Reaction Mechanism Catalyzed by the Dissimilatory Sulfite Reductase - The Role of the Siroheme-[4FeS4] Cofactor.

The present work is another part of our investigation on the pathway of dissimilatory sulfate reduction and covers a theoretical study on the reaction catalyzed by dissimilatory sulfite reductase (dSIR). dSIR is the terminal enzyme involved in this metabolic pathway, which uses the siroheme-[4Fe4S] cofactor for six-electron reduction of sulfite to sulfide. In this study we use a large cluster model containing siroheme-[4Fe4S] cofactor and protein residues involved in the direct interactions with the substrate, to get insight into the most feasible reaction mechanism and to understand the role of each considered active site component. In combination with earlier studies reported in the literature, our results lead to several interesting insights. One of the most important conclusions is that the reaction mechanism consists of three steps of two-electron reduction of sulfur and the probable role of the siroheme-[4Fe4S] cofactor is to ensure the delivery of packages of two electrons to the reactant.

ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC).

The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.

Technological readiness and implementation of genomic-driven precision medicine for complex diseases.

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged.

Mutations in ASIP and MC1R: dominant black and recessive black alleles segregate in native Swedish sheep populations.

By studying genes associated with coat colour, we can understand the role of these genes in pigmentation but also gain insight into selection history. North European short-tailed sheep, including Swedish breeds, have variation in their coat colour, making them good models to expand current knowledge of mutations associated with coat colour in sheep. We studied ASIP and MC1R, two genes with known roles in pigmentation, and their association with black coat colour. We did this by sequencing the coding regions of ASIP in 149 animals and MC1R in 129 animals from seven native Swedish sheep breeds in individuals with black, white or grey fleece. Previously known mutations in ASIP [recessive black allele: g.100_105del (D5 ) and/or g.5172T>A] were associated with black coat colour in Klövsjö and Roslag sheep breeds and mutations in both ASIP and MC1R (dominant black allele: c.218T>A and/or c.361G>A) were associated with black coat colour in Swedish Finewool. In Gotland, Gute, Värmland and Helsinge sheep breeds, coat colour inheritance was more complex: only 11 of 16 individuals with black fleece had genotypes that could explain their black colour. These breeds have grey individuals in their populations, and grey is believed to be a result of mutations and allelic copy number variation within the ASIP duplication, which could be a possible explanation for the lack of a clear inheritance pattern in these breeds. Finally, we found a novel missense mutation in MC1R (c.452G>A) in Gotland, Gute and Värmland sheep and evidence of a duplication of MC1R in Gotland sheep.

The Parkinson's Disease Composite Scale: results of the first validation study.

BACKGROUND AND PURPOSE: The aim was to validate the Parkinson's Disease Composite Scale (PDCS). METHODS: The study included 194 Parkinson's disease (PD) patients in five countries. Investigators completed the following scales: PDCS, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale Version 2, Montreal Cognitive Assessment, the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease and the Clinical Impression of Severity Index for PD (CISI-PD). For test-retest analysis, a second administration of the PDCS was carried out in 61 stable patients (as per the CISI-PD) in 7-14 days after the first evaluation. The PDCS is a novel scale for PD with a total of 17 items divided into four domains: motor, non-motor, treatment complications and disability. RESULTS: Parkinson's Disease Composite Scale mean and median values were close. Skewness values were into the criterion limits (-1 to +1). The complete range of scores was covered for 14 of the 17 items (83.4%). A floor effect of 25.26% and 28.25% was observed in the complications and disability level dimensions due to the proportion of patients free of these difficulties. No relevant floor or ceiling effect was observed for the PDCS total score (1.03% and 0.52%, respectively). The stability of the scale appeared excellent with most items meeting weighted kappa and intraclass correlation coefficient values >0.80. The convergent validity of the PDCS with corresponding scores of the MDS-UPDRS showed high correlation values (rS  ≥ 0.60). The internal validity was into acceptable limits, with the majority of values higher than the minimal 0.30 threshold. The standard error of measurement suggested a satisfactory precision (SEM 3.81, <30% of the PDCS total score standard deviation). CONCLUSION: The PDCS appears to be a feasible, acceptable, reproducible and valid scale.

Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients.

BACKGROUND: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics. METHODS: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral). RESULTS: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment. CONCLUSION: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.

Reliability of an adherence monitoring sensor embedded in an oral appliance used for treatment of obstructive sleep apnoea.

The aim of this study was to test whether digitally registered use of a mandibular advancement device (MAD) by a built-in thermal sensor was reliable compared to a self-reported diary of MAD use. Eighty consecutive patients referred to a specialist outpatient sleep medicine clinic (HUS) were recruited. Patients of both genders, aged from 25 to 70 years with a diagnosis of mild, moderate or severe, were included. All participants signed a written informed consent when they received the MAD. For the purpose of this reliability study, we found it sufficient to include the first 30 nights of MAD use in the reliability analysis. At the 30th night follow-up visit, the self-reported diary with duration of MAD use was returned and data on the duration of MAD use with the built-in sensor were retrieved. From a total of 2400 nights, complete data from both methods were retrieved for 2108 nights (84.6%). Missing data were largely a result of missing self-reported diaries, whereas technical failure occurred in 6 nights (0.002%). The relative reliability was very high with ICC3,1 0.847, and the absolute reliability for digitally registered MAD usage was calculated to -0.17 (95% CI: 1.47 to -1.81) hours in decimal conversion. Objectively collected data from built-in thermal sensors in MADs are as reliable as those of the self-report assessments. This opens new possibilities for more accurate measurements of MAD adherence.

Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project).

Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses is important. In the present study, we analysed the immunoglobulin (Ig)G subclasses regarding reactivity against cyclic citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status and IgA and pan-IgG anti-CCP antibodies. All patients, regardless of pan-IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity. Sixty-nine per cent were positive in any IgG anti-CCP subclass, and of these 67% tested positive regarding IgG1, 35% IgG2, 32% IgG3, and 59% IgG4 anti-CCP. Among ever-smokers the percentages of IgG2 anti-CCP (P = 0·01) and IgA anti-CCP (P = 0·002)-positive cases were significantly higher compared to never-smokers. A positive IgG anti-CCP subclass -negative cases. Combining SE and smoking data revealed that IgG1 and IgG4 anti-CCP were the IgG anti-CCP isotypes associated with expression of SE, although the lower number of patients positive for IgG2 or IgG3 anti-CCP could, however, have influenced the results. High levels of IgG2 anti-CCP were shown to correlate with expression of the 'non-SE' allele human leucocyte antigen (HLA)-DRB1*15. In conclusion, in this study we describe different risk factor characteristics across the IgG anti-CCP subclasses, where IgG2 appears similar to IgA anti-CCP regarding the predominant association with smoking, while IgG1 and IgG4 related more distinctly to the carriage of SE genes.

Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples.

The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.

High-risk regions and outbreak modelling of tularemia in humans.

Sweden reports large and variable numbers of human tularemia cases, but the high-risk regions are anecdotally defined and factors explaining annual variations are poorly understood. Here, high-risk regions were identified by spatial cluster analysis on disease surveillance data for 1984-2012. Negative binomial regression with five previously validated predictors (including predicted mosquito abundance and predictors based on local weather data) was used to model the annual number of tularemia cases within the high-risk regions. Seven high-risk regions were identified with annual incidences of 3·8-44 cases/100 000 inhabitants, accounting for 56·4% of the tularemia cases but only 9·3% of Sweden's population. For all high-risk regions, most cases occurred between July and September. The regression models explained the annual variation of tularemia cases within most high-risk regions and discriminated between years with and without outbreaks. In conclusion, tularemia in Sweden is concentrated in a few high-risk regions and shows high annual and seasonal variations. We present reproducible methods for identifying tularemia high-risk regions and modelling tularemia cases within these regions. The results may help health authorities to target populations at risk and lay the foundation for developing an early warning system for outbreaks.

The cagE gene sequence as a diagnostic marker to identify JP2 and non-JP2 highly leukotoxic Aggregatibacter actinomycetemcomitans serotype b strains.

BACKGROUND AND OBJECTIVE: Aggregatibacter actinomycetemcomitans is involved in oral and systemic infections, and is associated with, eg aggressive forms of periodontitis and with endocarditis. The cagE gene encodes a ≈39 kDa putative exotoxin expressed by A. actinomycetemcomitans. The level of conservation of cagE, and its possible significance in periodontal disease, has not yet been thoroughly investigated. In the present study, the role of the cagE gene as a diagnostic marker has been investigated. MATERIAL AND METHODS: We have used conventional polymerase chain reaction (PCR), quantitative PCR and whole genome sequencing data to determine the prevalence of cagE in A. actinomycetemcomitans based on analysis of: (i) 249 isolates, collected and cultivated in a Ghanaian longitudinal cohort study; (ii) a serotype b collection of 19 strains; and (iii) the 36 A. actinomycetemcomitans genomes available in the NCBI database. RESULTS: Whereas cagE was absent in the other serotypes, our data support that this gene sequence is linked to a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes of A. actinomycetemcomitans. CONCLUSION: We propose that cagE has the potential to be used as a PCR-based gene marker for the identification of a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes. This finding might be of importance in the risk assessment of the development of periodontal attachment loss in young individuals and hence suggested to be a relevant discovery in future development of new diagnostic tools and/or treatment strategies.

