Social inequality in obesity in an Eastern Mediterranean population: evidence from a national health survey in Cyprus.

Background: We aimed to explore socioeconomic factors associated with obesity among adults and to investigate social inequality in obesity prevalence in Cyprus. Study design: Cross-sectional study. Methods: We conducted a survey among 3,021 Greek-Cypriots aged 25-64 years, collecting self-reported demographics, health behaviors, socioeconomic characteristics and anthropometric measurements. We performed univariable and multivariable (adjusting for demographics and health behaviors) sex-specific Poisson's regression with robust variance, reporting adjusted prevalence ratios (PRs) and 95% confidence intervals. Results: The prevalence of obesity was 22% among males and 17% among females. According to univariable analyses, higher obesity prevalence was associated with increased age, decreased physical activity and decreased alcohol consumption in both genders. In addition, obesity was associated with refugee status and former smoking in males and with a higher healthy diet score in females. There was a clear linear decrease in obesity prevalence each step up the socioeconomic hierarchy in both genders. In the fully adjusted model, a clear inverse gradient in obesity prevalence by educational attainment was observed in females (p=0.002), while, in males, lower obesity prevalence remained significantly associated with the highest level of family-net income and educational attainment (aPR:0.48; 95% CI:0.27-0.84 and aPR:0.46; 95% CI:0.25-0.84, respectively). Occupational social class was not associated with obesity. Conclusions: This study highlights striking social inequalities in obesity in an Eastern Mediterranean population, which only recently moved from rural living to high levels of development. We recommend that public health interventions should address education - and income-related barriers, as a means of tackling health inequalities.

Hospitalised cancer patients' perceptions of individualised nursing care in four European countries.

The aim of this study was to describe hospitalised cancer patients' perceptions of individualised care in four European countries and compare these perceptions using the patients' socio-demographic characteristics and the Individualized Care Scale. The patients' socio-demographic characteristics used were: education, age, gender, type of hospital admission, previous hospitalisation and hospital length of stay. The Individualized Care Scale has two parts (1) nurses' support of individuality and (2) patients' receipt of individuality. Data (n = 599) were collected in Cyprus (n = 150), Finland (n = 158), Greece (n = 150) and Sweden (n = 141). Multivariate analysis of variance models were constructed and differences in perceptions of individualised care were analysed using the patients' socio-demographic characteristics as covariates. The level of support for individuality and receipt of individualised care was reported as moderate and good respectively. Generally, the highest assessments were made by the Swedish respondents and the lowest by those in Greece. This study revealed some between-country differences in patients' perceptions of care individualisation. These differences, for example, conceptual, educational, based in clinical practice or in the health organisation, require further research. Enquiry into the individualised care perceptions of health care providers and the families of cancer patients would also be useful.

Preliminary validation and reliability of the Short Form Chronic Respiratory Disease Questionnaire in a lung cancer population.

The Short Form Chronic Respiratory Questionnaire (SF-CRQ) is frequently used in patients with obstructive pulmonary disease and it has demonstrated excellent psychometric properties. Since there is no psychometric information for its use with lung cancer patients, this study explored its validity and reliability in this population. Forty-six patients were assessed at two time points (with a 4-week interval) using the SF-CRQ, the modified Borg Scale, five numerical rating scales related to Perceived Severity of Breathlessness, and the Hospital Anxiety and Depression Scale. Internal consistency reliability was investigated by Cronbach's alpha reliability coefficient, test-retest reliability by Spearman-Brown reliability coefficient (P), content validity as well as convergent validity by Pearson's correlation coefficient between the SF-CRQ, and the conceptual similar scales mentioned above were explored. A principal component factor analysis was performed. The internal consistency was high [α = 0.88 (baseline) and 0.91 (after 1 month)]. The SF-CRQ had good stability with test-retest reliability ranging from r = 0.64 to 0.78, P < 0.001. Factor analysis suggests a single construct in this population. The preliminary data analyses supported the convergent, content, and construct validity of the SF-CRQ providing promising evidence that this can be a valid and reliable instrument for the assessment of quality of life related to breathlessness in lung cancer patients.

Prevalence and social determinants of smoking in the adult Greek Cypriot population.

