[Hitting and yelling during sleep: diagnosis and implications of REM sleep behavior disorder]. / Slaan en schreeuwen in de slaap.

Rapid eye movement (REM) sleep behavior disorder is characterized by dream enactment during REM sleep. Due to different treatment requirements, it is important to distinguish REM sleep behavior disorder from other causes of nocturnal restlessness, including sleep apnea, non-REM parasomnia and sleep-related hypermotor epilepsy. In addition, a diagnosis of isolated REM sleep behavior disorder is impactful, because it carries a greatly increased risk for the later development of Parkinson's disease and related synucleinopathies. In this clinical lesson we describe three patients with abnormal nocturnal movements and vocalizations. The history can provide important clues towards the diagnosis, but a video-polysomnography is required before REM sleep behavior disorder can be diagnosed.

Coccidioidomycosis presenting years after returning from travel.

After having traveled to California in 2017, a 26-year old Dutch man presented in 2020 with persisting cough and shortness of breath. Radiology showed cystic bronchiectasis with peri-bronchial consolidation in his right upper lobe. Laboratory studies in August 2021 showed an increased total IgE, specific Aspergillus IgE, eosinophilia and positive BAL culture for Coccidioides immitis/posadasii. After 6 weeks of itraconazole treatment for suspected allergic bronchopulmonary aspergillosis, symptoms persisted and respiratory cultures remained positive. The infection was cleared after a 6-month course of fluconazole. (max 75 words).

Inflammatory Blood Biomarkers Are Associated with Long-Term Clinical Disease Severity in Parkinson's Disease.

An altered immune response has been identified as a pathophysiological factor in Parkinson's disease (PD). We aimed to identify blood immunity-associated proteins that discriminate PD from controls and that are associated with long-term disease severity in PD patients. Immune response-derived proteins in blood plasma were measured using Proximity Extension Technology by OLINK in a cohort of PD patients (N = 66) and age-matched healthy controls (N = 52). In a selection of 30 PD patients, we evaluated changes in protein levels 7-10 years after the baseline and assessed correlations with motor and cognitive assessments. Data from the Parkinson's Disease Biomarkers Program (PDBP) cohort and the Parkinson's Progression Markers Initiative (PPMI) cohort were used for independent validation. PD patients showed an altered immune response compared to controls based on a panel of four proteins (IL-12B, OPG, CXCL11, and CSF-1). The expression levels of five inflammation-associated proteins (CCL23, CCL25, TNFRSF9, TGF-alpha, and VEGFA) increased over time in PD and were partially associated with more severe motor and cognitive symptoms at follow-up. Increased CCL23 levels were associated with cognitive decline and the APOE4 genotype. Our findings provide further evidence for an altered immune response in PD that is associated with disease severity in PD over a long period of time.

European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study.

The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.

The therapeutic potential of opioids in narcolepsy type 1: A systematic literature review and questionnaire study.

OBJECTIVE: Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study. METHODS: We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported. RESULTS: The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7). CONCLUSIONS: Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.

Nakaseomyces glabrata endocarditis: A therapeutic dilemma.

Candida infective endocarditis is a rare but serious entity that often requires aggressive treatment. However, treatment can be challenging in patients infected with drug-resistant fungi and/or with substantial comorbidity. Moreover, recommendations in treatment guidelines for these patients are based on limited clinical data due to their rarity. Here we report a case of Nakaseomyces glabrata (Candida glabrata) prosthetic valve endocarditis in a patient with congenital heart disease. This case illustrates a therapeutic dilemma for Nakaseomyces glabrata prosthetic valve endocarditis and the need for novel antifungal drugs and further clinical studies.

Clinicians' view on the management of oral health in Parkinson's disease patients: a qualitative study.