Titanium ions form particles that activate and execute interleukin-1ß release from lipopolysaccharide-primed macrophages.

BACKGROUND AND OBJECTIVE: Peri-implantitis is a destructive inflammatory process characterized by destruction of the implant-supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri-implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples. MATERIAL AND METHODS: Human macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell-culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin-1ß (IL-1ß) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively. RESULTS: Ti ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL-1ß release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 µm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 µm) to stimulate secretion of IL-1ß from human macrophages in vitro. CONCLUSION: Ti ions form particles that act as secondary stimuli for a proinflammatory reaction.

Arbuscular mycorrhizas are present on Spitsbergen.

A previous study of 76 plant species on Spitsbergen in the High Arctic concluded that structures resembling arbuscular mycorrhizas were absent from roots. Here, we report a survey examining the roots of 13 grass and forb species collected from 12 sites on the island for arbuscular mycorrhizal (AM) colonisation. Of the 102 individuals collected, we recorded AM endophytes in the roots of 41 plants of 11 species (Alopecurus ovatus, Deschampsia alpina, Festuca rubra ssp. richardsonii, putative viviparous hybrids of Poa arctica and Poa pratensis, Poa arctica ssp. arctica, Trisetum spicatum, Coptidium spitsbergense, Ranunculus nivalis, Ranunculus pygmaeus, Ranunculus sulphureus and Taraxacum arcticum) sampled from 10 sites. Both coarse AM endophyte, with hyphae of 5-10 µm width, vesicles and occasional arbuscules, and fine endophyte, consisting of hyphae of 1-3 µm width and sparse arbuscules, were recorded in roots. Coarse AM hyphae, vesicles, arbuscules and fine endophyte hyphae occupied 1.0-30.7, 0.8-18.3, 0.7-11.9 and 0.7-12.8% of the root lengths of colonised plants, respectively. Principal component analysis indicated no associations between the abundances of AM structures in roots and edaphic factors. We conclude that the AM symbiosis is present in grass and forb roots on Spitsbergen.

Deceased Donor Intervention Research: A Survey of Transplant Surgeons, Organ Procurement Professionals, and Institutional Review Board Members.

Innovative deceased donor intervention strategies have the potential to increase the number and quality of transplantable organs. Yet there is confusion over regulatory and legal requirements, as well as ethical considerations. We surveyed transplant surgeons (n = 294), organ procurement organization (OPO) professionals (n = 83), and institutional review board (IRB) members (n = 317) and found wide variations in their perceptions about research classification, risk assessment for donors and organ transplant recipients, regulatory oversight requirements, and informed consent in the context of deceased donor intervention research. For instance, when presented with different research scenarios, IRB members were more likely than transplant surgeons and OPO professionals to feel that study review and oversight were necessary by the IRBs at the investigator, donor, and transplant center hospitals. Survey findings underscore the need to clarify ethical, legal, and regulatory requirements and their application to deceased donor intervention research to accelerate the pace of scientific discovery and facilitate more transplants.

What is the impact of chronic systemic inflammation such as rheumatoid arthritis on mortality following cancer?

BACKGROUND: Emerging evidence links inflammation and immune competence to cancer progression and outcome. Few studies addressing cancer survival in the context of rheumatoid arthritis (RA) have reported reduced survival without accounting for the underlying mortality risk in RA. Whether this increased mortality is a cancer-specific phenomenon, an effect of the decreased lifespan in RA or a combination of both remains unknown. METHODS: Using Swedish register data (2001-2009), we performed a cohort study of individuals with RA (N=34 930), matched to general population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14 291). Using stratified Cox models, we estimated HRs of death associated with RA in the presence and absence of cancer, by stage and time since cancer diagnosis, for all cancers and specific sites. RESULTS: In the absence of cancer, RA was associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the presence of cancer, the relative effect of RA on mortality was varied by stage. For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative effect of RA on mortality was the same as in the absence of cancer. For cancers diagnosed at advanced stages with absolute higher mortality, the effect decreased (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer diagnosis and were reasonably similar across cancer sites. CONCLUSIONS: Much of the increase in mortality in patients with RA diagnosed with cancer seems to reside with effects of RA independently of the cancer.

