A noninvasive ultrasound vibro-elastography technique for assessing ocular lesions.

Objective: This research aims to develop a noninvasive ultrasound vibro-elastography technique for assessing ocular lesions including intraocular melanoma and nevus lesions.

Method: Wave speed (WS) was noninvasively measured in the lesions at three different frequencies (i.e.

Failure to repair endogenous DNA damage in β-cells causes adult-onset diabetes in mice.

Age is the greatest risk factor for the development of type 2 diabetes mellitus (T2DM). Age-related decline in organ function is attributed to the accumulation of stochastic damage, including damage to the nuclear genome. Islets of T2DM patients display increased levels of DNA damage.

What Should the Surgeons Do at the Family Meeting: A Multi-Disciplinary Qualitative Description of Surgeon Participation in Palliative Care Discussions.

Objective: National guidelines have suggested that quality surgical care should incorporate effective palliative care (PC). Numerous barriers to surgeon participation remain and the domains of optimal surgeon participation are unclear.

Design: Eight semi-structured and multi-professional focus groups with 34 total participants.

Supporting surgical residents learning clinical palliative care: Insights from multi-disciplinary focus groups.

Background: A shortage of palliative care (PC) sub-specialists highlights the need for quality PC provided by treating surgeons, although no established curriculum exists to teach surgical residents PC skills. To guide curriculum development, we sought to determine what modifiable factors contribute to surgical residents successfully providing PC.

Methods: Eight focus groups with 34 participants were conducted.

Teaching primary palliative care to general surgical residents: A novel pedagogical approach drawn from multi-disciplinary focus group data.

Background: Primary palliative care (PPC) is provided by the primary team and is essential for high-quality surgical care. There is a recognized PPC clinical and research need but little work on the optimal way to teach PPC to general surgery residents. We sought to define important factors of PPC pedagogy (i.

Critical decisions in the trauma intensive care unit: Are we practicing primary palliative care?

Background: Devastating injuries require both urgent assessment by a trauma service and early attention to patients' goals of care (GOC). American College of Surgeons Trauma Quality Improvement Program (TQIP) guidelines recommend an initial palliative assessment within 24 hours of admission and family meeting, if needed, within 72 hours. We hypothesize that a primary palliative care-based practice improves adherence to TQIP guidelines in trauma patients.

Adnexal Torsion Predictive Tool Maintains Applicability in a Heterogeneous Pediatric Population.

Study Objective: A previously published scoring system showed promise in identifying adnexal torsion in adolescents. However, published patients were homogeneously Caucasian/White. We sought to assess whether this scoring system was generalizable to a more diverse population that is predominantly African American and overweight.

Microbial symbionts regulate the primary Ig repertoire.

The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape preimmune Ig repertoires, expressed on IgM IgD B cells as B cell receptors (BCRs), are poorly defined. Here, we studied germ-free mice and conventionalized littermates to explore the hypothesis that symbiotic microbes help shape the preimmune Ig repertoire.

Identification of a highly neurotoxic α-synuclein species inducing mitochondrial damage and mitophagy in Parkinson's disease.

Exposure of cultured primary neurons to preformed α-synuclein fibrils (PFFs) leads to the recruitment of endogenous α-synuclein and its templated conversion into fibrillar phosphorylated α-synuclein (pα-synF) aggregates resembling those involved in Parkinson's disease (PD) pathogenesis. Pα-synF was described previously as inclusions morphologically similar to Lewy bodies and Lewy neurites in PD patients. We discovered the existence of a conformationally distinct, nonfibrillar, phosphorylated α-syn species that we named "pα-syn*.

Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin's Anorectic Signaling Actions.

The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.

Serum- and Glucocorticoid-Inducible Kinase 1 Confers Protection in Cell-Based and in In Vivo Neurotoxin Models via the c-Jun N-Terminal Kinase Signaling Pathway.

Serum glucocorticoid kinase 1 (SGK1) has been shown to be protective in models of Parkinson's disease, but the details by which it confers benefit is unknown. The current study was designed to investigate the details by which SGK1 confers neuroprotection. To do this we employed a cellular neurodegeneration model to investigate c-Jun N-terminal kinase (JNK) signaling and endoplasmic reticulum (ER) stress induced by 6-hydroxydopamine.

Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.

The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high potency and selectivity and appropriate pharmacokinetic properties through systematic SAR studies is reported. Docking studies supported the observed SAR. Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 μM), and good in vitro and in vivo pharmacokinetic properties.

Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats.

To build upon recent findings that mitochondrial JNK signaling is inhibited by selectively blocking the interaction between JNK and Sab, we utilized a cell-permeable peptide to demonstrate that ischemia/reperfusion (I/R) injury could be protected in vivo and that JNK mitochondrial signaling was the mechanism by which reactive oxygen species (ROS) generation, mitochondrial dysfunction, and cardiomyocyte cell death occur. We also demonstrated that 5 mg/kg SR-3306 (a selective JNK inhibitor) was able to protect against I/R injury, reducing infarct volume by 34% (p < 0.05) while also decreasing I/R-induced increases in the activity of creatine phosphokinase and creatine kinase-MB.

Blocking c-Jun N-terminal kinase (JNK) translocation to the mitochondria prevents 6-hydroxydopamine-induced toxicity in vitro and in vivo.

Because oxidative stress and mitochondrial dysfunction are well known contributors to Parkinson disease (PD), we set out to investigate the role mitochondrial JNK plays in the etiology of 6-hydroxydopamine-induced (6-OHDA) oxidative stress, mitochondrial dysfunction, and neurotoxicity in SHSY5Y cells and neuroprotection and motor behavioral protection in vivo. To do this, we utilized a cell-permeable peptide of the outer mitochondrial membrane protein, Sab (SH3BP5), as an inhibitor of JNK mitochondrial translocation. In vitro studies showed that 6-OHDA induced JNK translocation to the mitochondria and that inhibition of mitochondrial JNK signaling by Tat-Sab(KIM1) protected against 6-OHDA-induced oxidative stress, mitochondrial dysfunction, and neurotoxicity.

Small Molecule c-jun-N-terminal Kinase (JNK) Inhibitors Protect Dopaminergic Neurons in a Model of Parkinson's Disease.

There are currently no drugs to treat neurodegeneration in Parkinson's disease (PD) and all existing medications only treat symptoms, lose efficacy over time, and produce untoward side effects. In the current work, we report the first highly selective, orally bioavailable, c-jun-N-terminal kinase (JNK) inhibitor for protection of dopaminergic neurons in vitro and in vivo. At 300 nM this compound showed statistically significant protection of primary dopaminergic neurons exposed to 1-methyl-4-phenylpyridinium (MPP(+)), had pharmacokinetic properties in rodents consistent with twice daily (b.