Immune checkpoint inhibitors in sarcomas: a systematic review.

Sarcomas are tumors that originate from mesenchymal cells. The variety of sarcomas' response to chemotherapy and the wide range of prognosis reflect their heterogeneity. In order to improve the rates of response, the research has been orientated toward other forms of therapy, such as targeted therapies and immunotherapy or toward combinations of them. Immune checkpoint inhibitors (ICIs) have been the highlight of immunotherapy in the last decade. Although ICIs are already included in the guidelines of different malignancies, their clinical benefit in sarcomas is still under study. Alveolar soft part sarcomas, undifferentiated pleomorphic sarcomas and other subtypes of sarcoma with high presence of tertiary lymphoid structures tend to respond to ICIs, but further investigation is still needed. Furthermore, the search of predictive biomarkers to determine the type of sarcomas that are sensitive to ICIs is still very challenging. This review will focus on the results of clinical trials, which examine the effect of ICIs and their combination with chemotherapy, targeted therapies and other forms of immunotherapy in sarcomas.

Effects of hunger state on the brain responses to food cues across the life span.

The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span.

Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol.

This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

Novel crystalline phase and first-order phase transitions of human insulin complexed with two distinct phenol derivatives.

The primary focus of the present work is the study of the effects that two ligands and the crystallization pH have on the crystalline forms of human insulin. For this purpose, human insulin (HI) was co-crystallized with two distinct phenolic derivatives: the organic ligands meta-cresol (m-cresol) and 4-nitrophenol. The formation of polycrystalline precipitates was then followed by means of structural characterization of the individual specimens in terms of unit-cell symmetry and parameters. In both cases, two different polymorphs were identified via X-ray powder diffraction measurements, the first of hexagonal symmetry (R3 space group) at higher pH values and the second of monoclinic symmetry (space group P21) with unit-cell parameters a = 87.4282 (5), b = 70.5020 (3), c = 48.3180 (4) Å, ß = 106.8958 (4)°, the latter of which to our knowledge has never been observed before.

Criterion validity of the Physical Activity Questionnaire for Schoolchildren (PAQ-S) in assessing physical activity levels: the Healthy Growth Study.

AIM: The aim of this paper was to evaluate the criterion validity of the Physical Activity Questionnaire for Schoolchildren (PAQ-S). METHODS: The current study is a subcohort of the Healthy Growth Study, a large-scale cross-sectional study. 202 schoolchildren aged 9-13 years from Greece completed the PAQ-S and wore an accelerometer for 4 consecutive days. Time spent moderate (MPA), moderate to vigorous (MVPA) and vigorous (VPA) physical activity was calculated based on PAQ-S and accelerometer data. RESULTS: The average time spent on MPA and MVPA as derived from PAQ-S and from accelerometers were significantly moderately correlated (r=0.462, P<0.001 and r=0.483, P<0.001, respectively). No significant correlation was detected between PAQ-S and accelerometer-measured time spent performing VPA (rho=0.150, P=0.057). Intraclass Correlation Coefficient (ICC) indicated a moderate agreement between PAQ-S and accelerometer in estimating MPA (ICC=0.592, P<0.001) and MVPA (ICC=0.581, P<0.001). Bland-Altman analysis revealed a small mean difference (the "bias"), between the two methods, in estimating MPA, although this difference was found to be significantly higher than zero ("bias"=27.4% of the accelerometer-measured mean score, P=0.006). On the other hand, Bland-Altman analysis revealed a large mean difference in estimating MVPA and VPA ("bias"=84.2% and 357% of the accelerometer-measured mean score for MVPA and VPA, respectively and P<0.001). The high correlation coefficient between the average and difference values between all physical activity scores derived from accelerometers and PAQ-S, indicate a systematic overestimation of physical activity time with increasing physical activity for PAQ-S. CONCLUSION: The validity of PAQ-S for the estimation of MPA and MVPA was found to be slightly similar self-reported measures for schoolchildren. Therefore, this questionnaire could be used as a tool for physical activity assessment in large population studies.

