Effects of activator treatment - evidence for the occurrence of two different types of reaction

A longitudinal cephalometric study was made of 12 boys and 13 girls with Class 11, Division 1 malocclusion treated with activators. The findings were compared with an untreated control group of 24 boys and 15 girls. The children were aged about 9 years at the start of the investigation and they were treated, or observed, for about two years. Possible alterations of mandibular condylar growth were investigated and the results were compared with previously published hypotheses on the mode of action of the activator. Since there were significant differences in the growth increments of control boys and control girls, the sexes were treated statistically as separate groups. Mandibular growth was found to be altered by activator therapy; in the boys growth was increased and redirected posteriorly while in the girls growth was only redirected. The maxilla and the dental arches were differently affected by the treatment. The differences in the observed results are probably explained by variation in the amount of vertical activation of the appliance but the possibility that boys and girls generally react differently could not be excluded. It is also possible that at least some of the differences were due to special growth patterns associated with certain features in the initial cephalometric pattern. There was no indication that modes of appliance action led to the different reactions. The results as a whole support the concept of the activator as an appliance which transduces elastic soft tissue forces to the skeletal and dental unit

Malformations of the tooth root in humans

The most common root malformations in humans arise from either developmental disorders of the root alone or disorders of radicular development as part of a general tooth dysplasia. The aim of this review is to relate the characteristics of these root malformations to potentially disrupted processes involved in radicular morphogenesis. Radicular morphogenesis proceeds under the control of Hertwig's epithelial root sheath (HERS) which determines the number, length, and shape of the root, induces the formation of radicular dentin, and participates in the development of root cementum. Formation of HERS at the transition from crown to root development appears to be very insensitive to adverse effects, with the result that rootless teeth are extremely rare. In contrast, shortened roots as a consequence of impaired or prematurely halted apical growth of HERS constitute the most prevalent radicular dysplasia which occurs due to trauma and unknown reasons as well as in association with dentin disorders. While odontoblast differentiation inevitably stops when growth of HERS is arrested, it seems to be unaffected even in cases of severe dentin dysplasias such as regional odontodysplasia and dentin dysplasia type I. As a result radicular dentin formation is at least initiated and progresses for a limited time. The only condition affecting cementogenesis is hypophosphatasia which disrupts the formation of acellular cementum through an inhibition of mineralization. A process particularly susceptible to adverse effects appears to be the formation of the furcation in multirooted teeth. Impairment or disruption of this process entails taurodontism, single-rooted posterior teeth, and misshapen furcations. Thus, even though many characteristics of human root malformations can be related to disorders of specific processes involved in radicular morphogenesis, precise inferences as to the pathogenesis of these dysplasias are hampered by the still limited knowledge on root formation

Abnormal mandibular growth and the condylar cartilage

Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their oftendisfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritits (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilag

Principles of cartilage tissue engineering in TMJ reconstruction

Diseases and defects of the temporomandibular joint (TMJ), compromising the cartilaginous layer of the condyle, impose a significant treatment challenge. Different regeneration approaches, especially surgical interventions at the TMJ's cartilage surface, are established treatment methods in maxillofacial surgery but fail to induce a regeneration ad integrum. Cartilage tissue engineering, in contrast, is a newly introduced treatment option in cartilage reconstruction strategies aimed to heal cartilaginous defects. Because cartilage has a limited capacity for intrinsic repair, and even minor lesions or injuries may lead to progressive damage, biological oriented approaches have gained special interest in cartilage therapy. Cell based cartilage regeneration is suggested to improve cartilage repair or reconstruction therapies. Autologous cell implantation, for example, is the first step as a clinically used cell based regeneration option. More advanced or complex therapeutical options (extracorporeal cartilage engineering, genetic engineering, both under evaluation in pre-clinical investigations) have not reached the level of clinical trials but may be approached in the near future. In order to understand cartilage tissue engineering as a new treatment option, an overview of the biological, engineering, and clinical challenges as well as the inherent constraints of the different treatment modalities are given in this paper

Effect of Bilateral Mandibular Osteodistration on the Condylar Cartilage: An Experimental Study on Rabbits

Although various aspects of bone formation during distraction osteogenesis have been studied extensively, there are only limited experimental data concerning the influence of hyper-physiologic mandibular distraction rate on structural alterations in the temporomandibular joint (TMJ) condylar cartilage. The purpose of this study was to evaluate the effect of bilateral distraction osteogenesis of the mandibular body, at a hyper-physiologic rate and length, on the integrity of the condylar cartilage in rabbits. MATERIALS AND METHODS: Eighteen healthy adult male rabbits weighing 2 to 3 kg were assigned to 1 of 2 groups: the control group (n = 2 rabbits, 4 joints) or the study group (n = 16 rabbits, 32 joints) four rabbits (8 joints) in each subgroup according to the post-distraction period (1,2,3 or 4 weeks). In the control group, rabbits received sham surgery (Osteotomy without distraction) and then left to live for 4 weeks under the same condition of the study group then euthanized using intravenous overdose of pentobarbital sodium. In the study group, an extra oral custom-made distracter was employed to achieve bilateral mandibular hyper physiologic distraction (1.5 mm twice daily for 5 days) distraction. All animals were evaluated clinically and histomorphometrically and results analyzed by MINITABE 13.1 statistical package using ANOVA test. RESULTS: Animals underwent distraction showed obvious changes in condylar surface contour related to length of the follow up period, compared to the control; these changes seemed to be partly reversible. The most pronounced observation was the irregularities and resorption in the anterior part of the condylar cartilage and the subcondylar bone. Moreover, at the first two weeks, the area of resorption was invaded by large number of osteoclasts and chronic inflammatory cells which declined later in the 3rd and 4th weeks and replaced with osteoblastic activities. CONSLUSION: These experimental data showed that distraction rate of 3 mm per day may lead to degenerative or even early arthritic changes in the TMJ condylar cartilage in the 1st and 2nd post-distraction weeks. However, all condyles showed adaptive and remodeling sings in the following 3rd and 4th weeks

Fatores de risco cardiovascular em pessoas semabrigo e na população geral da cidade do Porto, Portugal

We described the distribution of risk factors for cardiovascular disease among homeless people living in the city of Porto, Portugal. Comparisons were made between subsamples of homeless people recruited in different settings and between the overall homeless sample group and a sample of the general population. All "houseless" individuals attending one of two homeless hostels or two institutions providing meal programs on specific days were invited to participate and were matched with subjects from the general population. We estimated sex, age and education-adjusted prevalence ratios or mean differences. The prevalence of previous illicit drug consumption and imprisonment was almost twice as high among the homeless from institutions providing meal programs. This group also showed lower mean systolic and diastolic blood pressure. Prevalence of smoking was almost 50% higher in the overall homeless group. Mean body mass index and waist circumference were also lower in the homeless group and its members were almost five times less likely to report dyslipidemia. Our findings contribute to defining priorities for interventions directed at this segment of society and to reducing inequalities in this extremely underprivileged populatio

Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis

Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential

The role of DNA microarrays in Toxoplasma gondii research, the causative agent of ocular toxoplasmosis

Ocular toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii, is the leading cause of retinochoroiditis. Toxoplasma is an obligate intracellular pathogen that replicates within a parasitophorous vacuole. Infections are initiated by digestion of parasites deposited in cat feces or in undercooked meat. Parasites then disseminate to target tissues that include the retina where they then develop into long-lived asymptomatic tissue cysts. Occasionally, cysts reactivate and growth of newly emerged parasites must be controlled by the host’s immune system or disease will occur. The mechanisms by which Toxoplasma grows within its host cell, encysts, and interacts with the host’s immune system are important questions. Here, we will discuss how the use of DNA microarrays in transcriptional profiling, genotyping, and epigenetic experiments has impacted our understanding of these processes. Finally, we will discuss how these advances relate to ocular toxoplasmosis and how future research on ocular toxoplasmosis can benefit from DNA microarrays

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health