Melatonin and melatonin receptor agonists in the treatment of nocturia: A systematic review.

AIM: Causes of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of melatonin and melatonin receptor agonists as a primary treatment for nocturia hypothesized to be secondary to sleep disorders. We aim to systematically review the efficacy and reported safety of melatonin and melatonin receptor agonists in the treatment of nocturia. METHODS: A search strategy of EMBASE and Pubmed/Medline databases was utilized to identify eligible studies. Two thousand and twenty-eight unique references were identified in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines for systematic reviews, of which nine papers met the inclusion criteria. The Cochrane Collaboration risk of bias criteria in the open label and nonplacebo studies was used to assess bias. RESULTS: The nine studies identified included 3 randomized double-blinded placebo-controlled trials, 2 randomized non-placebo trial, and 4 prospective open-label trials. Three utilized the melatonin-receptor agonist ramelteon (8 mg) and six utilized melatonin (four 2 mg extended release, two 2 mg normal release). Nocturia improved in 8 studies varying from moderate to low efficacy related to reduction in nocturia episodes. Five studies evaluated sleep parameters finding improvement in both nocturia and sleep quality. Male subjects represented 76.8% of 371 total subjects in prospective and randomized trials. Ramelteon and melatonin were both reported as well tolerated during nocturia treatment. A meta-analysis was not able to be performed due to the heterogeneity of bladder diagnoses. CONCLUSIONS: At this time, there is insufficient evidence to routinely recommend melatonin as an effective treatment for nocturia given the limitations of current clinical studies. Randomized placebo-controlled trials and prospective open label studies in non-neurogenic populations report a trend towards nocturia improvement with good tolerability and rare side effects. Therefore, further larger scale randomized trials with focused urologic diagnoses in well-characterized patient populations are warranted.

An accelerated course of TMS using intermittent theta burst for veterans with major depressive disorder: A case series.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a neuro-modulation technique for treatment-resistant major depressive disorder (MDD). Standard TMS protocols for MDD involve once-daily treatment for 6 to 9 weeks. We report a case series of an accelerated TMS protocol for outpatient MDD treatment. METHODS: From July 2020 through January 2021, patients deemed appropriate candidates for TMS treatment were offered an accelerated TMS protocol consisting of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex, localized by the Beam F3 method, and consisting of 5 treatments daily for 5 days. Assessment scales were obtained as part of standard clinical care. RESULTS: A total of 19 veterans received the accelerated protocol and 17 completed treatment. Statistically significant mean reductions from baseline to end of treatment were observed across all assessment scales. Remission and response rates, as defined by changes in Montgomery-Åsberg Depression Rating Scale scores, were 47.1% and 64.7%, respectively. Treatments were well tolerated without unexpected or serious adverse events. CONCLUSIONS: This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days. Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.

Novel genetic testing model: A collaboration between genetic counselors and nephrology.

Many barriers to genetic testing currently exist which delay or prevent diagnosis. These barriers include wait times, staffing, education, and cost. Specialists are able to identify patients with disease that may need genetic testing, but lack the genetics support to facilitate that testing in the most cost, time, and medically effective manner. The Nephrology Division and the Genetic Testing Stewardship Program at Nemours A.I. duPont Hospital for Children created a novel service delivery model in which nephrologists and genetic counselors collaborate in order to highlight their complementary strengths (clinical expertise of nephrologists and genetics and counseling skills of genetic counselors). This collaboration has reduced many barriers to care for our patients. This workflow facilitated the offering of genetic testing to 76 patients, with 86 tests completed over a 20-month period. Thirty-two tests were deferred. Twenty-seven patients received a diagnosis, which lead to a change in their medical management, three of whom were diagnosed by cascade family testing. Forty-two patients had a negative result and 16 patients had one or more variants of uncertain significance on testing. The inclusion of genetic counselors in the workflow is integral toward choosing the most cost and time effective genetic testing strategy, as well as providing psychosocial support to families. The genetic counselors obtain informed consent, and review genetic test results and recommendations with the patient and their family. The availability of this program to our patients increased access to genetic testing and helps to provide diagnoses and supportive care.

Denying renal transplantation to an adolescent medical cannabis user: An ethical case study.

Medical cannabis is now legal in over half of the United States. As more patients adopt this unconventional therapy, it is inevitable that potential transplant recipients will disclose their cannabis use during transplant evaluation. Transplant teams are tasked with the decision to utilize a pressure resource, often with little guidance from international and national professional organizations. Many healthcare providers remain uniformed or misinformed about the risks of cannabis use and organ transplantation. In order to illustrate the multifaceted and complex evaluation of transplant patients using medical cannabis, this article presents the case of a 20-year-old woman recommended for renal transplant who was originally denied active listing due to her medical cannabis use. A review of the literature explores the perceived and actual risks of cannabis use in the immunocompromised patient. Furthermore, a discussion of the ethics of medical cannabis use and organ transplantation is included with recommendations for multidisciplinary transplant teams.

Discovery of acylurea isosteres of 2-acylaminothiadiazole in the azaxanthene series of glucocorticoid receptor agonists.

Acylureas and acyclic imides are found to be excellent isosteres for 2-acylamino-1,3,4-thiadiazole in the azaxanthene-based series of glucocorticoid receptor (GR) agonists. The results reported herein show that primary acylureas maintain high affinity and selectivity for GR while providing improved CYP450 inhibition and pharmacokinetic profile over 2-acylamino-1,3,4-thiadiazoles. General methods for synthesis of a variety of acylureas and acyclic imides from a carboxylic acid were utilized and are described.

Digital adaptation of the Standing up for Myself intervention in young people and adults with intellectual disabilities: the STORM feasibility study.

Background: Stigma contributes to the negative social conditions persons with intellectual disabilities are exposed to, and it needs tackling at multiple levels. Standing Up for Myself is a psychosocial group intervention designed to enable individuals with intellectual disabilities to discuss stigmatising encounters in a safe and supportive setting and to increase their self-efficacy in managing and resisting stigma. Objectives: To adapt Standing Up for Myself to make it suitable as a digital intervention; to evaluate the feasibility and acceptability of Digital Standing Up for Myself and online administration of outcome measures in a pilot; to describe usual practice in the context of the coronavirus disease 2019 pandemic to inform future evaluation. Design: Adaptation work followed by a single-arm pilot of intervention delivery. Setting and participants: Four third and education sector organisations. Individuals with mild-to-moderate intellectual disabilities, aged 16+, members of existing groups, with access to digital platforms. Intervention: Digital Standing Up for Myself intervention. Adapted from face-to-face Standing Up for Myself intervention, delivered over four weekly sessions, plus a 1-month follow-up session. Outcomes: Acceptability and feasibility of delivering Digital Standing Up for Myself and of collecting outcome and health economic measures at baseline and 3 months post baseline. Outcomes are mental well-being, self-esteem, self-efficacy in rejecting prejudice, reactions to discrimination and sense of social power. Results: Adaptation to the intervention required changes to session duration, group size and number of videos; otherwise, the content remained largely the same. Guidance was aligned with digital delivery methods and a new group member booklet was produced. Twenty-two participants provided baseline data. The intervention was started by 21 participants (four groups), all of whom were retained at 3 months. Group facilitators reported delivering the intervention as feasible and suggested some refinements. Fidelity of the intervention was good, with over 90% of key components observed as implemented by facilitators. Both facilitators and group members reported the intervention to be acceptable. Group members reported subjective benefits, including increased confidence, pride and knowing how to deal with difficult situations. Digital collection of all outcome measures was feasible and acceptable, with data completeness ≥ 95% for all measures at both time points. Finally, a picture of usual practice has been developed as an intervention comparator for a future trial. Limitations: The pilot sample was small. It remains unclear whether participants would be willing to be randomised to a treatment as usual arm or whether they could be retained for 12 months follow-up. Conclusions: The target number of groups and participants were recruited, and retention was good. It is feasible and acceptable for group facilitators with some training and supervision to deliver Digital Standing Up for Myself. Further optimisation of the intervention is warranted. Future work: To maximise the acceptability and reach of the intervention, a future trial could offer the adapted Digital Standing Up for Myself, potentially alongside the original face-to-face version of the intervention. Study registration: This study was registered as ISRCTN16056848. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/149/03) and is published in full in Public Health Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

People with intellectual disabilities (or 'learning disabilities' in United Kingdom language) are more likely to experience poor physical and mental health than the general population. Stigma (negative stereotypes, prejudice and discrimination) has been linked to lower self-esteem, quality of life, and mental and physical ill health. Efforts to empower people with intellectual disabilities themselves to challenge stigma with a view to improving well-being, health and self-esteem are lacking. In 2017, we developed Standing Up for Myself, a brief group-based programme for people with mild-to-moderate intellectual disabilities aged 16+ to address this gap. As this study got underway, face-to-face meetings were suspended due to the coronavirus disease 2019 pandemic. We used the opportunity to assess whether Standing Up for Myself could be delivered through web-based meetings. We adapted Standing Up for Myself for digital delivery, with close input from advisors with intellectual disabilities and experienced group facilitators. We then tested the digital version in charity and education settings to evaluate if Digital Standing Up for Myself could be delivered as planned and how acceptable it was to group facilitators and participants. Four groups, with a total of 22 members, signed up to try Digital Standing Up for Myself. One participant dropped out before starting Standing Up for Myself, and the other 21 continued until the end of the programme. Retention and attendance were good; participants on average attended four of the five sessions. Ninety per cent of the core programme requirements were fully delivered as detailed in the Digital Standing Up for Myself manual. Problems with technology were manageable, although facilitators found using the Standing Up for Myself Wiki platform (an online platform for storage and sharing of resources) difficult, particularly when sharing video content. Facilitators felt acceptable levels of privacy were achieved and there were no reports of undue distress. All facilitators and many group members said they would recommend Digital Standing Up for Myself to others. Group members shared how the programme benefitted them, noting increased awareness about disabilities, and for some increased confidence, pride and independence. Some had learnt how to stand up for themselves and manage difficult situations and took pride in this. Completing outcome and health cost measures via web-based meetings was acceptable and data were largely fully complete and useable.

Standing up for Myself (STORM): Adapting and piloting a web-delivered psychosocial group intervention for people with intellectual disabilities.

BACKGROUND: Our STORM intervention was developed for people (16 +) with intellectual disabilities to enhance their capacity to manage and resist stigma. The current study describes the adaptation of STORM for (synchronous) on-line delivery in the context of the Covid-19 pandemic. AIMS: To adapt the manualised face-to-face STORM group intervention for delivery via web-based meeting platforms and to conduct an initial pilot study to consider its acceptability and feasibility. METHODS AND PROCEDURES: The 5-session STORM intervention was carefully adapted for online delivery. In a pilot study with four community groups (N = 22), outcome, health economics and attendance data were collected, and fidelity of delivery assessed. Focus groups with participants, and interviews with facilitators provided data on acceptability and feasibility. OUTCOMES AND RESULTS: The intervention was adapted with minimal changes to the content required. In the pilot study, 95% of participants were retained at follow-up, 91% attended at least three of the five sessions. Outcome measure completion and fidelity were excellent, and facilitators reported implementation to be feasible. The intervention was reported to be acceptable by participants. CONCLUSIONS AND IMPLICATIONS: When provided with the necessary resources and support, people with intellectual disabilities participate actively in web-delivered group interventions.

Strategic thinking.

The new framework is seen as a positive move to improve the nation's mental health and wellbeing. However, despite the strategy highlighting the needs of people with learning disabilities, the framework offers very little specifically for this group. This raises concern that this group will remain off the radar for those in mainstream services and organisations that could support them to maintain their mental health and wellbeing. With the Valuing People Now team disbanded, there is no nationally-accredited body given the role to champion people with learning disabilities. Those with a learning disability and a mental illness should be able to access services and be treated in the same way as anyone else with reasonable adjustments being made in accordance with the Disability Discrimination Act (2005) and the Disability Equality Duty (2006). But as the implementation framework is lacking in attention to this group more work will be required by mainstream and specialist organisations to ensure the key messages from the frameworks are applicable to people with learning disabilities.

Risk factors for postoperative ileus after cesarean delivery.

BACKGROUND: Despite extensive data regarding risk factors for postoperative ileus in the general and colorectal surgery literature, few studies have identified risk factors specific to the obstetrical population. OBJECTIVE: This study aimed to identify factors associated with postoperative ileus following cesarean delivery. STUDY DESIGN: This retrospective case-control study identified women who underwent cesarean delivery at a single hospital between January 2000 and January 2020 and subsequently developed postoperative ileus. Cases were matched in a 1:2 ratio with controls who underwent cesarean delivery and did not develop postoperative ileus. They were matched by age (±1 year) and body mass index (±1 kg/m2). Demographics, common comorbidities, obstetrical history, and delivery characteristics were analyzed. RESULTS: A total of 147 cases and 294 controls were identified. Cases and controls were similar in terms of parity, number of previous cesarean deliveries, labor preceding their cesarean delivery, incidence of chorioamnionitis, and presurgical diagnosis of hypothyroidism or chronic hypertension. Cases tended to have a diagnosis of preeclampsia (cases 23.1% vs controls 10.5%; P<.001) and were more likely to have been exposed to magnesium sulfate (cases 34.0% vs controls 15.0%; P<.001). Surgical considerations that were common in cases were exposure to general anesthesia (cases 37.4% vs controls 4.1%; P<.001), midline vertical skin incisions (cases 13.6% vs controls 1.4%; P<.001), classical hysterotomy (cases 8.8% vs controls 1.7%; P=.001), estimated blood loss >1000 mL (cases 44.4% vs controls 11.6%; P<.001), transfusion of blood products (cases 25.8% vs controls 2.0%; P<.001), and hysterectomy at the time of cesarean delivery (cases 6.1% vs controls 0.7%; P=.001). After a multivariable modeling using stepwise logistic regression of all variables found to be statistically significant, transfusion of blood products, estimated blood loss >1000 mL, and exposure to general anesthesia were the remaining surgical factors associated with the development of ileus. These variables reflect both the complexity and most likely the duration of surgery that was required, although we note that we did not have operative time as a variable to explore. Preeclampsia was also identified as a comorbidity linked to the development of ileus. CONCLUSION: A diagnosis of preeclampsia, exposure to general anesthesia, estimated blood loss >1 L, and transfusion of blood products were identified as potential risk factors for postcesarean ileus.

Age: is it all in the head? Factors influencing mortality in elderly patients with head injuries.

BACKGROUND: Elderly patients, an increasing segment of the population, who sustain traumatic brain injury (TBI) are known to have worse outcomes, including higher mortality. This objective of this study was to examine the Crash Injury Research Engineering Network and to determine at what age motor vehicle crash fatalities from head injuries increased. METHODS: The Crash Injury Research Engineering Network database was queried from 1996 to 2009. Study inclusion criteria were adult vehicle occupants with TBI, with an Abbreviated Injury Scale score ≥2. The age at which mortality increased was calculated. Patients younger and older than this cutoff age were compared to determine differences in crash characteristics. The determined cutoff age was compared with one found in a larger, population-based database. RESULTS: There were 915 patients who met the study criteria. An increase in mortality was seen at age 60 years despite no difference in Injury Severity Score and a decrease in crash severity. Patients ≤60 years were more likely to have alcohol involved, to be in a rollover crash, and had higher crash speeds. Comparing the element of the crash attributed to the head injury, the patients >60 years were more likely to have struck the airbag, door, and seat. An analysis of the larger database revealed an increase in mortality at age 70 years. CONCLUSIONS: There was a higher mortality secondary to head injuries in those older than 60 years involved in motor vehicle crashes. Improved safety measures in vehicle design may decrease the number of head injuries seen in the older population.

