Seborrheic dermatitis (SD) is a chronic inflammatory skin disease with a multifactorial aetiology. Malassezia yeasts have been associated with the disease but the role of bacterial composition in SD ...has not been thoroughly investigated. To profile the bacterial microbiome of SD patients and compare this with the microbiome of individuals with no inflammatory skin disease (controls). This was a cross sectional study embedded in a population-based study. Skin swabs were taken from naso-labial fold from patients with seborrheic dermatitis (lesional skin: n = 22; non-lesional skin SD: n = 75) and controls (n = 465). Sample collection began in 2016 at the research facility and is still ongoing. Shannon and Chao1 alpha- diversity metrics were calculated per group. Associations between the microbiome composition of cases and controls was calculated using multivariate statistics (permANOVA) and univariate statistics. We found an increased alpha-diversity between SD lesional cases versus controls (Shannon diversity: Kruskal-Wallis rank sum: Chi-squared: 19.06; global p-value = 7.7x10.sup.-5). Multivariate statistical analysis showed significant associations in microbiome composition when comparing lesional SD skin to controls (p-value = 0.03;R.sup.2 = 0.1%). Seven out of 13 amplicon sequence variants (ASVs) that were significantly different between controls and lesional cases were members of the genus Staphylococcus, most of which showed increased composition in lesional cases, and were closely related to S. capitis S. caprae and S. epidermidis. Microbiome composition differs in patients with seborrheic dermatitis and individuals without diseases. Differences were mainly found in the genus Staphylococcus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, ...implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome.
Summary
Background
Seborrhoeic dermatitis is a chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms.
Objectives
To establish which lifestyle and physiological ...determinants are associated with seborrhoeic dermatitis.
Methods
Seborrhoeic dermatitis was diagnosed by a trained physician during a full‐body skin examination within the Rotterdam Study, a prospective population‐based cohort study in middle‐aged and elderly people. The current design is a comparative cross‐sectional study embedded in the Rotterdam Study. Potential factors were identified from the literature and analysed in a multivariable logistic regression, including: age, sex, obesity, skin colour, stress, depression, education level, hypertension, climate, xerosis cutis, alcohol and tobacco use.
Results
Of the 5498 participants, 788 participants were diagnosed with seborrhoeic dermatitis (14·3%). We found associations between seborrhoeic dermatitis and male sex adjusted odds ratio (OR) 2·09, 95% confidence interval (CI) 1·77–2·47, darker skin (adjusted OR 0·39, 95% CI 0·22–0·69), season (summer vs. winter: adjusted OR 0·63, 95% CI 0·48–0·82) and generalized xerosis cutis (adjusted OR 1·41, 95% CI 1·11–1·80).
Conclusions
Seborrhoeic dermatitis is one of the most common inflammatory dermatoses in middle‐aged and elderly individuals, especially during winter. Men, and people with a light and dry skin were most likely to have seborrhoeic dermatitis.
What's already known about this topic?
Seborrhoeic dermatitis is a common chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms.
Numerous host and environmental factors have been implicated in the pathogenesis of seborrhoeic dermatitis, but most have not been validated.
What does this study add?
Male sex, light skin colour, the season winter and generalized dry skin increased the likelihood of having seborrhoeic dermatitis.
Interventions aiming to improve skin‐barrier function could become a target in the treatment of patients with seborrhoeic dermatitis.
Linked Comment: Drucker and Doiron. Br J Dermatol 2018; 178:22–23.
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Aims
Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or ...antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms.
Methods
Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times.
Results
In the untreated biofilm, growth up to 1.8×10
11
colony-forming units (CFU)/cm
2
was observed. Treatment with ciprofloxacin, flucloxacillin, vancomycin, cefuroxime, and amoxicillin all with rifampicin gave 6.0 log, 6.1 log, 1.4 log, 4.8 log, and 3.6 log reduction in CFU/cm
2
, respectively. Mechanical cleaning alone resulted in 4.9 log reduction and induction heating in 7.3 log reduction. There was an additional effect of ciprofloxacin, flucloxacillin, and induction heating when used in combinations. There was no additional effect for mechanical cleaning. No bacterial growth could be detected after induction heating followed by seven days of ciprofloxacin with rifampicin.
Conclusion
Mechanical cleaning, antibiotics, and non-contact induction heating reduced the bacterial load of mature S. aureus biofilms with approximately 5 log or more as a single treatment. The effect of mechanical cleaning on mature S. aureus biofilms was limited when used in combination with antibiotics and/or induction heating. Cite this article: Bone Joint Res 2022;11(9):629–638.
Non-contact induction heating (NCIH) is a noninvasive treatment modality that can be used to cause thermal damage to bacterial biofilms on a metal implant surface in the context of a prosthetic joint ...infection. The purpose of this study was (1) to determine the effectiveness of NCIH on killing Staphylococcus aureus from biofilm and (2) to determine the possible synergistic effect of NCIH and cocktails of antibiotics and N-acetylcysteine (NAC).
Staphylococcus aureus biofilms were grown on titanium alloy (Ti6Al4V) coupons. These coupons were heated to 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C for 3.5 min and subsequently exposed to cocktails of vancomycin, rifampicin and NAC at clinically relevant concentrations over 24 h.
In the control group without induction heating, 2.2*10
7
colony forming units (CFU)/cm
2
were observed. At 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C, a reduction of 0.3-log, 3.9-log, 4.2-log, 4.3-log, and 6.6-log CFU/cm
2
were observed, respectively. There was synergy between antibiotics and induction heating that resulted in less than 100 CFU/cm
2
remaining after 3.5 min at 60 °C, and exposure to vancomycin and rifampicin. Total eradication was observed at 80 °C. Total eradication was also observed at 60 °C and a cocktail of antibiotics with NAC.
Induction heating of titanium alloy coupons is effective for the reduction of bacterial load in vitro in S. aureus biofilms. Induction heating and cocktails of antibiotics and NAC have a synergistic effect that results in the total eradication of the biofilm at 60 °C and higher for clinically relevant concentrations of vancomycin, rifampicin and NAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Because of increased geometric freedom at a widening range of length scales and access to a growing material space, additive manufacturing has spurred renewed interest in topology optimization of ...parts with spatially varying material properties and structural hierarchy. Simultaneously, a surge of micro/nanoarchitected materials have been demonstrated. Nevertheless, multiscale design and micro/nanoscale additive manufacturing have yet to be sufficiently integrated to achieve free-form, multiscale, biomimetic structures. We unify design and manufacturing of spatially varying, hierarchical structures through a multimicrostructure topology optimization formulation with continuous multimicrostructure embedding. The approach leads to an optimized layout of multiple microstructural materials within an optimized macrostructure geometry, manufactured with continuously graded interfaces. To make the process modular and controllable and to avoid prohibitively expensive surface representations, we embed the microstructures directly into the 3D printer slices. The ideas provide a critical, interdisciplinary link at the convergence of material and structure in optimal design and manufacturing.
The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both ...classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.
Via a retrospective multicenter study, the authors investigate the impact of pretransplant donor‐specific HLA antibodies on long‐term graft survival in deceased and living donor kidney transplantations.
Induction heating is a noninvasive, nonantibiotic treatment modality that can potentially be used to cause thermal damage to the bacterial biofilm on the metal implant surface. The purpose of this ...study was to determine the effectiveness of induction heating on killing
from biofilm and to determine the possible synergistic effect of induction heating and antibiotics.
biofilms were grown on titanium alloy (Ti6Al4V) coupons for 24 hours (young biofilm) and seven days (mature biofilm). These coupons with biofilm were heated to temperatures of 50°C, 55°C, 60°C, 65°C, 70°C, 80°C, and 90°C for 3.5 minutes and subsequently exposed to vancomycin and rifampicin at clinically relevant concentrations.
For the young biofilm, total eradication was observed at 65°C or higher for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. For the mature biofilm, total eradication was observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. Total eradication was also observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 1 mg/l and rifampicin 1 mg/l followed by another thermal shock of 60°C for 3.5 minutes (two thermal shocks).
Induction heating of Ti6Al4V coupons is effective in reducing bacterial load in vitro for
biofilms. Induction heating and antibiotics have a synergistic effect resulting in total eradication of the biofilm at 60°C or higher for clinically relevant concentrations of vancomycin and rifampicin.
2020;9(4):192-199.
Innate and adaptive immune cells participate in the homeostatic regulation of hematopoietic stem cells (HSCs). Here, we interrogate the contribution of myeloid cells, the most abundant cell type in ...the mammalian bone marrow, in a clinically relevant mouse model of neutropenia. Long-term genetic depletion of neutrophils and eosinophils results in activation of multipotent progenitors but preservation of HSCs. Depletion of myeloid cells abrogates HSC expansion, loss of serial repopulation and lymphoid reconstitution capacity and remodeling of HSC niches, features previously associated with hematopoietic aging. This is associated with mitigation of interferon signaling in both HSCs and their niches via reduction of NK cell number and activation. These data implicate myeloid cells in the functional decline of hematopoiesis, associated with activation of interferon signaling via a putative neutrophil-NK cell axis. Innate immunity may thus come at the cost of system deterioration through enhanced chronic inflammatory signaling to stem cells and their niches.
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