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1.
Int Nurs Rev ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953437

ABSTRACT

AIMS: To investigate how nursing students' professional identity, clinical learning environment, financial incentives, and career opportunities influence their intention to migrate. BACKGROUND: There is a preponderance of studies about nurse migration and its impact on the global nursing workforce. However, a critical gap remains about nursing students' intentions to migrate, particularly among developing countries like the Philippines. METHODS: Using a cross-sectional design, third- and fourth-year nursing students (n = 316) from the largest comprehensive university in Manila were conveniently recruited. Data were collected from November to December 2023 using five validated self-report scales. Descriptive (e.g., mean, standard deviation) and inferential statistics (e.g., Spearman rho, covariance-based structural equation modeling) were used to analyze data. RESULTS: The emerging model demonstrated acceptable model fit indices. Nursing students' professional identity (ß = 0.18, p = 0.043) and financial incentives (ß = 0.10, p = 0.046) significantly and positively influence the intention to migrate. The satisfaction with future career opportunities (ß = -0.12, p = 0.038) and clinical learning environment perception (ß = -0.15, p = 0.048) negatively influence the intention to migrate. These four predictors accounted for 4.60% of the total variance of intention to migrate. CONCLUSION: Nursing students' professional identity and financial incentives directly impact intent to migrate, whereas future career opportunities satisfaction and clinical learning environment inversely affect intent to migrate. IMPLICATIONS FOR NURSING PRACTICE AND POLICY: This study underscores the imperative for nursing colleges and faculty to promote positive professional identity and provide a conducive clinical learning environment to develop sustainable nurses' migration policies.

2.
Nat Commun ; 15(1): 5033, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866783

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to gradual motoneurons (MN) degeneration. Among the processes associated to ALS pathogenesis, there is the formation of cytoplasmic inclusions produced by aggregation of mutant proteins, among which the RNA binding protein FUS. Here we show that, in neuronal cells and in iPSC-derived MN expressing mutant FUS, such inclusions are significantly reduced in number and dissolve faster when the RNA m6A content is diminished. Interestingly, stress granules formed in ALS conditions showed a distinctive transcriptome with respect to control cells, which reverted to similar to control after m6A downregulation. Notably, cells expressing mutant FUS were characterized by higher m6A levels suggesting a possible link between m6A homeostasis and pathological aggregates. Finally, we show that FUS inclusions are reduced also in patient-derived fibroblasts treated with STM-2457, an inhibitor of METTL3 activity, paving the way for its possible use for counteracting aggregate formation in ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Induced Pluripotent Stem Cells , Motor Neurons , RNA-Binding Protein FUS , RNA-Binding Protein FUS/metabolism , RNA-Binding Protein FUS/genetics , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/pathology , Humans , Motor Neurons/metabolism , Motor Neurons/pathology , Induced Pluripotent Stem Cells/metabolism , Cytoplasmic Granules/metabolism , Fibroblasts/metabolism , Adenosine/metabolism , Adenosine/analogs & derivatives , Methyltransferases/metabolism , Methyltransferases/genetics , Mutation , Inclusion Bodies/metabolism , Stress Granules/metabolism , Transcriptome
5.
Genes (Basel) ; 15(5)2024 05 03.
Article in English | MEDLINE | ID: mdl-38790210

ABSTRACT

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples' reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit-harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems.


Subject(s)
Genetic Testing , Neonatal Screening , Prenatal Diagnosis , Humans , Genetic Testing/methods , Neonatal Screening/methods , Prenatal Diagnosis/methods , Female , Pregnancy , Infant, Newborn
6.
Reprod Biomed Online ; 49(1): 103857, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38643517

