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Background and Objectives: Vitamin D binding protein (DBP) is biosynthesised in the liver and is predominantly expressed in serum. Its primary role centres on facilitating the systemic transportation of vitamin D and its metabolites, notably 25‐hydroxyvitamin D, to specific target tissues where vitamin D exerts its biological functions. Due to the paucity of studies, it is unclear whether there is an association between DBP and periodontal status and thus its potential use as a diagnostic biomarker. Therefore, the aim of the systematic review is to investigate the association between DBP in periodontal disease. Methods: Two independent reviewers (YD and RG) performed a systematic literature search of English publications using several databases including MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1974 onwards), and Global Health (OVID interface, 1973 onwards). This search strategy enabled the identification of relevant publications and the development of a comprehensive library of studies. Studies were included based on previously agreed eligibility criteria. Of the eight studies included as part of this systematic review, seven were case–control studies and one was a cross‐sectional study. The quality assessment was based on the Newcastle–Ottawa Scale (NOS) for case–control studies and the modified NOS for the cross‐sectional study. Results: The NOS quality assessment was 'favorable' for 6 included case control studies; and 'fair' for one study. The modified NOS quality assessment for the single cross‐sectional study demonstrated a medium risk of bias. The results of the majority of the included studies indicated a statistically significant higher concentration of DBP levels in individuals with periodontitis in comparison to those who were periodontally healthy. This trend held true irrespective of the sampling method employed for the assessment of DBP concentration. Conclusion: The results summarised in this systematic review indicate a positive association between DBP and periodontitis. Nonetheless, there is a need for longitudinal, prospective trials, to confirm the use of DBP as a potential biomarker for the diagnosis of periodontitis. [ABSTRACT FROM AUTHOR]

Kristina Simacek,1 Christopher Curran,1 Peter Fenici,2 Ricardo Garcia-Sanchez3 1PatientsLikeMe, Inc., Cambridge, MA, USA; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA Purpose: This study aimed to assess awareness of glycated hemoglobin (A1C) testing and targets, perceived level of glycemic control and risk of complications, attitudes toward medications and self-management, and regimen-related distress in an international sample of patients with type 2 diabetes (T2D).Methods: The descriptive study used a single time-point survey of adults in online health communities in the USA, Canada, the UK, Germany, Spain, and Mexico, who self-reported T2D diagnosed by a physician.Results: In total, 661 patients participated. Awareness of their A1C value at last test varied considerably between countries (42%–89%), as did awareness of having an A1C target (26%–70%). Self-reported A1C values were similar across US, Canadian, and European respondents (mean, 6.8%–7.3%). Approximately two-thirds of respondents from these countries (66%–71%) reported that their T2D was very or fairly well controlled, and few (5%–15%) expected to experience serious complications within 1 year. However, many respondents expected to experience microvascular (rather than macrovascular) complications in this time frame (eg, nerve pain, 5%–47%). Self-reported adherence to oral medication was generally high, with most respondents (86%–98%) taking their pills or tablets as directed by their healthcare provider, although for insulin injections adherence was lower in the USA (71%) and Mexico (78%) than in the other countries (86%–95%). The majority of respondents across countries (71%–79%) reported that taking injectable medications was not at all or a little burdensome. Respondents across countries appeared to be reasonably confident that they could adequately manage their blood sugar levels; despite this, a sizeable minority (21%–35%) had clinically significant levels of regimen-related distress.Conclusion: Limited patient awareness of their A1C value and the potential complications of poorly controlled T2D, particularly regarding cardiovascular complications, may be a widespread problem. Furthermore, greater patient support may be needed to improve self-management of T2D and to reduce regimen-related distress. Keywords: diabetes mellitus, type 2, diabetes complications, glycated hemoglobin, self-management, surveys

Aims: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. Methods: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg–1; maintenance dose 12 mg kg–1 day–1 or 20 mg kg–1 day–1, respectively, for infants <30 weeks or ≥30 weeks’ corrected gestational age) or micafungin (loading dose 15 mg kg–1 day–1; maintenance dose 10 mg kg–1 day–1). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks’ corrected gestational age or hospital discharge. Results: Thirty‐six neonates were enrolled. The median (range) gestational age was 28.2 (24.1–40.1) and 26.8 (23.5–40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h–1 kg–1) and volume of distribution (l kg–1) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. Conclusion: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration–time curve target attainment rate in neonates. [ABSTRACT FROM AUTHOR]

Background/objective: Pharmaceutical care is needed in hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAA). We describe the implementation of a comprehensive pharmaceutical care programme (CPCP) for HCV-infected patients treated with DAA in a tertiary-care hospital and provide data about health outcomes and costs.Methods: Quasi-experimental study between 1 April 2015 and 30 June 2016. A group of hospital pharmacists collaborating on HCV infection implemented interventional measures for validation of drug prescriptions, detection of clinically relevant drug-drug interactions and adverse drug events (ADEs), and patient education. Quality, health and cost-effectiveness outcomes were evaluated.Results: A total of 1070 patients were enrolled. Pharmacists made 327 interventions that led to the prevention of 299 (91.4%) medication errors, 16 of which were grade G-H (NCC MERP classification). The main reasons for the pharmacist's intervention were management of 143 drug-drug interactions. The overall sustained virologic response at week 12 posttreatment (SVR12) rate was 93.0% (95% CI 91.4-94.6). The SVR12 was higher than 90.0% in all populations, except in genotype 3 patients (86.0%, 95% CI 78.7-93.9), decompensated cirrhotic patients (81.1%, 95% CI 69.7-92.6) and transplant recipients (86.8%, 95% CI 76.7-96.9). ADEs occurred in 85.5% of the study patients, but only 1.0% (11 patients) experienced an ADE that led to premature discontinuation. The total cost of treatment was €18 279 225 (€17 083 per patient). The most cost-effective treatment was selected in 93.1% of patients.Conclusions: The implementation of a CPCP developed by hospital pharmacists in patients treated with DAAs for HCV infection is an effective approach that improves patient safety and education. The active involvement of the pharmacist in improving adherence to local guidelines promoted the selection of the most cost-effective treatment in the majority of cases. [ABSTRACT FROM AUTHOR]

Hydrological ensemble prediction systems (HEPS) have in recent years been increasingly used for the operational forecasting of floods by European hydrometeorological agencies. The most obvious advantage of HEPS is that more of the uncertainty in the modelling system can be assessed. In addition, ensemble prediction systems generally have better skill than deterministic systems both in the terms of the mean forecast performance and the potential forecasting of extreme events. Research efforts have so far mostly been devoted to the improvement of the physical and technical aspects of the model systems, such as increased resolution in time and space and better description of physical processes. Developments like these are certainly needed; however, in this paper we argue that there are other areas of HEPS that need urgent attention. This was also the result from a group exercise and a survey conducted to operational forecasters within the European Flood Awareness System (EFAS) to identify the top priorities of improvement regarding their own system. They turned out to span a range of areas, the most popular being to include verification of an assessment of past forecast performance, a multi-model approach for hydrological modelling, to increase the forecast skill on the medium range (>3 days) and more focus on education and training on the interpretation of forecasts. In light of limited resources, we suggest a simple model to classify the identified priorities in terms of their cost and complexity to decide in which order to tackle them. This model is then used to create an action plan of short-, medium- and long-term research priorities with the ultimate goal of an optimal improvement of EFAS in particular and to spur the development of operational HEPS in general. [ABSTRACT FROM AUTHOR]

Hydrological ensemble prediction systems (HEPS) have in recent years been increasingly used for the operational forecasting of floods by hydrometeorological agencies. The most obvious advantages of HEPS are that more of the uncertainty in the modelling system can be assessed; and that ensemble prediction systems generally have better skill than deterministic systems both in the terms of the mean forecast performance and the potential forecasting of extreme events. Research efforts have so far mostly been devoted to the improvement of the technical aspects of the model systems themselves. However, in this paper we argue that there are other areas of HEPS that need urgent attention; such as assessment of the full uncertainty in the forecast chain, multimodel approaches, robust forecast skill assessment and further collaboration and knowledge exchange between operational forecasters and the model development community. In light of limited resources we suggest a simple model to classify the identified priorities in terms of their cost and complexity to decide in which order to tackle them This model is then used to create an action plan of short-, medium-and long-term research priorities with the ultimate goal of an optimal improvement in operational HEPS. [ABSTRACT FROM AUTHOR]

Abstract: We test the hypothesis that the noise in belemnite records through time results from changing climate. We do so by comparing palaeo-proxies (Mg/Ca, Sr/Ca, Na/Ca, δ18O, δ13C) in two species of Toarcian belemnites, Acrocoelites (Odontobelus) vulgaris (14 specimens) and Acrocoelites (Acrocoelites) subtenuis (10 specimens), deposited in a period of time that was short relative to the timescale of climate change. The specimens are interpreted to have been regurgitated from the stomach of a marine predator and so were deposited together in a geological instant of Early Jurassic time. In A. (O.) vulgaris, isotopic and elemental palaeo-proxies group tightly, suggesting that this belemnite occupied a restricted environmental niche. In A. (A.) subtenuis, elemental and isotopic compositions spread more widely, suggesting that this species occupied a greater range of habitats. Possible sexual dimorphism in A. (O.) vulgaris is reflected in bimodal Mg/Ca and differing intra-rostral distribution of Mg in putative dimorphs; concentrations decline by 30% from apical line to rim in specimens with high Mg/Ca, but are largely invariant radially in specimens with lower Mg/Ca. Sexual dimorphism in A. (A.) subtenuis yields a bimodality in size, Mg/Ca, and intra-rostral distribution of Mg; larger specimens have a higher Mg/Ca, and Mg concentrations that increase along radial traverses from apical line to rim, whilst the smaller specimens show a mid-rostral minimum in Mg concentration. Radial profiles of concentrations for Sr and Na vary little in all forms. Toarcian belemnites of these species thus show strong biofractionation effects on Mg/Ca, and little or no observable biofractionation of Sr/Ca or Na/Ca. It follows that much of the noise in belemnite records results from biofractionation, and from a cosmopolitan life-style of some belemnite species, rather than climate-change. For Toarcian belemnites, we suggest that Sr/Ca is the best indicator of palaeo-temperature. [Copyright &y& Elsevier]

Various studies have emphasized the importance of identifying the optimal Trigger Timing (TT) for the trigger shot in In Vitro Fertilization (IVF), which is crucial for the successful maturation and release of oocytes, especially in minimal ovarian stimulation treatments. Despite its significance for the ultimate success of IVF, determining the precise TT remains a complex challenge for physicians due to the involvement of multiple variables. This study aims to enhance TT by developing a machine learning multi-output model that predicts the expected number of retrieved oocytes, mature oocytes (MII), fertilized oocytes (2 PN), and useable blastocysts within a 48-h window after the trigger shot in minimal stimulation cycles. By utilizing this model, physicians can identify patients with possible early, late, or on-time trigger shots. The study found that approximately 27 % of treatments administered the trigger shot on a suboptimal day, but optimizing the TT using the developed Artificial Intelligence (AI) model can potentially increase useable blastocyst production by 46 %. These findings highlight the potential of predictive models as a supplementary tool for optimizing trigger shot timing and improving IVF outcomes, particularly in minimal ovarian stimulation. The experimental results underwent statistical validation, demonstrating the accuracy and performance of the model. Overall, this study emphasizes the value of AI prediction models in enhancing TT and making the IVF process safer and more efficient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. The authors certify that the submission is original work and is not under review at any other publication., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: The aim of this study is to compare the aesthetic outcomes of metal porcelain (C), lithium disilicate (T1) and porcelain-layered zirconium (T2) immediate implant-supported single crowns in the anterior maxilla., Materials and Methods: Forty-five immediate dental implants were provided for 45 patients that required the extraction of a single tooth in the anterior maxilla. A temporary prosthesis was provided at 8 weeks after placement followed by the final prosthesis at 24 weeks post-implantation. The patients were randomly allocated into 3 groups: 15 patients in the control group (C) received a metal-porcelain restoration, 15 patients (T1) received a lithium disilicate (LD) restoration and 15 patients (T2) received a porcelain-layered, zirconium (Z) restoration. Pink (PES) and White (WES) esthetic scores, radiographic bone levels, periodontal parameters and patient's esthetic satisfaction using a visual analogue scale (VAS) were evaluated at the time of final restoration placement (t0) and at 12-months post-loading (t12)., Results: No implants were lost during the duration of this study. Statistically significant higher WES and VAS scores (p < 0.05) were recorded in T1 vs C and T1 vs T2 groups respectively. Similar radiographic bone levels and periodontal parameters were recorded in all groups., Conclusion: Within the limitations of this study, it was concluded that T1 restorations provided better WES outcomes when compared to C restorations and better VAS scores when compared to T2 restorations at 12 months post-loading. Besides, different material interphases did not have an impact in PES, bone levels or periodontal parameters., Clinical Relevance: There is limited data comparing aesthetic outcomes of implant supported single crowns made of different ceramic materials based on accepted and comparable indexes and the evaluation of the patient's perspective regarding these aesthetic outcomes., Competing Interests: Declaration of competing interest The authors do not report any conflict of interest related to the present study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes., Materials and Methods: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months., Results: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively., Conclusions: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects., Clinical Trial Registration: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy., Methods: An electronic search (Medline, Embase and the Cochrane Library Database and OpenGray) and a hand search were carried out to identify all types of studies investigating interdental papilla reconstruction (except for reviews) with a minimum of 3 months follow-up., Results: Forty-five studies were included in the study including 7 RCTs, 2 cohort studies, 19 case series and 17 case reports. Fifteen studies reported on the use of hyaluronic acid, 6 studies on platelet-rich fibrin, 16 studies on soft tissue grafting, 4 studies on orthodontics and 4 on additional modalities. The most common outcome measures were black triangle dimensions and papillary fill percentage. Meta-analysis was not possible due to the high heterogeneity of the studies., Conclusion: There are various options for interdental papilla reconstruction of which hyaluronic acid injections, PRF, surgical grafting and orthodontics seem to improve outcomes at a minimum 3 months. The use of soft tissue grafting with sub-epithelial connective tissue graft seems to be associated with the most robust evidence for the longer-term reduction of 'black triangles'. There is insufficient evidence to make recommendations to clinicians. Further research is needed in the form of well conducted RCTs with longer follow ups and patient reported outcome measures., Clinical Relevance: Patients frequently complain about the appearance of black triangles and their management options seem unclear. This systematic review provides insight into the available reconstructive options., (© 2024. The Author(s).)

Improved agricultural and industrial production organisms are required to meet the future global food demands and minimize the effects of climate change. A new resource for crop and microbe improvement, designated FIND-IT (Fast Identification of Nucleotide variants by droplet DigITal PCR), provides ultrafast identification and isolation of predetermined, targeted genetic variants in a screening cycle of less than 10 days. Using large-scale sample pooling in combination with droplet digital PCR (ddPCR) greatly increases the size of low-mutation density and screenable variant libraries and the probability of identifying the variant of interest. The method is validated by screening variant libraries totaling 500,000 barley ( Hordeum vulgare ) individuals and isolating more than 125 targeted barley gene knockout lines and miRNA or promoter variants enabling functional gene analysis. FIND-IT variants are directly applicable to elite breeding pipelines and minimize time-consuming technical steps to accelerate the evolution of germplasm.

Objective: Two focused questions were addressed: Focused question (Q1) 1) Are there any differences between immediate and delayed placement in terms of (i) survival rate, (ii) success rate, (iii) radiographic marginal bone levels, (iv) height/(v)thickness of buccal wall, (vi) peri-implant mucosal margin position, (vii) aesthetics outcomes and (viii) patient reported outcomes? Focused question 2 (Q2) What is the estimated effect size of immediate implant placement for all parameters included in Q1?, Materials and Methods: An electronic search (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials and OpenGray) and hand search were conducted up to November 2019. Randomised controlled trials (RCT) with delayed implant placement as controls were eligible in the analysis for Q1. Immediate dental implant arms RCTs, controlled clinical trials (CCTs) and prospective case series of immediate implant placement were eligible in the analysis for Q2., Results: Six papers (RCTs) were included in the analysis for Q1 and 53 papers (22 RCTs, 11 CCTs and 20 case series) for Q2. Q1: Meta-analyses did not show any significant difference in implant survival, but it did for bone levels and PES scores at 1 year post-loading, favouring the immediate group. Q2: Meta-analyses showed that immediate implants had a high survival rate (97%) and presented high PES scores (range 10.36 to 11.25). Information regarding marginal bone loss and gingival/papillary recession varied among all included studies., Conclusion: Similar survival rate was found between immediate and delayed implants. Immediate implants presented threefold early complications and twofold delayed complications. Success criteria should be reported more consistently, and the incidence/type of complications associated with immediate implants should be further explored., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Objectives: COVID-19 has had a significant impact on dentistry in unforeseen ways, including a substantial rise in the development and implementation of video consultations. The research aimed to investigate dentists' and patients' attitudes towards dental video consultations (tele-dentistry) and to identify potential ways to improve the experience., Methods: A cross-sectional, pre-post design, online survey was carried out with patients' and dentists' before and after video consultations. A total of 249 participants accessed the survey and 228 of them consented to take part in the study and answered the online questions. Participants' attitudes towards video consultations were assessed using a questionnaire constructed by a multidisciplinary team of periodontists and psychologists. The measure assessed the perceived efficacy of the video consultations on patients and the dental team. Video consultations were performed to risk assess, triage and manage remotely via a video link out at (deleted name of institution as double blinded peer review) via NHS England's Attend Anywhere platform., Results: The majority of patients strongly agreed and were satisfied using tele-dentistry in the five domains which we explored: the ease, comprehensiveness and helpfulness of the video consultations and the anxiety and satisfaction levels of the patient. Dentists and students alike felt more confident and competent after having carried out a video consultation. The majority of clinicians found the tele-dentistry platform helpful and easy to perform. Just over 70% of patients strongly agreed that the video consultation ran smoothly and 75.7% strongly agreed that they were comfortable accessing the consultation from home rather than travelling in for the consultation. Just under 80% of patients stated that they would recommend the video consultation., Conclusions: This study shows that tele-dentistry may be a valid option to help service providers and dental patients, as it seems to be well accepted by both patients and dentists. JM to typesetter., Clinical Significance: Patients' and dentists' perceptions of Tele-Dentistry at the time of COVID-19. A questionnaire-based study. To our knowledge this is one of the first studies evaluates perceptions of patients and clinicians before and after a tele-dentistry encounter in and across different dental departments. The majority of survey participants expressed positive views towards tele-dentistry across all domains including ease and comprehensiveness of the video consultation, perceived helpfulness and anxiety and satisfaction of the patient. Dentists appear to be competent and confident to carry out these video consultations and find them to be helpful and easy to complete. As a result, we suggest readers adopt tele-dentistry in their daily activities to help patients and clinicians alike., (Copyright © 2021 Elsevier Ltd. All rights reserved.)