Search

Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic in late-phase development for uncomplicated urinary tract infection and uncomplicated urogenital gonorrhea. Two clinical studies were conducted to assess the pharmacokinetics (PK) and interethnic comparisons of oral gepotidacin (free-base and to-be-marketed mesylate formulations) administered as single doses ranging from 1500 to 3000 mg in fed and fasted states, and as 2 × 3000-mg doses given 12 hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration-time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non-Japanese participant data showed slightly higher plasma maximum concentration (7%-30%) yet similar plasma AUCs; slightly lower urine AUCs (11%-18%) were observed. The slightly higher plasma exposures in healthy Japanese versus White participants in the same study were attributed to lower mean body weights (64 kg versus ≈80 kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety-risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies.

BackgroundGepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is active against most strains ofNeisseria gonorrhoeae(N. gonorrhoeae). Phase II data suggested higher exposures were needed for efficacy and to suppress resistance development. A translational approach using in vitro pharmacokinetic/pharmacodynamic (PK/PD) and clinical data was used to select a gepotidacin dose for a phase III study. In this narrative review of previously shown data, we summarise how a translational approach based on in vitro PK/PD and population PK modelling and simulation data was undertaken to select a dosing regimen for the ongoing phase III gepotidacin study in participants with uncomplicated urogenital gonorrhoea.MethodsFor dose selection, prior in vitro minimum inhibitory concentrations (MICs) and PK/PD data were available. PK modelling was conducted to determine a dose that would limit plasma concentrations to less than 14 µg/mL (as concentrations above this are associated with QT prolongation and effects associated with acetylcholinesterase inhibition) while maintaining ≥90% probability of target attainment (PTA) for efficacy and resistance suppression againstN. gonorrhoeaeisolates with gepotidacin MICs ≤1 µg/mL.ResultsTwo 3000 mg gepotidacin doses, administered 10–12 hours apart, resulted in PTA of ≥97.5% and ≥91.7% for gepotidacin MICs ≤1 µg/mL for the ratio of the area under the free drug plasma concentration–time curve over 24 hours to the MIC (fAUC0–24/MIC) efficacy, and resistance suppression targets of 40 and 46, respectively, but limited the occurrence of maximum plasma concentrations ≥14 µg/mL.ConclusionsTwo gepotidacin 3000 mg oral doses 10–12 hours apart provide ~2-fold higher systemic exposures, increase efficacy for higher gepotidacin MICN. gonorrhoeaeisolates, reduce resistance potential and limit plasma concentrations of potential safety concern, compared with higher doses.

BACKGROUND Lateral pelvic lymph node dissection for rectal cancer is a difficult technique due to the complex pelvic anatomy. Recent series have underlined the importance of lateral lymphadenectomy in selective patients to prevent local recurrence of rectal cancer. METHODS A 65-year-old woman was diagnosed with locally advanced rectal adenocarcinoma of the low rectum with right and left lateral pelvic lymph nodes of respectively 9 and 13 mm. After chemotherapy followed by radiotherapy, the size of the right internal iliac lymph nodes remained enlarged to 5 mm. A laparoscopic extraperitoneal approach was used for total mesorectal excision, complete mesocolic excision, and bilateral lateral lymph node dissection. The extraperitoneal space was divided into the subperitoneal space dissected by a transanal approach and the retroperitoneal space dissected by a transabdominal approach. RESULTS The operating time was 303 min, and the estimated blood loss was 270 ml. No intraoperative adverse events occurred. Bilateral lymph node dissection was performed with obturator nerve and neurovascular bundle sparing. A postoperative complication classified as Clavien 3a arose with a pelvic infection but no anastomotic leakage. Final pathology disclosed T3N1M0 adenocarcinoma with free surgical margins. The patient never had urinary dysfunction. CONCLUSIONS The laparoscopic extraperitoneal approach to lateral pelvic lymph node dissection is feasible. For lateral lymph node dissection, the transanal approach may have some advantages over the standard transabdominal approach, with better visibility of and access to the distal internal iliac area. This video may help oncological surgeons to perform this new and complex procedure.

Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo‐CII and CIII and Apo‐E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP‐3 and MMP‐9, TIMP‐1 and TIMP‐2, Apo‐CII, Apo‐CIII and Apo‐E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP‐3 and MMP‐9 plasma levels in CAD patients were significantly increased (P

L’administration locale de chimiothérapie est une technique ayant pour but de cibler les lésions tumorales au niveau de leur site anatomique. Pour les métastases péritonéales, la voie intrapéritonéale (IP) permet d’augmenter les concentrations locales des substances de chimiothérapies et de limiter la toxicité systémique. Cette voie d’administration s’est largement développée durant les 40 dernières années. Ce développement s’est accompagné d’une grande hétérogénéité dans le type de substance, les doses, les dilutions et les modalités d’administrations utilisés. Des études randomisées récentes et de nouvelles innovations thérapeutiques modifient la place de la chimiothérapie IP dans le traitement des carcinoses péritonéales. Le but de cet article est de faire un résumé de la littérature concernant l’efficacité et la sécurité des principales modalités de chimiothérapies IP pour le traitement des métastases péritonéales d’origine colorectale.

Antibiotics are the current standard-of-care treatment for uncomplicated urinary tract infections (uUTIs). However, increasing rates of bacterial antibiotic resistance necessitate novel therapeutic options. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that selectively inhibits bacterial DNA replication by interaction with the bacterial subunits of DNA gyrase (GyrA) and topoisomerase IV (ParC). Gepotidacin is currently in clinical development for the treatment of uUTIs and other infections. In this article, we review data for gepotidacin from nonclinical studies, including

Campylobacter jejuni é pouco conhecida quanto às características epidemiológicas e morfológicas, principalmente no estado viável não cultivável (VNC), não detectável em metodologias tradicionais de cultivo e identificação. Objetivou-se observar aspectos comportamentais, morfológicos e a organização intracelular de C. jejuni na forma VNC. Utilizou-se 27 cepas sob estresse térmico, nutricional e oxidativo, avaliou-se o tempo de aquisição integral de VNC. Em seguida, analisou-se a ultraestrutura em microscopia eletrônica de transmissão (MET) e varredura (MEV). As cepas apresentaram períodos diversos para formar VNC (média: 26 dias). A contagem inicial média foi 7,8 log UFC/mL, sendo os primeiros quatro dias determinantes para maior redução da contagem logarítmica (3,2 log UFC/mL) e média de 0,33 log UFC/mL para os demais. Observou-se estruturas semelhantes a bastonetes, forma cocóide em descaracterização progressiva em relação à forma típica da espécie em microscopia óptica. MEV e MET evidenciaram a transição de espiralada para VNC, inicialmente como bastão curvo assumindo formato reto, seguido da perda de flagelos, subdivisão em até 11 cocos imperfeitos em cadeia, ricos em conteúdo celular até sua liberação. Na forma VNC, há atividade celular e parede celular espessada, indicando mecanismo de proteção. Nos resultados do MET, ambas as formas apresentaram estruturas bacterianas típicas e o flagelo só foi identificado na forma viável. Os resultados demonstraram a continuidade na atividade celular do microrganismo VNC, variação no tempo para aquisição dessa forma de vida e o paradoxo entre a alteração expressiva na morfologia externa bacteriana acompanhada da manutenção da morfologia interna.

Fanconi anemia (FA) is a rare human genetic disorder characterized by bone marrow failure, predisposition to cancer and developmental defects including hypogonadism. Reproductive defects leading to germ cell aplasia are the most consistent phenotypes seen in FA mouse models. We examined the role of the nuclear FA core complex gene Fancg in the development of primordial germ cells (PGCs), the embryonic precursors of adult gametes, during fetal development. PGC maintenance was severely impaired in Fancg−/− embryos. We observed a defect in the number of PGCs starting at E9.5 and a strong attrition at E11.5 and E13.5. Remarkably, we observed a mosaic pattern reflecting a portion of testicular cords devoid of PGCs in E13.5 fetal gonads. Our in vitro and in vivo data highlight a potential role of Fancg in the proliferation and in the intrinsic cell motility abilities of PGCs. The random migratory process is abnormally activated in Fancg−/− PGCs, altering the migration of cells. Increased cell death and PGC attrition observed in E11.5 Fancg−/− embryos are features consistent with delayed migration of PGCs along the migratory pathway to the genital ridges. Moreover, we show that an inhibitor of RAC1 mitigates the abnormal migratory pattern observed in Fancg−/− PGCs.

La gastrectomia per cancro mediante laparoscopia standard o con assistenza robotica e una tecnica minimamente invasiva che facilita la riabilitazione precoce e il ritorno accelerato a un’attivita normale. Queste tecniche restano complesse e impongono di limitare le indicazioni ai tumori che non richiedono una linfoadenectomia estesa (gastrectomia profilattica, cancro precoce, gastrointestinal stromal tumor [GIST]). L’assistenza robotica facilita la realizzazione degli svuotamenti linfonodali e delle anastomosi. Le regole di sicurezza oncologica devono essere rispettate. Le anastomosi digestive sono principalmente meccaniche, ma l’assistenza robotica consente di eseguire anastomosi manuali di buona qualita.

The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), causes severe damages in strawberry (Fragaria × ananassa Duchesne ex Rozier; Rosaceae) fields in Québec, Canada. Currently, only chemical insecticides successfully control that major pest. Lygus lineolaris aggregate in trap crops such as buckwheat (Fagopyrum esculentum Moench; Polygonaceae) and white mustard (Sinapis alba Linnaeus; Brassicaceae) but do not remain long enough on these plants to significantly reduce damages on strawberries. However, the attractiveness of the trap crop gives the opportunity to gather L. lineolaris in an area of the field where chemical treatments could be applied more efficiently. The aim of this study was to test the effectiveness of the combination of trap crop (buckwheat and white mustard) and chemical treatments to control L. lineolaris. Randomised complete-block design included treatment with either no trap crop, buckwheat, or white mustard row planted close to strawberry plants. Half blocks were treated with insecticide (cypermethrin) sprayed on strawberry plants (in treatment without trap crop) or directly on trap crop. We found that L. lineolaris was more abundant on buckwheat than on white mustard or strawberry plants. Insecticide application on trap crops reduced the population on these hosts, but did not reduce L. lineolaris on adjacent strawberry plants. Behavioural avoidance and physiological pesticide resistance could explain this result.

Decreasing mitochondrial energy-production efficiency in skeletal muscle can confer protection against diet-induced obesity., Unbalanced energy partitioning participates in the rise of obesity, a major public health concern in many countries. Increasing basal energy expenditure has been proposed as a strategy to fight obesity yet raises efficiency and safety concerns. Here, we show that mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis display increased basal energy expenditure and protection against high-fat diet–induced obesity. Mechanistically, muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of the inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and adenosine 5′-triphosphate (ATP) synthase, which was restored by cardiolipin enrichment. Our study reveals that selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.

Storage requirements and outdating of platelets represent a continued challenge for blood banks. These hurdles are confounded for rural area hospitals or in military deployments. Over 60 years of research and development into frozen platelets have generated a stable and reproducible product. Valeri's method to freeze platelets in 6% dimethyl sulfoxide (DMSO) and storage at -80°C allows for long-term storage alleviating burdens placed on blood banks. Clinical studies show that frozen platelet transfusions are safe with no related thrombotic or other serious adverse events. There are ongoing efforts to demonstrate cryopreserved platelet (CPP) superiority in efficacy studies designed in trauma or cardiac surgery patients. Technical advances in CPP manufacturing including closed system manufacturing, applications of pathogen reduction technology and potency standard characterization add to the appeal of CPP as an alternative to traditional liquid-stored platelets (LP) in settings of supply shortages, mass casualty, active bleeding, rapid provision of HLA-compatible platelets, and remote care.

Background Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients. Methods This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated. Results Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum. Conclusion Recurrence of PMP was rare after 5 years and exceptional after 10 years.

La gastrectomia per cancro a scopo curativo comporta una resezione completa R0 senza effrazione tumorale, con margine sano parietale e linfoadenectomia estesa. Una perfetta conoscenza dell’anatomia vascolare e della modalita di estensione linfonodale e parietale e essenziale, prima di eseguire questo tipo di intervento chirurgico. Le gastrectomie sono interventi con una morbimortalita e un impatto nutrizionale significativi. Questi interventi sono, quindi, riservati ai pazienti in buone condizioni di salute e a scopo curativo, nella maggior parte dei casi. Una valutazione preoperatoria completa permette di giudicare l’estensione locale e a distanza. In Occidente, una chemioterapia perioperatoria e un trattamento standard per i tumori localmente avanzati. La linfoadenectomia ampia detta D2 senza splenopancreatectomia aumenta le possibilita di recupero ed e, quindi, una componente importante della chirurgia del cancro gastrico. Una diffusione del tumore agli organi vicini puo richiedere la loro rimozione. L’approccio laparoscopico ha scarse indicazioni in Occidente ed e giustificato principalmente per le gastrectomie preventive su mutazione di CDH1. Dopo gastrectomia, sono possibili diverse modalita di ricostruzione digestiva e queste hanno lo scopo di limitare i disturbi funzionali a medio e a lungo termine.

Las gastrectomias por cancer con fines curativos implican una reseccion completa R0 sin ruptura tumoral, con margen parietal sano y vaciamiento ganglionar ampliado. Un perfecto conocimiento de la anatomia vascular y del modo de extension ganglionar y parietal es indispensable antes de hacer este tipo de cirugia. Las gastrectomias son intervenciones con una morbimortalidad notable y un impacto nutricional significativo. Por lo tanto, estas intervenciones estan reservadas para pacientes en buen estado general y tienen fines curativos en la mayoria de los casos. Una evaluacion preoperatoria completa permite juzgar la extension locorregional y a distancia. En Occidente, la quimioterapia perioperatoria es un estandar terapeutico para el cancer localmente avanzado. El vaciamiento ganglionar ampliado o D2 sin esplenopancreatectomia aumenta las posibilidades de curacion y, por lo tanto, es un elemento importante de la cirugia de cancer gastrico. Una extension del tumor a organos vecinos puede requerir su exeresis. El enfoque laparoscopico tiene pocas indicaciones en Occidente y esta principalmente justificado para gastrectomias preventivas en pacientes con mutacion de CDH1. Despues de la gastrectomia, hay varios modos posibles de reconstruccion digestiva destinados a limitar los trastornos funcionales a medio y largo plazo.

En este articulo, se presentan los datos mas importantes que deben conocerse sobre la realizacion tecnica de los distintos modelos de colostomias, sus complicaciones intrinsecas y su tratamiento. La colostomia es un procedimiento basico en cirugia digestiva que puede realizarse en cirugia programada o en situacion de urgencia en condiciones dificiles. En este articulo, se describe en primer lugar el enfoque global de la colostomia y la importancia del tratamiento preoperatorio. Se describen las tecnicas quirurgicas propias de cada tipo de colostomias: lateral, terminal y seudocontinente, asi como sus variantes. Los autores han incluido las practicas recientes representadas por la laparoscopia y las tecnicas de estimulacion electrica. En la segunda parte, se describen las complicaciones y su tratamiento. Se dividen en dos grupos. Por una parte, las complicaciones precoces: necrosis del estoma, hemorragias, oclusiones y retracciones, que con mucha frecuencia requieren una reintervencion de urgencia y que suelen ser secundarias a una tecnica inadecuada. Por otra parte, las complicaciones tardias: prolapso, estenosis, eventraciones periestomiales y perforaciones ostomiales, que son muy frecuentes, pero cuyo tratamiento no siempre es quirurgico. La prevencion de las complicaciones es un objetivo principal. Se basa en particular en la utilizacion de materiales protesicos con fines profilacticos, asi como en la realizacion de la cirugia con laparoscopia.

BackgroundThe prognostic value of the primary neoplasm responsible for pseudomyxoma peritonei (PMP) remains poorly studied. The aim of this study was to determine the prognosis for patients with extra-appendicular PMP (EA-PMP) treated optimally with complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsAll patients treated for PMP with CCRS and HIPEC between 1994 and 2016 were selected retrospectively from a French multicentre database. Patients with EA-PMP had pathologically confirmed non-neoplastic appendices and were matched in a 1 : 4 ratio with patients treated for appendicular PMP (A-PMP), based on a propensity score.ResultsSome 726 patients were identified, of which 61 (EA-PMP group) were matched with 244 patients (A-PMP group). The origins of primary tumours in the EA-PMP group included the ovary (45 patients), colon (4), urachus (4), small bowel (1), pancreas (1) and unknown (6). The median peritoneal carcinomatosis index was comparable in EA-PMP and A-PMP groups (15·5 versus 18 respectively; P = 0·315). In-hospital mortality (3 versus 2·9 per cent; P = 1·000) and major morbidity 26 versus 25·0 per cent; P = 0·869) were also similar between the two groups. Median follow-up was 66·9 months. The 5-year overall survival rate was 87·8 (95 per cent c.i. 83·2 to 92·5) per cent in the A-PMP group and 87 (77 to 96) per cent in the EA-PMP group. The 5-year disease-free survival rate was 66·0 (58·7 to 73·4) per cent and 70 (53 to 83) per cent respectively.ConclusionOverall and disease-free survival following treatment with CCRS and HIPEC is similar in patients with pseudomyxoma peritonei of appendicular or extra-appendicular origin.

With the increase in performance of machining operations, noise levels have become an occupational health and safety problems. Identification of the main sources of noise emission when milling an aluminium component was analyzed. A machining centre, equipped with microphones, was installed in an anechoic chamber. Testing demonstrated that the part's stiffness is the most critical parameter. Cutting speed, feed and axial depth of cut tend to increase sound pressure level by increasing the impact energy, whereas radial depth of cut is not a sensitive parameter. Moreover the diameter of mills, as well as their unbalance, should be limited.

Le eviscerazioni pelviche per cancro sono interventi tecnicamente complessi, tanto per l’exeresi quanto per la ricostruzione. Queste pelvectomie sono giustificate solo con un obiettivo curativo, attraverso l’ottenimento di una resezione completa, ampia, monoblocco e con margini sani (R0), e sono destinate a pazienti in buone condizioni generali. Questi interventi richiedono un bilancio preoperatorio accurato e completo e una perfetta conoscenza dell’anatomia pelvica, delle modificazioni locali indotte dal tumore e dai trattamenti precedenti e della prognosi della malattia. Essi fanno ricorso a tecniche di resezione oncologica e a tecniche urologiche, ginecologiche, digestive e plastiche riparative. Queste eviscerazioni sono all’origine di un’importante morbimortalita e di sequele funzionali che possono essere limitate con tecniche di ricostruzione d’organo e di riempimento pelviperineale.

Using a home-made, anvil pressure-cell mounted to a probe suitable for use with a commercial magnetometer, the photo and thermal responses of the magnetism of CoFe@CrCr-PBA (PBA = Prussian blue analogue) core@shell nanoparticles were studied down to 5 K and up to 0.5 GPa in 100 G. The effect of pressure on the magnetic ordering temperatures of the CoFe-PBA core (≈25 K) and the CrCr-PBA shell (≈200 K) along with a shift of the relaxation temperature of the photo-CTIST (charge-transfer-induced spin-transition) of the CoFe-PBA core (≈125 K), were similar to the behaviors reported for the single-phase materials. Specifically, although the magnetic ordering temperature of the CrCr-PBA shell shifted to higher temperatures, the relaxation temperature of the photo-CTIST of the CoFe-PBA core moved to lower temperatures when the pressure was increased, thereby lowering the temperature range under which the CrCr-PBA component can be photoswitched.

Introduction Mitochondrial dysfunction plays a major role in the Heart Failure (HF) pathophysiology.The AMP activated protein kinase (AMPK) is activated by a high AMP-ADP/ATP ratio and regulates a number of metabolic pathways. Many studies have highlighted a protective role of AMPK in HF, but its relevance to cardiac tissue, its metabolic part and its sex specificity are not well established. Purpose Then, the aim of this study is to determine the role of AMPK in the healthy and failing heart in male and female mice. Methods We developed and validated a mouse strain with an adult-inducible cardiac-specific deletion of AMPKα2, the major cardiac isoform, using the Cre-Lox system (40mg/kg tamoxifen injection on two consecutive days at adult age). At four months after the deletion, cardiac contractility, morphology and metabolism were studied in control and KO mice from both sexes. Results We observed only in male KO mice a decrease of left ventricular ejection fraction (−10%), an increase of the total fibrosis (+64%) and defects in mitochondrial structures. Male KO mice also showed a reduced (−28%) mitochondrial respiration via complex I associated with a different cardiolipin species distribution. Conclusion Our results reveal in adult healthy hearts, a sex-specificity in the effects of AMPKα2 deletion, leading to impaired contractile function related to metabolic and non-metabolic alterations only in male mice.

SummaryThe tubular shape of mitochondrial cristae depends upon a specific composition of the inner mitochondrial membrane, including cardiolipin that allows strong curvature and promotes optimal organization of ATP synthase. Here we identifyHacd1,which encodes an enzyme involved in very long chain fatty acid biosynthesis, as a key regulator of composition, structure and functional properties of mitochondrial membranes in muscle. InHacd1-deficient mice, the reduced cardiolipin content was associated with dilation of cristae and caused defective phosphorylating respiration, characterized by absence of proton leak and oxidative stress.The skeletal muscle-specific mitochondrial coupling defect produced a global elevation in basal energy expenditure with increased carbohydrate and lipid catabolism, despite decreased muscle mass and locomotor capacities. Mice were protected against diet-induced obesity despite reduced muscle activity, providing anin vivoproof of concept that reducing mitochondrial coupling efficiency in skeletal muscle might be an actionable mechanism in metabolic disease conditions.

BACKGROUND Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P

The number of frequency bands requiring BAW filters is expected to grow significantly with the launch of 5G mobile applications. BAW is in particular well suited to address the new radio bands below 6 GHz also referred to as nr-1. RF integration is the only path forward to achieve full connectivity in LTE + 5G wireless due to the complexity of the antenna systems and the resulting coexistence challenges. The article gives an overview and describes recent trends regarding BAW for high frequency bands, wide bandwidth filters, miniaturization and thermal management. Evolution of RF content and the challenges of developing complex RF modules are discussed.

Objectives/Hypothesis A prototype tympanostomy tube, composed of polybutyl/methyl methacrylate-co-dimethyl amino ethyl methacrylate (PBM), was tested to 1) evaluate the effect of PBM tubes on rat dermis as a corollary for biocompatibility and (2) to observe the efficacy of dissolution with isopropyl alcohol (iPrOH) and ethanol (EtOH). Study Design Original animal experiment and bench testing. Methods A two-part study was conducted to assess biocompatible substance with inducible dissolvability as a critical characteristic for a newly engineered tympanostomy tube. First, tympanostomy tubes were inserted subcutaneously in 10 rats, which served as an animal model for biosafety, and compared to traditional tubes with respect to histologic reaction. Tissue surrounding the PBM prototype tubes was submitted for histopathology and demonstrated no tissue reactivity or signs of major inflammation. In the second part, we evaluated the dissolvability of the tube with either isopropyl alcohol, ethanol, ofloxacin, ciprodex, water, and soapy water. PBM tubes were exposed to decreasing concentrations of iPrOH and EtOH with interval qualitative assessment of dissolution. Results Histologic examination did not reveal pathology with PBM tubes. Concentrations of at least 50% iPrOH and EtOH dissolve PBM tubes within 48 hours, whereas concentrations of at least 75% iPrOH and EtOH were required for dissolution when exposure was limited to four 20-minute intervals. Conclusions PBM is biocompatible in the rat model. Additionally, PBM demonstrates rapid dissolution upon alcohol-based stimuli, validating the proof-of-concept of dissolvable on-command or biocommandible ear tubes. Further testing of PBM is needed with a less ototoxic dissolver and in a better simulated middle ear environment before testing can be performed in humans. Level of Evidence NA Laryngoscope, 2016

Due to the increasing demand on many transmissions parts, such as synchronizing gears, crankshafts or camshafts, surface integrity along with appropriate fatigue performance is becoming a key issue in automotive industry. This paper proposes an experimental study covering the influence of three superfinishing processes on surface integrity of a SAE 5120 steel: belt-finishing, ball burnishing and mass-finishing. Surface and sub- surface properties, i.e. residual stresses, near surface microstructure, surface roughness and bearing parameters, have been analyzed to highlight the influence of different process parameters, to compare each process to another and assess the benefits compared to conventional turning.

Background Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. Objective To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. Material and methods A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. Results Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3–26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. Conclusion Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

To prove the concept that a dissolvable "on-command" tympanostomy tube placed into the tympanic membrane of a chinchilla can dissolve when a benign solution is applied and result in a well healed tympanic membrane without histologic evidence of injury.Prospective Randomized Single-Subject Controlled Trial.Prototype tympanostomy tubes were fabricated from poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co- methyl methacrylate) (PBM). "In vitro" dissolution studies were performed with applications of the benign chemical, hydrogen peroxide (HP). PBM tubes were placed into ten chinchilla tympanic membranes matched with standard plastic tubes placed into the contralateral side. All 20 tubes were exposed to HP for 21 days with serial endoscopic examinations. In vitro PBM tubes were weighed before and after interventions and compared to control tubes. In vivo photo documentation was used to show progression of dissolution and histologic slides were obtained to show the effect of the PBM on surrounding tissues.Compared to control tubes, all those exposed to hydrogen peroxide had a statistically significant reduction in weight (p 0.01). After placement into the tympanic membrane of chinchillas, all PBM tubes dissolved within 21 days of hydrogen peroxide treatment leaving behind histologically normal, intact tympanic membranes.Our PBM tubes dissolve "on-command" in a chinchilla model when exposed to treatment with a benign chemical. Dissolvable "on-command" tympanostomy tubes may reduce significant complications related to pediatric tympanostomy tube use.

Background The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy. Methods A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI. Results Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI. Conclusion Laparoscopy may underestimate the extent of CRPM.

International audience

Matthieu F Dumont,1 Sridevi Yadavilli,2 Raymond W Sze,1,4 Javad Nazarian,2,3 Rohan Fernandes1,4,5 1Sheikh Zayed Institute for Pediatric Surgical Innovation, 2Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC, USA; 3Department of Integrative Systems Biology, 4Department of Radiology, 5Department of Pediatrics, George Washington University, Washington, DC, USA Abstract: Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn2+ ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling fluorescence imaging and functioning as a platform for the attachment of biotinylated ligands that target PBTs. The surfaces of our nanoparticles are modified with biotinylated antibodies targeting neuron-glial antigen2or biotinylated transferrin. Both neuron-glial antigen2and the transferrin receptor are protein markers overexpressed in PBTs. We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles. Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro. Finally, we demonstrate the potential of these nanoparticles as PBT imaging agents by measuring their organ and brain biodistribution in an orthotopic mouse model of PBTs using ex vivo fluorescence imaging. Keywords: Prussian blue, nanoparticles, imaging, pediatric brain tumors, fluorescence, magnetic resonance imaging, manganese, multimodal

X-ray absorption spectroscopy experiments of core@shell, photomagnetic, and Prussian Blue analogue heterostructures obtain the local structure around the magnetic transition-metal ions before and after illumination. Two samples, containing nickel hexacyanochromate (Ni–Cr) and cobalt hexacyanoferrate (Co–Fe) in Ni–Cr@Co–Fe and Co–Fe@Ni–Cr geometries, were studied. Both materials display the well-known photoinduced valence tautomerism for Co–Fe, accompanied by a large change in cobalt to nitrogen distances. Furthermore, these experimental results show a structural coupling of the photoactive Co–Fe layer to the passive Ni–Cr layer. Finally, the strain across the heterostructured interface in Co–Fe and Ni–Cr containing core@shell models is investigated with simulations that use custom potentials derived from density functional theory calculations.

The proposed paper is focusing on the influence of cryogenic lubrication on friction within the context of machining TiAl6V4 and Inconel 718 alloys with carbide cutting tools. Several wear improvements have been reported in the literature when using liquid or gas nitrogen as cooling-lubrication fluids compared with dry machining or to conventional emulsion lubrication. However, it is always questionable whether cryogenic lubrication is responsible for a decrease in the cutting temperature or for a decrease in the friction coefficient at the contact interfaces and whether liquid nitrogen lubrication is more effective than gas nitrogen lubrication. In order to simulate the tribological conditions corresponding to those occurring at these interfaces under dry and cryogenic conditions, a specially designed open tribometer has been used to characterise macroscopic friction coefficient, heat transfer and adhesion in the contact for a large range of sliding velocities. Friction, cryogenic, superalloys, heat transfer and adhesion Copyright © 2014 John Wiley & Sons, Ltd.