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Aim: To investigate the influence of diabetes mellitus (DM) in a murine model of peri‐implantitis (PI). Materials and Methods: Twenty‐seven 4‐week‐old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro‐CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one‐way ANOVA, followed by Tukey's test. Results: Gingival tissue oedema was detected in the PI and DM + PI groups. Micro‐CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD‐11b) counts and matrix metalloproteinases (MMP‐2 and MMP‐8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP‐2) levels in the DM + PI group compared to the C and PI groups. Conclusions: DM exacerbates PI‐induced soft‐tissue inflammation, matrix degradation and bone loss. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effects of post-ruminal supply of urea (PRU) on nutritional status, and liver metabolism of pregnant beef cows during late gestation. Twenty-four Brahman dams, pregnant from a single sire, and weighing 545 kg ± 23 kg were confined into individual pens at 174 ± 23 d of gestation, and randomly assigned into one of two dietary treatments up to 270 d of gestation: Control (CON, n = 12), consisting of a basal diet supplemented with conventional urea, where the cows were fed with diets containing 13.5 g conventional urea per kg dry matter; and PRU (PRU, n = 12), consisting of a basal diet supplemented with a urea coated to extensively prevent ruminal degradation while being intestinally digestible, where the cows were fed with diets containing 14,8 g urea protected from ruminal degradation per kg dry matter. Post-ruminal supply of urea reduced the urine levels of 3-methylhistidine (P = 0.02). There were no differences between treatments for dry matter intake (DMI; P = 0.76), total digestible nutrient (TDN) intake (P = 0.30), and in the body composition variables, such as, subcutaneous fat thickness (SFT; P = 0.72), and rib eye area (REA; P = 0.85). In addition, there were no differences between treatments for serum levels of glucose (P = 0.87), and serum levels of glucogenic (P = 0.28), ketogenic (P = 0.72), glucogenic, and ketogenic (P = 0.45) amino acids, neither for urea in urine (P = 0.51) as well as urea serum (P = 0.30). One the other hand, enriched pathways were differentiated related to carbohydrate digestion, and absorption, glycolysis, pyruvate metabolism, oxidative phosphorylation, pentose phosphate pathway, and biosynthesis of amino acids of the exclusively expressed proteins in PRU cows. Shifting urea supply from the rumen to post-ruminal compartments decreases muscle catabolism in cows during late gestation. Our findings indicate that post-ruminal urea supplementation for beef cows at late gestation may improve the energy metabolism to support maternal demands. In addition, the post-ruminal urea release seems to be able to trigger pathways to counterbalance the oxidative stress associated to the increase liver metabolic rate.

Abstract Background Tuberculosis (TB) is still one of the leading causes of death worldwide. Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with the risk of diseases caused by Mycobacterium tuberculosis (Mtb) infection. Methods A systematic review was performed on PubMed, EMBASE, Scientific Electronic Library Online (SciELO), and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) to examine the association between single nucleotide polymorphisms (SNP) and risk of Mtb diseases. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS), and the linkage disequilibrium was calculated for all SNPs using a webtool (Package LDpop). Results Thirteen studies matched the selection criteria. Of those, 9 investigated CD14 SNPs, and 6 reported a significant association between the T allele and TT genotypes of the rs2569190 SNP and increased risk of Mtb diseases. The genotype CC was found to be protective against TB disease. Furthermore, in two studies, the CD14 rs2569191 SNP with the G allele was significantly associated with increased risk of Mtb diseases. Four studies reported data uncovering the relationship between NOD2 SNPs and risk of Mtb diseases, with two reporting significant associations of rs1861759 and rs7194886 and higher risk of Mtb diseases in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower risk of Mtb diseases in African Americans. Conclusions The CD14 rs2569190 and rs2569191 polymorphisms may influence risk of Mtb diseases depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of Mtb diseases, especially in persons of Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in risk of Mtb diseases and pathology and may be affected by ethnicity. Systematic review registration CRD42020186523

Background: This study evaluated the anti-hyperglycemic, anti-bone-resorptive, and anti-inflammatory efficacy of the probiotic Lactobacillus rhamnosus EM1107 in an experimental model of ligature-induced periodontitis in diabetic rats treated with metformin.Methods: 114 male Wistar rats randomly divided into six groups: 1) Control, 2) Experimental Periodontitis (EP), 3) EP + diabetes mellitus (DM), 4) EP + Probiotic (Prob), 5) EP + DM + Prob and 6) EP + DM + Prob + metformin (Met). The animals received probiotic gavage during the 30 days of the experiment. DM was induced on the 14th day of the experiment with a single injection of Streptozotocin (STZ) into the penile vein, followed by ligature for EP induction and metformin gavage on the 19th day, and euthanasia on the 30th day. Heart blood, gingival and periodontal tissue, and hemimaxillae were collected. Biomolecular analysis, immunoenzymatic assays, histomorphology, and microtomographic analysis were performed. Data were statistically analyzed (p<0.05).Results: There was a significant reduction in IL-1β and TNF-α in the probiotic groups (p<0.05), as well as in blood glucose levels in the Prob and metformin groups (p<0.001). In addition, the histomorphological analysis revealed that probiotic groups had a reduction in inflammatory infiltrate. TRAP and microtomographic analyzes showed that the EP/DM/Prob/Met group had significantly lower linear and volumetric bone loss than those who had no treatment (p<0.01). SOD and GPx immunostaining decreased in all groups receiving probiotics.Conclusion: The findings suggest the immuno-inflammatory efficacy of the probiotic Lactobacillus rhamnosus EM1107 administered either alone or in association with metformin in type 1 diabetes mellitus associated with periodontitis. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Recent climate extremes in Mongolia have ignited a renewed interest in understanding past climate variability over centennial and longer time scales across north-central Asia. Tree-ring width records have been extensively studied in Mongolia as proxies for climate reconstruction, however, the climate and environmental signals of tree-ring stable isotopes from this region need to be further explored. Here, we evaluated a 182-year record of tree-ring δ13C and δ18O from Siberian Pine (Pinus sibirica Du Tour) from a xeric site in central Mongolia (Khorgo Lava) to elucidate the environmental factors modulating these parameters. First, we analyzed the climate sensitivity of tree-ring δ13C and δ18O at Khorgo Lava for comparison with ring-width records, which have been instrumental in reconstructing hydroclimate in central Mongolia over two millennia. We also compared stable isotope records of trees with partial cambial dieback ('strip-bark morphology'), a feature of long-lived conifers growing on resource-limited sites, and trees with a full cambium ('whole-bark morphology'), to assess the inferred leaf-level physiological behavior of these trees. We found that interannual variability in tree-ring δ13C and δ18O reflected summer hydroclimatic variability, and captured recent, extreme drought conditions, thereby complementing ring-width records. The tree-ring δ18O records also had a spring temperature signal and thus expanded the window of climate information recorded by these trees. Over longer time scales, strip-bark trees had an increasing trend in ring-widths, δ13C (and intrinsic water-use efficiency, iWUE) and δ18O, relative to whole-bark trees. Our results suggest that increases in iWUE at this site might be related to a combination of leaf-level physiological responses to increasing atmospheric CO2, recent drought, and stem morphological changes. Our study underscores the potential of stable isotopes for broadening our understanding of past climate in north-central Asia. However, further studies are needed to understand how stem morphological changes might impact stable isotopic trends., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540-43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Science China Press. Published by Elsevier B.V. All rights reserved.)

Background: Professionalism has come to be associated with competence in medical education, with the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, values, and reflection in daily practice for the benefit of the individual and community being served. Recent studies indicate students should have the opportunity to observe the application of knowledge and skills by their mentors to improve patient health and safety. A noticeable detail that needs implementation into the curriculum is the inclusion of student perspectives. This review will explore students' understanding and experience of professionalism in undergraduate medical education (UME)., Objective: This paper presents the protocol for a review that aims to develop an integrated synthesis of qualitative and quantitative studies resulting in recommendations for medical school curricula to incorporate the learners' perspectives in teaching professionalism in UME., Methods: We will take an integrated approach to synthesis. Data will be extracted from the included studies, and quantitative data will be "qualitized." PubMed (Medline), Embase, PsycInfo, and ERIC (Education Resources Information Center) will be searched for studies published in English from 2010 to 2021. Studies will be screened and critically appraised for methodological quality using the Mixed Methods Appraisal Tool by 2 researchers, with disagreements resolved by a third researcher. Qualitative, quantitative, and mixed methods studies will be considered. Our population of interest is undergraduate medical students; hence, studies on medical residents and graduate medical students will be excluded. We will consider studies that explore how concepts of professionalism are understood, experienced, and taught in undergraduate medicine and on how medical students understand and develop the identified constructs of professionalism., Results: This study is in the screening phase; therefore, no results are available at this time. However, we had initiated the searches, screening, and are currently in the critical appraisal stage. We will commence preparation to clean and convert the data for coding in July 2022, and analysis will be ongoing from the end of July 2022 until submission for publication in November 2022., Conclusions: This research will contribute to the student perspectives on professionalism in medical education literature. The findings will aid in the creation of a checklist to guide the development of a curriculum on professionalism in UME., International Registered Report Identifier (irrid): PRR1-10.2196/37473., (©Nagina Khan, Walther van Mook, Subodh Dave, Sohyun Ha, Joshua Sagisi, Nicole Davi, Chantel Aftab, Sucheta Tiwari, Marie Hickman, Wolfgang Gilliar. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 25.08.2022.)

The original version of this Article contained an error in the Data Availability section, which incorrectly read 'All data will be freely available via https://www.ams.ethz.ch/research.html .' The correct version states ' http://www.ams.ethz.ch/research/published-data.html ' in place of ' https://www.ams.ethz.ch/research.html '. This has been corrected in both the PDF and HTML versions of the Article.

Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the 14 C content in 484 individual tree rings formed in the periods 770-780 and 990-1000 CE. Distinct 14 C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved 14 C measurements are needed.

Hydroclimate variations since 1300 in central and monsoonal Asia and their interplay on interannual and interdecadal timescales are investigated using the tree-ring based Palmer Drought Severity Index (PDSI) reconstructions. Both the interannual and interdecadal variations in both regions are closely to the Pacific Decadal Oscillation (PDO). On interannual timescale, the most robust correlations are observed between PDO and hydroclimate in central Asia. Interannual hydroclimate variations in central Asia are more significant during the warm periods with high solar irradiance, which is likely due to the enhanced variability of the eastern tropical Pacific Ocean, the high-frequency component of PDO, during the warm periods. We observe that the periods with significant interdecadal hydroclimate changes in central Asia often correspond to periods without significant interdecadal variability in monsoonal Asia, particularly before the 19th century. The PDO-hydroclimate relationships appear to be bridged by the atmospheric circulation between central North Pacific Ocean and Tibetan Plateau, a key area of PDO. While, in some periods the atmospheric circulation between central North Pacific Ocean and monsoonal Asia may lead to significant interdecadal hydroclimate variations in monsoonal Asia.

Traditional detrending methods assign equal mean value to all tree-ring series for chronology developments, despite that the mean annual growth changes in different time periods. We find that the strength of a tree-ring model can be improved by giving more weights to tree-ring series that have a stronger climate signal and less weight to series that have a weaker signal. We thus present an ensemble weighting method to mitigate these potential biases and to more accurately extract the climate signals in dendroclimatology studies. This new method has been used to develop the first annual precipitation reconstruction (previous August to current July) at the Songmingyan Mountain and to recalculate the tree-ring chronology from Shenge site in Dulan area in northeastern Tibetan Plateau (TP), a marginal area of Asian summer monsoon. The ensemble weighting method explains 31.7% of instrumental variance for the reconstructions at Songmingyan Mountain and 57.3% of the instrumental variance in the Dulan area, which are higher than those developed using traditional methods. We focus on the newly introduced reconstruction at Songmingyan Mountain, which showsextremely dry (wet) epochs from 1862-1874, 1914-1933 and 1991-1999 (1882-1905). These dry/wet epochs were also found in the marginal areas of summer monsoon and the Indian subcontinent, indicating the linkages between regional hydroclimate changes and the Indian summer monsoon.

Ethnopharmacological Relevance: Byrsonima verbascifolia is used in folk medicine to treat diarrhea, intestinal infections, chronic wounds, Chagas disease, inflammation and as a diuretic. However there is no investigation regarding the Byrsonima verbascifolia hydrometanolic extract (BVHME) used during gestation., Materials and Methods: The pregnant females were randomly divided into 5 groups. Control group received saline plus DMSO (1%) in a volume of 0.1 mL/10 g (b.w.), via gavage, for at least 15 days prior to mating and throughout the gestational period. The Pre-treatment group received the BVHME, via gavage, at a dose of 50 mg/kg (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The Organogenesis group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, on the 5-15th gestational day. The Gestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The Pre+Gestational group received the BVHME at a dose of 50mg/kg (b.w.), via gavage, for at least 15 days prior to mating and up to throughout the gestational period. The clinical signals of maternal and fetuses toxicity were evaluated, as the mutagenicity and immunomodulation tests were performed., Results and Conclusions: The present investigation shows, for the first time, that the use of Byrsonima verbascifolia extract in pregnant Swiss mice, did not alter the female reproductive function, mutagenicity or immunostimulation as well as not interfere with embryofetal development at least in our experimental conditions., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

We have examined the effects of pulsed electric fields on the separation of single-stranded DNA molecules in polyacrylamide sequencing gels. Using different electric field pulsing regimens, the mobilities of single-stranded DNA molecules can be retarded or increased as compared to conventional electrophoresis. These results indicated that pulsed field techniques can be applied to gel electrophoresis of small single-stranded DNA molecules.