Mouth breathing syndrome can cause sleep disturbances that compromise the performance of children in school. It might also cause postural abnormalities involving the head and cervical spine; however, the association between postural abnormalities and mouth breathing in children is unclear.

The aim of this study was to explore root shape abnormalities, to investigate the influence of root form abnormalities on periodontal attachment loss, and to gather basic data to assist in the diagnosis and treatment of aggressive periodontitis.

Thermal imagers have been used in a number of disciplines to record animal surface temperatures and as a result detect temperature distributions and abnormalities requiring a particular course of action. Some work, with animals infected with foot-and-mouth disease virus, has suggested that the technique might be used to identify animals in the early stages of disease. In this study, images of 19 healthy cattle have been taken over an extended period to determine hoof and especially coronary band temperatures (a common site for the development of FMD lesions) and eye temperatures (as a surrogate for core body temperature) and to examine how these vary with time and ambient conditions.

Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 (n = 6) or 7.5 (n = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro, trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p < 0.0001; Wilcoxon signed rank test, p = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy.

Heparan sulfate belongs to the group of glycosaminoglycans (GAGs), highly sulfated linear polysaccharides. Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) is one of several specialized enzymes required for heparan sulfate synthesis and catalyzes the transfer of the sulfate groups to the sugar moiety of heparan sulfate. We report bi-allelic pathogenic variants in HS2ST1 in four individuals from three unrelated families. Affected individuals showed facial dysmorphism with coarse face, upslanted palpebral fissures, broad nasal tip, and wide mouth, developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, flexion contractures, brachydactyly of hands and feet with broad fingertips and toes, and uni- or bilateral renal agenesis in three individuals. HS2ST1 variants cause a reduction in HS2ST1 mRNA and decreased or absent heparan sulfate 2-O-sulfotransferase 1 in two of three fibroblast cell lines derived from affected individuals. The heparan sulfate synthesized by the individual 1 cell line lacks 2-O-sulfated domains but had an increase in N- and 6-O-sulfated domains demonstrating functional impairment of the HS2ST1. As heparan sulfate modulates FGF-mediated signaling, we found a significantly decreased activation of the MAP kinases ERK1/2 in FGF-2-stimulated cell lines of affected individuals that could be restored by addition of heparin, a GAG similar to heparan sulfate. Focal adhesions in FGF-2-stimulated fibroblasts of affected individuals concentrated at the cell periphery. Our data demonstrate that a heparan sulfate synthesis deficit causes a recognizable syndrome and emphasize a role for 2-O-sulfated heparan sulfate in human neuronal, skeletal, and renal development.

Neural oscillations are ubiquitous measurements of cognitive processes and dynamic routing and gating of information. The fundamental and so far unresolved problem for neuroscience remains to understand how oscillatory activity in the brain codes information for human cognition. In a biologically relevant cognitive task, we instructed six human observers to categorize facial expressions of emotion while we measured the observers' EEG. We combined state-of-the-art stimulus control with statistical information theory analysis to quantify how the three parameters of oscillations (i.e., power, phase, and frequency) code the visual information relevant for behavior in a cognitive task. We make three points: First, we demonstrate that phase codes considerably more information (2.4 times) relating to the cognitive task than power. Second, we show that the conjunction of power and phase coding reflects detailed visual features relevant for behavioral response--that is, features of facial expressions predicted by behavior. Third, we demonstrate, in analogy to communication technology, that oscillatory frequencies in the brain multiplex the coding of visual features, increasing coding capacity. Together, our findings about the fundamental coding properties of neural oscillations will redirect the research agenda in neuroscience by establishing the differential role of frequency, phase, and amplitude in coding behaviorally relevant information in the brain.

To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g., the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g., the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300.

Objectives. The primary objectives of this retrospective study were first to compare the upper and lower pharyngeal airway spaces between orthodontic patients with and without maxillary constriction and second to evaluate the effect of rapid maxillary expansion (RME) on these airway spaces. A secondary objective was to compare the mode of breathing between groups. Materials and Methods. The experimental (RME) group consisted of 30 patients (mean age, 14.2 ± 1.3 years, 16 boys and 14 girls) with maxillary constriction who were treated with hyrax-type RME. The control group comprised the records of age- and gender matched patients (mean age, 13.8 ± 1.5 years, 16 boys and 14 girls) with no maxillary constriction but requiring nonextraction comprehensive orthodontic treatment. Cephalometric measurements in the sagittal dimension of upper and lower airway spaces for the initial and final records were recorded. Mode of breathing and length of treatment were also compared. Results. The sagittal dimension of the upper airway increased significantly in the RME group (mean = 1.3 mm) compared to the control group (mean = 0.5 mm), P = 0.016. However, there was no significant difference in the lower pharyngeal airway measurement between the RME group (mean = 0.2) and the control group (mean = 0.4), P = 0.30. There was no significant difference with respect to mode of breathing between the two groups (P = 0.79). Conclusion. Rapid maxillary expansion (RME) during orthodontic treatment may have a positive effect on the upper pharyngeal airway, with no significant change on the lower pharyngeal airway.

Considerable interest has been shown in the field of sleep medicine in recent decades. Obstructive sleep apnoea (OSA) is a common condition that remains neglected in most parts of the world. Data are scarce, if any, when it comes to developing countries. We sought to describe the patient population in a single private tertiary care center from such a country.

Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.

Whether or not chronic fatigue is reflected in structural changes in the brain is a matter of debate. Primary SS (pSS) is characterized by dryness of the mouth and eyes, migrating muscle and joint pain and prominent fatigue. We aimed to investigate whether the severity of fatigue in pSS was associated with cerebral MRI findings.

Breast cancer has one of highest morbidity and mortality rates for women. Abnormalities regarding epigenetics modification and pyruvate dehydrogenase kinase 1 (PDK1)-induced unusual metabolism contribute to breast cancer progression and chemotherapy resistance. However, the role and mechanism of epigenetic change in regulating PDK1 in breast cancer remains to be elucidated.

Conductive olfactory dysfunction (COD) is caused by an obstruction in the nasal cavity and is characterized by changeable olfaction. COD can occur even when the olfactory cleft is anatomically normal, and therefore, the cause in these cases remains unclear. Herein, we used computational fluid dynamics to examine olfactory cleft airflow with a retrospective cohort study utilizing the cone beam computed tomography scan data of COD patients. By measuring nasal-nasopharynx pressure at maximum flow, we established a cut-off value at which nasal breathing can be differentiated from combined mouth breathing in COD patients. We found that increased nasal resistance led to mouth breathing and that the velocity and flow rate in the olfactory cleft at maximum flow were significantly reduced in COD patients with nasal breathing only compared to healthy olfactory subjects. In addition, we performed a detailed analysis of common morphological abnormalities associated with concha bullosa. Our study provides novel insights into the causes of COD, and therefore, it has important implications for surgical planning of COD, sleep apnea research, assessment of adenoid hyperplasia in children, and sports respiratory physiology.

Background: Oral health issues are commonly reported in systemic sclerosis (SSc), comprising a broad spectrum of manifestations, e.g., reduced mouth opening, periodontal disease, increased periodontal ligament (PDL) space width, and mandibular resorption. We aimed to assess oral radiographic abnormalities, particularly PDL space widening and erosions, and to identify potential relations with disease measures. Methods: cross-sectional study in 43 SSc and matching controls receiving systematic oral assessments (full mouth dental/periodontal) and imaging (radiographs and cone beam computed tomography (CBCT)). Associations between disease variables and radiologic findings were investigated by univariate and multivariate analysis (SPSS-v.20, p < 0.05). Results: CBCT demonstrated generalized PDL space widening in up to half SSc, with at least one tooth involved, essentially in the posterior region (p < 0.05). Significant correlations between number of teeth with PDL space widening and disease severity, skin score, disease subset, topoisomerase I specificity, age, and disease duration were reported (p < 0.05). Additionally, mandibular erosions were described in one out of four patients, commonly condylar erosions. Conclusions: Tridimensional CBCT approach confirmed widening of PDL and mandibular erosions as common dental findings in scleroderma. Furthermore, widened PDL spaces correlated with several disease characteristics including severity, skin extent, and antibody profile.

Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type. Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features. Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities. Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome. Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.

The aim of this cross-sectional study was to investigate the occurrence of chromosomal abnormalities through the frequency of micronuclei and other genomic damage markers in patients with chronic generalized periodontitis and without periodontal disease. Micronucleus assay was performed in exfoliated gingival epithelial cells of 35 patients with generalized chronic periodontitis and 30 control subjects with healthy periodontium. Full mouth clinical examination was performed to define periodontal condition. The mean number of cells with micronuclei observed in chronic periodontitis and control groups was 1.8 (±1.49) and 2.0 (±1.34), respectively. Differences between the groups were not significant (p=0.574). Compared to control subjects, patients with chronic periodontitis showed a significant increase in the number of binucleated cells (p≤0.001) and number of cells with nucleoplasmic bridges (p=0.042). Study results indicated that chronic periodontitis was not associated with higher occurrence of chromosomal damage in gingival cells compared to individuals with healthy periodontium.

Pesticide contamination is an important factor in the global decline of amphibians. The herbicides glyphosate and 2,4-D are the most applied worldwide. These herbicides are often found in surface waters close to agricultural areas. This study aims at evaluating the chronic effects caused by glyphosate + 2,4-D mixture in Boana faber and Leptodactylus latrans tadpoles. The combined solution of the glyphosate and 2,4-D, in 5 different concentrations, was applied for 168 h. Herbicide mixtures did not affect the survival of the exposed tadpoles but growth and swimming activity were altered; besides causing several damages in the mouth and intestine. The erythrocytes showed micronuclei and other nuclear abnormalities. There is an ecological risk in the exposure of tadpoles of B. faber and L. latrans from the mixture of glyphosate + 2,4-D. Therefore, the approach used in this study provides important information on how commonly used pesticides can affect non-target organisms.

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.

We report on a 27 month old boy presenting with psychomotor delay and dysmorphic features, mainly mild facial asymmetry, prominent cup-shaped ears, long eyelashes, open mouth appearance and slight abnormalities of the hands and feet. Array comparative genomic hybridization revealed a 393 kb microdeletion in 7p11.2. We discuss the possible involvement of CHCHD2, GBAS, MRPS17, SEPT14 and PSPH on our patient's phenotype. Additionally, we studied the expression of two other genes deleted in the patient, CCT6A and SUMF2, for which there is scarce data in the literature. Based on current knowledge and the de novo occurrence of this finding in our proband we presume that the aberration is likely to be pathogenic in our case. However, a single gene disorder, elsewhere in the genome or in this very region cannot be ruled out. Further elucidation of the properties of this chromosomal region, as well as of the role of the genes involved will be needed in order to draw safe conclusions regarding the association of the chromosomal deletion with the patient's features.

Impaired tactile acuity in people with chronic pain conditions has been suggested to reflect altered cortical representation of the painful body part, and treatments that aim to improve tactile acuity in these conditions have shown clinical benefit. Whether abnormalities in tactile acuity are a consistent feature of chronic pain remains largely unknown. The aim of this review was to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is altered in people with chronic non-neuropathic pain. We systematically searched the literature for studies that investigated tactile acuity in people with chronic non-neuropathic pain and compared it to an appropriate control group. Sixteen studies, reporting data from 5 chronic pain conditions, were included. Data were available for 18 chronic pain populations (n = 484) and 15 control populations (n = 378). Our results suggest that tactile acuity is diminished in arthritis, complex regional pain syndrome, and chronic low back pain but not in burning mouth syndrome. The strength of the available evidence is weakened by somewhat inconsistent results and the high risk of bias observed in all of the included studies.