Cyanomethylene-bis(phosphonate) as ditopical ligand: stepwise formation of a 2-D heterometallic Fe(III)-Ag(I) coordination network

A new heteroditopic ligand, cyanomethylene-bis(5,5-dimethyl-2-oxo-1,3,2 lambda(5)-dioxa-phosphorinane) 1 (bphosCN), has been reacted with Fe(ClO4)(3) to afford the mononuclear complex Fe(bphosCN)(3) 2 which crystallized in the cubic system, space group Pa (3) over bar. The iron center, chelated by the oxygen atoms of the ligand, shows an almost perfect octahedral geometry, with the CN groups disposed at 120 degrees each other. Further reaction with AgClO4 provided the heterometallic coordination polymer (infinity)(2) {[(Fe (bphosCN)(3))(3)Ag-3(H2O)(2)]center dot(ClO4)(3)} 3 as the unique crystalline polymorph, in the monoclinic space group P21/a. The targeted 2D honeycomb type structure has been achieved through an interplay between coordinative CN-Ag bonds and CN center dot center dot center dot H2O bonds. The magnetic measurements demonstrate the existence of isolated paramagnetic Fe(III) centers in both complexes

Incisional hernias – results of present therapy options

Sp. Sf. Pantelimon, București, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Hernia incizională este cea mai frecventă complicație după operațiile abdominale. Este dificil de estimat exact costul acestei patologii pentru societate. Dacă adăugam la costul intervenției chirurgicale și costul spitalizării, dificultățile operațiilor de recidivă multiplă, costul protezelor, morbiditățile pacienților neoperați, afectarea capacității de muncă și a calității vieții, vom avea magnitudinea problemei dezvoltate de această complicație redutabilă a tuturor intervențiilor chirurgicale. Material și metodă: Am analizat rezultatele mai multor studii de prestigiu ale unor colective românești și internaționale în domeniul herniilor incizionale. Rezultate: Din nefericire rezultatele globale ale tratamentului în hernia incizională oscilează între 12-63% pentru procedeele tisulare și între 2-36% pentru procedeele allopalstice. Abordul chirurgical este cel mai adesea bazat pe traditie si pe liberul arbitru, decat pe evidențe statistice sau ghiduri de tratament. Nu este deloc surprinzător faptul că, în ciuda noilor cuceriri în domeniul defectelor parietale și a folosirii explozive a protezelor, rata de re-operații pentru recidiva incizională se situează la același nivel. Concluzii: Componența operatorie ca unică etiologie în hernia incizională este supraestimată. Datorită faptului că și alți factori etiologici, cunoscuți sau nu, concura la apariția herniei incizionale și la re-recidivă, și datorită faptului că acești “factori” nu sunt deocamdată influențabili de tratamentul medical nu ne rămțne decât să analizăm lucid și responsabil factorii chirurg-dependenți. Greselile de tactică/tehnică chirurgicală trebuie evidențiate, explicate, și înlăturate. Soluția nu este o abordare pur tehnică, ci una fiziologică, în termeni de elasticitate, complianța și rezistența a întregului perete abdominal, deseori modificat profund de marile defecte incizionale.Introduction: incisional hernia is the most common complication after abdominal surgery. It is difficult to estimate the exact cost to society of this pathology. If we add to the cost of surgery and hospitalization costs, the difficulties of relapse multiple operations, the cost of prostheses, unoperated patient morbidity, impaired work capacity and quality of life, the magnitude of the problem we have developed this redoubtable complication of all surgical procedures. Methods: We analyzed the results of several studies of prestigious romanian and international collectives about incisional hernias. Results: Unfortunately, the overall results of treatment in incisional hernia procedures vary between 12-63% for tissular procedures and between 2-36% for allopalstic procedures. Surgical approach is most often based on tradition and the free will, rather than obvious statistical treatment guidelines. Not surprisingly, despite the new advancements in the field of herniology and the use of new parietal prosthesis, the rate of re-operations for recurrent incisional fall at the same level. Conclusions: Surgery as the only component in etiology of incisional hernias is overestimated. Due to the fact that other etiological factors, known or not compete in the emergence and re-incision hernia recurrence, and because these “factors” are not influenced by medical treatment for now, we are just lucid and analyze the factors responsible - surgeon dependent. Mistakes tactics/surgical technique must be highlighted, explained and removed. The solution is not a purely technical approach, but a physiological, in terms of elasticity, compliance and resistance of the entire abdominal wall

Children's International Polyposis (CHIP) study : a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Objective: To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP). Methods: In this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10-17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of >= 20 polyps (> 2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided. Results: Of 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (>= 20 polyps, > 2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs. Conclusion: In children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained

A Regional Modeling Study of the Entraining Mediterranean Outflow

[1] We have evaluated a regional-scale simulation of the Mediterranean outflow by comparison with field data obtained in the 1988 Gulf of Cadiz Expedition. Our ocean model is based upon the Hybrid Coordinate Ocean Model (HYCOM) and includes the Richardson number-dependent entrainment parameterization of Xu et al. (2006). Given realistic topography and sufficient resolution, the model reproduces naturally the major, observed features of the Mediterranean outflow in the Gulf of Cadiz: the downstream evolution of temperature, salinity, and velocity profiles, the mean path and the spreading of the outflow plume, and most importantly, the localized, strong entrainment that has been observed to occur just west of the Strait of Gibraltar. As in all numerical solutions, there is some sensitivity to horizontal and vertical resolution. When the resolution is made coarser, the simulated currents are less vigorous and there is consequently less entrainment. Our Richardson number-dependent entrainment parameterization is therefore not recommended for direct application in coarse-resolution climate models. We have used the high-resolution regional model to investigate the response of the Mediterranean outflow to a change in the freshwater balance over the Mediterranean basin. The results are found in close agreement with the marginal sea boundary condition (MSBC): A more saline and dense Mediterranean deep water generates a significantly greater volume transport of the Mediterranean product water having only very slightly greater salinity

Surgical atitude in suppurative acute pancreatitis

UMF Carol Davila, București, Sp. Sf. Pantelimon, București, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Managementul chirurgical al pancreatitei acute severe(SAP) rămâne încă controversat. Stabilirea indicație chirurgicale și a momentului operator optim este în legătură directă cu morbiditatea și mortalitatea acestei afecțiuni. Decizia chirurgicală se bazează pe criterii clinice,morfologice- examenul computer-tomografic și criterii bacteriologice- necroza sterilă sau infectată. Infecția necrozei pancreatice reprezintă o indicație de necontestat pentru necrozectomia chirurgicală. Material și metodă: Din 2007 până în 2010, un total de 104 de pacienți cu diagnostic de SAP şi cu indicație de intervenție chirurgicală au fost admişi în secția de chirurgie generală. Rezultate: Valoarea medie a scorului APACHE II la internare a fost de 16,4 (în intervalul 8-35). Toți pacienții au necesitat intervenție chirurgicală. Mortalitatea generală a fost 13,4% (14 pacienți). Insuficiență multiplă de organ a fost evidențiată la 41 de pacienți (39,4%). Infarctul miocardic sau embolia pulmonară au fost cauzele de deces la 3 pacienți (2,88%). Vârsta (p <0.0002), scorul APACHE II la internare (p<0,0001) , prezența sau dezvoltarea insuficienței (unice sau multiple) de organ (p<0.002), infecțiile (p<0,02) şi gradul extensiei necrozei pancretice (p <0.04), gradul de control al necrosectomiei (p <0,0001) par a fi în directa relație cu supraviețuirea. Concluzii: Evaluarea chirurgicală, în dinamică,se bazează pe determinările de laborator proprii identificării sepsisului cât și pe o imagistică CT sau RMN care să cuprindă obligatoriu reconstrucții de calitate. Acestea vor asigura o evacuare completă a necrozelor infectate, încă de la intervenția primară.Introduction: Surgical management of severe acute pancreatitis (SAP) remains controversial. Establishing the surgical indication and the optimal timing for surgery is directly related to surgical morbidity and mortality. Surgical approach is based on clinical-morphological criterias, computer tomography criteria, bacteriological-sterile or infected necrosis of pancreas. Infected necrosis represent an unquestionable indication for surgery. Methods: From 2007 to 2010, a total of 104 patients with a diagnosis of SAP and indication for surgery were admitted in department of general surgery. Results: The mean APACHE II score on the day of admission was 16.4(range 8-35). All patients required operative therapy. The overall mortality was 13,4% (14 patients). Septic organ failure in 41 patients (39,4%) and myocardial infarction or pulmonary embolism in 3 patients (2,88%) were the causes of death. The patient’s age (p <0.0002), APACHE II scores at admission (p <0.0001), presence or development of (single or multiple) organ failure (p <0.002), infections (p <0.02) and extent (p <0.04) of pancreatic necrosis, and surgical control of local necrosis (p <0.0001) significantly determined survival. Conclusions: The surgical evaluation, in dynamics, is based on both the laboratory determinations proper to the identification of the sepsis, and also on a CT or MRI imagistics which must necessarily contain quality reconstructions. These will ensure a complete evaluation of the infected necrosis, from the primary intervention

The R403Q Myosin Mutation Implicated in Familial Hypertrophic Cardiomyopathy Causes Disorder at the Actomyosin Interface

Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the beta-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype.Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow beta-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface.These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state

Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding