Sagittal, rotational and transverse changes with three intraoral distalization force systems : Jones jig, distal jet and first class

To compare the maxillary dentoalveolar changes of patients treated with three distalization force systems: Jones Jig, Distal Jet and First Class appliances, using digitized models. The retrospective sample comprised 118 digitized models of 59 patients

Class II malocclusion treatment changes with the Jones jig, Distal jet and First Class appliances

Objective: Maxillary molar distalization with intraoral distalizer appliances is a non-extraction orthodontic treatment used to correct molar relationship in patients with Class II malocclusion presenting maxillary dentoalveolar protrusion and minor skeletal discrepancies. This study compares the changes caused by three distalizers with different force systems. Methodology: 71 patients, divided into three groups, were included. The Jones jig group (JJG, n=30; 16 male, 14 female, 13.17 years mean age) was treated with the Jones jig for 0.8 years. The Distal jet group (DJG, n=25; 8 male, 17 female, 12.57 years mean age) was treated with the Distal jet for 1.06 years. The First Class group (FCG, n=16; 6 male, 10 female, 12.84 years mean age) was treated with the First Class for 0.69 years. Intergroup treatment changes were compared using one-way ANOVA, followed by post-hoc Tukey’s tests. Results: Intergroup comparisons showed significantly greater maxillary incisor protrusion in DJG than in FCG (2.56±2.24 mm vs. 0.74±1.39mm, p=0.015). The maxillary first premolars showed progressive and significantly smaller mesial angulation in JJG, FCG and DJG, respectively (14.65±6.31º, 8.43±3.99º, 0.97±3.16º; p<0.001). They also showed greater mesialization in JJG than FCG (3.76±1.46 mm vs. 2.27±1.47 mm, p=0.010), and greater extrusion in DJG compared to JJG (0.90±0.77 mm vs 0.11±0.60 mm, p=0.004). The maxillary second premolars showed progressive and significantly smaller mesial angulation and mesialization in JJG, FCG and DJG, respectively (12.77±5.78º, 3.20±3.94º, -2.12±3.71º and 3.87±1.34 mm, 2.25±1.40 mm, 1.24±1.26 mm, respectively; p<0.001). DJG showed smaller distal angulation of maxillary first molars (-2.14±5.09º vs. -7.73±4.28º and -6.05±3.76º, for the JJG and FCG, respectively; p<0.001) and greater maxillary second molars extrusion (1.17±1.41 mm vs -0.02±1.16 mm and 0.16±1.40 mm, for the JJG and FCG, respectively; p=0.003). Overjet change was significantly larger in DJG compared to FCG (1.79±1.67 mm vs 0.68±0.84; p=0.046). Treatment time was smaller in FCG (0.69±0.22 years vs 0.81±0.33 years and 1.06±0.42 years, comparing it with the JJG and DJG, respectively; p=0.005). Conclusion: The three appliances corrected the Class II molar relationship by dentoalveolar changes. The Distal jet produced smaller molar distal angulation than the Jones jig and First Class. The First Class appliance showed less anchorage loss, greater percentage of distalization and shorter treatment time than the Jones jig and Distal jet

Trickle infection with Heligmosomoides polygyrus results in decreased worm burdens but increased intestinal inflammation and scarring

IntroductionIntestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known.ResultsUsing a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels of Adamts gene expression.DiscussionTo our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

<i>In vitro</i> antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

BackgroundCurrent approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity.MethodsSARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19.ResultsDaclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans.ConclusionsDaclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Comparative cephalometric study of Class II malocclusion treatment with the pendulum and jones jig appliances followed by fixed corrective orthodontics

