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Tom Kornhauser,1 Christian M Ponder,1 Philip W Dockery,1 Anna B Sharabura,2 Wade Brock,2,3 John Nguyen,4 John D Pemberton1 1Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 3Arkansas Oculoplastic Surgery, PLLC, Little Rock, AR, USA; 4West Virginia University, Department of Ophthalmology and Visual Sciences, Department of Otolaryngology and Head and Neck Cancer, Morgantown, WV, USACorrespondence: Tom Kornhauser, Jones Eye Institute, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR, 72207, USA, Tel +501-686-5822, Fax +501-686-7037, Email tkornhauser@uams.eduPurpose: To elicit, from a survey of oculoplastic surgeons, the timing and reason for delaying Jones tube placement after the excision of nasal or lacrimal drainage system malignancy.Methods: The authors reviewed current literature and distributed an anonymous survey to 627 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) to determine the length of time members wait to perform a Jones tube placement after the removal of nasal or lacrimal drainage system malignancy. The survey also included questions about the rationale for this waiting period.Results: Fifty-eight members of ASOPRS (9.3%) responded to our survey, 49 (84.4%) of whom had performed Jones tube placement on patients who had an excision of a nasal or lacrimal drainage system malignancy. Nearly 52% of respondents waited one year for Jones tube placement. However, a sizeable number of respondents opted to wait five years (15.1%). The most common rationale for waiting was a concern for tumor recurrence (42 responses).Conclusion: There is no consensus on when to perform Jones tube placement after the excision of nasal or lacrimal drainage system malignancy. This survey demonstrates a broad array of waiting periods between operations, although most surgeons wait 12 months.Keywords: Conjunctivodacryocystorhinostomy, cDCR, Jones Tube, Malignant Neoplasm

Anthony Kim,1 Jennifer Nguyen,2 Mahsa Babaei,2 Ahlee Kim,1,2 David H Geller,1,2 Alaina P Vidmar1,2 1Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Children’s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Department of Pediatrics, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, CA, USACorrespondence: Alaina P Vidmar, Diabetes & Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Department of Pediatrics, 4650 Sunset Boulevard, Mailstop #61, Los Angeles, CA, 90027, USA, Tel +1 323 361-3385, Fax +1 323 361-1301, Email avidmar@chla.usc.eduAbstract: The prevalence of pediatric obesity has increased exponentially over the past four decades. The American Academy of Pediatrics recently released updated clinical practice guidelines highlighting the importance of identifying pediatric obesity as a chronic disease. The guidelines support consideration of concurrent treatment with intensive lifestyle interventions, obesity pharmacotherapy, and bariatric surgery. The dramatic rise in pediatric obesity has spurred interest in utilizing obesity pharmacotherapy to support sustained weight reduction in pediatric cohorts, in the hopes of preventing the emergence of later-appearing, significant co-morbidities. Despite the enormous demand, the obstacles posed by performance of needed clinical trials in the pediatric population markedly limits available pharmacotherapy for the treatment of obesity in pediatrics. Currently, there are five medications approved by the Food and Drug Administration for use in youth with obesity. In 2022, the phentermine/topiramate (PHEN/TPM), once-daily, controlled-release, combination product received FDA approval, for the indication of chronic weight management, in youth with obesity, ages 12 years and older. The objectives of this narrative review are to: (1) Review the mechanism of action of phentermine and topiramate, (2) Summarize the safety and efficacy data of topiramate and phentermine use as both monotherapies and in combination, and (3) Discuss clinical practice guidelines and clinical implications, for the use of these agents in youths with obesity.Keywords: phentermine, topiramate, pediatric obesity, obesity pharmacotherapy

Jinli Wang,1,2,* Min Jeong Seo,1,* Michael B Deci,1 Brian R Weil,3 John M Canty,3,4 Juliane Nguyen1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, USA; 2Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA; 3Department of Medicine, Department of Physiology and Biophysics, Department of Biomedical Engineering, The Clinical and Translational Research Center, University at Buffalo, Buffalo, NY, USA; 4VA Western New York Healthcare System, Buffalo, NY, USA *These authors contributed equally to this work Background: After myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.Materials and methods: Here, we developed poly(ethylene glycol) (PEG)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles loaded with a small molecule CCR2 antagonist to inhibit monocyte recruitment to the infarcted myocardium. To specifically target CCR2-expressing cells, PEG-DSPE micelles were further surface decorated with an anti-CCR2 antibody.Results: Targeted PEG-DSPE micelles showed eight-fold greater binding to CCR2-expressing RAW 264.7 monocytes than plain, non-targeted PEG-DSPE micelles. In a mouse model of MI, CCR2-targeting PEG-DSPE micelles loaded with a CCR2 small molecule antagonist significantly decreased the number of Ly6Chigh inflammatory cells to 3% of total compared with PBS-treated controls. Furthermore, CCR2-targeting PEG-DSPE micelles significantly reduced the infarct size based on epicardial and endocardial infarct arc lengths.Conclusion: Both non-targeted and CCR2-targeting PEG-DSPE micelles showed a trend toward improving cardiac function. As such, PEG-DSPE micelles represent a promising cardiac therapeutic platform. Keywords: CCR2, inflammatory monocytes, micelles, myocardial infarction

Mark D Mifflin,1 Brent S Betts,2 Jason Nguyen,3 Severin Pouly4 1Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 2Intermountain Eye and Laser Center, Boise, ID, USA; 3Department of Ophthalmology, West Virginia University School of Medicine, Morgantown, WV, USA; 4Little Rock Eye Clinic, Little Rock, AR, USA Purpose: To present refractive outcomes from consecutive cases with the Alcon Wavelight® EX500 excimer laser using photorefractive keratectomy (PRK) in patients with high myopia.Methods: A retrospective chart review of consecutive cases of high myopic eyes (≥6.0 Diopters [D]) undergoing PRK with the Alcon Wavelight EX500 excimer laser (Alcon Laboratories, Fort Worth, TX, USA) was done. Moderately high myopic eyes (6.0 to

Abstract Background Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA). Methods From self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed to in vivo influences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology. Results At the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA. PSPH exhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (PSPHL) hidden within the PSPH probe set. Among other significantly different genes were: for AA > CA, SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B. Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR CA) for 46/157 genes within that system. Conclusions Many of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of endothelial cells in vascular disease (hypertension, stroke) and cancer (via angiogenesis). Also, they are consistent with our over-arching hypothesis that genetic influences stemming from ancestral continent-of-origin could impact upon endothelial cell biology and thereby contribute to disparity of vascular-related disease burden among AA. The method used here could be productively employed to bridge the gap between information from structural genomics (for example, disease association) and cell function and pathophysiology.

Triple negative breast cancer (TNBC) is known for its heterogeneous nature and aggressive onset, limited unresponsiveness to hormone therapies and immunotherapy as well as high likelihood of metastasis and recurrence. Since no targeted standard treatment options are available for TNBC, novel and effective therapeutic targets are urgently needed. Ion channels have emerged as possible novel therapeutic candidates for cancer therapy. We previously showed that GABAA β3 subunit are expressed at higher levels in TNBC cell lines than non-tumorigenic MCF10A cells. GABAA β3 subunit knockdown causes cell cycle arrest in TNBC cell lines via decreased cyclin D1 and increased p21 expression. However, it is not known if the upregulated GABAAR express at the cell-surface in TNBC and mediate Cl- flux. Cl- ions are known to play a role in cell-cycle progression in other cancers such as gastric cancer. Here, using surface biotinylation and (N-(Ethoxycarbonylmethyl)-6-Methoxyquinolinium Bromide) MQAE-dye based fluorescence quenching, we show that upregulated GABAAR are on the cell-surface in TNBC cell lines and mediate significantly higher chloride (Cl-) flux as compared to non-tumorigenic MCF10A cells. Moreover, this GABAAR mediated Cl- flux can be modulated by pharmacological agents and is decreased in TNBC cells with GABAA β3 subunit knockdown. Further, treatment of TNBC cells with bicuculline, a GABAAR antagonist reduced cell viability in TNBC cells Overall, these results point to an unexplored role of GABAAR mediated Cl- flux in TNBC. [ABSTRACT FROM AUTHOR]

A key uncertainty in interpreting observations of bimodal merging galaxy clusters is the unknown angle between the subcluster separation vector and the plane of the sky. We present a new method for constraining this key parameter. We find analogs of observed systems in cosmological n-body simulations, and quantify their likelihood of matching the observed projected separation and relative radial velocities between subclusters, as a function of viewing angle. We derive constraints on the viewing angle of many observed bimodal mergers including the Bullet Cluster (1E 0657-558) and El Gordo (ACT-CL J0102-4915). We also present more generic constraints as a function of projected separation and relative radial velocity, which can be used to assess additional clusters as information about them becomes available. The constraints from these two observables alone are weak (typically ≳-75° at 68% confidence and ≳-60° at 95% confidence), but they incorporate much more cosmological context than the classical timing argument, marginalizing over many realizations of substructure, peculiar velocities, and so on. Compared with the MCMAC code, which implements the timing argument on NFW halos, our constraints generally predict subcluster separation vectors closer to the plane of the sky. This is because in realistic mergers, the subcluster velocity vectors are not entirely parallel to the separation vector (i.e., the mergers are not perfectly head-on). As a result, observation of a non-zero relative radial velocity does not exclude a separation vector in the plane of the sky, as it does in the head-on timing argument employed by MCMAC.

Purpose:Previous studies have suggested an association between increased thoracic kyphosis and neural axis abnormalities in patients with adolescent idiopathic scoliosis (AIS). However, the basis for this finding is unclear, and this association has been mainly noted in retrospective studies on a non-consecutive series of patients. The purpose of this study was to assess the relationship between thoracic kyphosis and neural axis abnormalities in patients with AIS. Methods:We studied a consecutive series of AIS patients treated with spinal fusion. Thoracic kyphosis (T2 to T12) was measured from preoperative lateral radiographs. All patients underwent a spine magnetic resonance imaging (MRI) prior to surgery, and MRI reports were reviewed to determine the presence of neural axis abnormalities. Statistical analyses included descriptive statistics and chi-squared analysis. Results:This study included 210 patients with AIS. There were no significant differences in age or gender between patients with thoracic hypokyphosis (kyphosis < 20°), normal thoracic kyphosis (kyphosis 20° to 40°) and thoracic hyperkyphosis (kyphosis > 40°) (p > 0.05). Neural axis abnormalities were present in 17.9% of patients with thoracic hypokyphosis, 9.8% of patients with normal thoracic kyphosis and 13.6% of patients with thoracic hyperkyphosis (p = 0.60). There were no significant differences in rates of Chiari malformation, syrinx, intra-spinal masses and other central nervous system abnormalities between groups (p > 0.05). Conclusions:Thoracic kyphosis was not associated with neural axis abnormalities in our consecutive series of patients with AIS. Increased thoracic kyphosis may not be a reliable indicator for the presence of neural axis abnormalities in patients with AIS. Level of Evidence:IV.

Six hundred and fifty-four inpatients who participated in a spiritual group therapy intervention provided qualitative feedback regarding what helped them and what could be improved. Patients revealed that enjoying a sense of connection with other people and a sense of openness in the groups and simply talking about spirituality with other people was helpful to them. Many group members requested that groups go on for a longer amount of time than 12 sessions, to have longer sessions, and to have more frequent meetings. In addition, members described improvements that could be made to the group, including members' being better screened, leaders preventing individual members from dominating discussions or from being quiet or leaving the group early, and members' wanting more structure as well as more open discussion. The findings highlight the importance of connection, openness, and spirituality when implementing spiritual group interventions in hospital settings. Implications for future research, training, and clinical interventions are discussed. [ABSTRACT FROM AUTHOR]

Although recipients of donor lungs from smokers have worse clinical outcomes, the underlying mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema (as estimated by lung weight), the rate of alveolar fluid clearance (AFC; measured by airspace instillation of 5% albumin) and biomarkers of lung epithelial injury and inflammation (bronchoalveolar lavage [BAL] surfactant protein-D (SP-D) and IL-8) in ex vivo lungs recovered from 298 organ donors. The extent of pulmonary edema was higher in current smokers (n = 127) compared to nonsmokers (median 408 g, interquartile range [IQR] 364-500 vs. 385 g, IQR 340-460, p = 0.009). Oxygenation at study enrollment was worse in current smokers versus nonsmokers (median PaO2 /FiO2 214 mm Hg, IQR 126-323 vs. 266 mm Hg, IQR 154-370, p = 0.02). Current smokers with the highest exposure (≥20 pack years) had significantly lower rates of AFC, suggesting that the effects of cigarette smoke on alveolar epithelial fluid transport function may be dose related. BAL IL-8 was significantly higher in smokers while SP-D was lower. These findings indicate that chronic exposure to cigarette smoke has important effects on inflammation, gas exchange, lung epithelial function and lung fluid balance in the organ donor that could influence lung function in the lung transplant recipient.

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p

Bone continually adapts to meet changing physical and biological demands. Osteoblasts, osteoclasts, and osteocytes cooperate to integrate these physical and biochemical cues to maintain bone homeostasis. Although TGFβ acts on all three of these cell types