Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.
Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.
Amblyopia, informally called "lazy eye," is reduced vision in an eye due to abnormal visual development as a child. Amblyopia is a condition in which an eye has reduced vision due to abnormal development of the visual pathways during childhood. When the brain receives poor information from one eye, it stops communicating with that eye. This means that the brain relies on information from the other, "stronger" eye. It is possible for amblyopia to occur in both eyes. Causes of AmblyopiaAmblyopia can be present at birth, but children may also develop it as they grow. Amblyopia can be caused by other eye problems, such as refractive errors (nearsightedness, farsightedness), strabismus or squint (when the eyes do not move together as a pair), and cataracts. In some cases, the cause is a combination of these factors.
Wearing contact lenses is generally safe, but complications can occur.As many as 45 million people in the US wear contact lenses to improve their vision. Contacts are generally safe, but several serious complications can occur, especially if proper care is not taken.
Nystagmus is a condition in which the eyes move involuntarily, typically in a rhythmic pattern. Types and Causes of NystagmusNystagmus can be categorized in different ways, including based on age at onset, type of eye movement, or specific cause.There are 2 major categories of nystagmus related to when the disease occurs. Congenital nystagmus is present shortly after birth. Acquired nystagmus begins after 6 months of life. Congenital motor nystagmus is the most common type of congenital nystagmus. This usually occurs by itself, is not associated with any other congenital abnormalities, and does not go away but can lessen with time. Other causes of congenital nystagmus include developmental abnormalities in the eye structures, such as the cornea, lens, retina, and optic nerve, or abnormalities in the visual pathways in the brain.Acquired nystagmus has several medical and neurologic causes, including certain medications, stroke, brain injuries or tumors, and diseases of the vestibular system. When vestibular organs are not functioning normally, the body has a difficult time balancing and may induce nystagmus. A clinician can evaluate for the different causes by taking a thorough history, by physical examination, and sometimes with blood tests and imaging.
As patient survival after cardiac transplantation has improved over the course of the last several decades, clinicians are now faced with late complications. This includes aortic stenosis which, traditionally, has been treated with reoperative sternotomy and aortic valve replacement. Transcather aortic valve replacement (TAVR) offers a minimally invasive alternative in this high‐risk population. A small but growing number of cases of TAVR after heart transplantation in high‐risk patients have been reported in the last 10 years; we now present a case of aortic valve replacement via a transcatheter approach 24 years after cardiac transplantation.
As the online education environment continues to grow, the use of online mechanisms for discussion have become important for enhancing the development of a learning community. Changing the way online discussion boards are used today, from teacher-generated prompts to student-created videos, which include a discussion question, may improve the learning experience and engagement. Therefore, there is always more to learn and more to try with instructional technology.
An infographic is a type of picture that, if done correctly, blends complex data with understandable design. College students today are inundated by visually stimulating screen-based environments. Infographics utilize that environment to enhance the process of summarizing educational material. Data visualization can provide students with multiple dimensions of competency including searching, systematic thinking, and effective interdisciplinary teamwork.
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