Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions.

Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis.

BACKGROUND: Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy. We hereby present a case of Heerfordt syndrome with unilateral facial nerve palsy as a presentation of sarcoidosis. HISTORY AND SIGNS: A 29-year-old male patient from Sri Lanka presented with eye redness OU, blurred vision OD, fever, headache, night sweat, fatigue, and weight loss (5 kg over 1 month). Examination revealed mild anterior uveitis OU, mild vitritis OD, fundus whitish lesions OU, left otalgia, taste disorders, bilateral parotid gland enlargement, and left facial nerve palsy. Work-up for infection or tumour was negative. Chest computed tomography and transbronchial lymph node biopsy set the diagnosis of sarcoidosis. THERAPY AND OUTCOME: The patient recovered completely within 2 months under therapy with prednisone and azathioprine. One year after onset of treatment, no recurrence was noted. CONCLUSIONS: Heerfordt syndrome is a rare manifestation of neurosarcoidosis and has to be included in the differential diagnosis of facial nerve palsy.

Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible?

Peroxisome proliferator-activated receptor (PPAR) dysfunction has been implicated in the manifestation of many diseases and illnesses, ranging from obesity to cancer. Herein, we discuss the role of PPARbeta, one of the three PPAR isotypes, during wound healing. While PPARbeta expression is undetectable in unchallenged and healthy adult interfollicular mouse skin, it is robustly re-activated in stress situations, such as upon phorbol ester treatment, hair plucking and cutaneous wounding. The inflammatory reaction associated with a skin injury activates the keratinocytes at the edges of the wound. This activation involves PPARbeta, whose expression and activity as transcription factor are up-regulated by pro-inflammatory signals. The re-activation of PPARbeta influences three important properties of the activated keratinocytes that are vital for rapid wound closure, namely, survival, migration and differentiation. The anti-apoptotic and, thus, survival role of PPARbeta is mediated by the up-regulation of expression of integrin-linked kinase and 3-phosphoinositide-dependent kinase-1. Both kinases are required for the full activation of the Akt1 survival cascade. Therefore, the up-regulation of PPARbeta, early after injury, appears to be important to maintain a sufficient number of viable keratinocytes at the wound edge. At a later stage of wound repair, the stimulation of keratinocyte migration and differentiation by PPARbeta is also likely to be important for the formation of a new epidermis at the wounded area. Consistent with these observations, the entire wound healing process is delayed in PPARbeta +/- mice and wound closure is retarded by 2-3 days. The multiple roles of PPARbeta in the complex keratinocyte response after injury and during skin repair certainly justify a further exploration of its potential as a target for wound healing drugs.

Les gangs en Suisse : délinquance, victimisation et facteurs de risque

Abstract Gang membership constitutes one of the strongest risk factors of delinquency. Research on this topic found that gang members commit more offences in general and are particularly more prone to violent offences than other juveniles. Indeed, they are responsible for approximately 50 to 86% of the total offences perpetrated by juvenile offenders. In Switzerland, as in other European countries, there is a reluctance to use the term of gang to talk about delinquent youth groups. However, this term implies many stereotypes that do not apply to the majority of juvenile American gangs. Thus, it appears that some delinquent youth groups in European countries can be described as gangs. This manifestation of juvenile delinquency is increasingly studied by European researchers, whose studies demonstrate the high level of delinquency committed by gang members. This research assesses the proportion of gangs in Switzerland and their level of involvement in delinquency. Victimization of gang members as well as risk factors of gang membership are also analyzed. For this research, data of two self-reported juvenile delinquency surveys were used, namely the survey of "les jeunes et l'insécurité" and the second wave of the International Self-Reported Delinquency Survey (ISRD-2). The first survey took place in the canton of Vaud among 4'690 teenagers, and the second one was conducted across Switzerland by interviewing 3'648 teenagers aged 12 to 16. The results from the ISRD-2 survey show that 4.6% of young Swiss belong to a gang, whereas this is the case for 6.5% of teenagers in the canton of Vaud. About a third of the gang members ara girls. A strong link between the commission of offences and gang membership was found in both surveys. A teenager who does not belong to a gang commits on average 1.9 offences per year, whereas this number increases to 7.2 offences for teenagers who have delinquent peers and to 16 offences for gang members. The risk of victimization is also stronger for a gang member than for a non-gang member, as it is 4 to 5 times higher for assaults and robberies. International comparisons based on the ISRD-2 survey have been conducted, highlighting the high level of delinquency of gang members and their vulnerability to victimization. Risk factors of gang membership include the influence of accessibility to drugs in the neighbourhoods, the lack of self-control of the teenagers and their consumption of cannabis. Résumé Un des facteurs de risque les plus importants de la délinquance juvénile est l'appartenance à un gang. Les recherches faites sur cette problématique indiquent que les membres de gangs commettent plus de délits et des délits plus violents que les autres jeunes et qu'ils sont responsables d'environ 50 â 86% des actes délinquants perpétrés. En Suisse, tout comme dans d'autres pays européens, une réticence existe à utiliser le terme de gang pour parler des bandes de jeunes délinquants. Pourtant, ce terme implique de nombreux stéréotypes qui ne correspondent toutefois pas à la majorité des gangs américains. Ainsi, il apparaît que certaines bandes de jeunes délinquants présentes dans des pays européens peuvent être qualifiées de gangs. Cette manifestation de ta délinquance juvénile est de plus en plus étudiée par les chercheurs européens qui démontrent également la sur-criminalité de leurs membres. I La présente recherche évalue dans quelle proportion tes membres de gangs existent en Suisse et Quel est leur niveau d'implication dans la délinquance. Leur victimisation ainsi que les facteurs de risque de l'affiliation à de tels groupes y sont également analysés. Pour ce faire, les données de deux enquêtes ont été utilisées, à savoir l'enquête des jeunes et de l'insécurité portant sur 4'690 élèves de 8'? et 9*? année scolaire du canton de Vaud, ainsi que la deuxième vague du sondage de délinquance auto-reportée portant sur 3'648 jeunes suisses ayant entre 12 et 16 ans (ISRD-2 -International Self Reported Delinquency-). Ainsi, 4.6% des jeunes suisses, selon la recherche de l'ISRD-2, et 6.5% des jeunes vaudois, selon l'enquête des jeunes et de l'insécurité, appartiennent à un gang ; un tiers des membres étant de sexe féminin. Un lien fort entre la commission de délits et l'affiliation à un gang a été mis en évidence dans les deux enquêtes. Un adolescent qui ne fait pas partie d'un gang commet en moyenne 1.9 délits par année, un jeune qui a des pairs délinquants en commet en moyenne 7.2, alors que la moyenne annuelle des jeunes qui appartiennent à un gang s'élève à 16. Le risque de devenir victime est également plus important lorsqu'un jeune fait partie de tels groupes, puisqu'il est 4 à 5 fois plus élevé pour les agressions et les brigandages. Des comparaisons internationales, basées sur l'enquête de l'lSRD-2, ont pu être effectuées, mettant en exergue la sur-criminalité des membres de gangs ainsi que leur vulnérabilité face à la victimisation. Des facteurs de risque de l'affiliation è un gang, tels que l'influence de l'accessibilité à la drogue dans les quartiers où habitent les jeunes, le manque d'autocontrôlé de ces derniers ou leur consommation de cannabis ont été relevés

Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis.

To evaluate the incidence and characteristics of musculoskeletal manifestations in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS The records of 163 cases of PMR or TA diagnosed over a 15 year period in one area of Spain were reviewed for the presence and type of musculoskeletal manifestations. RESULTS Of 163 patients, 90 had isolated PMR and 73 had TA. Eighteen of the 90 patients (20%) with isolated PMR developed distal peripheral arthritis either at diagnosis or during the course of the disease. When it occurred, synovitis was mild, monoarticular or pauci-articular, asymmetrical, transient, and not destructive. Other distal manifestations observed in these patients were carpal tunnel syndrome and distal extremity swelling with pitting oedema. In all cases these manifestations occurred in conjunction with active PMR. As expected, PMR was the most frequent musculoskeletal manifestation in patients with TA, occurring in 56% of cases. On the contrary, only 11% of patients with TA developed peripheral arthritis. An important finding was that peripheral arthritis in these patients appears to be linked only temporally to the presence of simultaneous PMR and is not observed in its absence. Distal extremity swelling or defined polyarthritis were not observed. CONCLUSION The spectrum of distal musculoskeletal manifestations of PMR in our series is similar to that reported in other populations. By contrast, distal musculoskeletal symptoms are uncommon in TA. The almost complete absence of distal musculoskeletal manifestations in patients with pure TA suggests different mechanisms of disease in PMR and TA, supporting the view of two separate conditions or one common disease in which host susceptibility influences the clinical expression.

Hand-arm vibration syndrome with proximal ulnar artery occlusion.

The case of a man exposed during 25 years to vibration while maneuvering a heavy earth moving tractor is reported. The first clinical manifestation of hand-arm vibration syndrome was a bilateral Raynaud's phenomenon followed five years later by digital necrosis. The arteriography revealed a proximal and bilateral ulnar artery occlusion. Bilateral median nerve conduction abnormalities were also present. Vibration exposure level was much higher than the threshold level proposed by the European Commission. Laboratory examinations for vasculitis and other vascular diseases were all negative. The purpose of this report is to show that vibration can be responsible for proximal occlusion of a medium sized artery and severe neurovascular abnormalities which must be distinguished from the usual vasospastic Raynaud's phenomenon and the classical hypothenar hammer syndrome. An early and correct diagnosis is crucial because continued repetitive trauma can result in irreversible ischemic injury and loss of digits.

Atypical headache following dural puncture in obstetrics.

BACKGROUND: In obstetrics, post-dural puncture headache is a well-recognised complication. Typical symptoms include fronto-temporal or occipital headache, worsening with ambulation and improving in the decubitus position. Occasionally, patients present with non-postural headache, although relatively little is known about this atypical presentation. The purpose of this study was to determine the incidence, associated signs and risk factors for this atypical manifestation of post-dural puncture headache. METHODS: We analysed a series of 27 064 parturients having a neuraxial procedure between January 2001 and December 2010. Using data from electronic anaesthesia patient records, medical charts and a postpartum quality audit, we identified all parturients with atypical post-dural puncture headache. We assessed the incidence and used uni- and multivariate analysis to identify associated risk factors. RESULTS: Amongst 142 parturients with post-dural puncture headache, eight (5.6%, 95% CI 1.7-9.4%) had atypical non-postural headache. Associated symptoms were stiffness and pain in the cervical, thoracic or lumbar vertebral area, visual disturbances and vertigo. Significant risk factors for developing atypical signs were previous migraine, odds ratio 6.1 (95% CI 1.2-28.7), a more cephalad level of needle insertion, odds ratio 17.2 (95% CI 1.4-210.1) and identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter, odds ratio 5.5 (95% CI 1.2-24.4). Following multivariate analysis, recognition of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter was the most significant predictor of non-orthostatic postdural puncture headache. CONCLUSION: Anaesthetists should be aware of this atypical clinical presentation, particularly if there is a past history of migraine, a more cephalad level of needle insertion or identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter.

Changes in anatomy and root cell ultrastructure of soybean genotypes under manganese stress

The deleterious effects of both Mn deficiency and excess on the development of plants have been evaluated with regard to aspects of shoot anatomy, ultrastructure and biochemistry, focusing mainly on the manifestation of visual symptoms. However, there is little information in the literature on changes in the root system in response to Mn supply. The objective of this study was to evaluate the effects of Mn doses (0.5, 2.0 and 200.0 μmol L-1) in a nutrient solution on the anatomy of leaves and roots of the Glycine max (L.) cultivars Santa Rosa, IAC-15 and IAC-Foscarin 31. Visual deficiency symptoms were first observed in Santa Rosa and IAC-15, which were also the only cultivars where Mn-toxicity symptoms were observed. Only in IAC-15, a high Mn supply led to root diameter thickening, but without alteration in cells of the bark, epidermis, exodermis and endodermis. The degree of disorganization of the xylem vessels, in particular the metaxylem, differed in the cultivars. Quantity and shape of the palisade parenchyma cells were influenced by both Mn deficiency and toxicity. A reduction in the number of chloroplasts was observed in the three Mn-deficient genotypes. The anatomical alterations in IAC-15 due to nutritional stress were greater, as expressed in extensive root cell cytoplasm disorganization and increased vacuolation at high Mn doses. The degree of changes in the anatomical and ultrastructural organization of roots and leaves of the soybean genotypes studied differed, suggesting the existence of tolerance mechanisms to different intensities of Mn deficiency or excess.

Sweet taste loss in myasthenia gravis: more than a coincidence?

Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti-acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old man reported progressive loss of sweet taste evolving for almost 10 weeks, revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception paralleled reduction of the MG composite score during the 15 months follow up period, with immunosuppressive and surgical treatments. We suggest that sweet dysgeusia is a non-motor manifestation of MG that may result from a thymoma-dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr) transgenic mice with autoimmune disease.

Unusual fatal petrositis presenting as myofascial pain and dysfunction of the temporal muscle.

