Thermodynamic Description of Synergy in Solvent Extraction: I. Enthalpy of Mixing at the Origin of Synergistic Aggregation.

Revisiting aggregation of extractant molecules into water-poor mixed reverse micelles, we propose in this paper to identify the thermodynamic origins of synergy in solvent extraction. Considering that synergistic extraction properties of a mixture of extractants is related to synergistic aggregation of this mixture, we identify here the elements at the origin of synergy by independently investigating the effect of water, acid, and extracted cations. Thermodynamic equations are proposed to describe synergistic aggregation in the peculiar case of synergistic solvent extraction by evaluating critical aggregation concentration (CAC) as well as specific interactions between extractants due to the presence of water, acid and cations. Distribution of two extractant molecules in the free extractants and in reverse micelles was assessed, leading to an estimation of the in-plane interaction parameter between extractants in the aggregates as introduced by Bergström and Eriksson ( Bergström, M.; Eriksson, J. C. A Theoretical Analysis of Synergistic Effects in Mixed Surfactant Systems . Langmuir 2000 , 16 , 7173 - 7181 ). Based on this model, we study the N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide (DMDOHEMA) and di(2-ethylexyl) phosphoric acid (HDEHP) mixture and show that adding nitric acid enhances synergistic aggregation at the equimolar ratio of the two extractants and that this configuration can be related to a favored enthalpy of mixing.

LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.

Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.

European outbreaks of atypical myopathy in grazing equids (2006-2009): spatiotemporal distribution, history and clinical features.

REASONS FOR PERFORMING STUDY: Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. OBJECTIVES: This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. METHODS: The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affected countries and from the large outbreaks were made with Fisher's exact and Welch's tests with Bonferroni correction. RESULTS: Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. CONCLUSIONS AND POTENTIAL RELEVANCE: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies.

European outbreaks of atypical myopathy in grazing horses (2006-2009): determination of indicators for risk and prognostic factors.

REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. METHODS: An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. RESULTS: From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.

[Examination of horses with acute colic: clinical and legal aspects]. / Untersuchung des akut kolikkranken Pferdes - klinische und forensische Aspekte.

The article provides hands-on advice and scientific background information regarding the management of the equine acute colic patient. It summarizes essential information on the patient's history, clinical examination, and legal aspects. The scope of the history is based on the clinical appearance of the patient. In horses with violent and barely controllable signs of pain, it is limited to colic-associated information such as onset, course and severity of colic signs, and the last time of defecation, as well as prior therapeutic intervention. In these patients, the clinical examination is focussed primarily on the assessment of cardiovascular parameters, rectal temperature, and the patient's behaviour. The nasogastric intubation is an essential part of the examination of a horse with colic to prevent a gastric rupture due to gastric distension. Transrectal palpation is equally important and should always be performed unless there are important reasons to object to this procedure. In most cases, a thorough patient history and clinical examination of an acute colic patient allows the examining veterinarian to make a tentative diagnosis and a prognostic evaluation. This helps with the decision to start a conservative or a surgical therapy. Due to the existing obligatory documentation requirement and the duty to inform patient owners, it is of utmost importance to promptly document one's findings, therapeutic measures, consultations, and information of the patient owner in written form. This supports further therapy and it can also be of relevance in a potentially resulting lawsuit.

In vivo induction of interferon gamma expression in grey horses with metastatic melanoma resulting from direct injection of plasmid DNA coding for equine interleukin 12.

Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples were analysed using quantitative real-time PCR. Plasmid DNA was quantified in blood samples and mRNA expression for IFN-g in tissue samples. Plasmid DNA showed fast elimination kinetics with more than 99 % of the plasmid disappearing within 36 hours. IFN-g expression increased quickly after IL-12 plasmid injection, but varied between individual horses. Intratumoural injection of plasmid DNA is a feasible method for inducing transgene expression in vivo. Biological activity of the transgene IL-12 was confirmed by measuring expression of IFN-g.

Tratamiento quirúrgico de fractura cervical en el Hospital Regional Rancagua: análisis de un periodo de 4 años / Surgical treatment of cervical fracture in the Rancagua Regional Hospital: analysis of a period of 4 years

Introducción: La gravedad, las implicancias neurológicas y el alto costo del tratamiento de la fractura cervical, hacen de esta lesión un tema de suma importancia. Esta injuria provoca graves limitaciones e invalidez a los afectados, en su mayoría en plena actividad laboral, impactando en lo médico, social y económico. Objetivos: Describir los pacientes tratados quirúrgicamente de fractura cervical traumática en el Hospital Regional Rancagua, por el equipo de Neurocirugía dentro de un periodo de 4 años. Materiales y Métodos: Se evaluó - 24 pacientes con antecedente de fractura cervical el mecanismo del trauma, el tiempo transcurrido desde el ingreso hospitalario hasta la cirugía, nivel y compromiso de la lesión medular, tipo de abordaje quirúrgico, complicaciones médicas, quirúrgicas y seguimiento post-operatorio, entre otros. Resultados: 5 mujeres y 19 hombres, edad promedio 39 años (rango de edad 14 a 75 años), principales mecanismos de trauma fueron los accidentes automovilísticos-atropello (58 por ciento). El nivel medular más frecuentemente lesionado fue C4-C5 (25 por ciento). En el 50 por ciento de los pacientes se clasificó de entrada como Frankel A, por lo que un 50 por ciento de todos los pacientes ingresaron tetrapléjicos, y de estos, un 33 por ciento egresó tetraparéticos. Del ingreso a cirugía hubo un tiempo de espera promedio 5 días. Dentro de las complicaciones médicas la causa respiratoria (46 por ciento) fue la más frecuente, necesitando 64 por ciento de estos pacientes ventilación mecánica. Se registró 1 infección de herida operatoria donde el abordaje fue posterior. El Índice de Barthel promedio de 14 pacientes fue de 49 puntos. De 6 pacientes con puntaje Cero, 85 por ciento de estos ingresaron como Frankel A y 50 por ciento egresaron tetrapléjicos. Los pacientes se rehabilitaron en promedio de 2.5 meses. Discusión: Logramos objetivar nuestra realidad. La técnica quirúrgica fue prácticamente uniforme entre los pacientes, sin complicaciones...

Introduction: Gravity, neurological implications and high costs of treating cervical fracture, makes of this injury an issue of most importance. This injury causes severe limitations and disability to those affected, mostly in full working activity, impacting on the medical, social and economic. Objectives: To describe patients surgically treated for traumatic cervical fracture at the Rancagua Regional Hospital, by the team of Neurosurgery Department, within a period of 4 years. Materials and Methods: We evaluated 24 patients with an history of cervical fracture mechanism of trauma, the time from hospital admission to surgery, and commitment level of spinal cord injury, type of surgery, medical and surgical complications and follow-up post -operation, among others. Results: 5 women and 19 men, average age 39 years (ranging age from 14 to 75 years), major trauma mechanisms were motor vehicle accidents (58 percent). The most frequently injured spinal level was C4-C5 (25 percent). 50 percent of patients were classified as Frankel A at the admission, so that 50 percent of all patients admitted were quadriplegics, and of these, 33 percent were discharged as tetraparétic. Admission to the surgery were an average of 5 days. Within cause respiratory medical complications (46 percent) was the most frequent, requiring 64 percent of these patients mechanical ventilation. There was only 1 wound infection where the approach was posterior. The average Barthel Index of 14 patients was 49 points. In 6 patients with zero score, 85 percent were admitted as Frankel A and 50 percent egressed as tetraplejic. Patients were rehabilitated an average of 2.5 months. Conclusions: We were able to objectify our reality. The surgical technique was nearly uniform among patients without severe postoperative surgical complications...

Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks.

Modulation of serotonin transporter (5-HTT) function causes changes in affective behavior, both in humans and rodents. Stressful life events likewise affect emotional behavior. In humans, a low-expressing genetic 5-htt variant, the s allele of the 5-htt linked promoter region, has been associated with increased risk for depression only where there was a history of stressful life events. To investigate this gene by environment interaction in mice, we compared the effects of inescapable shocks on the behavior of wild-type (5-htt+/+), heterozygote (5-htt+/-) and serotonin transporter deficient (5-htt-/-) mice. Inescapable shocks induce behavioral changes including a shock escape deficit, in a subsequent test when escape is possible. Confirming a gene by environment interaction, we found that stress increases escape latencies in a gene-dose dependent manner (5-htt-/->5-htt+/->5-htt +/+), where as there were no differences among the genotypes in the unstressed condition. The vulnerability to increased escape latency could not be accounted for by enhanced fear learning, as 5-htt-/- mice did not show heightened fear conditioning. The interaction of 5-htt genotype and stress appeared to produce a selective behavioral vulnerability, because no interaction of 5-htt genotype and stress was observed in other measures of anxiety and depression-linked behavior, including the open field, novelty suppressed feeding, and forced swim tests. We replicated prior findings that the 5-htt-/- displays heightened anxiety and depression-like behavior at baseline (unstressed condition). In conclusion, our data offer the possibility for future investigation of the neural basis underlying 5-htt genotype-by-stress interaction shown here.

[A pelvic "blue" node. What's your diagnosis?]. / Un ganglion pelvien "bleu". Quel est votre diagnostic?

We report a case of 31-year-old woman presented with a chronic pelvic pain and a 3-cm left ovarian cyst on ultrasonography. At the time of laparoscopy, we observed two blue peritoneal lesions at the pelvic insertion of left round ligament. Histopathological examination of a biopsy showed a pigmentation due to a decorative tattoo of the left thigh.

Resection of ectopic mediastinal parathyroid glands with the da Vinci robotic system.

BACKGROUND: Mediastinal ectopic parathyroid adenoma is a frequent cause of persistent or recurrent hyperparathyroidism, traditionally treated by open surgery. Thoracoscopic access is associated with reduced morbidity in mediastinal surgery. The aim of this study was to evaluate the feasibility and effectiveness of robot-assisted dissection for mediastinal ectopic parathyroid glands. METHODS: Two patients with recurrent secondary hyperparathyroidism and three with complicated primary hyperparathyroidism were operated on between July 2004 and August 2008 for ectopic mediastinal parathyroid glands. Fusion of single-photon emission computed tomography and computed tomography led to an exact identification of the culprit glands. Surgery was performed thoracoscopically with the da Vinci robotic system using a three-trocar approach. RESULTS: All procedures were completed successfully with the robotic system. No perioperative morbidity or mortality was noted. Median operating time was 58 (range 42-125) min. Intraoperative parathyroid hormone reduction indicated complete resection. Median hospital stay was 3 (range 2-4) days. CONCLUSION: Robot-assisted dissection is a promising approach for resection of ectopic parathyroid glands in remote narrow anatomical locations such as the mediastinum.

["Fast-track" rehabilitation to enhance recovery after ileostomy closure--a prospective clinical trial]. / "Fast-track"-Rehabilitation zur Beschleunigung der Rekonvaleszenz nach Ileostomarückverlagerung--eine prospektive kontrollierte Studie.

BACKGROUND AND AIMS: After colorectal resections, concepts for early recovery (ERAS or fast-track) could reduce the length of the hospital stay. Whether or not such a multimodal treatment can shorten the hospitalisation after loop ileostomy closure was investigated in the present study. PATIENTS AND METHODS: All patients admitted for elective closure of a loop ileostomy were prospectively investigated. The first group (n = 20) was postoperatively treated in a conventional manner. In the other group (n = 20), a concept for "fast-track" rehabilitation including early oral feeding, early mobilisation and abandonment of opioid analgesia was used. RESULTS: Oral feeding with liquids and solid food was tolerated in the "fast-track" group earlier than after conventional treatment. There was no increase in the incidence of postoperative complications. Patients of the "fast-track" group could be discharged 3 days earlier on average (p = 0,01). CONCLUSION: "Fast-track" rehabilitation can shorten the length of hospitalisation after elective ileostomy closure.

Influence of pre-operative fluid infusion on volume status during oesophageal resection--a prospective trial.

