Zirconia Implants Produced by Additive Manufacturing - A Scoping Review.

INTRODUCTION: Additive manufacturing is a tool with potential use in medicine and dentistry. The manufacture of metals and composites is already advanced, however, concerns about titanium hypersensitivity, tissue staining, and corrosion caused by gradual material degradation encourage research into more biocompatible alternatives. OBJECTIVE: This systematic scoping review aimed to gather studies that evaluated zirconia implants produced by additive manufacturing to describe the current stage of the printing technique and the final product. METHODS: Searches in Embase, PubMed, SCOPUS, Web of Science, and Google Scholar databases were enriched with manual searches between February and March 2021 and updated in June 2022 using keywords: zirconium implants, zirconium oxide, additive manufacturing, rapid prototyping, 3D printing, selective laser melting, and electron beam melting. The criteria included studies that evaluated or described zirconia implants obtained by 3D printing, with a direct relationship to dentistry or orthopedics. RESULTS: The database search resulted in 671 articles. Eight articles were selected for full reading and remained in this systematic review. CONCLUSION: The printing technique for zirconia implants is promising. However, further studies are required before implants produced by the printing technique can be tested clinically. The literature with results regarding the impression product is still limited.

Does the Incorporation of Graphene Oxide into PMMA Influence its Antimicrobial Activity?

INTRODUCTION: The increase in infectious diseases mediated by oral bacteria has been one of the most potent threats to human health, specifically to the elderly. Researchers seek to incorporate antimicrobial nanomaterials into PMMA to control the colonization of microorganisms and reduce deadly diseases. OBJECTIVE: To conduct a systematic review to answer the question: "Does graphene oxide incorporated into polymethylmethacrylate influence its antimicrobial activity?" METHODS: The electronic search was performed in PubMed, Embase, Web of Science, Scopus, and Google Scholar databases, and articles published until October 2021 were selected. The search terms were: ("acrylic resin" OR PMMA) AND (graphene OR "oxide graphene") AND (antimicrobial OR antibacterial OR "anti-infective agent"). The risk of bias analysis of the articles was performed using the quasi-experimental study assessment tool adapted from the JBI. RESULTS: Two hundred and fifty-nine articles were found in the databases. After removing the duplicates, 245 were analyzed by title and abstract. Of these, 06 were selected for full reading, of which 03 met the eligibility criteria and were included in this systematic review. CONCLUSION: This systematic review's findings can infer that the incorporation of graphene in the form of graphene-based coatings to PMMA showed antimicrobial effectiveness.

Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria.

OBJECTIVE: Idiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin ß-N-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities. DESIGN: To test the hypothesis, we treated wild-type mice, primary neuronal cultures, cell lines and isolated mitochondria with BMAA, and analysed its impact on gut microbiota composition, barrier permeability, inflammation and aSyn aggregation as well as in brain inflammation, dopaminergic neuronal loss and motor behaviour. To further examine the key role of mitochondria, we also determined the specific effects of BMAA on mitochondrial function and on inflammasome activation. RESULTS: BMAA induced extensive depletion of segmented filamentous bacteria (SFB) that regulate gut immunity, thus triggering gut dysbiosis, immune cell migration, increased intestinal inflammation, loss of barrier integrity and caudo-rostral progression of aSyn. Additionally, BMAA induced in vitro and in vivo mitochondrial dysfunction with cardiolipin exposure and consequent activation of neuronal innate immunity. These events primed neuroinflammation, dopaminergic neuronal loss and motor deficits. CONCLUSION: Taken together, our results demonstrate that chronic exposure to dietary BMAA can trigger a chain of events that recapitulate the evolution of the PD pathology from the gut to the brain, which is consistent with 'gut-first' PD.

Factors that Affect the Shear Bond Strength of Pit and Fissure Sealants to Tooth Structure: A Systematic Review.

INTRODUCTION: Pit and fissure sealants are effective in preventing caries disease, however, they may present flaws that damage the physical barrier leading to treatment failure. OBJECTIVE: To answer the question ''Do pit and fissure sealants present good adhering to the dental structure when analyzed by their resistance to shear/microshear?". METHODS: This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and was recorded in Open Science Framework. Embase, PubMed, SCOPUS, and Web of Science databases were used for the search strategy. The articles were selected according to the eligibility criteria. The risk of bias was performed with the adaptation of the quasi-experimental studies tool by Joanna Briggs Institute (JBI). RESULTS: 1245 studies were found in the databases when applying the search strategy, after removal of duplicates 881 were evaluated and 44 were selected. After applying the JBI tool, 30 studies presented low risk and 15 moderate risk of bias. Meta-analysis was not possible to performed due to the heterogeneity of the studies. CONCLUSION: The adhesion is dependent on the application protocol, and among the protocols evaluated, conditioning with 37% phosphoric acid for 60 seconds and contamination of the substrate, as these can affect sealant adhesion.