A proposta deste estudo foi comparar cefalometricamente os efeitos esqueléticos e dentoalveolares no tratamento da má oclusão de Classe II com os distalizadores Pendulum e Jones jig, seguidos do aparelho fixo corretivo e compará-los ao grupo controle. O grupo 1 foi composto de 23 pacientes com Classe II tratados com o distalizador Pendulum seguido do aparelho fixo corretivo, sendo que do número total de pacientes, 19 foram comparados ao grupo Jones jig, apresentando média de idade inicial de 13,86 anos; 18 pacientes foram comparados com os grupos Jones jig e controle, com média de idade inicial de 13,92 anos. O grupo 2 compreendeu 25 pacientes com Classe II tratados com o distalizador Jones jig seguido do aparelho fixo corretivo, com média de idade inicial de 12,90 comparados aos grupos Pendulum e controle; porém, somente 21 pacientes foram comparados com o grupo Pendulum, com média de idade inicial de 13,08 anos. Os pacientes foram dessa forma divididos a fim de compatibilizar média de idade inicial e tempo de tratamento, conferindo confiabilidade ao estudo comparativo. O grupo 3 compreendeu 19 jovens com má oclusão de Classe II não tratada e média de idade inicial de 12,88 anos. Os dois grupos experimentais foram avaliados individualmente por meio do teste ANOVA dependente e teste de Tukey, a fim de verificar as alterações intragrupos nos tempos inicial (T1), pós-distalização (T2) e final do aparelho fixo (T3). Os grupos experimentais foram também comparados por meio do teste t de Student nos três tempos avaliados e nas alterações entre as fases T2-T1 e T3-T2. Por fim, os grupos experimentais foram comparados ao grupo controle por meio do teste ANOVA a um critério e teste de Tukey, com o intuito de diferenciar as alterações do tratamento das alterações ocorridas pelo crescimento craniofacial. Os resultados demonstraram que os distalizadores não interferem no componente maxilar e mandibular, ou seja, não promovem alterações na relação maxilomandibular. Quanto à correção da Classe II, ambos os aparelhos promovem uma distalização eficiente dos primeiros molares, contudo o grupo Jones jig demonstrou maior perda de ancoragem, representada pela mesialização e extrusão significante dos primeiros e segundos pré-molares, provavelmente em virtude das diferenças no reforço de ancoragem e que resultou um maior aumento da AFAI ao final do tratamento. Os segundos molares superiores, após a distalização apresentaram maior distalização angular e linear e maior intrusão quando comparados ao grupo Jones jig. Comprovou-se que os efeitos adversos ocorridos na fase de distalização intrabucal são posteriormente corrigidos durante a mecânica corretiva. Em comparação ao grupo controle, ao final do tratamento ortodôntico, observou-se que o grupo Pendulum apresentou um crescimento maior da maxila e mandíbula, justificada provavelmente pela diferença significante na idade final entre os grupos. Verificou-se uma vestibularização significantemente maior dos incisivos inferiores nos grupos experimentais, ocorrido provavelmente pelo uso de elásticos de Classe II. Ao final do tratamento, foi observada a correção do trespasse horizontal e vertical nos grupos experimentais, alterações já esperadas na mecânica corretiva, contudo a distalização dos molares superiores seguida do aparelho fixo corretivo não promoveu alterações significantes no componente tegumentar.The purpose of this study was to compare cephalometric skeletal and dentoalveolar effects in the treatment of Class II malocclusion with Pendulum and Jones jig appliances, followed by fixed orthodontic appliances, and to compare it to a control group. Group 1 comprised 23 Class II patients treated with the Pendulum and fixed appliances; being that the total number of patients,19 were compared to the Jones jig group, at a mean initial age of 13.86 years; 18 patients were compared with the Jones jig and control groups, at a mean initial age of 13.92 years. Group 2 comprised 25 Class II patients treated with the Jones jig and fixed appliances, at a mean initial age of 12.90 years, compared to Pendulum and control groups; however, only 21 patients were compared only to the Pendulum group, at a mean initial age of 13.08 years. Patients were divided in this way in order to match average initial age and length of treatment, giving reliability to the comparative study. Group 3 comprised 19 young subjects with untreated Class II malocclusions. The two experimental groups were individually evaluated by dependent ANOVA and Tukey tests, to verify the intragroup changes among the initial (T1), postdistalization (T2) and end of fixed appliance (T3) stages. The experimental groups were also compared with t tests in the three times evaluated and the changes between T2-T1 and T3-T2. Finally, the experimental groups were compared to the control group by one-way ANOVA and Tukey tests in order to differentiate treatment changes from the craniofacial growth normal changes. Results showed that the appliances did not interfere in the maxillary and mandibular components, i.e., did not promote changes in the maxillomandibular relationship. Regarding the correction of the Class II, both devices promoted an efficient distalization of the maxillary first molars, but Jones jig group showed greater anchorage loss, represented by significant mesial movement and extrusion of the first and second premolars, probably due to differences in anchorage reinforcement and resulting in a greater increase in the LAFH at the end of treatment. The maxillary second molars after distalization were more angularly and linearly distalized and intruded than the Jones jig group. It was proved that the adverse effects that occurred during the intraoral distalization are subsequently corrected during the corrective mechanics. Compared to the control group at the end of orthodontic treatment, we observed that the Pendulum group had a greater maxillomandibular growth, probably justified by significant differences in the final ages between the groups. There was a significantly greater tipping of mandibular incisors and first molars in the experimental groups, probably due to the use of Class II elastics. At the end of treatment, it was observed the correction of the overjet and overbite in the experimental groups, changes already expected in the mechanical correction, however the distalization of maxillary molars followed by fixed corrective orthodontics did not promote significant changes in the soft tissue