GLP-1 increases heart rate by a direct action on the sinus node.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear. METHODS AND RESULTS: We employed a large animal model, the female landrace pig, and used multiple in-vivo and ex-vivo approaches including pharmacological challenges, electrophysiology and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate. In anaesthetized pigs, neither cervical vagotomy, adrenergic blockers (alpha, beta or combined alpha-beta blockade), ganglionic blockade (hexamethonium) nor inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ivabradine) abolished the marked chronotropic effect of GLP-1. GLP-1 administration to isolated perfused pig hearts also increased heart rate, which was abolished by GLP-1 receptor blockade. Electrophysiological characterization of GLP-1 effects in vivo and in isolated perfused hearts localized electrical modulation to the atria and conduction system. In isolated sinus nodes, GLP-1 administration shortened action potential cycle length of pacemaker cells and shifted the site of earliest activation. The effect was independent of HCN blockade. Collectively, these data support a direct effect of GLP-1 on GLP-1 receptors within the heart. Consistently, single nucleus RNA sequencing (snRNAseq) showed GLP-1 receptor expression in porcine pacemaker cells. Quantitative phosphoproteomics analyses of sinus node samples revealed that GLP-1 administration leads to phosphorylation changes of calcium cycling proteins of the sarcoplasmic reticulum, known to regulate heart rate. CONCLUSION: GLP-1 has direct chronotropic effects on the heart mediated by GLP-1 receptors in pacemaker cells of the sinus node, inducing changes in action potential morphology and the leading pacemaker site through a calcium signaling response characterized by PKA-dependent phosphorylation of Ca2+ cycling proteins involved in pace making. Targeting the pacemaker calcium clock may be a strategy to lower heart rate in GLP-1 RA recipients.

Prevalence of malocclusions requiring treatment according to the KIG classification : A multipart cross-sectional study over a 20-year period in the district of Viersen/North Rhine.

BACKGROUND AND AIM: In Germany, the reimbursement of orthodontic treatment costs within the framework of the statutory health insurance (GKV) was restricted on 01 January 2002 by the introduction of the orthodontic indication groups (KIG). The aim of this study was to evaluate the prevalence of findings requiring treatment in a specialist practice over a 20-year period. The results were then compared with data from existing older studies. PATIENTS AND METHODS: The distribution of treatment-eligible KIG (KIG classifications grades 3-5) among patients with statutory health insurance in an orthodontic practice in North Rhine was determined over a 20-year period (2002-2021) after the introduction of the KIG system. This period was additionally scrutinized in four 5­year periods according to the operating cycles of the practice. Findings were classified into the highest of 19 possible KIG treatment needs levels. Multiple classifications were not made. RESULTS: Orthodontic treatment was indicated in a total of 4537 (2393 female, 2144 male) patients according to current statutory health insurance guidelines. The KIG classification "D" (increased overjet) was the most frequent within the observed 20 years with 24.3%. Among 11 KIG classifications, 86.1% of the 6 most frequent and 13.9% of the 5 rarest findings were observed constantly over all periods. Of 19 possible indications, "D4" was the most frequent with 19.6%. Of 4537 patients, 20.7% had KIG grade 3, 63.6% KIG grade 4 and 15.7% KIG grade 5. The prevalence of sagittal deviations "D" and "M" was 35.0%, transverse "B" and "K" 17.9% and vertical "O" and "T" 3.7%. Tooth position anomalies "E" and "P" had a share of 24.6%. CONCLUSIONS: The present study confirms existing findings as well as the nationwide data of the National Association of Statutory Health Insurance Dentists (KZBV) from 2020: The sagittal deviations "D" (increased overjet) and "M" (negative overjet) represented the most frequent findings with KIG D4 as the most common classification. The prevalence and age distribution of KIG grades 3-5 requiring treatment corresponded to nationwide comparative data.

Modifications to the parasitological technique of Rugai increase the diagnostic sensitivity for strongyloidiasis.

