Odor modulates the temporal dynamics of fear memory consolidation.

Systems consolidation (SC) theory proposes that recent, contextually rich memories are stored in the hippocampus (HPC). As these memories become remote, they are believed to rely more heavily on cortical structures within the prefrontal cortex (PFC), where they lose much of their contextual detail and become schematized. Odor is a particularly evocative cue for intense remote memory recall and despite these memories being remote, they are highly contextual. In instances such as posttraumatic stress disorder (PTSD), intense remote memory recall can occur years after trauma, which seemingly contradicts SC. We hypothesized that odor may shift the organization of salient or fearful memories such that when paired with an odor at the time of encoding, they are delayed in the de-contextualization process that occurs across time, and retrieval may still rely on the HPC, where memories are imbued with contextually rich information, even at remote time points. We investigated this by tagging odor- and non-odor-associated fear memories in male c57BL/6 mice and assessed recall and c-Fos expression in the dorsal CA1 (dCA1) and prelimbic cortex (PL) 1 or 21 d later. In support of SC, our data showed that recent memories were more dCA1-dependent whereas remote memories were more PL-dependent. However, we also found that odor influenced this temporal dynamic, biasing the memory system from the PL to the dCA1 when odor cues were present. Behaviorally, inhibiting the dCA1 with activity-dependent DREADDs had no effect on recall at 1 d and unexpectedly caused an increase in freezing at 21 d. Together, these findings demonstrate that odor can shift the organization of fear memories at the systems level.

Traumatic Brain Injury, Sleep, and Melatonin-Intrinsic Changes with Therapeutic Potential.

Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity in the United States and is associated with numerous chronic sequelae long after the point of injury. One of the most common long-term complaints in patients with TBI is sleep dysfunction. It is reported that alterations in melatonin follow TBI and may be linked with various sleep and circadian disorders directly (via cellular signaling) or indirectly (via free radicals and inflammatory signaling). Work over the past two decades has contributed to our understanding of the role of melatonin as a sleep regulator and neuroprotective anti-inflammatory agent. Although there is increasing interest in the treatment of insomnia following TBI, a lack of standardization and rigor in melatonin research has left behind a trail of non-generalizable data and ambiguous treatment recommendations. This narrative review describes the underlying biochemical properties of melatonin as they are relevant to TBI. We also discuss potential benefits and a path forward regarding the therapeutic management of TBI with melatonin treatment, including its role as a neuroprotectant, a somnogen, and a modulator of the circadian rhythm.

Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear.

Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system in mice, we label dorsal dentate gyrus neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells are artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory is sufficient to update the memory during reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrate operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While memory-updating, induced by memory reactivation, involves a relatively small set of neurons, we also find that activating a large population of randomly labeled dorsal dentate gyrus neurons is effective in promoting reconsolidation. Importantly, memory-updating is specific to the fear memory. These findings implicate the dorsal dentate gyrus as a potential therapeutic node for modulating memories to suppress fear.

Artificially Enhancing and Suppressing Hippocampus-Mediated Memories.

Emerging evidence indicates that distinct hippocampal domains differentially drive cognition and emotion [1, 2]; dorsal regions encode spatial, temporal, and contextual information [3-5], whereas ventral regions regulate stress responses [6], anxiety-related behaviors [7, 8], and emotional states [8-10]. Although previous studies demonstrate that optically manipulating cells in the dorsal hippocampus can drive the behavioral expression of positive and negative memories, it is unknown whether changes in cellular activity in the ventral hippocampus can drive such behaviors [11-14]. Investigating the extent to which distinct hippocampal memories across the longitudinal axis modulate behavior could aid in the understanding of stress-related psychiatric disorders known to affect emotion, memory, and cognition [15]. Here, we asked whether tagging and stimulating cells along the dorsoventral axis of the hippocampus could acutely, chronically, and differentially promote context-specific behaviors. Acute reactivation of both dorsal and ventral hippocampus cells that were previously active during memory formation drove freezing behavior, place avoidance, and place preference. Moreover, chronic stimulation of dorsal or ventral hippocampal fear memories produced a context-specific reduction or enhancement of fear responses, respectively, thus demonstrating bi-directional and context-specific modulation of memories along the longitudinal axis of the hippocampus. Fear memory suppression was associated with a reduction in hippocampal cells active during retrieval, while fear memory enhancement was associated with an increase in basolateral amygdala activity. Together, our data demonstrate that discrete sets of cells throughout the hippocampus provide key nodes sufficient to bi-directionally reprogram both the neural and behavioral expression of memory.

Relationship Between Back Pain and Urinary Incontinence in the Canadian Population.

Background: Back problems and urinary incontinence (UI) have been found to co-occur more frequently than would be predicted by chance. Objective: The aim of this study was to estimate the associations between UI and back problems in the Canadian men and women. Design: This was an observational, cross-sectional study. Methods: The 2011-2012 Statistics Canada Canadian Community Health Survey (CCHS) provided the data. The CCHS surveyed 125,645 adults, providing a representative sample of the Canadian population. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to quantify the strength of the associations among the variables. Results: Having UI increased the risk of also having back problems in both men (OR = 2.45; 95% CI = 2.06-2.91) and women (OR = 2.97; 95% CI = 2.64-3.35) compared with not experiencing UI. Among those participants with UI, men and women were at equal risk of experiencing back problems. Limitations: The CCHS data are cross-sectional and self-reported, which prevents determining causality and carries a risk of response bias. Also, various diagnoses were grouped under the back problems and UI categories, which makes it difficult to propose possible explanations for this pattern of comorbidity. Conclusions: This study provides firm evidence to support clinically observed associations between UI and back problems. The strength of the associations was essentially equal in men and women. These findings reinforce the importance of screening for these frequently coincident conditions.

The cardiac implications of breast reconstruction using the internal mammary artery as the recipient vessel.

BACKGROUND: Microsurgical breast reconstruction is a popular choice in breast reconstruction. Recipient vessel use for these autologous tissue reconstructions has shifted from the thoracodorsal to the internal mammary vessels. Coronary artery bypass (CAB) surgery remains the optimal revascularization strategy in patients with significant, diffuse coronary artery disease. The conduits of choice for coronary revascularization are the internal mammary arteries (IMA) because of their superior long-term graft patency rate and improved patient survival. OBJECTIVE: To review the cardiac risk factors in the breast reconstruction population, and to report the incidence of postoperative cardiac events at the London Health Sciences Centre, London, Ontario. The authors present the index cases illustrating cardiac complications following the use of internal mammary vessels. METHOD: A retrospective, single-centre, cumulative audit of breast reconstruction practice from 2005 to 2009 was conducted. A total of 81 patients undergoing autologous breast reconstruction were reviewed. Two women were noted to have experienced postoperative myocardial infarction requiring intervention. Both were noted to have triple-vessel disease, an indication for CAB; however, during the breast reconstruction, their IMAs had been utilized. As a result, both women subsequently underwent triple-vesssel percutaneous intervention, with one woman later requiring CAB without IMA because of recurrent ischemia. CONCLUSION: While there is limited overlap with the breast reconstruction and cardiac disease population, there can be significant cardiac health implications in the postoperative status (both short and long term) of women undergoing autologous breast reconstruction using the IMAs as recipient vessels.

HISTORIQUE: La reconstruction mammaire microchirurgicale est un choix populaire. Le recours à des vaisseaux receveurs dans le cadre de ces reconstructions par tissus autologues est passé des vaisseaux thoracodorsaux aux vaisseaux mammaires internes. Le pontage aortocoronarien (PAC) demeure la stratégie de revascularisation optimale chez les patients ayant une coronaropathie diffuse. Les artères mammaires internes (AMI) représentent des conduits de choix pour la revascularisation coronarienne en raison du taux de perméabilité supérieur de la greffe à long terme et du meilleur taux de survie des patients. OBJECTIF: Analyser les facteurs de risque cardiaque des personnes subissant une reconstruction mammaire et signaler l'incidence d'événements cardiaques postopératoires survenus au London Health Sciences Centre de London, en Ontario. Les auteurs présentent les cas de référence démontrant des complications cardiaques après l'utilisation des vaisseaux mammaires internes. MÉTHODOLOGIE: Les chercheurs ont procédé à une vérification cumulative monocentriquerétrospective des pratiques de reconstruction mammaire entre 2005 et 2009. Au total, ils ont analysé 81 patients ayant subi une reconstruction mammaire par tissus autologues. Ils ont constaté que deux femmes avaient subi un infarctus du myocarde après l'opération, lequel avait nécessité une intervention. Toutes deux avaient unetriple vasculopathie, ce qui constitue une indication de PAC, mais pendant la reconstruction mammaire, on avait utilisé leurs AMI. Par conséquent, les deux femmes ont ensuite subi une triple intervention percutanée, et l'une d'elles a ensuite dû subir un PAC sans AMI en raison d'une ischémie récurrente. CONCLUSION: Le chevauchement entre la population de personnes qui subissent une reconstruction mammaire et celle qui est atteinte d'une maladie cardiaque est limité. Toutefois, les femmes qui subissent une reconstruction mammaire par tissus autologues chez qui les AMI servent de vaisseaux receveurs peuvent voir leur état postopératoire (à court et à long terme) entaché par d'importants effets cardiaques.

Can internal thoracic arteries be used for both coronary artery bypass and breast reconstruction?

OBJECTIVES: Recently, the internal thoracic arteries have been preferentially used in autologous breast reconstruction at the levels of the third or fourth intercostal spaces. This may compromise future treatment of occult coronary disease. We hypothesized that internal thoracic artery length at the fourth intercostal space would allow both breast reconstruction and future coronary artery bypass grafting (CABG). METHODS: Anatomic analysis of 20 female patients undergoing CABG was performed examining internal thoracic artery length from its origin to the third, fourth, fifth intercostal spaces and the left anterior descending (LAD) artery target. RESULTS: The left internal thoracic artery was anastamosed to the LAD target at a mean length of 11.4 ± 1.4 cm. The mean lengths of the pedicled left internal thoracic artery from its origin to the third, fourth and fifth intercostal space were 8.5 ± 1.0, 10.9 ± 1.2 and 13.0 ± 1.4 cm, respectively. Therefore, the left internal thoracic artery length was adequate at the fourth intercostal space in 6 of 20 (30%) patients. CONCLUSIONS: Dissection of the left internal thoracic artery to the fourth intercostal space would allow for concomitant use in CABG and breast reconstruction in one-third of cases. However, skeletonization of the internal thoracic artery at the level of the fourth intercostal space would be sufficient for CABG in all cases following autologous breast reconstruction.

Feasibility of internal mammary vessel use in breast reconstruction versus coronary artery bypass surgery: an anatomic, cadaveric evaluation.

BACKGROUND: Autologous free flap breast reconstruction using the internal mammary artery is common; however, its use may compromise treatment of occult coronary artery disease. The authors investigated whether internal mammary artery harvest for breast reconstruction is compatible with future use for coronary bypass. METHODS: An anatomic analysis of 10 preserved female cadavers was performed. Internal mammary artery measurements, including the length from its origin to the third, fourth, and fifth intercostal spaces, were taken, and the minimum length required to reach the left anterior descending coronary artery was determined. RESULTS: The left internal mammary artery reached the left anterior descending target at a mean length of 10.0 cm. The mean lengths to the left third, fourth, and fifth intercostal spaces were 8.2 cm, 11.3 cm, and 13.7 cm, respectively, on the left, and 7.6 cm, 10.7 cm, and 13.2 cm, respectively, on the right. The right internal mammary artery reached the left anterior descending target at a mean of 12.0 cm. CONCLUSIONS: The left internal mammary artery was found to reach the estimated coronary target by the level of the fourth intercostal space consistently, while the right was more variable and required a greater length. If the fourth intercostal space was used to harvest the internal mammary artery, the length necessary for in situ coronary bypass surgery is preserved on the left, and may still be used as a free graft on the right.

Klebsiella oxytoca necrotizing fasciitis after orthotopic heart transplant.

We report a case of Klebsiella necrotizing fasciitis after heart transplantation. The infection required debridement of discontinuous areas on three extremities as well as on the trunk. Klebsiella sp necrotizing fasciitis is a rare entity and has not been described previously in concert with heart transplantation. Klebsiella cases classically have skip lesions as described herein. Klebsiella oxytoca is a rare cause of necrotizing fasciitis in North America and presents with multifocal infection sites. This along with the patient's blunted immune response after organ transplantation necessitated a high index of suspicion for diagnosis and treatment.

Reconstruction of the pelvic ring with vascularized double-strut fibular flap following internal hemipelvectomy.

BACKGROUND: After internal hemipelvectomy, successful pelvic reconstruction can provide a durable and pain-free reconstruction for the young, active patient. Such reconstruction is extremely challenging, and often patients have less than optimal ambulation with a limp, leg length discrepancy, or leg instability. The authors present an innovative method for pelvic ring reconstruction using a vascularized double-strut fibular bone flap that provides a stable pelvis and recovery of normal or near-normal gait. METHODS: From December of 2003 to November of 2005, six sarcoma patients underwent internal hemipelvectomy and pelvic ring reconstruction with a vascularized double-strut fibular bone flap. The length of each strut was 7 to 12 cm. RESULTS: All bone flaps survived. The mean follow-up was 18 months (range, 8 to 32 months). Radiographic evidence of bone bridging was seen at a mean of 2.5 months (range, 2 to 4 months). The mean time to ambulation without assistance was 8 months (range, 5 to 18 months). One patient died as a result of metastatic disease. The remaining five patients are ambulatory with a mild limp or no limp. CONCLUSION: Use of a vascularized double-strut fibular bone flap for pelvic ring reconstruction is effective in facilitating early ambulation and restoring normal to near-normal gait in patients undergoing internal hemipelvectomy.

Cosmetic outcomes following breast conservation therapy: in search of a reliable scale.

INTRODUCTION: Multiple scales to evaluate breast cosmesis following breast conserving treatment (BCT) have been developed, however reliability is a problem. Panel scores, where scores from two or more individuals are combined, were assessed to examine their effect on reliability for two different cosmetic scales. METHODS: Women, two or more years following BCT, were recruited from a single breast centre. Photographs of each participant were evaluated independently by six health care professionals on two separate occasions. A simple four-point scale and more involved multi-item scale were used to assess cosmetic outcome. Reliability was assessed with the weighted kappa statistic for increasing panel sizes. RESULTS: Ninety-nine women were evaluated. Intra rater reliability increased from 0.73 to 0.83 for the four-point scale, for increasing panel sizes, however 95% confidence intervals generally overlapped. A smaller and more unpredictable effect was seen on the multi-item subscale, range 0.69 to 0.73. Inter rater reliability increased from 0.68 to 0.93 for the four-point scale, and 0.75 to 0.96 for the multi-item scale, for increasing panel sizes; 95% confidence intervals did not overlap. A panel of three for either scale provided almost perfect kappa values with only small improvements with larger panel sizes. CONCLUSIONS: Care should be used in interpreting results where cosmetic outcomes have been obtained from a single evaluator. Panel scores can be used to significantly improve inter-rater, but not intra rater reliability, for the scales studied. Comparable reliability, in combination with simplicity of use and interpretation, would favour the four-point scale for breast cosmetic evaluation over the multi-item scale.

Thoracodorsal artery perforator (TAP) flap reconstruction of a soft-tissue defect of the knee following below-knee amputation.

Soft-tissue coverage of lower extremity defects with thin, sensate, mobile, and durable soft tissue is challenging. Reconstructive options are further limited in the setting of a below-knee amputation. The authors present the first report of an innervated thoracodorsal artery perforator (TAP) flap for coverage of an anterior knee soft-tissue defect in a patient with bilateral below-knee amputations following disseminated meningococcemia. The soft-tissue defect measured 11 x 17 cm2 centered over the patella, and the TAP flap provided adequate pedicle length, with optimal soft-tissue thickness and pliability with the potential for innervation and minimal donor-site morbidity. Six months postoperatively, the patient is ambulating well with prostheses fitted over her well-healed, stable, knee coverage.