Kinetics of selective oxidation of lactose to lactobionic acid over Pd-active carbon catalyst

Laktoosi eli maitosokeri on tärkein ainesosa useimpien nisäkkäiden tuottamassa maidossa. Sitä erotetaan herasta, juustosta ja maidosta. Laktoosia käytetään elintarvike- ja lääketeollisuuden raaka-aineena monissaeri tuotteissa. Lääketeollisuudessa laktoosia käytetään esimerkiksi tablettien täyteaineena. Hapettamalla laktoosia voidaan valmistaa laktobionihappoa, 2-keto-laktobionihappoa ja laktuloosia. Laktobionihappoa käytetään biohajoavien pintojen ja kosmetiikkatuotteiden valmistuksessa, sekä sisäelinten säilöntäliuoksissa, joissa laktobionihappo estää happiradikaalien aiheuttamien kudosvaurioiden syntymistä. Tässä työssä laktoosia hapetettiin laktobionihapoksi sekoittimella varustetussa laboratoriomittakaavaisessa panosreaktorissa käyttäenkatalyyttinä palladiumia aktiivihiilellä. Muutamissa kokeissa katalyytin promoottorina käytettiin vismuttia, joka hidastaa katalyytin deaktivoitumista. Työn tarkoituksena oli saada lisää tietoa laktoosin hapettamisen kinetiikasta. Laktoosin hapettumisessa laktobionihapoksi havaittiin selektiivisyyteen vaikuttavan muunmuassa reaktiolämpötila, paine, pH ja käytetyn katalyytin määrä. Katalyyttiä kierrättämällä eri kokeiden välillä saatiin paremmat konversiot, selektiivisyydet ja saannot. Parhaat koetulokset saatiin hapetettaessa synteettisellä ilmalla 60 oC lämpötilassa ja 1 bar paineessa. Tehdyissä kokeissa pH:n säätö tehtiin manuaalisesti, joten pH ei pysynyt koko ajan haluttuna. Laktoosin konversio oli parhaimmillaan 95 %. Laktobionihapon suhteellinen selektiivisyys oli 100% ja suhteellinen saanto 100 %. Kinetiikan matemaattinen mallinnus tehtiin Modest-ohjelmalla käyttäen kokeista saatuja mittaustuloksia.Ohjelman avulla estimoitiin parametreja ja saatiin matemaattinen malli reaktorille. Tässä työssä tehtiin kineettinen mallinnus myös ravistelureaktorissa tehdyille laktoosin hapetuskokeille, missä pH pysyi koko ajan haluttuna 'in-situ' titrauksen avulla. Työn yhteydessä selvitettiin myös mahdollisuutta käyttää monoliittikatalyyttejä laktoosin hapetusreaktiossa.

Fibrosarcoma-like lipomatous neoplasm: a reappraisal of so-called spindle cell liposarcoma defining a unique lipomatous tumor unrelated to other liposarcomas

The term "spindle cell liposarcoma" has been applied to liposarcomas (LPSs) composed predominantly or exclusively of spindled cells. These tumors have been considered variants of well-differentiated LPS (WDL), myxoid LPS, and spindle cell lipoma, suggesting that this is a heterogenous group of lesions. Using strict morphologic criteria and molecular and immunohistochemical analyses, we have identified a homogenous group of spindle cell lipomatous tumors, histologically and genetically distinct from other forms of LPS, which we have called "fibrosarcoma-like lipomatous neoplasm." Cases classified as "spindle cell LPS" or "low-grade LPS with spindle cell features" were reviewed. Final selection criteria included: (1) an exclusive low-grade spindle cell component resembling fibrosarcoma; (2) a mixture of bland fibroblastic cells resembling the preadipocyte and early-adipocyte stage of embryonic fat; and (3) molecular-genetic analysis that excluded other forms of lipomatous tumors. Of the initial 25 cases identified, comparative genomic hybridization (CGH) was uninformative in 2 cases; 5 were reclassified as WDL on the basis of molecular data (MDM2 amplification) and 6 as spindle cell lipoma (CGH profiles with a few gains and losses including a constant loss of chromosome 13 and frequent losses of chromosomes 16 and 6). The 12 remaining cases showed flat CGH profiles; of these cases, 11 were negative for DDIT3 gene rearrangements, and 1 result was uninterpretable. Patients ranged in age from 15 to 82 years (mean 50 y); male patients were affected slightly more often (7:5). Tumors arose in the deep (6) and superficial (3) soft tissue of the groin (4), buttock (3), thigh (2), flank (1), shoulder (1), and paratesticular tissue (1) and ranged in size from 2 to 20 cm (mean 7.5 cm). Clinical follow-up in 11 patients (9 mo to 20 y; mean 68 mo) showed no recurrences or metastases. As defined above, "fibrosarcoma-like lipomatous neoplasm" is a unique lipomatous tumor that should be distinguished from WDL/(low-grade) dedifferentiated LPS and myxoid LPS on combined histologic/molecular features because of its better prognosis.

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

BACKGROUND: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. RESULTS: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.

Le syndrome de Moebius

Renal osteodystrophy is an amalgam of a number of distinct pathological conditions, in particular, hyperparathyroidism and osteomalacia. In addition, there may be a change in the guantity of bone, i.e., osteopenia (osteoporosis) or osteosclerosis. While bone biopsy may be the most reliable method for detecting these lesions, it is not yet a routine procedure in many centers. Radiological assessment of the bones, therefore, is the most widely used method for assessing the type and severity of the bone lesions in patients with chronic renal failure. This article reviews the world literature and pays attention to conventional radiological techniques as well as macroradiography. In addition, studies in which radiological appearances are correlated with histological appearances are described. Mention is also made of the effects on radiological bone disease of dialysis and transplantation. Consideration is also given to the manifestations of soft-tissue calcification, both of the vascular and subcutaneous type, and to the effects of treatment.

Xanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation.

Activation of the NLRP3 inflammasome by microbial ligands or tissue damage requires intracellular generation of reactive oxygen species (ROS). We present evidence that macrophage secretion of IL1β upon stimulation with ATP, crystals or LPS is mediated by a rapid increase in the activity of xanthine oxidase (XO), the oxidized form of xanthine dehydrogenase, resulting in the formation of uric acid as well as ROS. We show that XO-derived ROS, but not uric acid, is the trigger for IL1β release and that XO blockade results in impaired IL1β and caspase1 secretion. XO is localized to both cytoplasmic and mitochondrial compartments and acts upstream to the PI3K-AKT signalling pathway that results in mitochondrial ROS generation. This pathway represents a mechanism for regulating NLRP3 inflammasome activation that may have therapeutic implications in inflammatory diseases.

Léiomyosarcome de la veine cave inférieure. A propos de trois observations [Leiomyosarcoma of the inferior vena cava. Three cases].

We report three new cases of leiomyosarcoma of the inferior vena cava observed between 1985 and 1990. Two of them developed in women and one in a man. The age of the patients were 56, 29 and 57 years. The three tumors have been removed completely. One patient received postoperative radio- and chemotherapy and is well 68 months after excision. One patient developed liver metastasis 18 months after resection despite chemotherapy and died after 3 years. The last one refused postoperative radio- and chemotherapy, developed massive local recurrence and pulmonary metastasis three months postoperatively, and is still alive with disease after 8 months. The diagnostic modalities of these rare tumors as well as the problems created by their surgical resection and the need for a complementary treatment are discussed.

Eosinophilic fasciitis: Typical abnormalities, variants and differential diagnosis of fasciae abnormalities using MR imaging.

Eosinophilic fasciitis is a rare condition. It is generally limited to the distal parts of the arms and legs. MRI is the ideal imaging modality for diagnosing and monitoring this condition. MRI findings typically evidence only fascial involvement but on a less regular basis signal abnormalities may be observed in neighboring muscle tissue and hypodermic fat. Differential diagnosis of eosinophilic fasciitis by MRI requires the exclusion of several other superficial and deep soft tissue disorders.

Lymphoepithelial carcinoma in the maxillary sinus: a case report.

INTRODUCTION: Lymphoepithelial carcinoma of the maxillary sinus is a very rare malignancy and it can be difficult to make a pre-operative diagnosis. CASE PRESENTATION: A 72-year-old Caucasian woman presented to our facility with an isolated right-side epistaxis that had been present for three months, with the results of a computed tomography scan showing a soft tissue mass in the right maxillary sinus with an impacted tooth. The results of a transnasal endoscopic biopsy were compatible with a lymphoepithelial carcinoma, following which our patient underwent a radical excision of the mass. The final histology results revealed lymphoepithelial carcinoma of the maxillary sinus with negative assays for Epstein-Barr virus. Our patient was given post-operative external radiotherapy and has remained disease-free at three-year follow-up. CONCLUSIONS: This report details the diagnosis and management of a case of lymphoepithelial carcinoma of the maxillary sinus, which is a very rare malignant tumor with very little mention in the literature. Only a strong suspicion with systematic use of various patho-immunological tests helps to arrive at a definitive diagnosis by excluding other better-known tumors.