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

OBJECTIVES: In systemic sclerosis (SSc)-related interstitial lung disease (ILD), elevated eosinophil counts in bronchoalveolar lavage are associated with a worse outcome. We hypothesized that eosinophils may be activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients. METHOD: Expression levels of surface markers CD11b, CD44, CD48, CD54, CD69, CD81, and HLA-DR on CD16(low)CD9(high)-expressing eosinophils were measured by flow cytometry in whole blood from SSc patients (n = 32) and controls (n = 11). RESULTS: Expression levels of CD54, CD69, and HLA-DR were undetectable in all groups. CD44 and CD11b expression levels were similar between groups. CD81 expression was lower in patients compared to controls independent of disease duration (p = 0.001). CD48 expression was increased in patients with a short disease duration (< 2 years) compared to both controls (p = 0.042) and patients with longer disease duration (≥ 2 years; p = 0.027). In patients with short disease duration, increased CD48 expression was associated with alveolar inflammation as measured by an increased concentration of alveolar nitric oxide (r = 0.76, p = 0.003). CONCLUSIONS: Blood eosinophils change phenotype during disease evolution in SSc, and CD48 expression may be used as a biomarker for pulmonary inflammation.

A wide spectrum of fastidious and ampicillin-susceptible bacteria dominate in animal-caused wounds.

The main purpose of this study was to assess the actual occurrence of Gram-negative oxidase-positive bacteria (GNOP) in human wounds caused by animals, mostly cat and dog bites and scratches, and with signs of infection. We report a prospective series of 92 wound samples. Routine culturing was combined with a procedure optimised for fastidious GNOP. All GNOP isolates were identified by 16S rDNA sequencing to the species level. We observed a more prominent role of GNOP, including at least 30 species mostly in the families Flavobacteriaceae, Neisseriaceae and Pasteurellaceae, and less of Staphylococcus aureus and streptococci. The antibiotic susceptibility pattern was investigated, as GNOP are associated with sudden onset of serious infections, making an early decision on antibiotic treatment vital. All GNOP isolates judged to be clinically relevant displayed susceptibility to ampicillin and meropenem, but resistance to oxacillin, clindamycin and gentamicin was frequent. Our findings emphasise the need to cover GNOP as recommended in guidelines, and not only common wound pathogens, when treating an animal-caused wound.

Reactivity at the Cu2O(100):Cu-H2O interface: a combined DFT and PES study.

The water-cuprite interface plays an important role in dictating surface related properties. This not only applies to the oxide, but also to metallic copper, which is covered by an oxide film under typical operational conditions. In order to extend the currently scarce knowledge of the details of the water-oxide interplay, water interactions and reactions on a common Cu2O(100):Cu surface have been studied using high-resolution photoelectron spectroscopy (PES) as well as Hubbard U and dispersion corrected density functional theory (PBE-D3+U) calculations up to a bilayer water coverage. The PBE-D3+U results are compared with PBE, PBE-D3 and hybrid HSE06-D3 calculation results. Both computational and experimental results support a thermodynamically favored, and H2O coverage independent, surface OH coverage of 0.25-0.5 ML, which is larger than the previously reported value. The computations indicate that the results are consistent also for ambient temperatures under wet/humid and oxygen lean conditions. In addition, both DFT and PES results indicate that the initial (3,0;1,1) surface reconstruction is lifted upon water adsorption to form an unreconstructed (1 × 1) Cu2O(100) structure.

Oral appliance treatment in moderate and severe obstructive sleep apnoea patients non-adherent to CPAP.

The aim of this retrospective study was to evaluate the effect of individually adjusted custom-made mandibular advancement device/oral appliance (OA) in treatment of patients with moderate and severe obstructive sleep apnoea (OSA), who were non-adherent to continuous positive airway pressure (CPAP) therapy. During 2007-2013, 116 patients with moderate (n = 82) and severe (n = 34) OSA non-adherent to CPAP treatment were referred for dental management with an individually adjusted OA at a specialist sleep clinic. Ten of the participants (8·6%) were lost to follow-up, leaving the data set to consist of 106 patients (71 men/35 women, mean age 57 year, range 28-90). Nocturnal respiratory polygraphic recordings were performed at baseline and follow-up. Average time between baseline polygraphy and follow-up was 12 months. A successful OA treatment outcome was based on polygraphy at the follow-up and divided into three groups: 1 = AHI <5; 2 = 5 ≤ AHI <10 and >50% reduction in baseline AHI; and 3. >50% reduction in baseline AHI. If there was a ≤ 50% reduction in baseline AHI at the follow-up, the treatment was considered as a failure. The overall treatment success rate was 75%. There was no significant difference in success rates between patients in the moderate and severe categories (69% and 77%, respectively). Low oxygen saturation (SpO2 nadir) had a high predictive value for OA treatment failure. OA treatment of patients non-adherent to CPAP is efficient and especially promising for the severe OSA group who are at greatest risks for developing serious comorbidities, if left untreated.