Immunohistochemical study of inhibin A and B expression in placentas from normal and pathological gestations.

OBJECTIVE: The aim of the study was to examine, by an immunohistochemical method, the distribution of Inhibin-A and -B, in placentas from normal and pathological gestations. MATERIALS AND METHODS: Sixty-two specimens of placental tissue were examined: i) ten cases from early gestations, ii) 28 cases from mature placentas, iii) six cases associated with intrauterine growth restriction, iv) four cases associated with diabetes mellitus and v) 14 placentas from gestations with fetal chromosome abnormalities. The expression of Inhibin A and B was studied by automatic Ventana method. RESULTS: i) Early gestation specimens: Inhibin A (+) immunoreaction was observed in the syncytiotrophoblast (8/10 cases) and in the intermediate trophoblast (6/10 cases). Inhibin B (+) immunoreaction was observed in the syncytiotrophoblast (10/10 cases) and in the intermediate trophoblast (4/10 cases), ii) Normal mature placentas: Inhibin A (+) immunostain was observed in 2/28 cases in the syncytiotrophoblast and in 7/28 cases in the intermediate trophoblast. Inhibin B (+) immunostain was observed in 28/28 cases in the syncytiotrophoblast and in 18/28 cases in the intermediate trophoblast. iii) Placentas associated with intrauterine growth restriction: Inhibin A (+) immunostain was observed in the intermediate trophoblast in 2/6 cases. Inhibin B (+) immunostain was observed in 5/6 cases in the syncytiotrophoblast and in 4/6 cases in the intermediate trophoblast. iv) Placentas associated with gestational diabetes mellitus: Inhibin A (+) immunostain was observed in 2/4 cases in the intermediate trophoblast. Inhibin B (+) immunostain was observed in 2/4 cases in the syncytiotrophoblast. v) Placentas from gestations with fetal chromosome abnormalities: no Inhibin A immunoreaction was observed. Inhibin B (+) immunostain was observed in 13/14 cases in the syncytiotrophoblast and in 9/14 cases in the intermediate trophoblast. The cytotrophoblast, the umbilical cord, and the membranes do not participate in the production of Inhibins. DISCUSSION: Inhibin A and B are located in the syncytiotrophoblast and the intermediate trophoblast of the placenta, during early pregnancy (Inhibin A) and present throughout pregnancy (Inhibin B). No remarkable findings in placentas of pathological gestations support the evidence that Inhibins do not participate in processes that affect the development of the placenta or the fetus, but may participate in,the mechanism of labor.

Epidermoid or dermoid cysts of the ovary? Clinicopathological characteristics of 28 cases and a new pathologic classification of an old entity.

OBJECTIVE: The aim of this study was to present the clinical and pathological findings that aid in the differential diagnosis between epidermoid and dermoid ovarian tumors. MATERIALS AND METHODS: This was a 15-year retrospective clinico-pathological study. A total of 28 cases of epidermoid ovarian cysts histologically confirmed after pathological examination at the Pathology Laboratory of Aretaieion University Hospital between January 1996 and December 2010, were analyzed and a literature review was performed. RESULTS: Patients with epidermoid cysts presented with a main complaint of either abdominal pain or a palpable abdominal mass. In the 28 cases studied, 18 patients underwent cystectomy and four cases underwent oophorectomy. In six cases of post-menopausal women, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. No recurrent disease in the pelvis was reported during the available follow-up period which was from 12 to 30 months. DISCUSSION: Epithelial epidermoid ovarian tumors represent less than one percent of ovarian surface epithelial tumors. The differential diagnosis of epidermoid cysts includes dermoid (mature cystic teratomas) tumors of the ovary. However, it should be mentioned that up to 17% of teratomas may include epidermoid tumors. In comparison to dermoid cysts which present at an earlier age but with a greater size, ovarian epidermoid tumors present as small- to medium-sized cystic lesions occurring at a significantly older age. The treatment of choice is conservative surgical therapy.

Dynamics of proteins: light scattering study of dilute and dense colloidal suspensions of eye lens homogenates.

We report a dynamic light scattering study on protein suspensions of bovine lens homogenates at conditions (pH and ionic strength) similar to the physiological ones. Light scattering data were collected at two temperatures, 20 and 37 degrees C, over a wide range of concentrations from the very dilute limit up to the dense regime approaching the physiological lens concentration. A comparison with experimental data from intact bovine lenses was advanced, revealing differences between dispersions and lenses at similar concentrations. In the dilute regime, two scattering entities were detected and identified with the long-time self-diffusion modes of alpha-crystallins and their aggregates, which naturally exist in lens nucleus. Upon increasing protein concentration, significant changes in time correlation function were observed starting at approximately 75 mg ml(-1), where a new mode originating from collective diffusive motions becomes visible. Self-diffusion coefficients are temperature insensitive, whereas the collective diffusion coefficient depends strongly on temperature revealing a reduction of the net repulsive interparticle forces with decreasing temperature. While there are no rigorous theoretical approaches on particle diffusion properties for multicomponent, nonideal hard sphere polydispersed systems, as the suspensions studied here, a discussion of the volume fraction dependence of the long-time self-diffusion coefficient in the context of existing theoretical approaches was undertaken. This study is purported to provide some insight into the complex light scattering pattern of intact lenses and the interactions between the constituent proteins that are responsible for lens transparency. This would lead to understand basic mechanisms of specific protein interactions that lead to lens opacification (cataract) under pathological conditions.

Inhibition of the growth of human melanoma metastases in nude mice by melanoma-specific murine monoclonal antibody.

The administration of anti-melanoma murine monoclonal antibody (MAB) 16.C8 (IgG2a) to nude mice bearing established human melanoma lung or liver metastases resulted in a significant inhibition of tumour growth. A total dose of 2 mg of affinity purified 16.C8 caused complete inhibition of tumour growth in 89 and 100% of animals in the liver and lung model, respectively. In contrast, a significant tumour growth was found in most control animals which received an irrelevant IgG2a MAB or 2% human serum albumin in Hanks Balanced Salt Solution (HBSS). The MAB was most effective when treatment was started on day 1 or 4 following tumour inoculation. When the 16.C8 MAB treatment was delayed 7 or 14 days, 33 and 67% of 16.C8 treated animals, respectively, developed tumours. The MAB-mediated anti-tumour activity appeared to be dose dependent, and the effect of a suboptimal dose was potentiated by the concomitant administration of recombinant interleukin 2 (rIL-2). Recombinant IL-2 alone in a similar dose did not elicit comparable anti-tumour activity. Moreover, the MAB 16.C8 inhibited tumour growth in irradiated animals which may suggest the involvement of host-radioresistant cellular elements in the 16.C8 antibody-mediated anti-tumour activities in nude mice. These results suggest that MAB 16.C8 alone or combined with rIL-2 may prove useful in the immunotherapy of metastatic melanoma.

[Mental health and nursing]. / Psychike ygeia kai noseleutike.

World Health Organization, contributing to the International Nurses Day proposes that mental health should be taught as a special subject, parallel to the subjects of psychiatry and psychiatric nursing. Mental health is a dynamic process though one can not ignore the role of heredity to it. Research has shown that sex, nationality, social status and occupation do influence mental health to a great extend. The first formative years of life, family relations, school experiences and the events of life are decisive factors for the mental health state, of an individual. Alcoholism and drug addiction form a permanent threat on mental health in the context of community mental health and psychiatric care. There can be certain interventions in the field of prevention: (a) early interventions, (b) help to people to overcome stressful situations, (c) help to people in the old age, (d) policy making to face alcoholism and drug addiction. The role of community psychiatric nurse, in the prevention of mental disease is very important. The reorientation of our educational programmes according to the directions given by the World Health Organization will enable us to meet our challenge and new role in 1992.

[The role of calcium ions and inositol phospholipids in platelet activation]. / Rola jonów wapnia i fosfolipidów inozytolowych w aktywowaniu krwinek plytkowych.

The present state of knowledge on the importance of calcium ions and inositol phospholipids in the metabolic changes associated with early stages of platelet activation is outlined, with stress laid in the biochemical mechanisms of intracellular rise of calcium ion concentration. The metabolism of inositol phospholipids is briefly discussed stressing the importance of the metabolites of these phospholipids--1,2-diacylglycerol and 1,4,5-inositol triphosphate which are of key importance in the transfer of information between platelet membrane and intracellular structures.

[Disorders of blood platelet homeostasis in patients with multiple myeloma before the treatment and during remission]. / Zaburzenia hemostazy plytkowej u chorych na szpiczaka plazmocytowego przed leczeniem i w okresie remisji choroby.

In 28 patients with plasmocytoma selected parameters of primary haemostasis were studied before treatment and 6-9 months later, in remission. We evaluated spontaneous aggregation, aggregation induced by ADP and adrenaline, platelet factor 3 availability and the realising platelet factor 4. Significant disturbances of primary haemostasis were particularly marked in patients with a high monoclonal protein concentration (greater than 3 g/dl). During remission an increase of platelet aggregation was noted. Its values, however, remained lower than in the control group.

[Activation and functions of blood platelets in patients with diabetes mellitus type 1 before and during the treatment with indobufen]. / Aktywacja i czynnosc krwinek plytkowych u chorych na cukrzyce typu I przed i w czasie leczenia indobufenem.

In 18 patients with type I diabetes the effect was studied of 10 days of Indobufen administration in daily doses of 400 mg on the activation and function of platelets. Spontaneous and ADP and adrenaline-induced aggregation, adhesiveness, platelet factors 3 and 4, and generation of malonyldialdehyde (MDA) in platelets were investigated. The results were compared with similar results in the same group prior to the treatment and in a control group of 19 healthy subjects. Highly significant inhibition was noted of spontaneous inhibition and that evoked by adrenaline and ADP, and a considerable reduction of MDA generation by platelets. These results indicate that the new platelet inhibitor--Indobufen, effectively inhibiting platelet activation and function may prevent development of thrombotic complications of diabetes.

The ST segment axis as a differential diagnostic feature between acute pericarditis and acute inferior myocardial infarction.

The ST segment electrical axis in the frontal plane was calculated in 20 patients with an acute inferior myocardial infarction (AIMI) and another 20 patients with the acute phase of pericarditis (AP). The ST segment axis of patients with AIMI ranged from 100 degrees-120 degrees (mean 114 degrees). The ST segment axis of patients with AP ranged from 30 degrees-60 degrees (mean 45 degrees). Thus, the ST segment axis can be used for the differential diagnosis in the early acute phase, especially when there are no other important distinguishing factors between these two conditions.

The effect of sulphinpyrazone and alpha-tocopherol on platelet activation and function in haemodialysed patients.

In 30 patients on chronic haemodialysis treatment the platelet activity and function were studied before and during antiplatelet therapy with alpha-tocopherol and sulphinpyrazone. In both kinds of treatment a significant decrease of ADP-induced and spontaneous aggregation was observed. Sulphinpyrazone exerts an inhibitory effect not only on platelet aggregation but also on platelet factor 3 and provokes a significant prolongation of the bleeding time.

[Effect of vitamin E on the function of blood platelets in patients with diabetes mellitus]. / Wplyw witaminy E na czynnosc krwinek plytkowych u chorych na cukrzyce.

An effect of vitamin E on blood platelets functioning was studied in 39 patients with diabetes mellitus type 1. Control group included 20 healthy blood donors. Vitamin E in a daily dose of 1000 mg produced statistically significant decrease in platelets aggregation, number of circulating platelet aggregates and release of the platelet factory 4 in diabetics after 7 days of treatment. No adverse reactions were seen in any patient treated with vitamin E. The obtained results indicate that vitamin E inhibits increased platelets activity in the patients with diabetes mellitus type 1 and does not exert toxic reactions during the treatment.