Strongyloidiasis is a neglected tropical disease caused mainly by Strongyloides stercoralis, a nematode that can persist for decades in the human host with a very low parasitic burden and without specific symptoms. Hence, it is difficult to diagnose and control. Larval concentration and culture methods with fecal samples show higher sensitivity for the diagnosis of Strongyloides-infected individuals; however, these techniques are not routinely used, primarily due to the challenges associated with processing a substantial volume of fecal samples. In the current study, we comparatively evaluated the sensitivity and applicability of modifications made to the Rugai parasitological method for the diagnosis of strongyloidiasis in fecal samples of experimentally infected rats and in 68 individuals from an urban community close to Maceió, Brazil. The presence and quantity of parasite larvae in the feces were comparatively evaluated using different parasitological techniques. In the experimental model, we demonstrated that the modified Rugai technique (RMOD) allowed for significantly higher recovery of larvae than the original Rugai technique (RO). Moreover, the sediment was cleaner and easier to evaluate using optical microscopy. Compared to other parasitological techniques, such as agar-plate culture (A-PC) and spontaneous sedimentation (SS), the RMOD technique showed higher sensitivity in the detection of larvae in all infected groups and presented comparatively better performance, especially in rats with a low parasite burden. In the human population, among the 68 stool samples evaluated, Strongyloides larvae were detected in the feces of six individuals with an estimated prevalence of 8.82%. However, the performance of each parasitological method was remarkably different. SS identified Strongyloides larvae in only two individuals and A-PC in three, whereas RMOD was able to identify six infected individuals, resulting in sensitivities of 33.3%, 50%, and 100%, respectively. In conclusion, the modifications introduced to the Rugai technique resulted in improved sensitivity for the detection of Strongyloides spp. infections, especially in stool samples with a low parasite burden, in comparison with other routinely used parasitological techniques.

Prevalence of KIG-grades 3-5 in an orthodontic practice in North Rhine Westphalia compared with results of the DMS•6 and with KZBV data.

BACKGROUND AND AIM: The prevalence of tooth and jaw malocclusions in 8- to 9-year-olds was surveyed in a nationwide setting as part of the orthodontic module of the Sixth German Study on Oral Health (DMS•6), using the orthodontic indication groups (KIG) as index. Aim of this study was the detection of the prevalence of malocclusions requiring treatment according to the KIG index in statutorily insured patients of an orthodontic practice in North Rhine Westphalia, Germany, and to compare results with corresponding DMS•6 and KZBV data. PATIENTS AND METHODS: Between 2017-2021, n = 953 statutorily insured patients called for an initial consultation and subsequent determination of the KIG-classification and -grades. The malocclusions were classified and graded in the highest possible KIG-grade according to valid SHI guidelines. Multiple classifications were not recorded. KIG-grade > 3 according to the valid guidelines was detected in n = 815 patients. Since the DMS•6 does not contain information on KIG classifications "U" and "S", their inclusion was waived despite evaluation, leaving data from n = 683 patients for analysis and comparison. RESULTS: During the study period, n = 235 patients (34.4%) had KIG-classification "D". More than 10% were classified as "K" (120 patients, 17.6%), "P" (98 patients, 14.2%), "M" (89 patients, 13.0%), and "E" (81 patients, 11.9%). Of 16 possible classifications with KIG-grade > 3, "D4" was the most common with 26.6% (182 patients). The results confirm the findings from the multicentric DMS•6 from2021 and corresponding KZBV data from 2020. CONCLUSIONS: Sagittal deviations described by classifications "D" and "M" represent with 47.4% almost half of the malocclusions with treatment need. KIG-grade D4 is the most frequent classification. There were no regional deviations of the prevalence of KIG-grades 3-5 in the district of Viersen / North Rhine compared with the national average, not even when scrutinizing a five-year-period.

Outcome differences after orthodontic camouflage treatment in hypo- and hyperdivergent patients - A retrospective cephalometric investigation.

OBJECTIVES: To compare differences in outcome in skeletal and dental parameters in hypo- and hyperdivergent Class II patients after extraction of upper first premolars and comprehensive orthodontic treatment. MATERIALS AND METHODS: 37 Class-II-patients with dental camouflage treatment were divided into a hypo- (n = 18) or a hyperdivergent (n = 19) group depending on the mandibular plane angle (hypo: < 34° or hyper: ≥ 34°). Lateral cephalograms were available before (T1) and after (T2) treatment and were analyzed with customized measurements. Data from a growth survey served as a control and were used to calculate the actual treatment effect. Data were analyzed by one-sample Student's t-tests and independent Student's t-tests. Statistical significance was set at p < 0.05. RESULTS: The measurements showed similar changes in both groups. The effects were mainly dentoalveolar. Hypodivergent patients showed an almost equal increase in anterior and posterior facial height, while hyperdivergent patients only showed an increase in anterior facial height. CONCLUSIONS: In hyperdivergent patients, the anterior facial height increases despite camouflage treatment. This indicates a tendency towards bite opening and backward rotation of the mandible. Hypodivergent patients do not experience deepening of the bite. CLINICAL RELEVANCE: In hyperdivergent patients with upper first premolars extraction the anterior facial height increased differently than in hypodivergent patients. This should be considered if a bite opening is a possible contraindication to treatment.

Frequency and severity of malocclusions in patients with statutory health insurance in a German orthodontic practice in North Rhine Westphalia - a multi-part cross-sectional study over a 20-year period.

OBJECTIVE: Since 2002, patients with statutory health insurance in Germany must undergo an assessment of orthodontic treatment need using the "Kieferorthopädische Indikationsguppen" (KIG; orthodontic indication groups) classification system. According to this system, tooth and jaw misalignment are divided into 11 subgroups and five grades. The objectives of this study were to determine the distribution of KIG classifications in patients with statutory insurance of a German orthodontic practice (North Rhine, Germany) and to analyze changes over a 20-year period. MATERIALS AND METHODS: Since the introduction of the KIG index in 2002, 4940 statutorily insured patients over a 20-year period (2330 m, 2610 f, min 3.2, max 49.5 years, peak between 10 and 12 years) were classified at their first appointment. According to the valid guidelines of the statutory health insurance (GKV), the division was made into the highest possible KIG classification. Multiple entries were thus not made. In accordance with the operating cycles of the practice, the progression was divided into four 5-year periods. RESULTS: Over a 20-year period, 24.98% of the patients were assigned to the classification "D". 86.52% of the patients were among the 6 most frequently ("D", "E", "K", "S", "P" and "M", > 10% each) and only 13.49% among the 5 least frequently recorded classifications ("U", "B", "T", "O" and "A", < 5% each). CONCLUSION: The distribution of the 6 most frequent and the 5 least frequent KIG classifications was constant over a 20-year-period. Among all possible tooth and jaw misalignment variants, the sagittal classifications "D" and "M" represent the most frequent malocclusions. CLINICAL RELEVANCE: The results and their comparison with historical data show that both frequency and severity of tooth and jaw misalignment with orthodontic treatment need appear identical for patients with statutory health insurance over a 20-year period.

Evaluation of isotype-based serology for diagnosis of Schistosoma mansoni infection in individuals living in endemic areas with low parasite burden.

Intestinal schistosomiasis is a chronic and debilitating disease that affects public health systems worldwide. Control interventions to reduce morbidity primarily involve the diagnosis and treatment of infected individuals. However, the recommended Kato-Katz (KK) parasitological method shows low sensitivity in individuals with low parasite loads and is not useful for monitoring elimination of parasite transmission at later stages. In the current study, we evaluated the accuracy of serum reactivity levels of different immunoglobulin isotypes in an enzyme-linked immunosorbent assay (ELISA), utilizing Schistosoma mansoni crude extracts, with the aim to improve the diagnosis of infected individuals with low parasite loads. The serum reactivity of IgM and IgG subclass antibodies (IgG1, IgG3, and IgG4) against soluble adult worm and egg antigen preparations was evaluated in residents from a schistosomiasis-endemic area in northern Minas Gerais, Brazil. The parasitological status of the study population was determined through fecal examination with multiple parasitological tests to create a consolidated reference standard (CRS) plus a fecal DNA detection test (q-PCR). Twelve months after praziquantel treatment, a second serum sample was obtained from the population for reexamination. A two-graph receiver operating characteristic curve (TG-ROC) analysis was performed using the serum reactivity of non-infected endemic controls and egg-positive individuals, and the cut-off value was established based on the intersection point of the sensibility and specificity curves in TG-ROC analyses. The diagnostic accuracy of each serological test was evaluated in relation to the parasitological CRS and to the combination of CRS plus qPCR results. The data revealed that serum reactivity of IgM and IgG3 against S. mansoni antigens did not allow identification of infected individuals from the endemic area. In contrast, serum IgG1 and IgG4-reactivity against schistosome antigens could distinguish between infected and non-infected individuals, with AUC values ranging between 0.728-0.925. The reactivity of IgG4 anti-soluble egg antigen - SEA (sensitivity 79 %, specificity 69 %, kappa = 0.49) had the best diagnostic accuracy, showing positive reactivity in more than 75 % of the infected individuals who eliminated less than 12 eggs per gram of feces. Moreover, serum IgG4 reactivity against SEA and against soluble worm antigen preparation (SWAP) was significantly reduced in the serum of infected individuals after 12 months of confirmed parasitological cure and in the absence of re-infection. These results reinforce that the described IgG4 anti-SEA ELISA assay is a sensitive alternative for the diagnosis of active intestinal schistosomiasis in individuals from endemic areas, including in those with a very low parasite load.

Schistosoma and Leishmania: An Untold Story of Coinfection.

A remarkable characteristic of infectious diseases classified as Neglected Tropical Diseases (NTDs) is the fact that they are mostly transmitted in tropical and subtropical regions with poor conditions of sanitation and low access to healthcare, which makes transmission areas more likely to overlap. Two of the most important NTDs, schistosomiasis and leishmaniasis, despite being caused by very different etiological agents, have their pathogenesis heavily associated with immune-mediated mechanisms, and Schistosoma spp. and Leishmania spp. have been shown to simultaneously infect humans. Still, the consequences of Schistosoma-Leishmania coinfections remain underexplored. As the inflammatory processes elicited by each one of these parasites can influence the other, several changes have been observed due to this coinfection in naturally infected humans, experimental models, and in vitro cell assays, including modifications in susceptibility to infection, pathogenesis, prognostic, and response to treatment. Herein, we review the current knowledge in Schistosoma-Leishmania coinfections in both human populations and experimental models, with special regard to how schistosomiasis affects tegumentary leishmaniasis, discuss future perspectives, and suggest a few steps to further improve our understanding in this model of parasite-host-parasite interaction.

Effects of fixed functional orthodontic treatment in hypodivergent and hyperdivergent class II patients-a retrospective cephalometric investigation.

OBJECTIVE: To compare skeletal and dentoalveolar changes after orthodontic treatment of class II malocclusion in patients with hypodivergent and hyperdivergent growth patterns through cast splint fixed functional appliances (FFA). MATERIALS AND METHODS: N = 42 out of n = 47 patients with mandibular plane angles < 34° or ≥ 34° were divided into a hypodivergent (n = 24) and a hyperdivergent (n = 18) group. All patients received a single-step mandibular advancement protocol through an FFA. Lateral cephalograms were analyzed after initial leveling and alignment (T1) and immediately after FFA removal (T2). The therapeutic effect was calculated through comparison with age-matched controls from a growth survey. Statistical significance was set at p < 0.05. RESULTS: Hypodivergent and hyperdivergent patients showed different treatment outcomes, but significant differences existed only for overbite and interincisal angle. Nearly all measurements suggested similar treatment-related changes for both groups with exception for dentoalveolar parameters. CONCLUSION: Treatment with FFA causes similar skeletal and dentoalveolar effects in hypodivergent and in hyperdivergent patients. The correction of overjet and molar relationship is mainly caused by dentoalveolar changes. CLINICAL RELEVANCE: Hyperdivergent patients do not respond unfavorably to FFA treatment compared to hypodivergent patients. Lower incisor protrusion occurs more pronounced in hypodivergent patients. The growth pattern ought to be considered when choosing FFA for class II treatment.

Development and evaluation of an indirect ELISA using a multiepitope antigen for the diagnosis of intestinal schistosomiasis.

The laboratory diagnosis of intestinal schistosomiasis, carried out by detecting parasite eggs in feces, has low sensitivity when applied to individuals with low parasitic load. Serological tests can be more sensitive for the diagnosis of the disease. Therefore, the objective of this work was to develop and evaluate an ELISA-based immunoenzymatic assay, using a Schistosoma mansoni multiepitope antigen (ELISA IgG anti-SmME). For this, the amino acid sequences of S. mansoni cathepsin B and asparaginyl endopeptidase were submitted to the prediction of B cell epitopes and, together with peptide sequences obtained from earlier works, were used in the construction of a minigene. The multiepitope protein was expressed in Escherichia coli and the performance of the ELISA IgG anti-SmME for schistosomiasis was evaluated using serum samples from 107 individuals either egg positive or negative. In addition, 11 samples from individuals with other helminth infections were included. The ELISA IgG anti-SmME showed a sensitivity of 81.1% and a specificity of 46.1%. Further analysis revealed a 77.2% sensitivity in diagnosis of individuals with egg counts of ≤12 epg (eggs per gram feces) and 87.5% for individuals with 13­99 epg. It is worth mentioning that, to our knowledge, this was the first study using a multiepitope recombinant antigen in an ELISA for diagnosis of intestinal schistosomiasis, which demonstrated promising results in the diagnosis of individuals with low parasitic loads.

Long-Term Training Increases Atrial Fibrillation Sustainability in Standardbred Racehorses.

Atrial fibrillation (AF) is more prevalent in athletes, and currently, the mechanisms are not fully understood. Atrial fibrillation inducibility and stability was investigated in trained and untrained Standardbred racehorses. The horses underwent echocardiography for evaluation of atrial size. High-density mapping during AF was performed, and the presence of structural remodeling, as well as the expression of inflammatory and pro-inflammatory markers in the atria, was studied. Atrial fibrillation sustained significantly longer after tachypacing in the trained horses, whereas no difference in AF inducibility was found. The untrained horses displayed a significant difference in the AF complexity when comparing right and left atria, whereas such difference was not observed in the trained animals. No evidence of increased structural remodeling or inflammation could be identified. Left atrial dimensions were not significantly increased. The increased AF sustainability in trained horses was not related to fibrosis or inflammation as seen in other animal exercise models.

Response shift in hearing related quality of life after cochlear implantation - effect size and clinical significance: a then-test study.

BACKGROUND: Quality of life questionnaires are often used in the assessment of rehabilitation of hearing-impaired patients with a cochlear implant. However, a prospective study with a systematic retrospective evaluation of the preoperative quality of life after surgery has not yet been conducted and may reveal a change in internal standards, such as a response shift, due to the implantation and hearing rehabilitation. METHODS: The Nijmegen Cochlear Implant Questionnaire (NCIQ) was used for assessing hearing related quality of life. It has three general domains (physical, psychological and social) and six subdomains. Seventeen patients were tested before (t0) and retrospectively (then-test; pre-t1) and acutely postoperative (post-t1) after cochlear implantation. Observed changes, then-test changes, response shifts and effect sizes were calculated. Non-parametric statistical methods were used. RESULTS: The NCIQ total score was 52.32 ± 18.69 (mean, standard deviation) for t0, 59.29 ± 14.06 for pre-t1 and 67.65 ± 26.02 for post-t1 questioning. The observed change was statistically significant in all domains but in speech production. Response shift was statistically significant in the total score and in part of the domains. The effect sizes for the response shift were moderate (> 0.5) in the total score, psychological, social general scores and subdomains. CONCLUSIONS: In this study we found that response shift does exist in adults with severe to profound hearing loss undergoing cochlear implantation. By advising the participants to deactivate the implant for the then-test, recall bias and noise were minimized. The clinical significance of the response shift was present in the total score and in the social and psychological domains. TRIAL REGISTRATION: This study was retrospectively registered with the German Clinical Trial Register, TRN DRKS00029467, on 07/08/2022.

3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide.

Aim: To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs. Materials and methods: Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination. Results: We present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2-4 individual veins as well as 1-2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered. Conclusion: Fluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.

Accuracy Study of Kato-Katz and Helmintex Methods for Diagnosis of Schistosomiasis Mansoni in a Moderate Endemicity Area in Sergipe, Northeastern Brazil.

Schistosomiasis is a neglected tropical disease (NTD) caused by blood flukes from the genus Schistosoma. Brazil hosts the main endemic area in the Americas, where Schistosoma mansoni is the only species causing the disease. Kato-Katz (KK) thick smear is the WHO recommended screening test for populational studies, but there is growing evidence for the sensitivity limitations associated with KK, especially in areas with low parasite loads. Helmintex (HTX) is another highly sensitive egg-detection method, based on the magnetic properties of S. mansoni eggs and their isolation in a magnetic field. The objective of this study is to evaluate both KK and HTX in a moderate endemic locality, Areia Branca, located in the municipality of Pacatuba, in the state of Sergipe in northeastern Brazil. From 234 individual fecal samples, two KK thick smears were prepared and evaluated for each sample. Similarly, 30 g of each fecal sample was processed by HTX protocol. Eggs were detected in 80 (34.18%) residents. Twenty-three (9.83%) samples were positive for eggs (only by KK), and 77 (32.91%) samples showed positive for eggs (only by HTX). Sensitivity, specificity, and accuracy estimates gave values of 28.75%, 100% and 75.64%, respectively, for KK, and 96.25%, 100% and 98.72% respectively, for HTX. The positive predictive value was 100% for both methods, while the negative predictive value was 72.99% for KK and 98.09% for HTX. Overall, HTX presented a superior performance compared to the one sample, two slides KK examination. The study confirms the role of HTX as a reference method for the definition of true-positive samples in comparative accuracy studies and its potential role in the late stages when the certification of schistosomiasis transmission interruption is required. Diagnostic tests are important tools for the elimination of this NTD, besides the effective implementation of safe water, basic sanitation, snail control, and the treatment of infected populations.

Age-dependent effects on palate volume and morphology during orthodontic RME treatment.

OBJECTIVES: Rapid maxillary expansion (RME) shows different age-dependent effects. It has been shown that RME leads to a parallel expansion prior to the age of 10, while later and especially from the age of 12, a V-shaped expansion happens (transverse, anterior > posterior; horizontal, inferior > superior). However, it is not clear to what extent these effects influence palatal volume and morphology and eventually maxillary functional space. The aim of the present study was to examine possible age-related effects of treatment with a dental anchored RME appliance upon volume and width/height ratio of the anterior and posterior palate. MATERIALS AND METHODS: Sixty children and adolescents with documented treatment histories after RME were divided into three equal groups according to age at treatment begin (PG 1, < 10 years, n=20; PG 2, 10 ≤ 12 years, n=20; PG 3, > 12 years, n=20). Maxillary dental casts before and after therapy were digitised. Changes in palatal volume were determined using 3D analyses. RESULTS: In all patients, the palatal volume increases significantly after RME. Older patients experienced smaller increases in total and posterior volume in absolute and percentage terms. The anterior palate volume increases are almost equal in all patients. Since palatal width increases more markedly than palatal height, the width/height ratio always increases. Except for the posterior region in PG 3, its increase is significant in all groups, both anteriorly and posteriorly. After successful RME, the palatal morphology appears normal anteriorly in PG 1, PG 2 and PG 3 and rather steep posteriorly in PG 3. CONCLUSIONS: RME treatment with identical force application causes different, age-dependent effects upon palate volume and morphology. Width changes have a greater influence on palate volume than height changes. CLINICAL RELEVANCE: It is preferable to use an RME prior to the age of 10 if homogeneous changes of the anterior and posterior palate regarding maxillary symmetry and functional space are desired.

Estado nutricional e segurança alimentar de famílias em vulnerabilidade social no município de Contagem, Minas Gerais, 2014 / Nutritional status and food security of socially vulnerable families in the municipality of Contagem, Minas Gerais, 2014

Este é um estudo transversal avaliando estado nutricional e insegurança alimentar em uma comunidade vulnerável de Contagem, região metropolitana de Belo Horizonte. Um total de 273 indivíduos de 67 famílias foram avaliados. Para a avaliação antropométrica, determinou-se o peso, a estatura, o índice de massa corporal, a circunferência da cintura e a razão cintura-estatura. A insegurança alimentar foi analisada por meio da Escala Brasileira de Insegurança Alimentar. As concentrações de colesterol total, triglicerídeos, glicose e albumina sérica também foram determinadas. Das 67 famílias avaliadas, 51% (n = 34) apresentaram insegurança alimentar, sendo 79,4% leve, 17,7% moderada e 2,9% grave. Em crianças e adolescentes, sobrepeso e obesidade foram diagnosticados em 9,3% (n = 4) e 19,5% (n=16), respectivamente. Entre os adultos, 34,1% (n = 42) foram classificados com sobrepeso, 27,6% (n = 34) com obesidade grau I e 59,3% (n = 73) apresentaram risco aumentado de doenças cardiovasculares. Nos idosos, o excesso de peso foi diagnosticado em 44,0% (n = 11) e 80,0% (n = 20) apresentaram risco aumentado para doenças cardiovasculares. Hiperglicemia, hipercolesterolemia e hipertrigliceridemia foram diagnosticadas em 17, 45 e 72% da população, respectivamente. Houve correlação positiva entre os parâmetros antropométricos e bioquímicos, com exceção da albumina e glicose, que apresentaram correlação negativa em crianças e adultos. Nosso estudo confirma o impacto da vulnerabilidade social na ocorrência de elevadas proporções de insegurança alimentar, ocasionando alta prevalência de sobrepeso e obesidade e risco aumentado para desordens cardiovasculares. Além disso, nossos achados endossam o uso de concentrações séricas de albumina como indicador de alterações no metabolismo da glicose.

This is a cross-sectional study evaluating nutritional status and food insecurity in a vulnerable community in Contagem, in the metropolitan region of Belo Horizonte. A total of 273 individuals from 67 families were evaluated. For the anthropometric assessment, weight, height, body mass index, waist circumference, and waist-to-height ratio were determined. Food insecurity was analyzed using the Brazilian Food Insecurity Scale. Total cholesterol, triglycerides, glucose, and serum albumin concentrations were also determined. Of the 67 families evaluated, 51% (n = 34) had food insecurity, of which 79.4% were mild, 17.7% were moderate, and 2.9% were severe. In children and adolescents, overweight and obesity were diagnosed in 9.3% (n = 4) and 19.5% (n = 16), respectively. Among adults, 34.1% (n = 42) were classified as overweight, 27.6% (n = 34) had grade I obesity, and 59.3% (n = 73) had an increased risk of cardiovascular disease. In the elderly, overweight was diagnosed in 44.0% (n = 11), and 80.0% (n = 20) had an increased risk for cardiovascular diseases. Hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were diagnosed in 17, 45, and 72% of the population, respectively. There was a positive correlation between anthropometric and biochemical parameters, with the exception of albumin and glucose, which showed a negative correlation in children and adults. Our study confirms the impact of social vulnerability on the occurrence of high proportions of food insecurity, leading to a high prevalence of overweight and obesity and an increased risk for cardiovascular disorders. Furthermore, our findings support the use of serum albumin concentrations as an indicator of changes in glucose metabolism.

Age-dependent interactions of maxillary sutures during RME and their effects on palatal morphology : CBCT and dental cast analysis.

PURPOSE: The effects of rapid maxillary expansion (RME) on the transverse palatine and midfacial sutures have been extensively scrutinized. Unlike the dentition stage, age-dependency was not yet regarded when investigating morphological changes of the tooth-bearing palate. Therefore, the first aim of the present study was to analyse age-dependent sutural and morphological changes of the palate in selected patients by cone-beam computed tomography (CBCT) and dental cast analysis. Secondly, age-dependent effects of RME on width, height, and depth of the palate in the region of the maxillary palatine processes were investigated by a comprehensive dental cast study, so that the combination of results could be used to provide a biomechanical explanation of the occurring changes. METHODS: CBCT datasets of 9 patients (between 7.3 and 13.8 years) were measured around the median palatal suture and compared with the results of an individualised dental cast analysis. In addition, possible effects on other maxillary sutures were investigated. In the dental cast study, changes after RME in the tooth-bearing palate were analysed three-dimensionally in 60 children and adolescents. It was possible to divide those into three equally sized, age-dependant groups (PG1: < 10 years, n = 20; PG2: ≥ 10 < 12 years, n = 20; PG3: ≥ 12 years, n = 20). RESULTS: The CBCT analysis reveals age-related differences in sutural responses. The opening width of the median palatine suture decreases cranially (frontal) and dorsally (horizontal). The opening mode thus changes from parallel to triangular in both planes. The transverse palatine suture completely opens in younger patients only (PG1 and PG2). The width increases are always significant in all patients. While in PG1 the width increase is greater posteriorly than anteriorly, this is always reversed in PG2 and PG3. The palatal height always increases significantly anteriorly, but posteriorly only in the youngest patients (PG 1) median and paramedian. In PG 2 and PG 3, the posterior height change is very small. That is the reason why the anteroposterior comparison reveals a much more pronounced height increase anteriorly than posteriorly. CONCLUSION: The comparison of selected CBCT data with a dental cast analysis allows the conclusion that the maxillary expansion after RME in children up to 10 years is rather parallel, whereas it occurs V­shaped (anterior > posterior transversal, inferior > superior vertical) with increasing age, especially in adolescents from the age of 12. In addition to an age-progressive rigidity of the pterygopalatomaxillary junction, morphological changes of the transverse palatine suture during growth seem to be causal. Thus, age-dependent effects of palatal expansion occur due to a positional change of maxillary centres of rotation and resistance. From dental cast measurements, especially at the skeletal-basal level, conclusions can be drawn about the median palatal suture opening mode.

Applications of the Novel Quantitative Pharmacophore Activity Relationship Method QPhAR in Virtual Screening and Lead-Optimisation.

Pharmacophores are an established concept for the modelling of ligand-receptor interactions based on the abstract representations of stereoelectronic molecular features. They became widely popular as filters for the fast virtual screening of large compound libraries. A lot of effort has been put into the development of sophisticated algorithms and strategies to increase the computational efficiency of the screening process. However, hardly any focus has been put on the development of automated procedures that optimise pharmacophores towards higher discriminatory power, which still has to be done manually by a human expert. In the age of machine learning, the researcher has become the decision-maker at the top level, outsourcing analysis tasks and recurrent work to advanced algorithms and automation workflows. Here, we propose an algorithm for the automated selection of features driving pharmacophore model quality using SAR information extracted from validated QPhAR models. By integrating the developed method into an end-to-end workflow, we present a fully automated method that is able to derive best-quality pharmacophores from a given input dataset. Finally, we show how the QPhAR-generated models can be used to guide the researcher with insights regarding (un-)favourable interactions for compounds of interest.

Necropsy Validation of a Novel Method for Left Ventricular Mass Quantification in Porcine Transthoracic and Transdiaphragmal Echocardiography.

Introduction: Increased left ventricular mass (LVM) is one of the most powerful predictors of adverse cardiovascular events. Clinical evaluation requires reliable, accurate and reproducible echocardiographic LVM-quantification to manage patients. For this purpose, we have developed a novel two-dimensional (2D) method based on adding the mean wall thickness to the left ventricular volume acquired by the biplane method of disks, which has recently been validated in humans using cardiac magnetic resonance as reference value. We assessed the hypothesis that the novel method has better accuracy than conventional one-dimensional (1D) methods, when compared to necropsy LVM in pigs. Materials and Methods: Echocardiography was performed during anesthesia in 34 Danish Landrace pigs, weight 47-59 kg. All pigs were euthanized, cardiac necropsy was performed and the left ventricle was trimmed and weighed for necropsy LVM. Trans-thoracic echocardiography was applied for parasternal images. Transdiaphragmal echocardiography was applied for the apical images, which are otherwise difficult to obtain in pigs. We compared the conventional 1D- and 2D-methods and the novel 2D-method to the LVM from cardiac necropsy. Results: Necropsy LVM was 132 ± 11 g (mean ± SD). The novel method had better accuracy than other methods (mean difference ± 95% limits of agreement; coefficients of variation; standard error of the estimate, Pearson's correlation). Novel (-1 ± 20 g; 8%; 11 g; r = 0.70), Devereux (+26 ± 37 g; 15%; 33 g; r = 0.52), Area-Length (+27 ± 34 g; 13 %; 33 g; r = 0.63), Truncated Ellipsoid (+10 ± 30 g; 12%; 19 g; r = 0.63), biplane endo-/epicardial tracing (-3 ± 2 g; 10%; 14 g; r = 0.57). No proportional bias in linear regression was detected for any method, when compared to necropsy LVM. Conclusion: We confirm high accuracy of the novel 2D-based method compared to conventional 1D/2D-methods.