ABSTRACT

RESEARCH QUESTION: What are the main arguments of reproductive healthcare providers in favour or against their involvement in offering expanded carrier screening (ECS) for recessive disorders at fertility clinics in the Netherlands? DESIGN: Semi-structured interview study with 20 reproductive healthcare providers between May 2020 and January 2021. Participants included 11 gynaecologists, seven fertility doctors, one nurse practitioner and one clinical embryologist, recruited from academic medical centres (n = 13), peripheral facilities associated with academic centres (n = 4), and independent fertility treatment centres (n = 3) in the Netherlands. An interview guide was developed, and thematic content analysis was performed using ATLAS.ti software. RESULTS: Arguments of reproductive healthcare providers in favour of their potential involvement in offering ECS included: (i) opportunities offered by the setting; (ii) motivation to assist in reproduction and prevent suffering; and (iii) to counter unwanted commercialization offers. Arguments against involvement included: (i) lack of knowledge and familiarity with offering ECS; (ii) insufficient staff and resources, and potential high costs for clinics and/or couples; (iii) the emotional impact it may have on couples; (iv) perceived complexity of counselling and expected elongation of waiting lists; and (v) expected low impact on reducing the burden of diseases. Participants felt that more evidence and research on the costs-benefits, implications and demand are needed prior to their involvement. CONCLUSION: While agreeing that the field of medically assisted reproduction provides a unique opportunity to offer ECS, reproductive healthcare workers feel a lack of capability and limited motivation to offer ECS to all or a selection of couples at their fertility clinics.


Subject(s)
Attitude of Health Personnel , Fertility Clinics , Genetic Carrier Screening , Qualitative Research , Humans , Female , Genetic Carrier Screening/methods , Male , Health Personnel/psychology , Netherlands , Adult , Genetic Counseling/psychology
7.
Genes (Basel) ; 15(4)2024 04 20.
Article in English | MEDLINE | ID: mdl-38674451

ABSTRACT

Background: Previous studies have suggested that information offered by sellers of health-related direct-to-consumer genetic tests (DTC-GTs) is often incomplete, unbalanced, or too difficult to understand. The extent to which this is the case for sellers accessible to Dutch consumers has not previously been studied. Methods and Goals: The present study aimed to assess the completeness, balance, readability, and findability of informational content on a selection of websites from several health-related DTC-GT sellers accessible to Dutch consumers. An in-depth content analysis was performed based on a recently published checklist outlining key items for policy guidance regarding DTC-GT services. Results: The information provided by sellers did not equally cover all aspects relevant to health-related DTC-GT service provision. The provided information was slightly unbalanced, with benefits of health-related DTC-GT usage being overemphasized compared to its risks and limitations. The readability of the provided information was low, on average requiring college education for proper understanding. A findability analysis showed that information concerning all themes is overall relatively evenly distributed across analyzed sellers' websites. Conclusions: Information provision by assessed health-related DTC-GT sellers is suboptimal regarding completeness, balance, and readability. To better empower potential consumers to make an informed decision regarding health-related DTC-GT usage, we advocate industry-wide enhancement of information provision.


Subject(s)
Direct-To-Consumer Screening and Testing , Genetic Testing , Internet , Humans , Genetic Testing/methods , Netherlands , Consumer Health Information , Comprehension
8.
Eur J Pharm Biopharm ; 199: 114303, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657740

ABSTRACT

Dissolvable microneedles (DMNs), fabricated from biocompatible materials that dissolve in both water and skin have gained popularity in dermatology. However, limited research exists on their application in compromised skin conditions. This study compares the hyaluronic acid-based DMNs penetration, formation of microchannels, dissolution, and diffusion kinetics in intact, barrier-disrupted (tape stripped), and dry (acetone-treated) porcine ear skin ex vivo. After DMNs application, comprehensive investigations including dermoscopy, stereomicroscope, skin hydration, transepidermal water loss (TEWL), optical coherence tomography (OCT), reflectance confocal laser scanning microscopy (RCLSM), confocal Raman micro-spectroscopy (CRM), two-photon tomography combined with fluorescence lifetime imaging (TPT-FLIM), histology, and scanning electron microscopy (SEM) were conducted. The 400 µm long DMNs successfully penetrated the skin to depths of ≈200 µm for dry skin and ≈200-290 µm for barrier-disrupted skin. Although DMNs fully inserted into all skin conditions, their dissolution rates were high in barrier-disrupted and low in dry skin, as observed through stereomicroscopy and TPT-FLIM. The dissolved polymer exhibited a more significant expansion in barrier-disrupted skin compared to intact skin, with the smallest increase observed in dry skin. Elevated TEWL and reduced skin hydration levels were evident in barrier-disrupted and dry skins compared to intact skin. OCT and RCLSM revealed noticeable skin indentation and pronounced microchannel areas, particularly in barrier-disrupted and dry skin. Additional confirmation of DMN effects on the skin and substance dissolution was obtained through histology, SEM, and CRM techniques. This study highlights the impact of skin condition on DMN effectiveness, emphasizing the importance of considering dissolvability and dissolution rates of needle materials, primarily composed of hyaluronic acid, for optimizing DMN-based drug delivery.


