Foreign body extrusion associated with N-butyl-2-cyanoacrylate glue used with rectus muscle hang-back recession.

OBJECTIVE: Standard rectus muscle recessions require suturing muscle to sclera posterior to the insertion, which is dangerous as the sclera is thin. Extraocular muscle hang-back recession can avoid the posterior scleral needle pass but has been reported to be unstable. The purpose of this study is to assess the use of N-butyl-2-cyanoacrylate to aid reattachment of rectus muscle to sclera during hang-back recession. DESIGN: 2 Phase Study: Phase 1 was a wet lab animal study; Phase 2 was a small case series. PARTICIPANTS: Phase 1, 14 frozen bank rabbit heads; Phase 2, 4 human adult patients with myopia and large exotropia. METHODS: Phase 1: Frozen bank rabbit heads were used to simulate human hang-back rectus muscle recession. Fourteen rectus muscles were recessed by hang-back and glued to sclera with either cyanoacrylate glue alone (group 1) or glue over prolene mesh for greater stability (group 2). Primary outcome was muscle detachment force measured at 20, 30, and 40 seconds. Phase 2: Four patients with myopia and large exotropia who underwent bilateral hang-back lateral rectus recessions with cyanoacrylate glue were retrospectively studied. RESULTS: Phase 1: Group 1 mean detachment force measured at 30 seconds was 172.07 g versus 376.5 g in group 2 (p < 0.01). Phase 2: All patients had excellent postoperative alignment within 5 PD of orthophoria and no overcorrections. Two patients had unilateral glue extrusion at 1 month requiring in-office removal under topical anaesthesia. CONCLUSIONS: Cyanoacrylate glue with or without mesh resulted in adequate muscle-to-sclera adhesion with a detachment force at least 2 times the force of a normal rectus muscle contraction. Patients undergoing hang-back lateral rectus recession with cyanoacrylate glue had excellent stable postoperative alignment; however, half had the complication of late extrusion of glue foreign body.

Validation of a novel strabismus surgery 3D-printed silicone eye model for simulation training.

PURPOSE: To demonstrate the validity of a new 3D-printed silicone model for practicing strabismus surgery, compared with the rabbit head, in terms of simulator fidelity. METHODS: In this multicenter study, a validated questionnaire was developed to assess fidelity of the model and rabbit head. Participants were asked to rate overall globe, conjunctiva, muscle, and scleral fidelity using a 5-point scale. The survey instrument was disseminated at three strabismus instruction courses: at two meetings, participants practiced on the model and rabbit head prior to completing the questionnaire; at the third, instructors demonstrated advanced surgical skills using only the model and then completed the questionnaire. Repeated measures analysis of variance compared ratings. Pearson's or Spearman's correlation evaluated correlation between years of experience to participants' responses. Qualitative data were coded into themes. RESULTS: A total of 47 participants completed the questionnaire. The model rated 18% higher than rabbit head for anatomical accuracy (mean difference, 0.667; P = 0.001) and 25% higher for position of eyes within the head (mean difference, 0.867; P = 0.006). More experienced participants were more likely to strongly agree that the silicone conjunctiva effectively mimics real conjunctiva (ρ = 0.337; P = 0.036) and that scleral tissue effectively mimics real sclera (ρ = 0.298, P = 0.042). Qualitative data supported the model. CONCLUSIONS: This study demonstrated the validity of the surgical model in terms of fidelity compared to the rabbit head.

Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome.

CONTEXT: To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS. OBJECTIVE: To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI. DESIGN: Cross-sectional study. PARTICIPANTS: Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33). OUTCOME MEASURES: Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis. RESULTS: All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing. CONCLUSION: Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.

Sensitivity of the circadian system to evening bright light in preschool-age children.

Although the light-induced melatonin suppression response is well characterized in adults, studies examining the dynamics of this effect in children are scarce. The purpose of this study was to quantify the magnitude of evening light-induced melatonin suppression in preschool-age children. Healthy children (n = 10; 7 females; 4.3 ± 1.1 years) participated in a 7-day protocol. On days 1-5, children followed a strict sleep schedule. On day 6, children entered a dim light environment (<15 lux) for 1-h before providing salivary samples every 20- to 30-min from the afternoon until 50-min after scheduled bedtime. On day 7, subjects remained in dim light conditions until 1-h before bedtime, at which time they were exposed to a bright light stimulus (~1000 lux) for 1-h and then re-entered dim light conditions. Saliva samples were obtained before, during, and after bright light exposure and were time anchored to samples taken the previous evening. We found robust melatonin suppression (87.6 ± 10.0%) in response to the bright light stimulus. Melatonin levels remained attenuated for 50-min after termination of the light stimulus (P < 0.008). Furthermore, melatonin levels did not return to 50% of those observed in the dim light condition 50-min after the light exposure for 7/10 children. Our findings demonstrate a robust light-induced melatonin suppression response in preschool-age children. These findings have implications for understanding the role of evening light exposure in the development of evening settling difficulties and may serve as experimental evidence to support recommendations regarding light exposure and sleep hygiene practices in early childhood.

Beach-cast debris surveys on Triangle Island, British Columbia, Canada indicate the timing of arrival of 2011 Tohoku tsunami debris in North America.

We conducted beach-cast debris transect surveys on Triangle Island, British Columbia, Canada in 2012-2017 to (1) establish a baseline against which to track future changes in stranded debris on this small, uninhabited island; and (2) time the arrival in western North America of debris released by the 2011 Tohoku tsunami. Most (90%) of the six-year total of 6784 debris items tallied was composed of Styrofoam or plastic. The number of debris items peaked in 2014 (waste Styrofoam, rope) and 2015 (waste plastic, wood), and cumulative totals for all debris types were ca. 50% higher in 2014-15 than in 2012-13 and 2016-17. The peaks in 2014-15 probably represented the arrival of the bulk of the tsunami debris, based on close correspondence with forecasting models and debris surveys elsewhere. A fuller understanding of the movement of the Tohoku tsunami debris will require information from other beach monitoring programs.

Histologic examination of teeth with necrotic pulps and periapical lesions treated with 2 scaffolds: an animal investigation.

INTRODUCTION: Traditional pulp regeneration procedures that use a blood clot as a scaffold have produced histologic evidence of bone, cementum, and connective tissue growth within the root. Platelet-rich plasma (PRP) is a bioactive scaffold containing growth factors that enhance wound healing. AIM: The aim of this study was to histologically compare the tissues generated when PRP or a blood clot is placed into teeth with preexisting necrotic pulps and periapical lesions. METHODS: Twenty-four canine teeth from 6 immature ferrets were used. Two ferrets served as positive controls. Sixteen experimental canine teeth from 4 ferrets were infected, debrided, treated with a triple antibiotic paste, and randomly distributed to the following groups: group 1 (blood clot/Gelfoam), group 2 (PRP), and group 3 (no scaffold). At 3 months, the ferrets were sacrificed, and the tissues were evaluated histologically. Data were analyzed by using the Fisher exact test (P < .05). RESULTS: In 3 of 6 teeth in the PRP group, 2 of 6 teeth in the blood clot group, and 1 of 4 teeth in the no scaffold group, an ingrowth of hard tissues was observed in the apical third of the roots. When using PRP or a blood clot as a scaffold, we found significantly more apical narrowing and hard tissue deposition in comparison to not using a scaffold (P < .05). CONCLUSIONS: The use of PRP or blood clots as scaffolds results in the ingrowth of bone-like, cementum-like, and connective tissue in the apical third of the roots at inconsistent rates.

The Timing of the Circadian Clock and Sleep Differ between Napping and Non-Napping Toddlers.

The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napping and non-napping sleep schedules (monitored with actigraphy) for 5 days before an in-home salivary dim light melatonin onset (DLMO) assessment. On average, napping children fell asleep during their nap opportunities on 3.6±1.2 of the 5 days before the DLMO assessment. For these napping children, melatonin onset time was 38 min later (p = 0.044; d = 0.93), actigraphically-estimated bedtime was 43 min later (p = 0.014; d = 1.24), sleep onset time was 59 min later (p = 0.006; d = 1.46), and sleep onset latency was 16 min longer (p = 0.030; d = 1.03) than those not napping. Midsleep and wake time did not differ by napping status. No difference was observed in the bedtime, sleep onset, or midsleep phase relationships with DLMO; however, the wake time phase difference was 47 min smaller for napping toddlers (p = 0.029; d = 1.23). On average, nappers had 69 min shorter nighttime sleep durations (p = 0.006; d = 1.47) and spent 49 min less time in bed (p = 0.019; d = 1.16) than non-nappers. Number of days napping was correlated with melatonin onset time (r = 0.49; p = 0.014). Our findings indicate that napping influences individual variability in melatonin onset time in early childhood. The delayed bedtimes of napping toddlers likely permits light exposure later in the evening, thereby delaying the timing of the clock and sleep. Whether the early developmental trajectory of circadian phase involves an advance associated with the decline in napping is a question necessitating longitudinal data as children transition from a biphasic to monophasic sleep-wakefulness pattern.

Identification of hard tissue after experimental pulp capping using dentin sialoprotein (DSP) as a marker.

The purpose of this study was to identify the hard tissue formed early in experimental pulp exposures capped with mineral trioxide aggregate (MTA) or bone morphogenetic protein (BMP)-7 using dentin sialoprotein (DSP) as a marker. The pulps of 35 maxillary first, second, and third molar teeth from 10 male rats were experimentally exposed. The pulps were capped with MTA alone as a pulp-capping agent and final restoration or with BMP-7 followed by restoration with MTA. Five teeth with class I occlusal preparations, no exposure, and no restoration served as positive controls. Five teeth that received pulp exposures and no restoration served as negative controls. Five untreated third molars served as additional controls. The animals were killed at 2 weeks. The specimens were prepared and evaluated histologically and with immunohistochemistry using polyclonal antibodies raised against rat DSP. Pulps capped with MTA formed hard tissue that demonstrated significantly more immunostaining for DSP compared with BMP-7 (p = 0.0031). MTA-capped pulps also showed significantly more complete bridge formation compared with BMP-7 (p = 0.0008). Pulps capped with BMP-7 demonstrated a hard tissue that was bone-like in appearance and devoid of DSP staining.

Histologic examinations of teeth treated with 2 scaffolds: a pilot animal investigation.

INTRODUCTION: A growing body of evidence is building a case for the possibility of tissue regeneration within the root canal of necrotic teeth, allowing for continued root development. However, it remains unknown what type of tissue is produced after regenerative endodontics. The purpose of this study was to use blood clots and platelet-rich plasma (PRP) as scaffolds in regenerative endodontics under ideal conditions in a ferret model to examine the tissues generated within the root canals. METHODS: The pulps of 21 canine teeth from 7 young ferrets were extirpated using broaches without filing the canal walls. Bleeding was stimulated from the periapical tissues, and a blood clot was induced in the canal space to the level of the cementoenamel junction in 12 teeth. PRP was prepared and placed in the canals to the level of the cementoenamel junction in 9 teeth. The coronal access was sealed with mineral trioxide aggregate. Seven canines were not operated on and served as controls. Three months later, block sections including each canine and its surrounding tissues were removed for histologic evaluation. The tissues found in the canals of experimental teeth were compared with those in the control teeth. RESULTS: Almost all of the experimental teeth showed the presence of intracanal bonelike tissue. No evidence of dentinal wall thickening or apical narrowing was noted in the experimental teeth. CONCLUSIONS: In this experimental model, the use of either PRP or blood clots during regenerative endodontics leads to the formation of intracanal bonelike tissue without continual root maturation.

Circadian phase and its relationship to nighttime sleep in toddlers.

Circadian phase and its relation to sleep are increasingly recognized as fundamental factors influencing human physiology and behavior. Dim light melatonin onset (DLMO) is a reliable marker of the timing of the circadian clock, which has been used in experimental, clinical, and descriptive studies in the past few decades. Although DLMO and its relationship to sleep have been well documented in school-aged children, adolescents, and adults, very little is known about these processes in early childhood. The purpose of this study was 1) to describe circadian phase and phase angles of entrainment in toddlers and 2) to examine associations between DLMO and actigraphic measures of children's nighttime sleep. Participants were 45 healthy toddlers aged 30 to 36 months (33.5 ± 2.2 months; 21 females). After sleeping on a parent-selected schedule for 5 days (assessed with actigraphy and diaries), children participated in an in-home DLMO assessment involving the collection of saliva samples every 30 minutes for 6 hours. Average bedtime was 2015 ± 0036 h, average sleep onset time was 2043 ± 0043 h, average midsleep time was 0143 ± 0038 h, and average wake time was 0644 ± 0042 h. Average DLMO was 1929 ± 0051 h, with a 3.5-hour range. DLMO was normally distributed; however, the distribution of the bedtime, sleep onset time, and midsleep phase angles of entrainment were skewed. On average, DLMO occurred 47.8 ± 47.6 minutes (median = 39.4 minutes) before bedtime, 74.6 ± 48.0 minutes (median = 65.4 minutes) before sleep onset time, 6.2 ± 0.7 hours (median = 6.1 hours) before midsleep time, and 11.3 ± 0.7 hours before wake time. Toddlers with later DLMOs had later bedtimes (r = 0.46), sleep onset times (r = 0.51), midsleep times (r = 0.66), and wake times (r = 0.65) (all p < 0.001). Interindividual differences in toddlers' circadian phase are large and associated with their sleep timing. The early DLMOs of toddlers indicate a maturational delay in the circadian timing system between early childhood and adolescence. These findings are a first step in describing the fundamental properties of the circadian system in toddlers and have important implications for understanding the emergence of sleep problems and the consequences of circadian misalignment in early childhood.

Combination of light and melatonin time cues for phase advancing the human circadian clock.

STUDY OBJECTIVES: Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. DESIGN: Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. SETTING: Sleep and chronobiology laboratory environment free of time cues. PARTICIPANTS: Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). RESULTS: Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. CONCLUSION: Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model.

PURPOSE: This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. MATERIALS AND METHODS: Fifteen VX2 tumor-bearing rabbits were randomized into five groups (n = 3 in each group) that received either IV (64)Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA (64)Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated (64)Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated (64)Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA (64)Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity. RESULTS: At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001). CONCLUSION: Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection.

Mini-plication to treat small-angle strabismus: A minimally invasive procedure.

BACKGROUND: Mini-plication is a new rectus muscle tightening procedure for the correction of small-angle strabismus that can be performed under topical anesthesia. The purpose of this study was to report the outcomes of mini-rectus muscle plication. METHODS: We retrospectively reviewed the medical records of patients who underwent mini-plication. In this procedure, 6-0 polyglactin 910 suture was secured to the central 3 to 4 mm of the muscle belly 5 mm posterior to the insertion and was then passed through the sclera just anterior to the muscle insertion to plicate the central portion of the muscle. This differs from the standard procedure, in which the entire width of the muscle is plicated. Two groups were analyzed: those who underwent mini-plication alone and those who underwent mini-plication after prior antagonist muscle-weakening surgery. RESULTS: Our review identified nine patients aged 5 to 78 years. Topical anesthesia was used for all adults, who experienced no local or systemic complications. Mini-plication reduced vertical and horizontal deviations an average (± SD) of 6.7(Δ) ± 3.5(Δ). The mini-plication-only group (3 patients) had an average postoperative correction of 5.5(Δ) ± 2.6(Δ); the prior surgery group (6 patients), an average of 9(Δ) ± 2.7(Δ). Diplopia was noted in 50% of the adults preoperatively and none postoperatively. All patients experienced a decrease in strabismus, with an average outcome of <5(Δ) of postoperative deviation. CONCLUSIONS: Mini-plication, which can be performed under topical anesthesia, corrected small deviations and was especially useful for adult strabismus patients with diplopia.

An animal model to study regenerative endodontics.

INTRODUCTION: A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. METHODS: Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. RESULTS: The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. CONCLUSIONS: Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days.

Hepatic arterial embolization with doxorubicin-loaded superabsorbent polymer microspheres in a rabbit liver tumor model.

OBJECTIVES: The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. METHODS: Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. RESULTS: The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. CONCLUSIONS: Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.

A biodegradable filament for controlled drug delivery.

Biodegradable filaments (diameters of 250-300 microm) for the controlled delivery of dexamethasone or levofloxacin are described. Filaments are prepared by wet-spinning solutions of poly(lactide-co-glycolide) (PLGA) and drug dissolved in dimethyl sulfoxide (DMSO) into a coagulation bath of water. Compositional analyses of the filaments by independent measurements of drug, DMSO, water, and polymer give drug loadings up to 40% of filament mass and drug retention (drug in filament per drug in solution) greater than 40%. Drug release kinetics, and thermal and mechanical properties, of the filaments are reported. Three filaments with levofloxacin contents of 46+/-2, 85+/-4, and 36+/-2 microg/cm (denoted 506-L1, 506-L2, and 506-L3, respectively) are implanted in the conjunctiva of New Zealand white rabbits. The time dependent, in-vivo tear concentrations of levofloxacin from filament implants in New Zealand white rabbit eyes are in general agreement with the results from the in-vitro release profiles, with one of the filaments (506-L1) showing effective levels of levofloxacin in the tears for 6 days. The filaments are generally well tolerated by the rabbits. Filament failure occurs at 6-8 days within the rabbit eyes, essentially the same time to failure observed from in-vitro mechanical properties testing results.