Predictors of health-related quality of life in Serbian patients with head and neck cancer.

BACKGROUND: The aim of this study was to identify predictors of the Health-Related Quality of Life (HRQoL) in patients with head and neck cancers (HNCs). MATERIAL AND METHODS: In total, 345 patients with HNCs were interviewed. A self-report questionnaire was administered to collect data about demographic characteristics, health status, smoking, alcohol consumption habits, and HRQoL. It were used the EORTC Instruments - Quality of Life Questionnaire-Core 30-questions (QLQ-C30), Quality of Life Questionnaire - Head and Neck Module 35-questions (QLQ-H&N 35) and OHIP-14 instrument for HRQoL assessments. Clinical information and treatment data were collected from medical records. RESULTS: Five groups of HRQoL predictors were identified: demographic, socioeconomic, behavioral, psychophysical, and clinical/treatment. These HRQoL predictors had a strong (i.e., age, level of social support and social contact, level of education, depression, fatigue, presence of gastrostomy, comorbidities, and use of pain medications and supplements), a moderate (i.e., marital status, smoking, sexuality problems, time since diagnosis, presence of tracheostomy, and side effects outcomes of radio and chemotherapy) and a small impact (i.e., employment/financial difficulties, tumor site and stage, and surgical procedure). CONCLUSIONS: Study identified nineteen predictors that had significant, moderate and small impact on the HRQoL of patients with HNCs. Some of the predictors, like levels of social support and social contact, depression, and comorbidities could be targets for innervations to improve HRQoL.

Validation of the oral health impact profile - 14 in patients with head and neck cancer.

BACKGROUND: The Oral Health Impact Profile-14 (OHIP-14) was designed to assess patients' perception of the impact of oral disorders on their quality of life (QoL). Although the OHIP-14 is now frequently used in patients with head and neck cancer, data related to its measurement properties in this population are scarce. The aim of the present study was to evaluate the reliability and validity of the OHIP-14 in a sample of Serbian patients with head and neck cancer. MATERIAL AND METHODS: Data were available for 345 patients (257 [74.5%] males; aged 30-92 years), with head and neck cancer. All patients completed the OHIP-14 and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35. Factor analyses, internal consistency reliability (i.e., Cronbach's α coefficient), and construct validity were analyzed. RESULTS: The factor analyses confirmed that 14 OHIP items were measuring a single underlying factor. Cronbach's α coefficient was 0.98 and corrected item-total correlations ranged 0.77-0.93. Lower OHIP-14 scores (i.e., lower impacts on oral health) were more frequently present among patients who had only surgery as a therapeutic procedure compared to those who had surgery accompanied with radio- and chemotherapy (p < 0.01). Patients with a tumor stage 0-II also had lower OHIP-14 scores compared to those who had a tumor stage III-IV (p < 0.01). The OHIP-14 correlated significantly with the QLQ-C30 and QLQ-H&N35 scales. CONCLUSIONS: As a unidimensional instrument, the OHIP-14 provides oral QoL assessments with sound internal consistency reliability and construct validity among patients with head and neck cancer.

Ferrocene-containing tetrahydropyrazolopyrazolones: Antioxidant and antimicrobial activity.

A series of ferrocenes which contain dinitrogen-fused pyrazolidinone ring were synthesized from acryloylferrocene (4) and N,N'­cyclic azomethine imines (3). Novel 5­aryl­6­ferrocenoyltetrahydropyrazolo[1,2­a]pyrazol­1(5H)-ones were obtained as mixtures of two diastereoisomers (trans and cis) which were separated and isolated as pure substances. Ortho-substituted N,N'­cyclic azomethine imines 5-oxo-2-(2,4,6-trimethylbenzylidene)pyrazolidin-2-ium-1-ide (3e) and 2-(2-methoxybenzylidene)-5-oxopyrazolidin-2-ium-1-ide (3f) reacted stereoselectively affording only trans-6-ferrocenoyl-5-mesityltetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (5e) and 6-ferrocenoyl-5-(2-methoxyphenyl)tetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (5f). Ferrocenyl derivatives were screened for in vitro antioxidant and antifungal activities and excellent DPPH and ABTS radicals scavenging activity was observed with majority of tested 5­aryl­6­ferrocenoyltetrahydropyrazolo[1,2­a]pyrazol­1(5H)-ones. Several tested compounds showed selective scavenging properties neutralizing ABTS•+ radical cations in contrast to inactivity toward DPPH radicals. Trans-5-aryl-6-ferrocenoyltetrahydropyrazolo[1,2-a]pyrazol-1(5H)-ones 5b, 5c, 5d, 5j as well as cis-6-ferrocenoyl-5-(p-tolyl)tetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (6d) displayed fungal growth inhibition at low concentration against C. albicans and/or A. brasiliensis. Molecular docking studies revealed that the cis-6-ferrocenoyl-5-(4-nitrophenyl)tetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (6l) and cis-6-ferrocenoyl-5-(naphthalen-2-yl)tetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (6n) have potential to become lead molecules in drug discovery process.

Cross-cultural measurement invariance of the Revised Child Anxiety and Depression Scale across 11 world-wide societies.

BACKGROUND: In order to compare estimates by one assessment scale across various cultures/ethnic groups, an important aspect that needs to be demonstrated is that its construct across these groups is invariant when measured using a similar and simultaneous approach (i.e., demonstrated cross-cultural measurement invariance). One of the methods for evaluating measurement invariance is testing for differential item functioning (DIF), which assesses whether different groups respond differently to particular items. The aim of this study was to evaluate the cross-cultural measurement invariance of the Revised Child Anxiety and Depression Scale (RCADS) in societies with different socioeconomic, cultural, and religious backgrounds. METHODS: The study was organised by the International Child Mental Health Study Group. Self-reported data were collected from adolescents residing in 11 countries: Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, Palestinian Territories, the Philippines, Portugal, Romania and Serbia. The multiple-indicators multiple-causes model was used to test the RCADS items for DIF across the countries. RESULTS: Ten items exhibited DIF considering all cross-country comparisons. Only one or two items were flagged with DIF in the head-to-head comparisons, while there were three to five items flagged with DIF, when one country was compared with the others. Even with all cross-culturally non-invariant items removed from nine language versions tested, the original factor model representing six anxiety and depressive symptoms subscales was not significantly violated. CONCLUSIONS: There is clear evidence that relatively small number of the RCADS items is non-invariant, especially when comparing two different cultural/ethnic groups, which indicates on its sound cross-cultural validity and suitability for cross-cultural comparisons in adolescent anxiety and depressive symptoms.

Musculoskeletal Pain and Vitamin D Deficiency in Children: A Pilot Follow-up Study of Vitamin D Therapy in Musculoskeletal/Orthopedic Conditions.

PURPOSE OF THE STUDY: The prevalence of vitamin D deficiency in pediatric populations is high. In the present study we analyzed associations between vitamin D therapy and pain, mobility, fatigue, and daily functioning in children with musculoskeletal/orthopedic conditions suffering from chronic and recurrent pain, but also diagnosed with vitamin D deficiency. MATERIAL AND METHODS: Children with different musculoskeletal/orthopedic conditions and vitamin D deficiency were prescribed to receive vitamin D over 6 months. Thirty-five children (18 males; age 10.48 ± 3.87 years) completed a 6-month follow-up. Self- and parent/proxy rating scales were used to evaluate pain, movement, fatigue, and daily functioning. RESULTS: At a six-month follow-up assessment involving child- and parent-reported scores, worst pain intensity significantly decreased (p ≤ 0.03) after vitamin D therapy, as well as functioning problems related to pain (p ≤ 0.01). The children reported better movement and balance with less fatigue. The parents reported better functioning in everyday activities of their children. CONCLUSION: This pilot study showed that vitamin D therapy possibly reduces pain intensity and improves mobility and daily functioning in children with musculoskeletal/orthopedic disorders, chronic recurrent pain, and vitamin D deficiency. Further follow-up and randomized studies are required in order to assess the validity of clinical recommendations.

Does the Strengths and Difficulties Questionnaire - self report yield invariant measurements across different nations? Data from the International Child Mental Health Study Group.

