Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release.

Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small 'extinction burst', further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair.

PURPOSE: The objective was to evaluate the host response, resorption, and strength properties, and to assess the performance in the presence of bacteria for Phasix™ Mesh (Phasix™) and Gore® Bio-A® Tissue Reinforcement (Bio-A®) in preclinical models. METHODS: In a rat model, one mesh (2 × 2 cm) was implanted subcutaneously in n = 60 rats. Animals were euthanized after 2, 4, 8, 12, 16, or 24 weeks (n = 5/mesh/time point), and implant sites were assessed for host inflammatory response and overall fibrotic repair thickness. In a rabbit model, meshes (3.8 cm diameter) were bilaterally implanted in subcutaneous pockets in n = 20 rabbits (n = 10 rabbits/mesh) and inoculated with 108 CFU clinically isolated methicillin-resistant Staphylococcus aureus (MRSA). One mesh type was implanted per animal. Animals were euthanized after 7 days, and implants were assessed for abscess formation, bacterial colonization, and mechanical strength. RESULTS: In the rat study, Phasix™ and Bio-A® exhibited similar biocompatibility, although Bio-A® demonstrated a significantly greater inflammatory response at 4 weeks compared to Phasix™ (p < 0.01). Morphometric analysis demonstrated rapid resorption of Bio-A® implants with initially thicker repair sites at 2, 4, 8, and 12 weeks (p < 0.0001), which transitioned to significantly thinner sites compared to Phasix™ at 16 and 24 weeks (p < 0.0001). In the rabbit bacterial inoculation study, Phasix™ exhibited significantly lower abscess score (p < 0.001) and bacterial colonization (p < 0.01), with significantly greater mechanical strength than Bio-A® (p < 0.001). CONCLUSIONS: Host response, resorption, repair thickness, strength, and bacterial colonization suggest a more stable and favorable outcome for monofilament, macroporous devices such as Phasix™ relative to multifilament, microporous devices such as Bio-A® over time.

Intrapartum management of trial of labour after caesarean delivery: evidence and experience.

Few studies have focused specifically on the intrapartum management of patients following a prior caesarean delivery. Contemporary assessments and recommendations on attempting vaginal birth after caesarean delivery (VBAC) vary. The actual conduct of labour and delivery of the infant in an uncomplicated trial of labour after caesarean (TOLAC) is similar to the management of a patient without a previous caesarean. Intrapartum management of TOLAC differs primarily in the need for caution with induction of labour in women with an unfavourable cervix, the avoidance of overstimulation with oxytocin augmentation, and surveillance for prompt recognition of the rare case of uterine rupture.

Male mastectomy: an oncoplastic solution to improve aesthetic appearance.

Mastectomy for breast cancer in men typically results in an unsatisfactory aesthetic appearance due to loss of the normal male chest contour. In this article we present two case studies and a new oncoplastic surgical technique that has given excellent aesthetic results for this challenging problem.

Dental microwear texture analysis of two families of subfossil lemurs from Madagascar.

This study employs dental microwear texture analysis to reconstruct the diets of two families of subfossil lemurs from Madagascar, the archaeolemurids and megaladapids. This technique is based on three-dimensional surface measurements utilizing a white-light confocal profiler and scale-sensitive fractal analysis. Data were recorded for six texture variables previously used successfully to distinguish between living primates with known dietary differences. Statistical analyses revealed that the archaeolemurids and megaladapids have overlapping microwear texture signatures, suggesting that the two families occasionally depended on resources with similar mechanical properties. Even so, moderate variation in most attributes is evident, and results suggest potential differences in the foods consumed by the two families. The microwear pattern for the megaladapids indicates a preference for tougher foods, such as many leaves, while that of the archaeolemurids is consistent with the consumption of harder foods. The results also indicate some intraspecific differences among taxa within each family. This evidence suggests that the archaeolemurids and megaladapids, like many living primates, likely consumed a variety of food types.

The timing of autologous latissimus dorsi breast reconstruction and effect of radiotherapy on outcome.

INTRODUCTION: The optimal timing of breast reconstruction is controversial. Immediate breast reconstruction (IBR) has been gaining in popularity due to the aesthetic and psychological benefits, although its role is less certain when postoperative radiotherapy may be required. There is some evidence that long term cosmetic outcome of IBR using the autologous latissimus dorsi (ALD) flap may be impaired if the reconstruction is subjected to postoperative radiotherapy. We compared the long term cosmetic outcome and patient satisfaction between a group of patients who underwent IBR with postoperative radiotherapy and a group who underwent delayed ALD reconstruction. METHODS: Patients who underwent ALD breast reconstruction between 1997 and 2000 were invited to attend a research clinic. At the clinic up-to-date photographs were obtained and a quality of life questionnaire was completed. Cosmetic outcome was assessed by a panel of judges including surgeons, nurses and lay people. RESULTS: Thirteen patients who had IBR and postoperative radiotherapy and 11 patients who had delayed reconstruction attended for follow up. In the long term both groups fell within an acceptable cosmetic outcome range. However, there was a trend towards a better outcome in patients undergoing delayed reconstruction, with the volume and contour of the upper pole being most affected in the irradiated reconstructions. Patient satisfaction was similar between the two groups, however most patients in retrospect would have preferred an immediate reconstruction. CONCLUSIONS: Immediate ALD breast reconstruction, even in the setting of postoperative radiotherapy, yields satisfactory results. We continue to offer it to patients undergoing mastectomy operations, even when postoperative radiotherapy is likely to be required.

Prelaminated free radial forearm flap for a total nasal reconstruction.

A prelaminated osteocutaneous radial forearm flap has previously been described for total nasal reconstruction, but achieving good aesthetics at the dorsum and tip tends to be difficult with a flap that can be too bulky. We present a case of total nasal reconstruction in a burns patient where a tight adherent scar at the forehead precluded the use of a forehead flap, ideal for such reconstructions. We successfully used a prelaminated free radial forearm flap, with a non-vascularised bone graft. The existing scarred skin at the dorsum was turned down as pedicled flaps for the lining. We were able to achieve a successful total nasal reconstruction which was aesthetically pleasing and made a tremendous impact on the quality of life of the patient.

Prevention of paediatric ring avulsions - a cadaveric study.

Finger ring avulsion injuries can be functionally, cosmetically and emotionally devastating for the patient. This cadaveric study assessed a simple way to prevent ring avulsion injuries. Fresh cadaver fingers were used to test the incidence of avulsion injury with ordinary rings and when a single slot was cut in the ring. Intact rings mostly produced significant digital injuries, while the rings with slots did not.

Immunotherapy for recurrent miscarriage.

BACKGROUND: Because immunological aberrations might be the cause of miscarriage in some women, several immunotherapies have been used to treat women with otherwise unexplained recurrent pregnancy loss. OBJECTIVES: The objective of this review was to assess the effects of any immunotherapy, including paternal leukocyte immunization and intravenous immune globulin on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2004, Issue 3), MEDLINE (1966 to September 2004) and EMBASE (1980 to September 2004). SELECTION CRITERIA: Randomized trials of immunotherapies used to treat women with three or more prior miscarriages and no more than one live birth after, in whom all recognised non-immunologic causes of recurrent miscarriage had been ruled out and no simultaneous treatment was given. DATA COLLECTION AND ANALYSIS: The review author and the two co-authors independently extracted data and assessed study quality for all studies considered for this review. MAIN RESULTS: Twenty trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups in terms of subsequent live births: paternal cell immunization (12 trials, 641 women), Peto odds ratio (Peto OR) 1.23, 95% confidence interval (CI) 0.89 to 1.70; third party donor cell immunization (three trials, 156 women), Peto OR 1.39, 95% CI 0.68 to 2.82; trophoblast membrane infusion (one trial, 37 women), Peto OR 0.40, 95% CI 0.11 to 1.45; intravenous immune globulin, Peto OR 0.98, 95% CI 0.61 to 1.58. AUTHORS' CONCLUSIONS: Paternal cell immunization, third party donor leukocytes, trophoblast membranes, and intravenous immune globulin provide no significant beneficial effect over placebo in improving the live birth rate.

Cotransfection of heme oxygenase-1 prevents the acute inflammation elicited by a second adenovirus.

The acute inflammatory response elicited by adenovirus vectors results in loss of gene expression and tissue injury in the target organ. This acute inflammation is now believed to be the major limiting factor for the use of adenovirus vectors in gene therapy. While exploring the level of acute inflammation caused by the adenovirus encoding the gene for the anti-inflammatory enzyme heme oxygenase-1, we discovered that this adenovirus not only did not elicit acute inflammation, but could prevent the inflammation caused by a second adenovirus. Here we describe a new approach to gene therapy, which uses the encoding of the potent anti-inflammatory enzyme heme oxygenase-1 to prevent early host inflammatory responses normally associated with adenovirus vectors.

Immunotherapy for recurrent miscarriage.

BACKGROUND: Immunologic aberrations might be the cause of recurrent early pregnancy loss in some women. OBJECTIVES: The objective of this review was to assess the effects of leukocyte immunisation or other immunologic treatments such as intravenous immune globulin (IVIG) on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched (September 2002). Individual patient data were obtained from the American Society for Reproductive Immunology. SELECTION CRITERIA: Randomised trials of immunotherapy in women with three or more prior miscarriages and no more than one live birth; all recognised non-immunologic causes ruled out and no simultaneous treatment intervention. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. MAIN RESULTS: Nineteen trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups in terms of subsequent live births: paternal cell immunisation (11 trials, 596 women), odds ratio (OR) 1.05, 95% confidence intervals (CI) 0.75 to 1.47; third party donor cell immunization (3 trials, 156 women), OR 1.39, 95% CI 0.68 to 2.82; trophoblast membrane infusion (1 trial, 37 women), OR 0.40, 95% CI 0.11 to 1.45; intravenous immune globulin (IVIG), OR 0.98, 95% CI 0.61 to 1.58. REVIEWER'S CONCLUSIONS: Paternal cell immunization, third party donor leukocytes, trophoblast membranes, and intravenous immune globulin provide no significant beneficial effect over placebo in preventing further miscarriages.