Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Working in fours: generational communication in the emergency department.

BACKGROUND: This study examined the conflicts between different generations working in US emergency departments (ED). We sought to record generational differences involving communication preferences, perceived areas of conflict, work motivations, and attitudes regarding work-life balance. METHODS: We developed a survey to assess the physician perspective on generational conflict in the ED. The survey was distributed to members of the American College of Emergency Physicians, a professional organization comprising emergency medicine physicians in the USA. RESULTS: We received 696 completed responses. Men represented 60% of respondents and the largest proportion of respondents were emergency physicians working in community settings (53%); 11% were residents. Generation representation was smallest for Traditionalist (2%) and largest for Gen X (43%). Seventy percent reported observing conflict due to generational communication with the largest frequency being once a week (26%). In the associated open-ended questions, 247 (33%) provided 316 anecdotal descriptions of observed conflict. Responses clustered into seven themes (ordered by frequency): Work Ethic, Treatment Approach, Technology Application, Entitlement, Professionalism, Work Life/Balance, and Communication Style. Comparing Work Ethic responses, 52-70-year-olds reported that younger providers are less interested in "accomplishing anything" while 26-34-year-olds resented that attitude. Respondents completing the open-ended questions regarding preventing and responding to conflict provided some insight into helpful strategies including actions supportive of clear communication and standardized policies and expectations. Only 5% of respondents reported that they had discussed generational communication in department meetings with the odds of a woman reporting conflict being less than males (p = .01). CONCLUSION: Conflicts in the ED in the USA can be attributed to how an individual views the values of someone from another generation. Understanding the frequency and areas of generational conflict in the ED can help medical leaders find strategies to mitigate negative workplace interactions.

Mitophagy: An Emerging Target in Ocular Pathology.

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.

iWorkHealth: An instrument to identify workplace psychosocial risk factors for a multi-ethnic Asian working population.

OBJECTIVE: The current study aimed to develop iWorkHealth, a valid and reliable self-administered instrument which identifies workplace psychosocial risk factors in Singapore. METHODS: The survey was conducted among 2718 employees who were primarily salaried workers and working in five companies from the healthcare, banking and finance, and legal sectors in Singapore. Factor extraction and item reduction were conducted using exploratory factor analysis (EFA) and Mokken scale analysis (MSA). Construct validity, internal consistency and convergent validity of the final scale were confirmed using confirmatory factor analysis (CFA), Cronbach's alpha and Pearson correlation coefficients, respectively. Multiple Indicators Multiple Causes model was used to detect Differential Item Functioning (DIF). RESULTS: EFA and MSA identified a five-factor solution (job demand, job control, employee and management engagement, supervisor support and colleague support) for the 27 items iWorkHealth instrument. CFA demonstrated that the five-factor model fitted the data with high internal consistency (Cronbach's alpha ranged from 0.79 to 0.92). The convergent validity was shown through significant association with existing scales-high job demand was significantly associated with high burnout and depression, while high job control, employee and management engagement, supervisor support and coworker support were significantly associated with low burnout and depression. Ten items were detected with significant DIF, but impact was minimal on the associations between socio-demographics factors and iWorkHealth subscales. CONCLUSIONS: The findings provided evidence that the iWorkHealth instrument which comprises 27 items in five domains of psychosocial risk at the workplace is a reliable and valid instrument that could be used to measure and compare the level of psychosocial risk factors across companies and industries in Singapore.

Anesthetic management for resection of para-aortic paraganglioma and unexpected aortic resection: A case report.

Paragangliomas account for 15-20% of pheochromocytomas derived from chromaffin cells and secretes catecholamines. It has a high mortality rate due to hypertension and challenging anesthetic management. The present report is of a case of the successful management of paraganglioma resection with unexpected aortic resection. The patient presented for paraganglioma resection. The blood pressure (BP) was well controlled with α blockade followed by ß blockade prior to surgery. The patient was under general anesthesia, with multiple intravenous lines, catheters and an arterial line. Induction was achieved by the administration of narcotic and volatile agents. During the procedure, the aorta was found to require resection in order to complete the tumor resection. The BP changed markedly with clamping and unclamping, tumor vein ligation and tumor resection. The increased BP due to catecholamine release and unclamping was controlled with phentolamine, nitroprusside, esmolol and labetolol. Drops in BP due to tumor vein ligation and clamping were managed with norepinephrine and vasopressin. With close communication and monitoring, the surgery on the patient was successfully completed and the patient was discharged days later in a hemodynamically stable condition. The diagnosis was further confirmed by pathology. This was a challenging case of paraganglioma resection with unexpected aortic resection. The success achieved suggests that the resection of paraganglioma and an aortic segment requires delicate anesthetic management. The key are α blockade and ß blockade as necessary to control BP pre-operatively, frequent communication between the anesthesiologist and surgeons, intra-operative intervention in excess catecholamine release with phentolamine, nitroprusside and labetalol prior to tumor removal, and vasopressin for catecholamine deficiency when clamping or subsequent to tumor removal. It is a delicately orchestrated process requiring team work.

Obesity, inflammation, and lung injury (OILI): the good.

Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were reduced significantly in obesity, which is associated with increased inflammation, indicated by increase of TNF α and IL-6, through activation of toll-like receptor (TLR4) and nuclear factor light chain κ B (NF- κ B) signaling pathways. Administration of these adipocytokines promotes weight loss and reduces inflammation. Zinc-α 2-glycoprotein (ZAG), vaspin, IL-10, interleukin-1 receptor antagonist (IL-1RA), transforming growth factor ß (TGF-ß1), and growth differentiation factor 15 (GDF15) are also regarded as anti-inflammatories. There were controversial reports. Furthermore, there is a huge lack of studies for obesity related lung injury. The effects of adiponectin on lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD), and pneumonia were anti-inflammatory and protective in lung injury. Administration of IL-10 agonist reduces mortality of acute lung injury in rabbits with acute necrotizing pancreatitis, possibly through inhibiting proinflammation and strengthening host immunity. Very limited information is available for other adipocytokines.