AIMS: This study evaluated the measurement invariance of the strengths and difficulties questionnaire (SDQ) self-report among adolescents from seven different nations. METHODS: Data for 2367 adolescents, aged 13-18 years, from India, Indonesia, Nigeria, Serbia, Turkey, Bulgaria and Croatia were available for a series of factor analyses. RESULTS: The five-factor model including original SDQ scales emotional symptoms, conduct problems, hyperactivity-inattention problems, peer problems and prosocial behaviour generated inadequate fit degree in all countries. A bifactor model with three factors (i.e., externalising, internalising and prosocial) and one general problem factor yielded adequate degree of fit in India, Nigeria, Turkey and Croatia. The prosocial behaviour, emotional symptoms and conduct problems factor were found to be common for all nations. However, originally proposed items loaded saliently on other factors besides the proposed ones or only some of them corresponded to proposed factors in all seven countries. CONCLUSIONS: Due to the lack of a common acceptable model across all countries, namely the same numbers of factors (i.e., dimensional invariance), it was not possible to perform the metric and scalar invariance test, what indicates that the SDQ self-report models tested lack appropriate measurement invariance across adolescents from these seven nations and it needs to be revised for cross-country comparisons.

Role of personal and family factors in alcohol and substance use among adolescents: an international study with focus on developing countries.

Most studies examining adolescent alcohol and substance use or abuse hardly include samples from developing countries. To bridge some gap, the prevalence and associated social correlates of alcohol and substance use and abuse was examined among a cohort of school-going adolescents sampled from seven developing countries. Alcohol and substance abuse was measured using the CRAFFT instrument, independent socio-demographic correlates were determined using regression models. A total of 2454 adolescents completed the study, among which 40.9% reported using either alcohol or at least one other substance during the previous 12 months. This was mostly alcohol (37.8%), followed by marijuana/hashish (8.6%) and other substances (8.1%). Among the adolescents who reported using at least one substance, 45% (18.3% of total sample) had CRAFFT scores indicative of problematic or hazardous substance use. Several personal and family factors were independently associated with use/abuse, and the modifiable nature of these factors calls for appropriate intervention strategies.

The feasibility of sentinel lymph node biopsy for gastric cancer: the experience from Serbia.

PURPOSE: The prediction of outcome for patients with gastric cancer is determined largely by the presence of lymph node metastases, which could be detected by sentinel lymph node (SLN) biopsy (SLNB). The purpose of this work was to determine the feasibility of SLNB in patients with gastric cancer for the assessment of regional lymph node status, including performing immunohistochemical (IHC) staining of SLN tissue. METHODS: We reviewed 137 consecutive patients with operable gastric cancer over a 10-year period using a retrospective (to examine skip metastases) and prospective (to evaluate successful mapping) study design. SLNs were mapped, biopsied and subsequently explored by routine hematoxylin & eosin (H&E) staining and by IHC staining using a cytokeratin 8/18 antibody. RESULTS: The retrospective study showed a low incidence of skip metastases (3.7%). Mapping of SLNs in the prospective study was highly successful (98.2%). During the prospective study, IHC examination of SLNs from 56 patients showed statistically significant change in disease stage. CONCLUSION: This study demonstrated highly successful mapping and biopsy of SLNs (98.2%), as well as highest specificity (100%), sensitivity (100%) and accuracy (100%) to predict metastasis in the surrounding lymph nodes of gastric carcinoma. In addition, we believe that IHC study might enable "ultra staging" and additional selection of patients for further cancer treatment.

Effects of mental health on quality of life in children and adolescents living in residential and foster care: a cross-sectional study.

AIMS: This study was conducted in order to evaluate the effects of mental health and quality of life (QOL) in children and adolescents living in residential and foster care. METHODS: Two hundred and sixteen children and adolescents, aged 8-18 years, from residential and foster care participated. QOL was assessed using the Pediatric Quality-of-Life Inventory (PedsQL), levels of anxiety and depressive symptoms using the screen for child anxiety-related emotional disorders (SCARED) questionnaire and the short mood and feeling questionnaire (SMFQ), and general mental health through use of the strengths and difficulties questionnaire (SDQ). RESULTS: The children and adolescents from residential care had significantly low QOL and more frequently had mental health problems. A stepwise linear regression was performed to test the associations between the SCARED, SMFQ and SDQ scores, and PedsQL (QOL). Anxiety, depressive symptoms and general mental difficulties account for significant variations in QOL (p < 0.001). CONCLUSIONS: Mental health problems have significant negative effects on the QOL of children and adolescents living in residential and foster care.

