Complementary remineralizing effect of self-assembling peptide (P11-4) with CPP-ACPF or fluoride : an in vitro study

Self-assembling peptide has been recently introduced to promote hard tissue regeneration for treating early non-cavitated carious lesions. This study investigates the efficacy of biomimetic self-assembling peptide (P11-4) on enamel remineralization combined with CPP-ACPF or fluoride. Artificial enamel lesions were created on buccal surface of 60 specimens and were randomly assigned to six groups according to the remineralizing agent: G1-(Control, artificial saliva), G2-(Fluoride varnish), G3-(CPP-ACPF varnish), G4-(Self-assembling peptide), G5-(Self-assembling peptide+fluoride varnish), G6-(Self-assembling peptide+CPP-ACPF varnish). All products were applied according to manufacturer?s instructions and specimens were stored in a daily renewed artificial saliva. Surface microhardness (SMH) and scanning electron microscope (SEM) were assessed at baseline, after demineralization, 1 week and 4 weeks storage. SMH values were analyzed using ANOVA and Tukey?s post-hoc test. The highest statistically significant SMH values were found in G6 followed by G5, G4, G2 and G3 while the lowest values were found in G1. No statistically significant difference was found between G5 and G6. Also, no statistically significant difference was found between G2 and G3. SEM showed that G4, G5, G6 resulted in more pronounced remineralization, reversing the demineralized enamel fish scale pattern compared to G2 and G3 after 1 week and 4 week remineralization. Complementary effect was obtained after combining self-assembling peptide with CPP-ACPF or fluoride showing the highest remineralizing potential early after 1 week and even after 4 weeks compared to when each agent used alone. Added benefits can be obtained through combining self-assembling peptide with other remineralzing agents allowing faster and enhanced regeneration of non-cavitated caries lesions

Dvanaestomjesečna klinička procjena: debeloslojni kompozit ojačan vlaknima u usporedbi sa slojevito apliciranim nanohibridnim kompozitom za restauraciju dubokih aproksimalnih lezija na trajnim kutnjacima – randomizirano kontrolirano istraživanje

Objective: The present clinical trial was conducted to evaluate the clinical performance of the biomimetic, bilayered structure utilizing a fiber reinforced bulk fill resin composite with a nanohybrid capping layer, compared to incremental packing of nanohybrid resin composite, in deep proximal cavities in permanent molars. Materials and methods: A total of 36 deep proximal cavities in vital molars were restored either with a bilayered structure of fiber reinforced composite resin as a dentine substitute and a capping layer of nanohybrid composite resin (n=18) or conventional, nanohybrid composite resin incrementation (n=18). The restorations were assessed over a period of 12 months using the modified USPHS criteria. The criteria evaluated were: fracture and retention, marginal integrity, marginal discoloration, anatomic form, proximal contact, surface texture, radiographic evaluation, postoperative sensitivity and secondary caries. Results: There was no statistically or clinically significant difference between fiber-reinforced resin composite and conventional incremental resin composite. There was no risk for failure regarding all the evaluated modified USPHS criteria for both materials after 12 months (RR= 1(95% CI 0.0209 to 47.8503; P =1.0000)). Conclusion: The biomimetic approach utilizing a fiber reinforced resin composite dentine substitute showed a comparable clinical performance to nanohybrid resin composite incrementation. Bulk fill fiber reinforced resin composite is an efficient alternative in restoration of deep proximal cavities in posterior teeth. Further long term studies are necessary to confirm these results.Svrha rada: Ovo kliničko istraživanje provedeno je da bi se procijenila klinička učinkovitost biomimetičke, dvoslojne strukture debeloslojnoga kompozita ojačanoga vlaknima s nanohibridnim pokrovnim slojem u usporedbi sa slojevito apliciranom nanohibridnim kompozitom u dubokim aproksimalnim kavitetima trajnih kutnjaka. Materijal i metode: Ukupno 36 dubokih aproksimalnih kaviteta na vitalnim kutnjacima restaurirano je ili dvoslojnom strukturom debeloslojnoga kompozita ojačanoga vlaknima kao zamjenom za dentin i pokrovnim slojem nanohibridnoga kompozita (n = 18), ili konvencionalnim nanohibridnim kompozitnim materijalom (n = 18) ). Korištenjem modificiranih kriterija USPHS-a, restauracije su se procjenjivale tijekom 12 mjeseci. Kriteriji koji su se procjenjivali bili su fraktura i retencija, rubni integritet, rubna diskoloracija, anatomski oblik, aproksimalni kontakt, tekstura površine, radiološka procjena, postoperativna osjetljivost i sekundarni karijes.Rezultati: Nije bilo statistički i klinički značajne razlike između debeloslojnoga kompozita ojačanoga vlaknima i konvencionalnoga kompozita za slojevitu tehniku. Nije bilo rizika od neuspjeha kod svih procijenjenih modificiranih kriterija USPHS-a za oba materijala nakon 12 mjeseci (RR = 1 (95 % CI 0,0209 do 47,8503; P =1,0000). Zaključak: Biomimetički pristup u kojemu se primjenjuje tehnika nadomještanja dentina debeloslojnim kompozitom ojačanim vlaknima pokazao je kliničku učinkovitost usporedivu sa slojevitom aplikacijom nanohibridne kompozitne smole. Debeloslojni kompoziti ojačani vlaknima učinkovita su alternativa u restauraciji dubokih aproksimalnih kaviteta stražnjih zuba, no za potvrdu tih rezultata potrebna su daljnja dugoročna istraživanja

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Spectacle measurements versus contact lens measurements of the angle of deviation in myopic patients with strabismus

Purpose To compare the measurements of the angle of deviation through spectacles versus contact lenses and with the theoretically calculated angle. Patients and methods A total of 20 patients with comitant strabismus, more than 20 PD with spectacles, associated with bilateral myopia (spherical equivalent >1 D in both eyes) were included. Angle of deviation was measured using prism and cover test with spectacles and with contact lenses fitted according to the cycloplegic refraction and refined by subjective refraction. Agreements between the measurements obtained with contact lenses and those obtained with spectacles as well as the theoretically calculated angle were analyzed. Results The mean age was 15.6±10.9 years. Average spherical equivalent was −9.1±4.2 D. Measurements obtained with contact lenses were significantly lower than those with spectacles (P<0.001) with coefficient of variation of 27.7%, indicating poor agreement of both measurements. Limits of agreement in Bland–Altman plots were more than 9 PD ([INLINE:1] ± 2 s, −8.8 to 6 PD). The agreement was lower with larger angles. Measurements obtained with contact lenses were significantly lower than theoretical angles (P=0.002) but coefficient of variation between both measurements was 8.8%, indicating good agreement of measurements. There was little systematic or proportionate bias between the contact lens measurements and the theoretical angle. Conclusions Contact lens measurements were significantly lower than spectacle measurements in myopic patients. The contact lens measurements were in good agreement with the theoretically calculated angle. This overestimation of the angle with spectacles might be responsible for overcorrection of myopic patients with exotropia after surgery

Fault-Tolerant high-rate ethernet-based networked control system

[abstract not available