BACKGROUND: Smoking remains a major public health concern in Europe. In the current study, we investigate the prevalence and socioeconomic factors that contribute to smoking disparities in Greek Cypriot adults.  Material and methods: In 2009, using the Countrywide Integrated Noncommunicable Disease Intervention questionnaire a representative sample of Greek Cypriot adults was surveyed (response rate 100%).  Socioeconomic and demographic data were collected and analyzed. RESULTS: The prevalence of smoking in Greek Cypriot adults was 50.8 % among men and 21.2 % among women. Sociodemographic disparities in smoking prevalence were identified, characterized by higher prevalence in urban vs rural centers (especially among women), and higher prevalence among employed women vs housewives. Socioeconomic inequalities in prevalent smoking were gender-specific, with occupational social class showing an inverse association among men and a direct among women, with income showing an inverse association (mostly among men), and educational attainment showing a clear inverse gradient among men and a direct gradient among women. CONCLUSION: Striking gender-specific bidirectional associations between socioeconomic factors and smoking prevalence were identified among Greek Cypriot adults, which may promote targeted intervention programmes aiming at halting and reversing smoking behaviors in Cyprus. Hippokratia 2016, 20(4): 284-291.

The effect of resistance inspiratory muscle training in the management of breathlessness in patients with thoracic malignancies: a feasibility randomised trial.

OBJECTIVES: Breathlessness in patients with lung cancer is a common and distressing symptom affecting 50-70 % of patients, rising to some 90 % for those with advanced lung cancer. The aim of the current study was to assess how feasible inspiratory muscle training (IMT) is in the lung cancer population and explore changes in outcome variables. MATERIALS AND METHODS: A pilot feasibility randomised trial was conducted in patients with clinically stable lung cancer. The experimental group received training using a pressure threshold device. Patients were instructed to carry out five IMT sessions weekly for 12 weeks for a total of 30 mins/day. Patients in the control group received standard care. Outcome measures were completed at baseline and monthly for 3 months, and included: physiological parameters (FEV1, FVC); perceived severity of breathlessness using six 10-point NRS; modified Borg Scale; quality of life using the short form Chronic Respiratory Disease Questionnaire; Hospital Anxiety and Depression Scale, and safety. RESULTS: Forty-six patients (M = 37, F = 9) at a mean age of 69.5 years old and a mean of 16 months post-diagnosis who were not currently receiving chemotherapy and/or radiotherapy were recruited. Seventy-percent had NSCLC and advanced disease. Statistical (area under the curve-AUC) and clinically important differences were seen with regard to distress from breathlessness (p = 0.03), ability to cope with breathlessness (p = 0.01), satisfaction with breathlessness management (p = 0.001), fatigue (p = 0.005), emotional function (p = 0.011), breathlessness mastery (p = 0.015) and depression (p = 0.028). The m-Borg difference between the two groups at 3 months was 0.80, which is borderline clinically significant. Changes were more evident in the 3-month assessment where the effect of the intervention came to its peak. CONCLUSION: This trial shows the IMT is feasible and potentially effective in patients with lung cancer. These findings warrant a fully powered larger randomised controlled trial.

Individualised care and the professional practice environment: nurses' perceptions.

AIM: To describe individualised care and the professional practice environment from nurses' point of view and to explore the associations between them. BACKGROUND: There is an increasing emphasis on individualised nursing care within the literature and the health-care context. Preliminary evidence suggests that the implementation of individualised care is associated with the practice style of care, work organization and the practice environment. METHODS: An exploratory correlational survey was used. Data were collected using the Individualised Care Scale and Revised Professional Practice Environment instruments from nurses and nurse managers (n=207, response rate 59%) working in in-patient wards of three acute hospitals' 13 different units in Finland in 2008. Data were analysed based on descriptive statistics and Spearman's rho correlations. FINDINGS: Nurses perceived that they generally support patient individuality and that the care they provided was individualised. Nurses' perceptions about the support of individuality and views on individuality of care provided were associated with handling conflict, work motivation, control over practice, leadership and autonomy, relationships with physicians and cultural sensitivity. DISCUSSION: The findings support the perception that individualised care and the professional practice environment are associated. There is a need for further studies to examine these associations more closely. Manipulating aspects of the environment may possibly be used to increase the ability of the nurses to provide individualised care. Patient perspectives should be included in future studies. Because of the national data, the results are indicative only. CONCLUSIONS: The recognition of the associations between individualised care and professional practice environment elements may help to develop individualised clinical nursing care.

Preregistration programme for medical practice: a survey of Cypriot trainees (2000 and 2002).

This paper reports the attitudes of medical school graduates participating in the preregistration training programme in Cyprus. There were 2 independent samples, one in the year 2000 of 34 trainees and one in 2002 of 45 trainees. The trainees responded to 45 statements of attitude on a 5-point Likert scale covering 3 areas: workload, educational environment and lifestyle issues. The sample means for each statement were reported in both years and differences between the 2 years were analysed. In general, the trainees had an overall neutral to negative attitude towards the programme in both years and there was little change over the 2 years.

Preregistration programme for medical practice: a survey of Cypriot trainees [2000 and 2002]

This paper reports the attitudes of medical school graduates participating in the preregistration training programme in Cyprus. There were 2 independent samples, one in the year 2000 of 34 trainees and one in 2002 of 45 trainees. The trainees responded to 45 statements of attitude on a 5-point Likert scale covering 3 areas: workload, educational environment and lifestyle issues. The sample means for each statement were reported in both years and differences between the 2 years were analysed. In general, the trainees had an overall neutral to negative attitude towards the programme in both years and there was little change over the 2 years

Synthesis and biological evaluation of novel daunorubicin-estrogen conjugates.

The synthesis of two novel daunorubicin-estrogen conjugates with a steroidal and a non-steroidal ligand was undertaken in an attempt to target the cytotoxicity of anthracycline to estrogen-receptor positive cells. These conjugates (3 and 4), in contrast to their corresponding ligands, displayed weak binding affinities of 0.079 and 0.851 for the estrogen receptor. Conjugate 3 was consistently more cytotoxic than 4, which however showed some selectivity to estrogen receptor positive cell lines.

Identification of a cell type-specific silencer in the first exon of the His-1 gene.

The His-1 gene is developmentally expressed in the murine choroid plexus but is silenced in the adult brain. To test the hypothesis that the gene contains cis-acting elements that contribute to this repression, we have analyzed segments of the proximal promoter for negative regulatory sequences by transient transfection analysis. The activity of the proximal promoter was moderately influenced by positively and negatively acting sequences located from -335 to -168 and -617 to -335, respectively. A strong His-1-positive regulatory element (HPRE, +18 to +29) was essential for maximal promoter activity and could also enhance the activity of the heterologous SV40 promoter in an orientation-dependent manner. The HPRE contains homology to the neuronal restrictive silencer element (NRSE) but interacted with nuclear proteins that were distinct from the NRSE-binding factor (NRSF). By contrast, a potent negative regulatory sequence (HNRE) was identified in the first exon that repressed either the His-1 or SV40 promoters by greater than 80%. This negative regulatory sequence interacted with nuclear proteins from cells that contain a silent His-1 gene but showed no interaction with nuclear proteins from cells that actively transcribe the endogenous gene. HNRE-mediated repression was orientation independent; most of this activity was mapped to a minimal 26-bp sequence. These findings suggest that the first exon of the His-1 gene contains a cell type-specific silencer that contributes to the regulation of His-1 transcription.

Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I.

The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C]dihydrorotenol ([11C]DHROL: 40%) and in vitro binding of [3H]dihydrorotenone ([3H]DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C]DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C]DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C]iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases.

Alterations in colonic arterial and venous plasma neuropeptide concentrations in horses during low-flow ischemia and reperfusion of the large colon.

OBJECTIVE: To measure colonic arterial (CA) and colonic venous (CV) plasma neuropeptide concentrations during low-flow ischemia and reperfusion of the large colon in horses. ANIMALS: 10 adult horses. PROCEDURE: CA and CV plasma samples collected from anesthetized horses during experimentally induced low-flow colonic ischemia and reperfusion were assayed for vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and substance P (SP), using radioimmunoassays. In 6 anesthetized horses, colonic ischemia (20% of baseline (BL]) was maintained for 3 hours, then blood flow was restored and monitored for 3 hours. Hemodynamic variables were monitored continuously and recorded at 30-minute intervals. CA resistance was calculated from colonic blood flow (Q(colon)) and mean CA pressure values at each time. Blood was obtained from CA and CV catheters at 0, 1, 2, 3, 3.25, 3.5, 4, 5, and 6 hours; plasma VIP, CGRP, and SP concentrations were quantified, using radioimmunoassays. In 4 additional horses, VIP and CGRP were measured in CA and CV blood at 0, 0.25, 0.5, 0.75, and 1 hour. RESULTS: Heart rate was significantly increased at 5.5 and 6 hours; other alterations in systemic hemodynamic variables were not significant. Decrease in Q(colon) during ischemia was significant; Q(colon) rebounded to a value significantly greater than BL value within 5 minutes of reperfusion and was maintained above the BL value during 3 hours of reperfusion. Mean CA pressure was significantly decreased during ischemia, but returned to a value not different from the BL value by 3.25 hours. Mean CV pressure remained unchanged from the BL value during ischemia, but increased to a value significantly greater than the BL value by 3.25 hours and remained increased through 6 hours. CA resistance began to decrease during early ischemia and was significantly less than the BL value by 3.25 hours; it remained less than the BL value through 4 hours. Increase in CV VIP concentration was significant by 0.25 hour of ischemia, but decreased to a value not different from BL value by 3.25 hours. Increase in CV CGRP was significant at 3.25 hours, but this variable returned to a value not different from BL value by 3.5 hours. CONCLUSIONS: CV VIP concentration increases during low-flow colonic ischemia, and CV and CA CGRP and CA SP concentrations increase during early reperfusion.

Synthesis and biological evaluation in mice of (2-[11C]methoxy)-6',7'-dihydrorotenol, a second generation rotenoid for marking mitochondrial complex I activity.

Evidence has accumulated suggesting that impairment of the function of the complexes of the mitochondrial respiratory chain might be involved in the pathology of neurological diseases including Parkinson's and Huntington's diseases. Recently we reported the synthesis of (2-[11C]methoxy)rotenone ([11C]ROT) as a tool for in vivo studies of complex I. In an effort to develop a complex I imaging radiotracer which might be easier to synthesize and less likely to be metabolized, we prepared (2-[11C]methoxy)-6',7'-dihydrorotenol ([11C]DHROT). The radiotracer was synthesized by [11C]methylation of 2-O-desmethyl-6',7'-dihydrorotenol under basic [11C]alkylation conditions. (2-[11C]Methoxy)-6',7'-dihydrorotenol was produced in 30-35% radiochemical yields (decay corrected), with synthesis times shorter than 35 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol. The brain distributions of [11C]ROT and [11C]DHROT were investigated in mice after intravenous injections. For both radiotracers, distribution of radioactivity was similar in all brain regions examined. However, significantly higher uptake was observed with [11C]DHROT than with [11C]ROT, indicating that the alterations introduced in the structure of rotenone during the design of [11C]DHROT resulted in a tracer with greater brain barrier permeability.

Synthesis of (2-[11C]methoxy)rotenone, a marker of mitochondrial complex I activity.

Recent studies suggest that defects in the function of the complexes of the electron transport chain might be involved in the pathology of neurological diseases such as mitochondrial encephalopathies, Parkinson's, Huntington's and Alzheimer's disease. Rotenone is a potent reversible competitive inhibitor of complex I (NADH-CoQ reductase). To study the possible involvement of complex I in such diseases, we synthesized (2-[11C]methoxy)rotenone by [11C]alkylation of 2-O-desmethyl rotenone methyl enol ether followed by hydrolysis of the enol ether to the ketone using aqueous trifluoroacetic acid. (2-[11C]Methoxy)rotenone was purified by high pressure liquid chromatography (silica gel) and was obtained in 7-10% yields decay corrected to end of bombardment in synthesis times typically shorter than 48 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol at end of synthesis.

Insight in schizophrenia and mood disorders and its relation to psychopathology.

The authors assessed insight on admission on the 15th, 30th and discharge day in 77 female inpatients (42 schizophrenic, 13 manic, 22 depressives) using McEvoy's Insight and Treatment Attitude Questionnaire (ITAQ) and studied its relation to psychopathology, which was assessed by completion of the Brief Psychiatric Rating Scale (18-item version). The data suggest that depressives had good initial (on admission) insight, schizophrenics the poorest, followed shortly by manics. Insight (ITAQ total score) improved significantly after treatment in both mania and schizophrenia. Moreover a constantly significant negative correlation existed between ITAQ and BPRS in mania but not in schizophrenia, indicating that other factors besides psychopathology might influence insight in schizophrenia.

Pharmacological evaluation of iodo and nitro analogs of delta 8-THC and delta 9-THC.

One aspect of cannabinoid structure-activity relationships (SARs) that has not been thoroughly investigated is the aromatic (A) ring. Although halogenation of the side chain enhances potency, our recent observation that iodination of the A ring also enhanced activity was surprising. The purpose of this investigation was to establish the steric and electrostatic requirements at these sites of the cannabinoid molecule via molecular modeling, while determining pharmacological activity. Molecular modeling was performed using the Tripos molecular mechanics force field and the semiempirical quantum mechanical package AM1. The Ki values for novel cannabinoids were determined in a [3H]CP-55,940 binding assay and ED50 values generated from four different evaluations in a mouse model. The present studies underscore the increase in potency produced by a dimethylheptyl (DMH) side chain. Trifluoro substitutions on the pentyl side chain, or bromination of the DMH side chain, had little effect on the pharmacological activity. Any substitution at the C4 position of the aryl ring resulted in a loss of activity, which appears to be due to steric hindrances. Nitro, but not iodo, substitution at the C2 position essentially produces an inactive analog, and the drastic alteration of the electrostatic potential appears to be responsible. The altered pharmacological profile of the 2-iodo analog seems to be related to an alteration in the highest occupied molecular orbital because there is no alteration in the electron density map compared to delta 8-tetrahydrocannibinol.

PET studies in the primate brain and biodistribution in mice using (-)-5'-18F-delta 8-THC.

Cannabinoids, the active constituents of marijuana, are known to have many therapeutic properties; however, their exact mechanism of action is not well understood. In an effort to obtain more information concerning the pharmacokinetics and biodistribution of psychoactive THC analogs we synthesized (-)-18F-delta 8-THC and studied its biodistribution in mice and baboon brains. The analog was obtained by nucleophilic fluorination of the ditriflate ester of (-)-5'-OH-delta 8-THC with K18F/Kryptofix followed by deprotection with LiAIH4 and purification with HPLC in 8% yield in a 90-min synthesis from EOB. The uptake of (-)-5'-18F-delta 8-THC in mouse tissue was high at 5 min, but radioactivity declined rapidly in almost all the tissues studied. Following IV administration, (-)-5'-18F-delta 8-THC uptake in baboon brain was similar in the basal ganglia, thalamus and cerebellum, and the clearance from these regions was relatively rapid. Also, a study from baboon plasma clearance of (-)-5'-18F-delta 8-THC showed rapid metabolism of the analog.

Pharmacological evaluation of halogenated delta 8-THC analogs.

-(-)-5'-Bromo-delta 8-THC, (-)-5'-trifluoromethyl-delta 8-THC, (-)-5'-iodo-delta 8-THC, (-)-5'-fluoro-delta 8-THC, (-)-11-fluoro-delta 8-THC and (-)-2-iodo-delta 8-THC were synthesized and evaluated in male ICR mice for their effects on sedation, temperature, catalepsy and antinociception following intravenous injection. The analogs were also tested for relative affinities for cannabinoid binding sites derived from rat cortex membranes, using [3H] CP-55,940 as the tritiated ligand. The results showed that the 5'-bromo, 5'-iodo and 5'-trifluoromethyl analogs were 2-40 times more potent than (-)-delta 8-THC in all biological tests, while the 5'-fluoro and 11-fluoro derivatives were less active. With the 2-iodo analog, a 12-fold separation was observed between antinociception and sedation, pointing to the importance of the side chain orientation in determining cannabinoid activity and to the possible involvement of more than one cannabinoid receptor site. The pharmacological data closely paralleled the data obtained from the binding assay.

Solid state 2H-NMR as a method for determining the orientation of cannabinoid analogs in membranes.

In order to investigate the correlation between the pharmacological activities of cannabinoids and the geometric features of their interactions with membranes, we have calculated the molecular orientations of five analogs in model membrane bilayers. The studies involved the stereospecific 2H-labeling of each analog in different positions and the use of solid state 2H-NMR. The cannabinoids included in our study are (-)-delta 9-tetrahydrocannabinol (THC), (-)-delta 8-THC and its methylated ether analog (-)-O-methyl-delta 8-THC, as well as two hexahydrocannabinols (HHC) having an additional hydroxyl in the 11-position, (-)-11-OH-9 alpha-HHC and (-)-11-OH-9 beta-HHC. A new algorithm is used to circumvent the problem of deuterium quadrupolar splitting signs. The method has general applicability for calculating the orientation of a molecule in a anisotropic environment. Our calculations show that the biological inactive O-methyl-delta 8-THC orients with its long axis parallel to the lipid acyl chains, whereas the psychoactive cannabinoids assume "awkward" orientations in which the hydroxyl groups are pointing towards the bilayer interface, presumably to maximize the amphipathic interaction with the membrane. To produce their biological effects, cannabinoids may need to acquire an appropriate location and orientation in the membrane bilayer so that, through lateral diffusion, they can reach their sites of action and interact productively with these sites.