An Evaluation of Ethograms Measuring Distinct Features of Enrichment Use by Captive Chimpanzees (Pan troglodytes).

Environmental enrichment provides mental stimulation and minimizes abnormal behaviors in captive animals. In captive chimpanzees, individual animals may vary in the ways in which they benefit from enrichment or use enrichment devices, so investigating nuances in enrichment use may improve the welfare of captive chimpanzees. In the current study, three ethograms measuring distinct features of enrichment use (i.e., enrichment object, manipulation behavior, and social context) were evaluated by coding videos of captive chimpanzees (Pan troglodytes) at Chimpanzee Sanctuary Northwest in Cle Elum, WA. A total of 732 min and 58 s of video footage was coded from a larger video archive (i.e., 2054 videos) of enrichment use that spanned a decade. A principal component analysis (PCA) revealed that different categories of enrichment objects were more often associated with specific manipulation behaviors and social contexts, suggesting that enrichment objects might fulfill different behavioral and social needs in captivity. Specifically, toy objects were associated with active tactile behaviors in affiliative contexts while oral behaviors were used with foraging objects in solitary contexts. Additionally, individual chimpanzees showed unique preferences for enrichment objects, indicating that caregivers of captive chimpanzees should consider individual needs instead of a "one size fits all" approach to enrichment provisions.

Discovery of a selective, state-independent inhibitor of NaV1.7 by modification of guanidinium toxins.

The voltage-gated sodium channel isoform NaV1.7 is highly expressed in dorsal root ganglion neurons and is obligatory for nociceptive signal transmission. Genetic gain-of-function and loss-of-function NaV1.7 mutations have been identified in select individuals, and are associated with episodic extreme pain disorders and insensitivity to pain, respectively. These findings implicate NaV1.7 as a key pharmacotherapeutic target for the treatment of pain. While several small molecules targeting NaV1.7 have been advanced to clinical development, no NaV1.7-selective compound has shown convincing efficacy in clinical pain applications. Here we describe the discovery and characterization of ST-2262, a NaV1.7 inhibitor that blocks the extracellular vestibule of the channel with an IC50 of 72 nM and greater than 200-fold selectivity over off-target sodium channel isoforms, NaV1.1-1.6 and NaV1.8. In contrast to other NaV1.7 inhibitors that preferentially inhibit the inactivated state of the channel, ST-2262 is equipotent in a protocol that favors the resting state of the channel, a protocol that favors the inactivated state, and a high frequency protocol. In a non-human primate study, animals treated with ST-2262 exhibited reduced sensitivity to noxious heat. These findings establish the extracellular vestibule of the sodium channel as a viable receptor site for the design of selective ligands targeting NaV1.7.

Strong Dependence of Atmospheric Feedbacks on Mixed-Phase Microphysics and Aerosol-Cloud Interactions in HadGEM3.

We analyze the atmospheric processes that explain the large changes in radiative feedbacks between the two latest climate configurations of the Hadley Centre Global Environmental model. We use a large set of atmosphere-only climate change simulations (amip and amip-p4K) to separate the contributions to the differences in feedback parameter from all the atmospheric model developments between the two latest model configurations. We show that the differences are mostly driven by changes in the shortwave cloud radiative feedback in the midlatitudes, mainly over the Southern Ocean. Two new schemes explain most of the differences: the introduction of a new aerosol scheme and the development of a new mixed-phase cloud scheme. Both schemes reduce the strength of the preexisting shortwave negative cloud feedback in the midlatitudes. The new aerosol scheme dampens a strong aerosol-cloud interaction, and it also suppresses a negative clear-sky shortwave feedback. The mixed-phase scheme increases the amount of cloud liquid water path (LWP) in the present day and reduces the increase in LWP with warming. Both changes contribute to reducing the negative radiative feedback of the increase of LWP in the warmer climate. The mixed-phase scheme also enhances a strong, preexisting, positive cloud fraction feedback. We assess the realism of the changes by comparing present-day simulations against observations and discuss avenues that could help constrain the relevant processes.

Signs of mood and anxiety disorders in chimpanzees.

BACKGROUND: In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD) and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders? METHODOLOGY/PRINCIPAL FINDINGS: In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196) and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168). In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04), and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04). CONCLUSIONS/SIGNIFICANCE: Chimpanzees display behavioral clusters similar to PTSD and depression in their key diagnostic criteria, underscoring the importance of ethical considerations regarding the use of chimpanzees in experimentation and other captive settings.

Use of penile implants in the constructed neophallus.

Creation of a neophallus in cases of loss of the penis or female to male trans-sexual is a challenge. The forearm flap is the most popular method used. A penile implant may be placed at the original procedure or at a later date to provide support for intercourse. The hydraulic nondistally expanding types provide the best support with less chance of distal erosion. Covering the device with cadaver pericardium or porcine small intestinal submucosa has been helpful in creating a neocorpus cavernosum.

Treatment alternatives for the infected penile implant.

Infection associated with placement of a penile prosthesis is rare. When it does occur, the implant and all associated foreign material should be removed. The surgeon has the option of leaving the device out, allowing the wound to heal, and returning at a future date for prosthesis replacement if the patient wishes, or cleansing the wound and replacing the implant at the same procedure, termed a salvage procedure. The success rate of 'salvage' in this series of 101 patients was 84%. This approach is less likely to succeed when the infection is manifest soon (weeks) after the placement procedure, is accompanied by extensive cellulitis and is caused by virulent organisms. Relative contraindications to salvage include, sepsis, ketoacidosis, penile necrosis, and bilateral urethral erosion of the cylinders.

Management of Peyronie's disease with penile prostheses.

Peyronie's disease is a common malady affecting men mostly between the ages of 40 and 60. When penile curvature and erectile softening are present and the erectile dysfunction does not respond to Viagra a penile implant will strengthen and usually straighten the penis. If curvature persists after implant placement 'modeling' the erect penis will successfully achieve straightening in most patients. Plaque incision and grafting or a Nesbit procedure are rarely necessary to straighten the penis but will afford excellent results when employed. A thorough explanation of the pathogenesis of Peyronie's disease and effects of the disease and treatment on penile size will help avoid some of the disappointment seen when a shorter erection occurs.

Progenipoietin-1: a multifunctional agonist of the granulocyte colony-stimulating factor receptor and fetal liver tyrosine kinase-3 is a potent mobilizer of hematopoietic stem cells.

OBJECTIVE: Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral blood was evaluated. METHODS: Cohorts of donor mice were treated with either progenipoietin-1, fetal liver tyrosine kinase-3 ligand, granulocyte colony-stimulating factor, or a vehicle control. Hematopoietic progenitor/stem-cell activity in donor blood was assayed by radioprotection, multilineage reconstitution, secondary transplantation, and competitive repopulation. RESULTS: Only 1 microL of peripheral blood from progenipoietin-1-treated donors was required to protect 80% of lethally irradiated mice, while in contrast 1 microL of peripheral blood from granulocyte colony-stimulating factor-treated donors failed to protect any recipients. The radioprotected recipients of progenipoietin-1-treated donor cells showed donor-derived (Ly5.2) multilineage hematopoietic reconstitution for up to 6 months. Serial transplantation studies using bone marrow from radioprotected, chimeric recipients demonstrated long-term donor-derived hematopoiesis, indicating the successful transplantation of multipotent hematopoietic stem cells. The engraftment potential of progenipoietin-1 donor-derived cells was directly compared with donors treated with granulocyte colony-stimulating factor or fetal liver tyrosine kinase-3 ligand alone or in combination. Both spleen colony-forming activity and competitive repopulating activity was highest in the blood from progenipoietin-1-treated donors. CONCLUSIONS: These studies demonstrate that progenipoietin-1 is a potent mobilizer of transplantable hematopoietic stem cells and indicate that this dual-receptor agonist has greater biologic activity than its constituent molecules.

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.

Surgical management of penile prosthesis complications.

Penile implants are mechanical devices used to treat erectile dysfunction. Parts of the implants may wear out with time, and the implants themselves may damage the body cavities in which they have been placed, especially with excessive or aggressive use. Techniques to replace parts, repair body cavities, and deal with infection associated with prosthesis placement have been developed. Satisfaction with the resulting erections is the highest among all the modalities available for treating erectile dysfunction. International Journal of Impotence Research (2000) 12, Suppl 4, S108-S111.

Efficacy, safety and patient satisfaction outcomes of the AMS 700CX inflatable penile prosthesis: results of a long-term multicenter study. AMS 700CX Study Group.

PURPOSE: We performed a long-term multicenter study of the AMS 700CX 3-piece inflatable penile prosthesis, focusing on longevity, morbidity and patient satisfaction in men implanted up to 134 months with a median followup of 47.7 months. MATERIALS AND METHODS: We performed a large scale retrospective multicenter study in 2 phases. Phase 1 was a medical record review of 372 men who underwent implantation with the AMS 700CX penile prosthesis from 1987 to 1996 by 7 frequent penile prosthesis implanters. Phase 2 included a structured telephone interview of 207 patients by a neutral observer. RESULTS: For the 372 men in phase 1 mean device mechanical reliability plus or minus standard deviation was 92.1% + or - 3.3% after 3 and 86.2% + or - 4.6% after 5 years. Patient age was 21 to 79 years (mean 57.6 + or - 11.0) at implantation. The etiology of erectile dysfunction was vascular in 27.7% of the cases, Peyronie's disease in 16.9%, diabetes mellitus in 12.9% and radical surgery in 11.6%. Of the men 55.6% received previous treatment for erectile dysfunction. Postoperative infection and device malfunction developed in 3.2% and 17.5% of the cases, respectively. Of the 207 men interviewed in phase 2, 86% still had an AMS 700CX penile prosthesis implanted, including 87.1% with erection suitable for coitus. Currently 79% of those with a device use it at least twice monthly and 88.2% would recommend an implant to a relative or friend. CONCLUSIONS: The AMS 700CX penile implant produced suitable erection and excellent patient satisfaction at long-term followup in the majority of men. Implant reliability is excellent and postoperative morbidity is low.

Erectile function after radical prostatectomy.

The early detection of prostate cancer through the use of prostate-specific antigen screening has resulted in the performance of many more radical prostatectomy procedures as a curative treatment for this disease. Many patients who are candidates for this procedure already suffer from erectile dysfunction, and the incidence of inadequate erections following radical prostatectomy is certainly high. Nerve-sparing procedures during performance of this operation are encouraged as the incidence of erectile dysfunction is lower if one or both nerves are spared. If the patient is already impotent before the procedure, medical treatments with oral agents, intraurethral compounds, or intracorporally injected medications may be more effective with the nerves intact. Early institution of medical therapy, specifically intracorporal injections, after 2 months postoperatively has resulted in a higher incidence of spontaneous return of erections at 1 year. Vacuum erection devices may be successful in restoring erections but extensive practice in their use is necessary, and they may be unappealing to many patients. A penile prosthesis will restore erections if the patient is so motivated for implantation of such a device. These are expensive and require invasive surgery, but satisfaction rates among patients and partners who have used them have been in the range of 85%, the highest satisfaction rate among all of the treatments of erectile dysfunction.

Long-term experience with salvage of infected penile implants.

PURPOSE: The effectiveness of treating patients with an infected penile implant by removing the device, cleansing the wound with a series of antiseptic solutions and placing a new device at the same procedure was assessed. MATERIALS AND METHODS: A total of 65 patients were included in the study. All foreign material was removed from the infected wound followed by copious wound irrigations with a protocol of 7 antibacterial solutions. A new prosthesis was inserted and the patient was placed on antibiotics. RESULTS: Followup ranged from 6 to 93 months. Recent status was determined in 85% of cases (55 of 65). Of the 55 patients 45 (82%) showed no sign of infection. In 5 patients recurrent infection was documented and in 5 others erosion of parts to the exterior possibly related to infection was noted. CONCLUSIONS: Salvage of an infected penile implant has been successful and is gaining in popularity among urologists to reduce morbidity associated with infection.

Use of the artificial urinary sphincter in women.

Persistent urinary incontinence after failed surgical repair can be successfully treated with the artificial urinary sphincter. The English literature was reviewed from 1985 to 1996. Eleven articles and abstracts addressing placement of the artificial urinary sphincter in women were identified. Discussion includes two operative techniques. Success rates were in the range of 91%-99%. Erosion rates were 7%-29%. The artificial urinary sphincter is an effective treatment for women failing other procedures. Appropriate work-up and diagnosis for type III stress urinary incontinence is crucial.

Management of cuff erosion of the double cuff artificial urinary sphincter.

PURPOSE: We report on a series of patients with erosion of 1 cuff of an AMS800 double cuff artificial urinary sphincter and determine the success rate of removing the eroded cuff, leaving the other components behind and converting the device to a single cuff system. MATERIALS AND METHODS: In 9 patients with a double cuff artificial sphincter 1 eroded cuff was removed and the system was converted to a single cuff sphincter. RESULTS: Followup was based on an incontinence scoring system. In 1 patient the remaining cuff was removed because it also eroded. In another patient a wound infection developed 5 months after placement and the entire device was removed. The remaining 7 patients had better continence scores than before artificial sphincter placement but each remarked that continence was better with 2 cuffs. CONCLUSIONS: An eroded cuff of a double cuff artificial urinary sphincter system can be successfully removed and the device can be converted to a single cuff system.