Presence of 2-hydroxyethyl methacrylate (HEMA) and other (meth)acrylates in nail cosmetics, and compliance with EU legislation: An online market survey.

BACKGROUND: During the last 15-20 years, allergic contact dermatitis from acrylates-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been increasingly reported. 2-Hydroxyethyl methacrylate (HEMA) is considered to be the major allergenic culprit; few data on its presence in nail cosmetics are available. OBJECTIVES: To investigate (1) the frequency in which HEMA and di-HEMA trimethylhexyl dicarbamate are present in nail cosmetics; (2) whether nail cosmetics comply with EU regulations; (3) which other (meth)acrylates are present in nail cosmetics and how often. METHODS: One-line market survey. RESULTS: HEMA was present in nearly 60% of 394 cosmetic nail products and di-HEMA trimethylhexyl dicarbamate in 34%. Mandatory warnings on the packages of products containing HEMA were absent in 35% ('For professional use only') resp. 55% ('Can cause an allergic reaction'). Forty-five other (meth)acrylates were identified, of which the most frequent were hydroxypropyl methacrylate (25%), isobornyl methacrylate (16%) and trimethylolpropane triacrylate (12%). Some ingredient lists mentioned non-INCI names or non-specific names. CONCLUSIONS: HEMA was by far the most common ingredient of nail cosmetics, being present in nearly 60% of the products. Violations of EU legislation occurred in >30% (mandatory warnings missing) resp. 10% (mislabelling) of nail cosmetics.

Acrylates in artificial nails-Results of product analyses and glove penetration studies.

BACKGROUND: Artificial nail materials are mixtures that are prone to contain several sensitizing (meth)acrylates. It is not known whether the listing of (meth)acrylates is correct in these products' packages. Protective gloves suited for nail work are needed. OBJECTIVES: To analyse (meth)acrylates in gel nail and acrylic nail products chemically and to compare the results with the information in the product labels, and to study penetration of artificial nail materials through selected disposable gloves. METHODS: We analysed 31 gel nail products and 6 acrylic nail products for their (meth)acrylate content by gas chromatography-mass spectrometry (GC-MS). We tested the penetration of two nail products through three disposable gloves: nitrile rubber, neoprene rubber and polyvinyl chloride (PVC). RESULTS: Altogether 32/37 products contained (meth)acrylates. In all of them, there was discrepancy between the listed (meth)acrylates and those discovered in the analysis. The commonest (meth)acrylates were hydroxyethyl methacrylate (HEMA, 20/37 samples) and hydroxypropyl methacrylate (HPMA, 9/37 samples), but many of the product packages failed to declare them. Isobornyl acrylate (IBA) was discovered in nine gel nail products. The neoprene glove could withstand nail gel for 20 min and thin nitrile glove and PVC glove for 5 min. Acrylic nail liquid penetrated through disposable gloves quickly. CONCLUSIONS: Labelling of artificial nail products was notably incorrect on most products. Requirements for product labelling must be updated so that the risk of sensitization associated with artificial nail products is clearly indicated. Disposable gloves can probably be used short-term in gel nail work, whereas disposable gloves do not protect the user from acrylic nail liquids.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis. Part 2. Cross- and co-sensitization, other skin reactions to HEMA, position of HEMA among (meth)acrylates, sensitivity as screening agent, presence of HEMA in commercial products and practical information on patch test procedures.

This is the second part of a literature review of the clinical aspects of contact allergy to and allergic contact dermatitis from 2-hydroxyethyl methacrylate (HEMA). Topics include cross- and co-sensitization, atypical manifestations of contact allergy, frequency of positive patch tests to HEMA compared with other (meth)acrylates, sensitivity of HEMA as a screening agent, the presence of HEMA in commercial products, and practical information on patch testing procedures. Primary sensitization to methacrylates including HEMA may result in methacrylate and acrylate cross-sensitization. There is a strong cross-allergy between HEMA, ethylene glycol dimethacrylate (EGDMA), and hydroxypropyl methacrylate; many reactions to EGDMA are cross-reactions to primary HEMA sensitization. Rare atypical manifestations of HEMA-allergy include lichen planus, lymphomatoid papulosis, systemic contact dermatitis, leukoderma after positive patch tests, and systemic side effects such as nausea, diarrhoea, malaise, and palpitations. The occurrence of respiratory disease caused by methacrylates such as asthma is not infrequent. HEMA is the most frequently patch test-positive methacrylate. It is a good screening agent for allergy to other (meth)acrylates. Patch test sensitization to HEMA 2% pet. is extremely rare. There are (some) indications that HEMA is frequently used in dental products and nail cosmetics.

Contact allergy to acrylate-containing nail cosmetics: A retrospective 8-year study.

BACKGROUND: Over the last 10 years, allergic contact dermatitis (ACD) from acrylate-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been reported repeatedly. OBJECTIVES: To investigate the frequency and clinical features of ACD in nail cosmetics in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: A retrospective study in patients diagnosed with ACD from acrylate-containing nail cosmetics at the Amsterdam University Medical Centers between January 2015 and August 2023. RESULTS: Sixty-seven patients, all women, were diagnosed with ACD from nail cosmetics, representing 1.6% of all individuals and 2.3% of all women patch tested in this period. Sixty-five of sixty-seven (97%) subjects had a positive patch test to 2-hydroxyethyl methacrylate (HEMA). Forty-nine patients (73%) were consumers and 18 (27%) were professional nail stylists. The sites most frequently affected with dermatitis were the fingers (79%), hands (40%) and the head and/or neck. Avoidance of contact with acrylate-containing products resulted in complete clearing of dermatitis in 80% of patients. CONCLUSIONS: ACD from acrylate-containing nail cosmetics is frequent in women patch tested in Amsterdam. Nearly all were identified by a positive patch test to 2-hydroxyethyl methacrylate in the (meth)acrylate series or the European baseline series.

Results of patch testing 2-hydroxyethyl methacrylate (HEMA) in the European baseline series: A 4-year retrospective study.

BACKGROUND: 2-Hydroxyethyl methacrylate (HEMA) was added to the European baseline series (EBS) in 2019. Few recent data are available on the frequency and relevance of positive reactions to this hapten. OBJECTIVES: To investigate the frequency and relevance of positive patch tests to HEMA in the EBS in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: Retrospective study in patients with positive patch tests to HEMA investigated between June 2019 and August 2023. RESULTS: Of 2927 consecutive patients, 88 (79 women and 9 men; 3.0%) had a positive reaction to HEMA. The prevalence in women was 3.9%, in men 1.0%. Forty-three (49%) reactions were judged to be of current clinical relevance and 21 (24%) of past relevance. In this group of 64 patients with relevant reactions, 18 (28%) had occupational contact with (meth)acrylate-containing products, of who 11 (61%) were nail stylists. In 46 patients with non-occupational allergic contact dermatitis, 31 (67%) had allergic reactions to nail cosmetics. Glues and glue-containing products accounted for 22% of the materials causing allergic contact dermatitis and dental products for 8%. CONCLUSIONS: Allergic reactions to HEMA are very frequent in women investigated in Amsterdam. Nearly two thirds of cases were caused by nail cosmetics.

HEMA-Lysine-Based Cryogels for Highly Selective Heparin Neutralization.

Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood purification therapies such as cardiovascular surgery and dialysis. The anticoagulant effect of heparin is essential for the optimal execution of extracorporeal blood circulation. However, at the end of these procedures, to avoid the risk of bleeding, it is necessary to neutralize it. Currently, the only antidote for heparin neutralization is protamine sulphate, a highly basic protein which constitutes a further source of serious side events and is ineffective in neutralizing LMWH. Furthermore, dialysis patients, due to the routine administration of heparin, often experience serious adverse effects, among which HIT (heparin-induced thrombocytopenia) is one of the most severe. For this reason, the finding of new heparin antagonists or alternative methods for heparin removal from blood is of great interest. Here, we describe the synthesis and characterization of a set of biocompatible macroporous cryogels based on poly(2-hydroxyethyl methacrylate) (pHEMA) and L-lysine with strong filtering capability and remarkable neutralization performance with regard to UFH and LMWH. These properties could enable the design and creation of a filtering device to rapidly reverse heparin, protecting patients from the harmful consequences of the anticoagulant.

