Effects of Cortisol on Reconsolidation of Reactivated Fear Memories

The return of conditioned fear after successful extinction (eg, following exposure therapy) is a significant problem in the treatment of anxiety disorders and posttraumatic stress disorder (PTSD). Targeting the reconsolidation of fear memories may allow a more lasting effect as it intervenes with the original memory trace. Indeed, several pharmacological agents and behavioral interventions have been shown to alter (enhance, impair, or otherwise update) the reconsolidation of reactivated memories of different types. Cortisol is a stress hormone and a potent modulator of learning and memory, yet its effects on fear memory reconsolidation are unclear. To investigate whether cortisol intervenes with the reconsolidation of fear memories in healthy males and how specific this effect might be, we built a 3-day reconsolidation design with skin conductance response (SCR) as a measure of conditioned fear: Fear acquisition on day 1; reactivation/no-reactivation of one conditioned stimulus and pharmacological intervention on day 2; extinction learning followed by reinstatement and reinstatement test on day 3. The groups differed only in the experimental manipulation on day 2: Reactivation+Cortisol Group, Reactivation+Placebo Group, or No-reactivation+Cortisol Group. Our results revealed an enhancing effect of cortisol on reconsolidation of the reactivated memory. The effect was highly specific, strengthening only the memory of the reactivated conditioned stimulus and not the non-reactivated one. Our findings are in line with previous findings showing an enhancing effect of behavioral stress on the reconsolidation of other types of memories. These results have implications for the understanding and treatment of anxiety disorders and PTSD.     

“Habitual Adnexal Torsions”—Recurrence after Two Oophoropexies in a Prepubertal Girl: A Case Report and Review of the Literature

BackgroundRecurrent adnexal torsion rarely affects girls. Various surgical techniques for its prevention are available. We describe a case of recurrent asynchronous bilateral torsions in a prepubertal patient.CaseAn 8-year-old girl first presented with a right adnexal torsion and underwent a laparoscopic untwisting. During the following 3 years, 4 additional laparoscopies were required for treatment of left adnexal torsions. Although undergoing bilateral utero-ovarian ligament plication twice, torsion recurred. After examining the various options, we fixated the left ovary to the sidewall just below the pelvic brim.Summary and ConclusionIn the absence of clear evidence, treatment should be flexible and dependent on the individual case. Thorough patient education is imperative in order to prevent a delay in diagnosis and treatment of recurrent adnexal torsion.     

Effects of a Standard American Diet and an anti‐inflammatory diet in male and female mice

Background

Obesity and chronic pain are prevalent concerns. Pain is frequently experienced in weight‐bearing joints, but is common in other areas of the body as well, suggesting other factors. Poor diet often contributes to obesity and can directly influence the immune system. We have shown that poor diet prolongs recovery from inflammatory injury. Therefore, our goal was to determine whether poor‐quality diet‐induced consequences could be prevented or reversed by an anti‐inflammatory diet (AID).

Methods

A Standard American Diet (SAD) was developed to investigate the effects of poor diet on pain. The SAD includes amounts of refined sugar, carbohydrates and fats that better model the typical American diet, as compared to high‐fat diets. We developed an AID to explore whether the effects of the SAD could reverse or whether the AID would enhance recovery prophylactically. The AID was developed using ingredients (epigallocatechin gallate, sulforaphane, resveratrol, curcumin and ginseng) with known anti‐inflammatory properties. Following 15 weeks of diet [SAD, AID or regular (REG)] exposure, male and female mice underwent inflammatory injury, at which point some animals had their diets switched for the remainder of the study.

Results

Animals who consumed the SAD showed longer recovery compared to the AID‐ and REG‐fed animals. Animals switched off the SAD had faster recovery times, with AID‐fed animals recovering as fast as REG‐fed animals.

Conclusions

Poor diet prolonged recovery from inflammatory injury. Substitution of SAD with AID or REG promoted faster recovery. These findings suggest diet can be used as a non‐pharmacological intervention following injury.

Significance

Obesity may increase susceptibility to chronic pain often due to poor diet. Diet has potential to be used as treatment for pain. This study investigates the use of a novel translatable diet to act as a preventative (i.e. prior to surgery) or an intervention (i.e. following an injury).     

Data to Decisions: Creating a Culture of Model-Driven Drug Discovery

Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a “model-driven” culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a “Design Cycle” that makes use of all the data possible, internally and externally, to drive decision-making. These data can take the form of bioactivity, 3D structures, genomics, pathway, PK/PD, safety data, etc. Synthesis of high-quality data into models utilizing both well-established and cutting-edge methods has been shown to yield high confidence predictions to prioritize decision-making and efficiently reposition resources within R&D. The goal is to design an adaptive research operating plan that uses both modeled data and experiments, rather than just testing, to drive project decision-making. To support this emerging culture, an ambitious information management (IT) program has been initiated to implement a harmonized platform to facilitate the construction of cross-domain workflows to enable data-driven decision-making and the construction and validation of predictive models. These goals are achieved through depositing model-ready data, agile persona-driven access to data, a unified cross-domain predictive model lifecycle management platform, and support for flexible scientist-developed workflows that simplify data manipulation and consume model services. The end-to-end nature of the platform, in turn, not only supports but also drives the culture change by enabling scientists to apply predictive sciences throughout their work and over the lifetime of a project. This shift in mindset for both scientists and IT was driven by an early impactful demonstration of the potential benefits of the platform, in which expert-level early discovery predictive models were made available from familiar desktop tools, such as ChemDraw. This was built using a workflow-driven service-oriented architecture (SOA) on top of the rigorous registration of all underlying model entities.     

Doppler‐guided haemorrhoidal artery ligation in patients with Crohn’s disease

Aim: The outcome of Doppler‐guided haemorrhoidal artery ligation (DGHAL) was assessed in patients with Crohn’s disease (CD) suffering from grade III haemorrhoids. Method: A retrospective study was carried out of patients with CD and symptomatic Grade III haemorrhoids treated by DGHAL. Perioperative and follow‐up data were retrieved from our database of patients undergoing DGHAL. Results: The study included seven men and six women. The mean age was 34 years old. All had CD without anorectal involvement. The median duration of haemorrhoidal symptoms was 6.3 years. There was no mortality, new incontinence, faecal impaction, urinary retention, abscess formation or persistent pain following the procedure. Mean pain score based on a visual analogue scale (VAS) decreased from 2.4 at 24 h postoperatively to 1.6 on the seventh postoperative day. All patients had completely recovered by the third postoperative day. At 18 months, three (77%) of the patients were asymptomatic and three had recurrent symptoms. Conclusion: Doppler‐guided haemorrhoidal artery ligation is safe and effective in treating Grade III haemorrhoids in patients with CD without rectal involvement.     

3D-echo in preoperative assessment of aortic cusps effective height

Effective height,which represents the height difference between the central free margins and the aortic insertion lines can be easily determined by 2-D echocardiography and allows for identification of prolapse in the native cusps and assessment of prolapse correction after valve repair.Nonetheless,it allows to see only two of three aortic valve(AV)coaptation planes and this may lead to misunderstanding of the underlying pathophysiological mechanism for aortic regurgitation and hence in unsuccessful repair.In contrast,3D transoesophageal echocardiography and multiple plane reconstruction lets visualize all the three coaptation planes between the AV cusps and it represents an invaluable tool in the assessment of aortic valve geometry.It is highly recommendable before AV repair to accurately study the complex three dimensional cusps anatomy and their geometric interrelation with aortic root.     

Electromagnetic navigation during flexible bronchoscopy

BACKGROUND: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. OBJECTIVES: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. METHODS: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. RESULTS: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. CONCLUSIONS: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.     

Iatrogenic forearm compartment syndrome in a cardiac intensive care unit induced by brachial artery puncture and acute anticoagulation

A previously healthy patient developed late compartment syndrome in the cardiac intensive care unit after a brachial artery puncture due to acute heparinization after successful percutaneous transluminal coronary angioplasty (PTCA) and stent implantation. The cardiologists recognized the problem and immediately consulted an orthopedic surgeon, who promptly performed surgery. The latter consisted of decompression and fasciotomy. The patient recovered excellent hand function without any neurologic or muscular deficits. Knowledge and understanding of the clinical aspects of this complication are crucial in this devastating syndrome.     

Fever of unknown origin (FUO) due to babesiosis in a immunocompetent host

Fevers of unknown origin (FUOs) are defined as prolonged fevers of 101 degrees F or greater lasting 3 or more weeks that remain undiagnosed after comprehensive inpatient/outpatient laboratory testing. Tick-borne infections are uncommon causes of FUOs. Any infectious disease accompanied by prolonged fevers can present as an FUO if the diagnosis is not suspected or if specific laboratory testing is not done to confirm the diagnosis. Babesiosis is transmitted by the Ixodes scapularis ticks endemic to areas in the northeastern United States. We present the case of a 73-year-old, non-human immunodeficiency virus, male from Long Island who presented with FUO for 6 weeks. As with malaria, there are usually few or no localizing signs in babesiosis. During the patient's hospitalization, babesiosis was suspected on the basis of nonspecific laboratory findings, that is, relative lymphopenia, thrombocytopenia, thrombocytopenia, and an elevated lactate dehydrogenase. When babesiosis was considered in the differential diagnosis, stained blood smears demonstrated the red blood cell inclusions of babesiosis. In the hospital, the patient developed noncardiac pulmonary edema, which rapidly resolved which has been described as a rare complication of babesiosis. He also had an elevated immunoglobulin-M Lyme titer indicating coinfection with Lyme disease. Although his hemolytic anemia persisted for weeks, he only had 3% parasitemia and intact splenic function. We believe this to be the first case of babesiosis presenting as an FUO in a normal host.