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
Previous reports provided recommendations for familial renal glucosuria diagnosis without complex view on differential diagnosis of glucosuria. The aim of this review was to provide an overview of the causes of glucosuria and to create an evidence-based diagnostic approach for children with glucosuria. We searched the current literature with a focus to identify the possible etiology of glucosuria, gaining insight into the pathophysiology of glucosuria. Urinary glucose is completely reabsorbed in the proximal tubule of kidneys. It only appears in the urine if the plasma glucose concentration exceeds the renal threshold for glucose or in the case of insufficient renal glucose reabsorption. The proteins that provide glucose reabsorption are SGLT2 and SGLT1 - sodium-dependent co-transporters that transport glucose from the lumen into epithelial cells - and GLUT2 - a passive transporter providing facilitative glucose transport from epithelial cells to plasma. Renal glucose reabsorption is affected in case of acquired or inherited complex dysfunction of proximal tubule called Fanconi Syndrome or due to pathogenic variants of genes encoding glucose transporters. Prior to diagnosing any of these, diabetes mellitus must be excluded together with other conditions leading to hyperglycemia. In conclusion, glucosuria is always an abnormal finding. The review provides a simple evidence-based diagnostic approach to navigate the differential diagnosis of glucosuria.
- MeSH
- Diagnosis, Differential MeSH
- Child MeSH
- Fanconi Syndrome diagnosis complications MeSH
- Glucose * metabolism MeSH
- Glycosuria * diagnosis etiology MeSH
- Humans MeSH
- Glucose Transporter Type 2 metabolism MeSH
- Kidney Tubules, Proximal metabolism MeSH
- Glycosuria, Renal * diagnosis etiology physiopathology MeSH
- Sodium-Glucose Transporter 1 metabolism MeSH
- Sodium-Glucose Transporter 2 metabolism MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review 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
The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
OBJECTIVES: Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage. METHODS: First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles. The single-voided specimens were collected without acidification, after which they were divided into three groups for storage: samples without acidification ("NON"), acidification before storage ("PRE"), or acidification after storage ("POST"). The analyses were conducted on the day of arrival (day 0, "baseline"), or after storage for 2 or 7 days at room temperature. The maximum permissible difference (MPD) was defined as ±20 % from the baseline. RESULTS: The urine concentrations of all stone-related metabolites remained within the 20 % MPD limits in NON and POST samples after 2 days, except for calcium in NON sample of one patient, and oxalate of three patients and citrate of one patient in POST samples. In PRE samples, stability failed in urine samples for oxalate of three patients, and for uric acid of four patients after 2 days. Failures in stability often correlated with high baseline concentrations of those metabolites in urine. CONCLUSIONS: Detailed procedures are needed to collect urine specimens for analysis of urinary stone-related metabolites, considering both patient safety and stability of those metabolites. We recommend specific preservation steps.
- MeSH
- Urinalysis methods MeSH
- Adult MeSH
- Hydrogen-Ion Concentration MeSH
- Uric Acid urine MeSH
- Middle Aged MeSH
- Humans MeSH
- Urinary Calculi * urine MeSH
- Specimen Handling methods MeSH
- Recurrence * MeSH
- Urine Specimen Collection methods MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
S postupující digitalizací patologie se do popředí zájmu dostávají i aplikace metod strojového učení a umělé inteligence. Výzkum a vývoj v této oblasti je velmi rychlý, ale aplikace učících systémů v klinické praxi stále zaostávají. Cílem tohoto textu je přiblížit proces tvorby a nasazení učících systémů v digitální patologii. Začneme popisem základních vlastností dat produkovaných v rámci digitální patologie. Konkrétně pojednáme o skenerech a skenování vzorků, o ukládání a přenosu dat, o kontrole jejich kvality a přípravě pro zpracování pomocí učících systémů, zejména o anotacích. Naším cílem je prezentovat aktuální přístupy k řešení technických problémů a zároveň upozornit na úskalí, na která lze narazit při zpracování dat z digitální patologie. V první části také naznačíme, jak vypadají aktuální softwarová řešení pro prohlížení naskenovaných vzorků a implementace diagnostických postupů zahrnujících učící systémy. Ve druhé části textu popíšeme obvyklé úlohy digitální patologie a naznačíme obvyklé přístupy k jejich řešení. V této části zejména vysvětlíme, jak je nutné modifikovat standardní metody strojového učení pro zpracování velkých skenů a pojednáme o konkrétních aplikacích v diagnostice. Na závěr textu poskytneme rychlý náhled dalšího možného vývoje učících systémů v digitální patologii. Zejména ilustrujeme podstatu přechodu na velké základní modely a naznačíme problematiku virtuálního barvení vzorků. Doufáme, že tento text přispěje k lepší orientaci v rapidně se vyvíjející oblasti strojového učení v digitální patologii a tím přispěje k rychlejší adopci učících metod v této oblasti.
With the advancing digitalization of pathology, the application of machine learning and artificial intelligence methods is becoming increasingly important. Research and development in this field are progressing rapidly, but the clinical implementation of learning systems still lags behind. The aim of this text is to provide an overview of the process of developing and deploying learning systems in digital pathology. We begin by describing the fundamental characteristics of data produced in digital pathology. Specifically, we discuss scanners and sample scanning, data storage and transmission, quality control, and preparation for processing by learning systems, with a particular focus on annotations. Our goal is to present current approaches to addressing technical challenges while also highlighting potential pitfalls in processing digital pathology data. In the first part of the text, we also outline existing software solutions for viewing scanned samples and implementing diagnostic procedures that incorporate learning systems. In the second part of the text, we describe common tasks in digital pathology and outline typical approaches to solving them. Here, we explain the necessary modifications to standard machine learning methods for processing large scans and discuss specific diagnostic applications. Finally, we provide a brief overview of the potential future development of learning systems in digital pathology. We illustrate the transition to large foundational models and introduce the topic of virtual staining of samples. We hope that this text will contribute to a better understanding of the rapidly evolving field of machine learning in digital pathology and, in turn, facilitate the faster adoption of learning-based methods in this domain.
Správný odběr biologického materiálu je důležitým předpokladem pro získání spolehlivých laboratorních výsledků. Laboratorní vyšetření zahrnuje tři hlavní fáze (preanalytickou, analytickou a postanalytickou), přičemž zejména preanalytická fáze je nejčastějším zdrojem chyb. Zásadní význam má zejména řádné poučení pacienta, přesná identifikace vzorků a požadovaných vyšetření, volba vhodných odběrových nádob, samotný postup při odběru biologického materiálu a podmínky uchování a transportu odebraného materiálu. Tento článek shrnuje klíčové aspekty správného odběru různých typů biologického materiálu a upozorňuje na nejčastější chyby, které mohou vést ke znemožnění vyšetření, zkreslení výsledků a mít tak negativní vliv na správnou interpretaci laboratorního nálezu.
Proper collection of biological material is essential for obtaining reliable laboratory results. Laboratory testing includes three main phases: pre-analytical, analytical, and post-analytical. The pre-analytical phase is the most frequent source of error. Thorough patient instruction, accurate sample and test identification, appropriate container selection, proper collection procedures, and adherence to the collected material's specific storage and transport conditions are all of particular importance. This article summarises the crucial aspects of the proper collection of various types of biological material (e.g. blood, urine, and sputum) and highlights the most common errors that can result in failed tests, inaccurate results, or a negative impact on the interpretation of results.
- MeSH
- Clinical Laboratory Techniques MeSH
- Humans MeSH
- Specimen Handling * MeSH
- Pre-Analytical Phase MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Previous research has studied the extent to which men are the default members of social groups in terms of memory, categorization, and stereotyping, but not attitudes which is critical because of attitudes' relationship to behavior. Results from our survey (N > 5000) collected via a globally distributed laboratory network in over 40 regions demonstrated that attitudes toward Black people and politicians had a stronger relationship with attitudes toward the men rather than the women of the group. However, attitudes toward White people had a stronger relationship with attitudes toward White women than White men, whereas attitudes toward East Asian people, police officers, and criminals did not have a stronger relationship with attitudes toward either the men or women of each respective group. Regional agreement with traditional gender roles was explored as a potential moderator. These findings have implications for understanding the unique forms of prejudice women face around the world.
- MeSH
- White People MeSH
- Black People MeSH
- Adult MeSH
- Humans MeSH
- Attitude * MeSH
- Prejudice * MeSH
- Sex Factors MeSH
- Stereotyping MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND OBJECTIVES: N-acetyl-l-leucine (NALL) has been established to improve the neurologic manifestations of Niemann-Pick disease type C (NPC) after 12 weeks in a placebo-controlled trial. In the open-label extension phase (EP) follow-up, data were obtained after 12 and 18 months to evaluate the long-term effects of NALL for NPC. METHODS: This is an ongoing, multinational, multicenter EP. Patients with a genetic diagnosis of NPC aged 4 years or older who completed the placebo-controlled trial were eligible to continue in the EP and receive orally administered NALL 2-3 times per day in 3 tiers of weight-based dosing. The primary end point is the modified 5-domain NPC Clinical Severity Scale (NPC-CSS) (range 0-25 points; lower score representing better neurologic status); data from the EP cohort are compared with the expected annual trajectory of decline (i.e., disease progression) established in natural history studies. Analyses are also performed on exploratory end points, including the 15-domain and 4-domain NPC-CSSs and the Scale for Assessment and Rating of Ataxia (SARA). RESULTS: Fifty-three patients aged 5-67 years (45.3% female, 54.7% male) were enrolled in the EP. After 12 months, the mean (±SD) change from baseline on the 5-domain NPC-CSS was -0.27 (±2.42) with NALL vs +1.5 (±3.16) in the historical cohort (95% CI -3.05 to -0.48; p = 0.009), corresponding to a 118% reduction in annual disease progression. After 18 months, the mean (±SD) change was +0.05 (±2.95) with NALL vs +2.25 (±4.74) in the historical cohort (95% CI -4.06 to -0.35; p = 0.023). The 15-domain and 4-domain NPC-CSSs were consistent with the 5-domain NPC-CSS. The improvements in neurologic manifestations demonstrated in the placebo-controlled trial on the primary SARA end point were sustained over the long-term follow-up. NALL was well tolerated, and no treatment-related adverse events or serious reactions occurred. DISCUSSION: Treatment with NALL was associated with a significant reduction in NPC disease progression after 12 and 18 months, demonstrating a disease-modifying, neuroprotective effect. TRIAL REGISTRATION INFORMATION: The trial is registered with ClinicalTrials.gov (NCT05163288; registered December 6, 2021), EudraCT (2021-005356-10). The first patient was enrolled into the EP on March 8, 2023. The trial was funded by IntraBio Inc. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that NALL reduces disease progression in NPC.
- MeSH
- Child MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Leucine * analogs & derivatives therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Neuroprotective Agents * therapeutic use MeSH
- Niemann-Pick Disease, Type C * drug therapy MeSH
- Child, Preschool MeSH
- Disease Progression MeSH
- Severity of Illness Index MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
In this study, simple oil-in-water emulsions (O/W) and multiple O/W/O emulsions were employed as carriers for a curcumin delivery system. The stability of emulsions was evaluated using DSC (differential scanning calorimetry), accompanied by particle size measurement by DLS (dynamic light scattering) and rheological analysis. The amount of freezable water (Wfs) in O/W emulsion was determined to be 80.4%, while that in O/W/O emulsion was 23.7%. Multiple emulsions had a more complex structure than simple emulsions, being characterized by higher stability with predominant loss modulus over storage modulus (G" > G'). The mean surface diameter for O/W emulsion was 198.7 ± 9.8 nm, being approximately two times lower than that for multiple emulsions. Curcumin in vitro digestibility was observed for both emulsions and, additionally, the digestibility of fresh and dried curcuma root powders was investigated. Multiple emulsions were found to be a superior matrix for curcumin delivery, with higher stability and emulsion digestibility of 50.6% for the stomach and small intestine. In vitro digestion of dried curcuma powders and curcuma root samples was monitored by HPLC (high-performance liquid chromatography). The DMD (dry matter digestibility) for dried curcuma powders ranged between 52.9% to 78.8%, and for fresh curcuma (KF) was 95.5%.