Probiotic properties of yeasts isolated from Brazilian fermented table olives.

AIMS: To investigate the probiotic potential of yeasts isolated from naturally fermented Brazilian table olives. METHODS AND RESULTS: Eighteen yeast strains were tested in terms of: safety; survival of gastrointestinal and digestion conditions; antimicrobial activity; cellular hydrophobicity; autoaggregation ability and adhesion to epithelial cells; coaggregation and inhibition of pathogenic bacteria adhesion. Six yeasts showed favourable results for all probiotic attributes: Saccharomyces cerevisiae CCMA 1746, Pichia guilliermondii CCMA 1753, Candida orthopsilosis CCMA 1748, Candida tropicalis CCMA 1751, Meyerozyma caribbica CCMA 1758 and Debaryomyces hansenii CCMA 1761. These yeasts demonstrated resistance to 37°C, pH 2·0 and bile salts, and survived in vitro digestion (≥106  CFU per ml). Furthermore, the yeasts exhibited a hydrophobic cell surface (42·5-92·2%), autoaggregation capacity (41·0-91·0%) and adhesion to Caco-2 (62·0-82·8%) and HT-29 (57·6-87·3%) epithelial cell lines. Also, the strains showed antimicrobial activity against Salmonella Enteritidis as well as the ability to coaggregate and reduce the adhesion of this pathogen to intestinal cells. CONCLUSIONS: Autochthonous yeasts from naturally fermented Brazilian table olives have probiotic properties, with potential for development of new probiotic food products. SIGNIFICANCE AND IMPACT OF STUDY: These data are important and contribute to the knowledge of new potential probiotic yeasts capable of surviving gastrointestinal tract conditions and inhibiting pathogenic bacteria.

Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer's disease features in cortical neurons.

BACKGROUND: After decades of research recognizing it as a complex multifactorial disorder, sporadic Alzheimer's disease (sAD) still has no known etiology. Adding to the myriad of different pathways involved, bacterial neurotoxins are assuming greater importance in the etiology and/or progression of sAD. ß-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by some microorganisms namely cyanobacteria, was previously detected in the brains of AD patients. Indeed, the consumption of BMAA-enriched foods has been proposed to induce amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), which implicated this microbial metabolite in neurodegeneration mechanisms. METHODS: Freshly isolated mitochondria from C57BL/6 mice were treated with BMAA and O2 consumption rates were determined. O2 consumption and glycolysis rates were also measured in mouse primary cortical neuronal cultures. Further, mitochondrial membrane potential and ROS production were evaluated by fluorimetry and the integrity of mitochondrial network was examined by immunofluorescence. Finally, the ability of BMAA to activate neuronal innate immunity was quantified by addressing TLRs (Toll-like receptors) expression, p65 NF-κB translocation into the nucleus, increased expression of NLRP3 (Nod-like receptor 3), and pro-IL-1ß. Caspase-1 activity was evaluated using a colorimetric substrate and mature IL-1ß levels were also determined by ELISA. RESULTS: Treatment with BMAA reduced O2 consumption rates in both isolated mitochondria and in primary cortical cultures, with additional reduced glycolytic rates, decrease mitochondrial potential and increased ROS production. The mitochondrial network was found to be fragmented, which resulted in cardiolipin exposure that stimulated inflammasome NLRP3, reinforced by decreased mitochondrial turnover, as indicated by increased p62 levels. BMAA treatment also activated neuronal extracellular TLR4 and intracellular TLR3, inducing p65 NF-κB translocation into the nucleus and activating the transcription of NLRP3 and pro-IL-1ß. Increased caspase-1 activity resulted in elevated levels of mature IL-1ß. These alterations in mitochondrial metabolism and inflammation increased Tau phosphorylation and Aß peptides production, two hallmarks of AD. CONCLUSIONS: Here we propose a unifying mechanism for AD neurodegeneration in which a microbial toxin can induce mitochondrial dysfunction and activate neuronal innate immunity, which ultimately results in Tau and Aß pathology. Our data show that neurons, alone, can mount inflammatory responses, a role previously attributed exclusively to glial cells.

Investigation of boron carbide and iridium thin films, an enabling technology for future x-ray telescopes.

We present an experimental examination of iridium and boron carbide thin-film coatings for the purpose of fabricating x-ray optics. We use a combination of x-ray reflectometry and x-ray photoelectron spectroscopy to model the structure, composition, density, thickness, and micro-roughness of the thin films. We demonstrate in our analyses how the two characterization techniques are complementary, and from this we derive that an overlayer originating from atmospheric contamination with a thickness between 1.0-1.6 nm is present on the surface. The magnetron sputtered iridium films are measured to have a density of 22.4g/cm3. The boron carbide film exhibits a change in chemical composition in the top ∼2nm of the film surface when exposed to the ambient atmosphere. The chemical reaction occurring on the surface is due to an incorporation of oxygen and hydrogen present in the ambient atmosphere. Lastly, we present a correlation between the absorption edges and the emission lines exhibited by the thin films in an energy range from 50-800 eV and the impact on the reflectivity performance due to contamination in thin films.

Sound exposure and its beneficial effects on embryonic growth and hatching of broiler chicks.

1. The physical factors that involve artificial incubation determine embryonic growth and hatching of broiler chicks, and have important implications for the poultry production chain and chick welfare. This study explored the effects of sound exposure on incubation responses (hatching, embryonic development and chick quality).2. A 2 × 2 factorial experiment with the factors 'sound pressure level' (at 70 and 90 dB) and 'species-specific vocalisations' (at 75dB - 85dB) was performed in four experimental incubators (loaded with 90 eggs each) for eight consecutive cycles of incubation, totalling 2880 Cobb-500® broiler breeder eggs.3. Embryonic growth was not influenced by any experimental factor, but the highest sound pressure level (90 dB) led to earlier hatching, higher hatchability, better chick quality and lower weight at hatching. Additional effects of species-specific vocalisations were found at 70 dB noise, which caused early hatching and better chick quality.4. It was concluded that the loud noise found in commercial hatcheries (at 90 dB) can be beneficial. Furthermore, the presence of species-specific vocalisations could improve the hatching time and chick quality from experimental incubators (at 70 dB). However, this would not provide additional benefits in commercial hatcheries, due to the machinery noise masking them.

Impact of new ingredients obtained from brewer's spent yeast on bread characteristics.

The impact of bread fortification with ß-glucans and with proteins/proteolytic enzymes from brewers' spent yeast on physical characteristics was evaluated. ß-Glucans extraction from spent yeast cell wall was optimized and the extract was incorporated on bread to obtain 2.02 g ß-glucans/100 g flour, in order to comply with the European Food Safety Authority guidelines. Protein/proteolytic enzymes extract from spent yeast was added to bread at 60 U proteolytic activity/100 g flour. Both ß-glucans rich and proteins/proteolytic enzymes extracts favoured browning of bread crust. However, breads with proteins/proteolytic enzymes addition presented lower specific volume, whereas the incorporation of ß-glucans in bread lead to uniform pores that was also noticeble in terms of higher specific volume. Overall, the improvement of nutritional/health promoting properties is highlighted with ß-glucan rich extract, not only due to bread ß-glucan content but also for total dietary fibre content (39% increase). The improvement was less noticeable for proteins/proteolytic enzymes extract. Only a 6% increase in bread protein content was noted with the addition of this extract and higher protein content would most likely accentuate the negative impact on bread specific volume that in turn could impair consumer acceptance. Therefore, only ß-glucan rich extract is a promising bread ingredient.

Randomized clinical trial of percutaneous tibial nerve stimulation versus sham electrical stimulation in patients with faecal incontinence.

BACKGROUND: The aim was to assess the effects of percutaneous tibial nerve stimulation (PTNS) in the treatment of faecal incontinence (FI) by means of an RCT. METHODS: Patients aged over 18 years with FI were included in a multicentre, single-blinded RCT. The primary endpoint was reduction in the median or mean number of FI episodes per week. Secondary endpoints were changes in measures of FI severity, and disease-specific and generic quality of life. Outcomes were compared between PTNS and sham stimulation after 9 weeks of treatment. RESULTS: A higher proportion of patients in the PTNS (13 of 29) than in the sham (6 of 30) group showed a reduction of at least 50 per cent in the median number of FI episodes/week (incidence rate ratio (IRR) 2·40, 95 per cent c.i. 1·10 to 5·24; P = 0·028), but not in the mean number of episodes/week (10 of 29 versus 8 of 30; IRR 1·42, 0·69 to 2·92; P = 0·347). The absolute median number of FI episodes per week decreased in the PTNS but not in the sham group (IRR 0·66, 0·44 to 0·98; P = 0·041), as did the mean number (IRR 0·65 (0·45 to 0·97); P = 0·034). Scores on the Cleveland Clinic Florida faecal incontinence scale decreased significantly in both groups, but more steeply in the PTNS group (mean difference -1·3, 95 per cent c.i. -2·6 to 0·0; P = 0·049). The aggregated mental component score of Short Form 36 improved in the PTNS but not in the sham group (mean difference 5·1, 0·5 to 9·6; P = 0·028). CONCLUSION: PTNS may offer a small advantage in the clinical management of FI that is insufficiently responsive to conservative treatment. The key challenge will be to identify patients who may benefit most from this minimally invasive surgical procedure. Registration number: NCT00974909 (http://www.clinicaltrials.gov).

Study of genetic variability in pigs after the traditional breeding program.

Molecular markers are tools used to improve genetic gains. The objective of this study was to analyze the security of alleles of molecular marker genes for characteristics of economic interest in a pure population of pigs. After the extraction of DNA from the hair of 272 Large White matrices, the allele and genotype frequency of single nucleotide polymorphism was performed using the ARMS-PCR Multiplex technique in the DGAT1, LEPR, H-FABP, MC4R, and SREBF1 genes using RFLP-PCR for the GH gene. After capillary electrophoresis in an automated DNA sequencing of the DGAT1, LEPR, H-FABP, and SREBF1 genes, no polymorphisms were found. Only the MC4R marker presented 100% heterozygosity. For the GH gene, 209 of the initial population samples were genotyped. The PCR product (605 bp) was digested with the restriction enzyme DdeI, with fragments being of 335, 148, and 122 bp for the D1 allele and 457 and 148 bp for the D2 allele. The genotypic frequency obtained of D1D2 was 88% and of D2D2 was 22%. The D1 allele presented a frequency of 11% and the D2 allele of 89%. The high intensity of selection for commercial breeds justifies the absence or the low number of polymorphisms for the genes studied.

All-electron Gaussian basis sets of double zeta quality for the actinides.

For the actinides, two segmented all-electron basis sets of valence double zeta quality plus polarization functions (DZP) are developed. One of them must be used along with the non-relativistic Hamiltonian, whereas the other with the Douglas-Kroll-Hess (DKH) one. Adding diffuse functions of s, p, d, f, and g symmetries to the non-relativistic and relativistic sets, augmented basis sets are developed. These functions are essential to describe correctly electrons far away from the nuclei. For some compounds, geometric parameters, atomic charges and valence orbital populations of the actinides, and bond dissociation energies are calculated using the Becke 3-parameter (exchange) and the Lee, Yang, and Parr (correlation) functional in conjunction with the DZP-DKH basis set. For Am and No, the static electric mean dipole polarizabilities are also reported. Comparison with benchmark theoretical and experimental values found in the literature is carried out. It is verified that the performances of the relativistic compact size basis sets generated in this work are regular, efficient, and reliable. They will be extremely helpful in molecular property calculations that need explicitly to consider the core electrons.

The Healthy Primary School of the Future: study protocol of a quasi-experimental study.

BACKGROUND: Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined. METHODS: In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019. DISCUSSION: A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific foundation, these integrated programmes have the potential to form a template for primary schools worldwide. The effects of this approach may extend further than the outcomes associated with well-being and academic achievement, potentially impacting legal and cultural aspects in our society. TRIAL REGISTRATION: The study protocol was registered in the database ClinicalTrials.gov on 14-06-2016 with the reference number NCT02800616 .

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

How gamma-rays and electron-beam irradiation would affect the antimicrobial activity of differently processed wild mushroom extracts?

AIMS: The effects of irradiation (gamma-rays and electron-beams), up to 10 kGy, in the antimicrobial activity of mushroom species (Boletus edulis, Hydnum repandum, Macrolepiota procera and Russula delica) differently processed (fresh, dried, freeze) were evaluated. METHODS AND RESULTS: Clinical isolates with different resistance profiles from hospitalized patients in Local Health Unit of Mirandela, Northeast of Portugal, were used as target micro-organisms. The mushrooms antimicrobial activity did not suffer significant changes that might compromise applying irradiation as a possible mushroom conservation technology. CONCLUSIONS: Two kGy dose (independently of using gamma-rays or electron-beams) seemed to be the most suitable choice to irradiate mushrooms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides important results in antimicrobial activity of extracts prepared from irradiated mushroom species.

Clinicopathologic significance of BubR1 and Mad2 overexpression in oral cancer.

OBJECTIVES: BubR1 and Mad2 are central components of the mitotic checkpoint complex that inhibits anaphase onset until all chromosomes are correctly aligned at the metaphase plate. We propose to analyse the combined expression of BubR1 and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC) diagnosis and prognosis. MATERIALS AND METHODS: BubR1 and Mad2 expression was assessed by real-time PCR in OSCC cell lines and in normal human oral keratinocytes, and by immunohistochemistry in 65 patients with OSCC. The results were compared regarding clinicopathological parameters, proliferative activity and survival. RESULTS: BubR1 and Mad2 transcripts were overexpressed in OSCC cell lines which also exhibited attenuated spindle assembly checkpoint activity. BubR1 and Mad2 were also overexpressed in patients with OSCC. BubR1 expression was associated with advanced stages and larger tumour size in univariate analysis, and with shorter overall survival both in univariate and multivariate analysis. Mad2 overexpression was associated with that of BubR1 and, importantly, high expression of Mad2 and BubR1 was associated with increased cellular proliferation. CONCLUSION: Our data propose a role for BubR1 and Mad2 in OSCC cellular proliferation, progression and prognosis.

Vitamin C prevents the effects of high rearing temperatures on the quality of broiler thigh meat1.

We investigated the effects of incubation temperatures and vitamin C injections into eggs (treatments: 37.5ºC, 39ºC, 39ºC+vitamin C) on resultant chick pectoralis major and sartorius muscle fiber hypertrophy, as well as their effects on the quality of breast and over-thigh meat of broilers reared under cold, control, or hot temperatures. Incubation at 39ºC increased the shear force and reduced meat redness in breast meat (P < 0.05). Vitamin C prevented these high temperature incubation effects [shear force (kgf cm(-2)): 37.5ºC = 2.34, 39ºC = 2.79, 39ºC+vitamin C = 2.44; redness: 37.5ºC = 2.64, 39ºC = 1.90, 39ºC+vitamin C = 2.30], but reduced water content (37.5ºC = 74.81%, 39ºC = 74.53%, 39ºC+vitamin C = 69.39%) (P < 0.05). Cold rearing temperatures increased breast meat redness (a*: cold = 2.78, control = 2.12, hot = 1.98), while hot rearing temperatures reduced the muscle fiber area (cold = 5.413 µm(2), control = 5.612 µm(2), hot = 4.448 µm(2)) (P < 0.05) without altering meat quality (P > 0.05). Hot rearing temperatures increased the cooking loss (cold = 30.10%, control = 33.66%, hot = 37.01%), shear force (cold = 3.05 kgf cm(-2), control = 3.43 kgf cm(-2), hot = 4.29 kgf cm(-2)) and redness (a*: cold = 4.63, control = 3.55, hot = 3.20) in the over-thigh meat of broilers from eggs incubated at 37.5ºC, increasing the area of muscle fibers, while cold rearing temperatures diminished cooking loss and shear force, reducing the muscle fiber area (P < 0.05). Incubation at 39ºC and 39ºC+vitamin C prevented the effects of hot and cold rearing temperatures, by diminishing and increasing the muscle fiber area, respectively.

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate.

UNLABELLED: Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study. INTRODUCTION: A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate). METHODS: In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed. RESULTS: In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups. CONCLUSIONS: Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

Wild mushroom extracts potentiate the action of standard antibiotics against multiresistant bacteria.

AIMS: The main objective of this study was to evaluate the capacity of wild mushroom extracts to potentiate the action of standard antibiotics, through synergisms that allow a decrease in their therapeutic doses and ultimately contribute to the reduction of resistances. METHODS AND RESULTS: Wild mushroom extracts were applied to different multiresistant micro-organisms (Escherichia coli, extended-spectrum beta-lactamase-producing (ESBL) E. coli and methicillin-resistant Staphylococcus aureus (MRSA), combined with commercial antibiotics (penicillin, ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, cotrimoxazol, levofloxacin). Microdilution method was used to determine minimum inhibitory concentrations (MICs). The results obtained showed higher synergistic effects against MRSA than against E. coli. Mycena rosea and Fistulina hepatica were the best extracts for synergistic effects against MRSA. The efficiency of Russula delica extract against E. coli 1 (resistant to ampicillin, ciprofloxacin and trimethoprim/sulfasoxazole) and E. coli 2 (resistant to amoxicillin/clavulanic acid and ampicillin) was higher than that of Leucopaxillus giganteus extract; nevertheless, the latter extract exhibited better synergistic effects against ESBL E. coli. CONCLUSIONS: This study shows that, similarly to plants, some mushroom extracts can potentiate the action of antibiotics extensively used in clinical practice for Gram-positive or Gram-negative bacteria, with positive action even against multiresistant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Mushroom extracts could decrease therapeutic doses of standard antibiotics and reduce micro-organism's resistance to those drugs.