Quality of Life Enjoyment and Satisfaction Questionnaire-short form for quality of life assessments in clinical practice: a psychometric study.

The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and its short form (Q-LES-Q-SF) are among the most frequently used outcome measures in psychiatry research. The aim of this study was to analyse the measurement properties of the Q-LES-Q-SF for quality of life assessments in the clinical settings. Fifty-seven adults with a psychiatric diagnosis participated. Psychometric evaluation included descriptive analysis, internal consistency, test-retest reliability, validity, sensitivity and responsiveness analysis. The amount of missing data was 5.3%, while no floor or ceiling effects were observed. The internal consistency and test-retest coefficients were 0.9 and 0.93, respectfully. Almost all items significantly correlated to the total score and other measures used in the study, with the correlations ranging 0.41-0.81. Finally, the responsiveness parameters indicated the Q-LES-Q-SF is 80% sensitive and 100% specific measure. This preliminary analysis of the Q-LES-Q-SF demonstrated that it could produce reliable and valid clinical assessments of quality of life.

[Solitary hyperfunctioning thyroid gland carcinomas]. / Unifokale hyperfunktionelle Karzinome der Schilddrüse.

BACKGROUND: Thyroid gland carcinomas usually appear as afunctional and hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid carcinoma with scintigraphic hyperfunctional lesions have also been reported. The aim of our retrospective study was to elucidate the frequency of carcinomas in patients operated for solitary hyperfunctional thyroid nodules and to represent their demographic and clinical features. PATIENTS AND METHODS: During one decade (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid nodules in the Centre for Endocrine Surgery in Belgrade. RESULTS: Malignancy was revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases papillary microcarcinomas were found adjacent to dominant hyperfunctional adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma in one. All 3 patients were preoperatively hyperthyroid. In both patients with follicular carcinoma we performed lobectomies. In the third case we carried out a total thyroidectomy considering the intraoperative frozen section finding of a papillary carcinoma. CONCLUSIONS: According to our results the frequency of solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the possibility that a hyperfunctional nodule is malignant should be considered in the treatment of such lesions.

Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women.

OBJECTIVE: To compare the concentrations of cytokines belonging to Th17 axis (interleukin (IL)-17 and IL-23) and Th1 axis (IL-12 and interferon (IFN)-gamma) in obese and lean women, and to investigate their relationships with the proinflammatory adipokine leptin, proinflammatory cytokine macrophage migration inhibitory factor (MIF) and anthropometric and metabolic parameters of obesity. DESIGN: Cross-sectional study. SUBJECTS: Twenty-six obese women (age 20-52 years, body mass index (BMI): 30-48 kg/m(2)) and 20 healthy lean women (age 23-46 years, BMI: 18-25 kg/m(2)). MEASUREMENTS: Plasma levels of cytokines and leptin, BMI, waist circumference (WC) and insulin resistance index HOMA (homeostatic model assessment). RESULTS: Blood concentrations of IL-17, IL-23, MIF and leptin, but not IL-12 or IFN-gamma, were higher in obese compared with lean women (P=0.002, 0.046, 0.006 and 0.002, respectively). There was a positive correlation between IL-17 and IL-23 (r(s)=0.530), which was at the border of statistical significance (P=0.065). Neither IL-17 nor IL-23 correlated with leptin or MIF, and there was no association between IL-17 and IL-23 levels with BMI, WC or HOMA index. CONCLUSION: Interleukin-23/IL-17 axis is stimulated in obese women independently of the increase in abdominal fat, insulin resistance, leptin and MIF levels.

Centrally applied ghrelin affects feeding dynamics in male rats.

