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Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation...

PURPOSE: To investigate whether microfracture with a cannulated hollow awl can yield more patent marrow channels and allow greater mobilization of the reparable cells to the defect compared to the conventional awl with blunt end in human knee joints. METHODS: Patients who were planned for 1-stage bilateral total knee arthroplasty due to degenerative osteoarthritis with well-preserved lateral femoral condylar cartilage were retrospectively included. A 10-mm × 20-mm, rectangular, full-thickness chondral defect was made on the lateral femoral condyle on each knee joint...

Brain death is known to be associated with physiologic derangements but their incidence is poorly described. Knowledge of the changes that occur during brain death is important for management of the potential organ donor. Thus, we sought to characterize the pathophysiology that occurs during brain death in patients with traumatic injuries. All brain-dead patients over a 10-year period were identified from the trauma registry at a level 1 urban trauma center. Patient demographics, injury characteristics, and clinical data for defining organ dysfunction were reviewed for the 24 hours surrounding brain-death declaration...

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Traumatic globe dislocation into the maxillary sinus is a rare event and usually associated with a poor visual outcome if not managed appropriately. We report a 45-year-old female patient who presented to the emergency after blunt injury to her face with a door. Initial evaluation revealed nil perception of light and an apparently anophthalmic socket. Neuroimaging revealed large floor and medial wall fracture with dislocation of the globe into the maxillary sinus. The patient underwent exploration with repositioning of the globe and fracture repair...

PURPOSE: Enlargement of the ilioinguinal nerve at the external inguinal ring is observed in 34% of patients undergoing primary open inguinal herniorrhaphy; in 88% of patients it occurs at the fascial edge where the hernia mushrooms with abdominal pressure. Compression neuropathy occurs near many anatomical nerve constriction sites and is associated with enlargement of the peripheral nerve accompanied by sensory changes. METHODS: In this prospective study, Carolina Comfort Scale (CCS) questionnaire data was collected for 35 primary hernia repairs...

BACKGROUND AND AIMS: The brain reward system is key to understanding adolescent obesity in the current obesogenic environment, rich in highly appetising stimuli, to which adolescents are particularly sensitive. We aimed to examine the association between body fat levels and brain reward system responsivity to general (monetary) rewards in male and female adolescents. METHOD: Sixty-eight adolescents (34 females; mean age [standard deviation]=16.56 [1.35]) were measured for body fat levels with bioelectric impedance, and underwent a functional magnetic resonance imaging (fMRI) scan during the Monetary Incentive Delay (MID) task...

Heterotrimeric G proteins are usually activated by the guanine-nucleotide exchange factor (GEF) activity of GPCRs. However, some non-receptor proteins are also GEFs. GIV (a.k.a Girdin) was the first non-receptor protein for which the GEF activity was ascribed to a well-defined protein sequence that directly binds Gαi. GIV expression promotes metastasis and disruption of its binding to Gαi blunts the pro-metastatic behavior of cancer cells. Although this suggests that inhibition of the Gαi-GIV interaction is a promising therapeutic strategy, protein-protein interactions (PPIs) are considered poorly "druggable" targets requiring case-by-case validation...

Humans with a patent foramen ovale (PFO) have a higher esophageal temperature (Tesoph) than humans without a PFO (PFO-) . Thus, the presence of a PFO might also be associated with differences in thermal responsiveness to passive cooling and heating, such as shivering and hyperpnea, respectively. The purpose of this study was to determine if thermal responses to passive cooling and heating are different between PFO- subjects and subjects with a PFO (PFO+). We hypothesized that compared to PFO- subjects, PFO+ subjects would cool down more rapidly and heat up slower, and PFO+ subjects that experienced thermal hyperpnea would have a blunted increase in ventilation...

The aim of this study was to determine reactive oxygen species (ROS) could play a role in blunting Thr(172)-AMPKα phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30s sprint (Wingate test) in two occasions while breathing hypoxic gas (PIO2=75 mmHg): one after the ingestion of placebo (P) and another following the intake of antioxidants (A) (α-lipoic acid, vitamin C, and vitamin E), with a randomized double-blind design...

The underlying cause of systolic heart failure is the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, some vertebrate species and immature mammals are capable of full cardiac regeneration following multiple types of injury through cardiomyocyte proliferation. Little is known about what distinguishes proliferative cardiomyocytes from terminally differentiated, non-proliferative cardiomyocytes. Recently, several reports have suggested that oxygen metabolism and oxidative stress play a pivotal role in regulating the proliferative capacity of mammalian cardiomyocytes...

Activated lymphocytes perform a clonal balancing act, yielding a daughter cell that differentiates owing to intense PI3K signaling, alongside a self-renewing sibling cell with blunted anabolic signaling. Divergent cellular anabolism versus catabolism is emerging as a feature of several developmental and regenerative paradigms. Metabolism can dictate cell fate, in part, because lineage-specific regulators are embedded in the circuitry of conserved metabolic switches. Unequal transmission of PI3K signaling during regenerative divisions is reminiscent of compartmentalized PI3K activity during directed motility or polarized information flow in non-dividing cells...

Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...

Fosmid end sequencing has been widely utilized in genome sequence assemblies and genome structural variation studies. We have developed a new approach to construct fosmid paired-end libraries that is suitable for Illumina sequencing platform. This approach employs a newly modified fosmid vector (pFosClip) which contains two loxP sites with identical orientation and two inverse Illumina adaptor priming sites flanking the cloning site. DNA prepared from the fosmid library constructed with pFosClip can be treated with the Cre recombinase to remove most of the vector DNA, leaving only 107 bp of the vector sequence with insert DNA...

The ventromedial prefrontal cortex (vmPFC) has consistently appeared altered in post-traumatic stress disorder (PTSD). Although the vmPFC is thought to support the extinction of learned fear responses, several findings support a broader role for this structure in the regulation of fear. To further characterize the relationship between vmPFC dysfunction and responses to traumatic stress, we examined the effects of pretraining vmPFC lesions on trauma reactivity and enhanced fear learning in a rodent model of PTSD...

BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). METHODS: The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed...

Abdominal trauma is present in approximately 25% of pediatric patients with major trauma and is the most common cause of unrecognized fatal injury in children. Pediatric abdominal trauma is typically blunt in nature with the spleen being the most common organ injured. Non-operative management is employed in over 95% of patients. Penetrating injuries are less common but often require operative management. Knowledge of specific mechanisms of injury aids the clinician in the diagnosis of specific injuries. Computed tomography (CT) is the gold standard in the identification of intra-abdominal injury...

INTRODUCTION: LY3045697 is a potent and selective aldosterone synthase (CYP11B2) inhibitor that was developed as a safer alternative to mineralocorticoid receptor antagonists. Effects of LY3045697 on aldosterone and cortisol synthesis, as well as potassium ion homeostasis, were evaluated in two clinical studies in healthy subjects. MATERIALS AND METHODS: Two incomplete, placebo-controlled crossover-design clinical studies examined safety, pharmacodynamics, and pharmacokinetics under single and repeated dose conditions in healthy subjects...

BACKGROUND: TGFβ1, a decisive regulator of megakaryocyte maturation and platelet formation, has previously been shown to up-regulate both, store operated Ca2+ entry (SOCE) and Ca2+ extrusion by Na+/Ca2+ exchange. The growth factor thus augments the increase of cytosolic Ca2+ activity ([Ca2+]i) following release of Ca2+ from intracellular stores and accelerates the subsequent decline of [Ca2+]i. The effect on SOCE is dependent on a signaling cascade including p38 kinase, serum & glucocorticoid inducible kinase SGK1, and nuclear factor NFκB...

INTRODUCTION: Gastrointestinal disorders become more prevalent with ageing. This study is aimed to describe morphological changes that occur in the jejunal mucosa of male albino rats as a result of ageing and the protective effect of green tea supplements. MATERIAL AND METHODS: The experiment was performed on sixty rats: thirty young-adult (6-month old, body mass 200-220 g) and thirty old (24-month-old, body mass 220-260 g) animals. Each group was further divided into two subgroups (n = 15 each): control rats and green tea-treated rats that received 1...