Publications by authors named "Shadiack A"

Background: With increasing numbers of human-animal interactions, there has been an increase in animal-related injuries. While canine bites are the most commonly reported animal injury, little data exists in regard to the other classes of animals, particularly marine life. The last comprehensive report on injuries related to noncanine bites and stings seen in emergency departments (EDs) across the US was between 2011 and 2015.

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Description In this review, we argue that exercise (physical activity) be monitored as a vital sign since no other basic sign or symptom provides as much information about a patient's health status. The influence of regular exercise on patient health is indisputable, with strong evidence to show the power of exercise to mitigate chronic disease and improve overall health. Several simple tools, such as Physical Activity as a Vital Sign and Exercise as a Vital Sign are available to assess patient physical activity.

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Blood products are likely to be critical components of the medical response to nuclear detonation, as the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) includes depletion of platelets and red blood cells that can lead to lethal hemorrhage and anemia. There is, however, only limited clinical information on the use of blood products to treat H-ARS. As currently configured, the US blood supply cannot meet the predicted surge in blood product demand that is likely to occur short-term and possibly long-term in the event of a large nuclear detonation.

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Context: Concussions are the most common type of traumatic brain injury (TBI) and can often occur in athletes. These injuries have many deleterious acute symptoms and can lead to the development of postconcussive syndrome (PCS). Osteopathic manipulative treatment (OMT) is a treatment option that may benefit patients with concussions and PCS.

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Background: The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury algorithm is used to identify children at low risk of clinically significant traumatic brain injuries to reduce computed tomography (CT) exposure. Adapting PECARN rules based on population-specific risk stratification has been suggested to improve diagnostic accuracy.

Objective: This study sought to identify center-specific patient variables, beyond PECARN rules, that may enhance the identification of patients requiring neuroimaging.

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Background: Cytokine release syndrome is a life-threatening condition known to cause fever and multiple organ dysfunction and is suspected to be related to the severity of coronavirus disease 2019 (COVID-19). We sought to examine the utility of the HScore and non-cytokine markers of inflammation for predicting COVID-19 outcomes. We hypothesized that cytokine storm, assessed by a modified HScore, would be linked to more severe COVID-19 symptoms and higher mortality.

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Objective: TX-004HR is a low-dose estradiol (E2) softgel vaginal insert designed to be rapidly dissolving and mucoadhesive. This report describes the physical attributes and pharmacokinetic parameters of the softgel vaginal insert evaluated for the treatment of moderate to severe dyspareunia due to menopausal vulvar and vaginal atrophy.

Methods: In vitro dissolution studies with 25-μg E2 inserts were performed and media samples were analyzed for E2 by high-performance liquid chromatography.

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Objective: In the REPLENISH trial, women receiving TX-001HR-an oral, softgel capsule, combining 17β-estradiol (E2) and progesterone (E2 mg/P4 mg 1/100, 0.5/100), had significantly improved vasomotor symptoms, while having their endometrium protected from hyperplasia. The objective here was to describe P4 levels sufficient to counteract the potential endometrial effects of 1 or 0.

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Stress fractures are a frequent cause of lower extremity pain in athletes, and especially in runners. Plain imaging has a low sensitivity. Magnetic resonance imaging (MRI) or bone scan scintigraphy is the criterion standard, but expensive.

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Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores.

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The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here.

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The neurobiology of sexual behavior involves the interrelationships between sex steroids and neurotransmitters that result in both central nervous system (CNS) effects and effects in the genitalia. Tools such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scanning can help determine what areas of the brain are activated under sexual stimulation. Our understanding of the role of various neurotransmitters, neurosteroids and other CNS-acting compounds is improving.

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Melanocortinergic agents are currently being investigated for a possible therapeutic role in male and female sexual dysfunction. These investigations were sparked by findings that systemic administration of a synthetic analog of alpha-MSH, MT-II, causes penile erections in a variety of species, including humans. Several other melanocortinergic agents including HP-228, THIQ, and bremelanotide (PT-141) have since been shown to have erectogenic properties thought to be due to binding to melanocortin receptors in the central nervous system, particularly the hypothalamus.

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Disorders of sexual desire affect an estimated 30% of women in North America and Europe, with etiologies based on interpersonal, personal, and physiological factors. There are currently no pharmacological agents approved for use in the treatment of female sexual dysfunction. This is due, in part, to a focus on the effects of experimental drugs on reflexive components of sexual behavior, such as lordosis, in animal models.

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PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following subcutaneous administration to healthy male subjects and to patients with erectile dysfunction (ED) who report an inadequate response to Viagra. An inadequate response was defined for this study by patient report indicating that achievement of an erection suitable for vaginal penetration occurred < or =50% of the time while taking 100 mg Viagra. Erectile responses were assessed by RigiScan in healthy subjects in the absence of visual sexual stimulation (VSS) and in ED patients in the presence of VSS.

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PT-141, a synthetic peptide analogue of alpha-MSH, is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Administration of PT-141 to rats and nonhuman primates results in penile erections. Systemic administration of PT-141 to rats activates neurons in the hypothalamus as shown by an increase in c-Fos immunoreactivity.

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Transecting the axons of neurons in the adult superior cervical ganglion (SCG; axotomy) results in the survival of most postganglionic neurons, the influx of circulating monocytes, proliferation of satellite cells, and changes in neuronal gene expression. In contrast, transecting the afferent input to the SCG (decentralization) results in nerve terminal degeneration and elicits a different pattern of gene expression. We examined the effects of decentralization on macrophages in the SCG and compared the results to those previously obtained after axotomy.

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Axonal transection of adult sympathetic and sensory neurons leads to a decrease in their content of target-derived nerve growth factor (NGF) and to dramatic changes in the expression of several neuropeptides and enzymes involved in transmitter biosynthesis. For example, axotomy of sympathetic neurons in the superior cervical ganglion (SCG) dramatically increases levels of galanin, vasoactive intestinal peptide (VIP), and substance P and their respective mRNAs and decreases mRNA levels for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Axotomy of sensory neurons in lumbar dorsal root ganglia (DRG) increases protein and mRNA levels for galanin and VIP and decreases levels for substance P and calcitonin gene-related peptide (CGRP).

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Peripheral neurons begin to express galanin after axotomy. When neurons in the superior cervical ganglion were axotomized near (about 2 mm) from the ganglion, galanin-like immunoreactivity (IR) was maximal within 72 h. Axotomy of neurons in the middle and inferior cervical ganglion complex (MICG), which could be performed 2 cm from the ganglia, led to an additional galanin increase 7 and 14 days later.

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Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor.

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Adult peripheral neurons undergo dramatic shifts in gene expression following axotomy that are collectively referred to as the cell body reaction. Changes in neuropeptide expression are a prominent feature of these axotomized neurons. For example, while sympathetic, sensory, and motor neurons do not normally express the neuropeptides galanin and vasoactive intestinal peptide, they begin to do so within days after axotomy.

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Following peripheral nerve transection, a series of biochemical changes occurs in axons and Schwann cells both at the site of the lesion and distal to it. Macrophages differentiated from monocytes that invade the area in response to transection (elicited macrophages) and, perhaps, also macrophages normally present in the tissue (resident macrophages) play important roles in these changes. In addition, nerve transection produces changes in the cell bodies of axotomized neurons and their surrounding glial cells, located at some distance from the lesion.

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