Intercalated amygdala clusters orchestrate a switch in fear state.

Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and 'trauma- and stressor-related' disorders1. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the nature of the interaction between these circuits remains poorly understood2-6. Here, through a combination of in vivo calcium imaging, functional manipulations, and slice physiology, we show that distinct inhibitory clusters of intercalated neurons (ITCs) in the mouse amygdala exert diametrically opposed roles during the acquisition and retrieval of fear extinction memory. Furthermore, we find that the ITC clusters antagonize one another through mutual synaptic inhibition and differentially access functionally distinct cortical- and midbrain-projecting amygdala output pathways. Our findings show that the balance of activity between ITC clusters represents a unique regulatory motif that orchestrates a distributed neural circuitry, which in turn regulates the switch between high- and low-fear states. These findings suggest that the ITCs have a broader role in a range of amygdala functions and associated brain states that underpins the capacity to adapt to salient environmental demands.

Effectiveness of informational decision aids and a live donor financial assistance program on pursuit of live kidney transplants in African American hemodialysis patients.

BACKGROUND: African Americans have persistently poor access to living donor kidney transplants (LDKT). We conducted a small randomized trial to provide preliminary evidence of the effect of informational decision support and donor financial assistance interventions on African American hemodialysis patients' pursuit of LDKT. METHODS: Study participants were randomly assigned to receive (1) Usual Care; (2) the Providing Resources to Enhance African American Patients' Readiness to Make Decisions about Kidney Disease (PREPARED); or (3) PREPARED plus a living kidney donor financial assistance program. Our primary outcome was patients' actions to pursue LDKT (discussions with family, friends, or doctor; initiation or completion of the recipient LDKT medical evaluation; or identification of a donor). We also measured participants' attitudes, concerns, and perceptions of interventions' usefulness. RESULTS: Of 329 screened, 92 patients were eligible and randomized to Usual Care (n = 31), PREPARED (n = 30), or PREPARED plus financial assistance (n = 31). Most participants reported interventions helped their decision making about renal replacement treatments (62%). However there were no statistically significant improvements in LDKT actions among groups over 6 months. Further, no participants utilized the living donor financial assistance benefit. CONCLUSIONS: Findings suggest these interventions may need to be paired with personal support or navigation services to overcome key communication, logistical, and financial barriers to LDKT. TRIAL REGISTRATION: ClinicalTrials.gov [ NCT01439516 ] [August 31, 2011].

Acute and Chronic Suppurative Osteomyelitis of the Jaws: A 10-Year Review and Assessment of Treatment Outcome.

PURPOSE: To review cases of suppurative osteomyelitis of the jaws treated at the Massachusetts General Hospital (Boston, MA) over a 10-year period, evaluate specifics of disease presentation, and answer the clinical question: are there identifiable variables associated with treatment outcome? MATERIALS AND METHODS: A retrospective cohort study was completed using patients treated for suppurative osteomyelitis of the jaws at the Massachusetts General Hospital from April 2006 to October 2016. Inclusion criteria were a diagnosis of suppurative osteomyelitis of the jaw, age older than 18 years, and complete medical records. Patients with nonsuppurative disease, radiation history, or antiresorptive exposure were excluded. Candidate variables included demographic information, medical and dental history, presenting signs and symptoms, and radiologic and laboratory findings. The outcome variable was successful treatment, defined as resolution of symptoms and radiographic evidence of healing after initial treatment. Appropriate statistical analyses were performed with significance set a P value less than .05. RESULTS: Forty-two patients met the inclusion criteria. Mean age was 53 years (range, 20 to 80 yr) and 26 were women (62%). Common comorbidities included cardiovascular disease (52%), tobacco use (45%), and psychiatric disorders (45%). Pain (90%), swelling (86%), and neurosensory change (50%) were the most common findings. Common microbacterial isolates included Streptococcus milleri (74%) and coagulase-negative Staphylococcus species (43%), which showed marked antibiotic resistance. Surgical debridement was the most common intervention (93%). Successful treatment was found in 86%. Of 6 persistent cases, 4 resolved with a second debridement and continued antibiotics and 2 required resection. Increased white blood cell (WBC) count at presentation (P = .005) and associated psychiatric diagnoses (P = .037) were statistically associated with unsuccessful initial treatment. CONCLUSION: The results of this study indicate that antibiotic resistance is commonly encountered in this patient population, although it was not associated with unsuccessful outcome. Patients presenting with increased WBC count and concurrent psychiatric comorbidities required protracted treatment.

Deep Brain Stimulation for Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views on Candidacy Factors.

INTRODUCTION: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS. OBJECTIVES: To explore mental health clinicians' views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates. MATERIALS AND METHODS: In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient's previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity. CONCLUSIONS: Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice.

Divergence Between Clinician and Patient Perspectives on Polygenic Embryo Screening: A Qualitative Study.

Objective: To explore and compare the perspectives of clinicians and patients on polygenic embryo screening. Design: Qualitative. Subjects: Fifty-three participants: 27 reproductive endocrinology and infertility specialists and 26 patients currently undergoing in vitro fertilization or had done so within the last five years. Main Outcome Measures: Qualitative thematic analysis of interview transcripts. Results: Both clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more often than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer polygenic embryo screening to patients or were willing to do so only under certain circumstances, while many patients expressed interest in polygenic embryo screening. Both sets of stakeholders envisioned multiple potential benefits or uses of polygenic embryo screening; the most common included selection and/or prioritization of embryos, receipt of more information about embryos, and preparation for the birth of a predisposed or "affected" child. Both sets of stakeholders also raised multiple potential, interrelated concerns about polygenic embryo screening. The most common concerns among both sets of stakeholders included the potential for different types of "biases" - most often in relation to selection of embryos with preferred genetic chances of traits -, the probabilistic nature of polygenic embryo screening that can complicate patient counseling and/or lead to excessive cycles of in vitro fertilization, and a lack of data from long-term prospective studies supporting the clinical use of polygenic embryo screening. Conclusion: Despite patients' interest in polygenic embryo screening, clinicians feel such screening is premature for clinical application. Though now embryos can be screened for their genetic chances of developing polygenic conditions and traits, many clinicians and patients maintain different attitudes depending on what is specifically screened, despite the blurry distinction between conditions and traits. Considerations raised by these stakeholders may help guide professional societies as they consider developing guidelines to navigate the uncertain terrain of polygenic embryo screening, which is already commercially available.

Clinician Perspectives on Levels of Evidence and Oversight for Deep Brain Stimulation for Treatment-Resistant Childhood OCD.

Approximately 10-20% of children with obsessive-compulsive disorder (OCD) have treatment-resistant presentations, and there is likely interest in developing interventions for this patient group, which may include deep brain stimulation (DBS). The World Society for Stereotactic and Functional Neurosurgery has argued that at least two successful randomized controlled trials should be available before DBS treatment for a psychiatric disorder is considered "established." The FDA approved DBS for adults with treatment-resistant OCD under a humanitarian device exemption (HDE) in 2009, which requires that a device be used to manage or treat a condition impacting 8,000 or fewer patients annually in the United States. DBS is currently offered to children ages 7 and older with treatment-resistant dystonia under an HDE. Ethical and empirical work are needed to evaluate whether and under what conditions it might be appropriate to offer DBS for treatment-resistant childhood OCD. To address this gap, we report qualitative data from semi-structured interviews with 25 clinicians with expertise in this area. First, we report clinician perspectives on acceptable levels of evidence to offer DBS in this patient population. Second, we describe their perspectives on institutional policies or protocols that might be needed to effectively provide care for this patient population.

Participant perceptions of changes in psychosocial domains following participation in an adaptive deep brain stimulation trial.

BACKGROUND: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior. OBJECTIVE/HYPOTHESIS: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS. METHODS: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life. RESULTS: Patients (n = 21) who were enrolled in adaptive DBS trials for Parkinson's disease, essential tremor, obsessive-compulsive disorder, Tourette's syndrome, or dystonia participated. Qualitative data revealed that participants, in general, reported positive experiences with alterations in what was described as 'personality, mood, and behavior changes.' The majority of participants reported increases in quality of life. No participants reported 'regretting the decision to undergo DBS.' CONCLUSION(S): The findings from this patient sample do not support the narrative that DBS results in substantial adverse changes to dimensions of personality, mood, and behavior. Changes reported as "negative" or "undesired" were few in number, and transient in nature.

Enhancing care for hospitalized older adults with cognitive impairment: a randomized controlled trial.

BACKGROUND: Approximately 40% of hospitalized older adults have cognitive impairment (CI) and are more prone to hospital-acquired complications. The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system. OBJECTIVE: Evaluate the efficacy of a clinical decision support system (CDSS) to improve the quality of care for hospitalized older adults with CI. DESIGN: A randomized controlled clinical trial. SETTING: A public hospital in Indianapolis. POPULATION: A total of 998 hospitalized older adults were screened for CI, and 424 patients (225 intervention, 199 control) with CI were enrolled in the trial with a mean age of 74.8, 59% African Americans, and 68% female. INTERVENTION: A CDSS alerts the physicians of the presence of CI, recommends early referral into a geriatric consult, and suggests discontinuation of the use of Foley catheterization, physical restraints, and anticholinergic drugs. MEASUREMENTS: Orders of a geriatric consult and discontinuation orders of Foley catheterization, physical restraints, or anticholinergic drugs. RESULTS: Using intent-to-treat analyses, there were no differences between the intervention and the control groups in geriatric consult orders (56% vs 49%, P = 0.21); discontinuation orders for Foley catheterization (61.7% vs 64.6%, P = 0.86); physical restraints (4.8% vs 0%, P = 0.86), or anticholinergic drugs (48.9% vs 31.2%, P = 0.11). CONCLUSION: A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI.

Young urban women and the nutrition transition in Jordan.

OBJECTIVE: To determine the nutrition transition stage of female Jordanian college students. DESIGN: A cross-sectional survey was used to assess eating styles, disordered eating attitudes and behaviours, body esteem and dissatisfaction, and media influence. SETTING: Public and private universities in Jordan. SUBJECTS: A total of 255 subjects were recruited through a government-initiated youth campaign. RESULTS: The majority of participants had a normal BMI (70.6%) with almost all (99.4%) reporting restrained eating behaviour. Scores on the Eating Attitudes Test (EAT-26) indicated that 45.2% of these female college students should be screening for eating disorders. Subscales of the Body Esteem Scale (BES) showed that these women did not have substantial body esteem issues and mean scores on the Sociocultural Attitudes Towards Appearance Questionnaire (SATAQ-3) indicated that overall these women did not feel the media was dictating the way their body should look. Where Jordanian women did feel pressure from Western media, there was a 6.7-fold increase in the likelihood that they wanted to lose weight. In addition, 48.2% of the female college students desired to lose weight and 14.4% desired weight gain, indicating a certain level of body dissatisfaction. CONCLUSIONS: With low levels of overweight and obesity and a propensity towards eating based on external hunger cues, college-aged Jordanian women may be less advanced in their development through the nutrition transition than the general population of women. However, high levels of restrained eating and disordered eating attitudes and behaviours indicate the need for an intervention to address healthy weight-loss strategies, assess eating disorders and help maintain healthy body esteem.

Using Extinction-Renewal to Circumvent the Memory Strength Boundary Condition in Fear Memory Reconsolidation.

Reconsolidation is a process by which memories are destabilized, updated, and then restabilized. Strong memories are resistant to undergoing reconsolidation. Here, we addressed whether an overtrained fear memory could be made susceptible to reconsolidation by first extinguishing, and then renewing, the memory. Rats were trained with ten tone-footshock pairings, followed by eight days of tone extinction in the training context. The next day, rats were placed into a second context and memory for the tone was renewed/reactivated with a single tone presentation. Immediately following reactivation, rats received an injection of midazolam or vehicle. Rats were then tested for freezing to the tone in a third context. Midazolam had no effect in rats that did not undergo tone extinction, but significantly attenuated freezing to the tone in extinguished rats. Thus, rats that received tone extinction underwent tone memory reconsolidation following its renewal. In a second experiment, we administered the reactivation session and midazolam injections prior to extinction. Midazolam had no effect and rats extinguished at a rate similar to controls. These data suggest that strong emotional memories are capable of updating following weakening of memory expression through extinction.

Combined administration of MK-801 and cycloheximide produces a delayed potentiation of fear discrimination memory extinction.

Mixed evidence exists regarding the role of N-methyl-D-aspartate (NMDA) receptors in memory reconsolidation. We provide no evidence that NMDA receptors are involved with memory reconsolidation, but instead demonstrate that prereactivation systemic MK-801 injection, combined with postreactivation intrabasolateral amygdala (BLA) cycloheximide infusion, produces a delayed potentiation of extinction learning. These data suggest that an interaction between NMDA antagonism and protein synthesis inhibition may enhance extinction by exerting effects outside of the intended reconsolidation manipulation window. The present work demonstrates a novel pharmacological enhancement of extinction, and underscores the importance of employing proper control procedures in reconsolidation research. (PsycINFO Database Record

Clinical decision support system and incidence of delirium in cognitively impaired older adults transferred to intensive care.

BACKGROUND: Elderly patients with cognitive impairment are at increased risk of developing delirium, especially in the intensive care unit. OBJECTIVE: To evaluate the efficacy of a computer-based clinical decision support system that recommends consulting a geriatrician and discontinuing use of urinary catheters, physical restraints, and unnecessary anticholinergic drugs in reducing the incidence of delirium. METHODS: Data for a subgroup of patients enrolled in a large clinical trial who were transferred to the intensive care units of a tertiary-care, urban public hospital in Indianapolis were analyzed. Data were collected on frequency of orders for consultation with a geriatrician; discontinuation of urinary catheterization, physical restraints, or anticholinergic drugs; and the incidence of delirium. RESULTS: The sample consisted of 60 adults with cognitive impairment. Mean age was 74.6 years; 45% were African American, and 52% were women. No differences were detected between the intervention and the control groups in orders for consultation with a geriatrician (33% vs 40%; P = .79) or for discontinuation of urinary catheters (72% vs 76%; P = .99), physical restraints (12% vs 0%; P=.47), or anticholinergic drugs (67% vs 36%; P=.37). The 2 groups did not differ in the incidence of delirium (27% vs 29%; P = .85). CONCLUSION: Use of a computer-based clinical decision support system may not be effective in changing prescribing patterns or in decreasing the incidence of delirium.

Improving delirium care in the intensive care unit: the design of a pragmatic study.

BACKGROUND: Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. METHODS/DESIGN: This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. DISCUSSION: The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00842608.

Christchurch experience of pulmonary embolism with and without thrombolysis.

AIMS: Thrombolysis for normotensive patients with large clot burden pulmonary embolism remains debatable. We aim to document our current management of pulmonary embolism, examining determinants of therapy and outcomes. METHOD: A retrospective chart-based review of all patients admitted with pulmonary embolism under Cardiology service in Christchurch Hospital between 2002-2007. All related CT pulmonary angiograms were also reviewed for quantification of clot burden and evidence of right ventricular strain. RESULTS: 120 patients were admitted during the audit period. Hypotensive patients had a significantly higher troponin level and Qanadli scores. RV/LV ratio >1 in CTPA was 80% sensitive and 57% specific in predicting RV strain on echocardiogram. Forty-six patients were thrombolysed, most with large clot burden and right ventricular strain. No treatment related death or intracranial haemorrhages occurred; however six patients required blood transfusion and six patients had persistent pulmonary hypertension at 6 months. There was a higher in-patient event rate in thrombolysed group, due to increased bleeding, compared to non-thrombolysed patients. CONCLUSION: Thrombolysis was successfully performed with relatively low in-patient and 6-month event rate. Long term advantage over routine anticoagulation was not demonstrated. The role of thrombolysis in normotensive patients with large clot burden remains uncertain. CTPA markers of RV strain correlated well with echocardiography.

Young urban women and the nutrition transition in China: a familiar pattern emerges.

The purpose of this study was to assess the nutrition transition being experienced by urban Chinese college females. The self-administered cross-sectional survey was given to female students attending universities in the urban area of Xi'an, China. The survey was a collection of previously validated instruments measuring motivations for eating, disordered attitudes and behaviors, societal and media influences on body image and eating disturbances, body esteem, body dissatisfaction, and demographic questions. Results from 207 Chinese college females indicated that they had high levels of dietary restraint, despite the large proportion of participants who were considered underweight and normal weight. In addition, the results indicated that these college females ate primarily based on hunger cues. They also had a strong desire to lose weight sometimes to ultra thin and unhealthy levels, but with only moderate levels of disordered eating attitudes and behaviors. It appears that for participants in this study, at their current point in the nutrition transition, the full negative impact of Americanized media may not yet be fully internalized. The study has revealed a need for the development of health education programs to promote healthy eating styles and appropriate dieting behaviors. Future research needs to develop strategies for better understanding the impact of Americanization on the body image of women in this type of transitional population.