Related ArticlesEffects of locally applied Insulin-like Growth Factor-I on osseointegration. Med Oral Patol Oral Cir Bucal. 2019 Aug 19;: Authors: López-Quiles J, Forteza-López A, Montiel M, Clemente C, Fernández-Tresguerres JA, Fernández-Tresguerres I Abstract BACKGROUND: The aim of this study was to assess the effect of local application of IGF-I on osseointegration of dental implants placed in osteoporotic bones. MATERIAL AND METHODS: 16...
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Related ArticlesIs the re-use of sterilized implant abutments safe enough? (Implant abutment safety). Med Oral Patol Oral Cir Bucal. 2019 Aug 19;: Authors: Sánchez-Garcés MA, Jorba M, Ciurana J, Vinas M, Vinuesa MT Abstract BACKGROUND: The reuse of implant healing abutments is common in dental practice. Effective elimination of bacteria and viruses is accomplished by conventional sterilization. The aim of this work was to explore the eventual survival...
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Related ArticlesStomatological disorders in older people: An epidemiological study in the brazil southern. Med Oral Patol Oral Cir Bucal. 2019 Aug 19;: Authors: Fattori E, Teixeira DS, de Figueiredo MA, Cherubini K, Salum FG Abstract BACKGROUND: The aim of this retrospective, cross-sectional and observational study was to perform a survey of the stomatological conditions of elderly patients seen in a period of 40 years at a Stomatology Service in Southern...
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The publisher regrets that the Conflict of Interests statements provided by the author were not added as supplementary items. Please see below a summary statement of the conflicts of interest for this manuscript: (Source: Lung Cancer)
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A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers comparing modulating effects of intermittent versus continuous low dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low dose...
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Patients with oral potentially malignant disorders (OPMD) must undergo regular clinical surveillance to ensure that any progression to malignancy is detected promptly. Autofluorescence imaging (AFI) is an optical modality that can assist clinicians in detecting early cancers and high-grade dysplasia. Patients with OPMD undergoing surveillance for development of oral cancer were examined using AFI at successive clinic visits. Autofluorescence images acquired at 133 clinical visits from sites in 15...
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Since the contribution of genetic factors to the burden of breast cancer has not well investigated in Iran, we aimed to examine the prevalence of mutations in breast cancer susceptibility genes, BRCA1/2 and PALB2, and to investigate the predictive potential of hereditary breast cancer risk criteria for genetic testing in Iranian population. Next Generation Sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria...
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Direct-acting antivirals(DAA) are now the mainstay of treatment for patients with chronic hepatitis C virus(HCV); however, there is some controversy over whether use of DAAs for HCV, as compared with interferon(IFN)-based regimens, leads to an increased risk of hepatocellular carcinoma (HCC) development. We investigated the association between use of DAAs and subsequent development of HCC in longitudinal data from HCV patients of diverse backgrounds (various ages, ethnicities, and geographic regions)...
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MDM2 regulates a variety of cellular processes through its dual protein:protein interaction and ubiquitin ligase activities. One major function of MDM2 is to bind and ubiquitinate P53, thereby regulating its proteasomal degradation. This function is in turn controlled by the cell fate determinant NUMB, which binds to and inhibits MDM2 via a short stretch of 11 amino acids, contained in its phosphotyrosine-binding (PTB) domain, encoded by exon 3 of the NUMB gene. The NUMB-MDM2-P53 circuitry is relevant...
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Bacteria with multi-replicon genome organizations, including members of the family Rhizobiaceae, often carry a variety of niche-associated functions on large plasmids. While evidence exists for cross-replicon interactions and co-evolution between replicons in many of these systems, remarkable strain-to-strain variation is observed within secondary replicons, suggesting environment-dependent fitness benefits of the accessory genome. Here, we show that curing of the tumor-inducing virulence plasmid...
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Objectives: To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes...
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Objectives: To compare tidal volumes, inflating pressures and other ventilator variables of infants receiving synchronized intermitted mandatory ventilation with volume guarantee during emergency neonatal transport with those of infants receiving synchronized intermitted mandatory ventilation without volume guarantee. Design: Retrospective observational study. Setting: A regional neonatal emergency transport service. Patients: We enrolled 77 infants undergoing emergency neonatal...
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Planta MedDOI: 10.1055/a-0998-5125Comfrey is a medicinal plant, extracts of which are traditionally used for the treatment of painful inflammatory muscle and joint problems, because the plant contains allantoin and rosmarinic acid. However, its medicinal use is limited because of its toxic pyrrolizidine alkaloid (PA) content. PAs encompass more than 400 different compounds that have been identified from various plant lineages. To date, only the first pathway-specific enzyme, homospermidine synthase...
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Abstract Advances in microfabrication allow for highly sensitive calorimeters with dramatically reduced volume, decreased response time and increased energy resolution. These calorimeters hold the potential for designs of ELISA platforms competitive with fluorescent and chemiluminescent technologies. We have developed a new assay platform using conventional ELISA reagents to produce a thermal signal quantifiable using calorimetry. Our optimized micromachined calorimeters have...
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Abstract In this study, a novel film-based immunochromatographic microfluidic device (IMD) has been developed for malaria diagnosis. A microfluidic channel was patterned on a polyethylene terephthalate (PET) double-sided adhesive film using a plotting cutter and was assembled with a polycarbonate (PC) film. The PC film used for the probe immobilization layer was activated using oxygen plasma treatment to modify the film surface with avidin-biotin linker to immobilize a capture...
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Epidermal growth factor receptor (EGFR)-mutated lung cancer represents about one-third of non-small cell lung cancer (NSCLC) patients worldwide.1 Prior to 2018, lung cancers harboring EGFR mutations sensitive to tyrosine kinase inhibitors (TKIs) were treated with erlotinib, gefitinib, or afatinib in the front-line setting.2-4 Dacomitinib was also FDA approved in the front-line setting for TKI-sensitive EGFR-mutated lung cancer.5 Nearly all patients develop progressive disease, many due to secondary...
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Purpose. The current study aimed at assessing vitamin D level and vitamin D receptor polymorphism in hypothyroid Egyptian patients and its effect on hypothyroidism and thyroid morphology, also to find a causal relation between vitamin D and hypothyroidism. Methods. This case-control study was conducted on 35 hypothyroid patients and 35 matched unrelated healthy controls. Total serum 25-hydroxyvitamin D3 and thyroid antibodies were measured using a human ELISA kit. Genotyping was performed by using...
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Abstract Recent studies have shown that re-expression of stem cell factors contribute to pathogenesis, therapy resistance, and recurrent disease in ovarian carcinomas. In this study, we compare the expression and co-expression of stem cell markers ALDH1 and SOX2 in different types of serous ovarian tumors. A total of 215 serous ovarian tumors (161 high-grade serous carcinomas (HGSC), 17 low-grade serous carcinomas (LGSC), 37 atypical proliferative serous tumors (APST)), and 10...
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Background: The choice of anesthetic technique for ischemic stroke patients undergoing endovascular thrombectomy is controversial. Intravenous propofol and volatile inhalational general anesthetic agents have differing effects on cerebral hemodynamics, which may affect ischemic brain tissue and clinical outcome. We compared outcomes in patients undergoing endovascular thrombectomy with general anesthesia who were treated with propofol or volatile agents. Methods: Consecutive endovascular...
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Background: Anesthetic technique affects the neuroendocrine stress response to surgery. In this retrospective study, we compared the neuroendocrine stress response in patients undergoing endoscopic transsphenoidal pituitary adenoma surgery (ETSPAS) with total intravenous anesthesia (TIVA) with propofol-remifentanil or balanced anesthesia (BAL) with sevoflurane-remifentanil. Materials and Methods: Eighty-nine patients undergoing ETSPAS were anesthetized with either propofol-remifentanil (TIVA...
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Key PointsUBL4A is a novel IFN-stimulated gene.UBL4A positively regulates innate immune response.UBL4A interacts with and targets TRAF6 for K63-linked ubiquitination.
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Key PointsSpecific Jun family members cooperate with BATF in promoting IL-9 in Th9 cells.Bach2 cooperates with BATF to promote IL-9 in Th9 cells.Expression and function of bZIP factors dictate IL-9 activation in Th17 cells.
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Key PointsMSC EV may stimulate increased antimicrobial activity during bacterial pneumonia.Increased antimicrobial activity is associated with increased LTB4 production.MSC EV may increase LTB4 production via transfer of miR145 to target cells.
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Key PointsATG16L2-deficient mice are viable and exhibit intact canonical autophagy.Intestinal infection reveals ATG16L2–(epithelial) ATG16L1 genetic interaction.
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Key PointsActive immunization with DJ NS1 plus NS3 induces a strong Ab response.Active immunization with DJ NS1 plus NS3 induces specific T cell responses.Combined DJ NS1 plus NS3 provides enhanced protection against DENV infection.
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The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the “metabolic memory” and the Developmental Origins of Health and Disease (DOHaD) hypothesis. The mechanism of “metabolic memory” has become a hot topic in the field of DM worldwide and could...
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New drugs with novel mechanisms of resistance are desperately needed to address both community and nosocomial infections due to Gram-negative bacteria. One such potential target is LpxC, an essential enzyme that catalyzes the first committed step of Lipid A biosynthesis. Achaogen conducted an extensive research campaign to discover novel LpxC inhibitors with activity against Pseudomonas aeruginosa. We report here the in vitro antibacterial activity and pharmacodynamics of ACHN-975, the only molecule...