BACKGROUND: due to numerous motor and non-motor symptoms, dental treatment in patients with Parkinson's Disease (PD) can be challenging. Knowledge regarding optimal management of oral health in PD patients is lacking. AIM: to gain a deeper understanding of the experiences of dentists regarding oral health care for PD patients in the Netherlands. MATERIAL AND METHOD: semi-structured interviews were conducted with (specialized) dentists working with PD patients. A thematic analysis was performed using a framework-based approach. RESULTS: ten dentists were interviewed. They reported that dental care in PD patients requires 1) adaptation of timing and length of treatments and consultations, and 2) intensifying preventive measures. Dentists experienced the organization as bureaucratic and difficult. Moreover, differences between being institutionalized or living at home were present. Education and research are needed to improve PD patients' oral health. The experience level and affinity for treating PD patients positively influences confidence levels of the practitioner. Finally, points of improvement were suggested. CONCLUSION: managing oral health in PD patients is challenging, and interdisciplinary collaboration is needed to overcome difficulties. Reducing the bureaucratic burden and improving knowledge could help and stimulate oral health care providers to treat PD patients more effectively and, consequently, improve their oral health.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples. This was a multicenter retrospective study in the Netherlands and Belgium. BAL fluid samples were collected from patients with underlying hematological diseases with a suspected invasive fungal infection. Diagnosis of IPA was based on the 2020 European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) consensus definitions. GM results were reported as optical density index (ODI) values. ODI cutoff values for positive results that were evaluated were 0.5, 0.8, and 1.0 for the EIA and 0.16, 0.18, and 0.20 for the CLIA. Probable IPA cases were compared with two control groups, one with no evidence of IPA and another with no IPA or possible IPA. Qualitative agreement was analyzed using Cohen's κ, and quantitative agreement was analyzed by Spearman's correlation. We analyzed 141 BAL fluid samples from 141 patients; 66 patients (47%) had probable IPA, and 56 cases remained probable IPA when the EIA GM result was excluded as a criterion, because they also had positive culture and/or duplicate positive PCR results. Sixty-three patients (45%) had possible IPA and 12 (8%) had no IPA. The sensitivity and specificity of the two tests were quite comparable, and the overall qualitative agreement between EIA and CLIA results was 81 to 89%. The correlation of the actual CLIA and EIA values was strong at 0.72 (95% confidence interval, 0.63 to 0.80). CLIA has similar performance, compared to the gold-standard EIA, with the benefits of faster turnaround because batching is not required. Therefore, CLIA can be used as an alternative GM assay for BAL fluid samples.

Parkinson's disease and oral health: A systematic review.

OBJECTIVE: in patients with Parkinson's Disease (PD), oral health can be affected by motor and non-motor symptoms and/or medication use. Therefore, the aim was to systematically review the literature on oral health and associated factors of oral health in PD patients. DESIGN: a literature search was performed from inception up to April 5th, 2023. Original studies that assessed oral health-related factors in PD patients and were written in English or Dutch, were included. RESULTS: 11276 articles were identified, of which 43 met the inclusion criteria (quality range poor-good). A higher prevalence of dental biofilm, bleeding/gingivitis, pocket depth (≥4 mm), tooth mobility, caries, and number of decayed missing filled teeth/surfaces was found in PD patients than in controls. However, no difference between both groups was found when analysing edentulism and wearing dentures. Poor oral health of PD patients was associated with a longer disease duration, higher disease severity, and more prescribed medications. CONCLUSIONS: oral health of PD patients is worse than that of healthy individuals. It is associated with the duration and severity of PD and medication use. Therefore, we advise regular appointments with oral health care professionals, with an important focus on prevention.

Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study.

BACKGROUND: Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. METHODS: In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA. RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83). CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).

A role for heritable transcriptomic variation in maize adaptation to temperate environments.

BACKGROUND: Transcription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments. RESULT: We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes. Genes involved in core processes such as cell division, chromosome organization and cytoskeleton organization showed lower heritability of gene expression, while genes involved in anti-oxidation activity exhibited higher expression heritability. An expression genome-wide association study (eGWAS) identified 19,602 expression quantitative trait loci (eQTLs) associated with the expression of 11,444 genes. A GWAS for alternative splicing identified 49,897 splicing QTLs (sQTLs) for 7614 genes. Genes harboring both cis-eQTLs and cis-sQTLs in linkage disequilibrium were disproportionately likely to encode transcription factors or were annotated as responding to one or more stresses. Independent component analysis of gene expression data identified loci regulating co-expression modules involved in oxidation reduction, response to water deprivation, plastid biogenesis, protein biogenesis, and plant-pathogen interaction. Several genes involved in cell proliferation, flower development, DNA replication, and gene silencing showed lower gene expression variation explained by genetic factors between temperate and tropical maize lines. A GWAS of 27 previously published phenotypes identified several candidate genes overlapping with genomic intervals showing signatures of selection during adaptation to temperate environments. CONCLUSION: Our results illustrate how maize transcriptional regulatory networks enable changes in transcriptional regulation to adapt to temperate regions.

Association of Proton Pump Inhibitor Use With Risk of Acquiring Drug-Resistant Enterobacterales.

