INTRODUCTION: The use of signal dogs for cancer detection is not yet routinely performed,but dogs and their powerful olfactory system have proven to be a unique and valuable tool for many lineages and are beginning to be incorporated into medical practice. This method has great advantages; the dog can detect a tumour in the human body already in preclinical stages, when the patient has no symptoms yet. The identification of cancer biomarkers to enable early diagnosis is a need for many types of cancer, whose prognosis is strongly dependent on the stage of the disease. However, this method also has its various pitfalls that must be taken into account. AIM: The aim of the study was to identify and highlight the factors that affect the level of detection accuracy, but also the conditions associated with olfactometric diagnosis. METHODS: The study included 48 dogs and 48 handlers, that were part of the training between 2016 and 2023.All those who started olfactometry training and remained in training for at least one year were included in the study. The dogs ranged in age from 8 months to 12 years and were of different races and sexes. After long-term observation, a qualitative analysis was performed and factors that may play a role in the early detection of the disease were listed. RESULTS: The results of the search for the different factors have been compiled into two groups, focussing on the actual handling of the patient biological sample from collection, processing, storage until transport, preparation of the sample,and detection. Focus on the actual work and behaviour of the dog and handler. CONCLUSION: There are many factors; however, it is worth addressing them because the canine sense of smell is one of the possible uses as a diagnostic method.
- Publication type
- Journal Article MeSH
BACKGROUND: Charcot-Marie-Tooth is the most common inherited neuromuscular disorder. Rarely, it can be associated with heart failure and various arrhythmic disturbances. This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease. CASE SUMMARY: A 69-year-old male with a history of Type 1A Charcot-Marie-Tooth disease was admitted due to repetitive runs of ventricular tachycardia. Twelve-lead electrocardiogram, echocardiography, selective coronary angiography, and cardiac magnetic resonance did not clarify the cause of the electrical storm. As conservative therapy was not successful, radiofrequency ablation was chosen to treat the electrical storm. After this procedure, implantable cardioverter defibrillator (ICD) was implanted. The follow-up revealed severe perforation by the ventricular lead. An extraction was performed with no complications and a new lead was immediately implanted. The patient remains asymptomatic. Three episodes of non-sustained ventricular tachycardia were recorded during the last follow-up. DISCUSSION: This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease after successful ablation for electrical storm. Due to a lack of evidence, atypical origin of arrhythmia, and clinical presentation, we did not consider this as idiopathic arrhythmia and decided to implant an ICD, which was complicated by severe perforation by the lead. Specific recommendations for preventing sudden cardiac death in rare cardiac conditions, such as Charcot-Marie-Tooth disease, still need to be refined.
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Lipids from microorganisms, and especially lipids from Archaea, are used as taxonomic markers. Unfortunately, knowledge is very limited due to the uncultivability of most Archaea, which greatly reduces the importance of the diversity of lipids and their ecological role. One possible solution is to use lipidomic analysis. Six radioactive sources were investigated, two of which are surface (Wettinquelle and Radonka) and four deep from the Svornost mine (Agricola, Behounek, C1, and Curie). A total of 15 core lipids and 82 intact polar lipids were identified from the membranes of microorganisms in six radioactive springs. Using shotgun lipidomics, typical Archaea lipids were identified in spring water, namely dialkyl glycerol tetraethers, archaeol, hydroxyarchaeol and dihydroxyarchaeol. Diverse groups of polar heads were formed in archaeal IPLs, whose polar heads are formed mainly by hexose, deoxyhexose, and phosphoglycerol. The analysis was performed using shotgun lipidomics and the structure of all molecular species was confirmed by tandem mass spectrometry. After acid hydrolysis, a mixture of polar compounds was obtained from the polar head. Further analysis by GC-MS confirmed that the carbohydrates were glucose and rhamnose. Analysis by HPLC-MS of diastereoisomers of 2-(polyhydroxyalkyl)-3-(O-tolylthiocarbamoyl)thiazolidine-4(R)-carboxylates revealed that both L-rhamnose and D-glucose are present in spring samples only in varying amounts. The glycoside composition depends on the type of spring, that is, Wettinquelle and Radonka springs are basically shallow groundwater, while the samples from the Svornost mine are deep groundwater and do not contain glycosides with rhamnose. This method enables quick screening for characteristic Archaea lipids, allowing decisions on whether to pursue further analyses, such as metagenomic analysis, to directly confirm the presence of Archaea.
BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.
- Publication type
- Journal Article MeSH
BACKGROUND: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven. OBJECTIVES: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use. METHODS: From a retrospective, multicenter study on heart failure-related outcome in individuals with SRV, those who were taking an ACEI/ARB, beta-blocker, or both of these medication were identified. We performed a propensity analysis to match them to those not using these medications at their initial visit. Matching was based on a propensity score, which captured co-morbidities, demographics, and baseline echocardiographic parameters. Primary outcome of death, transplant, or mechanical circulatory support, and secondary outcomes of heart failure hospitalizations/atrial arrhythmias were analyzed respectively. RESULTS: We identified 393 patients taking ACEI/ARB or beta-blocker, or taking both a beta-blocker and ACEI/ARB (62.1% male, median age 31.3 years) and 484 patients (56.4% male, median age of 26.0 years) who were neither on a beta-blocker nor on ACEI/ARB at the time of initial clinic visit. Median follow-up was ∼8 years. After propensity matching, medication use was not associated with decreased mortality, heart failure hospitalizations, or arrhythmias. Hazard ratios remained positive for beta blockers, implying potential harm rather than benefit. CONCLUSIONS: In this large multicenter propensity-matched observational study, patients with SRV taking beta-blockers or ACEI/ARB did not have a benefit in survival or reduced hospitalization. The likelihood of demonstrating favorable effects in larger studies appears remote.
- Publication type
- Journal Article MeSH
BACKGROUND: Advances in paediatric type 1 diabetes management and increased use of diabetes technology have led to improvements in glycaemia, reduced risk of severe hypoglycaemia, and improved quality of life. Since 1993, progressively lower HbA1c targets have been set. The aim of this study was to perform a longitudinal analysis of HbA1c, treatment regimens, and acute complications between 2013 and 2022 using data from eight national and one international paediatric diabetes registries. METHODS: In this longitudinal analysis, we obtained data from the Australasian Diabetes Data Network, Czech National Childhood Diabetes Register, Danish Registry of Childhood and Adolescent Diabetes, Diabetes Prospective Follow-up Registry, Norwegian Childhood Diabetes Registry, England and Wales' National Paediatric Diabetes Audit, Swedish Childhood Diabetes Registry, T1D Exchange Quality Improvement Collaborative, and the SWEET initiative. All children (aged ≤18 years) with type 1 diabetes with a duration of longer than 3 months were included. Investigators compared data from 2013 to 2022; analyses performed on data were pre-defined and conducted separately by each respective registry. Data on demographics, HbA1c, treatment regimen, and event rates of diabetic ketoacidosis and severe hypoglycaemia were collected. ANOVA was performed to compare means between registries and years. Joinpoint regression analysis was used to study significant breakpoints in temporal trends. FINDINGS: In 2022, data were available for 109 494 children from the national registries and 35 590 from SWEET. Between 2013 and 2022, the aggregated mean HbA1c decreased from 8·2% (95% CI 8·1-8·3%; 66·5 mmol/mol [65·2-67·7]) to 7·6% (7·5-7·7; 59·4mmol/mol [58·2-60·5]), and the proportion of participants who had achieved HbA1c targets of less than 7% (<53 mmol/mol) increased from 19·0% to 38·8% (p<0·0001). In 2013, the aggregate event rate of severe hypoglycaemia rate was 3·0 events per 100 person-years (95% CI 2·0-4·9) compared with 1·7 events per 100 person-years (1·0-2·7) in 2022. In 2013, the aggregate event rate of diabetic ketoacidosis was 3·1 events per 100 person-years (95% CI 2·0-4·8) compared with 2·2 events per 100 person-years (1·4-3·4) in 2022. The proportion of participants with insulin pump use increased from 42·9% (95% CI 40·4-45·5) in 2013 to 60·2% (95% CI 57·9-62·6) in 2022 (mean difference 17·3% [13·8-20·7]; p<0·0001), and the proportion of participants using continuous glucose monitoring (CGM) increased from 18·7% (95% CI 9·5-28·0) in 2016 to 81·7% (73·0-90·4) in 2022 (mean difference 63·0% [50·3-75·7]; p<0·0001). INTERPRETATION: Between 2013 and 2022, glycaemic outcomes have improved, parallel to increased use of diabetes technology. Many children had HbA1c higher than the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 target. Reassuringly, despite targeting lower HbA1c, severe hypoglycaemia event rates are decreasing. Even for children with type 1 diabetes who have access to specialised diabetes care and diabetes technology, further advances in diabetes management are required to assist with achieving ISPAD glycaemic targets. FUNDING: None. TRANSLATIONS: For the Norwegian, German, Czech, Danish and Swedish translations of the abstract see Supplementary Materials section.
- MeSH
- Diabetes Mellitus, Type 1 * epidemiology blood drug therapy MeSH
- Child MeSH
- Glycated Hemoglobin * analysis MeSH
- Hypoglycemia epidemiology MeSH
- Hypoglycemic Agents * therapeutic use MeSH
- Infant MeSH
- Blood Glucose * analysis MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Registries * statistics & numerical data MeSH
- Glycemic Control statistics & numerical data methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: This study was performed to compare the efficacy and safety of PreserFlo MicroShunt (PMS) implantation with mitomycin C (MMC) applied by sub-tenon injection versus conventional application by MMC-soaked sponges. METHODS: This retrospective, 1-year cohort study included 100 eyes of 100 patients with glaucoma who underwent PMS implantation with MMC (0.4 mg/ml) delivered either by sub-tenon injection (50 eyes) or via soaked sponges (50 eyes). The primary outcome measure at 1 year was intraocular pressure (IOP) reduction, with complete success defined as an IOP reduction of ≥ 20% and achieving a target IOP of ≤ 21 or 18 mmHg without the use of medication. Secondary outcomes, including corneal endothelial cell density (CECD) loss, the number of medications, and complications, were assessed and compared between the groups. RESULTS: Sustained reductions in mean IOP were observed in both groups over the 1-year follow-up, with no significant differences between the groups. The complete success rate, with a target IOP of ≤ 21 mmHg after 1 year, was 19.3% in the sponge group and 26.4% in the injection group. The qualified success rate was 59.0% and 87.4% in the sponge and injection groups, respectively. A longer survival rate was observed in the injection group than in the sponge group when IOP was below 21 mmHg. The mean CECD significantly decreased (P < 0.01) from baseline to each postoperative follow-up time point in both groups. At 1 year postoperatively, the percentage of total CECD loss was 8.1% in the sponge group and 8.0% in the injection group. However, no significant differences in mean CECD values, the number of medications, or adverse events were found between the groups. CONCLUSIONS: PMS implantation with sub-tenon injection of MMC was comparable in terms of efficacy and safety to traditional MMC delivery via soaked sponges. However, the injection group demonstrated a significantly higher success rate than the sponge group.
- Publication type
- Journal Article MeSH
Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.
- MeSH
- White Matter pathology diagnostic imaging MeSH
- Adult MeSH
- Hepatolenticular Degeneration * pathology diagnostic imaging MeSH
- Liver pathology diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Young Adult MeSH
- Brain * pathology diagnostic imaging MeSH
- Gray Matter pathology diagnostic imaging MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND AND OBJECTIVES: For thousands of years, betel nut has been used as a psychoactive agent in Asian and Oceanian populations. Betel nut chewing was associated with the alteration of human oral microbiome and with diseases such as oral cancer and periodontitis, but only in populations of Asian cultural background. We studied the influence of betel nut chewing on the oral microbiome in Papua New Guinea, where half of the population uses betel nut and the prevalence of these diseases is one of the highest in the world. METHODOLOGY: We characterized the oral microbiomes of 100 Papua New Guineans. We defined two cohorts of betel chewers (n = 50) and non-chewers (n = 50) based on a genetic approach to identify the presence of betel nut in saliva. We statistically compared the alpha and beta microbial diversities between the two cohorts. We performed linear discriminant analyses to identify bacterial species more prevalent in each cohort. RESULTS: We found that oral microbial diversity is significantly different between betel chewers and non-chewers. The dysbiosis observed in betel chewers, led to an increase of pathogenic bacterial species including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, known to be in the aetiology of periodontal diseases. CONCLUSIONS AND IMPLICATIONS: Our study strongly supports the alteration of human oral microbiome by betel nut use, potentially leading to periodontal diseases. It also shows the need to consider local specificities (e.g. different habits, betel nut types, and oral microbial diversities) to better characterize the impact of betel nut chewing on health.
- Publication type
- Journal Article MeSH
Cyanobacteria are prokaryotic organisms characterised by their complex structures and a wide range of pigments. With their ability to fix CO2, cyanobacteria are interesting for white biotechnology as cell factories to produce various high-value metabolites such as polyhydroxyalkanoates, pigments, or proteins. White biotechnology is the industrial production and processing of chemicals, materials, and energy using microorganisms. It is known that exposing cyanobacteria to low levels of stressors can induce the production of secondary metabolites. Understanding of this phenomenon, known as hormesis, can involve the strategic application of controlled stressors to enhance the production of specific metabolites. Consequently, precise measurement of cyanobacterial viability becomes crucial for process control. However, there is no established reliable and quick viability assay protocol for cyanobacteria since the task is challenging due to strong interferences of autofluorescence signals of intercellular pigments and fluorescent viability probes when flow cytometry is used. We performed the screening of selected fluorescent viability probes used frequently in bacteria viability assays. The results of our investigation demonstrated the efficacy and reliability of three widely utilised types of viability probes for the assessment of the viability of Synechocystis strains. The developed technique can be possibly utilised for the evaluation of the importance of polyhydroxyalkanoates for cyanobacterial cultures with respect to selected stressor-repeated freezing and thawing. The results indicated that the presence of polyhydroxyalkanoate granules in cyanobacterial cells could hypothetically contribute to the survival of repeated freezing and thawing.
