Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner ...highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.
From the middle of the twentieth century, think tanks have played an indelible role in the rise of American conservatism. Positioning themselves against the alleged liberal bias of the media, ...academia, and the federal bureaucracy, conservative think tanks gained the attention of politicians and the public alike and were instrumental in promulgating conservative ideas. Yet, in spite of the formative influence these institutions have had on the media and public opinion, little has been written about their history. Here, Jason Stahl offers the first sustained investigation of the rise and historical development of the conservative think tank as a source of political and cultural power in the United States.What we now know as conservative think tanks--research and public-relations institutions populated by conservative intellectuals--emerged in the postwar period as places for theorizing and "selling" public policies and ideologies to both lawmakers and the public at large. Stahl traces the progression of think tanks from their outsider status against a backdrop of New Deal and Great Society liberalism to their current prominence as a counterweight to progressive political institutions and thought. By examining the rise of the conservative think tank, Stahl makes invaluable contributions to our historical understanding of conservatism, public-policy formation, and capitalism.
In this review, we summarize recent advances in understanding the etiology, risk factors and pathophysiology of focal task specific dystonia (FTSD), movement disorders characterized by abnormal motor ...activation during the performance of specific, repetitive actions. We focus on two common FTSD, musician’s dystonia and writer’s cramp. FTSD may pose a threat to the patient’s livelihood, and improved therapeutic treatments are needed.
Objective: To summarize the accumulated data on metabolic syndrome prevalence in patients with schizophrenia, examine evidence for a biological contribution of the mental illness to metabolic risk ...and review novel options available for management of prediabetic states.
Method: A Medline search using metabolic syndrome, insulin resistance and insulin sensitivity cross‐referenced with schizophrenia was performed on articles published between 1990 and May 2008.
Results: Recent evidence indicates that schizophrenia increases predisposition towards metabolic dysfunction independent of environmental exposure. Both fasting and non‐fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP‐1 modulators may prove promising tools for managing insulin resistance.
Conclusion: Because of lifestyle, disease and medication effects, schizophrenia patients have significant risk for cardiometabolic disease. Routine monitoring, preferential use of metabolically neutral antipsychotics and lifestyle education are critical to minimizing risk, with a possible role for antidiabetic medications for management of insulin resistant states that do not respond to other treatment strategies.
Background:
Optimal doses of iv glucocorticoids for Graves' orbitopathy (GO) are undefined.
Methods:
We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of ...three doses of iv methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit.
Results:
Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit.
Conclusions:
The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.
Objective: To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose ...hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment.
Method: A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross‐referenced with schizophrenia was performed on articles published between 1990 and May 2008.
Results: Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics.
Conclusion: Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic‐related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death.
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