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The available antifungal therapeutic arsenal is limited. The search for alternative drugs with fewer side effects and new targets remains a major challenge. Decyl gallate (G14) is a derivative of gallic acid with a range of biological activities and wide spectra antifungal activity. Previously, our group demonstrated the promising anti-Paracoccidioides activity of G14. In this work, aiming to evaluate the antifungal characteristics of G14 for P. lutzii, chemical-genetic interaction analysis was conducted...
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The bedaquiline regimen for the treatment of MDR-TB in adults is a loading dose of 400 mg QD for 2 weeks followed by 200 mg t.i.w. for 22 weeks. Most TB antibiotics administered with bedaquiline are given QD. Using pharmacokinetic simulations, we explored alternative QD bedaquiline regimens and determined that 200 mg QD for 8 weeks followed by 100 mg QD provides comparable exposures to the approved regimen. This simpler regimen is under clinical evaluation.
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Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways, and analyzed this transmission network in the context of statewide patient transfer data and patient-level...
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Mutants with enhanced growth in the presence of an antibiotic are more difficult to identify than mutants where the antibiotic's minimum inhibitory concentration increases, because they are not amenable to lethal selection in vitro. We report that activatory mutations in the CreC signal sensor enhance growth of Escherichia coli in the presence of cefoxitin, cefotaxime and meropenem without increasing their minimum inhibitory concentrations. Enhanced growth is dependent on over-production of the inner-membrane...
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The physiological factors that contribute to Mycobacterium abscessus lung infections remain unclear. We determined if antibiotic treatment targeting a major CF pathogen (i.e. Pseudomonas aeruginosa) could provide the ideal conditions for the establishment of M. abscessus infection. Our data showed that P. aeruginosa inhibits M. abscessus biofilm formation under control conditions, and that antimicrobial therapy selectively targeting P. aeruginosa diminishes this competitive interaction, hereby increasing...
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Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have now demonstrated the therapeutic potential of bacteriophage EF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains...
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ACC-1 is a plasmid-encoded class C β-lactamase identified in clinical isolates of Klebsiella pneumoniae, Proteus mirabilis, Salmonella enterica, and Escherichia coli. ACC-1-producing bacteria are susceptible to cefoxitin whereas they are resistant to oxyimino cephalosporins. Here, we depict crystal structures of apo ACC-1, adenylylated ACC-1, and acylated ACC-1 complexed with cefotaxime and cefoxitin. ACC-1 has noteworthy structural alterations in the R2-loop, the - loop, and the Phe119-loop along...
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in vitro activities of rifampin, rifabutin, rifapentine and rifaximin were tested against 200 PJI-associated staphylococci. Seven rifampin-resistant isolates had MICs ≥4 μg/mL. Three isolates had rifampin MICs 0.25-1μg/mL and harbored a Asp471Gly RpoB variant. The remaining isolates had rifampin MICs ≤0.016 μg/mL. Rifampin, rifabutin, rifapentine and rifaximin MBBC50 values for rifampin-susceptible isolates were 8, 1, 2, 4 (S. aureus), and 2, 0.06, 0.25, 0.5 (S. epidermidis) μg/mL, respectively....
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Plant defensins are a large family of proteins, most of which have antifungal activity against a broad spectrum of fungi. However, little is known about how they exert their activity. The mechanism of action of only a few members of the family have been investigated and, in most cases, there are still a number of unknowns. To gain a better understanding of the antifungal mechanisms of a set of 4 defensins, NaD1, DmAMP1, NbD6 and SBI6, we screened a pooled collection of the non-essential gene deletion...
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The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. Cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus. This study aimed to determine if azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles. The cyp51A gene of clinical and environmental...
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Trichomoniasis is a sexually transmitted disease with hundreds of millions of annual cases worldwide. Approved treatment options are limited to two related nitro-heterocyclic compounds, yet resistance to these drugs is an increasing concern. New antimicrobials against the causative agent, Trichomonas vaginalis are urgently needed. We show here that clinically approved anti-cancer drugs that inhibit the proteasome, a large protease complex with a critical role in degrading intracellular proteins in...
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Antibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-targeting drugs. However, rescue by isopentenyl pyrophosphate was variable, ranging from 2700-fold for clindamycin to just 1.7-fold...
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Background: Recurrent Vulvovaginal Candidiasis (RVVC) is a widespread chronic infection that has a substantial negative impact on work and quality of life. The development of antimicrobial resistance and biofilm formation are speculated to contribute to Candida pathogenicity and treatment ineffectiveness. Designed antimicrobial peptides (dAMPs) are chemically modified from endogenous antimicrobial peptides that provide the first line of defense against pathogens. The goal here is to identify a dAMP...
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