Deformazioni indotte da flussi idrici sotterranei nel Carso Triestino

Il Carso Classico \ue8 un vasto areale a carso maturo sviluppato in una potente idrostruttura, caratterizzata da intensa e diffusa carsifi cazione anche ben al di sotto del livello del mare. La zona satura \ue8 potente ed estesa con una zona di oscillazione che verso monte raggiunge il centinaio di metri di spessore durante le piene importanti, come risulta dagli strumenti posizionati nell\u2019Abisso di Trebiciano, circa 20 km in linea d\u2019aria dalle sorgenti. Fra l\u2019Abisso di Trebiciano e le foci, a circa 12 km da queste ultime, si apre la Grotta Gigante, all\u2019interno della quale, dal 1960, \ue8 presente una stazione geodetica per la registrazione delle deformazioni crostali. Si analizzano le deformazioni indotte dalle variazioni di livello delle acque di fondo del Carso confrontando i dati geodetici della Grotta Gigante con quelli idrologici dell\u2019Abisso di Trebiciano. Analizzando i dati con campionamento giornaliero, si riconosce una correlazione fra il segnale clinometrico e le piene; i due segnali hanno sfasamento temporale massimo di un giorno. Il segnale clinometrico \ue8 un transiente, per cui il clinometro torna alla posizione iniziale successivamente al passaggio della piena ed ha un\u2019orientazione caratteristica lungo la direttrice N150W-N30E. Il segnale clinometrico \ue8 proporzionale al livello raggiunto nell\u2019Abisso di Trebiciano (100 nrad di inclinazione corrispondono a 9.7 m di incremento di livello). Le piene nell\u2019Abisso di Trebiciano devono superare 23.2 m, per provocare il segnale clinometrico a Grotta Gigante

The centrosomal Deubiquitylase USP21 regulates Gli1 transcriptional activity and stability

USP21 is a centrosome-associated deubiquitylase (DUB) that has been implicated in the formation of primary cilia – crucial organelles for the regulation of the Hedgehog (Hh) signaling pathway in vertebrates. Here, we identify KCTD6 – a cullin-3 E3-ligase substrate adapter that has been previously linked to Hh signaling – as well as Gli1, the key transcription factor responsible for Hh signal amplification, as new interacting partners of USP21. We identify a cryptic structured protein interaction domain in KCTD6, which is predicted to have a similar fold to Smr domains. Importantly, we show that both depletion and overexpression of catalytically active USP21 suppress Gli1-dependent transcription. Gli proteins are negatively regulated through protein kinase A (PKA)-dependent phosphorylation. We provide evidence that USP21 recruits and stabilises Gli1 at the centrosome where it promotes its phosphorylation by PKA. By revealing an intriguing functional pairing between a spatially restricted deubiquitylase and a kinase, our study highlights the centrosome as an important hub for signal coordination

Intermediates of Metabolism: From Bystanders to Signalling Molecules

British Heart Foundation Fellowship FS/12/38/2964

A prospective evaluation of survivorship of asymptomatic degenerative rotator cuff tears

BACKGROUND: The purpose of this prospective study was to report the long-term risks of rotator cuff tear enlargement and symptom progression associated with degenerative asymptomatic tears. METHODS: Subjects with an asymptomatic rotator cuff tear in one shoulder and pain due to rotator cuff disease in the contralateral shoulder enrolled as part of a prospective longitudinal study. Two hundred and twenty-four subjects (118 initial full-thickness tears, fifty-six initial partial-thickness tears, and fifty controls) were followed for a median of 5.1 years. Validated functional shoulder scores were calculated (visual analog pain scale, American Shoulder and Elbow Surgeons [ASES], and simple shoulder test [SST] scores). Subjects were followed annually with shoulder ultrasonography and clinical evaluations. RESULTS: Tear enlargement was seen in 49% of the shoulders, and the median time to enlargement was 2.8 years. The occurrence of tear-enlargement events was influenced by the severity of the final tear type, with enlargement of 61% of the full-thickness tears, 44% of the partial-thickness tears, and 14% of the controls (p < 0.05). Subject age and sex were not related to tear enlargement. One hundred subjects (46%) developed new pain. The final tear type was associated with a greater risk of pain development, with the new pain developing in 28% of the controls, 46% of the shoulders with a partial-thickness tear, and 50% of those with a full-thickness tear (p < 0.05). The presence of tear enlargement was associated with the onset of new pain (p < 0.05). Progressive degenerative changes of the supraspinatus muscle were associated with tear enlargement, with supraspinatus muscle degeneration increasing in 4% of the shoulders with a stable tear compared with 30% of the shoulders with tear enlargement (p < 0.05). Nine percent of the shoulders with a stable tear showed increased infraspinatus muscle degeneration compared with 28% of those in which the tear had enlarged (p = 0.07). CONCLUSIONS: This study demonstrates the progressive nature of degenerative rotator cuff disease. The risk of tear enlargement and progression of muscle degeneration is greater for shoulders with a full-thickness tear, and tear enlargement is associated with a greater risk of pain development across all tear types. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Dental Shape Variation and Phylogenetic Signal in the Rattini Tribe Species of Mainland Southeast Asia

We would like to thank Pierre-Henri Fabre for providing the phylogeny for this study. The collection of specimens used was funded by the French ANR Biodiversity, grant ANR 07 BDIV 012 CERoPath project (www.ceropath.org), and by the French ANR CP&ES, grant ANR 11 CPEL 002 BiodivHealthSEA project (www.biodivhealthsea.org). We also thank Madoudou Garba and Gauthier Dobigny (CBGP-IRD) for providing additional specimens. We greatly thank all local communities and their leaders for permission and invaluable help during field trapping. Special thanks to the CERoPath and BiodivHealthSEA teams and the drivers for their invaluable help during fieldwork. We would also like to thank Maeve McMahon for help with manuscript editing and preparation.Peer reviewedPublisher PD

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Evaporite sinkholes of the Friuli Venezia Giulia region (NE Italy)

Sinkholes are common in the Friuli Venezia Giulia (FVG) Region (NE Italy), where the presence of karstifiable rocks favours their occurrence accelerated by intense rainfalls. Their existence has been reported since the end of the 1800s along the Tagliamento Valley, in correspondence with the mantled evaporites (gypsum). Furthermore, tens of evaporite sinkholes have been documented on the reliefs adjacent to the village of Sauris and along the narrow W\u2013Eoriented valleys, where regional faults have played a major role in their spatial distribution. This paper reports for the first time an inventory of the sinkholes affecting the evaporites of the FVG Region. These phenomena were mapped and categorised using a genetic classification. The main output is an A0-format map, which incorporates a 1:50,000 scale Sinkhole Inventory Map (SIM). The SIM encompasses 552 sinkholes. The cover suffosion sinkholes are the most abundant, followed by bedrock collapses. There is a clear prevalence of the circular shape (65%) over other shapes. Diameters are 1\u2013140 m, with depths ranging 0.1\u201340 m with a mean value of 4.5 m. The SIM can motivate regional planning authorities to perform further investigations aimed to understand the geomorphological evolutions of these phenomena

T.E.A. Study: three-day ertapenem versus three-day Ampicillin-Sulbactam.

Background: Intra-abdominal infections are one of the most common infections encountered by a general surgeon. However, despite this prevalence, standardized guidelines outlining the proper use of antibiotic therapy are poorly defined due to a lack of clinical trials investigating the ideal duration of antibiotic treatment. The aim of this study is to compare the efficacy and safety of a three-day treatment regimen of Ampicillin-Sulbactam to that of a three-day regimen of Ertapenem in patients with localized peritonitis ranging from mild to moderate severity. Methods: This study is a prospective, multi-center, randomized investigation performed in the Department of General, Emergency, and Transplant Surgery of St. Orsola-Malpighi University Hospital in Bologna, Italy. Discrete data were analyzed using the Chi-squared and Fisher exact tests. Differences between the two study groups were considered statistically significant for p-values less than 0.05. Results: 71 patients were treated with Ertapenem and 71 patients were treated with Ampicillin-Sulbactam. The two groups were comparable in terms of age and gender as well as the site of abdominal infection. Post-operative infection was identified in 12 patients: 10 with wound infections and 2 with intra-abdominal infections. In the Ertapenem group, 69 of the 71 patients (97%) were treated successfully, while the therapy failed in 2 cases (3%). Therapy failures were more frequent in the Unasyn group, amounting to 10 of 71 cases (p = 0.03). Conclusion: According to these preliminary findings, the authors conclude that a three-day Ertapenem treatment regimen is the most effective antibiotic therapy for patients with localized intra-abdominal infections ranging from mild to moderate severity

It&#8217;s time to change perspective! New diagnostic tools for lateral elbow pain

Purpose: The presence of intra-articular findings that may complement the extra-articular pathology in lateral epicondilytis has been suggested, and a role for minor instability of the elbow as part of the causative process of this disease has been postulated. This study was designed to describe two new clinical tests, aimed at detecting intra-articular pathology in patients affected by recalcitrant lateral epicondylitis and investigate their diagnostic performance. Methods: Ten patients suffering of atraumatic lateral elbow pain unresponsive to conservative treatment were considered in this study. Two clinical tests were developed and administrated prior to arthroscopy: Supination and Antero-Lateral pain Test (SALT); Posterior Elbow Pain by Palpation-Extension\uc2\ua0of the Radiocapitellar joint (PEPPER). Sensitivity, specificity, predictive values and accuracy of SALT and PEPPER as diagnostic tests for seven intra-articular findings were calculated. Results: In 90% of the patients, at least one test was positive. All patients with signs of lateral ligamentous patholaxity or intra-articular abnormal findings had a positive response to at least one of the two tests. SALT proved to have a high sensitivity but a low specificity and is accurate in detecting the presence of intra-articular abnormal findings, especially synovitis. PEPPER test was sensible, specific and accurate in the detection of radial head chondropathy. Conclusions: Two new diagnostic tests (SALT and PEPPER) were specifically designed to evoke pain from intra-articular structures. These tests could be a valid support in the diagnostic algorithm of recalcitrant lateral elbow pain. Positive findings may be indicative of a minor instability of the lateral elbow condition. Level of evidence: Diagnostic study, development of diagnostic criteria on basis of consecutive patients, level II