Ghrelin is 28-amino acid peptide, which is produced mainly in the stomach. Since plasma ghrelin are strictly dependent on food intake, this hormone has significant effects on appetite and energy balance. The aim of this investigation was to examine the effects of centrally applied ghrelin on feeding dynamism by measuring the approaches to food container and the amount of food and water intake within 2 hours immediately after ghrelin or PBS injections. Body weight was obtained daily, while ending retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT) contents as well as blood levels of leptin and insulin were measured. Five injections of rat ghrelin or PBS (n = 8 per group) were administered once per day (1 microg = 0.15 nmol of ghrelin in 5 microL of PBS), into lateral cerebral ventricle (ICV) of free feeding adult male rats. Results showed that in the first and the second 30-min intervals number of approaches to food container were significantly increased already after the 2(nd) ICV ghrelin application (p < 0.05), by 50% and 67% respectively, in comparison with control rats. Centrally applied ghrelin increased body weight after the 2(nd) injection till the end of treatment (p < 0.05), which was followed by increased food and water intake (p < 0.05). At the end of treatment, RP and EPI WAT contents were increased (by 221%, p < 0.01 and 82%, p < 0.05, respectively). Serum insulin levels were elevated (by 41%, p < 0.05) while serum leptin levels were decreased (by 75%, p < 0.05). These data and the available literature strongly support the opinion that repetitive subnanomolar doses of central ghrelin administration play essential role in food initiation and feeding dynamics in freely feeding adult male rats.

Consummatory behavior and metabolic indicators after central ghrelin injections in rats.

Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 microg/5 muL PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p<0.05), but not feces mass or urine volume (p>0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p<0.001), EPI WAT (by 85%, p<0.05) and serum insulin levels (by 43%, p<0.05), and decreased serum leptin levels (by 77%, p<0.05) without (p>0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity.

Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis.

The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin.

The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats.

Ghrelin is a brain-gut peptide known for its growth hormone (GH)-releasing and appetite-inducing activities. This natural GH secretagogue (GHS) was originally purified from rat stomach, but it is expressed widely in different tissues where it may have endocrine and paracrine effects. The central effects of ghrelin on adrenocorticotropic hormone (ACTH) cells, ACTH release and subsequent corticosterone release from adrenal glands remains to be clarified. The aim of this study was to specifically determine the morphological features of ACTH-producing pituicytes and blood concentration of ACTH and corticosterone after central administration of ghrelin. Five doses of rat ghrelin or PBS (n=10 per group) were injected every 24 h (1 microg of ghrelin in 5 muL PBS), into the lateral cerebral ventricle of male rats. Results showed that ghrelin increased (p<0.05) absolute and relative pituitary weights compared to controls (58% and 41% respectively). Morphometric parameters, i.e. the volume of the ACTH cells, nuclear volume, and volume density were all increased (p<0.05), by 17%, 6% and 13%, respectively, 2 h after the last ghrelin treatment. Ghrelin increased circulating concentrations of ACTH and corticosterone (p<0.05) by 62% and 66%, respectively. The data provide clear documentation that intracerebroventricular ghrelin stimulates ACTH cell hypertrophy and proliferation, and promotes ACTH and corticosterone release. Determining the role of ghrelin in physiological stress responses and whether control of the peptide's activity would be useful for prevention and/or treatment of stress-induced diseases remain important research goals.

Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats.

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from rat stomach; subsequently, ghrelin neurons were found in the arcuate nuclei of rats. Central effects of the peptide on GH release, however, remain to be clarified. The aim of the present study was to determine the morphologic features of GH-producing pituicytes and serum GH concentration after central administration of ghrelin. Five injections of rat ghrelin or phosphate-buffered saline (PBS; n = 10 rats/group) were given every 24 hrs (1 microg of ghrelin in 5 microl of PBS) into the lateral cerebral ventricle of male rats. Significant (P < 0.05) increases in absolute and relative pituitary weights occurred in ghrelin-treated rats versus controls (58% and 41%, respectively). Morphometric parameters (i.e., the volume of GH cells, volume of their nuclei, and volume density) all significantly (P < 0.05) increased by 17%, 18%, and 19%, respectively, in the ghrelin-treated group versus controls. Terminal serum concentration of GH was significantly (P < 0.05) increased by 15% with ghrelin treatment. The results clearly document that daily nanomolar doses of ghrelin into the lateral cerebral ventricle stimulate GH cell proliferation and promote GH release. Thus, achieving pharmacologic control of central ghrelin receptors is a promising modality to modulate the actions of GH.