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It is our position that, given the present limitations of our therapeutic arsenal, both researchers and clinicians would be well-advised to pay closer attention to human specific factors such as the role of language, the creation of personal narratives, and how factors such as these interface with underlying biological diatheses in mental illness. These interactions between pathophysiology and intrapersonal processes may be critical to both the in vivo expression of the underlying biological mechanisms of psychiatric disease states, and to the development of enhancements in therapeutic efficacy. Lastly, we discuss the implications of more coherently integrating neuroscientific research and clinical practice for more effectively addressing the challenges of understanding and treating mental illness.Pornography addiction and sexual dysfunction are increasingly prevalent in young men. Previous studies suggest that prenatal androgen exposure plays a role in addiction and sexual functionality. Here, we tested whether lower second-to-fourth finger length ratio (2D4D) and later age at spermarche, both putative indicators of higher androgen levels in utero, correlate with online sexual compulsivity (OSC scale of ISST), erectile function (IIEF-5), and ejaculatory control (PEPA) in 4,370 young men (age IQR 25-26 years) of the Cohort Study on Substance Use Risk Factors. Statistical analyses revealed that lower 2D4D correlated with higher scores on the OSC scale. Moreover, higher age at spermarche correlated with higher OSC scores and decreased erectile function. Interestingly, OSC severity, but not the frequency of pornography use, correlated negatively with erectile function and ejaculatory control. This is the first study to associate two independent proxies of prenatal testosterone level with OSC. These findings provide novel insight into intrauterine predisposition of sexual behavior and related sexual function in adulthood.Wooden breast (WB) is a degenerative myopathy seen in modern broiler birds resulting in quality downgrade of breast fillets. Affected filets show increased toughness both before as well as after cooking and have decreased water holding capacity and marinade pick up compared to normal fillets. Although the exact etiology is unknown, the circulatory insufficiency and increased oxidative stress in the breast muscles of modern broiler birds could be resulting in damage and degeneration of muscle fibers leading to myopathies. Three independent experiments were conducted to evaluate the effect of various dietary interventions on the incidence of WB when birds are exposed to oxidative stress associated with feeding oxidized fat and mild heat stress. Feed additives such as dietary antioxidant [Ethoxyquin (ETX)], mineral methionine hydroxy analog chelate (MMHAC) of Zn, Cu, and Mn, and organic selenium (Org Se) were tested at recommended levels. In experiment 1, ETX reduced (P less then 0.05) the incidence of severe oxidative stress, and improving tissue healing process of the bird.Non-reversible fibrosis is common in various diseases such as chronic renal failure, liver cirrhosis, chronic pancreatitis, pulmonary fibrosis, rheumatoid arthritis and atherosclerosis. Transforming growth factor beta 1 (TGF-β1) is involved in virtually all types of fibrosis. We previously described the involvement of Ras GTPase isoforms in the regulation of TGF-β1-induced fibrosis. The guanine nucleotide exchange factor Son of Sevenless (Sos) is the main Ras activator, but the role of the ubiquitously expressed Sos1 in the development of fibrosis has not been studied. check details For this purpose, we isolated and cultured Sos1 knock-out (KO) mouse embryonic fibroblasts, the main extracellular matrix proteins (ECM)-producing cells, and we analyzed ECM synthesis, cell proliferation and migration in the absence of Sos1, as well as the role of the main Sos1-Ras effectors, Erk1/2 and Akt, in these processes. The absence of Sos1 increases collagen I expression (through the PI3K-Akt signaling pathway), total collagen proteins, and slightly increases fibronectin expression; Sos1 regulates fibroblast proliferation through both PI3K-Akt and Raf-Erk pathways, and Sos1-PI3K-Akt signaling regulates fibroblast migration. These study shows that Sos1 regulates ECM synthesis and migration (through Ras-PI3K-Akt) and proliferation (through Ras-PI3K-Akt and Ras-Raf-Erk) in fibroblasts, and describe for the first time the role of the Sos1-Ras signaling axis in the regulation of cellular processes involved in the development of fibrosis.

Abnormal synchronization of neuronal activity in dopaminergic circuits is related to motor impairment in Parkinson’s disease (PD). Vibrotactile coordinated reset (vCR) fingertip stimulation aims to counteract excessive synchronization and induce sustained unlearning of pathologic synaptic connectivity and neuronal synchrony. Here, we report two clinical feasibility studies that examine the effect of regular and noisy vCR stimulation on PD motor symptoms. Additionally, in one clinical study (study 1), we examine cortical beta band power changes in the sensorimotor cortex. Lastly, we compare these clinical results in relation to our computational findings.

examines six PD patients receiving noisy vCR stimulation and their cortical beta power changes after 3 months of daily therapy. Motor evaluations and at-rest electroencephalographic (EEG) recordings were assessed off medication pre- and post-noisy vCR.

follows three patients for 6+ months, two of whom received daily regular vCR and one patient from stdy 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.

In these feasibility studies of eight PD patients, regular vCR and noisy vCR were well tolerated, produced no side effects, and delivered sustained cumulative improvement of motor performance, which is congruent with our computational findings. In study 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.