Comparative kinome analysis to identify putative colon tumor biomarkers

Kinase domains are the type of protein domain most commonly found in genes associated with tumorigenesis. Because of this, the human kinome (the protein kinase component of the genome) represents a promising source of cancer biomarkers and potential targets for novel anti-cancer therapies. Alterations in the human colon kinome during the progression from normal colon (NC) through adenoma (AD) to adenocarcinoma (AC) were investigated using integrated transcriptomic and proteomic datasets. Two hundred thirty kinase genes and 42 kinase proteins showed differential expression patterns (fold change ≥ 1.5) in at least one tissue pair-wise comparison (AD vs. NC, AC vs. NC, and/or AC vs. AD). Kinases that exhibited similar trends in expression at both the mRNA and protein levels were further analyzed in individual samples of NC (n = 20), AD (n = 39), and AC (n = 24) by quantitative reverse transcriptase PCR. Individual samples of NC and tumor tissue were distinguishable based on the mRNA levels of a set of 20 kinases. Altered expression of several of these kinases, including chaperone activity of bc1 complex-like (CABC1) kinase, bromodomain adjacent to zinc finger domain protein 1B (BAZ1B) kinase, calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D), serine/threonine-protein kinase 24 (STK24), vaccinia-related kinase 3 (VRK3), and TAO kinase 3 (TAOK3), has not been previously reported in tumor tissue. These findings may have diagnostic potential and may lead to the development of novel targeted therapeutic interventions for colorectal cancer

The plants, rituals and spells that 'cured' helminthiasis in Sicily

<p>Abstract</p> <p>Background</p> <p>The author reports on the plants, rituals and spells used against worms and the so-called <it>scantu </it>(fright) in some areas of Sicily. The work is based on ethnobotanical research carried out, prevalently, between 2002-2006, in some areas of Eastern, South-Eastern, North-Central and South-Central Sicily.</p> <p>Methods</p> <p>This research is based on dialogue. Senior 'healers' were contacted; furthermore, doctors, teachers, farmers and in general 'experts' with herbs and 'magic' rituals. Information was collected about the way the plants of folk medicine are prepared. The interviewees were also invited to recite prayers and spells against helminthiasis.</p> <p>Results</p> <p>The author has highlighted the importance of how, in some parts of Sicily, some ailments like helminthiasis and other correlated pathologies like <it>scantu </it>are 'treated' and, especially within the rural social classes, by folk medicine remedies, herbal practises, particular prayers, rituals and spells.</p> <p>Conclusion</p> <p>As regards health/illness, it should be noted that in the last ten years conventional medicine has provided very satisfactory results even resolving potentially mortal pathologies. However, in certain social classes, there is no real collaboration between conventional and folk medicine; so for some senior citizens, the 'healer' with his rituals and empirical and magical herbs is still the person to turn to for the 'cure' of particular ailments. Interest in these practises from ancestral heritage in an advanced country like Italy, is only relevant if the aim is to recoup a cultural identity which is already in decline.</p> <p>It is significant to report a piece: on 14 October 2007 the news on a well-known national Italian TV channel reported an interview with a 94 year-old man from Arbatax (Sardinia) referred to as a 'healer' because both his townspeople and others from all over the world go to him for his cures. He is not paid except in kind and has been known to cure St. Anthony's fire, burns, scalding and marine fungal infections, by smearing his saliva over the infected part and reciting 'special words'.</p

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Practice guideline for the treatment of patients with eating disorders (revision). American Psychiatric Association Work Group on Eating Disorders.

A. CODING SYSTEM: Each recommendation is identified as falling into one of three categories of endorsement, indicated by a bracketed Roman numeral following the statement. The three categories represent varying levels of clinical confidence regarding the recommendations: [I] recommended with substantial clinical confidence. [II] recommended with moderate clinical confidence. [III] may be recommended on the basis of individual circumstances. B. GENERAL CONSIDERATIONS: Patients with eating disorders display a broad range of symptoms that frequently occur along a continuum between those of anorexia nervosa and bulimia nervosa. The care of patients with eating disorders involves a comprehensive array of approaches. These guidelines contain the clinical factors that need to be considered when treating a patient with anorexia nervosa or bulimia nervosa. 1. Choosing a site of treatment: Pretreatment evaluation of the patient with an eating disorder is essential for determining the appropriate setting of treatment. The most important physical parameters that affect this decision are weight and cardiac and metabolic status [I]. Patients should be psychiatrically hospitalized before they become medically unstable (i.e., display abnormal vital signs) [I]. The decision to hospitalize should be based on psychiatric, behavioral, and general medical factors [I]. These include rapid or persistent decline in oral intake and decline in weight despite outpatient or partial hospitalization interventions, the presence of additional stressors that interfere with the patient's ability to eat (e.g., intercurrent viral illnesses), prior knowledge of weight at which instability is likely to occur, or comorbid psychiatric problems that merit hospitalization. Most patients with uncomplicated bulimia nervosa do not require hospitalization. However, the indications for hospitalization for these patients can include severe disabling symptoms that have not responded to outpatient treatment, serious concurrent general medical problems (e.g., metabolic abnormalities, hematemesis, vital sign changes, and the appearance of uncontrolled vomiting), suicidality, psychiatric disturbances that warrant hospitalization independent of the eating disorders diagnosis, or severe concurrent alcohol or drug abuse. Decisions to hospitalize on a psychiatric versus a general medical or adolescent/pediatric unit depend on the patient's general medical status, the skills and abilities of local psychiatric and general medical staffs, and the availability of suitable intensive outpatient, partial and day hospitalization, and aftercare programs to care for the patient's general medical and psychiatric problems. 2. Psychiatric management: Psychiatric management forms the foundation of treatment for patients with eating disorders and should be instituted for all patients in combination with other specific treatment modalities. Important components of psychiatric management for patients with eating disorders are as follows: establish and maintain a therapeutic alliance; coordinate care and collaborate with other clinicians; assess and monitor eating disorder symptoms and behaviors; assess and monitor the patient's general medical condition; assess and monitor the patient's psychiatric status and safety; and provide family assessment and treatment [I]. 3. Choice of specific treatments for anorexia nervosa: The aims of treatment for patients with anorexia nervosa are to 1) restore patients to healthy weight (at which means and normal ovulation in females, normal sexual drive and hormone levels in males, and normal physical and sexual growth and development in children and adolescents are restored); 2) treat physical complications; 3) enhance patients' motivations to cooperate in the restoration of healthy eating patterns and to participate in treatment; 4) provide education regarding healthy nutrition and eating patterns; 5) correct core maladaptive thoughts, attitudes, and feelings related to the eating disorder; 6) treat associated psychiatric conditions, including defects in mood regulation, self-esteem, and behavior; 7) enlist family support and provide family counseling and therapy where appropriate; and 8) prevent relapse. a. Nutritional rehabilitation: A program of nutritional rehabilitation should be established for all patients who are significantly underweight [I]. Nutritional rehabilitation programs should establish healthy target weights and have expected rates of controlled weight gain (e.g., 2-3 lb/week for most inpatient and 0.5-1 lb/week for most outpatient programs). Intake levels should usually start at 30-40 kcal/kg per day (approximately 1000-1600 kcal/day) and should be advanced progressively. During the weight gain phase, this may be increased to as high as 70-100 kcal/kg per day. During weight maintenance and for ongoing growth and development in children and adolescents, intake levels should be 40-60 kcal/kg per day. Patients who require higher caloric intakes may be discarding food, vomiting, or exercising frequently or have more nonexercise motor activity (e.g., fidgeting); others may have a truly higher metabolic rate. Patients also benefit from vitamin and mineral supplements (and in particular may require phosphorus before serum hypophosphatemia occurs). Medical monitoring during refeeding is essential [I]. It should include assessment of vital signs as well as food and fluid intake and output; monitoring of electrolytes (including phosphorus); and observation for edema, rapid weight gain (associated primarily with fluid overload), congestive heart failure, and gastrointestinal symptoms, particularly constipation and bloating. For children and adolescents who are severely malnourished (weight <70% of the standard body weight), cardiac monitoring may be useful, especially at night. Physical activity should be adapted to the food intake and energy expenditure of the patient. Nutritional rehabilitation programs should also include helping patients deal with their concerns about weight gain and body image changes, educating them about the risks of their eating disorder, and providing ongoing support to patients and their families [I]. b. Psychosocial interventions: The establishment and maintenance of a psychotherapeutically informed relationship is beneficial [II]. Once weight gain has started, formal psychotherapy may be very helpful. There is no clear evidence that any specific form of psychotherapy is superior for all patients. Psychosocial interventions need to be informed by understanding psychodynamic conflicts, cognitive development, psychological defenses, and complexity of family relationships as well as the presence of other psychiatric disorders. Psychotherapy alone is generally not sufficient to treat severely malnourished patients with anorexia nervosa. Ongoing treatment with individual psychotherapeutic interventions is usually required for at least a year and may take 5-6 years because of the enduring nature of many of the psychopathologic features of anorexia nervosa and the need for support during recovery. Family therapy and couples psychotherapy are frequently useful for the alleviation of both the symptoms of the eating disorder and the problems in familial relationships that may be contributing to the maintenance of these disorders [II]. Group psychotherapy is sometimes used as an adjunctive treatment for anorexia nervosa, but caution must be taken that patients do not compete to be the thinnest or sickest patient or become excessively demoralized through bearing witness to the difficult, ongoing struggles of other patients in the group. c. Medications: Psychotropic medications should not be used as the sole or primary treatment for anorexia nervosa [I]. The role for antidepressants is usually best assessed following weight gain, when the psychological effects of malnutrition are resolving. These medications should be considered for the prevention of relapse among weight-restored patients or to treat associated features of anorexia nervosa, such as depression or obsessive-compulsive problems [II]. 4. Choice of specific treatments for bulimia nervosa: a. Nutritional rehabilitation/counseling: Nutritional counseling as an adjunct to other treatment modalities may be useful for reducing behaviors related to the eating disorder, minimizing food restriction, increasing the variety of foods eaten, and encouraging healthy but not excessive exercise patterns [I]. b. Psychosocial interventions: Psychosocial interventions should be chosen on the basis of a comprehensive evaluation of the individual patient, considering cognitive and psychological development, psychodynamic issues, cognitive style, comorbid psychopathology, patient preferences, and family situation [I]. Cognitive behavioral psychotherapy is the psychosocial treatment for which the most evidence for efficacy currently exists, but controlled trials have also shown interpersonal psychotherapy to be very useful. Behavioral techniques (e.g., planned meals, self-monitoring) may also be helpful. Clinical reports have indicated that psychodynamic and psychoanalytic approaches in individual or group format may be useful once bingeing and purging are improving. Patients with concurrent anorexia nervosa or severe personality disorders may benefit from extended psychotherapy. Family therapy should be considered whenever possible, especially for adolescents still living with parents or older patients with ongoing conflicted interactions with parents [II]

Impact of nitrogen seeding on confinement and power load control of a high-triangularity JET ELMy H-mode plasma with a metal wall

This paper reports the impact on confinement and power load of the high-shape 2.5MA ELMy H-mode scenario at JET of a change from an all carbon plasma facing components to an all metal wall. In preparation to this change, systematic studies of power load reduction and impact on confinement as a result of fuelling in combination with nitrogen seeding were carried out in JET-C and are compared to their counterpart in JET with a metallic wall. An unexpected and significant change is reported on the decrease of the pedestal confinement but is partially recovered with the injection of nitrogen.Comment: 30 pages, 16 figure