Inhibitory Receptors Beyond T Cell Exhaustion.

Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing -unprecedented results in the treatment of cancer patients. Consequently, the clinical potential in this field is broad, calling for increased research efforts and rapid refinements in the understanding of iR function. In this review, we provide an overview on the significance of iR expression for the interpretation of T cell functionality. We summarize how iRs have been strongly associated with "T cell exhaustion" and illustrate the parallel evidence on the importance of T cell differentiation and activation for the expression of iRs. The differentiation subsets of CD8 T cells (naïve, effector, and memory cells) show broad and inherent differences in iR expression, while activation leads to strong upregulation of iRs. Therefore, changes in iR expression during an immune response are often concomitant with T cell differentiation and activation. Sustained expression of iRs in chronic infection and in the tumor microenvironment likely reflects a specialized T cell differentiation. In these situations of prolonged antigen exposure and chronic inflammation, T cells are "downtuned" in order to limit tissue damage. Furthermore, we review the novel "checkpoint blockade" treatments and the potential of iRs as biomarkers. Finally, we provide recommendations for the immune monitoring of patients to interpret iR expression data combined with parameters of activation and differentiation of T cells.

Development of cardiovascular magnetic resonance imaging techniques for improved characterization of atherosclerotic disease

Atherosclerosis is a chronic cardiovascular disease that involves the thicken¬ing of the artery walls as well as the formation of plaques (lesions) causing the narrowing of the lumens, in vessels such as the aorta, the coronary and the carotid arteries. Magnetic resonance imaging (MRI) is a promising modality for the assessment of atherosclerosis, as it is a non-invasive and patient-friendly procedure that does not use ionizing radiation. MRI offers high soft tissue con¬trast already without the need of intravenous contrast media; while modifica¬tion of the MR pulse sequences allows for further adjustment of the contrast for specific diagnostic needs. As such, MRI can create angiographic images of the vessel lumens to assess stenoses at the late stage of the disease, as well as blood flow-suppressed images for the early investigation of the vessel wall and the characterization of the atherosclerotic plaques. However, despite the great technical progress that occurred over the past two decades, MRI is intrinsically a low sensitive technique and some limitations still exist in terms of accuracy and performance. A major challenge for coronary artery imaging is respiratory motion. State- of-the-art diaphragmatic navigators rely on an indirect measure of motion, per¬form a ID correction, and have long and unpredictable scan time. In response, self-navigation (SM) strategies have recently been introduced that offer 100% scan efficiency and increased ease of use. SN detects respiratory motion di¬rectly from the image data obtained at the level of the heart, and retrospectively corrects the same data before final image reconstruction. Thus, SN holds po-tential for multi-dimensional motion compensation. To this regard, this thesis presents novel SN methods that estimate 2D and 3D motion parameters from aliased sub-images that are obtained from the same raw data composing the final image. Combination of all corrected sub-images produces a final image with reduced motion artifacts for the visualization of the coronaries. The first study (section 2.2, 2D Self-Navigation with Compressed Sensing) consists of a method for 2D translational motion compensation. Here, the use of com- pressed sensing (CS) reconstruction is proposed and investigated to support motion detection by reducing aliasing artifacts. In healthy human subjects, CS demonstrated an improvement in motion detection accuracy with simula¬tions on in vivo data, while improved coronary artery visualization was demon¬strated on in vivo free-breathing acquisitions. However, the motion of the heart induced by respiration has been shown to occur in three dimensions and to be more complex than a simple translation. Therefore, the second study (section 2.3,3D Self-Navigation) consists of a method for 3D affine motion correction rather than 2D only. Here, different techniques were adopted to reduce background signal contribution in respiratory motion tracking, as this can be adversely affected by the static tissue that surrounds the heart. The proposed method demonstrated to improve conspicuity and vi¬sualization of coronary arteries in healthy and cardiovascular disease patient cohorts in comparison to a conventional ID SN method. In the third study (section 2.4, 3D Self-Navigation with Compressed Sensing), the same tracking methods were used to obtain sub-images sorted according to the respiratory position. Then, instead of motion correction, a compressed sensing reconstruction was performed on all sorted sub-image data. This process ex¬ploits the consistency of the sorted data to reduce aliasing artifacts such that the sub-image corresponding to the end-expiratory phase can directly be used to visualize the coronaries. In a healthy volunteer cohort, this strategy improved conspicuity and visualization of the coronary arteries when compared to a con¬ventional ID SN method. For the visualization of the vessel wall and atherosclerotic plaques, the state- of-the-art dual inversion recovery (DIR) technique is able to suppress the signal coming from flowing blood and provide positive wall-lumen contrast. How¬ever, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. In response and as a fourth study of this thesis (chapter 3, Vessel Wall MRI of the Carotid Arteries), a phase-sensitive DIR method has been implemented and tested in the carotid arteries of a healthy volunteer cohort. By exploiting the phase information of images acquired after DIR, the proposed phase-sensitive method enhances wall-lumen contrast while widens the window of opportunity for image acquisition. As a result, a 3-fold increase in volumetric coverage is obtained at no extra cost in scanning time, while image quality is improved. In conclusion, this thesis presented novel methods to address some of the main challenges for MRI of atherosclerosis: the suppression of motion and flow artifacts for improved visualization of vessel lumens, walls and plaques. Such methods showed to significantly improve image quality in human healthy sub¬jects, as well as scan efficiency and ease-of-use of MRI. Extensive validation is now warranted in patient populations to ascertain their diagnostic perfor¬mance. Eventually, these methods may bring the use of atherosclerosis MRI closer to the clinical practice. Résumé L'athérosclérose est une maladie cardiovasculaire chronique qui implique le épaississement de la paroi des artères, ainsi que la formation de plaques (lé¬sions) provoquant le rétrécissement des lumières, dans des vaisseaux tels que l'aorte, les coronaires et les artères carotides. L'imagerie par résonance magné¬tique (IRM) est une modalité prometteuse pour l'évaluation de l'athérosclérose, car il s'agit d'une procédure non-invasive et conviviale pour les patients, qui n'utilise pas des rayonnements ionisants. L'IRM offre un contraste des tissus mous très élevé sans avoir besoin de médias de contraste intraveineux, tan¬dis que la modification des séquences d'impulsions de RM permet en outre le réglage du contraste pour des besoins diagnostiques spécifiques. À ce titre, l'IRM peut créer des images angiographiques des lumières des vaisseaux pour évaluer les sténoses à la fin du stade de la maladie, ainsi que des images avec suppression du flux sanguin pour une première enquête des parois des vais¬seaux et une caractérisation des plaques d'athérosclérose. Cependant, malgré les grands progrès techniques qui ont eu lieu au cours des deux dernières dé¬cennies, l'IRM est une technique peu sensible et certaines limitations existent encore en termes de précision et de performance. Un des principaux défis pour l'imagerie de l'artère coronaire est le mou¬vement respiratoire. Les navigateurs diaphragmatiques de pointe comptent sur une mesure indirecte de mouvement, effectuent une correction 1D, et ont un temps d'acquisition long et imprévisible. En réponse, les stratégies d'auto- navigation (self-navigation: SN) ont été introduites récemment et offrent 100% d'efficacité d'acquisition et une meilleure facilité d'utilisation. Les SN détectent le mouvement respiratoire directement à partir des données brutes de l'image obtenue au niveau du coeur, et rétrospectivement corrigent ces mêmes données avant la reconstruction finale de l'image. Ainsi, les SN détiennent un poten¬tiel pour une compensation multidimensionnelle du mouvement. A cet égard, cette thèse présente de nouvelles méthodes SN qui estiment les paramètres de mouvement 2D et 3D à partir de sous-images qui sont obtenues à partir des mêmes données brutes qui composent l'image finale. La combinaison de toutes les sous-images corrigées produit une image finale pour la visualisation des coronaires ou les artefacts du mouvement sont réduits. La première étude (section 2.2,2D Self-Navigation with Compressed Sensing) traite d'une méthode pour une compensation 2D de mouvement de translation. Ici, on étudie l'utilisation de la reconstruction d'acquisition comprimée (compressed sensing: CS) pour soutenir la détection de mouvement en réduisant les artefacts de sous-échantillonnage. Chez des sujets humains sains, CS a démontré une amélioration de la précision de la détection de mouvement avec des simula¬tions sur des données in vivo, tandis que la visualisation de l'artère coronaire sur des acquisitions de respiration libre in vivo a aussi été améliorée. Pourtant, le mouvement du coeur induite par la respiration se produit en trois dimensions et il est plus complexe qu'un simple déplacement. Par conséquent, la deuxième étude (section 2.3, 3D Self-Navigation) traite d'une méthode de cor¬rection du mouvement 3D plutôt que 2D uniquement. Ici, différentes tech¬niques ont été adoptées pour réduire la contribution du signal du fond dans le suivi de mouvement respiratoire, qui peut être influencé négativement par le tissu statique qui entoure le coeur. La méthode proposée a démontré une amélioration, par rapport à la procédure classique SN de correction 1D, de la visualisation des artères coronaires dans le groupe de sujets sains et des pa¬tients avec maladies cardio-vasculaires. Dans la troisième étude (section 2.4,3D Self-Navigation with Compressed Sensing), les mêmes méthodes de suivi ont été utilisées pour obtenir des sous-images triées selon la position respiratoire. Au lieu de la correction du mouvement, une reconstruction de CS a été réalisée sur toutes les sous-images triées. Cette procédure exploite la cohérence des données pour réduire les artefacts de sous- échantillonnage de telle sorte que la sous-image correspondant à la phase de fin d'expiration peut directement être utilisée pour visualiser les coronaires. Dans un échantillon de volontaires en bonne santé, cette stratégie a amélioré la netteté et la visualisation des artères coronaires par rapport à une méthode classique SN ID. Pour la visualisation des parois des vaisseaux et de plaques d'athérosclérose, la technique de pointe avec double récupération d'inversion (DIR) est capa¬ble de supprimer le signal provenant du sang et de fournir un contraste posi¬tif entre la paroi et la lumière. Pourtant, il est difficile d'obtenir un contraste optimal car cela est soumis à la variabilité du rythme cardiaque. Par ailleurs, l'imagerie DIR est inefficace du point de vue du temps et les acquisitions "mul- tislice" peuvent conduire à des temps de scan prolongés. En réponse à ce prob¬lème et comme quatrième étude de cette thèse (chapitre 3, Vessel Wall MRI of the Carotid Arteries), une méthode de DIR phase-sensitive a été implémenté et testé

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.

The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.

A descriptive study on the surgery and the microbiology of Gustilo type III fractures in an university hospital in Switzerland.

OBJECTIVE: To describe the epidemiology, the surgical treatment, the microbiology, the antibiotic prophylaxis and the outcome of patients with the most severe type of open fractures. METHODS: Retrospective chart reviews of patients with Gustilo type III open fracture admitted to an university hospital in Switzerland between January 2007 and December 2011. The patient's and fracture's characteristics, surgery, antibiotic prophylaxis, and microbiology findings at the initial and at the revision surgery were described. RESULTS: Thirty patients were included (83% male, mean age 41 years). More than half of the patients had polytrauma. In all patients, debridement and stabilization surgery (70% using external fixation) were performed at admission. Soft tissue reconstruction was performed in 87% and in 23% immediate bone graft was performed. Antibiotic prophylaxis were given in all patients for a median duration of 9 days (60% received amoxicillin/clavulanic acid). Positive bacterial culture was found in 53% of the patients at initial surgery and in 88% at revision surgery. At initial and revision surgery, 47% and 88% of the pathogens were amoxicillin/clavulanic acid-resistant. Treatment outcome was favorable in 24 of 30 patients (80%) and in six cases (20%) an amputation had to be performed. None of the patients had chronic bone infection. CONCLUSIONS: Positive cultures were found often in open fractures. Amoxicillin/clavulanic acid which is often mentioned in many guidelines as prophylaxis in open fractures does not cover the most common isolated organisms. The combination of surgery and antibiotic prophylaxis leads to good outcome in Gustilo type III fracture.

Intraosseous migration of tendinous calcifications: cortical erosions, subcortical migration and extensive intramedullary diffusion, a SIMS series.

Calcium hydroxyapatite crystal deposition is a common disorder, which sometimes causes acute pain as calcifications dissolve and migrate into adjacent soft tissue. Intraosseous calcium penetration has also been described. We illustrate the appearance of these lesions using a series of 35 cases compiled by members of the French Society of Musculoskeletal Imaging (Société d'Imagerie Musculo-Squelettique, SIMS). The first group in our series (7 cases) involved calcification-related cortical erosions of the humeral and femoral diaphyses, in particular at the pectoralis major and gluteus maximus insertions. A second group (28 cases) involved the presence of calcium material in subcortical areas. The most common site was the greater tubercle of the humerus, accompanying a calcifying tendinopathy of the supraspinatus. In addition, an extensive intramedullary diffusion of calcium deposits was observed in four of these cases, associated with cortical erosion in one case and subcortical lesions in three cases. Cortical erosions and intraosseous migration of calcifications associated with calcific tendinitis may be confused with neoplasm or infection. It is important to recognize atypical presentations of hydroxyapatite deposition to avoid unnecessary investigation or surgery.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability.