The professionals with less experience presented an improvement <

The professionals with less experience presented an improvement selleck Tipifarnib in the time between the two evaluations, probably due to the interest in and study of the classification, since they knew that they would be assessed for understanding of the topic again. The matter of length of studies can explain the greater agreement of the orthopedic R3 group and orthopedists specialized in feet, since the latter are familiar with the topic and come across it more frequently, and the former due to the studying necessary to acquire the title of specialist. There were some decrease of agreement levels in the second evaluation, in the radiology R2 and R3 groups, orthopedic R2 group and orthopedists. Such an occurrence signifies deterioration in the groups in the subject studied, but may mean evolution of observers inside the group, causing different grades due to study of the classification.

It would be a minor disagreement, which is believed to occur due to knowledge obtained in the interval between evaluations by only part of the observers from each group. Such a bias could be controlled by not informing the study participants of the existence of a second evaluation, which perhaps would not induce study geared towards the subject of many of the observers. Since a classification serves as a prognosis and treatment guideline, it is extremely necessary for there to be agreement among its users. According to the data encountered, we concluded that Hawkins’ classification has achieved goals, facilitating understanding of the case, treatment guidelines, prognosis of the injury and discussions, as it presents satisfactory agreement among its observers.

CONCLUSIONS In the majority of the groups the agreement of Hawkins’ classification can be considered substantial, ranging between 0.6 and 0.8. It is only among the third-year orthopedic residents in the second evaluation that agreement can be considered perfect (0.836). Such a fact can be correlated with the studies undertaken by these residents prior to the examination to achieve the title of orthopedist. However, this contradicts the agreement among orthopedic graduates, whose values were between 0.471 and 0.909, whereas high values are to be expected in both evaluations. The result showed substantial agreement in general in the first and second evaluations, averaging 0.627 and 0.668 respectively.

The data indicate a certain Cilengitide reliability of the classification, but that may vary a great deal according to the evaluator’s experience, confirmed by the greater agreement, in general, pursuant to the years of activity in the area and studies undertaken. Acknowledgments To the direct and indirect participants of this study who made its performance possible. Footnotes All the authors declare that there is no potential conflict of interest referring to this article. Study conducted at the Department of Orthopedics and Traumatology of Universidade Estadual de Campinas, SP.

An official agreement is signed between the investigator and comp

An official agreement is signed between the investigator and company and s/he may receive milestone payments. The investigator www.selleckchem.com/products/Erlotinib-Hydrochloride.html is expected to take the study all the way to publication (the researcher is not mandated to share the manuscript with the company) and update CTRI accordingly. In such studies there is no indemnification of the investigator or insurance of the patient by the company. The company only funds the investigator. All other liability rests with the investigator as outlined in the agreement. The investigator is expected to follow the law of the land (e.g., inclusion of the compensation clause in the informed consent form). In case a patent or data exclusivity may arise out of data generated from the study, the investigator has the right to decide whether s/he wishes to share the same with the company.

Some companies have an agreement with the investigator on co-sharing of patent holder rights. Similarly, the data may be submitted to the regulator in support of a new indication for a product. In such cases it is a different agreement (as with the patent case) and now the company does share liability and may decide to monitor such a study. Such IITs do serve to add to the body of generalizable evidence and advance medical science. It need not have anything to do with the company or its products or therapeutic area. Of course IITs can also be funded by non-industry, academic bodies or the government. There is always skepticism if industry funds any research though even in industry-sponsored studies, ultimately it is the investigators?? study as the data is of their patients, they have full access to the raw data, they review and approve the study report and publication.

So whose study is it anyway? One example of a large IIT is the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT). A good idea would be to simply fund an academic body Anacetrapib such as the European Association for Study in Diabetes (EASD) which writes and updates guidelines. If one reads guidelines one does come across areas where research is needed to answer hypotheses. Such research can be funded by industry although it may have nothing to do with their products. Thus one has more of evidence-based medicine and less of opinion- or eminence-based medicine. Industry (I) could come together with Academia (A) and set up an Institute of Real World Research (R) which can fund such IITs thus also clearing the AIR of misperceptions and increasing transparency.

Competitors could collaborate with each other and facilitate practical or pragmatic clinical trials and comparative effectiveness research. selleck compound It is not that one drug is better than another. The real issue is no longer the choice of the ??best?? agent, but rather the identification, on a rational basis, of the population of patients who will benefit from a given agent the most.[2] In practice when a doctor sees every patient s/he is in effect doing a clinical trial.

This is the first large-scale, multicenter, systematic effort to

This is the first large-scale, multicenter, systematic effort to use standardized instruments to identify and uniformly evaluate individuals with the site dominantly inherited AD. The DIAN aims to determine the chronological changes in cognition and biomarkers in relation to clinical onset and progression of dementia in a well-characterized and uniformly studied group of persons at risk for ADAD. The DIAN investigators will assess and quantify the ability of clinical, biological and imaging markers to predict and track the progression of AD. The DIAN’s overriding purpose is to contribute to the search for meaningful therapies for AD by helping elucidate the cascade of events that lead to dementia of the Alzheimer’s type. The specific aims for the DIAN include the following.

First, to establish an international registry of individuals (mutation carriers and noncarriers; presymptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes in which the individuals are evaluated in a uniform manner at entry and longitudinally thereafter. The second aim is to obtain clinical and cognitive batteries that comprise the Uniform Data Set of the National Institutes of Health-funded Alzheimer’s Disease Centers, supplemented by web-based neuropsychological tests. A further aim is to implement structural, functional, and amyloid imaging protocols (3T MRI, fluorodeoxyglucose-PET, PiB-PET).

The fourth aim is to collect biological fluids, including blood and CSF, for DNA analysis and assays of putative biomarkers of AD, including A??42 and tau – this will also provide a resource for exploratory studies of novel biochemical markers. Finally, the DIAN aims to perform uniform AV-951 histopathological examination of cerebral tissue in individuals who come to autopsy. The National Institute on Aging awarded a 6-year grant for the DIAN that funds 10 international performance sites that combine resources and research participants of the individual sites in a uniform and comprehensive manner. Currently, over 400 individuals who are members of families with a known causative mutation for AD (that is, APP, PSEN1, PSEN2) have been identified between the sites and are eligible for participation in the DIAN. Over the first 6 years, sites will recruit, enroll and evaluate these individuals to reach a sample size of 400 participants.

The DIAN cohort download catalog is predicted to comprise 80% asymptomatic individuals (with 50% of these being mutation carriers and 50% noncarriers) and 20% symptomatic individuals. Based on the participant population demographics, the DIAN is expected to enroll 50% of individuals within 3 years of parental age at disease onset, and 30% of individuals within 3 to 10 years before parental age at disease onset.

4 In chronic cases in

4 In chronic cases in selleck chem EPZ-5676 which the distal stump of the biceps tendon cannot be mobilized up to the radial tuberosity, various reconstruction methods were described including the use of fascia lata, semitendinosus tendon, palmaris longus tendon, calcaneal tendon and tendons of the flexor carpi radialis. CONCLUSION The method presents good results as do the other techniques, yet it reduces the risk of adhesion on the flexor fold of the elbow. Footnotes Study conducted at Hospital IFOR, S?o Bernardo do Campo, SP, Brazil. Citation: Pascarelli L, Righi LCS, Bongiovanni RR, Imoto RS, Teodoro RL, Ferro HFA. Technique and results after distal braquial biceps tendon reparation, through two anterior mini-incisions. Acta Ortop Bras. [online]. 2013;21(2):76-9. Available from URL: http://www.scielo.br/aob.

There are few methods for the treatment of spinal cord lesions, and no really effective treatment is available. 1 Surgical treatment for mechanical stabilization and decompression may be performed in cases of unstable fractures with spinal cord lesion, and the use of drugs for the treatment of spinal injuries has been extensively studied. Experiments with the use of chemicals are conducted mostly with the aim of promoting nerve regeneration, and in an attempt to inactivate or reduce the secondary cascade of events that follows spinal injuries. However, only two of these drugs are already used clinically: monosialoganglioside (GM1) and methylprednisolone, 2 although there is no consensus as to the benefits of their indication.

3 GM1 is an antineurotoxic, anti-inflammatory, neuroprotector agent, essential in neuronal excitability of myelinated and unmyelinated fibers. It also promotes neuronal development, growth, differentiation and maturation, and reduces the intensity of Walerian degeneration. 4 Many researchers also advocate the use of physical means in the treatment of spinal injuries in an attempt to obtain better results. Hypothermia is one such alternative; it reduces post-traumatic metabolism and energy consumption, decreasing the intensity of secondary lesions, hypoxia and ischemia, as well as apoptosis of neurons and glial cells. 5 – 7 A new type of laser used for drug administration was recently developed in Italy (Laser Ice Med). It allows transcutaneous penetration of particles mixed in a gel at low temperature, by means of 635nm, 50mW parallel beams.

Santos et al. presented, at the European Congress of Neuroscience, their research on the effects of laser with GM1 in trauma associated with cord and peripheral nerve injury in Wistar rats. GM1, administered daily by the transdermal route for 60 days, resulted in regeneration superior to that of the control group, in the Dacomitinib histological and functional evaluations of the sciatic nerves and spinal cords. 8 The results of each GM1 and “laser ice” therapies are, however, still not satisfactory, which prompted us to study a possible synergy between them.

Normalization of glucose levels in patients with diabetes should

Normalization of glucose levels in patients with diabetes should lead to improvement in hypertriglyceridemia. Conclusions The diagnosis sellckchem of PCOS implies increased cardiac risk. Weight loss and proper nutrition are paramount to decreasing this risk. Approximately half of these patients will be insulinresistant, and treatment may have far-reaching potential by decreasing their lifetime risk of type 2 diabetes. If the patient is planning to conceive, treatment of dyslipidemia with statins is not recommended until childbearing is completed. Ultimately, longstanding oligomenorrhea may lead to endometrial hyperplasia and, possibly, to endometrial adenocarcinoma, and thus OCPs are protective and a key recommendation. Future studies are warranted to establish cardiovascular screening guidelines for women with PCOS.

Clinicians may consider early cardiovascular screening and treatment of all modifiable cardiovascular risk factors to secondary prevention levels. Main Points Polycystic ovary syndrome (PCOS) is a symptom complex that includes amenorrhea, hirsutism, and enlarged polycystic ovaries. The incidence of impaired glucose tolerance, type 2 diabetes mellitus, obesity, hypertension, and dyslipidemia, as well as of coronary and vascular disease, may be higher in women with PCOS during their reproductive years than in patients with the cardiometabolic syndrome. In a recent study of women with PCOS, 46% also had the metabolic syndrome. Studies using noninvasive vascular assessment of atherosclerotic plaque, such as coronary calcium and carotid intimal medial thickness assessments, have confirmed a greater prevalence of cardiovascular disease in PCOS patients relative to the general population.

PCOS patients have been found to have a higher prevalence of aortic calcification, a marker of atherosclerotic disease. Weight loss and proper nutrition are paramount to decreasing the increased cardiac risk associated with PCOS.
Health outcomes differ substantially for mothers and infants who formula feed compared with those who breastfeed, even in developed countries such as the United States. A recent meta-analysis by the Agency for Healthcare Research and Quality reviewed this evidence in detail1: For infants, not being breastfed is associated with an increased incidence of infectious morbidity, including otitis media, gastroenteritis, and pneumonia, as well as elevated risks of childhood obesity, type 1 and type 2 diabetes, leukemia, and sudden infant death syndrome (SIDS).

Among premature infants, not receiving breast milk is associated with an increased risk of necrotizing Anacetrapib enterocolitis (NEC). For mothers, failure to breastfeed is associated with an increased incidence of premenopausal breast cancer, ovarian cancer, retained gestational weight gain, type 2 diabetes, and the metabolic syndrome. These findings suggest that infant feeding is an important modifiable risk factor for disease for both mothers and infants.

05) Fifteen days after bleaching, the ��E values were very simil

05). Fifteen days after bleaching, the ��E values were very similar in comparison with the postbleaching values, without statistically significant differences among the materials, in comparison with the previous treatment (P>.05). Table 2. Means (standard deviation) of ��E of aged samples (2-way ANOVA, Bonferroni, P<.05). Surface roughness The results after AAA (Table 3) indicated that there was no selleck chem statistically significant difference (P>.05) in roughness for any of the tested materials. When the materials were compared among them, there was statistically significant difference (P<.05) only for Heliomolar. After bleaching, Filtek Supreme and Heliomolar presented an increase in surface roughness values, with statistically significant difference (P>.05) in comparison to the post AAA values.

Fifteen days after bleaching, there was not statistically significant difference (P>.05) in comparison with the post bleaching situation. Table 3. Means (standard deviation) of surface roughness (Ra) of aged samples (2-way ANOVA, Bonferroni, P<.05). Microhardness As regards the microhardness values (Table 4), a large increase was verified after AAA, results differing statistically from the initial values (P<.05). After bleaching, there was an increase in the microhardness of Heliomolar (P<.05). For the other composites, there was a decrease, with statistically significant results (P>.05). After 15 days, there were no significant alterations (P>.05). Table 4. Means (standard deviation) of microhardness (KHN) of aged samples (2-way ANOVA, Bonferroni, P<.05).

DISCUSSION There is a consensus among researchers that direct composite resin restorations undergo color alteration with the passage of time,21�C28 and that one of the greatest challenges in modern dentistry is to find a material that has a color stability similar to that of the dental structure; and that this stability can be maintained in the oral environment as the years pass.29�C30 As regards the color stability, this study tested the hypothesis that the bleaching agent would promote bleaching of the studied composites. The results demonstrated that the color of composites could be significantly altered by AAA31 and bleaching, and this alteration is material dependent, results that are similar to other studies.7,32 This susceptibility to color alteration can be attributed to the composition of the resin matrix and the type and volume of load particles of the composite.

7 When bleached, the aged specimens did not presented significant alteration for ��E (P>.05), with the exception of the Cilengitide composite Charisma, and the same behavior was maintained 15 days after bleaching. This fact demonstrated that the action of the bleaching agent was more effective on the aged specimens, allowing one to agree with the tested hypothesis. After being bleached, the specimens remained without significant color alteration (P>.05). This may have occurred due to the stability of bleaching agents and their prolonged action.

The finding that one in five patients maintained an Hb concentrat

The finding that one in five patients maintained an Hb concentration in the range 11-12g/dL at months 7, 8, and 9 was consistent with the results of observational studies of C.E.R.A. therapy in patients receiving hemodialysis [37] or peritoneal dialysis [38]. These have reported Hb levels within selleck screening library the 11-12g/dL window at all three evaluation visits in 15.6% and 18.4% of patients, respectively. These findings should be interpreted against the background of a naturally high degree of Hb variability in patients with CKD [39, 40]. Indeed, it has been shown that the mean within-patient variability is greater than 1g/dL in CKD patients receiving ESA therapy [40, 41].

Comparisons of Hb stability between the current results and randomized trials of ESA therapies are not clinically relevant since this observational study applied no exclusion criteria for Hb cycling prior to inclusion, in contrast to controlled trials which have typically excluded patients with Hb fluctuation > 1g/dL during screening [34, 42�C44]. One previous study, AnemiaTrans, has examined the use of C.E.R.A. in kidney transplant recipients [45]. AnemiaTrans was a retrospective, multicenter study which included both de novo patients (n = 32) and maintenance patients (n = 286). As in the current study, the majority of maintenance patients were converted from another ESA therapy to C.E.R.A. Hb levels were monitored for six months from the time of conversion, and consistent with our results, the proportion of patients within the target Hb range of 11�C13g/dL was similar at baseline and at month 6.

In the majority of converted patients (52.5%), Hb level fluctuated by less than 1g/dL between baseline and month 6. The mean C.E.R.A. dose at month 6 (93��g) was remarkably similar to that used in our population (95.1��g). The findings of AnemiaTrans, although retrospective, support those of the present study. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the care of kidney transplant recipients recommend that anemia in kidney transplant patients should be monitored and treated in the same way as patients with CKD [46]. Regular monitoring of Hb levels is mandatory for all recipients [46], but certain subpopulations are at particular risk of anemia.

As in the nontransplant population, poor renal function is the strongest predictor [1, 4, 6], but low iron stores [1, 4, 6], probably female gender [4, 6, 47], increasing recipient age [4, 6, 33], donor age [1], poor nutrition, and chronic inflammation [48] also appear to contribute, exacerbated by frequent use of renin-angiotensin-aldosterone Drug_discovery system inhibitors [3, 46]. The risk of anemia following transplantation is compounded by immunosuppression with mTOR inhibitors [46, 49�C51] or mycophenolic acid [46, 52, 53], although this effect is less marked in the presence of higher GFR [54].

According to our estimation, for a patient with dialysis time of

According to our estimation, for a patient with dialysis time of approximately 4.1 years, the initial values of uNGAL (3�C6h after transplantation) are about 242ng/mL higher in patients who went on to develop DGF, and these values will rise even more in the following days. A significant interaction between time of measurement and DGF confirmed that longitudinal changes of uNGAL levels depend on whether the recipient had DGF or not. To clarify the meaning of this interaction, Figure 2 shows the predicted uNGAL trajectories over time for four hypothetical subjects: two recipients who developed DGF (one with 4years of dialysis and one with 10years), and two other patients with prompt graft function (similar time on dialysis, 4 and 10years). Hypothetically, the remaining variables were equal in all four patients. The predicted uNGAL values were estimated using the coefficients estimates of Table 3 (e.g., the predicted uNGAL values at the first day for a recipient with 4 years of dialysis with prompt function = exp [(5.46 ? 2.14) + 0.94 + 0.4 + (0.076 4 years of dialysis)] = 158ng/mL). Figure 2 Predicted uNGAL values over time of four hypothetical subjects, estimated from multiple linear mixed model presented in Table 3. Abbreviations: uNGAL: urinary neutrophil gelatinase associated lipocalin; DGF: delayed graft function; non-DGF: prompt graft … Table 3 Results of the final linear mixed model for dependent variable ln(uNGAL) (n = 171 observations derived from 40 patients). 3.3. Prediction of DGF by uNGAL Levels (ROC analysis) Receiver-operating characteristic (ROC) curves showed uNGAL on the first postoperative days were accurate in predicting DGF (Tables (Tables44 and and5).5). Table 4 displays the derived sensitivities, specificities, and predictive values for uNGAL at the cutoff concentrations that provided the maximum sum of sensitivity and specificity. Regarding the areas under the ROC curves (AUC), the ability of uNGAL to predict DGF was moderately accurate at baseline and first day, and highly accurate at second, fourth, and seventh days (Table 5, Figure 3). In the first two posttransplant days the diagnostic performance of uNGAL was better than of serum creatinine, and quite similar to that of cystatin C. The reduction in serum creatinine between first and second days resulted in AUC = 0.78 [0.64�C0.92] and was worse than uNGAL for DGF prediction. Figure 3 Receiver-operating characteristic curves for uNGAL, serum creatinine and changes in serum creatinine, and serum cystatin C measured at posttransplant days 1 and 2 for predicting delayed graft function. Abbreviations: uNGAL: urinary neutrophil gelatinase … Table 4 Sensitivity, specificity, and predictive values for DGF using specific uNGAL cut-off values. Table 5 Area under the receiver-operating characteristic curve at each time point for uNGAL, serum creatinine, and serum cystatin C for predicting DGF. 3.4.

Animals

Animals www.selleckchem.com/products/azd9291.html Healthy male Wistar strain albino rats, weighting between 140 and 160 g were used for this study. Rats were housed in our well ventilated animal house having six animals in polypropylene made cages and maintained standard condition with controlled temperature (25 �� 3��C), relative humidity (45 �� 5��C) and 12:12 h dark:light cycle. The animals were fed with standard laboratory diet and allowed to drinking water ad libitum. Experiments were conducted following the guidelines of our Institutional Animal Ethics Committee (IAEC). Chemicals STZ was purchased from Sigma, USA. Other chemicals like adenosine tri phosphate (ATP), nucleotide adenine dinucleotide phosphate (NADP), 2-[4-(2-Hydroxyethyl) 1-piperazinyl] ethanesulfonic acid (HEPES), were purchased from Sigma-Aldrich Diagnostic Ltd.

or Sisco Research Laboratory (SRL), India. Kits for the assessment of serum lipid profile level and glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) activities were purchased from Span Diagnostic Ltd. Surat, India. Induction of diabetes Rats were made diabetic by a single intramuscular injection of streptozotocin (STZ) at the dose of 40 mg/kg body weight in 0.1 M citrate buffer (pH 4.5).[3,14] Diabetic state was confirmed on seventh day of STZ injection considering the measurement of FBG as relevant biomarker. Animals with FBG level more than 300 mg/dL were selected for this experiment. Homeopathic remedy The homeopathic remedy S jambolanum (��), was purchased from ��Hahnemann Publishing Company (Hapco)��, 165, Bepin Behari Ganguly Street, Kolkata, India.

From this 1 ml of mother tincture of S jambolanum was finally diluted with 20 ml of double distilled water to make the stock solution. Each rat were fed 1 drop (0.06 ml) of S jambolanum twice a day from the stock solution using gavage. The drug feeding was made before food delivery in subsequent days till they were sacrificed for analysis. Experimental design To fulfil the aims of this study, animals were divided into four groups and each groups comprising of 6 rats. Group wise animal distribution was as follows: Untreated control Animals of this group were treated with 0.6 ml of diluted ethanol (vehicle) for 40 days at the time of mother tincture treatment to diabetic animals. Diabetic control Animals of this group were given vehicle solution for 40 days at the same time.

Diabetic + S jambolanum Animals of this group were treated Dacomitinib with 0.06 ml of mother tincture of S jambolanum for 40 days. The duration of the experiment was 40 days. On forty-first day, all the animals were sacrificed by decapitation. Blood was collected from dorsal aorta by a syringe, the serum was separated by centrifugation at 3000 g for 10 mins for the measurements of serum lipid profile level and activities of GOT and GPT in serum.

[3,4] APPLICATIONS OF CURCUMIN Therapeutic applications of turmer

[3,4] APPLICATIONS OF CURCUMIN Therapeutic applications of turmeric The active constituent of turmeric selleckbio is known as curcumin, which has been shown to have a wide range of therapeutic effects.[5] Antioxidant Curcumin protects against free radical damage because it is a strong antioxidant.[6] Water- and fat-soluble extracts of turmeric and its curcumin component exhibit strong antioxidant activity, comparable to that of vitamins C and E.[7] An in vitro study measuring the effect of curcumin on endothelial heme oxygenase-1, an inducible stress protein, was conducted utilizing bovine aortic endothelial cells. Incubation (for 18 hours) with curcumin resulted in enhanced cellular resistance to oxidative damage.[8] Anti-inflammatory It reduces inflammation by lowering histamine levels and possibly by increasing the production of natural cortisone by the adrenal glands.

[9] Oral administration of curcumin in instances of acute inflammation was found to be as effective as cortisone or phenylbutazone, and half as effective in cases of chronic inflammation.[10] Its anti-inflammatory properties may be attributed to its ability to inhibit both biosyntheis of inflammatory prostaglandins from arachidonic acid and neutrophil function during inflammatory states.[10] Hepatoprotective It protects the liver from a number of toxic compounds such as carbon tetrachloride (CCl4),[11,12] galactosamine,[13] acetaminophen (paracetamol),[14] and Aspergillus aflatoxin.[15] Turmeric’s hepatoprotective effect is mainly a result of its antioxidant properties as well as its ability to decrease the formation of proinflammatory cytokines.

Sodium curcuminate, a salt of curcumin, also exerts choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin as well as by increasing bile solubility, therefore, possibly preventing and treating cholelithiasis. Curcumin has choleretic activity that increases bile output and solubility, which may be helpful in treating gallstones.[16] Antiplatelet aggregation It has been shown to prevent platelets from clumping together, which in turn improves circulation.[17] Inhibition of platelet aggregation by curcumin constituents is thought to be via potentiation of prostacyclin synthesis and inhibition of thromboxane synthesis.[17] Antimutagenic Curcumin is antimutagenic as it potentially helps to prevent new cancers that are caused by chemotherapy or radiation therapy used to treat existing cancers.

It effectively inhibits metastasis (uncontrolled spread) of melanoma (skin cancer) cells and may be Drug_discovery especially useful in deactivating the carcinogens in cigarette smoke and chewing tobacco.[18,19] Animal studies involving rats and mice as well as in vitro studies utilizing human cell lines have demonstrated curcumin’s ability to inhibit carcinogenesis at three stages: Tumor promotion,[20] angiogenesis,[21] and tumor growth.