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Purpose: To describe 10-week and 12-month outcomes following treatment for divergence insufficiency-type esotropia in adults., Methods: In this prospective observational study, 110 adults with divergence insufficiency-type esotropia, with a distance esodeviation measuring 2 Δ to 30 Δ and at least 25% larger at distance than near, and binocular diplopia present at least "sometimes" at distance, were enrolled at 28 sites when initiating new treatment. Surgery, prism, or divergence exercises/therapy were chosen at the investigator's discretion. Diplopia was assessed at enrollment and at 10-week and 12-month outcome examinations using a standardized diplopia questionnaire (DQ). Success was defined as DQ responses of "rarely" or "never" when looking straight ahead in the distance, with no alternative treatment initiated., Results: Of the 110 participants, 32 (29%) were prescribed base-out prism; none had received prior treatment for esotropia. Success criteria were met by 22 of 30 at 10 weeks (73%; 95% CI, 54%-88%) and by 16 of 26 at 12 months (62%; 95% CI, 41%-80%). For the 76 (68%) who underwent strabismus surgery (82% of whom had been previously treated with prism), success criteria were met by 69 of 74 at 10 weeks (93%; 95% CI, 85%-98%) and by 57 of 72 at 12 months (79%; 95% CI, 68%-88%)., Conclusions: In this study cohort, both base-out prism as initial therapy and strabismus surgery (usually following prism) were successful in treating diplopia for most adults with divergence insufficiency-type esotropia when assessed during the first year of follow-up., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

A technological development is described through which the stable carbon-, oxygen-, and nonexchangeable hydrogen-isotopic ratios (δ(13)C, δ(18)O, δ(2)H) are determined on a single carbohydrate (cellulose) sample with precision equivalent to conventional techniques (δ(13)C 0.15‰, δ(18)O 0.30‰, δ(2)H 3.0‰). This triple-isotope approach offers significant new research opportunities, most notably in physiology and medicine, isotope biogeochemistry, forensic science, and palaeoclimatology, when isotopic analysis of a common sample is desirable or when sample material is limited.

Purpose: We describe the spontaneous resolution of hypertropia in a subset of patients with preoperative exotropia and hypertropia, who underwent surgery for intermittent exotropia alone., Design: This was a retrospective case series., Methods: The charts were reviewed of 17 patients who underwent surgical correction for an intermittent exotropia, who additionally were noted on preoperative exam to have greater than 5 prism dioptres of vertical deviation in primary position. Patients were excluded if they had prior strabismus surgery, dissociated vertical deviation, and paretic or restrictive deviations., Results: All patients were documented to have complete resolution of any vertical deviation in any field of gaze. This effect was noted to persist., Conclusions: We propose that the measured distance hypertropia, which is coincident with intermittent exotropia, even with the appearance of superior oblique dysfunction or inferior oblique overaction, is not created by a true vertical or cyclovertical muscle imbalance. Further, that the reduction of the hypertropia at near fixation predicts its resolution with horizontal muscle surgery. Therefore, vertical surgery should not be performed to address the coincident vertical deviation in these patients.

Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.

Epidermal growth factor (EGF) in rat salivary glands is regulated by testosterone, thyroxin, and growth hormone (GH). Salivary glands of 45-day-old giant and dwarf male and female transgenic mice were examined histologically and by immunohistochemistry (IHC) for EGF. Male giants showed no significant differences from wild-type (WT) parotid and submandibular glands. However, their sublingual glands expressed EGF diffusely and strongly in granular cells within the striated ducts, where they were not found in WT mice. Submandibular gland ducts of female WT were different, having individual granular cells strongly positive for EGF and distributed sporadically along the striated duct walls. Neither female GH-antagonist dwarf mice nor GH-receptor knockout mice had any granular cells expressing EGF in any gland. Obvious presence of granular duct cells in the sublingual glands of giant male mice suggests GH-upregulated granular cell EGF expression. Furthermore, absence of granular duct cells from all glands in female GH-antagonist and GH-receptor knockout transgenic mice suggests that GH is necessary for the differentiation of the granular cell phenotype in female salivary glands., (Copyright The Histochemical Society, Inc.)

Unlabelled: Growth hormone (GH) stimulates mandibular growth but its effect on the mandibular condylar cartilage is not well understood., Objective: This study was designed to understand the influence of GH on mitotic activity and on chondrocytes maturation. The effect of GH on cartilage thickness was also determined., Design: An animal model witt differences in GH status was determined by comparing mutant Lewis dwarf rats with reduced pituitary GH synthesis (dwarf), with normal rats and dwarf animals treated with GH. Six dwarf rats were injected with GH for 6 days, while other six normal rats and six dwarf rats composed other two groups. Mandibular condylar tissues were processed and stained for Herovici's stain and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and alkaline phosphatase (ALP). Measurements of cartilage thickness as well as the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance., Results: Cartilage thickness was significantly reduced in the dwarf animals treated with GH. PCNA expression was significant lower in the dwarf rats, but significantly increased when these animals were treated with GH. ALP expression was significant higher in the dwarf animals, while it was significantly reduced in the dwarf animals treated with GH., Conclusions: The results from this study showed that GH stimulates mitotic activity and delays cartilage cells maturation in the mandibular condyle. This effect at the cellular level may produce changes in the cartilage thickness.

Negative regulation of transcription is an important strategy in establishing and maintaining cell-specific gene expression patterns. Many neuronal genes are subject to active transcriptional repression outside the nervous system to establish neuronal specificity. NRSF/REST has been demonstrated to regulate at least 30 genes and contribute to their neuronal targeting by repressing transcription outside the nervous system. Further, human genome database searches reveal that over 800 genes contain an NRSE. Here we report that NRSF recruits the histone methylase G9a to silence NRSF target genes in nonneuronal cells. We show that G9a generates a highly localized domain of dimethylated histone H3-K9 around NRSEs, but H3-K27 remains unmethylated. The NRSEs are also associated with HP1. Finally, we demonstrate that dominant-negative G9a abrogates silencing of chromosomal neuronal genes. These findings implicate a role for histone methylation in targeting neuronal gene expression to the nervous system.

Unlabelled: The effect of altered occlusion on the mandibular condylar cartilage remains unclear., Objective: This study investigated the effect of unilateral incisor disocclusion on cartilage thickness, on mitotic activity and on chondrocytes maturation and differentiation in the mandibular condylar cartilage of rats., Design: The upper and lower left incisors were trimmed 2mm every second day in five rats. In other five rats, the incisor occlusion was not altered. Condylar tissues from both sides of each mandible were processed and stained for Herovici's stain and immunohistochemistry for bromodeoxyuridine (BrdU), transforming growth factor-beta1 (TGF-beta1), alkaline phosphatase (ALP) and osteocalcin (OCN). Measurements of cartilage thickness and the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance (ANOVA)., Results: No significant differences were observed in cartilage thickness after 7 days of unilateral incisor disocclusion. However, the numbers of immunopositive cells for BrdU as a marker of DNA synthesising cells, TGF-beta1 as a marker of chondrocytes differentiation, and ALP and OCN as markers of chondrocytes maturation, were significant higher in the cartilage cells on both sides when incisor occlusion was unilaterally altered. Interestingly, alkaline phosphatase was highly expressed on the condylar side of incisor disocclusion, whereas osteocalcin was highly expressed on the side opposite to the incisor disocclusion., Conclusions: It is demonstrated that after 7 days, unilateral incisor disocclusion affects the mandibular condylar cartilage at the cellular level by increasing the mitotic activity and by accelerating chondrocytes maturation. Chondrocytes maturation appears more accelerated on the side opposite to incisor disocclusion.

Cementum is known to be growth-hormone (GH)-responsive, but to what extent is unclear. This study examines the effects of extremes of GH status on cementogenesis in three lines of genetically modified mice; GH excess (giant), GH antagonist excess (dwarf), and GH receptor-deleted (GHR-KO) (dwarf). Age-matched mandibular molar tissues were processed for light microscope histology. Digital images of sections of first molar teeth were captured for morphometric analysis of lingual root cementum. Cross-sectional area of the cellular cementum was a sensitive guide to GH status, being reduced nearly 10-fold in GHR-KO mice, three-fold in GH antagonist mice, and increased almost two-fold in giant mice (p < 0.001). Cellular cementum length was similarly influenced by GH status, but to a lesser extent. Acellular cementum was generally unaffected. This study reveals cellular cementum to be a highly responsive GH target tissue, which may have therapeutic applications in assisting regeneration of the periodontium.

Background: Asthma medication places patients at risk of dental erosion by reducing salivary protection against extrinsic or intrinsic acids. But patterns of lesions in asthmatics may differ from patterns in non-asthmatics, because gastro-oesophageal reflux (GOR) is found in 60 per cent of asthmatics., Methods: The lesions in 44 asthma cases were compared to those of age and sex match controls with no history of asthma or medications drawn from the dental records of 423 patients referred concerning excessive tooth wear. The subjects were 70 males age range 15 to 55 years and 18 females age range 18 to 45. Anamnestic clinical data were compared between the two groups. Models of all 88 subjects were examined by light microscopy, and wear patterns were recorded on permanent central incisor, canine, premolar and first molar teeth., Results: Clinical differences were a higher incidence of tooth hypersensitivity, xerostomia, salivary gland abnormalities, gastric complaints, and self induced vomiting in the cases. No differences were found between the cases and controls on citrus fruit and acid soft drink consumption. More occlusal erosion sites were found in cases, whereas more attrition sites were found in the controls. There were no significant differences in palatal erosion on maxillary anterior teeth found between cases and controls. Lingual erosion of the mandibular incisors, found only in GOR patients, was not observed., Conclusions: A higher incidence of erosion was found in asthmatics. Gastro-oesophageal reflux symptoms were not associated with the sign of lingual mandibular incisor erosion. The clinical significance is that asthmatics are at risk of dental erosion from extrinsic acid, but GOR does not appear to contribute in a site-specific manner.

Glucocorticosteroids are widely used in the treatment of chronic illnesses and have been reported to cause premature obliteration of the pulp space. During the active stages of dentinogenesis, odontoblasts are growth hormone receptor (GHr) positive. The aims of this study were to determine if the glucocorticosteroid, prednisone, affected the rate of dentine deposition and odontoblast expression of GHr in the rat molar. Following subcutaneous injection of 0.05 mg/kg, 1.0 mg/kg or 5.0 mg/kg prednisone for 20 days, immature and mature molars from rats aged 3 and 6 weeks respectively, were examined histologically. Distribution of GHr expression was determined immunohistochemically. No morphological differences were observed in molars from prednisone treated animals. Prednisone did not appear to enhance dentine deposition in immature molars but in mature molars significantly increased dentine deposition on the roof of the pulp chamber at a dosage of 5.0 mg/kg (p < 0.001). In all immature molars, odontoblasts and pulp cells expressed GHr immunoreactivity. In mature molars, odontoblasts and pulpal cells from controls did not show GHr immunoreactivity. However, odontoblasts and pulp cells were GHr immunoreactive in mature molars from animals treated with prednisone.

Acid demineralization of teeth causes occlusal erosion and attrition, and shallow and wedge-shaped cervical lesions putatively involving abfraction. From 250 patients with tooth wear, 122 with cervical lesions were identified. From epoxy resin replicas of their dentitions, associations of occlusal attrition or erosion or no wear with cervical lesions were recorded at 24 tooth sites (total 2928 sites). Criteria used to discriminate occlusal attrition from erosion, and shallow from grooved, wedge-shaped or restored cervical lesions were delineated by scanning electron microscopy. A 96 per cent association was found between occlusal and cervical pathology. Shallow cervical lesions were more commonly found in association with occlusal erosion. Wedge-shaped lesions were found equally commonly in association with occlusal erosion, as with attrition. Grooved and restored cervical lesions were uncommon. Differences were appreciated in the associations within incisor, canine, premolar and molar tooth sites which related more to the site-specificity of dental erosion than to attrition from occlusal forces. Non-carious lesions on teeth then have multifactorial aetiology and pathogenesis in which erosion and salivary protection play central roles. Dentists should primarily consider erosion in the diagnosis, prevention and treatment of tooth wear.

The effect of orthodontic tooth movement on the dental pulp was assessed histologically in twelve subjects. The participants in this study required the extraction of at least two maxillary first premolars for orthodontic treatment. They were asked to wear a maxillary removable appliance that acted to move a randomly determined premolar in a buccal direction. The appliance was designed to avoid contacting the contra-lateral tooth that was used as the matched control. The appliance was initially worn for a week to ensure patient comfort and cooperation. The appliance was then activated and the patient dismissed. After two weeks, the appliance was reactivated. Both the control and experimental teeth were extracted three weeks later, on the thirty-fifth day of activated appliance wear. The teeth were fixed, decalcified and sectioned. The sections were stained with haematoxylin and eosin for histological examination. This investigation demonstrated that orthodontic tooth movement did have an effect upon the dental pulp, causing vasodilation in the pulp of an orthodontically stressed tooth.

Tooth-tissue loss from erosion and attrition from bruxism were associated findings in 104 patients with excessive toothwear from South East Queensland. Approximately one-third of these subjects had been given a diagnosis of bruxism prior to referral. After a structured interview and clinical examination, the prevailing diagnosis was tooth erosion associated with occupational or sports-related dehydration, and one-third of the subjects were provisionally classified as bruxers. Eight items of clinical history and examination, designed to differentiate bruxers from non-bruxers, were analysed retrospectively from their records. These clinical items, by which the diagnosis of bruxism might be made, segregated the subjects into three groups of equal size, 'bruxers, possible bruxers and non-bruxers,' by a notional score for bruxism. The presence of occlusal attrition or erosion on the sextants of the dentitions was determined by scanning electron microscopic criteria on epoxy resin dental casts. The incidence of attrition versus erosion was compared between the three groups. The hypothesis was that attrition would be found on more sextants of bruxers than non-bruxers. Erosion predominated in virtually all sextants in all three groups, to the virtual exclusion of attrition in the molar sextants. The exception was the mandibular anterior sextant, where more sextants in bruxers were affected by attrition. Thus extrinsic or intrinsic acid erosion was strongly associated with occlusal tooth wear found in bruxers. Conversely, tooth-wear patterns were unreliable indicators of a bruxing habit, for attrition alone was often found on acid-exposed teeth. Thus, even if a patient is suspected of having bruxism, dental erosion is more likely the cause of tooth-tissue loss than attrition, especially in the dehydrating environment of South East Queensland.

Fluoride exposure in early life has an effect on dental caries experience, but does it affect tooth wear in later life? Ninety-six South East Queensland subjects were studied. Their histories revealed three groups; a fluoride (F-) in water supply, a F- by supplement, and a non-fluoridated (non F-) group. Significantly higher caries experience was found in the non-F- group compared with F- in water group and the F- supplement group. No statistically significant difference in caries experience was found between the F- in water and F- supplement groups. Overall, tooth wear affected more sextants of the dentitions of non-fluoridated, high-caries subjects than of fluoridated low-caries subjects. Comparisons of wear patterns on sextants of the dentitions, between the fluoridated and non-fluoridated groups, revealed that in sextants where attrition was present no marked differences were discernible between the two groups. However, in most sextants where incisal, palatal, occlusal or non-occlusal erosion was found, this type of wear was commoner in non-fluoridated subjects. The exceptions were the mandibular molar sextants, where prior fluoride-exposure did not appear to protect against occlusal erosion patterns. This study showed that fluoride exposure during the first 12 years of life, which reduced dental caries in this population, may also protect teeth from wear to some extent.

Smears of buccal mucosa, dorsal surface of the tongue and floor of mouth were taken from 10 patients with histologically confirmed oral lichen planus and 12 healthy age- and sex-matched controls. In buccal smears, no significant differences in cytoplasmic and nuclear areas were observed between lesional, adjacent non-lesional and control tissues. However, the cytoplasmic area in smears from lichen planus lesions on the dorsum of the tongue and adjacent clinically normal mucosa was reduced compared with healthy controls. The cytoplasmic: nuclear ratio in smears from clinically normal floor of mouth in oral lichen planus was similarly reduced. Papanicolaou-stained smears from buccal lichen planus showed increased keratinization compared with normal buccal mucosa. These findings demonstrate that quantitative cytology can detect both cytoplasmic and nuclear changes in oral lichen planus.

Insulin-like growth factor-I(IGF-I) has both metabolic and growth-promoting activities in many cell and tissue types. Although IGF-I is present in serum, it is also thought to have important autocrine and paracrine functions. Immunohistochemistry for IGF-I and its receptor have shown that IGF-I is synthesised locally by the tooth forming cells which exhibit both the IGF-I and the growth hormone receptors. This concept required to be tested by in situ hybridization. Using a digoxigenin-labelled synthetic oligodeoxyribonucleotide probe for IGF-I, we investigated the distribution of IGF-I mRNA in the continuously erupting rat incisor by in situ hybridization. The distribution and intensity of the hybridization signal varied with the developmental stage of the rat incisor. The cells of the apical loop expressed a positive hybridization signal, but the earliest polarised odontoblasts and pre-ameloblasts did not show any positive signal. The onset of enamel secretion was accompanied by a strong hybridization signal in the secretory ameloblasts as well as the odontoblasts. Maturation ameloblasts also demonstrated IGF-I message in their cytoplasm as well as their nuclei. The cells of the pulp and the dental follicle were consistently negative. However, in the adjacent alveolar bone, the signal was high in the osteoblasts and osteoclasts. These findings support the notion of paracrine or autocrine function for IGF-I in tooth development.

Cord blood was anonymously screened to determine the prevalence of human immunodeficiency virus (HIV) seropositivity in neonates admitted to the neonatal intensive care unit (NICU) at the Bronx Lebanon Hospital Center, located in the South Bronx. We speculated that factors leading to admission to the NICU such as low birth weight, prematurity and being small for gestational age would also be associated with an increased prevalence of HIV seropositivity. During the study period the prevalence of HIV seropositivity was 11.6% in the NICU population. There was no significant difference in maternal age, gravidity, race and sex in HIV-seropositive vs. HIV-seronegative newborns. There was a significantly increased incidence of maternal drug use (P less than 0.01), babies small for gestational age (P less than 0.005) and microcephaly (P less than 0.02) in seropositive vs. seronegative NICU babies. The results of this study suggest that the NICU population may comprise a significant number of infants of HIV-infected mothers.

A family is described in which two females are more severely affected by hereditary opalescent dentine than the males. The genealogy of this family does not provide an accepted pattern of inheritance for this dentine anomaly. This may indicate that there is considerable variation in inheritance patterns for hereditary opalescent dentine and that this trait does not always exhibit 100 percent penetrance.

The purpose of this study is to determine whether the structural organization of Pattern 2 marsupial enamel in the Koala is disposed to resist wear on the sectorial crests of the molar teeth. The orientation of wear on the crests is uniformly delineated by parallel scratches on their polished surfaces. Twin blades, a leading and a trailing edge of enamel are formed on each crest by wear into dentine on which the differential wear at enamel to dentine interfaces indicates that the direction of wear is labial to lingual. 96 leading and trailing edges from 12 koala molars were examined by light and scanning electron microscopy as ground sections, polished and etched surfaces or polished and etched whole mount preparations sputter coated with gold. The results showed that the leading and trailing enamel edges are different in their thicknesses, and in the course of their rods. The rods in the thinner leading edge are angled at 25 degrees to the long axis of the tooth and cross the worn surface at 60-70 degrees. Trailing rods run at 5 degrees to the long axis to cross the worn surface at 90 degrees. The inter-rod sheets run parallel to the wear striations and thus hold the rods in palisades angled in the leading edge particularly to resist the vector of the occlusal forces in the direction of wear. Crystals in the rods emerge roughly perpendicular onto the worn surface which makes them more resistant to abrasion than those in the inter-rod substance which lie parallel to the worn surface and are more readily removed. Koala enamel on the sectorial crests is thus a simple Pattern 2 rod packing pattern but the angles of the rods and the alignment of the inter-rod substance appear to be adapted to resist occlusal forces and abrasion.

Staining reactions for a number of histochemical procedures for lipophilic staining and protein were studied in the enamel matrix along the length of rat incisors. Sudan Black gave a positive stain across the whole thickness of very early enamel (up to 30 micrometer) but this staining only continued as a narrow band close to the ameloblasts as the enamel matured. A variety of tests for protein produced almost identical staining patterns in enamel matrix up to 100 micrometer thick. Since the pattern of "lipid" staining persisted, after using a number of procedures which could normally be expected to remove lipid, it is suggested that Sudan Black positive staining may be due to lipophilic protein rather than lipid itself. Fluoride did not significantly alter the staining reactions for "lipid" and protein but did produce matrix which was much more effectively stained by cross-linking agents FFDNB and FF sulphone.

An Australian family in which two members were affected by focal palmoplantar and gingival mucosal hyperkeratosis syndrome is reported. The propositus and his daughter had symptoms which suggested that esophageal lesions might be present. In view of the association of tylosis with esophageal carcinoma in other families, both patients were investigated by barium swallow or endoscopy. No esophageal lesions were found. Previously unreported paranuclear bodies were described in the keratinocytes of the spinous and granular cell layers of the finely papillated gingival epithelium of the propositus. Similar paranuclear bodies, although rare, were identified in cytologic smears from the four members of the family examined, two of whom had slight whitening of the mucosa of the retromolar pads only. By electron microscopy and histochemistry, these bodies were characterized as condensations of tonofilaments and not heteromorphic keratohyalin.