifying 11 common plastics. Our findings reveal that the CNN method outperforms the other models, achieving an impressive accuracy of 93% and a mean area under the curve of 98 ± 0.02%. Furthermore, we demonstrate that miniaturized devices can effectively trap and identify microplastics smaller than 50 µm. Overall, this proposed approach facilitates efficient sampling and identification of small-sized microplastics, potentially contributing to crucial long-term monitoring and treatment efforts. [ABSTRACT FROM AUTHOR]

Dying with dignity is a right, defined as a process with the following characteristics. Dying with minimal suffering from symptoms and limited invasive treatment. The study aimed at understanding how the pandemic changed the way of dying in end-of-life care and what we can then add to what was done previously. A search was carried out in the PUBMED/Medline database to find articles that answered the research question. We carried out this research between December 2019 and June 2021. Articles with original data written in English, Portuguese and Spanish were used as keywords: 'end of life'; 'palliative care'; 'COVID-19'; 'dignity' and telemedicine'. Twenty-two studies met the inclusion criteria. There was significant heterogeneity in the origin of these studies conducted in 12 different countries. Five themes were found from the articles: Palliative care during the COVID-19 pandemic; end of life during the COVID-19 pandemic; the evolution of telemedicine during the COVID-19 pandemic; use of telemedicine in palliative care; and the use of telemedicine and dignity at the end of life. The results were relatively positive in terms of some parameters; however, some suggestions for improvement stood out. Telemedicine has enormous potential to improve care at the end of life in terms of quality of life, autonomy and adherence to pharmacological and non-pharmacological treatment. However, more intervention studies are needed to create protocols for monitoring these patients at home. [ABSTRACT FROM AUTHOR]

Hybrid argon plasma coagulation (hAPC) is a novel technique that combines conventional argon plasma coagulation and waterjet submucosal expansion. The aims of this metanalysis were to evaluate the efficacy and safety of hAPC in the setting of Barret's esophagus (BE) ablation and as an adjunct to colonic endoscopic mucosal resection (EMR). Four electronic databases were searched, and the results were analyzed by two independent authors. Random-effects meta-analyses of the proportions of endoscopic and histologic remission (for BE), recurrence, and post-procedure adverse events were performed using R. Studies' reporting quality was also assessed. From the 979 identified records, 13 studies were included (10 regarding BE and three colonic EMR). The pooled percentages of endoscopic and histologic remission after hAPC for BE were 95% (95% confidence interval [CI] 91–99, I2 = 34) and 90% (95%CI 84–95, I2 = 46), respectively, while major adverse events and recurrence were registered in 2% (95%CI 0–5, I2 = 41) and 11% (95%CI 2–27, I2 = 11), respectively. Concerning hAPC-assisted EMR, the pooled percentages of major adverse events and recurrence were 5% (95%CI 2–10, I2 = 0) and 1% (95%CI 0–3, I2 = 40). Evidence suggests that the main advantages of hAPC are the increase in safety in the setting of BE ablation and the reduction of local recurrence after colonic EMR. Trials comparing hAPC with standard strategies are required to support its use for these indications. [ABSTRACT FROM AUTHOR]

Objective: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We performed both clinical and molecular descriptions of four families with MEN1 in a follow-up at a tertiary center in Brası'lia. Methods: From a preliminary review of approximately 500 medical records of patients with pituitary neuroendocrine tumor (PitNET) from the database of the Neuroendocrinology Outpatient Clinic of the University Hospital of Brası'lia, a total of 135 patients met the criteria of at least two affected family members. From this cohort, we have identified 34 families: only four with a phenotype of MEN1 and the other 30 families with the phenotype of familial isolated pituitary adenoma (FIPA). Eleven patients with a clinical diagnosis of MEN1 from these four families were selected. Results: Variants in MEN1 gene were identified in all families. One individual from each family underwent genetic testing using targeted high-throughput sequencing (HTS). All patients had primary hyperparathyroidism (PHPT), and the second most common manifestation was PitNET. One individual had welldifferentiated liposarcoma, which has been previously reported in a single case of MEN1. Three variants previously described in the database and a novel variant in exon 2 have been found. Conclusions: The study allowed the genotypic and phenotypic characterization of families with MEN1 in a follow-up at a tertiary center in Brası'lia. [ABSTRACT FROM AUTHOR]

Tesamorelin, a synthetic growth hormone-releasing hormone, is indicated for the reduction of visceral adipose tissue (VAT) in people with HIV. Here, we performed a post hoc analysis of participants receiving tesamorelin for 26 weeks in a phase III clinical trial. Efficacy data were compared between individuals with and without dorsocervical fat, stratified by tesamorelin response. Among tesamorelin responders, VAT and waist circumference (WC) decreased in both dorsocervical fat groups and did not statistically differ (VAT P = 0.657, WC P = 0.093). These data demonstrate that tesamorelin is equally effective and should be considered in the treatment of excess VAT regardless of the presence of dorsocervical fat. [ABSTRACT FROM AUTHOR]

Background: The prosthetic screw fixes the prostheses to the implants. Upon osteointegration, the untightening of the prosthetic screw is the most common problem in oral rehabilitation with implants. Objective: To study the deformation of the implant retaining hexagonal screw head. Methods: This investigation used two methods for evaluating the screw head's area of deformation (mm2): a stereoscopic microscopy and micro computed tomography (microCT). For stereoscopic microscopy, 16 titanium alloy (T) and 16 titanium gold‐plated alloy (G) screws of the Zimmer Biomet™ brand were used, divided into eight groups: group 0 (control group), groups T1 and G1 (screws tightened 10 times to 20 Ncm), the groups T2 and G2 (screws tightened 20 times to 20 Ncm) and the groups T3 and G3 (screws tightened 10 times to 30 Ncm). In the study with microCT, one screw was randomly chosen from each of the groups described above to perform the scanning by microCT. Results: When comparing the type of screw material using stereoscopic microscopy, no statistically significant differences were found (p > 0.05). Contrarily, different number of successive grips and different torque value showed statistically significant differences in the head section of the retaining screws (p < 0.05). The observation by microCT showed the torque applied is crucial to the head deformation in titanium screws. In gold‐plated screws the successive tightening appears to be pivotal. Conclusion: Titanium and gold screws tend to behave similarly. By increasing the tightening cycles and the torque values of protocols greater levels of deformations can be expected. In general, microCT data showed better results for gold‐plated titanium alloy. Clinical Significance: To control severe screw head deformation and the impossibility of untightening the implant's restoration, clinicians should avoid extreme torque values and prevent surpassing 10 tightening cycles. [ABSTRACT FROM AUTHOR]

Effective environmental monitoring has become a worldwide concern, requiring the development of novel tools to deal with pollution risks and manage natural resources. However, a majority of current assessment methods are still costly and labor-intensive. Thanks to the rapid advancements in microfluidic technology over the past few decades, great efforts have been made to develop miniaturized tools for rapid and efficient environmental monitoring. Compared to traditional large-scale devices, microfluidic approaches provide several advantages such as low sample and energy consumption, shortened analysis time and adaptabilities to onsite applications. More importantly, it provides a low-cost solution for onsite environmental assessment leveraging the ubiquitous materials such as paper and plastics, and cost-effective fabrication methods such as inkjet printing and drawing. At present, devices that are disposable, reproducible, and capable of mass production have been developed and manufactured for a wide spectrum of applications related to environmental monitoring. This review summarizes the recent advances of low-cost microfluidics in the field of environmental monitoring. Initially, common low-cost materials and fabrication technologies are introduced, providing a perspective on the currently available low-cost microfluidic manufacturing techniques. The latest applications towards effective environmental monitoring and assessment in water quality, air quality, soil nutrients, microorganisms, and other applications are then reviewed. Finally, current challenges on materials and fabrication technologies and research opportunities are discussed to inspire future innovations. [ABSTRACT FROM AUTHOR]

The present study aimed to test, in vitro, the antimicrobial activity against Candida albicans and Streptococcus mutans and the surface roughness of a 3D-printed polymethylmethacrylate dental resin enhanced with graphene. A 3D-printed polymethylmethacrylate dental resin was reinforced with four different concentrations of graphene: 0.01, 0.1, 0.25 and 0.5 wt%. Neat resin was used as a control. The specimens were printed in a liquid crystal display printer. Disc specimens were used in antimicrobial evaluation, and bar-shaped specimens were used to measure surface roughness. The study of antimicrobial activity included the inhibition of the growth of C. albicans and S. mutans and their adhesion to the resin's surface. Surface roughness increased with the increase in the graphene concentration. The growth inhibition of C. albicans was observed in the different concentrations of graphene after 24 h, with no recovery after 48 h. The specimens doped with graphene were capable of inactivating S. mutans after 48 h. The surface-adhesion studies showed that the density of microbial biofilms decreases in the case of specimens doped with graphene. Graphene, despite increasing the resin's surface roughness, was effective in inhibiting the growth and the adhesion to the resin's surface of the main inducers of prosthetic stomatitis. [ABSTRACT FROM AUTHOR]

