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OBJECTIVES: Chewing gums containing antiseptics or other antimicrobial substances may be effective in reducing plaque and gingivitis. Therefore, the aim of this randomized placebo-controlled clinical trial was to investigate the efficacy of a novel antimicrobial chewing gum containing essential oils (cinnamon, lemon, peppermint) and extracts on reduction of dental plaque and gingivitis as well as on oral health-related quality of life (OHRQoL) in adolescent orthodontic patients. MATERIALS: 52 patients (11-22 years of age) were randomly assigned to use a test chewing gum (COVIDGUM, Clevergum) or a commercially available control chewing gum over a period of 10 days. Approximal plaque index (API), papillary bleeding index (PBI) and an OHRQoL questionnaire for children (COHIP-G19) were assessed at baseline (BL), after 10 days (10d) and 30 days (30d). In addition, oral health and oral hygiene related questions of the COHIP-G19 questionnaire were evaluated separately in subscales at each timepoint. Data were analyzed using non-parametrical statistical procedures (α = 0.05). RESULTS: API and PBI decreased significantly over time from BL to 10d and from BL to 30d in both groups, without significant differences between the groups. In both groups, the COHIP-G19 score, oral health subscale and oral hygiene subscale decreased significantly over time. Regarding the oral hygiene subscale, the test group showed significantly better scores at 30d (p = 0.011). CONCLUSION: Both chewing gums performed similarly effective in terms of reducing plaque accumulation and gingival inflammation and improving OHRQoL. CLINICAL RELEVANCE: Chewing gums without antimicrobial ingredients may be sufficient to decrease plaque accumulation and gingival inflammation.
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Goma de Mascar , Placa Dentária , Gengivite , Qualidade de Vida , Humanos , Gengivite/prevenção & controle , Adolescente , Feminino , Masculino , Placa Dentária/prevenção & controle , Criança , Adulto Jovem , Inquéritos e Questionários , Anti-Infecciosos/uso terapêutico , Resultado do Tratamento , Óleos Voláteis/uso terapêutico , Índice de Placa Dentária , Índice PeriodontalRESUMO
OBJECTIVES: Aerosols and splatter are routinely generated in dental practice and can be contaminated by potentially harmful bacteria or viruses such as SARS-CoV-2. Therefore, preprocedural mouthwashes containing antiseptic agents have been proposed as a potential measure for infection control in dental practice. This review article aims to summarize the clinical (and, if insufficient, preclinical) evidence on preprocedural mouthwashes containing antiseptic agents and to draw conclusions for dental practitioners. METHODS: Literature on preprocedural mouthwashes for reduction of bacterial or viral load in dental aerosols was searched and summarized. RESULTS: Preprocedural mouthwashes, particularly those containing chlorhexidine digluconate (CHX), cetylpyridinium chloride (CPC), or essential oils (EO), can significantly reduce the bacterial load in dental aerosols. With respect to viruses such as HSV-1, there are too little clinical data to draw any clear recommendations. On the other hand, clinical data is consolidating that CPC-containing mouthwashes can temporarily reduce the intraoral viral load and infectivity in SARS-CoV-2 positive individuals. Nevertheless, potential risks and side effects due to regular antiseptic use such as ecological effects or adaptation of bacteria need to be considered. CONCLUSIONS: The use of preprocedural mouthwashes containing antiseptics can be recommended according to currently available data, but further studies are needed, particularly on the effects on other viruses besides SARS-CoV-2. When selecting a specific antiseptic, the biggest data basis currently exists for CHX, CPC, EO, or combinations thereof. CLINICAL RELEVANCE: Preprocedural mouthwashes containing antiseptics can serve as part of a bundle of measures for protection of dental personnel despite some remaining ambiguities and in view of potential risks and side effects.
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Anti-Infecciosos Locais , COVID-19 , Óleos Voláteis , Humanos , Antissépticos Bucais/uso terapêutico , Odontólogos , SARS-CoV-2 , COVID-19/prevenção & controle , Papel Profissional , Aerossóis e Gotículas Respiratórios , Anti-Infecciosos Locais/uso terapêutico , Clorexidina/uso terapêutico , Bactérias , Controle de Infecções , Odontologia , Cetilpiridínio/uso terapêuticoRESUMO
The surfactants polysorbate 20 (PS20) and polysorbate 80 (PS80) are utilized to stabilize protein drugs. However, concerns have been raised regarding the degradation of PSs in biologics and the potential impact on product quality. Oxidation has been identified as a prevalent degradation mechanism under pharmaceutically relevant conditions. So far, a systematic stability comparison of both PSs under pharmaceutically relevant conditions has not been conducted and little is known about the dependence of oxidation on PS concentration. Here, we conducted a comparative stability study to investigate (i) the different oxidative degradation propensities between PS20 and PS80 and (ii) the impact of PS concentration on oxidative degradation. PS20 and PS80 in concentrations ranging from 0.1 mgâ mL-1 to raw material were stored at 5, 25, and 40 °C for 48 weeks in acetate buffer pH 5.5 and water, respectively. We observed a temperature-dependent oxidative degradation of the PSs with strong (40 °C), moderate (25 °C), and weak/no degradation (5 °C). Especially at elevated temperatures such as 40 °C, fast oxidative PS degradation processes were detected. In this case study, a stronger degradation and earlier onset of oxidation was observed for PS80 in comparison to PS20, detected via the fluorescence micelle assay. Additionally, degradation was found to be strongly dependent on PS concentration, with significantly less oxidative processes at higher PS concentrations. Iron impurities, oxygen in the vial headspaces, and the pH values of the formulations were identified as the main contributing factors to accelerate PS oxidation.
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To ensure the stability of biologicals over their entire shelf-life, non-ionic surface-active compounds (surfactants) are added to protect biologics from denaturation and particle formation. In this context, polysorbate 20 and 80 are the most used detergents. Despite their benefits of low toxicity and high biocompatibility, specific factors are influencing the intrinsic stability of polysorbates, leading to degradation, loss in efficacy, or even particle formation. Polysorbate degradation can be categorized into chemical or enzymatic hydrolysis and oxidation. Under pharmaceutical relevant conditions, hydrolysis is commonly originated from host cell proteins, whereas oxidative degradation may be caused by multiple factors such as light, presence of residual metal traces, peroxides, or temperature, which can be introduced upon manufacturing or could be already present in the raw materials. In this review, we provide an overview of the current knowledge on polysorbates with a focus on oxidative degradation. Subsequently, degradation products and key characteristics of oxidative-mediated polysorbate degradation in respect of different types and grades are summarized, followed by an extensive comparison between polysorbate 20 and 80. A better understanding of the radical-induced oxidative PS degradation pathway could support specific mitigation strategies. Finally, buffer conditions, various stressors, as well as appropriate mitigation strategies, reagents, and alternative stabilizers are discussed. Prior manufacturing, careful consideration and a meticulous risk-benefit analysis are highly recommended in terms of polysorbate qualities, buffers, storage conditions, as well as mitigation strategies.
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Castellaniella defragrans is a Betaproteobacterium capable of coupling the oxidation of monoterpenes with denitrification. Geraniol dehydrogenase (GeDH) activity was induced during growth with limonene in comparison to growth with acetate. The N-terminal sequence of the purified enzyme directed the cloning of the corresponding open reading frame (ORF), the first bacterial gene for a GeDH (geoA, for geraniol oxidation pathway). The C. defragrans geraniol dehydrogenase is a homodimeric enzyme that affiliates with the zinc-containing benzyl alcohol dehydrogenases in the superfamily of medium-chain-length dehydrogenases/reductases (MDR). The purified enzyme most efficiently catalyzes the oxidation of perillyl alcohol (k(cat)/K(m) = 2.02 × 10(6) M(-1) s(-1)), followed by geraniol (k(cat)/K(m) = 1.57 × 10(6) M(-1) s(-1)). Apparent K(m) values of <10 µM are consistent with an in vivo toxicity of geraniol above 5 µM. In the genetic vicinity of geoA is a putative aldehyde dehydrogenase that was named geoB and identified as a highly abundant protein during growth with phellandrene. Extracts of Escherichia coli expressing geoB demonstrated in vitro a geranial dehydrogenase (GaDH) activity. GaDH activity was independent of coenzyme A. The irreversible formation of geranic acid allows for a metabolic flux from ß-myrcene via linalool, geraniol, and geranial to geranic acid.
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Alcaligenaceae/enzimologia , Oxirredutases do Álcool/metabolismo , Aldeído Desidrogenase/metabolismo , Regulação Bacteriana da Expressão Gênica , Monoterpenos/metabolismo , Terpenos/metabolismo , Monoterpenos Acíclicos , Alcaligenaceae/genética , Alcaligenaceae/crescimento & desenvolvimento , Oxirredutases do Álcool/genética , Aldeído Desidrogenase/genética , Anaerobiose , Meios de Cultura , Escherichia coli/enzimologia , Escherichia coli/genética , Dados de Sequência Molecular , Monoterpenos/química , Análise de Sequência de DNARESUMO
Objective: Disrupted sleep and training behaviors in athletes have been reported during the COVID-19 pandemic. We aimed at investigating the combined effects of Ramadan observance and COVID-19 related lockdown in Muslim athletes. Methods: From an international sample of athletes (n = 3,911), 1,681 Muslim athletes (from 44 countries; 25.1 ± 8.7 years, 38% females, 41% elite, 51% team sport athletes) answered a retrospective, cross-sectional questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: (i) Pittsburgh sleep quality index (PSQI); (ii) insomnia severity index (ISI); (iii) bespoke questions about training, napping, and eating behaviors, and (iv) questions related to training and sleep behaviors during-lockdown and Ramadan compared to lockdown outside of Ramadan. The survey was disseminated predominately through social media, opening 8 July and closing 30 September 2020. Results: The lockdown reduced sleep quality and increased insomnia severity (both p < 0.001). Compared to non-Muslim (n = 2,230), Muslim athletes reported higher PSQI and ISI scores during-lockdown (both p < 0.001), but not pre-lockdown (p > 0.05). Muslim athletes reported longer (p < 0.001; d = 0.29) and later (p < 0.001; d = 0.14) daytime naps, and an increase in late-night meals (p < 0.001; d = 0.49) during- compared to pre-lockdown, associated with lower sleep quality (all p < 0.001). Both sleep quality (χ2 = 222.6; p < 0.001) and training volume (χ2 = 342.4; p < 0.001) were lower during-lockdown and Ramadan compared to lockdown outside of Ramadan in the Muslims athletes. Conclusion: Muslim athletes reported lower sleep quality and higher insomnia severity during- compared to pre-lockdown, and this was exacerbated by Ramadan observance. Therefore, further attention to Muslim athletes is warranted when a circadian disrupter (e.g., lockdown) occurs during Ramadan.
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OBJECTIVE: In a convenience sample of athletes, we conducted a survey of COVID-19-mediated lockdown (termed 'lockdown' from this point forward) effects on: (i) circadian rhythms; (ii) sleep; (iii) eating; and (iv) training behaviors. METHODS: In total, 3911 athletes [mean age: 25.1 (range 18-61) years, 1764 female (45%), 2427 team-sport (63%) and 1442 elite (37%) athletes] from 49 countries completed a multilingual cross-sectional survey including the Pittsburgh Sleep Quality Index and Insomnia Severity Index questionnaires, alongside bespoke questions about napping, training, and nutrition behaviors. RESULTS: Pittsburgh Sleep Quality Index (4.3 ± 2.4 to 5.8 ± 3.1) and Insomnia Severity Index (4.8 ± 4.7 to 7.2 ± 6.4) scores increased from pre- to during lockdown (p < 0.001). Pittsburgh Sleep Quality Index was predominantly influenced by sleep-onset latency (p < 0.001; + 29.8%), sleep efficiency (p < 0.001; - 21.1%), and total sleep time (p < 0.001; - 20.1%), whilst Insomnia Severity Index was affected by sleep-onset latency (p < 0.001; + 21.4%), bedtime (p < 0.001; + 9.4%), and eating after midnight (p < 0.001; + 9.1%). During lockdown, athletes reported fewer training sessions per week (- 29.1%; d = 0.99). Athletes went to bed (+ 75 min; 5.4%; d = 1.14) and woke up (+ 150 min; 34.5%; d = 1.71) later during lockdown with an increased total sleep time (+ 48 min; 10.6%; d = 0.83). Lockdown-mediated circadian disruption had more deleterious effects on the sleep quality of individual-sport athletes compared with team-sport athletes (p < 0.001; d = 0.41), elite compared with non-elite athletes (p = 0.028; d = 0.44) and older compared with younger (p = 0.008; d = 0.46) athletes. CONCLUSIONS: These lockdown-induced behavioral changes reduced sleep quality and increased insomnia in athletes. Data-driven and evidence-based recommendations to counter these include, but are not limited to: (i) early outdoor training; (ii) regular meal scheduling (whilst avoiding meals prior to bedtime and caffeine in the evening) with appropriate composition; (iii) regular bedtimes and wake-up times; and (iv) avoidance of long and/or late naps.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adolescente , Adulto , Atletas , Cafeína , Ritmo Circadiano , Controle de Doenças Transmissíveis , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Sono , Qualidade do Sono , Inquéritos e Questionários , Adulto JovemRESUMO
Objective: To investigate the effect of 1) lockdown duration and 2) training intensity on sleep quality and insomnia symptoms in elite athletes. Methods: 1,454 elite athletes (24.1 ± 6.7 years; 42% female; 41% individual sports) from 40 countries answered a retrospective, cross-sectional, web-based questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: 1) Pittsburgh sleep quality index (PSQI); 2) Insomnia severity index (ISI); bespoke questions about 3) napping; and 4) training behaviors. The association between dependent (PSQI and ISI) and independent variables (sleep, napping and training behaviors) was determined with multiple regression and is reported as semi-partial correlation coefficient squared (in percentage). Results: 15% of the sample spent < 1 month, 27% spent 1-2 months and 58% spent > 2 months in lockdown. 29% self-reported maintaining the same training intensity during-lockdown whilst 71% reduced training intensity. PSQI (4.1 ± 2.4 to 5.8 ± 3.1; mean difference (MD): 1.7; 95% confidence interval of the difference (95% CI): 1.6-1.9) and ISI (5.1 ± 4.7 to 7.7 ± 6.4; MD: 2.6; 95% CI: 2.3-2.9) scores were higher during-compared to pre-lockdown, associated (all p < 0.001) with longer sleep onset latency (PSQI: 28%; ISI: 23%), later bedtime (PSQI: 13%; ISI: 14%) and later preferred time of day to train (PSQI: 9%; ISI: 5%) during-lockdown. Those who reduced training intensity during-lockdown showed higher PSQI (p < 0.001; MD: 1.25; 95% CI: 0.87-1.63) and ISI (p < 0.001; MD: 2.5; 95% CI: 1.72-3.27) scores compared to those who maintained training intensity. Although PSQI score was not affected by the lockdown duration, ISI score was higher in athletes who spent > 2 months confined compared to those who spent < 1 month (p < 0.001; MD: 1.28; 95% CI: 0.26-2.3). Conclusion: Reducing training intensity during the COVID-19-induced lockdown was associated with lower sleep quality and higher insomnia severity in elite athletes. Lockdown duration had further disrupting effects on elite athletes' sleep behavior. These findings could be of relevance in future lockdown or lockdown-like situations (e.g., prolonged illness, injury, and quarantine after international travel).
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Citalopram, mirtazapine and risperidone are frequently prescribed for psychiatric illnesses such as depression and psychosis or for aggressive behavior in elderly patients with dementia. The plasma concentrations vary greatly between patients, especially in elderly patients. Thus, therapeutic drug monitoring (TDM) increases the safety of antipsychotic treatment and a more rapid response to treatment may be achieved. To facilitate TDM, the objectives of this study were to develop and validate a reliable dried blood spot method to simultaneously quantify citalopram, mirtazapine and risperidone including its active metabolite 9-hydroxyrisperidone. The blood punches were extracted by methanol using an ultrasonic bath, purified by liquid-liquid extraction and analyzed by liquid chromatography/mass spectrometry (LC-MS). All acceptance criteria of the EMA and FDA guidelines for method validation were fulfilled. Linearity was shown over the range of 2.5-300µg/L for all substances. The analytes were stable for at least one month at all investigated storage conditions, including storing at room temperature exposed to light. Retrieving capillary blood by finger-pricking the assay was successfully applied in elderly patients. Venous serum samples were drawn simultaneously to compare capillary blood with serum concentrations. Given the validated results and the calculated capillary blood:serum ratio, the studied dried blood spot method offers an excellent application in TDM and can be applied in ambulatory care.