Examining the Vitamin D Status of Children With Solid Tumors.

Objective: Our aims were to compare the vitamin D status of children with and without cancer and to examine the possible correlation between vitamin D levels in children with cancer before initiating treatment and prognosis. Method: We compared the data of 173 children with cancer with those of 569 children without cancer. Results: We measured a significant difference (p = 1.34E-08) between the vitamin D levels of children with cancer before treatment and children without cancer. There was a significant correlation between the initial vitamin D levels of children with cancer and the prognosis (p = 0.016, odds ratio = 51.33) at 5% significance. Conclusions: The average vitamin D level was 19.76% lower in the population with cancer compared with the average of the control group, and we found a correlation between the lower vitamin D levels in children with cancer and the adverse prognosis. We suggest that supplying vitamin D is reasonable and a prospective study of vitamin D in pediatric patients with cancer is recommended

Szomatosztatin receptor, mint lehetséges differenciál diagnosztikai, prognosztikai és terápiás faktor a gyermekkori medulloblastomák esetében = Somatostatin receptor Acts as a Potential Differential Diagnostic, Prognostic and Therapeutic Factor in Patients Treated with Medulloblastoma

A gyermekkori agytumorok terápiás eredményei nem kielégítőek. Célunk a medulloblastoma sejtjein kimutatott somatostatin receptorok (SSTR2) expressiojának vizsgálata volt; diagnosztikai-, prognosztikai és terápiás alkalmazhatóságának tanulmányozása. Az általunk vizsgált 21 medulloblastomában a SSTR2 kimutatható volt és recidivában nem változott. Az SSTR2 receptort Octreoscan vizsgálattal mutattuk ki, mely medulloblastomán kívül más agytumoros betegek egy részében is pozitiv volt (56 vizsgálat), tehát nincs differenciáldiagnosztikai jelentősége. Az Octreoscan vizsgálat az MRI nagyobb felbontóképessége ellenére hasznosnak bizonyult a medulloblastoma recidivának korai diagnosztikájában, mivel néhány MRI-vel negatív esetben is mutatott ki tumorszövetet. Szövettenyészetben az octreotid antipoliferativ, mitózisgátló hatással bír 40 ?m-nál nagyobb dózisban; apoptoticus hatása nincsen. Az octreotid vincristinnel, cisplatinnal és etoposiddal nem mutatott synergismust. Medulloblastoma xenograftban az octreotid magasabb dózisa gátolta a xenograft növekedését, de hatása a kezelés után egy héttel megszűnt. Mellékhatást nem észleltünk. Új terápiás eljárást dolgoztunk ki medulloblastomás betegek kezelésére, mellyel a 2 éves követési idő után (28 beteg) az eredmények, mind az előző, mind az átlagos nemzetközi eredményekhez képest jelentősen javultak (össztúlélés 82%); a jó prognozisú csoportban eddig egy betegnél észleltünk recidivát. | The present results of the therapy in paediatric brain tumors are unfavorable. Our aim was the study of the somatostatin receptors in medulloblastoma; the examination of its diagnostic-, prognostic- and antitumor effect. The somatostatin receptor (SSTR2) was shown by octreotid scintigraphy in 21 children with medulloblastoma, however, it was positive in some other brain tumors too. Hence it has no differencial diagnostic value. Instead of the greater sensitivity of MRI the application of Octreoscan my be useful in the early detection of a relapse in medulloblastoma, because in some MRI negativ cases it detected tumor tissue. The somatostatin in a higher dose, than 40 ?g had antiproliferativ effect in tissue culture and showed no synergetic effect with vincristin, cisplatin and etoposid. In xenograft the higher dose of octreotid showed antitumor effect, which lasted one week long after the end of treatmen. No side effect was seen. We set up a new treatment protocol for the patients with medulloblastoma. After 2 years long follow up (28 patients) the results are significantly better (OS 82%), than our previous or the international data: only one patient relapsed in the group of low risk patients

Academia Europaea Position Paper on Translational Medicine: The Cycle Model for Translating Scientific Results into Community Benefits

Translational science has gained prominence in medicine, but there is still much work to be done before scientific results are used optimally and incorporated into everyday health practice. As the main focus is still on generating new scientific data with financial resources primarily available for that purpose, other activities that are necessary in the transition from research to community benefit are considered less needy. The European Statistical Office of the European Commission has recently reported that 1.7 million people under 75 years of age died in Europe in 2016, with around 1.2 million of those deaths being avoidable through effective primary prevention and public health intervention. Therefore, Academia Europaea, one of the five Pan-European networks that form SAPEA (Science Advice for Policy by European Academies), a key element of the European Commission's Scientific Advice Mechanism (SAM), has launched a project to develop a model to facilitate and accelerate the utilisation of scientific knowledge for public and community benefit.During the process, leaders in the field, including prominent basic and clinical researchers, editors-in-chief of high-impact journals publishing translational research articles, translational medicine (TM) centre leaders, media representatives, academics and university leaders, developed the TM cycle, a new model that we believe could significantly advance the development of TM.This model focuses equally on the acquisition of new scientific results healthcare, understandable and digestible summation of results, and their communication to all participants. We have also renewed the definition in TM, identified challenges and recommended solutions.The authors, including senior officers of Academia Europaea, produced this document to serve as a basis for revising thinking on TM with the end result of enabling more efficient and cost-effective healthcare

Menthol can be safely applied to improve thermal perception during physical exercise : a meta-analysis of randomized controlled trials

Menthol is often used as a cold-mimicking substance to allegedly enhance performance during physical activity, however menthol-induced activation of cold-defence responses during exercise can intensify heat accumulation in the body. This meta-analysis aimed at studying the effects of menthol on thermal perception and thermophysiological homeostasis during exercise. PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched until May 2020. Menthol caused cooler thermal sensation by weighted mean difference (WMD) of - 1.65 (95% CI, - 2.96 to - 0.33) and tended to improve thermal comfort (WMD = 1.42; 95% CI, - 0.13 to 2.96) during physical exercise. However, there was no meaningful difference in sweat production (WMD = - 24.10 ml; 95% CI, - 139.59 to 91.39 ml), deep body temperature (WMD = 0.02 °C; 95% CI, - 0.11 to 0.15 °C), and heart rate (WMD = 2.67 bpm; 95% CI - 0.74 to 6.09 bpm) between the treatment groups. Menthol improved the performance time in certain subgroups, which are discussed. Our findings suggest that different factors, viz., external application, warmer environment, and higher body mass index can improve menthol's effects on endurance performance, however menthol does not compromise warmth-defence responses during exercise, thus it can be safely applied by athletes from the thermoregulation point of view

Az energetika biotelemetriás vizsgálata TRPV génhiányos és vad típusú egérben: testhőmérsékleti és aktivitási ritmusok változásai különböző tápláltsági és stressz állapotokban = Biotelemetric studies of energetics in TRPV knockout and wild type mice: modifications body temperature and activity rhythms under different feeding and stress situations

C57/BL egerek maghőmérsékletét és lokomotor aktivitását vizsgáltuk biotelemetriás módszerrel különböző környezeti hőmérsékleten. Normális és zsírdús táplálás hatásait követtük a napszaki hullámzásokra táplálás, több napos teljes éheztetés és újratáplálás ideje alatt, valamint ismételt laparotomiás beavatkozást követően is. Mindezen változások energetikai hátterének megismerése céljából releváns mediátorok, gátló anyagok centrális vagy perifériás infúzióját végeztük ALZET minipumpa segítségével. Szabadon mozgó egerek napszaki hőmérsékleti és aktivitási hullámzásának nagysága fokozódik teljes éhezés során és a maghőmérséklet 30 °C-ra való csökkenése jelzi a túlélhető éhezés végét az aktivitás fokozódása mellett. Újratápláláskor, hidegben, elhízásban, CNTF infúzió alatt és laparotomia után csökken a hullámzások amplitúdója. CNTF és CCK-8 icv infúziója lázat vált ki. Eredményeink több új információval szolgáltak a szabadon mozgó egerek normális és kóros energetikájának mechanizmusáról. | Changes of core temperature and locomotor activity were monitored in C57/BL mice under different thermal conditions by using a biotelemetric method. Effects of normal or fat-rich diet were observed on daily oscillatons during feeding, total fasting, re-feeding or on repeated laparotomy. To learn the energetic background of all these stimuli relevant meditors or blocker were infused either centrally or peripherally by using ALZET minipumps. Excursions of daily changes in core temperature and activity were found to be increased during total fasting with core temperature falling to about 30 °C as a sign of threshold of survivability with locomotor activity increasing progressively. Re-feeding, cold exposure, obesity, CNTF infusion or laparotomy led to reversible decreases of daily oscillations. Icv infusion of CNTF or CCK-8 induced fever. Our results furnished new information on the mechanisms of changes in energetics observed under normal and various types of pathological conditions in freely moving mice

Maternal overnutrition impairs offspring's insulin sensitivity: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's insulin sensitivity-following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies published in English before April 22, 2019, were identified through searches of four medical databases. After selection, 15 studies aiming to explore the association between prepregnancy body mass index (ppBMI) or gestational weight gain (GWG) of non-diabetic mothers and their offspring's insulin sensitivity (fasting insulin or glucose level and Homeostatic Measurement Assessment for Insulin Resistance [HOMA-IR]) were included in the meta-analysis. Associations of ppBMI and GWG with offspring's insulin sensitivity were analysed by pooling regression coefficients or standardized differences in means with 95% confidence intervals (CIs). Maternal ppBMI showed significant positive correlations with the level of both fasting insulin and HOMA-IR in offspring (standardized regression coefficient for fasting insulin: 0.107, CI [0.053, 0.160], p < 0.001 and that for HOMA-IR: 0.063, CI [0.006, 0.121], p = 0.031). However, the result of the analysis on coefficients adjusted for offspring's actual anthropometry (BMI and adiposity) was not significant. Independent from ppBMI, GWG tended to show a positive correlation with insulin level, but not after adjustment for offspring's anthropometry. Offspring of mothers with excessive GWG showed significantly higher HOMA-IR than those of mothers with optimal GWG (p = 0.004). Our results demonstrate that both higher ppBMI and GWG increase the risk of offspring's insulin resistance, but the effect of ppBMI on insulin sensitivity in offspring may develop as consequence of their adiposity

Probiotics have beneficial metabolic effects in patients with type 2 diabetes mellitus : a meta-analysis of randomized clinical trials

Probiotics have been reported to have a positive impact on the metabolic control of patients with type 2 diabetes. We aimed to systematically evaluate the effects of probiotics on cardiometabolic parameters in type 2 diabetes based on randomized controlled studies. MEDLINE, Embase, and CENTRAL databases were reviewed to search for randomized controlled trials that examined the effects of probiotic supplementation on cardiometabolic parameters in patients with type 2 diabetes. 32 trials provided results suitable to be included in the analysis. The effects of probiotics were calculated for the following parameters: BMI, total cholesterol levels, LDL, triglycerides, HDL, CRP, HbA1c levels, fasting plasma glucose, fasting insulin levels, systolic and diastolic blood pressure values. Data analysis showed a significant effect of probiotics on reducing total cholesterol, triglyceride levels, CRP, HbA1c, fasting plasma glucose, fasting insulin levels, and both systolic and diastolic blood pressure values. Supplementation with probiotics increased HDL levels however did not have a significant effect on BMI or LDL levels. Our data clearly suggest that probiotics could be a supplementary therapeutic approach in type 2 diabetes mellitus patients to improve dyslipidemia and to promote better metabolic control. According to our analysis, probiotic supplementation is beneficial in type 2 diabetes mellitus

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation - by protons - is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and - via the acido-antithermogenic and acido-antivasoconstrictor reflexes - modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist's potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed