Investigation of Genetic Variants Associated with Tryptophan Metabolite Levels via Serotonin and Kynurenine Pathways in Patients with Bipolar Disorder

The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants

Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD

A Clinical Study of Late Seroma in Breast Implantation Surgery

The use of mammary implants may lead to a variety of early and delayed complications. The most common delayed complications are capsular contracture and implant failure. Late seroma has seldom been reported. In a long-term prospective observational study, cases of late seroma were assessed and recorded. Between March 2005 and November 2009, suspected cases of late seroma in patients who had undergone breast augmentation or reconstruction with textured implants were evaluated clinically and with instrumental analyses. An ultrasound-guided needle aspiration of the fluid was performed. In this study, 13 cases of late seroma (8 augmentations and 5 reconstructions) were observed. The overall incidence of this complication was 1.68%. Chemical analyses confirmed the diagnosis of seroma, which recurred in all the patients within days of evacuation. For 12 patients, a reoperation was performed, during which the implant was removed, a total capsulectomy was performed, and in cases of subglandular breast augmentation, the implant pocket was changed to a submuscular placement before a new prosthesis was inserted. One patient underwent a second ultrasound-guided needle aspiration. No seroma recurrence was observed in any of the patients during the follow-up period. In case of unexpected breast enlargement after prosthesis implantation, the physician should first rule out infection, then investigate possible friction irritation from either a fold in the device or rubbing of a textured implant. According to the authors' experience and another report, this complication occurs in 1% to 2% of cases. The inclusion of this complication in the informed consent form should be considered. Long-term studies designed to investigate the underlying causes of late seroma are warranted for the prevention and treatment of this complication

Fibroepithelioma of Pinkus: variant of basal cell carcinoma or trichoblastoma? Case report

Introduction. Fibroepithelioma of Pinkus (FeP) is a rare tumor that most often affects women aged between 40 and 60 years. Clinically FeP presents as a soft, usually solitary, polypoid or papillomatous well circumscribed tumor of skin color. It is typically located to the trunk and extremities. Case report. A 75 year old male presented to our Department complaining for the presence of a lesion of the dorsal region. His medical history was free except for several basal cell carcinoma (BCC) surgically excised. Clinical examination revealed a pigmented lesion in the back. The lesion was surgically excised and histopathology showed of a fibroepithelioma of Pinkus. Discussion. Currently, FeP is considered a rare variant of basal cell carcinoma, with characteristic histopathological features, although this view is somewhat controversial as some authors considered FeP to be a variant of trichoblastoma. The pathogenesis of FeP is still under investigation. It is thought that a mutation in the tumor suppressor gene TP53 might predispose to the development of FeP. Conclusions. Our case is interesting for two reasons. First, in our case FeP is pigmented. Moreover we present a case of Fep in a patient with a history of BCC, a finding that supports the classification of fibroepithelioma of Pinkus as a variant of basal cell carcinoma

Reconstruction of posterior auricular ear surface defects: “Ear Keystone graft”

Malignant cutaneous tumors are common on the external ear1 and reconstruction of posterior auricular surface's defects after surgical removal of cancer can be performed using different strategies. These techniques can be not easy or not really quick to perform, therefore we believe that it can be useful to propose another strategy to evaluate between the different reconstructive options in this anatomical region. The Keystone Design Perforator Island Flap (KDPIF), a curvilinear shaped trapezoidal design flap described by Felix C Behan in 2003,2 is a solution to reconstruct soft tissue defects in head and neck, trunk, and extremities. Based on fasciocutaneous perforators, this flap offers both the robust vascularity of perforator flaps and the relative ease and speed of local tissue rearrangement. In this regard we present our experience with the use of the KDPIF for the posterior surface of the auricle's reconstruction after removal of a skin epithelioma. This application of KDPIF has never been described in literature and it is a special feature due to the lack of perforating vessels that supply blood to the flap in this anatomical region

Exposure of the IMA made easy

[No abstract available

Exposure of the IMA made easy

[No abstract available

Modified pull-out suture in zone one injuries: button or gasket?

[No abstract available

Correction of tuberous breast with small volume asymmetry by using a new adjustable implant

BACKGROUND: The tuberous breast syndrome is a rare anomaly of breast shape, which can be associated to volume breast asymmetry. We report our caseload in the correction of tuberous breasts with small volume asymmetry by using the Muti's technique associated to the implantation of a new adjustable implant. AIM: Purpose of the study is to evaluate the efficacy of treating tuberous breast deformity with two different types of implants (a textured round high profile cohesive I implant in the larger breast and a Spectra T implant in the smaller breast). PATIENTS AND METHODS: Since May 2008, patients affected by tuberous breast combined to small breast volume asymmetry were enrolled in a prospective study. After gland deformity correction, the adjustable implant was positioned in the smaller breast. A textured round implant was positioned in the contralateral breast. Standard pictures were taken before surgery and during follow-up visits over one year. A visual analogue scale (VAS) scale was used to evaluate patients' and external physicians' judgment. Standardized objective measurements of breast and chest were also taken. Statistical significance of any value variation was assessed with the Wilconxon's rank sum test. RESULTS: Eleven patients were treated with the proposed surgical approach. VAS scores from patients and external physicians were high. Deformity correction was obtained in all patients as evidenced by the significant modifications of objective measurements. No major late complications occurred. CONCLUSIONS: The new adjustable implant provides a reliable corrective option for hypoplastic tuberous breasts with small volume asymmetry. This device allows intra-operative modification of implant volume according to breast volume discrepancy. Although our findings are satisfying, a longer follow-up is required to evaluate long term results

Retention of polyurethane foam fragments during VAC therapy: A complication to be considered

Osmolalita parenterálních přípravků s obsahem neelektrolytů Lenka Křížová Summary In the theoretical part of theses, the problematic of formulation of parenteral products is summarized. The pharmacopoeial information about osmolality and osmolarity of solutions is also presented. In the experimental part, there are summarized results of pycnometric measurement of density and measurement of osmolality by osmometer for chosen aqueous solutions of used nonelectrolytes (fructose, glucose, lactose, mannitol and sorbitol) in graduated molality within the range of 0,1 - 1,0 mol/kg. There changes in volume of solution relating to the dissolution of investigated substances in relation to concentration of aqueous solutions were expressed. Methods of the determination of the theoretical and actual osmolarity from the measured osmolality were reported