Petrositis is a rare and severe complication of acute otitis media and mastoiditis. Although the extension of the inflammatory process from the petrous apex to the adjacent Meckel cave can lead to trigeminal pain, an irritation of the trigeminal nerve roots resulting in acute or chronic hyperactivity of masticatory muscles has never been reported. We report here the unusual case of an 86-year-old man who presented with a handicapping myofascial pain and dysfunction syndrome of the right temporal muscle as a heralding manifestation of an unusual form of petrositis. The patient progressively developed a retropharyngeal abscess, a right sphenoid sinusitis, and fatal meningitis. This case demonstrated that (1) myofascial pain and dysfunction syndrome that does not respond to conventional treatments may suggest an unusual etiology and warrant further medical investigations and a detailed medical history and that (2) petrositis can manifest itself with atypical clinical symptoms and radiologic signs. (Quintessence Int 2011;42:419-422).

A tennis player with hand claudication.

The case of a professional tennis player presenting exercise-induced hand pain with late appearance of digital blanching is reported. A bilateral hypothenar hammer syndrome and stenosis of the common palmar digital arteries close to the head of the metacarpals where the racket handle exerts its maximal force was observed with arteriography. As the patient decided to stop tennis practice, the condition improved without any medication. Six months after stopping tennis he was symptom free. Three conclusions can be drawn from this case report: 1) arteries of both hands can be injured by intense tennis practice, 2) pain in the dominant hand during tennis practice can be due to arterial insufficiency even in the absence of digital blanching which is a sign of severity, 3) hypothenar hammer syndrome is the main cause but stenosis of the common palmar digital arteries can possibly contribute to the ischemic phenomenon. Early recognition is important to avoid ineffective treatment and permanent symptoms. Therefore, we recommend an arterial examination in tennis players suffering from exercise-induced hand pain even in the absence of digital blanching which can be only a late manifestation.

Dielectric anomaly and magnetic response of epitaxial orthorhombic YMnO3 thin films

The structure, magnetic response, and dielectric response of the grown epitaxial thin films of the orthorhombic phase of YMnO3 oxide on Nb:SrTiO3 (001) substrates have been measured. We have found that a substrate-induced strain produces an in-plane compression of the YMnO3 unit cell. The magnetization versus temperature curves display a significant zero-field cooling (ZFC)-field cooling hysteresis below the Nel temperature (TN 45 K). The dielectric constant increases gradually (up to 26%) below the TN and mimics the ZFC magnetization curve. We argue that these effects could be a manifestation of magnetoelectric coupling in YMnO3 thin films and that the magnetic structure of YMnO3 can be controlled by substrate selection and/or growth conditions.

A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings.

Obstructive disease of the large coronary arteries is the prominent cause for angina pectoris. However, angina may also occur in the absence of significant coronary atherosclerosis or coronary artery spasm, especially in women. Myocardial ischaemia in these patients is often associated with abnormalities of the coronary microcirculation and may thus represent a manifestation of coronary microvascular disease (CMD). Elucidation of the role of the microvasculature in the genesis of myocardial ischaemia and cardiac damage-in the presence or absence of obstructive coronary atherosclerosis-will certainly result in more rational diagnostic and therapeutic interventions for patients with ischaemic heart disease. Specifically targeted research based on improved assessment modalities is needed to improve the diagnosis of CMD and to translate current molecular, cellular, and physiological knowledge into new therapeutic options.

Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report.

INTRODUCTION: Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. CASE PRESENTATION: We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. CONCLUSIONS: Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

An AdS/QCD model from tachyon condensation: II

A simple holographic model is presented and analyzed that describes chiral symmetry breaking and the physics of the meson sector in QCD. This is a bottom-up model that incorporates string theory ingredients like tachyon condensation which is expected to be the main manifestation of chiral symmetry breaking in the holographic context. As a model for glue the Kuperstein-Sonnenschein background is used. The structure of the flavor vacuum is analyzed in the quenched approximation. Chiral symmetry breaking is shown at zero temperature. Above the deconfinement transition chiral symmetry is restored. A complete holographic renormalization is performed and the chiral condensate is calculated for different quark masses both at zero and non-zero temperatures. The 0++, 0¿+, 1++, 1¿¿ meson trajectories are analyzed and their masses and decay constants are computed. The asymptotic trajectories are linear. The model has one phenomenological parameter beyond those of QCD that affects the 1++, 0¿+ sectors. Fitting this parameter we obtain very good agreement with data. The model improves in several ways the popular hard-wall and soft wall bottom-up models.