Plastic pollution has emerged as a growing concern worldwide. In particular, the most abundant plastic debris, microplastics, has necessitated the development of rapid and effective identification methods to track down the stages and evidence of the pollution. In this paper, we combine low-cost plastic staining technologies using Nile Red with the continuous feature offered by microfluidics to propose a low-cost 3D printed device for the identification of microplastics. It is observed that the microfluidic devices indicate comparable staining and identification performance compared to conventional Nile Red staining processes while offering the advantages of continuous recognition for long-term environmental monitoring. The results also show that concentration, temperature, and residency time possess strong effects on the identification performance. Finally, various microplastics have been applied to further demonstrate the effectiveness of the proposed devices. It is found that, among different types of microplastics, non-spherical microplastics show the maximal fluorescence level. Meanwhile, natural fibers indicate better staining quality when compared to synthetic ones. [ABSTRACT FROM AUTHOR]

The generation of degradation products (DPs) like ions and organo‐metallic particles from corroding metallic implants is an important healthcare concern. These DPs generate local and systemic toxicity. The impact on local toxicity is well documented, however, little is known about systemic toxicity. This is mainly due to the limited scope of the current microtiter plate‐based (static) toxicity assay techniques. These methods do not mimic the systemic (dynamic) conditions. In this study, it is hypothesized that DPs incubated with cells in static conditions might provide improper systemic toxicity results, as there is no movement mimicking the blood circulation around cells. This study reports the development of a three‐chambered prototype microfluidic system connected to the operational hip implant simulator to test the cellular response induced by the DPs. This setup is called a dynamic microfluidic bioreactor—hip simulator system. We hypothesize that a dynamic microfluidic system will provide a realistic toxicology response induced by DPs than a static cell culture plate. To prove the hypothesis, Neuro2a (N2a) cells were used as representative cells to study systemic neurotoxicity by the implant DPs. The microfluidic bioreactor system was validated by comparing the cell toxicity against the traditional static system and using COMSOL modeling for media flow with DPs. The hip implant simulator used in this study was a state‐of‐the‐art sliding hip simulator developed in our lab. The results suggested that static toxicity was significantly more compared to dynamic microfluidic‐based toxicity. The newly developed DMBH system tested for in situ systemic toxicity on N2a cells and demonstrated very minimum toxicity level (5.23%) compared to static systems (31.16%). Thus, the new DMBH system is an efficient tool for in situ implant metal systemic toxicity testing. [ABSTRACT FROM AUTHOR]

Abstract Background Heterosexual intercourse remains the major route of HIV-1 transmission worldwide, with almost 5 million new infections occurring each year. Women increasingly bear a disproportionate burden of the pandemic, thus there is an urgent need to develop new strategies to reduce HIV-1 transmission that could be controlled by women themselves. The potential of topical microbicides to reduce HIV transmission across mucosal surfaces has been clearly identified, and some agents are currently under evaluation in clinical trials. Many of these "first generation" microbicides consist of polyanionic compounds designed to interfere with viral attachment. Here we have evaluated two candidate polyanion compounds in clinical trials, PRO 2000 and dextrin sulphate (DxS) to determine their safety and efficacy against in vitro HIV-1 and HSV-2 infection using cellular and tissue explant models. Results PRO 2000 and DxS potently inhibited infection by HIV-1 X4 and R5 isolates when present during viral exposure. However PRO 2000 required 10-fold and DxS 2000-fold more compound to block infection with R5 virus than X4. While both compounds were virucidal for X4 HIV-1, neither was virucidal for R5 virus. PRO 2000 efficiently inhibited infection of cervical explants and dissemination of virus by migratory DC. DxS was less active, able to completely inhibit cervical explant infection, but providing only partial reduction of virus dissemination by DC. PRO 2000, but not DxS, also inhibited HIV-1 binding to DC-SIGN+ cells and trans infection of co-cultured target cells. The inflammatory potential of both compounds was screened by measurement of cytokine production from cervical explants, and statistically significant increases were only observed for IL-1β and RANTES following treatment with PRO 2000. Both compounds also demonstrated potent activity against HSV-2 infection of cervical epithelial cells. Conclusion Our results demonstrate that PRO 2000 is a potent inhibitor of R5 HIV-1 infection and dissemination pathways in human cervical explants. DxS, while demonstrating significant inhibition of R5 infection, was less active against DC mediated dissemination pathways. PRO 2000 has now entered human phase III efficacy trials.

Parental investment in Arapaima gigas includes nest building and guarding, followed by a care provision when a cephalic fluid is released from the parents’ head to the offspring. This fluid has presumably important functions for the offspring but so far its composition has not been characterised. In this study the proteome and peptidome of the cephalic secretion was studied in parental and non-parental fish using capillary electrophoresis coupled to mass spectrometry (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were significantly different between males and parental males (PC-males), 126 between females and parental females (PC-females), 51 between males and females and 9 between PC-males and PC-females. Identification revealed peptides were produced in the inner ear (pcdh15b), eyes (tetraspanin and ppp2r3a), central nervous system (otud4, ribeye a, tjp1b and syn1) among others. A total of 422 proteins were also identified and gene ontology analysis revealed 28 secreted extracellular proteins. From these, 2 hormones (prolactin and stanniocalcin) and 12 proteins associated to immunological processes (serotransferrin, α-1-antitrypsin homolog, apolipoprotein A-I, and others) were identified. This study provides novel biochemical data on the lateral line fluid which will enable future hypotheses-driven experiments to better understand the physiological roles of the lateral line in chemical communication. [ABSTRACT FROM AUTHOR]

Objective: In early 2015, an outbreak of an acute exanthematous illness with dengue-like symptoms occurred in northeastern Brazil. By the end of the same year, an unexpected increase in the number of cases of microcephaly was observed in the region. The microcephaly outbreak cause was unknown and rumors pointing to various potential causes arose. Since we were unaware at the time if this scenario would attract the interest of the broader scientific community, due to the neglected regions associated and as often happens with many others health conditions related to infectious diseases in Latin America. This coupled with the fact that diagnostic testing for Zika virus was not available, prompted us to design a study that could demonstrate the correlation between the development of an exanthematous illness with Zika-like symptoms during pregnancy and the delivery of a newborn with congenital microcephaly. Results: Mothers who experienced symptoms associated with the Zika virus during pregnancy had 10 times higher odds of delivering newborns with congenital microcephaly when compared with mothers who did not exhibit Zikalike symptoms. Thus, the acute exanthematous illness outbreak could be associated with the congenital microcephaly outbreak. We could not distinguish which virus caused the acute exanthematous illness in the study subjects (Zika, dengue or chikungunya), but these results could help to reduce the misquided speculation in regards to the cause of the microcephaly and could have expedited public health policies intended for controlling the mosquito vector. In addition to the lower head circumference, microcephalic neonates also had lower thoracic circumference, lower height and lower weight compared to non-microcephalic babies suggesting intrauterine growth restriction. Additionally, we found borderline association between mothers classified as homemakers and, who had past dengue infections with microcephaly. Prior contraction of dengue virus seems to play a role in the risk for the condition reflecting the domestication of the Aedes Aegypti and the enhancement of the Zika virus infection by dengue antibodies, respectively. The limitations of this study are: (a) participants recall bias, (b) absence of laboratory test results for Zika virus and other arboviruses and (c) incomplete test results for other pathogens that could lead to microcephaly. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infection of ectocervical tissues with HIV-1BaL among PRE women ( n = 20) in the follicular and luteal phases of the menstrual cycle and POST women ( n = 17) at baseline and after ∼1 month of treatment with 0.01% vaginal E2 cream. Compared to PRE women, we measured higher levels of p24 antigen after ex vivo infection in tissues from POST women. POST women had a significantly thinner vaginal epithelium with decreased tight junction proteins and a higher density of mucosal immune T cells and lower levels of CD1a antigen-presenting cells, antimicrobial peptides, and inflammatory cytokines in the CVL ( p values <.05). POST women had higher vaginal pH and lower vaginal Lactobacilli ( p values <.05) than PRE women. After vaginal E2 therapy, CV endpoints and ex vivo HIV replication in POST tissues were similar to those observed in PRE tissues. The CV mucosa in POST women is thinned and compromised, with increased HIV-target immune cells and decreased antimicrobial factors, being more susceptible to HIV infection. After POST women receive topical E2 treatment, mucosal endpoints are similar to PRE levels. [ABSTRACT FROM AUTHOR]

Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is tributyltin chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, dichloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to tributyltin chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, dichloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike tributyltin chloride, which is a full agonist of RXRα, dibutyltins dichloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts tributyltin chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and tributyltin chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins dichloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, tributyltin chloride and dibutyltin dilaurate reduced LPS-stimulated TNFa expression. Our findings indicate that dibutyltins diacetate, dichloride, dilaurate, and maleate are PPARγ partial agonists and that dibutyltins dichloride and dilaurate are also partial RXRα agonists. Furthermore, dibutyltins induce adipogenesis in a PPARγ-dependent manner and repress inflammatory genes in 3T3-L1 and RAW 264.7 cells. Although dibutyltins display some partial PPARγ/RXRα agonistic effects, the translation of cell-based results assays into in vivo effects on inflammation and insulin resistance is not entirely known. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the actions of organostanic compounds in whole-body context. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants ( n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) has been linked to an increased risk of human immunodeficiency virus (HIV) acquisition and transmission in observational studies, but the underlying biological mechanisms are unknown. We measured biomarkers of subclinical vaginal inflammation, endogenous antimicrobial activity, and vaginal flora in women with BV and repeated sampling 1 week and 1 month after completion of metronidazole therapy. We also compared this cohort of women with BV to a healthy control cohort without BV. A longitudinal, open label study of 33 women with a Nugent score of 4 or higher was conducted. All women had genital swabs, cervicovaginal lavage (CVL) fluid, and cervicovaginal biopsies obtained at enrollment and received 7 days of metronidazole treatment. Repeat sampling was performed approximately 1 week and 1 month after completion of therapy. Participant's baseline samples were compared to a healthy, racially matched control group ( n=13) without BV. The CVL from women with resolved BV (Nugent 0-3) had significantly higher anti-HIV activity, secretory leukocyte protease inhibitor (SLPI), and growth-related oncogene alpha (GRO-α) levels and their ectocervical tissues had significantly more CD8 cells in the epithelium. Women with persistent BV after treatment had significantly higher levels of interleukin-1β, tumor necrosis factor alpha (TNF-α), and intercellular adhesion molecule 1 (ICAM-1) in the CVL. At study entry, participants had significantly greater numbers of CCR5+ immune cells and a higher CD4/CD8 ratio in ectocervical tissues prior to metronidazole treatment, compared to a racially matched cohort of women with a Nugent score of 0-3. These data indicate that BV is associated with changes in select soluble immune mediators, an increase in HIV target cells, and a reduction in endogenous antimicrobial activity, which may contribute to the increased risk of HIV acquisition. [ABSTRACT FROM AUTHOR]

HIV may induce gastrointestinal (GI) mucosal immune dysregulation similar to inflammation observed in ulcerative colitis (UC). Colorectal biopsies from healthy controls ( N=12) and from participants with HIV ( N=20) or UC ( N=9) were subjected to real time (RT)-PCR for selected cytokines, chemokines, antimicrobial peptides, Toll-like receptors, and inflammatory signaling and epithelial barrier proteins. HIV long terminal repeat relative copy number (RCN) in HIV participant biopsies was quantified by RT-PCR. Mean interleukin (IL)-6 mRNA levels did not differ significantly between HIV and UC participants ( p=0.48) but were significantly higher relative to control mRNA levels only for HIV participants ( p=0.03). Mean IL-8 and human defensin (HD) 5 mRNA levels were similar between HIV and UC participants ( p=1.0 and p=0.35, respectively) and were significantly greater in both groups relative to controls ( p<0.05 for all). Human beta-defensin (HBD)-2 mRNA levels were higher in UC relative to HIV and control participants ( p<0.01 for both). Conversely, HBD-1 mRNA levels were downregulated in UC vs. HIV participants ( p=0.01). Mediator gene expression did not differ significantly between HIV participants with detectable ( N=10) or nondetectable ( N=10) plasma viral loads. Tissue HIV relative copy number (RCN) correlated with plasma viral load ( r=0.88, p<0.01) but not with mediator mRNA levels. The results of this study indicate that both chronic HIV infection and UC are associated with similar patterns of IL-6, IL- 8, and HD5 expression in colorectal biopsy tissue. These findings suggest overlapping mechanisms for GI mucosal inflammation in these two illnesses and merit further investigation in larger studies. [ABSTRACT FROM AUTHOR]

Background The limited success of recent HIV topical pre-exposure prophylaxis clinical trials highlights the need for more predictive models of drug efficacy that better simulate what may happen during sexual exposure. To address this gap, we developed complementary in vitro models to evaluate the ability of drugs to retain anti-HIV activity if cells were washed with seminal plasma (simulating what may happen following exposure to ejaculate), and to protect drugnaive T cells (representing newly recruited immune cells) co-cultured with explants that had been pretreated with drug. We focused on tenofovir disoproxil fumarate (TDF); the nonnucleoside reverse transcriptase inhibitors dapivirine (DPV) and IQP-0528; and the entry inhibitors maraviroc (MVC) and the D-peptide chol-PIE-12 trimer (PIE12).Studies were extended to macaques and the ability of cervical biopsies obtained from animals treated with an intravaginal ring formulation of IQP-0528 to protect ex vivo co-cultured T cells was determined. The antiviral activity of cervicovaginal lavage samples against a primary Clade C isolate were also measured and correlated with drug levels. Results Cells exposed to TDF were equally protected from HIV whether or not the drug-treated cells were washed with medium or seminal plasma prior to challenge. In contrast, several-fold higher concentrations of NNRTIs and entry inhibitors were needed to attain similar levels of HIV inhibition following a wash with seminal plasma. Conversely, the NNRTIs and PIE12, but not TDF or MVC, were effectively transferred from ex vivo treated explants and protected co-cultured T cells. Biopsies obtained from IQP-0528 ring-treated macaques also protected co-cultured T cells with viral inhibition ranging from 42-72%. Antiviral activity correlated with the concentration of drug recovered. Combinations of TDF with IQP-0528 protected in both in vitro models. Conclusions Together, these models suggest that intracellularly retained drugs such as TDF may protect resident immune cells following coitus but sustained delivery may be required to protect immune cells subsequently recruited into the genital tract. Sustained delivery may also be critical for NNRTIs, which are rapidly transported out of cells and could be lost following sexual intercourse. An ideal approach may be a combination of drugs with complementary bioavailability profiles formulated for sustained delivery. [ABSTRACT FROM AUTHOR]

In the past few years, the transdisciplinary field of HIV prevention has reached several milestones. Topically applied tenofovir gel provided significant protection from sexual transmission of HIV in a large-scale clinical trial and oral Truvada (emtricitabine/tenofovir disoproxil fumarate) was recently approved for preexposure prophylaxis (PrEP) following two successful clinical trials in men and women. These achievements are tempered by the disappointing results of other clinical trials, which highlight the complexities of prevention research. In this perspective, we discuss scientific and developmental gaps for topical chemoprophylaxis of the sexual transmission of HIV, which depends on the complex interactions between the pharmacokinetics and pharmacodynamics of drugs, formulation and delivery systems, anatomic site of transmission, and host mucosal immune defenses. Despite the considerable time and resources devoted to unraveling the initial steps in sexual transmission of HIV, current knowledge is based on animal models and human explanted tissue, which may not fully recapitulate what happens clinically. Understanding these events, including the role that sex hormones, semen, and mucosal secretions play in transmission, and the interplay between innate immunity, the mucosal environment, and drug efficacy is paramount. This drives some of the most pressing questions in the field. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to compare two commercially available screw--type sandblasted and acid-etched (SLA) Ti implant systems from Eckermann Laboratorium S.L., with similar geometry and distinct microtopography, regarding surface properties and osteoblastic cytocompatibility.Material and Methods: Implant I (referred as a conventional SLA system) and Implant II (a system patented as Eckcyte®) were characterized for macro and microtopograpphy, surface roughness and chemical composition. For the cytocompatibility studies, human bone marrow osteoblastic cells were seeded over the implants' surface, and the cell response was assessed for cell adhesion and proliferation, alkaline phosphatase (ALP) activity and matrix mineralization. Results: Implant I presented a rough surface with irregularly shaped and sized cavities among flatter appearing areas, whereas Implant II exhibited a homogeneous rough microporous surface. Compared to Implant I, Implant II presented higher Ra values (0.8 [SD 0.008] µm and 1.21 [SD 0.15] µm, respectively, P < 0.05) and also increased values of Rz, Rt and Rsm, a more negative value of Rsk, and similar RKu values. XPS showed the expected presence of Ti, O, C and N; Al, Si, F, P and Ca were detected in low concentrations. Implant II exhibited significantly lower Al levels. Both implants supported the adhesion, proliferation and differentiation of osteoblastic cells. Implant II showed a thicker fibrilar cell layer and an earlier onset and more abundant matrix mineralization.Conclusions: The homogeneous rough and microporous surface of Implant II is most probably a main contributor for its improved cell response. [ABSTRACT FROM AUTHOR]