Importance: Proton-pump inhibitors (PPIs) have been associated with the risk of colonization with drug-resistant bacteria; however, possible confounding by lifestyle-associated factors and disease severity casts doubt on this association, and whether the risk is dose dependent is not known. Objectives: To assess the association between PPI use and the risk of acquiring drug-resistant Enterobacterales and to examine interactions with possible microbiome-altering agents. Design, Setting, and Participants: This nested case-control study involved 2239 hospitalized adult (aged ≥18 years) patients identified from the microbiology laboratory database of Amsterdam University Medical Centers between December 31, 2018, and January 6, 2021. Patients in the case group had newly detected extended-spectrum ß-lactamase (ESBL)- or carbapenemase-producing Enterobacterales (identified by clinical specimens). Risk-set sampling was used to assign patients with negative results for ESBL- and carbapenemase-producing Enterobacterales to the control group, who were then matched on a 5:1 ratio with patients in the case group by age and culture date. A second validation case-control study included matched pairs (1:1 ratio; 94 in each group) of patients who were prospectively enrolled. Exposures: Proton pump inhibitor use and clinical data at 30 days (primary exposure) and 90 days (secondary exposure) before the date of culture. Main Outcomes and Measures: Adjusted incidence rate ratios (aIRRs) of ESBL- or carbapenemase-producing Enterobacterales acquisition by PPI dose and time risk windows (30 days for the primary outcome and 90 days for the secondary outcome) were estimated using conditional logistic regression models. Results: Among 2239 hospitalized patients (51.1% male; mean [SD] age, 60.9 [16.7] years), 374 were in the case group (51.6% male; mean [SD] age, 61.1 [16.5] years) and 1865 were in the matched control group (51.0% male; mean [SD] age, 60.9 [16.7] years). The aIRR for PPI use overall was 1.48 (95% CI, 1.15-1.91) at 30 days. Sensitivity analyses and the analysis of the pair-matched study with prospectively enrolled patients (aIRR, 2.96, 95% CI, 1.14-7.74) yielded similar results; findings were consistent in subgroups and corroborated by a negative-control exposure analysis. No association with microbiome-disturbing agents was found; laxatives and antibiotics were independently associated with a more than 2-fold increase in the risk of acquisition (antibiotics: aIRR, 2.78 [95% CI, 2.14-3.59]; laxatives: aIRR, 2.26 [95% CI. 1.73-2.94]). Conclusions and Relevance: In this study, after careful control for confounding and sensitivity analyses, PPI use was associated with increases in the risk of acquiring ESBL- or carbapenemase-producing Enterobacterales among adult hospitalized patients. These findings emphasize the need for judicious use of PPIs.

Incidence, risk factors and pre-emptive screening for COVID-19 associated pulmonary aspergillosis in an era of immunomodulant therapy.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment. MATERIALS AND METHODS: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria. RESULTS: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy. CONCLUSIONS: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation.

Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers: a systematic review and meta-regression analysis.

BACKGROUND: Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. METHODS: We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. FINDINGS: Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10-18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5-13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69-6·82) and cumulative incidence of infection (19%, 95% CI 15-25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. INTERPRETATION: The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention. FUNDING: The Netherlands Organization for Health Research and Development.

Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study.

BACKGROUND: In neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin -resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy. METHODS: Retrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days. RESULTS: A total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem. CONCLUSIONS: This retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.

Olecranon bursitis caused by Scedosporium apiospermum in a patient treated with CAR-T cells.

Chimeric antigen receptor (CAR-) T cell therapy is a relatively new form of immunotherapy for hematological malignancies. Although patients are at increased risk of infection following CAR-T cell therapy, reports of fungal infections are scarce. We report a case of Scedosporium apiospermum infection causing bursitis of the elbow in a lymphoma patient after treatment with CAR-T cells. The fungal bursitis relapsed under posaconazole treatment, but was cured after surgical extirpation of the bursa.

[Carbapenems: take it when needed but leave it if you can]. / Carbapenems: inzetten als het moet, vermijden als het kan.

Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective.

Comparative analysis of IMP-4- and OXA-58-containing plasmids of three carbapenemase-producing Acinetobacter ursingii strains in the Netherlands.

OBJECTIVES: A recent occurrence of carbapenemase-producing Acinetobacter ursingii was reported in the Netherlands and comprised three unrelated strains carrying the blaIMP-4 and blaOXA-58 encoding genes. The objective was to investigate a putative common source of the carbapenemase resistance genes and plasmids in these A. ursingii strains. METHODS: Hybrid assembly of short-read and long-read sequencing data was performed using Unicycler and assembled genomes were analysed by ResFinder and PlasmidFinder. RESULTS: Hybrid assemblies of A. ursingii genomes yielded a circular chromosome, a large plasmid harboring blaIMP-4 and blaOXA-58 genes (sizes 259-317kb), and four to five other smaller plasmids. ResFinder analyses revealed 16 other acquired resistance genes on the plasmids carrying the blaIMP-4 and blaOXA-58 genes. These 18 genes encode resistance towards eight antibiotic classes. The smaller plasmids did not carry acquired resistance genes. Comparative analysis showed that the three blaIMP-4/blaOXA-58 plasmids were similar (61%-83%) and shared 13 to 17 of the 18 resistance genes. BLAST analysis showed that the blaIMP-4/blaOXA-58 plasmids were not reported before. However, a close match with a 399 kb plasmid from Acinetobacter johnsonii was found (99% similarity, 80% coverage). This A. johnsonii plasmid contains the blaOXA-58 gene, but lacks blaIMP-4, and it shares eight other resistance genes with those present on the A. ursingii blaIMP-4/blaOXA-58 plasmids. CONCLUSION: Three blaIMP-4/blaOXA-58-carrying plasmids were characterized in three carbapenemase-producing A. ursingii strains. The plasmids were highly similar, suggesting a putative common source or co-selection of resistance genes from A. johnsonii. These results provide initial insights in the dissemination of carbapenem-resistance in A. ursingii in the Netherlands.

Orofacial pain and dysfunction in patients with Parkinson's disease: A scoping review.

BACKGROUND: Parkinson's disease (PD) is commonly known as a disorder that affects the smooth performance of body movements. In addition to the motor impairments, patients with PD often experience pain. Both motor impairments and pain can occur throughout the body, hence including the orofacial region. However, currently, there is a lack of knowledge on the orofacial manifestations. Since orofacial pain and dysfunction can, amongst others, reduce the quality of life of patients with PD, it is important to explore the prevalence of these symptoms in the PD population. OBJECTIVE: To provide a broad overview of the relevant literature on orofacial pain and dysfunction in patients with PD. Furthermore, we aim to generate hypotheses for future research on this topic. DATABASES AND DATA TREATMENT: A literature search (in PubMed, Embase.com, Web of Science [Core collection], and Cochrane Library) was performed on 20 January 2022, in collaboration with a medical librarian. In total, 7180 articles were found, of which 50 were finally included in this scoping review. RESULTS: In the included studies, pain (e.g. orofacial pain (N = 2) and temporomandibular disorder pain (N = 2)), orofacial motor dysfunction (e.g. limited jaw movements (N = 10), reduced maximum muscle output (N = 3), chewing difficulties (N = 9), unspecified TMD (N = 3), sensory disturbances (N = 1)), and bruxism (N = 3) were observed more often in patients with PD than in healthy controls. CONCLUSION: Patients with PD experience more pain in the orofacial area and more dysfunction of the masticatory system than their healthy peers. SIGNIFICANCE: This scoping review can increase health care providers' awareness of the problems that can be encountered in the orofacial area of PD patients, especially pain syndromes also occur in the orofacial region and not only in the extremities. Besides, dysfunction of the orofacial area is elaborated in this scoping review, which helps to understand that this limits PD patients' quality of life. Further, the outcomes of this scoping review can assist in encouraging collaboration between medicine and dentistry. Finally, this scoping review suggests new research areas, based on the gaps identified in the current literature on this topic. Ultimately, this will improve individualized strategies for reducing orofacial pain and/or dysfunction in PD patients.

Human Clinical Isolates of Pathogenic Fungi Are Host to Diverse Mycoviruses.

Fungi host viruses from many families, and next-generation sequencing can be used to discover previously unknown genomes. Some fungus-infecting viruses (mycoviruses) confer hypovirulence on their pathogenic hosts, raising the possibility of therapeutic application in the treatment of fungal diseases. Though all fungi probably host mycoviruses, many human pathogens have none documented, implying the mycoviral catalogue remains at an early stage. Here, we carried out virus discovery on 61 cultures of pathogenic fungi covering 27 genera and at least 56 species. Using next-generation sequencing of total nucleic acids, we found no DNA viruses but did find a surprising RNA virus diversity of 11 genomes from six classified families and two unclassified lineages, including eight genomes likely representing new species. Among these was the first jivivirus detected in a fungal host (Aspergillus lentulus). We separately utilized rolling circle amplification and next-generation sequencing to identify ssDNA viruses specifically. We identified 13 new cressdnaviruses across all libraries, but unlike the RNA viruses, they could not be confirmed by PCR in either the original unamplified samples or freshly amplified nucleic acids. Their distributions among sequencing libraries and inconsistent detection suggest low-level contamination of reagents. This highlights both the importance of validation assays and the risks of viral host prediction on the basis of highly amplified sequencing libraries. Meanwhile, the detected RNA viruses provide a basis for experimentation to characterize possible hypovirulent effects, and hint at a wealth of uncharted viral diversity currently frozen in biobanks. IMPORTANCE Fungal pathogens of humans are a growing global health burden. Viruses of fungi may represent future therapeutic tools, but for many fungal pathogens there are no known viruses. Our study examined the viral content of diverse human-pathogenic fungi in a clinical biobank, identifying numerous viral genomes, including one lineage previously not known to infect fungi.