Ambulatory blood pressure monitoring: A nurse practitioner run program.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) is a standard screening tool for the diagnosis of hypertension in children, adolescents, and adults. However, there is confusion and misunderstanding about which guidelines can provide the most accurate diagnostic values. LOCAL PROBLEM: At a large, free-standing pediatric hospital, ABPM testing was historically being conducted by both nephrology and cardiology departments. The nephrology service was using the American Heart Association (AHA) guidelines, published in 2014 for interpretation of results and for diagnosis of hypertension, whereas the cardiology service depended on the 2004 National High Blood Pressure Education Program (NHBEP) fourth report, which led to discrepancies in diagnosis of hypertension in this patient population. METHODS: A nurse practitioner-led quality improvement project was designed and implemented to determine the best method of ABPM monitoring and test interpretation based on comparing results of patients using height, gender, and application of either the 2004 NHBEP fourth report or 2014 AHA guidelines. INTERVENTIONS: Using a retrospective chart review, ABPM monitoring results from both cardiology and nephrology services were reviewed and compared to identify the most accurate methods and to recommend changes to practice. RESULTS: Accuracy of interpretation for ABPM is best accomplished using the 2014 AHA guidelines. CONCLUSIONS: Using a single method of interpretation provides consistent diagnosis and treatment of hypertension in children. Nurse practitioners can apply this knowledge in other settings to manage hypertension and provide similar services in different settings, including primary care.

Impact of Comorbid PTSD on Outcome of Repetitive Transcranial Magnetic Stimulation (TMS) for Veterans With Depression.

OBJECTIVE: A recent randomized controlled trial of repetitive transcranial magnetic stimulation (TMS) for major depressive disorder (MDD) in veterans raised the question of whether comorbid posttraumatic stress disorder (PTSD) negatively impacted the outcome of TMS in veterans. To address this, a quality database was analyzed to compare outcomes of MDD treated with TMS in veterans with and without comorbid PTSD. METHODS: The clinical outcomes of all consecutive veterans with MDD treated with TMS at the James A. Haley Veterans' Hospital as outpatients from October 2013 through September 2018 were included. Patients were initially evaluated by an experienced psychiatrist, and the diagnosis of MDD was made by clinical evaluation per DSM-IV-TR/DSM-5 criteria. At the start of treatment, after every 5 treatments, and at the end of treatment, patients were assessed with self-report and clinician-rated scales of depression. All data were abstracted from an existing quality database. RESULTS: Among the 118 patients treated with TMS for depression, 55 (47%) had comorbid PTSD and 63 (53%) had no comorbid PTSD. Response and remission rates by score on the Montgomery-Asberg Depression Rating Scale were similar between patients with PTSD (52.5% and 40.9%, respectively) and without PTSD (53.8% and 35.6%, respectively). No seizures or persistent adverse effects were observed or reported in either group. CONCLUSIONS: Comorbid PTSD did not impact the outcome of TMS for depression in this sample of veterans. Future studies should include formal ratings of PTSD to determine if the severity of PTSD affects the outcome.

Injury and side impact air bag deployment in near and far sided motor vehicle crashes, United States, 2000-2005.

BACKGROUND: Side impact crashes, the most lethal type, account for 26% of all motor vehicle crashes in the United States. The purpose of this study is to delineate side impact airbag (SIAB) deployment rates, injury rates, and analyze crash factors associated with SIAB deployment and occupant injury. METHODS: All passenger vehicles equipped with SIABs that were involved in a side impact crash were identified from the National Automotive Sampling System database. Crashes with multiple impacts, ejections, unbelted drivers or rollovers were excluded from the study. The outcome variables of interest were SIAB deployment and driver injury. SIAB deployment was compared in similar crashes to analyze the impact on driver's injury severity score. Other crash factors were also examined to analyze what role they play in SIAB deployment rates and injury rates, such as plane of contact, striking object and Delta-V. RESULTS: The data set for this study contained 247 drivers in near and far side crashes in vehicles with installed SIABs. Overall SIAB deployment was 43% in side impact crashes. A significant factor associated with both the SIAB deployment rate and the driver's injury rate was increased Delta-V. CONCLUSIONS: SIABs do not deploy consistently in crashes with a high Delta-V or with a lateral primary direction of force and a front plane of contact. In these two scenarios, further research is warranted on SIAB deployments. With SIAB deployment, it appears drivers are able to sustain a higher Delta-V impact without serious injury.

Development and validation of a multifactor mindfulness scale in youth: The Comprehensive Inventory of Mindfulness Experiences-Adolescents (CHIME-A).

Mindfulness-based interventions show consistent benefits in adults for a range of pathologies, but exploration of these approaches in youth is an emergent field, with limited measures of mindfulness for this population. This study aimed to investigate whether multifactor scales of mindfulness can be used in adolescents. A series of studies are presented assessing the performance of a recently developed adult measure, the Comprehensive Inventory of Mindfulness Experiences (CHIME) in 4 early adolescent samples. Study 1 was an investigation of how well the full adult measure (37 items) was understood by youth (N = 292). Study 2 piloted a revision of items in child friendly language with a small group (N = 48). The refined questionnaire for adolescents (CHIME-A) was then tested in Study 3 in a larger sample (N = 461) and subjected to exploratory factor analysis and a range of external validity measures. Study 4 was a confirmatory factor analysis in a new sample (N = 498) with additional external validity measures. Study 5 tested temporal stability (N = 120). Results supported an 8-factor 25-item measure of mindfulness in adolescents, with excellent model fit indices and sound internal consistency for the 8 subscales. Although the CFA supported an overarching factor, internal reliability of a combined total score was poor. The development of a multifactor measure represents a first step toward testing developmental models of mindfulness in young people. This in turn will aid construction of evidence based interventions that are not simply downward derivations of adult mindfulness programs. (PsycINFO Database Record

A randomized controlled evaluation of a secondary school mindfulness program for early adolescents: Do we have the recipe right yet?

OBJECTIVE: Mindfulness is being promoted in schools as a prevention program despite a current small evidence base. The aim of this research was to conduct a rigorous evaluation of the .b ("Dot be") mindfulness curriculum, with or without parental involvement, compared to a control condition. METHOD: In a randomized controlled design, students (Mage 13.44, SD 0.33; 45.4% female) across a broad range of socioeconomic indicators received the nine lesson curriculum delivered by an external facilitator with (N = 191) or without (N = 186) parental involvement, or were allocated to a usual curriculum control group (N = 178). Self-report outcome measures were anxiety, depression, weight/shape concerns, wellbeing and mindfulness. RESULTS: There were no differences in outcomes between any of the three groups at post-intervention, six or twelve month follow-up. Between-group effect sizes (Cohen's d) across the variables ranged from 0.002 to 0.37. A wide range of moderators were examined but none impacted outcome. CONCLUSIONS: Further research is required to identify the optimal age, content and length of mindfulness programs for adolescents in universal prevention settings. TRIAL REGISTRATION: ACTRN12615001052527.

Effectiveness of a school-based mindfulness program for transdiagnostic prevention in young adolescents.

Anxiety, depression and eating disorders show peak emergence during adolescence and share common risk factors. School-based prevention programs provide a unique opportunity to access a broad spectrum of the population during a key developmental window, but to date, no program targets all three conditions concurrently. Mindfulness has shown promising early results across each of these psychopathologies in a small number of controlled trials in schools, and therefore this study investigated its use in a randomised controlled design targeting anxiety, depression and eating disorder risk factors together for the first time. Students (M age 13.63; SD = .43) from a broad band of socioeconomic demographics received the eight lesson, once weekly.b ("Dot be") mindfulness in schools curriculum (N = 132) or normal lessons (N = 176). Anxiety, depression, weight/shape concerns and wellbeing were the primary outcome factors. Although acceptability measures were high, no significant improvements were found on any outcome at post-intervention or 3-month follow-up. Adjusted mean differences between groups at post-intervention were .03 (95% CI: -.06 to -.11) for depression, .01 (-.07 to -.09) for anxiety, .02 (-.05 to -.08) for weight/shape concerns, and .06 (-.08 to -.21) for wellbeing. Anxiety was higher in the mindfulness than the control group at follow-up for males, and those of both genders with low baseline levels of weight/shape concerns or depression. Factors that may be important to address for effective dissemination of mindfulness-based interventions in schools are discussed. Further research is required to identify active ingredients and optimal dose in mindfulness-based interventions in school settings.

Academic medical product development: an emerging alliance of technology transfer organizations and the CTSA.

To bring the benefits of science more quickly to patient care, the NIH National Center Advancing Translational Sciences (NCATS) supports programs that enhance the development, testing, and implementation of new medical products and procedures. The NCATS clinical and translational science award (CTSA) program is central to that mission; creating an academic home for clinical and translational science and supporting those involved in the discovery and development of new health-related inventions. The technology transfer Offices (TTO) of CTSA-funded universities can be important partners in the development process; facilitating the transfer of medical research to the commercial sector for further development and ultimately, distribution to patients. The Aggregating Intellectual Property (IP) Working Group (AWG) of the CTSA public private partnerships key function committee (PPP-KFC) developed a survey to explore how CTSA-funded institutions currently interface with their respective TTOs to support medical product development. The results suggest a range of relationships across institutions; approximately half have formal collaborative programs, but only a few have well-connected programs. Models of collaborations are described and provided as examples of successful CTSA/TTO partnerships that have increased the value of health-related inventions as measured by follow-on funding and industry involvement; either as a consulting partner or licensee.

Azaxanthene based selective glucocorticoid receptor modulators: design, synthesis, and pharmacological evaluation of (S)-4-(5-(1-((1,3,4-thiadiazol-2-yl)amino)-2-methyl-1-oxopropan-2-yl)-5H-chromeno[2,3-b]pyridin-2-yl)-2-fluoro-N,N-dimethylbenzamide (BMS-776532) and its methylene homologue (BMS-791826).

Structurally novel 5H-chromeno[2,3-b]pyridine (azaxanthene) selective glucocorticoid receptor (GR) modulators have been identified. A screening paradigm utilizing cellular assays of GR-mediated transrepression of proinflammatory transcription factors and transactivation of GR-dependent genes combined with three physiologically relevant assays of cytokine induction in human whole blood has allowed for the identification of high affinity, selective GR ligands that display a broad range of pharmacological profiles. Agonist efficacy in reporter assays can be tuned by halogenation of a pendent phenyl ring and correlates well with efficacy for cytokine inhibition in human whole blood. A hypothetical binding mode is proposed, invoking an expanded ligand binding pocket resembling that of arylpyrazole-bound GR structures. Two compounds of close structural similarity (35 and 37; BMS-776532 and BMS-791826, respectively) have been found to maintain distinct and consistent levels of partial agonist efficacy across several assays, displaying anti-inflammatory activity comparable to that of prednisolone 2 in suppressing cytokine production in whole blood and in rodent models of acute and chronic inflammation.

Orbital pseudotumor after an upper respiratory infection: a comprehensive review.

BACKGROUND: Idiopathic orbital inflammation (IOI), also known as orbital pseudotumor, is a nonspecific orbital inflammation of unknown etiology. IOI can clinically mimic many other orbital pathologies, some of which can be life-threatening, as in the case of orbital cellulitis. Thus, it is imperative for the clinician to emergently arrive at the correct diagnosis. In many cases, however, IOI presents as a clinical and therapeutic challenge, and conclusive diagnosis is only confirmed after all other etiologies have been ruled out. CASE REPORT: A 63-year-old man presented urgently with a red, proptotic, painful eye. After history, blood tests, radiologic testing, and ruling out other emergent etiologies, such as orbital cellulitis, the patient was placed on oral steroids. He responded immediately to the steroid treatment. However, the patient did have a recurrence. With the second IOI episode, the patient noted, as previously, a preceding upper respiratory infection. This case may possibly show an association between an infectious trigger leading to a nonspecific aberrant immune response in the orbit. CONCLUSION: IOI is a difficult condition to diagnose and treat. After ruling out other orbital pathologies, it is appropriate to begin treatment with oral steroids. In this case report, the patient noted an upper respiratory infection before each episode of IOI. Although there is no proof of cause, there is a strong case for the consideration of a viral respiratory infection leading to IOI.