Subject(s)
Administration, Cutaneous , Hyaluronic Acid , Needles , Skin Absorption , Skin , Solubility , Animals , Swine , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Skin Absorption/physiology , Hyaluronic Acid/chemistry , Hyaluronic Acid/administration & dosage , Drug Delivery Systems/methods , Tomography, Optical Coherence/methods , Microinjections/methods , Water Loss, Insensible/drug effects , Water Loss, Insensible/physiology , Biocompatible Materials/administration & dosage , Biocompatible Materials/chemistry
9.
Article in English | MEDLINE | ID: mdl-38683451

ABSTRACT

The use of lipases from animal sources for the synthesis of new biocatalysts is barely studied in the literature. The present work focused on the immobilization of lipases from kid goat's and lamb's epiglottis in different ionic supports. For this, anionic supports (monoaminoethyl-N-aminoethyl-agarose (MANAE) and diethylaminoethyl-agarose (DEAE)) and cationic supports (carboxymethyl-agarose and sulfopropyl-agarose) were used. The immobilization parameters were evaluated, as well as the thermal stability of the immobilized enzymes and their stability at different values of pH. Then, the performance of the biocatalysts was evaluated in hydrolysis reactions for obtaining omega-3 fatty acids from fish oil (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Values of 100% of recovered activity were obtained for lipase from goats, indicating that it was possible to maintain all the enzymatic activities of the immobilized enzymes on the supports. The immobilized enzymes were more stable in different pH conditions and at a temperature of 50 °C, reaching values of stabilization factor of 12.17 and t1/2 of 9.86 h-1, for lamb lipase immobilized in sulfopropyl agarose. In general, the anionic supports led to lower Km values and the cationic ones to a higher Vmax. Lamb lipase showed the highest selectivity values for EPA/DHA, reaching values of 6.43 using MANAE. Thus, the high potential for using such biocatalysts from animal sources in the food or pharmaceutical industries is observed.

10.
BMC Infect Dis ; 24(1): 320, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38491352

ABSTRACT

BACKGROUND: Multidrug resistance in Staphylococcus aureus continues to influence treatment complications in clinical settings globally. Multidrug-resistant-S. aureus (MDR-SA) is often genetically driven by resistance markers transferable in pathogenic strains. This study aimed to determine the distribution of resistance markers in clinical isolates of S. aureus in Nsukka, Nigeria. METHODS: A total of 154 clinical samples were cultured on mannitol salt agar. Isolates were characterized using conventional cultural techniques and confirmed by PCR detection of S. aureus-specific nuc gene. Antibiotic resistance profiles of the isolates were determined against selected antibiotics using the disk-diffusion method, while screening for antibiotic resistance genes (Mec A, Erm A, Erm B, Erm C, Van A, and Van B) was by PCR. RESULTS: A total of 98 isolates were identified as S. aureus by conventional methods. Of these, 70 (71.43%) were confirmed by PCR. Phenotypically, the isolates exhibited high degrees of resistance to oxacillin (95.72%), erythromycin (81.63%), and ertapenem (78.57%) and 75.51% and 47.30% against methicillin and vancomycin, respectively. Multiple antibiotic resistance indexes of the isolates ranged from 0.3 to 1, and the most prevalent pattern of resistance was oxacillin-ertapenem-vancomycin-erythromycin-azithromycin-clarithromycin-ciprofloxacin- cefoxitin-amoxicillin-clavulanic acid. PCR screening confirmed the existence of various antibiotic resistance makers among the strains, with the most common resistance genes found in the isolates being Mec A (32.14%), Van A (21.43%), Van B (10.71%), Erm B (10.71%), and Erm C (17.86%). None possessed the Erm A gene. CONCLUSION: The study supports the need for necessary action, including rational drug use, continuous surveillance, and deployment of adequate preventive and curative policies and actions.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Vancomycin , Ertapenem , Nigeria , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Staphylococcal Infections/epidemiology , Oxacillin , Erythromycin
12.
Eur J Pharm Biopharm ; 197: 114211, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38340877

ABSTRACT

The concentration of air pollution is gradually increasing every year so that daily skin exposure is unavoidable. Dietary supplements and topical formulations currently represent the protective strategies to guard against the effects of air pollution on the body and the skin. Unfortunately, there are not yet enough methods available to measure the effectiveness of anti-pollution products on skin. Here, we present two ex vivo methods for measuring the protective effect against air pollution of different cream formulations on the skin: Electron paramagnetic resonance (EPR) spectroscopy and autofluorescence excited by 785 nm using a confocal Raman microspectrometer (CRM). Smoke from one cigarette was used as a model pollutant. EPR spectroscopy enables the direct measurement of free radicals in excised porcine skin after smoke exposure. The autofluorescence in the skin was measured ex vivo, which is an indicator of oxidative stress. Two antioxidants and a chelating agent in a base formulation and a commercial product containing an antioxidant mixture were investigated. The ex vivo studies show that the antioxidant epigallocatechin-3-gallate (EGCG) in the base cream formulation provided the best protection against oxidative stress from smoke exposure for both methods.


Subject(s)
Antioxidants , Skin , Animals , Swine , Antioxidants/chemistry , Electron Spin Resonance Spectroscopy/methods , Skin/metabolism , Oxidative Stress , Free Radicals/chemistry
13.
J Cardiovasc Comput Tomogr ; 18(2): 203-210, 2024.
Article in English | MEDLINE | ID: mdl-38320905

ABSTRACT

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.


Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Calcium , Predictive Value of Tests , Chest Pain , Necrosis , Coronary Angiography/methods
14.
Sci Rep ; 14(1): 3488, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38347037

ABSTRACT

Melanin, the most abundant skin chromophore, is produced by melanocytes and is one of the key components responsible for mediating the skin's response to ultraviolet radiation (UVR). Because of its antioxidant, radical scavenging, and broadband UV absorbing properties, melanin reduces the penetration of UVR into the nuclei of keratinocytes. Despite its long-established photoprotective role, there is evidence that melanin may also induce oxidative DNA damage in keratinocytes after UV exposure and therefore be involved in the development of melanoma. The present work aimed at evaluating the dependence of UV-induced DNA damage on melanin content and distribution, using reconstructed human epidermis (RHE) models. Tanned and light RHE were irradiated with a 233 nm UV-C LED source at 60 mJ/cm2 and a UV lamp at 3 mJ/cm2. Higher UV-mediated free radicals and DNA damage were detected in tanned RHE with significantly higher melanin content than in light RHE. The melanin distribution in the individual models can explain the lack of photoprotection. Fluorescence lifetime-based analysis and Fontana-Masson staining revealed a non-homogeneous distribution and absence of perinuclear melanin in the tanned RHE compared to the in vivo situation in humans. Extracellularly dispersed epidermal melanin interferes with photoprotection of the keratinocytes.


Subject(s)
Melanins , Ultraviolet Rays , Humans , Ultraviolet Rays/adverse effects , Epidermis , Skin , Melanocytes
15.
Invest Ophthalmol Vis Sci ; 65(2): 27, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38349785

ABSTRACT

Purpose: Epigenetic alterations in uveal melanoma (UM) are still neither well characterized, nor understood. In this pilot study, we sought to provide a deeper insight into the possible role of epigenetic alterations in the pathogenesis of UM and their potential prognostic relevance. To this aim, we comprehensively profiled histone post-translational modifications (PTMs), which represent epigenetic features regulating chromatin accessibility and gene transcription, in UM formalin-fixed paraffin-embedded (FFPE) tissues, control tissues, UM cell lines, and healthy melanocytes. Methods: FFPE tissues of UM (n = 24), normal choroid (n = 4), human UM cell lines (n = 7), skin melanocytes (n = 6), and uveal melanocytes (n = 2) were analyzed through a quantitative liquid chromatography-mass spectrometry (LC-MS) approach. Results: Hierarchical clustering showed a clear separation with several histone PTMs that changed significantly in a tumor compared to normal samples, in both tissues and cell lines. In addition, several acetylations and H4K20me1 showed lower levels in BAP1 mutant tumors. Some of these changes were also observed when we compared GNA11 mutant tumors with GNAQ tumors. The epigenetic profiling of cell lines revealed that the UM cell lines MP65 and UPMM1 have a histone PTM pattern closer to the primary tissues than the other cell lines analyzed. Conclusions: Our results suggest the existence of different histone PTM patterns that may be important for diagnosis and prognosis in UM. However, further analyses are needed to confirm these findings in a larger cohort. The epigenetic characterization of a panel of UM cell lines suggested which cellular models are more suitable for epigenetic investigations.


Subject(s)
Melanoma , Uveal Neoplasms , Humans , Histones , Pilot Projects , Melanoma/metabolism , Melanocytes/metabolism , Uveal Neoplasms/pathology , Cell Line , Mass Spectrometry
16.
Exp Dermatol ; 33(1): e15002, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38284193

ABSTRACT

Excessive exposure to ultraviolet (UV) light leads to acute and chronic UV damage and is the main risk factor for the development of skin cancer. In most countries with western lifestyle, the topical application of sunscreens on UV-exposed skin areas is by far the most frequently used preventive measure against sunburn. Further than preventing sunburns, increasing numbers of consumers are appreciating sunscreens with a medium- to high-level sun protective factor (SPF) as basis for sustainable-skin ageing or skin cancer prevention programs. However, recent investigations indicate that clinically significant DNA damages as well as a lasting impairment of cutaneous immunosurveillance already occur far below the standard of one minimal erythema dose (MED) sunburn level, which contributes to the current discussion of the clinical value of high-protective SPF values. Ex vivo investigations on human skin showed that the application of SPF30 reduces DNA damage for a day long sun exposure (24 MED) drastically by about 53% but is significantly surpassed by SPF100 reducing DNA damage by approx. 73%. Further analysis on different SPF protection levels in UV-exposed cell culture assays focusing on IL-18, cell vitality and cis/trans-urocanic acid support these findings. Whereas SPF30 and SPF50+ sunscreens already offer a solid UVB cover for most indications, our results indicate that SPF100 provides significant additional protection against mutagenic (non-apoptotic-) DNA damage and functional impairment of the cutaneous immunosurveillance and therefore qualifies as an optimized sunscreen for specifically vulnerable patient groups such as immunosuppressed patients, or skin cancer patients.


Subject(s)
Skin Neoplasms , Sunburn , Humans , Sunburn/prevention & control , Sunburn/etiology , Sunscreening Agents/therapeutic use , Skin , Ultraviolet Rays/adverse effects , Skin Neoplasms/prevention & control , Skin Neoplasms/drug therapy
17.
Genet Med ; 26(4): 101071, 2024 04.
Article in English | MEDLINE | ID: mdl-38224026

ABSTRACT

PURPOSE: Rare genetic neurodevelopmental disorders associated with intellectual disability require lifelong multidisciplinary care. Clinical practice guidelines may support healthcare professionals in their daily practice, but guideline development for rare conditions can be challenging. In this systematic review, the characteristics and methodological quality of internationally published recommendations for this population are described to provide an overview of current guidelines and inform future efforts of European Reference Network ITHACA (Intellectual disability, TeleHealth, Autism, and Congenital Anomalies). METHODS: MEDLINE, Embase, and Orphanet were systematically searched to identify guidelines for conditions classified as "rare genetic intellectual disability" (ORPHA:183757). Methodological quality was assessed using the Appraisal of Guidelines, Research, and Evaluation II tool. RESULTS: Seventy internationally published guidelines, addressing the diagnosis and/or management of 28 conditions, were included. The methodological rigor of development was highly variable with limited reporting of literature searches and consensus methods. Stakeholder involvement and editorial independence varied as well. Implementation was rarely addressed. CONCLUSION: Comprehensive, high-quality guidelines are lacking for many rare genetic neurodevelopmental disorders. Use and transparent reporting of sound development methodologies, active involvement of affected individuals and families, robust conflict of interest procedures, and attention to implementation are vital for enhancing the impact of clinical practice recommendations.


Subject(s)
Intellectual Disability , Neurodevelopmental Disorders , Humans , Quality Improvement , Evidence-Based Medicine , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/therapy , Consensus
18.
Lab Invest ; 104(1): 100281, 2024 01.
Article in English | MEDLINE | ID: mdl-37924948

ABSTRACT

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.


Subject(s)
Melanoma , Melanosis , Skin Neoplasms , Humans , Melanoma/diagnosis , Melanoma/pathology , Prognosis , Reproducibility of Results , Eosine Yellowish-(YS) , Hematoxylin , Melanocytes , Skin Neoplasms/pathology , Melanosis/pathology , World Health Organization , Multicenter Studies as Topic
19.
Genet Med ; 26(2): 101033, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38007624

ABSTRACT

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over time, decision supports to assist using pharmacogenetic results in future treatment decisions, and sharing information in public databases to improve the clinical interpretation of pharmacogenetic variants identified in other children. We conclude by presenting a series of points to consider for clinicians and policymakers regarding whether, and under what circumstances, routine screening and return of pharmacogenomic variants unrelated to the indications for testing is appropriate in children who are undergoing genome-wide sequencing to assist in the diagnosis of a suspected genetic disease.


Subject(s)
Pharmacogenetics , Pharmacogenomic Variants , Humans , Child , Genomics , Chromosome Mapping , Exome
20.
Sci Rep ; 13(1): 22391, 2023 12 16.
Article in English | MEDLINE | ID: mdl-38104221

ABSTRACT

The inactivation of multi resistant pathogens is an important clinical need. One approach is UV-C irradiation, which was previously not possible in vivo due to cytotoxicity. Recently, far UV-C irradiation at λ < 240 nm was successfully used on skin with negligible damage. A potential application site is the nasal vestibule, where MRSA accumulates and cannot be treated using antiseptics. We irradiated 3D mucosa models and excised human mucosa with 222 and 233 nm far UV-C in comparison to 254 nm and broadband UV-B. Eradication efficiency was evaluated by counting colony forming units; irritation potential was evaluated by hen's egg-chorioallantoic membrane assay and trans epithelial electrical resistance; cell viability was assessed by MTT. DNA damage and cell protective mechanisms were evaluated immunohistopathologically. On mucosa models, MRSA reduced by ≈ 5 log10 for 60 mJ/cm2 irradiation at 233 nm. A slightly increased cell viability was observed after 24 h. Lower doses showed lower irritation potential than the positive controls or commercial mouthwash, while 80 mJ/cm2 had strong irritation potential. DNA damage occurred only superficially and decreased after 24 h. On excised human mucosa, < 10% of keratinocytes were affected after 150 mJ/cm2 222 nm or 60 mJ/cm2 233 nm.


Subject(s)
Cross Infection , Mouth Mucosa , Humans , Animals , Female , Chickens , DNA Damage , Skin , Ultraviolet Rays
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