BACKGROUND: Perioperative fluid therapy is controversially debated in surgery. In malnourished and hypovolaemic patients, a restrictive fluid regimen may lead to hypoperfusion and increased incidence of complications. The present prospective cohort study was performed to assess whether pre-operative i.v. fluid administration improves intraoperative cardiac preload in patients undergoing oesophageal resection. METHODS: Intraoperatively, the intrathoracic blood volume index (ITBVI) was monitored in 44 consecutive patients undergoing elective oesophagectomies with the transthoracic thermodilution technique. Twenty-two of these patients received a pre-operative i.v. fluid loading with a balanced crystalloid solution (1 ml/kg/h over 48 h). RESULTS: After induction of anaesthesia ITBVI was low but not different between the groups [767 (512-1314) vs. 775 (531-1200) ml/m(2), P=0.81]. In the intervention group, the extravascular lung water increased above normal levels during the operation. The groups did not differ in cardiac output, blood pressure, heart rate and central venous pressure. Post-operative morbidity was not different between the cohorts. CONCLUSION: Pre-operative i.v. fluid loading with crystalloid solutions could not be shown to improve the intraoperative volume status and cardiac function in this study. Randomised trials with other volume replacement techniques are recommended.

["Fast-track" rehabilitation in thoracic surgery. First experiences with a multimodal, interdisciplinary, and proven perioperative treatment course]. / "Fast-track-Rehabilitation" in der Thoraxchirurgie. Erste Erfahrungen mit einem interdisziplinären, multimodalen, beweisbegründeten und perioperativen Behandlungspfad.

OBJECTIVES: "Fast-track" rehabilitation is a multimodal perioperative treatment concept for accelerating postoperative recovery which has been already used successfully in visceral surgery. Of its use in thoracic surgery however, almost no data exist and the relevance of this concept for pulmonary operations is unknown. PATIENTS AND METHODS: In this prospective study we examined a new perioperative fast-track treatment concept for thoracic surgery and evaluated the results. This program employs detailed information of patients, intensive perioperative respiratory therapy, thoracic peridural analgesia, forced mobilization, and an early start of postoperative normal food intake. RESULTS: Fifty consecutive patients with benign or malignant diseases of the lung aged an average of 64 years (range 22-78) were operated on thoracoscopically (n=15) or with thoracotomy (n=35) and treated perioperatively using the fast-track program. All patients were mobilized beginning 4 h postoperatively and had normal food. The incidence of general postoperative complications was 0% in this study. Postoperative stay lasted 4.5 days (range 1.5-28.5). There was no increase in surgical complications, and 6% of the patients were readmitted. The patients' acceptance of this concept was high. CONCLUSION: Fast-track rehabilitation resulted in a decreased rate of general complications and accelerated rehabilitation in thoracic surgery.

[Minimally invasive thymus surgery]. / Minimal-invasive Chirurgie des Thymus.

There are absolute and relative indications for complete removal of the thymus gland. In the complex therapy of autoimmune-related myasthenia gravis, thymectomy plays a central role and is performed with relative indication. In case of thymoma with or without myasthenia, thymectomy is absolutely indicated. Thymus resection is further necessary for cases of hyperparathyroidism with ectopic intrathymic parathyroids or with certain forms of multiple endocrine neoplasia. The transcervical operation technique traditionally reflected the well-founded desire for minimal invasiveness for thymectomy. Due to the requirement of radicality however, most of these operations were performed using sternotomy. With the evolution of therapeutic thoracoscopy in thoracic surgery, several pure or extended minimally invasive operation techniques for thymectomy have been developed. At present uni- or bilateral, subxiphoid, and modified transcervical single or combination thoracoscopic techniques are in use. Recently a very precise new level of thoracoscopic operation technique was developed using robotic-assisted surgery. There are special advantages of this technique for thymectomy. An overview of the development and experiences with minimally invasive thymectomy is presented, including data from the largest series published so far.

Exploring the dynamics of social-ecological resilience in East and West Africa: Preliminary evidence from Tanzania and Niger.

BACKGROUND: Social-ecological resilience refers to the dynamic process of adaptive learning, reorganization and meaning-making demonstrated in linked human, animal, and plant ecosystems often organized in formal and/or informal social institutions, as they anticipate, withstand and/or judiciously engage with adversity while maintaining function without fundamentally losing their identity. OBJECTIVE: To present two sets of examples that illustrate the complex ways in which transformation and persistence, two key aspects of the adaptive cycle may work together to preserve established patterns of human and/or animal uses of water resources and food plant species, in rural East and West Africa, respectively around the Serengeti National Park (Tanzania), and "Park W" (Niger), with the aim of identifying possible indicators of social-ecological resilience. METHODS: Selective combinations of ecological and anthropological, quantitative and qualitative methods, including participatory tools of investigation and analysis. RESULTS AND DISCUSSION: Our preliminary results are presented with minimal commentary and discussion in order to avoid hasty and/or unwarranted interpretation of the ongoing purposely iterative processes of investigation and analysis in the two study sites. Nevertheless we have identified a number of possible indicators of social-ecological resilience that may be tested in other localities in Africa and elsewhere.

Omental leiomyoma in a male adult horse.

A well-circumscribed mass 70 x 35 x 28 cm in size and 41 kg in weight was detected at necropsy in a male adult horse within the omentum major without any association to the gastrointestinal tract. The tumor consisted of multiple white-to-yellow lobules and displayed a firm consistency. In addition, multiple cysts filled with blood-like fluid, and multifocal areas of necrosis were observed. Histologically, the mass consisted of slightly pleomorphic spindloid-shaped cells arranged in interlacing bundles containing elongated nuclei with blunt ends. The majority of tumor cells revealed a positive immunoreaction for alpha-smooth muscle actin, vimentin, and neuron-specific enolase and were negative for S-100, factor VIII-related antigen, and glial fibrillary acidic protein. Few tumor cells showed expression of desmin and c-kit. On the basis of macroscopy, histology, and immunohistochemistry, an omental leiomyoma was diagnosed.

Arteriocolic fistulae due to a stab wound: a rare cause of lethal lower gastrointestinal bleeding.

The authors describe the first reported case of lethal lower gastrointestinal bleeding due to an iliocolic fistulae following a single stab wound. They also discuss the pathophysiology of the enterovacscular fistulae, as well as a review of the literature and assess forensic characteristics. This unusual case underlines the importance of being aware of the victim's history in arteriocolic fistulae due to a stab wound.

[Demands of private gastroenterologists for collaborative treatment concepts with clinics. Results of a Germany-wide survey]. / Welche Anforderungen stellen niedergelassene Gastroenterologen an integrierte Versorgungskonzepte mit Kliniken? Ergebnisse einer deutschlandweiten Umfrage.

BACKGROUND: New demands and possibilities of collaboration between hospitals and private practices in Germany have appeared, now that the way has been opened legally. A poll was conducted to analyse the current status of collaboration between outpatient gastroenterologists and hospital surgical departments and to identify possible future collaborations. MATERIALS AND METHODS: One thousand twenty-six private practices specialising in endoscopy were found by contacting the Association of Statutory Health Insurance Physicians and additional internet research. Of these, 50% were randomly selected (513 private practices) and contacted by mail with anonymous questionnaires about cooperation with their clinical partners. Two hundred three (39.6%) practices responded, of which 200 could be analysed. RESULTS: Of all practices reached, 75% considered the cooperation with clinics very valuable or even exceptional. Still, almost half (46%) suggested necessary improvements in these collaborations. Around a third of all contacted colleagues were already involved in projects following integrated care models. In about 80% of all participants, the main interest in integrated models was specified to be common therapy planning. CONCLUSION: The data analysis of this study shows a substantial interest of private-practice gastroenterologists in close collaboration with hospitals. It is now up to the hospitals to open contracts with their medical outpatient partners.

Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality.

The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics. Gene disruption in Saccromyces cerevisiae, Drosophila melanogaster and Trypanosoma brucei demonstrated that p97 is essential in unicellular and multicellular organisms. To explore the requirement for p97 in mammalian cell function and embryogenesis, we disrupted the p97 locus by gene targeting. Heterozygous p97+/- mice were indistinguishable from their wild-type littermates, whereas homozygous mutants did not survive to birth and died at a peri-implantation stage. These results show that p97 is an essential gene for early mouse development.