2007). Increased glial activation is well known to occur in the Selleckchem RG7422 dorsal horn of the spinal cord in animal models of peripheral neuropathy, as demonstrated by increased production

of glial fibriliary acidic protein (GFAP) in astrocytes and ionized calcium binding adaptor molecule-1 (Iba-1) in microglia (Pekny and Pekna 2004; Racz et al. 2008b). When strongly activated, glia can increase expression of proinflammatory factors such as phosphorylated Inhibitors,research,lifescience,medical p38 mitogen-activated protein kinase (p-p38MAPK) that can lead to production and release of proinflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which subsequently bind and activate their respective receptors on nearby neurons and glia (De Leo et al. 2006; Watkins et al. 2007; Milligan Inhibitors,research,lifescience,medical and Watkins 2009). The cellular

anatomical localization of p-p38MAPK is predominantly expressed and is functionally important in spinal cord microglia and corresponding satellite cells in dorsal root ganglia (DRG) during neuropathic pain (Schafers et al. 2003; Svensson Inhibitors,research,lifescience,medical et al. 2005b; Boyle et al. 2006; Ji and Suter 2007; Sorkin et al. 2009). IL-1β mRNA and protein are upregulated within spinal cord homogenates of rats with pathological pain (Holguin et al. 2004). However, immunohistochemical detection of increased IL-1β protein, as well as alterations in the anti-inflammatory cytokine, interleukin-10 (IL-10), in intact spinal cord dorsal horn from rats with peripheral neuropathy has not yet been characterized. One goal of these studies is to quantify immunoreactivity Inhibitors,research,lifescience,medical (IR) for IL-1β as well as IL-10 in sections of the intact dorsal horn from rats with chronic peripheral neuropathy.

In addition, changes in immunoreactive p-p38MAPK levels Inhibitors,research,lifescience,medical were examined to verify prior reports that increase in p-p38MAPK occurs in combination with increased proinflammatory cytokine expression. Peripheral neuropathy is assessed by the presence of allodynia, characterized as a sensitivity to light mechanical touch that is not present under healthy conditions. AM1241 is a widely characterized cannabinoid agonist that controls hyperalgesia (exaggerated also nociceptive thresholds) and allodynia following intraperitoneal (i.p.) (Ibrahim et al. 2006; Rahn et al. 2008), intravenous (i.v.) (Beltramo et al. 2006), intra-DRG, or intrathecal (i.t.) (Hsieh et al. 2011) injection. In the current studies, we sought to determine the timecourse and dose-dependent changes in allodynia produced by unilateral chronic constriction injury (CCI) of the rat sciatic nerve following i.t. AM1241 administration to avoid known peripheral actions of the compound. The development of bilateral allodynia following unilateral CCI has been documented in numerous studies (Paulson et al. 2000, 2002; Milligan et al. 2006, 2007; Loram et al. 2009).

In contrast to the actual trauma, which had a beginning, middle, and end, the symptoms of PTSD take on a timeless character. The traumatic intrusions themselves are horrifying: they interfere with dealing with the past, while distracting from being able to attend to the present. This unpredictable exposure to unbidden memories of the Inhibitors,research,lifescience,medical trauma usually leads to a variety of (usually maladaptive) avoidance maneuvers, ranging from avoidance of people or actions that remind them of the trauma, to drug and alcohol abuse, to emotional withdrawal from friends or activities that used to be potential sources of solace. Problems

with attention and concentration keep them from being engaged with their

surroundings with zest and energy Uncomplicated activities like reading, conversing, and watching television require extra effort. Inhibitors,research,lifescience,medical This loss of ability to focus, in turn, often leads to problems with taking one thing at a time and gets in the way of organizing one’s life to get it back on track. Disorders of extreme stress (DESNOS) The DSM-TV Field Trial8 demonstrated that it was not the prevalence of PTSD symptoms themselves, but depression, outbursts of anger, self-destructive behaviors, and feelings Inhibitors,research,lifescience,medical of shame, self-blame, and Selleck Fedratinib distrust that distinguished a treatment-seeking sample from a non-treatment seeking community sample with PTSD. The majority of people who seek treatment for traumarelated problems have histories of multiple traumas. One recent treatment-seeking sample9 suffered from a variety of other psychological problems, which in most cases Inhibitors,research,lifescience,medical were the chief presenting complaints, in addition to their PTSD symptoms: 77% suffered from behavioral impulsivity, affective Inhibitors,research,lifescience,medical lability, and aggression against self and others, 84% suffered from depersonalization and other

dissociative symptoms, 75% were plagued by chronic feelings of shame, self-blame, and feeling permanently damaged, and 83% complained of being unable to negotiate satisfactory relationships with others. These problems contribute significantly to impairment about and disability above and beyond the PTSD symptoms.10-12 Focusing exclusively either on PTSD, or on the depression, dissociation and character pathology prevent adequate assessment and treatment of traumatized populations. As part of the DSM.-IV Field Trial, members of the PTSD task force delineated a syndrome of psychological problems that have been shown to be frequently associated with histories of prolonged and severe interpersonal abuse. They called this “Complex PTSD,” or “Disorders of Extreme Stress Not Otherwise Specified (DESNOS) .

Treatment resistance is particularly germane to LLD, for three reasons. First, high rates of comorbid anxiety and medical illness contribute to treatment failure. Second, older adults may have Epigenetics inhibitor greater pharmacodynamic variability as a result, of genetic variability (eg, at. serotonin receptors20) and ageor medical illness-related changes in brain structure or function (eg, decline in serotonin receptors21,22), interruptions in neurocircuitry integrity from cerebrovascular disease or prodromal Alzheimer’s disease.23,24 Third, older adults may have greater pharmacokinetic variability, as a result

of poor Inhibitors,research,lifescience,medical adherence (eg, due to cognitive impairment.) and metabolic variability (eg, due to age-related Inhibitors,research,lifescience,medical changes in drug metabolism).25 The serious consequences of persistent depressive symptoms in elderly persons include relapse and recurrence,26-29 functional disability,30 and cognitive decline, owing in part to the impact of long periods of untreated depression on hippocampal volume.31 Persisting LLD is also associated with an increased mortality,32 including suicide. Risk for suicide can be reduced with successful

treatment.33,34 Finally, treatment-resistant late-life depression (TRLLD) is associated Inhibitors,research,lifescience,medical with increased caregiver burden in family members of depressed elders (Martire L, personal communication, 2008). In these Inhibitors,research,lifescience,medical ways, incomplete response in late-life depression and the need to get to remission are major public health challenges. Despite this challenge, almost no data exist to guide the treatment of TRLLD. The best, current evidence guiding intervention for treatment-resistant depression comes from the Sequenced Treatment Alternatives to Relieve Depression Inhibitors,research,lifescience,medical (STAR*D study35). However, only a small minority of subjects who participated in STAR*D were elderly. Our collaborative group has carried out several examinations of treatment strategies for TRLLD, including open studies of switching from an SSRI to nortriptyline,36 venlafaxine,37 or duloxetine,38 a stepwise strategy of bupropion, nortriptyline,

or lithium augmentation of SSRI,39,40 and electroconvulsive therapy.41,42 Vasopressin Receptor Our findings suggest that, a significant proportion (40% to 50%) of SSRI nonresponders will respond to these strategies, consistent with a prior open sequential trial.43 In the only published placebo-controlled pharmacotherapy trial for TRLLD, Sunderland et al44 found that the monoamine oxidase inhibitor (MAOI) selegiline was efficacious. However, in a recent randomized comparison of lithium augmentation and the MAOI phenelzine for TRLLD, one third of those receiving lithium remitted versus none receiving phenelzine.19 These two controlled studies suffer from small sample size, short, duration, and inclusion of subjects with psychosis.

00 (95% CI 0.79–1.26), suggesting no such benefit with ICS. Observational Study 2 A variation of this bias was seen in another observational study of inhaled corticosteroids (ICS) in the treatment of chronic obstructive pulmonary disease (COPD), which claimed in its title to present “results from two observational designs free of immortal time bias.”29 This claim turned out to be in fact erroneous and reflected a grave misunderstanding of immortal time bias. The authors identified, from the United Kingdom’s General Research Practice Database (GRPD), the cohort of all 4,398 patients aged 50 years and older Inhibitors,research,lifescience,medical hospitalized for COPD

from 1990 to 1999. Cohort entry was taken as the date of discharge, with 1-year follow-up until readmission to hospital for COPD

or death. Patients were considered exposed to ICS if they received a prescription of ICS on the same day of discharge. Using a propensity Inhibitors,research,lifescience,medical scores matched cohort analysis, the hazard ratio of COPD readmission or death associated with ICS use was 0.69 (95% CI 0.52–0.93), suggesting a significant 31% reduction in this outcome with ICS use. Immortal time bias is Inhibitors,research,lifescience,medical in fact introduced again with the definition of ICS exposure. It is stated that “treatment status was selleck kinase inhibitor defined on the same day of discharge,” so that all 1,091 patients who were prescribed ICS on the day of discharge were correctly classified as ICS-exposed. However, of the remaining 3,307 patients, the non-users of ICS were incorrectly taken as merely the 538 patients “who were never exposed to ICS in their entire (one-year) follow-up period.” To comply with their stated Methods, they Inhibitors,research,lifescience,medical should have used all 3,307 patients from the cohort who were not prescribed ICS on the day of discharge. By excluding the 2,769 patients who were not prescribed

ICS on the day of discharge but received an ICS later in the year of follow-up, the authors excluded a crucial component Inhibitors,research,lifescience,medical of follow-up time which is both unexposed and immortal, thus introducing a significant degree of immortal time bias in the results (Figure 2). Had the authors followed the correct method they described in the paper, namely to use “only patients Ketanserin whose treatment status was defined on the day of discharge,” they would have included all 3,307 such patients in the non-ICS group, and the rate ratio of COPD hospitalization or all-cause death with ICS would have been 1.48, not the reported 0.70.33 Figure 2 Illustration of immortal time bias in the Kiri et al. observational cohort study of inhaled corticosteroids in patients discharged with COPD.29 Observational Study 3 A further variation of this bias was seen in another observational study of ICS in COPD, also conducted using the GRPD.

40 Taken together, serotonergic hallucinogens and psychotomimetic NM..DA antagonists produce schizophrenia-like deficits in behavioral measures of sensory gating such as PPI, and do so by actions localized to different parts of the CSPT circuitry. Despite their different primary mechanisms and sites of action, however, a common denominator of the effects of these drug classes is that they alter the dynamics of the integrated Inhibitors,research,lifescience,medical CSPT circuitry such that normal information processing is

distorted by deficits in fundamental forms of sensorimotor gating. Serotonergic amphetamines; MDMA Psychological effects In contrast to serotonergic hallucinogens and NMDA antagonists, a typical recreational and nontoxic dose of MDMA (1.5-7 mg/kg PO) produces an affective state of enhanced mood, profound Inhibitors,research,lifescience,medical well-being, happiness, increased extroversion and sociability, slight derealization and depersonalization, little anxiety, and moderate thought disturbances, but no hallucinations in normal volunteers.95 Depersonalization phenomena are mild and, in contrast to hallucinogens (eg, psilocybin), not experienced as problematic or psychotic fusion, but experienced as a pleasurable state of loosened ego boundaries as measured by the APZ questionnaire (Figure 2). Similar findings were reported with MDMA

and its congener MDE in healthy Inhibitors,research,lifescience,medical volunteers.96-100 Brain imaging studies To identify the functional neuroanatomy involved in the action of MDMA in humans, the effect of MDMA (1.7 mg/kg) versus placebo on regional cerebral blood flow (C.BF) was investigated in MDMA-naive human subjects using PET and Inhibitors,research,lifescience,medical [H2 15O]-PET.101 M.DMA moderately increased brain activity as indexed by CBF bilaterally in the ventromedial prefrontal cortex, the ventral NVP-BGJ398 molecular weight anterior cingulate, the inferior temporal lobe, and the medial occipital cortex and in the cerebellum. Decreases in CBF were found bilaterally in the motor and somatosensory cortex, Inhibitors,research,lifescience,medical the superior temporal lobe, the dorsal cingulate cortex, the insula, and the

thalamus. Unilateral decreases were found in the left amygdala, and the right parahippocampus. This activation pattern and associated affective state, which was characterized by heightened mood, increased extroversion, slight derealization, Cediranib (AZD2171) and intensification of vision, substantially differ from those seen in ketamine- and psilocybin-induced psychosis-like syndromes. The activation of prefrontal and related limbic/paralimbic structures in conjunction with deactivation of the amygdala may underlie the emotional effects of MDMA. This view is consistent with findings implicating the amygdala,102,103 orbitofrontal cortex,103 ventral anterior cingulate cortex,103,104 prefrontal cortex, temporal lobe, and thalamus104 in the regulation of mood and emotion. In this network, the amygdala appears to play a pivotal role in the mediation of both positive and negative emotions.

Randomized trials previously reported a reduction in prostate cancer diagnoses in men taking 5-alpha reductase inhibitors (5-ARIs).20,21 However, it was recently estimated that treatment of 200 men with 5-ARIs would result in three fewer Gleason 6 and one additional Gleason 8 to 10 tumors,

leading the US Food and Drug Administration to rule against their use in chemoprevention.22 In one abstract, O’Brien and colleagues compared pathologic tumor features between men who were and were not taking 5ARIs prior to radical prostatectomy.23 In this clinical Inhibitors,research,lifescience,medical cohort, they observed that long-term 5-ARI use (> 3 years) was associated with greater odds of non-organconfined and high-grade disease in Inhibitors,research,lifescience,medical the prostatectomy specimen. Other researchers further evaluated the relationship between 5-ARI use and long-term survival outcomes. In an Pfizer Licensed Compound Library order abstract from Denmark, Kjellman and colleagues examined the rates of metastasis and disease-specific mortality in 5-ARI users.24 Specifically, they compared 199 men taking 5-ARIs to 613 men using alpha-blockers and 2806 men not taking either of these medications. Overall, 5-ARI users had a significantly increased risk of metastatic disease (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.01–1.29), although the difference Inhibitors,research,lifescience,medical in prostate cancer

mortality did not reach statistical significance. Interestingly, alpha-blocker Inhibitors,research,lifescience,medical use

was associated with a significantly lower risk of both metastases (OR 0.89; 95% CI, 0.81–0.98) and disease-specific death (OR 0.78; 95% CI, 0.67–0.9). These results corroborate prior findings from the Finnish Prostate Cancer Screening Trial, in which 5-ARIs were associated with an increased risk and alphablockers with a decreased risk of high-grade prostate cancer.25 Statins represent another type of medication under investigation for a Inhibitors,research,lifescience,medical possible role in prostate cancer chemoprevention because of numerous epidemiologic studies suggesting a decreased risk of aggressive prostate cancer. Freedland and colleagues26 examined the association between statin use and biopsy findings in 6729 men from the Reduction of Dutasteride in Cancer Ketanserin Events (REDUCE) trial, of which 17.5% reported statin use. On multivariable analysis, there was no significant relationship between statin use with low-grade (P=.62) or high-grade (P=.34) prostate cancer detection on biopsy. A randomized study has not been performed to evaluate a role for statins for prostate cancer prevention. Nevertheless, these combined findings would suggest the need for ongoing active investigation into novel chemopreventive strategies. [Stacy Loeb, MD, Alan W.

All subjects were also tested on a number of other behavioral tasks; however, the active and sham SD groups showed equivalent performance. This suggested that the effects of rTMS were specific to the DMS task. Two cortical regions distinguished the active and sham SD groups. The sham group had greater fMRI activation in the right parahippocampal gyrus, while the active group had greater activation in a cortical region directly beneath where the coil had been placed in the TMS sessions. The results of the last step Inhibitors,research,lifescience,medical indicated that multiple sessions of rTMS applied AZD6244 ic50 concurrently with

DMS task performance over the course of SD worked to generate sufficient neuroplasticity and subsequent Inhibitors,research,lifescience,medical neural changes in the distributed circuitry involved in processing the DMS task. This enabled superior cognitive working memory performance in subjects who received active rTMS a day after the last rTMS session, presumably long after the acute action of rTMS wore off at the local site of stimulation. As such, we suggest that fMRI-guided rTMS increased the resilience of neural circuitry specifically involved in WM to prevent the full impact of SD. The TMS paradigm used here may be a useful tool to help remediate specific cognitive deficits by strengthening networks vital to particular processing Inhibitors,research,lifescience,medical but weakened by the effects of age. Magnetic seizure therapy At

subconvulsive levels, TMS has been found Inhibitors,research,lifescience,medical to have modest antidepressant effects, particularly in elderlypopulations. One way to overcome this limitation would be through increasing its dosage into the convulsive range, given the superior antidepressant potency of electroconvulsive therapy (ECT). While ECTis unparalleled in efficacy even in elderly populations, its risk of amnesia remains a limiting factor, particularly in elderly populations. The rationale behind magnetic seizure therapy (MST) is to preserve the efficacy of ECT while reducing its risk of amnesia through enhanced locality offered by

magnetic stimulation.84,85 When using subconvulsive TMS, the accidental Inhibitors,research,lifescience,medical induction of a seizure would be deemed an adverse effect, but under controlled conditions in a patient under anesthesia, the resultant seizure could confer robust antidepressant properties as Etomidate seen with ECT. The conceptualization of MST was based on combining the unique characteristics of TMS and ECT,86,87 that is, the use of magnetic pulses that can pass unimpeded through the scalp and skull of the former, to generate tonic-clonic seizure activity with known antidepressant activity of the latter. Moreover, TMS has been found to have neurocognitive advantages in that it has no known cognitive adverse effects when used to treat MDD,88 has been shown to enhance cognitive abilities,89 and has been found to be beneficial for neurorehabilitative paradigms.

Type of OPD visited, days of visit, medical condition on arrival, confidence on the hospital to get good treatment, and presence of discrimination/bad treatment of patients were statistically significantly associated determinants of patient satisfaction. Hospitals shall prepare themselves to address the increasing challenge of non-communicable disease emergencies that would result in longer duration of stay, high cost of care, and increasing Inhibitors,research,lifescience,medical hospital mortality. There has to be a mechanism to motivate staff to

handle patients of all categories of severity properly and equally without discrimination and bad treatment. There is a need for evidence-based interventions in emergency care services in physician care, nursing care, courtesy of staff, physical comfort, Inhibitors,research,lifescience,medical and equal treatment to improve satisfaction. Hospitals shall improve patient services to narrow the gap between health coverage and utilization. Competing interests This research was sponsored by the University of Gondar; however the sponsorship has no influence or linkage to the findings or publication of this manuscript. The authors declare that

there are no competing interests. Authors’ contributions BWT, MOY, and ZTK were involved in the concept, design, data collection and analysis. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-227X/14/2/prepub Inhibitors,research,lifescience,medical Acknowledgements The authors would like to thank University of Gondar for funding the research. The authors also want to Inhibitors,research,lifescience,medical forward their gratitude to the patients, care-takers and data collectors for their valuable time and responses.
Pre-hospital care in Ireland is provided by the Health Service Executive’s (HSE) National Ambulance Service (NAS) and (in parts Inhibitors,research,lifescience,medical of Dublin city) the ‘Dublin Fire Brigade’. Staff who respond to pre-hospital incidents are all trained to Paramedic or Advanced Paramedic (AP) level. In addition, pre-hospital care is provided at sporting and other public events by Emergency Medical Technicians (EMTs), mostly within the voluntary organisations: Civil Defence, Order of

Malta Ireland, St. John Ambulance and the Irish Red Cross. All of these practitioners ADP ribosylation factor are registered with the regulating authority, Ireland’s Pre-Hospital Emergency Care Council (PHECC) [1]. Currently, once registered as a practitioner with PHECC there is no requirement to show evidence of competence, other than annual certification in Cardiopulmonary Resuscitation (CPR). In order to re-register practitioners must also complete a self-declaration form stating that they are currently practicing, are of good character and in good health and will commit to the PHECC Code of Conduct and Ethics. There is no current requirement to show evidence of any patient contacts, or to maintain a learning portfolio, or participate in skill Epigenetic inhibitor solubility dmso maintenance programmes.

The more conservative treatment options demand better distinction between HGD, IMC, and SMC on mucosal biopsies. This large surgical series further provides evidence that it is important to separate IMC from SMC, as it may influence the choice of therapeutic intervention. Given the clear prognostic difference between HGD, IMC, and SMC, pathologists are often expected to reliably make this distinction

on small biopsy material. The approximately 40% adenocarcinoma rate in patients with Inhibitors,research,lifescience,medical a pre-operative diagnosis of HGD highlights the fact that it is not always possible for pathologists to make this distinction. The two main problems are: 1) sampling error – e.g., do more biopsies help pathologists distinguish HGD from IMC from SMC? and 2) interobserver variability – e.g., can pathologists reliably distinguish the higher end of Barrett’s neoplasia spectrum? In an attempt to assess histologic features on preoperative biopsies Inhibitors,research,lifescience,medical that would be associated with a higher risk of concurrent adenocarcinoma on resection, two recent studies performed at the University of Michigan (UM) (17) and Cleveland Clinic (CCF) (18) Inhibitors,research,lifescience,medical identified categories of HGD suspicious for adenocarcinoma (UM) and HGD

with marked glandular architectural distortion (CCF). Compared to HGD alone, both categories were significantly associated with IMC or SMC. Nevertheless, pathologists are relatively poor

at separating HGD from IMC and even SMC (18). In addition, pathologists rarely find diagnostic evidence of SMC in biopsy material. In Idarubicin another Inhibitors,research,lifescience,medical study performed at the Cleveland Clinic, the overall rate of SMC on Inhibitors,research,lifescience,medical esophageal resections from patients diagnosed with Barrett’s-related HGD or worse was 21.4% (24/112). Of these cases, only 3 cases (2.7%) had unequivocal evidence of submucosal invasion on biopsy (19). Pathologists also struggle with the distinction between SMC and IMC because of the well-recognized split muscularis mucosae (20),(21). On superficial biopsies, or even endoscopic because mucosal resection (EMR) specimens, it is often difficult to decide whether neoplasm below one layer of muscularis mucosae is within the submucosa or “pseudo-submucosa.” While all the available modalities of risk assessment including endoscopy, imaging, and histology do allow us to guide clinical intervention, none are perfect. Although EMR and ablation therapy are emerging as popular choices for management of Barrett’s-related HGD and IMC, recurrence of neoplasia at the rate of 11%-21% has been reported in these patients (22),(23). The advantages of these approaches, specifically EMR, are larger tissue samples that not only allow better evaluation of histologic landmarks, but also improve diagnostic accuracy and staging (24).

An additional factor that, increasingly may inform treatment decisions is sex. The following article will review both the theoretical evidence for, and the practical demonstrations of, the impact of gender and sex steroids on the response to treatment. The sexually dimorphic brain Two papers in Inhibitors,research,lifescience,medical the 1950s and 1960s were critical in demonstrating that the brain, like the gonads, was sexually dimorphic. First, Phoenix et al1

showed that, prenatal exposure of a female Selleckchem c-Met inhibitor guinea pig to testosterone resulted in masculinization and defeminization of behavior upon reexposure to testosterone in adulthood. This ability of gonadal steroids, when administered perinatally, to change the repertoire of adult behavioral response to the same steroid – a process Phoenix et al called “organization” – showed that the parts of the brain mediating sex-specific behavior were both Inhibitors,research,lifescience,medical developmental plastic and distinct (ie, different across sexes). The existence of sex-dependent structural differences in the brain was

subsequently confirmed by Pfaff, who showed both gross and cellular differences between sexes, with the dimorphisms altered by perinatal castration.2 Inhibitors,research,lifescience,medical There followed a number of papers in the 1970s amplifying these findings.3-6 In addition to the neuroanatomical differences (size of brain

nuclei, Inhibitors,research,lifescience,medical neuritic arborization patterns, and synapse formation), sexual differences were observed in the response to stimuli, with Rainbow et al7 demonstrating more robust, progesterone receptor induction by estrogen in the brains of females. Two processes, then, appear to underlie sexual dimorphisms in the response to pharmacological agents: the neuromodulatory Inhibitors,research,lifescience,medical actions of gonadal steroids; and sex-dependent differences that are independent, of ambient, gonadal steroid levels. Neuromodulatory effects The intxacytoplasmic/intranuclear Carnitine dehydrogenase receptors for gonadal steroids are transcription factors that bind to enhancer elements to regulate the transcription of a wide range of genes. These receptors, when activated by gonadal steroids, can also interact with coregulatory proteins called cointegrators (eg, CBP [cAMP response element binding protein-binding protein ]/GRIP [glucocorticoid receptor-interacting protein]), permitting the gonadal steroids to regulate genes that possess certain enhancer elements (eg, API [activator protein-!]) even in the absence of classical hormone response elements.