Robust preimplantation genetic testing of the common F8 Inv22 pathogenic variant of severe hemophilia A using a highly polymorphic multi-marker panel encompassing the paracentric inversion.

BACKGROUND: Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging. METHODS: Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity. RESULTS: All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term. CONCLUSION: Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers.

Challenges in the classification of chemical respiratory allergens based on human data: Case studies of 2-hydroxyethylmethacrylate (HEMA) and 2-hydroxypropylmethacrylate (HPMA).

Occupational asthma resulting from workplace exposure to chemical respiratory allergens is an important disease. No widely accepted or formally validated tests for the identification of chemical respiratory sensitizers. Consequently, there is a heavy reliance on human data from clinical examinations. Unfortunately, however, although such investigations are critical for the diagnosis of occupational asthma, and in guiding remedial actions, they do not reliably identify specific chemicals within the workplace that are the causative agents. There are several reasons for this, including the fact that specific inhalation tests conducted as part of clinical investigations are frequently performed with complex mixtures rather than single substances, that sometimes inhalation challenges are conducted at concentrations above the OEL and STEL, where effects may be confounded by irritation, and that involvement of immune mechanisms cannot be assumed from the observation of late asthmatic reactions. Further, caution should be taken when implicating substances on lists of "recognised" asthmagens unless they have undergone a formal weight of evidence assessment. Here the limitations of clinical investigations as currently performed for the purposes of regulatory classification and decision making are explored by reference to previously published case studies that implicate 2-hydroxyethylmethacrylate (HEMA) and/or 2-hydroxypropylmethacrylate (HPMA) as respiratory allergens.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis-Part 1. Introduction, epidemiology, case series and case reports.

2-Hydroxyethyl methacrylate (HEMA) has been increasingly recognised as a contact allergen and was added to the European baseline series in 2019. In this article (2 parts), the results of an extensive literature review of the clinical aspects of contact allergy/allergic contact dermatitis to HEMA are presented. In part 1, the epidemiology of HEMA contact allergy is discussed and detailed information on published case series and case reports presented. HEMA is an important cause of contact allergy/allergic contact dermatitis in North America and Europe with recent prevalences of >3% in the USA + Canada and 1.5%-3.7% in Europe. Currently, most cases are caused by nail cosmetics, both in consumers and professional nail stylists. In our literature review, we have found 24 studies presenting case series of patients with allergic contact dermatitis attributed to HEMA and 168 case reports. However, the presence of HEMA in the products causing ACD was established in only a minority. Part 2 will discuss cross- and co-sensitisation, and other skin reactions to HEMA, will assess whether HEMA is the most frequent (meth)acrylate allergen and how sensitive HEMA as a screening agent is, investigate the presence of HEMA in commercial products and provide practical information on patch testing procedures.

Anisotropic NMR data acquisition with a prototype 400 MHz cryogen-free NMR spectrometer.

High-temperature superconducting (HTS) materials have recently been incorporated into the construction of HTS cryogen-free magnets for nuclear magnetic resonance (NMR) spectroscopy. These HTS NMR spectrometers do not require liquid cryogens, thereby providing significant cost savings and facilitating easy integration into chemistry laboratories. However, the optimal performance of these HTS magnets against standard cryogen NMR magnets must be evaluated, especially with demanding modern NMR applications such as NMR in anisotropic media. The stability of the HTS magnets over time and their performance with complex pulse sequence experiments are the main unknown factors of this new technology. In this study, we evaluate the utility of our prototype 400 MHz cryogen-free power-driven HTS NMR spectrometer, installed in the fumehood of a chemistry laboratory, for stereochemical analysis of three commercial natural products (artemisinin, artemether, and dihydroartemisinin) via measurement of anisotropic NMR data, in particular, residual dipolar couplings. The accuracy of measurement of the anisotropic NMR data with the HTS magnet spectrometer is evaluated through the CASE-3D fitting protocol, as implemented in the Mestrenova-StereoFitter software program.

Methacrylate Ester Monomers.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 2005, along with updated information regarding product types and concentrations of use, and confirmed that these 22 methacrylate ester monomers are safe as used in nail enhancement products in the practices of use and concentration as described in this report, when skin contact is avoided.

Safety Assessment of Polyfluorinated Polymers as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 12 polyfluorinated polymers in cosmetic products; most of these ingredients have the reported function of film former in common. However, PTFE, the only ingredient that is reported as currently used in cosmetics, functions as a bulking agent and slip modifier, but not as a film former. The Panel reviewed data relevant to the safety of these ingredients under the intended conditions of use in cosmetic formulations, and concluded that PTFE and Hexafluoropropylene/Tetrafluoroethylene Copolymer are safe in cosmetics in the present practices of use and concentration described in the safety assessment; the data are insufficient to determine the safety of the 4 fluorinated-side-chain polymers and 6 fluorinated polyethers.

Function of ALA Content in Porphyrin Metabolism Regulation of Ananas comosus var. bracteatus.

Chlorophyll and heme are essential molecules for photosynthesis and respiration, which are competing branches of the porphyrin metabolism pathway. Chlorophyll and heme balance regulation is very important for the growth and development of plants. The chimeric leaves of Ananas comosus var. bracteatus were composed of central photosynthetic tissue (PT) and marginal albino tissue (AT), which were ideal materials for the study of porphyrin metabolism mechanisms. In this study, the regulatory function of ALA content on porphyrin metabolism (chlorophyll and heme balance) was revealed by comparing PT and AT, 5-Aminolevulinic Acid (ALA) exogenous supply, and interference of hemA expression. The AT remained similar in porphyrin metabolism flow level to the PT by keeping an equal ALA content in both tissues, which was very important for the normal growth of the chimeric leaves. As the chlorophyll biosynthesis in AT was significantly inhibited, the porphyrin metabolism flow was directed more toward the heme branch. Both tissues had similar Mg2+ contents; however, Fe2+ content was significantly increased in the AT. The chlorophyll biosynthesis inhibition in the white tissue was not due to a lack of Mg2+ and ALA. A 1.5-fold increase in ALA content inhibited chlorophyll biosynthesis while promoting heme biosynthesis and hemA expression. The doubling of ALA content boosted chlorophyll biosynthesis while decreasing hemA expression and heme content. HemA expression interference resulted in a higher ALA content and a lower chlorophyll content, while the heme content remained at a relatively low and stable level. Conclusively, a certain amount of ALA was important for the stability of porphyrin metabolism and the normal growth of plants. The ALA content appears to be able to regulate chlorophyll and heme content by bidirectionally regulating porphyrin metabolism branch direction.

Melatonin Mitigates iNOS-Related Effects of HEMA and Camphorquinone in Human Dental Pulp Cells: Relevance for Postoperative Sensitivity Mechanism in Type 2 Diabetes.

High elution and diffusion of 2-hydroxylethyl methacrylate (HEMA) and camphorquinone (CQ) through dentinal tubules may induce pulp injury and postoperative sensitivity. We aimed to investigate the melatonin protective effect in HEMA- and CQ-treated human dental pulp cells (hDPCs) as well as its relevance in a mechanism for postoperative sensitivity in diabetic patients. hDPCs were exposed to HEMA (5 mM) and/or CQ (1 mM) in the absence and presence of melatonin (MEL) (0.1 mM and 1 mM). Heme oxygenase-1 (HMOX1), NADPH oxidase-4 (NOX4), BCL-2-associated X-protein (BAX), B-cell lymphoma-2 (BCL-2) and caspase-3 (CASP3) gene expression levels, and superoxide dismutase (SOD) activity were measured in hDPCs while inducible nitric oxide synthase (iNOS) and melatonin protein expression were measured in human dental pulp as well, by RT-PCR, by ELISA, and spectrophotometrically. Bioinformatic analyses were performed by using the ShinyGO (v.0.75) application. Type 2 diabetic patients showed a higher incidence of postoperative sensitivity and lower melatonin and higher iNOS content in dental pulp tissue compared with non-diabetic patients. Melatonin, when co-added in hDPC culture, reverses HEMA and CQ cytotoxic effects via anti-apoptotic and anti-inflammatory/antioxidant iNOS-related effects. Enrichment analyses showed that genes/proteins, altered by HEMA and CQ and normalized by melatonin, are the most prominently overrepresented in type 2 diabetes mellitus pathways and that they share subcellular localization in different oligomeric protein complexes consisting of anti- and pro-apoptotic regulators. This is the first evidence of the ability of melatonin to counteract iNOS-mediated inflammatory and stress effects in HEMA- and CQ-treated hDPCs, which could be of significance for the modulation of presently observed immediate postoperative sensitivity after composite restoration in type 2 diabetic patients.

Short-Term Comparison of Clinical Performance of Universal Adhesives with Self-Etch Mode in NCCL Restorations.

OBJECTIVES: To evaluate the clinical performance of universal adhesives with self-etch mode regarding their functional monomer and HEMA contents. METHODS: The study involved 27 patients (108 restorations) aged between 34 and 69 (mean age: 53.8). Each restoration contained one of four different universal adhesives applied in self-etch mode: G-Premio Bond (HEMA-free, MDP and 4-MET containing), Xeno Select (HEMA and MDP-free), Tetric-n-Bond Universal (HEMA and MDP-containing) and Clearfil Universal Bond Quick (HEMA, MDP and amide monomers containing). The restorations were evaluated according to the FDI criteria at baseline, 6, and 12 months. The data were statistically analyzed using Friedman's and Kruskal-Wallis tests for significance in each pair (p⟨0.05). RESULTS: After 12 months, one restoration was lost in each of the G-Premio Bond and Clearfil Bond Quick groups. The success rate was 96.3% for both adhesives and 100% for Xeno Select and Tetric-n-Bond adhesives. There was no statistically significant difference between the four dentin adhesive groups among all the evaluation periods regarding any evaluation criteria. However, four universal adhesives showed clinically acceptable marginal discoloration and marginal deterioration in a few restorations. CONCLUSION: Monomer contents of universal adhesives with self-etch mode had no significant effect on the success of restorations.

Preparation of colloidal nanoparticles PVA-PHEMA from hydrolysis of copolymers of PVAc-PHEMA as anticancer drug carriers.

The novel pH-responsive polymer nanoparticles have been widely used for drug delivery and cancer therapy. The pH-sensitive nanoparticles include chemical structures that can accept or donate protons in response to an environmental pH change. Polybases which mostly contain alkaline groups such as amines and hydroxy, accept protons at low pH and are neutral at higher pH values. This study aimed to prepare pH-sensitive colloidal amphiphilic poly(vinyl alcohol-2-hydroxyethyl methacrylate) (PVA-PHEMA) copolymers in cancer therapy applications. For this purpose, poly(vinyl acetate-2-hydroxyethyl methacrylate) (PVAc-PHEMA) copolymer nanoparticles were synthesized in different polymerization medium fractions from water and methanol and different monomer feed concentration. Then acetate groups were hydrolyzed, and the PHEMA-PVA nanoparticles were synthesized. The nanoparticles were further characterized using dynamic light scattering, Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis to identify the structural and morphological changes. The Methotrexate (MTX) was loaded into the nanoparticles, and drug release kinetics were evaluated. The results confirmed that PHEMA-PVA copolymeric nanoparticles could be favorably used in cancer therapy.

Influence of bonding agent application method on the dentin bond durability of a two-step adhesive utilizing a universal-adhesive-derived primer.

This study investigated the effect of the bonding agent application method on the dentin bond durability of a two-step adhesive utilizing a universal-adhesive-derived primer. The bonding durability of a universal adhesive was compared with those of two conventional two-step adhesives by shear bond strength testing after thermal cycling. The primer was applied (with or without phosphoric acid pre-etching), and the specimens were divided into three groups based on the bonding agent application method used as follows: (i) strong air-flow application, (ii) gentle air-flow application, and (iii) gentle air-flow + second bonding application. The shear bond strength was determined after thermal cycling. All the factors (bonding agent application method, adhesive system, and storage condition) significantly influenced the dentin shear bond strength both with and without phosphoric acid pre-etching. The specimens exposed to gentle air-flow showed a higher shear bond strength than did those exposed to strong air-flow and gentle air-flow + second bonding. The bond durability of the tested adhesive systems was influenced by the bonding agent application method, and this trend was material dependent. The G2-Bond Universal exhibited the same or greater dentin bond durability to the other two-step adhesive systems.

Allergic contact dermatitis caused by 2-hydroxyethyl methacrylate and ethyl cyanoacrylate contained in cosmetic glues among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications: A systematic review.

Current cosmetic regulations primarily focus on protecting consumers, not the professional user who is subjected to a partly different, and certainly more intense exposure to hazardous substances. Against this background, this systematic review aims to compile and appraise evidence regarding skin toxicity of 2-hydroxyethyl methacrylate (HEMA; CAS no. 212-782-2) and ethyl cyanoacrylate (ECA; CAS no. 7085-85-0) contained in cosmetic glues used among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. This systematic review followed the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) 2020 recommendations for reporting systematic reviews and meta-analysis. In total, six publications from six countries were eligible for this systematic review. A meta-analysis revealed that hairdressers and beauticians have a ninefold increased risk of developing contact allergy to HEMA compared with controls who are not hairdressers and beauticians. Results for ECA are lacking. The results of this systematic review clearly show that-regarding contact allergy to acrylates-it is not appropriate to apply risk assessment for consumers to hairdressers and beauticians who occupationally handle cosmetic glues. The regulations in existence do not adequately address occupational risks for hairdressers and beauticians connected with the use of acrylate-containing cosmetic substances and need reconsideration.

Evaluation of residual monomer release after polymerization of different restorative materials used in pediatric dentistry.

BACKGROUND: The choice of the restorative resin material to be used in pediatric dentistry is of a great importance due to the cytotoxic effects caused by residual monomers. In this study, it was aimed to investigate the amount of residual monomer released over time from different resin-based restorative materials, which are widely used in pediatric dentistry, by using high performance liquid chromatography with photodiode array detector (HPLC-PDA). METHODS: The compomers in all colors (Twinky Star and Glasiositte A2), two composites with different hybrid properties (Arabesk-GrandioSO), and RMGIC (Ionolux) samples with 2 × 5 mm diameters were prepared. The samples were polymerized with an LED light unit (CELALUX 2, VOCO, Cuxhaven, Germany) and then finishing-polishing procedures were applied. A total of 156 samples were obtained, 13 samples in each of the 12 groups. The amount of residual monomer (BIS-GMA; HEMA, TEGDMA, UDMA) (µg/mL) released into the 75% ethanol solution was determined at different times, (1st hour, 1st, 7th, 14th, and 21st day) by using HPLC-PDA. RESULTS: The residual monomer release continued on day 21 and BIS-GMA was the most released monomer in all groups. HEMA release showed a maximum increase in all the materials at day 7. The highest amount of residual monomer was detected in the gold-colored compomer. HEMA and BIS-GMA release from RMGIC was less than others in all time frames. CONCLUSIONS: The color and composition of resin-based restorative materials affect the amount of residual monomer. Pediatric dentists should prefer gold-colored compomers less than others as a restorative material, especially in deep cavities. More studies are needed about the subject.

Live, Genetically Attenuated, Cold-Chain-Free Cholera Vaccine-A Research and Development Journey: Light at the End of a Long Tunnel.

Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)-licenced, killed, multiple-dose oral cholera vaccines demand 'cold-chain supply' at 2 °C-8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5-aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.