Cardiovascular magnetic resonance-guided right heart catheterization in a conventional CMR environment - predictors of procedure success and duration in pulmonary artery hypertension

Background Cardiovascular magnetic resonance imaging (CMR) is valuable for the investigation and management of pulmonary artery hypertension (PAH), but the direct measurement of pulmonary hemodynamics by right heart catheterization is still necessary. CMR-guided right heart catheterization (CMR-RHC) combines the benefits of CMR and invasive cardiac catheterization, but its feasibility in patients with acquired PAH has not been established. The aims of this study are to: (1) demonstrate the feasibility of CMR-RHC in patients being assessed for PAH in a conventional diagnostic CMR scanner room; (2) determine the predictors of (i) procedure duration, and (ii) procedural failure or technical difficulty as determined by the adjunctive need for a guidewire. Methods Fifty patients investigated for suspected or known PH underwent CMR-RHC. Durations of separate procedural components were recorded, including time taken to pass the catheter from the femoral vein to a stable wedge position (procedure time) and total time the patient spent in the CMR department (department time). Associations between procedural failure/guidewire usage and hemodynamic/CMR measures were assessed using logistic regression. Relationships between procedure times and hemodynamic/CMR measures were evaluated using Spearman’s correlation coefficient. Results A full CMR-RHC study was successfully completed in 47 (94%) patients. CMR-conditional guidewires were used in 6 (12%) patients. Metrics associated with guidewire use/procedural failure were higher mean pulmonary artery (PA) pressures (mPAP: OR = 1.125, p = 0.018), right heart dilatation (right ventricular (RV) end-systolic volume (RVESV): OR = 1.028, p = 0.018), RV hypertrophy (OR = 1.050, p = 0.0067) and RV ejection fraction (EF) (OR = 0.914, p = 0.014). Median catheter and department times were 3.6 (2.0–7.7) minutes and 60.0 (54.0–68.5) minutes, respectively. All procedure times became significantly shorter with increasing procedural experience (p < 0.05). Catheterization time was also associated with PH severity (RV systolic pressure: rho = 0.46, p = 0.0013) and increasing RV end-systolic volume (RVESV: rho = 0.41, p = 0.0043), hypertrophy (rho = 0.43, p = 0.0025) and dysfunction (RVEF: rho = − 0.32, p = 0.031). Conclusions This study demonstrates that CMR-RHC using standard technology can be incorporated into routine clinical practice for the investigation of PAH. Procedural failure was rare but more likely in patients with severe PAH. Procedure time is clinically acceptable and increases with worsening PAH severity

Differential attraction in mosquito-human interactions and implications for disease control: Differential attraction to mosquitoes

Mosquito-borne diseases are a major burden on human health worldwide and their eradication through vector control methods remains challenging. In particular, the success of vector control interventions for targeting diseases such as malaria is under threat, in part due to the evolution of insecticide resistance, while for other diseases effective control solutions are still lacking. The rate at which mosquitoes encounter and bite humans is a key determinant of their capacity for disease transmission. Future progress is strongly reliant on improving our understanding of the mechanisms leading to a mosquito bite. Here, we review the biological factors known to influence the attractiveness of mosquitoes to humans, such as body odour, the skin microbiome, genetics and infection by parasites. We identify the knowledge gaps around the relative contribution of each factor, and the potential links between them, as well as the role of natural selection in shaping vector-host-parasite interactions. Finally, we argue that addressing these questions will contribute to improving current tools and the development of novel interventions for the future. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'

Encephalomeningocele cases over 10 years in Thailand: a case series

BACKGROUND: Encephalomeningocele, especially in the frontoethmoidal region, is a form of neural tube defect which affects patients in Southeast Asia more commonly than in Western countries. Its underlying cause is not known but teratogenic environmental agents are suspected. However, nutritional deficiency, as in spina bifida, cannot be excluded. METHODS: This study reports 21 cases of meningocele (without brain tissue in the lesion) and encephalomeningocele (with brain tissue) that were admitted to our hospital for surgical corrections in the period of ten years, from 1990 to 1999. Clinicopathological findings, as well as occupations of family members and prenatal exposures to infectious agents or chemicals were reviewed and analyzed. RESULTS: The most commonly involved area was the frontoethmoidal region, found in 20 cases. The combined pattern between nasoethmoidal and nasoorbital defects was found most frequently (11 from 21 cases) and had more associated abnormalities. Encephalomeningocele had more related abnormalities than meningocele with proportions of 0.6 and 0.3, respectively. CONCLUSIONS: Here, we confirmed that genetic defects are not likely to be the single primary cause of this malformation. However, we could not draw any conclusions on etiologic agents. We suggest that case control studies and further investigation on the role of nutritional deficiencies, especially folic acid, in the pathogenesis of encephalomeningocele are necessary to clarify the underlying mechanisms

Prostate Indeterminate Lesions on Magnetic Resonance Imaging-Biopsy Versus Surveillance: A Literature Review

CONTEXT: The indeterminate multiparametric prostate magnetic resonance image (mpMRI) lesion is one which cannot be classified as "positive" or "negative" for suspected cancer. Currently, there is no consensus on how to manage patients with indeterminate mpMRIs where areas cannot be classified as positives or negatives (Prostate Imaging Reporting and Data System [PI-RADS] 3 or Likert 3). OBJECTIVE: To define the concept of indeterminate lesion and describe the management strategies that may be adopted for these patients. EVIDENCE ACQUISITION: A literature search of the PubMed database was performed including the search terms "prostate indeterminate lesions", "PI-RADS 3", "Likert 3", "magnetic resonance imaging", and "prostate cancer". EVIDENCE SYNTHESIS: There is no universally accepted definition of what constitutes an indeterminate lesion on mpMRI. This is partly due to the experience of the reporting radiologist and their willingness to call a lesion indeterminate, knowing that this may have consequences for biopsy decisions. This is also partly due to the significant variation in mpMRI acquisition parameters used between different sites. Strategies for managing the indeterminate lesion include: (1) biopsy, where there is a highly variable prevalence of prostate cancer (PCa), reflecting the differences in clinically significant PCa definitions, mpMRI protocols and interobserver variability in characterization of indeterminate lesions and (2) surveillance, where early results suggest that this strategy may be of value for some selected patients with prostate-specific antigen (PSA) monitoring and/or interval mpMRI. The use of prebiopsy MRI, in conjunction with traditional clinical parameters and secondary biomarkers-nomograms, may allow a more accurate selection of patients who can avoid biopsy. CONCLUSIONS: A strategy of close surveillance based on PSA monitoring and interval mpMRI is a feasible management option for motivated patients with indeterminate mpMRI. This surveillance strategy could result in fewer men needing to undergo biopsy, and although early results are promising, long-term results for such a strategy are awaited. PATIENT SUMMARY: In some patients who have an MRI scan of their prostate, the scan may identify an area which may or may not contain cancer. This area is typically called the "indeterminate" lesion. In this report, we attempted to define the concept of indeterminate lesion on multiparametric magnetic resonance (mpMRI) and described the strategies that may be performed for these patients. The use of mpMRI in conjunction with traditional clinical parameters may allow more accurate risk stratification and assessment of the need for prostate biopsy

Prevalence and definition of drooling in Parkinson’s disease: a systematic review

Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson’s disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44–67) for PD patients and 14% (95% CI 3–25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1–14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50–60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22–26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints

AmrZ is a major determinant of c-di-GMP levels in Pseudomonas fluorescens F113

The transcriptional regulator AmrZ is a global regulatory protein conserved within the pseudomonads. AmrZ can act both as a positive and a negative regulator of gene expression, controlling many genes implicated in environmental adaption. Regulated traits include motility, iron homeostasis, exopolysaccharides production and the ability to form biofilms. In Pseudomonas fluorescens F113, an amrZ mutant presents a pleiotropic phenotype, showing increased swimming motility, decreased biofilm formation and very limited ability for competitive colonization of rhizosphere, its natural habitat. It also shows different colony morphology and binding of the dye Congo Red. The amrZ mutant presents severely reduced levels of the messenger molecule cyclic-di-GMP (c-di-GMP), which is consistent with the motility and biofilm formation phenotypes. Most of the genes encoding proteins with diguanylate cyclase (DGCs) or phosphodiesterase (PDEs) domains, implicated in c-di-GMP turnover in this bacterium, appear to be regulated by AmrZ. Phenotypic analysis of eight mutants in genes shown to be directly regulated by AmrZ and encoding c-di-GMP related enzymes, showed that seven of them were altered in motility and/or biofilm formation. The results presented here show that in P. fluorescens, AmrZ determines c-di-GMP levels through the regulation of a complex network of genes encoding DGCs and PDEs

A multidimensional systems biology analysis of cellular senescence in aging and disease.

BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence

Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk