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Detection of mutagens in the urine of rats following topical application of hair dyes.

Mutagens were detected in the urine of rats following topical application of two commercial oxidative-type hair dye preparations. The test system used was induction of back mutation with the bacterial tester strain TA1538, a histidine-dependent mutant of Salmonella typhimurium. Various quantities of dye were applied to the shortened hair on the backs of the test animals. The dye was allowed to remain on the hair for 20 min after application and was then removed by shampooing and thorough rinsing. Maximal levels of mutagenic activity occurred with urine collected during first 24 h following dye application, and a dose--response was observed when increasing volumes of mutagenic urine were tested. Mutagens were detected in rat urine after intraperitoneal injection, and also after topical application of 4-nitro-o-phenylenediamine, one of the constituents of the hair-dye preparations.

Administration, Topical

Plasma concentrations of unconjugated and conjugated estrogens and gonadotrophins following application of various estrogen preparations after oophorectomy and in the menopause.

In 55 patients after oophorectomy and 20 women after natural menopause an oral estrogen replacement therapy was performed with estrone-sulfate, estradiol 17-valerate, estriol-succinate, a combination of micronized estradiol and estriol (Estrifam, Trisequens), and natural conjugated estrogens. In 4 patients a 3 mg estradiol per 5 g ointment substance was applied on the abdominal skin. The interindividual variations of estrogen increments during therapy were considerably high. Oral intake of 2 mg estriol-succinate daily was followed by a 500% increase of total (conjugated + unconjugated) estriol. Concentrations of unconjugated estrogens were not altered by this dosage. Following oral application of the other above mentioned preparations, prominent rises--especially of unconjugated estrogens in plasma--were noted. The concentration peaks occurred within 3--6 h after application. Unconjugated estradiol-17 beta in plasma was comparable with values of the follicular phase of a normal menstrual cycle, unconjugated estrone, however, was nonphysiologically high. Consequently, the E1/E2 ratio was greater than one whereas it is normally below one. 12 h after oral estrogen application, plasma estrogens dropped to almost initial values, so that a second medication seems to be necessary in order to guarantee an adequate supplementation over the course of the day. The hormone values determined in this study did not show significant differences between patients after a natural menopause and after oophorectomy. There was a positive correlation between rising estrogen levels and suppressed gonadotrophins during replacement therapy. The occurrence of climacteric symptoms did not exclusively depend on low estrogen and high gonadotrophin levels. Good tolerance of estrogen therapy with significantly elevated estrogen concentrations in plasma can be obtained transcutaneously in the form of estrogen ointments. Such therapy might simulate the physiological estrogen pattern even better than oral application does because of delayed and diluted steroid flow to the liver.

Castration

Applications of metal-organic frameworks in smart packaging for food freshness indication: a comprehensive review.

Smart packaging is extensively studied for its multifunctional capabilities in antimicrobial activity, preservation, and atmosphere modification. Recently emerged metal-organic frameworks (MOFs) freshness-indicating packaging becomes a key research direction in smart packaging owing to its distinctive functions and physicochemical properties. As multifunctional materials, the unique porous structure and tunable properties of MOFs provide a distinctive approach for developing food packaging applications dedicated to food freshness indication. Existing MOFs-based smart packaging still faces potential safety risks and technical challenges in practical applications, and there remains a lack of integrated discussion that combines synthesis strategies, packaging design, optimization, and safety assessment. This review elaborates on the application of MOFs in freshness-indicating smart packaging, focusing on diverse MOFs synthesis strategies, the formats of smart packaging, types of indicator signals, and qualitative/quantitative analytical methods. It also delves into the methodology concepts of MOFs-based smart packaging and evaluates MOFs safety in food packaging by addressing potential risks. Studies show that MOFs-based smart packaging achieves qualitative and semi-quantitative analysis of food freshness through multiple signal modalities such as visible color change, fluorescence, and photothermal effects. This review emphasizes that safe MOFs design is critically important and should comply with the overall migration limit of <10 mg/dm2 specified in Regulation (EC) No 1935/2004, lanthanide element limit of <0.05 mg/kg, and FDA threshold of 1.5 &#x3bc;g/person/day. Comprehensive safety assessment and intelligent sensing platforms will constitute pivotal directions for advancing MOFs-based smart packaging toward practical application.

Food Packaging

Clinical applications of digital twin technology in In Vitro Fertilisation.

BACKGROUND: Digital twin technology, originating from aerospace and manufacturing industries, has emerged as a transformative tool in healthcare. In vitro fertilisation (IVF) faces persistent challenges including suboptimal embryo selection, unpredictable treatment outcomes, and limited personalisation of protocols. Despite advances in assisted reproductive technology, existing literature exhibits fragmentation: artificial intelligence applications in embryo selection, ovarian stimulation, and endometrial assessment have been developed independently without systematic integration into comprehensive treatment frameworks. Digital twin technology offers unprecedented opportunities to create virtual replicas of biological systems, enabling real-time monitoring, predictive modelling, and personalised treatment strategies. AIM: This narrative review aims to critically examine the current applications of digital twin technology in IVF, evaluate its potential benefits and limitations, synthesize existing evidence into an integrative conceptual model, and identify future directions for implementation in reproductive medicine. METHOD: A comprehensive narrative review was conducted using PubMed, Scopus, Web of Science, and IEEE Xplore databases. A narrative review approach was selected over systematic review to accommodate the heterogeneity of evidence types in this emerging field, including theoretical frameworks, simulation studies, and proof-of-concept implementations that would be excluded from systematic reviews. Search terms included "digital twin," "IVF," "in vitro fertilisation," "assisted reproductive technology," "embryo selection," and "predictive modelling." Studies published between 2015 and 2025 were included, focusing on original research articles, systematic reviews, and proof-of-concept studies describing digital twin applications in reproductive medicine. RESULTS: Digital twin technology in IVF demonstrates significant potential across multiple domains including embryo development simulation, ovarian response prediction, endometrial receptivity modelling, and personalised stimulation protocols. Current applications integrate artificial intelligence, machine learning algorithms, time-lapse imaging, and omics data to create comprehensive virtual models. Early evidence suggests improvements in embryo selection accuracy, ovarian response prediction, and treatment protocol optimization, though large-scale randomized controlled trials remain limited. Implementation challenges include data integration complexity, computational requirements, regulatory considerations, and validation requirements. CONCLUSION: Digital twin technology represents a paradigm shift in IVF practice, offering personalised, predictive, and precision medicine approaches. This review synthesizes existing evidence to propose an integrative conceptual model for digital twin implementation across the IVF treatment spectrum, identifies critical knowledge gaps, and establishes research priorities to advance clinical translation. Despite current limitations, continued advancement promises improved success rates and patient outcomes.

Humans

Chromatography of biogenic amines. I. Generally applicable separation and detection methods.

This first part of the review on "Chromatography of Biogenic Amines" is devoted to the description of generally applicable separation and detection methods. Gas chromatographic and gas chromatographic-mass spectrometric methods, and applications of chromatographic methods to specific amines or groups of related amines and their metabolites, will be covered in Part II. Trends in the development of separation methods (paper and thin-layer chromatography, paper and thin-layer electrophoresis and ion-exchange methods) are described, using mostly aliphatic amines as examples as they do not exhibit features that permit their specific determination. Reagents suggested for the formation of coloured and fluorescent derivatives of amines are reviewed and their applications are described. Within the limitation of the reviewed and their applications are described. Within the limitation of the mostly inadequate information that is available, the relative usefulness of the different derivative-forming reactions are compared.

Biogenic Amines

[Standardisation of obtaining blood samples: influence of tourniquet application on 33 constituents of blood and serum (author's transl)].

The extent and dynamics of changes by short (1 min) or prolonged (6 min) tourniquet application while obtaining venous blood samples were analysed with respect ot 33 frequently measured constituents of blood and serum. After 6-minute tourniquet application the values for red cells, haemoglobin, packed cell volume, total protein, albumen, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, creatinekinase, bilirubin, cholesterol, total glycerol and calcium increased by an average of 4-9%. One-minute tourniquet application did not have a significant effect. Levels of sodium, potassium, carbon dioxide, creatinine, uric acid, ratio of electrophoretic fractions and the MCV, MCH and MCHC indices were not affected even by 6-minute tourniquet applications. The introduction of blood sampling under standardised conditions is proposed.

Adult

Comparison of male and female physician's associate program applicants.

Using personality measures, the author examined Physician's Associate Program applicants at the Duke University School of Medicine, comparing male and female applicants and the outcome for these applicants in terms of acceptance into paramedical training. The perecentage of women accepted into training was similar to the percentage who applied for training. However, women invited for interview were more aggressive, autonomous, impulsive, playful, and flexible than the males invited to interview, suggesting self-selection by women in applying for paramedical training. Women accepted for training were more "feminine" in the conventional sense, and bias against female applicants less accepting of social mores and the traditional female role was revealed. The implications of these findings are discussed.

Personality Inventory

Speed breeding: protocols, application and achievements.

One of the limiting factors in breeding and genetic research is the time required to develop pure lines. This is due, on the one hand, to the prolonged vegetative period of a single generation and, on the other hand, to the specifics of inbreeding, which typically requires 4-6 consecutive generations of self-pollination in plant material. Researchers have always sought approaches that enable the rapid development of homozygous plant lines. Consequently, methods such as greenhouse cultivation during the autumn-winter period, single-seed descent, shuttle breeding, embryo culture, and doubled haploid technology have been introduced into practice. All these methods have both advantages and limitations. One of the latest approaches facilitating a significant reduction in the vegetative period of plants is speed breeding (SB). This method is based on the application of factors that shorten the time from sowing to flowering, as well as techniques that accelerate the generative phase of development and overcome postharvest dormancy. This review provides a comprehensive list and characterization of all factors that influence the efficiency of speed breeding to varying degrees. Among the factors discussed that reduce the sowing-to-flowering period are photoperiod, light sources, spectral composition and light intensity, temperature, carbon dioxide levels, vernalization, mineral nutrition, substrate volume, mechanical shoot removal, and the use of plant growth regulators. To shorten the generative phase, the review summarizes the application of embryo culture and forced desiccation of immature seeds, along with methods to overcome postharvest dormancy. Additionally, applications of genetic approaches and genetic engineering for shortening generation time in speed breeding are described. The review also consolidates detailed protocols for approximately thirty crops. The high efficiency of speed breeding in reducing both the vegetative period per generation and the time required to develop pure lines has led to its increasing adoption in various research fields. This review highlights the application of speed breeding for hybridization and pure line development, introgression of target alleles, and genomic selection. A list of phenotypic traits exhibiting high correlation between controlled-environment and field conditions is provided.

accelerated flowering

[Acute and subchronic toxicity of 8-hydroxyquinolone derivatives in combined application].

The toxicity of combined application of broxychinoline and broxaldin (5:1) was investigated in experiments on white mice and white rats. The presence of higher species specific sensitivity was observed in white mice. LD50 was determined by intraperitoneal application of 0.125 (0.085 + 0.182)/kg body weight on white mice: 0.213 (0.167 + 0.270)/kg body weight on white rats, and by subcutaneous application of more than 1.0/kg body weight on white mice. After a 30-day peroral application of the named combination on white rats at a daily dose of 0.1 kg body weight/24 h no disturbances in the physical state and in the microstructure of the inner organs were scored. The use of a dose of 0.24 kg/kg t/24 h resulted in necrobiotic changes in the kidneys. A trend toward shortening the time of blood clotting and of reducing the relative weight of the kidneys, spleen, lungs and heart is established.

Animals

An analysis of the decline in dental school applicants, 1975-1978.

There has been a significant reduction over the past three years in the number of applicants to dental school. This paper, which is based on an analysis of over 30 variables contained in the American Association of Dental Schools Application Service data bases for the 1975, 1976, 1977, and 1978 entering class years, indicates that only four of these variables are related to the decline in applicants: (1) region of parents' residence, (2) grade point average, (3) college major, and (4) parents' socio-economic status. The decline in applicants from the socio-economic lower middle class documented here once again raises the possibility that access to dental education is being denied to the economically disadvantaged.

Aptitude Tests

The application of artificial intelligence in healthcare practice: A mapping review of systematic reviews.

Artificial intelligence (AI) is rapidly transforming healthcare practice, with growing evidence supporting its use in diagnosis, prognosis, treatment planning, and operational decision-making. The proliferation of systematic reviews in recent years underscores the need for an updated synthesis of the literature to inform research, policy, and practice. We searched PubMed, Web of Science, Scopus, IEEE Xplore, and CINAHL for systematic reviews and meta-analyses published between 2019 and February 2026. Eligible reviews focused on AI applications in healthcare practice, were peer-reviewed, and written in English. A total of 368 reviews met the inclusion criteria. Publication volume increased steadily, peaking in 2025. AI research was concentrated in high-density domains, such as radiology, oncology, and critical care. Across reviews, diagnostic imaging, electronic health record (EHR) data, and biomarkers/laboratory results accounted for 68% of training data sources, though newer data types, such as wearable device and sensor data, emerged from 2022 onward. Diagnosis, prognosis, and treatment comprised over 80% of AI applications, with novel uses emerging in recent years, such as AI-assisted clinical documentation (e.g., ambient documentation tools) and patient education. Ethical concerns were reported in 78.5% of reviews, with privacy, model accuracy, data and algorithmic bias, and explainability as recurrent themes. The proportion of reviews reporting ethical concerns increased from 2021 to 2025. AI applications in healthcare are expanding in scope, diversifying in data sources, and evolving toward novel clinical and operational uses. The human-centered AI or augmented intelligence paradigm, integrating computational precision with clinical expertise, holds significant promise but will require parallel advances in governance, regulatory frameworks, and ethical oversight to ensure safe adoption.

Artificial Intelligence

A new application tool for the ROCHE pH electrode.

Using this tool the application of the pH electrode is nearly as easy as the attachment of a common ECG-scalp-electrode [3]. Visual control and lithotomy position is not necessary any more. The different tools are adapted to each other so that incision place and the tip of the pH electrode are automatically centered perpendicularly. The first results by using this tool promise to be successful. Time of application is short, the maintenance of the pH electrode is good and the application for the patient no longer disagreeable.

Electrodes

A physiologic model of the dehydroepiandrosterone to estrogen conversion system in the fetoplacental unit. II. Preliminary clinical application--the dehydroepiandrosterone loading test.

A dehydroepiandrosterone (DHEA) loading test (DLT) is described. The results of 19 DHEA loading tests in as many third-trimester obstetric patients are presented. Analysis involves inspection of the raw data and the application of the physiologic model of the DHEA to estrogen conversion system described in the preceding paper (Part I). The DLT results show that within the population studied, the conversion rate of DHEA to estrogens is lower in patients with placental insufficiency than in normal patients (N = 5, p = 0.002) or in patients with various complications of pregnancy who deliver normally grown, undistressed infants (N = 6, p = 0.001). Routine clinical application must await more extensive evaluation to preclude the existence of forms of placental insufficiency not detected by this means, or normal states resulting in "false-positive" tests. These initial clinical results are intended primarily to demonstrate the potential clinical applicability of the physiologic model described in Part I.

Dehydroepiandrosterone

Effects of the unilateral nigral application of dopaminergic drugs on the in vivo release of dopamine in the two caudate nuclei of the cat.

The effects of the unilateral application of d-amphetamine, benztropine, haloperidol and thioproperazine to one substantia nigra on the release of 3H-dopamine (3H-DA) in the two caudate nuclei were examined in halothane-anesthetized cats. For this purpose animals were implanted with push-pull cannulae and 3H-DA was estimated in superfusates during the continuous delivery of L-3,5-3H-tyrosine. The nigral application of d-amphetamine (10-6 M) or benztropine (10-6 M) reduced the release of 3-H-DA in in the ipsilateral caudate nucleus and induced an opposite effect in the contralateral side. In contrast, the nigral application of haloperidol (10-6 M) or thioproperazine (10-6 M) slightly increased the release of 3H-DA in the ipsilateral caudate nucleus and induced a reduction of 3H-transmitter release in the contralateral side. These results emphasize the role of the dendritic release of DA in the control of the activity of dopaminergic neurons and confirm our previous findings concerning the existence of a reciprocal control in the activity of the two dopaminergic pathways.

Animals

Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata.

The effect of various catecholamines and alpha-mimetics, given by microinjection in the A2-region of the nucleus tractus solitarii (NTS), on blood pressure was investigated in anesthetized male rats. A dose-dependent decrease of blood pressure and heart rate was induced by adrenaline as the most effective drug, followed by noradrenaline, dopamine, alpha-methylnoradrenaline and octopamine. Ablation of the rostral or caudal part of the NTS, or removal of the area postrema did not diminish the effect of alpha-methylnoradrenaline. Higher doses of noradrenaline and alpha-methylnoradrenaline caused an initial rise of blood pressure, while the blood pressure lowering effect of noradrenaline was diminished, and that of alpha-methylnoradrenaline and dopamine delayed. Isoprenaline and the (+)-stereoisomers of noradrenaline and alpha-methylnoradrenaline were ineffective. The hypotensive effect of dopamine was not prevented by systemic injection of the dopamine beta-hydroxylase inhibitor FLA 63. Prior application of haloperidol, yohimbine and phentolamine antagonized the hypotensive response to dopamine and alpha-methylnoradrenaline. Application of peripherally effective alpha-mimetics into the A2-region had no or little effect, while high doses increased blood pressure. Tyramine and clonidine caused some decrease of blood pressure. Clonidine also decreased blood pressure when it was applied in the area of the locus coeruleus. Application of isoprenaline in the locus coeruleus also decreased blood pressure while in contrast adrenaline, noradrenaline, dopamine and alpha-methylnoradrenaline increased blood pressure. The present data suggest that the catecholaminergic receptors in the A2-region of the NTS differ from the classic vascular alpha-receptor and that the NTS also may contain structures which can antagonize the decrease in blood pressure.

Animals

Memantine and its analogs: Potential applications in cancer therapy.

Drug repurposing refers to the process of using an existing drug or drug candidate for a new treatment or medical condition for which it was not indicated before. The process of "drug repurposing" usually involves an FDA-approved entity which has undergone clinical development and have a with well-established safety and toxicity profile in patients. Several convergent studies show that repurposed drugs may present a promising strategy for the management and therapy of several human cancers. Memantine is used to combat dementia in moderate-to-severe Alzheimer's disease (AD) patients. Several convergent studies show that memantine (and its analogs) may have applications in multiple disease conditions associated with human cancers. Memantine and its related compounds have shown promise as neuroprotective agents, anti-fatigue agents and pain-relieving agents to alleviate the toxic side effects of radiation therapy and chemotherapy. Recent publications have revealed that memantine displays anti-cancer activity by exerting direct growth-suppressive activity on the primary tumor as modulating the genomic/cellular landscape of the tumor microenvironment. Currently, clinical trials are in progress, which aim to evaluate the potential applications of memantine in cancer treatment. The adamantane scaffold in memantine has proved to be a versatile tool for the discovery of synthetic memantine analogs with robust anti-cancer activity. The discovery of second-generation memantine analogs may have wider applications in combating cancer recurrence and addressing clinical challenges in the treatment of drug-resistant and metastatic cancers.

Humans

Biotic and abiotic degradation of PHAs: mechanisms, environments, and potential applications of degradation products.

This review seeks to compile Polyhydroxyalkanoates (PHAs) degradation studies published over the past 20&#xa0;years. It highlights the effect of physical properties, such as crystallinity and molecular weight, on the decomposition rate of these molecules. Both biotic processes, mediated by bacteria, fungi, and enzymes, as well as abiotic processes, such as hydrolysis and thermal degradation, are analyzed. A repertoire of diverse microorganisms, including their metabolic pathways and enzymes for PHA breakdown, is presented. Furthermore, this review presents the decomposition of PHAs in various environments, such as soil and seawater, highlighting their potential as a sustainable alternative. Finally, the resulting degradation products are described, emphasizing their potential applications in medicine and industry. Although degradation of PHAs has been extensively studied through these years, several knowledge gaps remain undisclosed, including the degradation of diverse polyester monomers. PHAs comprise numerous monomer compositions with variable properties, which present opportunities for different applications but pose a challenge in their degradation. The reader of this review can extract useful information for both the production of PHAs and their potential applications.

Biodegradation

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics