Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance.

Synthesis of triiodothyronine (T3) in the hypothalamus induces marked seasonal neuromorphology changes across taxa. How species-specific responses to T3 signaling in the CNS drive annual changes in body weight and energy balance remains uncharacterized. These experiments sequenced and annotated the Siberian hamster (Phodopus sungorus) genome, a model organism for seasonal physiology research, to facilitate the dissection of T3-dependent molecular mechanisms that govern predictable, robust, and long-term changes in body weight. Examination of the Phodopus genome, in combination with transcriptome sequencing of the hamster diencephalon under winter and summer conditions, and in vivo-targeted expression analyses confirmed that proopiomelanocortin (pomc) is a primary genomic target for the long-term T3-dependent regulation of body weight. Further in silico analyses of pomc promoter sequences revealed that thyroid hormone receptor 1ß-binding motif insertions have evolved in several genera of the Cricetidae family of rodents. Finally, experimental manipulation of food availability confirmed that hypothalamic pomc mRNA expression is dependent on longer-term photoperiod cues and is unresponsive to acute, short-term food availability. These observations suggest that species-specific responses to hypothalamic T3, driven in part by the receptor-binding motif insertions in some cricetid genomes, contribute critically to the long-term regulation of energy balance and the underlying physiological and behavioral adaptations associated with the seasonal organization of behavior.

The Relationship between Wormlike Micelle Scission Free Energy and Micellar Composition: The Case of Sodium Lauryl Ether Sulfate and Cocamidopropyl Betaine.

The scission energy is the difference in free energy between two hemispherical caps and the cylindrical region of a wormlike micelle. This energy difference determines the logarithm of the average micelle length, which affects several macroscopic properties such as the viscosity of viscoelastic fluids. Here we use a recently published method by Wang et al. ( Langmuir, 2018, 34, 1564-1573) to directly calculate the scission energy of micelles composed of monodisperse sodium lauryl ether sulfate (SLESnEO), an anionic surfactant. Utilizing dissipative particle dynamics (DPD), we perform a systematic study varying the number of ethoxyl groups (n) and salt concentration. The scission energy increases with increasing salt concentration, indicating that the formation of longer micelles is favored. We attribute this to the increased charge screening that reduces the repulsion between head groups. However, the scission energy decreases with increasing number of ethoxyl groups as the flexibility of the head group increases and the sodium ion becomes less tightly bound to the head group. We then extend the analysis to look at the effect of a common cosurfactant, cocamidopropyl betaine (CAPB), and find that its addition stabilizes wormlike micelles at a lower salt concentration.

Utilizing Machine Learning for Efficient Parameterization of Coarse Grained Molecular Force Fields.

We present a machine learning approach to automated force field development in dissipative particle dynamics (DPD). The approach employs Bayesian optimization to parametrize a DPD force field against experimentally determined partition coefficients. The optimization process covers a discrete space of over 40 000 000 points, where each point represents the set of potentials that jointly forms a force field. We find that Bayesian optimization is capable of reaching a force field of comparable performance to the current state-of-the-art within 40 iterations. The best iteration during the optimization achieves an R2 of 0.78 and an RMSE of 0.63 log units on the training set of data, these metrics are maintained when a validation set is included, giving R2 of 0.8 and an RMSE of 0.65 log units. This work hence provides a proof-of-concept, expounding the utility of coupling automated and efficient global optimization with a top down data driven approach to force field parametrization. Compared to commonly employed alternative methods, Bayesian optimization offers global parameter searching and a low time to solution.

In Vivo Effects of Retrobulbar Bimatoprost Injection on Orbital Fat.

PURPOSE: Recent publications have reported the adverse effects of prostaglandin analogues on the periocular tissues. These medications may cause periorbital lipodystrophy, enophthalmos, and deepening of the superior sulcus deformity. While these effects may have adverse consequences for some patients, the atrophy of the periorbital fat may have a useful role in diseases that lead to orbital and periorbital fat hypertrophy such as thyroid eye disease. In this pilot study, the authors investigated the effects of retrobulbar bimatoprost injection on the intraocular pressure and orbital fat in a rat animal model. METHODS: Three rats were sedated and intraocular pressure was measured. A 0.1 ml aliquot of bimatoprost was injected into the right orbit of all rats. In the left orbit, 0.1 ml of phosphate-buffered saline was injected as a control. Three weeks later, all rats were sedated and intraocular pressure was measured before euthanizing. Routine histologic staining was performed and thin sections through the intraconal orbital fat were obtained. Density of intraconal adipocytes was measured and adipocyte heterogeneity was determined using a computer image analysis algorithm. RESULTS: The specimens injected with bimatoprost demonstrated atrophy of orbital fat with significantly increased adipocyte density (p = 0.009) and heterogeneity (p = 0.008) when compared with control. Intraocular pressure was not significantly decreased at 3 weeks after injection of retrobulbar bimatoprost. CONCLUSIONS: In this pilot study, orbital injection of bimatoprost demonstrated atrophy of intraconal adipocytes when compared with control orbits injected with saline. The orbits injected with bimatoprost were noted to have smaller, more heterogeneous adipocytes that were densely packed in the intraconal space. The study limitations include the small sample size, which limited the ability for us to make conclusions about the effect on intraocular pressure. Nevertheless, the findings presented suggest that retrobulbar bimatoprost may present a nonsurgical alternative to induce atrophy of the orbital fat without inducing inflammation or hypotony.

Dissipative particle dynamics: Systematic parametrization using water-octanol partition coefficients.

We present a systematic, top-down, thermodynamic parametrization scheme for dissipative particle dynamics (DPD) using water-octanol partition coefficients, supplemented by water-octanol phase equilibria and pure liquid phase density data. We demonstrate the feasibility of computing the required partition coefficients in DPD using brute-force simulation, within an adaptive semi-automatic staged optimization scheme. We test the methodology by fitting to experimental partition coefficient data for twenty one small molecules in five classes comprising alcohols and poly-alcohols, amines, ethers and simple aromatics, and alkanes (i.e., hexane). Finally, we illustrate the transferability of a subset of the determined parameters by calculating the critical micelle concentrations and mean aggregation numbers of selected alkyl ethoxylate surfactants, in good agreement with reported experimental values.

Body weight loss, effective satiation and absence of homeostatic neuropeptide compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet.

Food structure contributes to the induction of satiation and the maintenance of satiety following intake of a meal. There is evidence from human studies that protein-crosslinking of a milk-protein based meal may enhance satiety, but the mechanism underpinning this effect is unknown. We investigated whether a rat model would respond in a similar manner and might provide mechanistic insight into enhanced satiety by structural modification of a food source. Rats were schedule fed a modified AIN-93M based diet in a liquid form or protein-crosslinked to produce a soft-solid form. This was compared to a modified AIN-93M solid diet. Average daily caloric intake was in the order solid > liquid > crosslinked. Body composition was unaltered in the solid group, but there was a loss of fat in the liquid group and a loss of lean and fat tissue in the crosslinked group. Compared to rats fed a solid diet, acute responses in circulating GLP-1, leptin and insulin were eliminated or attenuated in rats fed a liquid or crosslinked diet. Quantification of homeostatic neuropeptide expression in the hypothalamus showed elevated levels of Npy and Agrp in rats fed the liquid diet. Measurement of food intake after a scheduled meal indicated that reduced energy intake of liquid and crosslinked diets is not due to enhancement of satiety. When continuously available ad-libitum, rats fed a liquid diet showed reduced weight gain despite greater 24 h caloric intake. During the dark phase, caloric intake was reduced, but compensated for during the light phase. We conclude that structural modification from a liquid to a solidified state is beneficial for satiation, with less of a detrimental effect on metabolic parameters and homeostatic neuropeptides.

Systemic Allergic Response in the Setting of a Metallic Intraorbital Foreign Body With Intraoperative Magnet-Assisted Retrieval.

A 12-year-old boy with a past medical history of nickel allergy was referred to our service after sustaining an air rifle injury with a retained BB in his left inferior orbit. On examination, he had a palpable orbital mass and systemic urticaria. Plain films demonstrated a spherical metallic foreign body adjacent to the left inferior orbital rim. Given his worsening systemic reaction despite oral antihistamine therapy, decision was made to remove the foreign body. In the operating room, the Allergan Magna Finder-a prepackaged, sterile device normally used for retrieval of a port used in tissue expansion surgery-was placed over the inferior conjunctiva of the lower eyelid. With the magnet holding gentle anterior traction on the foreign body, it was easily dissected and removed. The patient tolerated the procedure well, and had rapid resolution of his systemic allergic response following removal of the BB.

Osteolytic Sarcoidosis of the Orbital Roof Masquerading as a Malignant Orbital Lesion.

A 51-year-old man without a significant past medical history presented with 4 weeks of progressive swelling and drooping of his left upper eyelid. A CT of the left orbit revealed an osteolytic mass lesion in the area of the lacrimal gland. A left orbitotomy with excisional biopsy was performed. The excised tissue was sent for infectious workup and histopathological examination, which revealed osteolytic sarcoidosis. The patient was treated with systemic and local injection corticosteroids, and followed over 10 months without evidence of recurrence. Systemic workup with CT of his chest, abdomen, and pelvis revealed no further evidence of sarcoidosis. To the best of the authors knowledge, this is the first report of an otherwise healthy patient presenting with isolated osteolytic sarcoidosis of the orbit and a negative systemic workup.

Prostaglandin-Associated Periorbital Lipodystrophy in Cosmetic Eyelid Surgery: A Novel Cause of Facial Asymmetry.

A 70-year-old woman presented to our practice with profound ptosis of the left upper eyelid and notable asymmetry of the periocular area. On examination, she was noted to have significant atrophy of the periocular tissues on the left side, with lower eyelid retraction. These features were present but less severe on the right side. Upon further questioning, she stated that she had cataract surgery on the left side that was complicated by a high intraocular pressure and required subsequent secondary surgery. She had taken a prostaglandin eyedrop for many months after her cataract surgery to keep the eye pressure low. Recently, a newly recognized adverse effect of prostaglandin eyedrops has been described in the ophthalmic literature in which patients develop periorbital lipodystrophy. This case emphasizes that this may occur unilaterally in patients taking the eyedrop in only one eye, and should be recognized prior to considering functional and aesthetic surgery of the periocular area.

Use of hyaluronic acid gel in the treatment of lagophthalmos in sunken superior sulcus syndrome.

PURPOSE: To evaluate the use of hyaluronic acid gel in the management of lagophthalmos in sunken superior sulcus syndrome. INTRODUCTION: Lagophthalmos associated with orbital fat atrophy and deep superior sulcus is a known entity described previously. Orbital fat atrophy results in deep superior sulcus where skin, orbicularis muscle, and orbital septum retract posteriorly in the deep superior sulcus, leading to lagophthalmos from suboptimal orbicularis function and effective skin shortening. The authors define this condition as sunken superior sulcus syndrome (SSSS) when the deep superior sulcus leads to exposure keratopathy. Thus, the syndrome consists of deep superior sulcus, lagophthalmos, and exposure keratopathy. Although the use of hyaluronic acid gel has been proposed as a management option for paralytic lagophthalmos, its application in the treatment of lagophthalmos in SSSS has not been reported. METHODS: In this study, 5 patients (10 eyelids) with SSSS were injected with hyaluronic acid gel in the superior sulcus of the upper eyelid. Injected amount was titrated until the desired point was reached: complete or nearly complete eyelid closure. RESULTS: After an average follow up of 9.5 months, lagoph thalmos improved by 2 mm or 69% (p = 0.02) on the right side and by 1 mm or 71% (p = 0.01) on the left side. Most patients also reported significantly improved ocular comfort and appearance of the superior sulcus. The only complications noted were bruising and temporary uneven contour of the upper eyelid sulcus. CONCLUSIONS: Management of lagophthalmos in SSSS with hyaluronic acid gel is an effective and safe alternative to surgery.

Myectomy for blepharospasm 2013.

PURPOSE OF REVIEW: Botulinum toxin (BTX) injections are the main medical treatment of facial dystonias, but injections are ineffective in some patients. This review discusses the indications for myectomy and surgical technique for treating benign essential blepharospasm (BEB) and apraxia of eyelid opening (ALO). RECENT FINDINGS: There are four reasons to consider myectomy for patients with BEB. The first is ALO associated with BEB. The second is patients with blepharospasm-associated deformities. The third is patients who are truly unresponsive to BTX. The fourth is patients who cannot afford or who refuse BTX injections. SUMMARY: Myectomy remains essential for treating blepharospasm patients and the most common indication is those with associated ALO.

Eye dominance and Hering's law effect on bilateral blepharotosis repair.

PURPOSE: Eye dominance and Hering's law dependence are postulated to influence eyelid position, and thus affect surgical outcomes following blepharoptosis surgery. Pseudoretraction of the contralateral eyelid, usually observed in the nondominant eye, is a well-recognized occurrence in the ophthalmic literature. In this article, these 2 phenomena were assessed preoperatively in blepharoptosis patients to evaluate their effect on postoperative outcomes. METHODS: In this retrospective cohort study, postoperative eyelid position and rates of reoperation were investigated in 38 patients with bilateral involutional ptosis, who underwent bilateral ptosis repair. Institutional Review Board approval was obtained. In addition to the standard ptosis preoperative evaluation, patients were tested for Hering's law dependence and eye dominance. RESULTS: None of the patients included in the study had significant postoperative eyelid asymmetry or required reoperation. CONCLUSIONS: Eye dominance and Hering's law dependence did not affect the surgical outcomes of the patients included in this study who had bilateral ptosis repair performed. It was postulated that this may be due to the balancing of these 2 factors intraoperatively, thus negating their effect on eyelid position postoperatively.

Can Machine Learning Predict the Phase Behavior of Surfactants?

We explore the prediction of surfactant phase behavior using state-of-the-art machine learning methods, using a data set for twenty-three nonionic surfactants. Most machine learning classifiers we tested are capable of filling in missing data in a partially complete data set. However, strong data bias and a lack of chemical space information generally lead to poorer results for entire de novo phase diagram prediction. Although some machine learning classifiers perform better than others, these observations are largely robust to the particular choice of algorithm. Finally, we explore how de novo phase diagram prediction can be improved by the inclusion of observations from state points sampled by an analogy to commonly used experimental protocols. Our results indicate what factors should be considered when preparing for machine learning prediction of surfactant phase behavior in future studies.

Phase Behavior of Alkyl Ethoxylate Surfactants in a Dissipative Particle Dynamics Model.

We present a dissipative particle dynamics (DPD) model capable of capturing the liquid state phase behavior of nonionic surfactants from the alkyl ethoxylate (CnEm) family. The model is based upon our recent work [Anderson et al. J. Chem. Phys. 2017, 147, 094503] but adopts tighter control of the molecular structure by setting the bond angles with guidance from molecular dynamics simulations. Changes to the geometry of the surfactants were shown to have little effect on the predicted micelle properties of sampled surfactants, or the water-octanol partition coefficients of small molecules, when compared to the original work. With these modifications the model is capable of reproducing the binary water-surfactant phase behavior of nine surfactants (C8E4, C8E5, C8E6, C10E4, C10E6, C10E8, C12E6, C12E8, and C12E12) with a good degree of accuracy.

Anterior filler displacement following injection of calcium hydroxylapatite gel (Radiesse) for anophthalmic orbital volume augmentation.

OBJECTIVE: To describe the complication of anterior filler displacement following injection of calcium hydroxylapatite gel (Radiesse) for anophthalmic enophthalmos correction. METHODS: Retrospective case series of patients who experienced anterior filler displacement following orbital injection of calcium hydroxylapatite. Data includes patient demographics, indication for injection, route and volume of injection, description of postinjection complications, and final outcome. RESULTS: Four cases of anterior filler displacement and expansion following injection of calcium hydroxylapatite were identified. The patients' ages ranged from 33 to 64 years old. All 4 patients underwent multiple prior orbital surgeries and suffered from anophthalmic enophthalmos. Injectable calcium hydroxylapatite was delivered transcutaneously, to the deep extraconal orbital space, via 27-gauge, 1.25-inch retrobulbar needles. Each patient received an initial 1.3 ml of filler, with 1 patient receiving an additional 0.8 ml. Within 1 week, all patients experienced prominent, edematous lower eyelids. A CT scan of 1 patient radiographically documented anterior migration of the filler material. Two patients required transconjunctival excision of the filler and infiltrated orbital fat. Histopathologic examination of 1 specimen revealed chronic foreign body granulomatous inflammation. Two patients were treated medically, with resolution of clinical findings over 6 to 9 months. CONCLUSIONS: Anterior filler displacement is a potential complication of orbital volume augmentation with injectable calcium hydroxylapatite. Patients should be counseled regarding this possibility when considering options for the treatment of anophthalmic enophthalmos. A history of multiple prior orbital surgeries, with associated tissue disruption and scarring, may be a risk factor for filler displacement.

Modeling Alkyl Aromatic Hydrocarbons with Dissipative Particle Dynamics.

Building on previous work studying alkanes, we develop a dissipative particle dynamics (DPD) model to capture the behavior of the alkyl aromatic hydrocarbon family under ambient conditions of 298 K and 1 atmosphere. Such materials are of significant worldwide industrial importance in applications such as solvents, chemical intermediates, surfactants, lubricating oils, hydraulic fluids, and greases. We model both liquids and waxy solids for molecules up to 36 carbons in size and demonstrate that we can correctly capture both the freezing transition and liquid-phase densities in pure substances and mixtures. We also demonstrate the importance of including specialized bead types into the DPD model (rather than solely relying on generic bead types) to capture specific local geometrical constructs such as the benzene ring found in the benzyl chemical group; this can be thought of as representing subtle real-world many-body effects via customized pairwise non-bonded potentials.

Lateral canthal resuspension sine canthotomy.

PURPOSE: The purpose of this study is to describe a novel canthopexy technique-the lateral canthal resuspension sine canthotomy (LCR-SC)-performed via an upper-eyelid incision and to compare it with the lateral tarsal strip procedure (LTS). METHODS: This is a retrospective study in which the pre- and postoperative photographs of 20 patients per group who had LCR-SC, LCR-SC + midface lift (LCR-SC+ML), or LTS were analyzed by using the Image-J 1.40 software. Parameters measured were as follows: the horizontal palpebral aperture margin-reflex distance 2 (MRD-2) and the height of lateral canthus. LCR-SC was performed through an upper-eyelid incision, by using a 4.0 Prolene suture. For the LCR-SC+ML, a large myocutaneous flap was created first and anchored to the orbital-rim periosteum. The surgical technique is described. Two-way ANOVA was used for analysis. RESULTS: The horizontal palpebral aperture was significantly increased by LCR-SC and LCR-SC+ML when compared with LTS (1.61 ± 0.22 mm and 1.56 ± 0.14 vs. 0.04 ± 0.12 mm; p < 0.01). LCR-SC and LCR-SC+ML decreased the MRD-2 more than the LTS (1.06 ± 0.26 and 1.50 ± 0.23 mm vs. 0.86 ± 0.1 mm; p < 0.01). All 3 procedures increased the lateral canthal height by less than 0.5 mm. CONCLUSIONS: LCR-SC is a safe and effective procedure for tightening the lower eyelids. It tightens both the upper and the lower cruri of the lateral canthal tendon, avoiding imbrication of the eyelids. LCR-SC obviates the need for a lateral canthal incision and widens the horizontal palpebral aperture. LCR-SC is more effective than LTS at decreasing the MRD-2. Concomitant midface elevation (LCR-SC+ML) further decreases MRD-2.

Orbital augmentation with injectable calcium hydroxylapatite for correction of postenucleation/evisceration socket syndrome.

PURPOSE: To demonstrate the utility of injectable calcium hydroxylapatite (Radiesse) for orbital volume augmentation to correct postenucleation/evisceration socket syndrome (PESS). METHODS: A retrospective chart review of all consecutive patients in our practice who received injectable calcium hydroxylapatite placed in the extraconal space to augment orbital volume was conducted. Patients with at least 6 months follow-up were included in the study. RESULTS: Among 26 patients with PESS who received injectable calcium hydroxylapatite for orbital volume augmentation, 15 individuals were identified with adequate follow-up. The mean amount of preoperative relative enophthalmos measured by Hertel exophthalmometry was 4 mm (range 0.5-7 mm). An average reduction of 2.4 mm of enophthalmos per syringe of filler was achieved. The mean follow-up obtained was 46 weeks (range 24-78 weeks). Most patients demonstrated clinical and aesthetic improvement that was observed to continue up to 1.5 years. Complications observed included anterior migration of filler, a peribulbar hemorrhage, and orbital discomfort. Two patients demonstrated little response to filler. CONCLUSIONS: Injectable calcium hydroxylapatite provides a novel, safe, simple, cost-effective technique to treat volume deficiency in the anophthalmic orbit. Augmentation achieved with this semipermanent filler has demonstrated a lasting effect in the orbit with little volume loss. Volume replacement can be titrated to the socket requirements. Correction of PESS using this technique may be limited in orbits that demonstrate significant fibrosis as a result of multiple surgeries, severe trauma, or radiation treatment.

Enduragen patch grafts for exposed orbital implants.

PURPOSE: To present a new technique using the recently introduced Enduragen(®) material (Tissue Science Laboratories) as a patch graft for exposed ocular implants. METHODS: A retrospective, interventional, non-comparative case series of 3 patients who had Enduragen patch grafts for the closure of Tenon's capsule and conjunctiva over exposed ocular implants. Medical records were reviewed and the following parameters were collected: age, gender, indication for surgery, type of surgery, laterality, type of orbital implant, complications after repair and length of follow-up. RESULTS: Three patients were identified, 2 males and 1 female. One patient had a secondary quad-motility implant with supertemporal exposure. The second patient had a secondary implant with a fistula at the lateral aspect of the socket. The third patient had a centrally exposed primary hydroxyapatite implant. All patients received Enduragen patch grafts to cover the implant. Follow up ranged from 40 to 43 months (mean, 41.3 months; SD, ± 1.5). None of the 3 patients had any signs of implant re-exposure at the time of the last post-operative visit. There were no intra-operative or early complications observed. CONCLUSIONS: This consecutive case series suggests that Enduragen could be used as a safe and effective patch graft for exposed ocular implants. However, a larger prospective study with longer follow-up would be useful in further defining the indications and limitations of the Enduragen patch graft for the treatment of exposed orbital implants.