Skeletal open bite correction by combined Le Fort I osteotomy and bilateral sagittal split of the mandibular ramus

Of over 300 surgically-treated skeletal open bite cases, 10 were corrected by simultaneous repositioning of the maxilla and mandible by means of a Le Fort I osteotomy and bilateral sagittal splitting of the mandibular ramus. The paucity of cases does not permit detailed statistical evaluation; however of the many parameters investigated, certain appeared to be associated with relapse in this series: short intermaxillary fixation period, skeletal class II, and the surgeon. Despite skeletal relapse in 3 cases, dental compensation precluded the need to re-operate on any of these relapsed cases. This surgical approach to the correction of a skeletal open bite, when indicated on aesthetic and occlusal grounds, is a particularly suitable method, and gives stable results.     

FRCSEd (Oral and Maxillofacial Surgery): a milestone in the history of Oral and Maxillofacial Surgery in the United Kingdom

The British Association of Oral and Maxillofacial Surgeons (BAOMS) and the Royal College of Surgeons of Edinburgh (RCSEd) have had leading roles in organisation, assessment and improvement of surgical training in the United Kingdom. This was particularly well illustrated by the establishment of the fellowship examination in Oral and Maxillofacial Surgery (FRCSEd, OMFS).     

An update on red blood cell storage lesions,as gleaned through biochemistry and omics technologies

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐stored RBCs and promote the rapid clearance of up to one‐fourth of long‐stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.     

Proteome Changes in Platelets After Pathogen Inactivation—An Interlaboratory Consensus

Pathogen inactivation (PI) of platelet concentrates (PCs) reduces the proliferation/replication of a large range of bacteria, viruses, and parasites as well as residual leucocytes. Pathogen-inactivated PCs were evaluated in various clinical trials showing their efficacy and safety. Today, there is some debate over the hemostatic activity of treated PCs as the overall survival of PI platelets seems to be somewhat reduced, and in vitro measurements have identified some alterations in platelet function. Although the specific lesions resulting from PI of PCs are still not fully understood, proteomic studies have revealed potential damages at the protein level. This review merges the key findings of the proteomic analyses of PCs treated by the Mirasol Pathogen Reduction Technology, the Intercept Blood System, and the Theraflex UV-C system, respectively, and discusses the potential impact on the biological functions of platelets. The complementarities of the applied proteomic approaches allow the coverage of a wide range of proteins and provide a comprehensive overview of PI-mediated protein damage. It emerges that there is a relatively weak impact of PI on the overall proteome of platelets. However, some data show that the different PI treatments lead to an acceleration of platelet storage lesions, which is in agreement with the current model of platelet storage lesion in pathogen-inactivated PCs. Overall, the impact of the PI treatment on the proteome appears to be different among the PI systems. Mirasol impacts adhesion and platelet shape change, whereas Intercept seems to impact proteins of intracellular platelet activation pathways. Theraflex influences platelet shape change and aggregation, but the data reported to date are limited. This information provides the basis to understand the impact of different PI on the molecular mechanisms of platelet function. Moreover, these data may serve as basis for future developments of PI technologies for PCs. Further studies should address the impact of both the PI and the storage duration on platelets in PCs because PI may enable the extension of the shelf life of PCs by reducing the bacterial contamination risk.     

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors overexpressing MDMX. Here, we identify small molecules that potently block p53 binding with both MDM2 and MDMX by inhibitor-driven homo- and/or heterodimerization of MDM2 and MDMX proteins. Structural studies revealed that the inhibitors bind into and occlude the p53 pockets of MDM2 and MDMX by inducing the formation of dimeric protein complexes kept together by a dimeric small-molecule core. This mode of action effectively stabilized p53 and activated p53 signaling in cancer cells, leading to cell cycle arrest and apoptosis. Dual MDM2/MDMX antagonists restored p53 apoptotic activity in the presence of high levels of MDMX and may offer a more effective therapeutic modality for MDMX-overexpressing cancers.     

Clinical trial of a monophasic estroprogestin oral formulation containing 20 micrograms ethinyl estradiol and 75 micrograms gestodene.

The attempt to decrease the hormonal components of combined estrogen/progestin-containing oral formulations has led to use of low-dose formulations. The monophasic formulation containing ethinyl estradiol 20 micrograms (EE20) plus gestodene 75 micrograms (GSD75) was studied in an open, non-comparative, multicenter, clinical trial investigating its efficacy, safety, effects on body weight, blood pressure and sexual function. To evaluate the impact on sexual function, the Golombok Rust Questionnaire on Sexual Satisfaction (GRISS) was used. The study population comprised 216 women treated for 1 year. The EE20/GSD75 formulation did not show any significant effect on blood pressure, hematological parameters, body weight or sexual function. The treatment was well tolerated with a high compliance rate by the patients, with a low rate of estrogen-dependent symptoms. Moreover, there was no overall effect on sexual function, with no disturbance of sexual behavior or activity. In conclusion, our data show that the EE20/GSD75 has a very good tolerability profile, without any significant side-effects.     

Skin improvement with two different oestroprogestins in patients affected by acne and polycystic ovary syndrome: clinical and instrumental evaluation

Background Despite it is accepted that acne is mostly caused by an hyper‐responsiveness of the pilo‐sebaceous unit to normal circulating androgen hormones, in a few patients, especially women, acneic lesions can be associated with increased serum androgen levels (hyperandrogenism), of which polycystic ovary syndrome (PCOS) is the most common cause. In women with acne and proven PCOS therapy with estroprogestins (EPs) can be an excellent option. Objective The aim of the study was to assess the effects of two estroprogestins (EPs), ethinyl‐estradiol (EE) 30 mcg/drospirenone (DRSP) 3 mg, and ethinyl‐estradiol (EE) 30 mcg/chlormadinone acetate (CMA) 2 mg, both on increased serum androgen levels and on several skin parameters in women affected by mild to severe acne and polycystic ovary syndrome (PCOS). Methods Fifty‐nine women were randomized to receive EE/DRSP (n = 32) or EE/CMA (n = 27) for six months. Evaluation of serum androgen levels, grading of acne and hirsutism (respectively with Pillsbury and Ferriman‐Gallwey score) and non‐invasive assessment of skin hydration, transepidermal water loss (TEWL) and skin homogeneity were performed at baseline, at 3 and 6 months (end of treatment). Results Both treatments were well tolerated and showed a significant improvement of skin and hormonal parameters, although EE/DRSP showed a more potent effect on acne and seborrhea. Conclusions Estroprogestins represent an effective and safe treatment in women with acne and polycystic ovary syndrome (PCOS). Nevertheless, the combination EE 30 mcg/DRSP 3 mg appears to be a more potent therapeutic option.     

Botryomycosis of the oral regions

Botryomycosis is an unusual bacterial infection capable of producing chronic granulomatous inflammation and characterised by the production of distinctive grains formed by the interaction of the infective bacteria with the host tissues. The occurrence of this infection in a healthy individual generally results in locally destructive lesions which can clinically mimic a sarcoma. A case is reported involving the oral regions of a healthy adult male which illustrated these features and a discussion is presented of the diagnostic features of this condition.